PMID-sentid	Pub_year	Sent_text	comp_official_name	comp_offset	protein_name	organism	prot_offset
23263862-1	2013	Frameshift mutations in the last coding exon of the 5-aminolevulinate synthase (ALAS) 2 gene were described to activate the enzyme causing increased levels of zinc- and metal-free protoporphyrin in patients with X-linked dominant protoporphyria (XLDPP).	Metals	169-174	5'-aminolevulinate synthase 2	Homo sapiens	80-87
24003969-3	2013	The most common form is X-linked sideroblastic anemia, due to mutations in the erythroid-specific delta-aminolevulinate synthase (ALAS2), which is the first enzyme of the heme biosynthesis pathway in erythroid cells.	Heme	171-175	5'-aminolevulinate synthase 2	Homo sapiens	130-135
23500306-9	2013	The rate-limiting enzyme in heme synthesis, delta-aminolevulinic acid synthase 2 (ALAS2), was significantly upregulated in HF.	Heme	28-32	5'-aminolevulinate synthase 2	Homo sapiens	44-80
23500306-9	2013	The rate-limiting enzyme in heme synthesis, delta-aminolevulinic acid synthase 2 (ALAS2), was significantly upregulated in HF.	Heme	28-32	5'-aminolevulinate synthase 2	Homo sapiens	82-87
23500306-10	2013	Overexpression of ALAS2 in H9c2 cardiac myoblasts resulted in increased heme levels, and hypoxia and erythropoietin treatment increased heme production through upregulation of ALAS2.	Heme	72-76	5'-aminolevulinate synthase 2	Homo sapiens	18-23
23500306-10	2013	Overexpression of ALAS2 in H9c2 cardiac myoblasts resulted in increased heme levels, and hypoxia and erythropoietin treatment increased heme production through upregulation of ALAS2.	Heme	136-140	5'-aminolevulinate synthase 2	Homo sapiens	176-181
23263862-1	2013	Frameshift mutations in the last coding exon of the 5-aminolevulinate synthase (ALAS) 2 gene were described to activate the enzyme causing increased levels of zinc- and metal-free protoporphyrin in patients with X-linked dominant protoporphyria (XLDPP).	protoporphyrin IX	180-194	5'-aminolevulinate synthase 2	Homo sapiens	80-87
24135682-1	2013	X-linked dominant protoporphyria (XLDPP) is a genetic disorder that affects the synthesis of the heme group due to an increase in delta-aminolaevulinate synthase 2 (ALAS2) enzyme activity.	Heme	97-101	5'-aminolevulinate synthase 2	Homo sapiens	130-163
23348515-2	2013	Previously, two exon 11 small deletions, c.1699_1670DeltaAT (DeltaAT) and c.1706_1709DeltaAGTG (DeltaAGTG), that prematurely truncated or elongated the ALAS2 polypeptide, were reported to increase enzymatic activity 20- to 40-fold, causing the erythroid accumulation of protoporphyrins, cutaneous photosensitivity and liver disease.	Protoporphyrins	270-285	5'-aminolevulinate synthase 2	Homo sapiens	152-157
23348515-9	2013	Thus, these ALAS2 gain-of-function mutations increased the specific activity (DeltaAT, DeltaAGTG and p.Q548X) or stability (DeltaG) of the enzyme, thereby leading to the increased erythroid protoporphyrin accumulation causing XLP.	erythroid protoporphyrin	180-204	5'-aminolevulinate synthase 2	Homo sapiens	12-17
24135682-1	2013	X-linked dominant protoporphyria (XLDPP) is a genetic disorder that affects the synthesis of the heme group due to an increase in delta-aminolaevulinate synthase 2 (ALAS2) enzyme activity.	Heme	97-101	5'-aminolevulinate synthase 2	Homo sapiens	165-170
24135682-4	2013	Protoporphyrin levels in serum and feces were significantly elevated and a heterozygous frameshift mutation in the exon 11 of the ALAS2 gene: c.1706-1709del (p.Glu569GlyfsX24) was identified.	protoporphyrin IX	0-14	5'-aminolevulinate synthase 2	Homo sapiens	130-135
21750082-6	2011	In agreement with these observations in beta-thalassemic cells we found decreased heme levels related to significantly reduced activity of the first enzyme of the heme pathway, delta-aminolevulinate synthase-2 without differences in its expression.	Heme	82-86	5'-aminolevulinate synthase 2	Homo sapiens	177-209
22740690-6	2012	In contrast, vitamin B6-responsive XLSA mutations p.Arg452Cys and p.Arg452His, with normal in vitro enzyme activity and stability, did not interfere with binding to SUCLA2 but instead had loss of positive cooperativity for succinyl-CoA binding, an increased K(m) for succinyl-CoA, and reduced vitamin B6 affinity.	Vitamin B 6	13-23	5'-aminolevulinate synthase 2	Homo sapiens	35-39
22740690-6	2012	In contrast, vitamin B6-responsive XLSA mutations p.Arg452Cys and p.Arg452His, with normal in vitro enzyme activity and stability, did not interfere with binding to SUCLA2 but instead had loss of positive cooperativity for succinyl-CoA binding, an increased K(m) for succinyl-CoA, and reduced vitamin B6 affinity.	succinyl-coenzyme A	223-235	5'-aminolevulinate synthase 2	Homo sapiens	35-39
22740690-6	2012	In contrast, vitamin B6-responsive XLSA mutations p.Arg452Cys and p.Arg452His, with normal in vitro enzyme activity and stability, did not interfere with binding to SUCLA2 but instead had loss of positive cooperativity for succinyl-CoA binding, an increased K(m) for succinyl-CoA, and reduced vitamin B6 affinity.	succinyl-coenzyme A	267-279	5'-aminolevulinate synthase 2	Homo sapiens	35-39
22740690-6	2012	In contrast, vitamin B6-responsive XLSA mutations p.Arg452Cys and p.Arg452His, with normal in vitro enzyme activity and stability, did not interfere with binding to SUCLA2 but instead had loss of positive cooperativity for succinyl-CoA binding, an increased K(m) for succinyl-CoA, and reduced vitamin B6 affinity.	Vitamin B 6	293-303	5'-aminolevulinate synthase 2	Homo sapiens	35-39
22876010-9	2012	RESULTS: In the ASB group, saline showed statistically higher bond strength values at the different concentrations of EDTA, while the micro-tensile bond strengths of the different concentrations of EDTA were not statistically different.	Sodium Chloride	27-33	5'-aminolevulinate synthase 2	Homo sapiens	16-19
22876010-9	2012	RESULTS: In the ASB group, saline showed statistically higher bond strength values at the different concentrations of EDTA, while the micro-tensile bond strengths of the different concentrations of EDTA were not statistically different.	Edetic Acid	118-122	5'-aminolevulinate synthase 2	Homo sapiens	16-19
21750082-6	2011	In agreement with these observations in beta-thalassemic cells we found decreased heme levels related to significantly reduced activity of the first enzyme of the heme pathway, delta-aminolevulinate synthase-2 without differences in its expression.	Heme	163-167	5'-aminolevulinate synthase 2	Homo sapiens	177-209
21750082-7	2011	We demonstrated that the activity of recombinant delta-aminolevulinate synthase-2 is inhibited by both reactive oxygen species and hemin as a protective mechanism in beta-thalassemic cells.	Reactive Oxygen Species	103-126	5'-aminolevulinate synthase 2	Homo sapiens	49-81
21750082-7	2011	We demonstrated that the activity of recombinant delta-aminolevulinate synthase-2 is inhibited by both reactive oxygen species and hemin as a protective mechanism in beta-thalassemic cells.	Hemin	131-136	5'-aminolevulinate synthase 2	Homo sapiens	49-81
21627978-4	2011	MATERIALS AND METHODS: Four patients had a deletion in ALAS2 that causes enzyme gain-of-function, resulting in increased formation of protoporphyrin; one had a heterozygous major deletion in FECH DNA.	protoporphyrin IX	134-148	5'-aminolevulinate synthase 2	Homo sapiens	55-60
21653323-3	2011	The discovery of a new type of erythroid porphyria, X-linked dominant protoporphyria (XLDPP), which results from increased activity of 5-aminolevulinate synthase 2 (ALAS2), the rate-controlling enzyme of erythroid heme synthesis, led us to hypothesize that the CEP phenotype may be modulated by sequence variations in the ALAS2 gene.	Heme	214-218	5'-aminolevulinate synthase 2	Homo sapiens	135-163
21653323-3	2011	The discovery of a new type of erythroid porphyria, X-linked dominant protoporphyria (XLDPP), which results from increased activity of 5-aminolevulinate synthase 2 (ALAS2), the rate-controlling enzyme of erythroid heme synthesis, led us to hypothesize that the CEP phenotype may be modulated by sequence variations in the ALAS2 gene.	Heme	214-218	5'-aminolevulinate synthase 2	Homo sapiens	165-170
21653323-7	2011	The rate of 5-aminolevulinate release from Y586F was significantly increased over that of wild-type ALAS2.	Aminolevulinic Acid	12-29	5'-aminolevulinate synthase 2	Homo sapiens	100-105
21348241-9	2010	The most common inherited sideroblastic anemia is X-linked sideroblastic anemia (XLSA) caused by mutations of the erythroid-specific delta-aminolevulinate synthase gene (ALAS2), which is the first enzyme involved in heme biosynthesis in erythroid cells.	Heme	216-220	5'-aminolevulinate synthase 2	Homo sapiens	170-175
21388451-1	2011	Pyridoxine, or vitamin B6, is commonly used to treat acquired idiopathic sideroblastic anaemia (AISA, including refractory anaemia with ring sideroblasts), but the efficacy of this therapy in an unselected AISA population (i.e. patients without confirmed ALAS2 or other pyridoxine-responsive germline mutations) has not been established.	Pyridoxine	0-10	5'-aminolevulinate synthase 2	Homo sapiens	255-260
21388451-1	2011	Pyridoxine, or vitamin B6, is commonly used to treat acquired idiopathic sideroblastic anaemia (AISA, including refractory anaemia with ring sideroblasts), but the efficacy of this therapy in an unselected AISA population (i.e. patients without confirmed ALAS2 or other pyridoxine-responsive germline mutations) has not been established.	Vitamin B 6	15-25	5'-aminolevulinate synthase 2	Homo sapiens	255-260
21252495-2	2011	The most common form is X-linked SA, which results from mutations in erythroid-specific delta-aminolevulinate synthase (ALAS2), the first enzyme in heme biosynthesis.	Heme	148-152	5'-aminolevulinate synthase 2	Homo sapiens	120-125
21252495-7	2011	A novel K156E substitution in ALAS2 was discovered in 1 pyridoxine-responsive patient.	Pyridoxine	56-66	5'-aminolevulinate synthase 2	Homo sapiens	30-35
21252495-10	2011	CONCLUSION: Our report extends the list of known ALAS2 mutations, with the addition of a novel K156E substitution that is responsive to pyridoxine treatment and contributes to the general knowledge of congenital SA cases characterized worldwide.	Pyridoxine	136-146	5'-aminolevulinate synthase 2	Homo sapiens	49-54
20848343-5	2010	The most common inherited sideroblastic anemia is X-linked sideroblastic anemia (XLSA) caused by mutations of the erythroid-specific delta-aminolevulinate synthase gene (ALAS2), which is the first enzyme of heme biosynthesis in erythroid cells.	Heme	207-211	5'-aminolevulinate synthase 2	Homo sapiens	170-175
20850938-11	2010	Finally, about 4% of unrelated EPP patients have X-linked dominant protoporphyria (XLDPP) (MIM 300752) caused by gain-of-function mutations in the ALAS2 gene leading to an increased erythroid heme biosynthesis and subsequently an accumulation of protoporphyrin without any FECH deficiency.	Heme	192-196	5'-aminolevulinate synthase 2	Homo sapiens	147-152
20850938-11	2010	Finally, about 4% of unrelated EPP patients have X-linked dominant protoporphyria (XLDPP) (MIM 300752) caused by gain-of-function mutations in the ALAS2 gene leading to an increased erythroid heme biosynthesis and subsequently an accumulation of protoporphyrin without any FECH deficiency.	protoporphyrin IX	246-260	5'-aminolevulinate synthase 2	Homo sapiens	147-152
18637800-2	2008	The most frequent form is X-linked sideroblastic anaemia, caused by mutations of delta-aminolevulinic acid synthase 2 (ALAS2), the enzyme that catalyses the first and regulatory step of haem synthesis in erythroid precursors and is post-transcriptionally controlled by the iron regulatory proteins.	Iron	273-277	5'-aminolevulinate synthase 2	Homo sapiens	81-117
19786205-3	2009	The most common X-linked sideroblastic anemia (XLSA), due to mutations of the first enzyme of the heme synthetic pathway, delta-aminolevulinic acid synthase 2 (ALAS2), has linked heme deficiency to mitochondrial iron accumulation.	Heme	98-102	5'-aminolevulinate synthase 2	Homo sapiens	122-158
19786205-3	2009	The most common X-linked sideroblastic anemia (XLSA), due to mutations of the first enzyme of the heme synthetic pathway, delta-aminolevulinic acid synthase 2 (ALAS2), has linked heme deficiency to mitochondrial iron accumulation.	Heme	98-102	5'-aminolevulinate synthase 2	Homo sapiens	160-165
19786205-3	2009	The most common X-linked sideroblastic anemia (XLSA), due to mutations of the first enzyme of the heme synthetic pathway, delta-aminolevulinic acid synthase 2 (ALAS2), has linked heme deficiency to mitochondrial iron accumulation.	Iron	212-216	5'-aminolevulinate synthase 2	Homo sapiens	122-158
19786205-3	2009	The most common X-linked sideroblastic anemia (XLSA), due to mutations of the first enzyme of the heme synthetic pathway, delta-aminolevulinic acid synthase 2 (ALAS2), has linked heme deficiency to mitochondrial iron accumulation.	Iron	212-216	5'-aminolevulinate synthase 2	Homo sapiens	160-165
18823803-4	2009	Genetic analyses identified a novel mutation in the iron responsive element of the ALAS2 gene.	Iron	52-56	5'-aminolevulinate synthase 2	Homo sapiens	83-88
18823803-6	2009	We suggest that the ALAS2 mutation together with chronic hepatitis C infection may have caused the severe iron overload phenotype.	Iron	106-110	5'-aminolevulinate synthase 2	Homo sapiens	20-25
18637800-2	2008	The most frequent form is X-linked sideroblastic anaemia, caused by mutations of delta-aminolevulinic acid synthase 2 (ALAS2), the enzyme that catalyses the first and regulatory step of haem synthesis in erythroid precursors and is post-transcriptionally controlled by the iron regulatory proteins.	Iron	273-277	5'-aminolevulinate synthase 2	Homo sapiens	119-124
18555711-2	2008	In this study, we investigated the mechanisms involved in NaBu-induced activation of erythroid-specific 5-aminolevulinate synthase gene (ALAS2).	sethoxydim	58-62	5'-aminolevulinate synthase 2	Homo sapiens	137-142
18555711-3	2008	We showed that NaBu upregulated ALAS2 gene transcription in different cell lineages.	sethoxydim	15-19	5'-aminolevulinate synthase 2	Homo sapiens	32-37
18555711-4	2008	By using site-directed mutagenesis of putative responsive elements at ALAS2 promoter and reporter gene analysis, we identified that the Sp1 binding sites within the ALAS2 promoter were responsive to NaBu stimulation.	sethoxydim	199-203	5'-aminolevulinate synthase 2	Homo sapiens	70-75
18555711-4	2008	By using site-directed mutagenesis of putative responsive elements at ALAS2 promoter and reporter gene analysis, we identified that the Sp1 binding sites within the ALAS2 promoter were responsive to NaBu stimulation.	sethoxydim	199-203	5'-aminolevulinate synthase 2	Homo sapiens	165-170
18555711-5	2008	Results from the chromatin immunoprecipitation (ChIP) assays indicated that upon the NaBu stimulation, binding of Sp1 protein to ALAS2 promoter increased significantly, with concurrent increases in acetylation level of histone H3 and dimethylation level of H3-Lysine4 at ALAS2 promoter.	sethoxydim	85-89	5'-aminolevulinate synthase 2	Homo sapiens	129-134
18555711-5	2008	Results from the chromatin immunoprecipitation (ChIP) assays indicated that upon the NaBu stimulation, binding of Sp1 protein to ALAS2 promoter increased significantly, with concurrent increases in acetylation level of histone H3 and dimethylation level of H3-Lysine4 at ALAS2 promoter.	sethoxydim	85-89	5'-aminolevulinate synthase 2	Homo sapiens	271-276
17768398-6	2007	RT-PCR analysis reveals that N-CoR is required for induction by Ara-C of 5-aminolevulinate synthase (ALA-S2), a key enzyme involved in heme biosynthesis.	Cytarabine	64-69	5'-aminolevulinate synthase 2	Homo sapiens	101-107
18760763-0	2008	C-terminal deletions in the ALAS2 gene lead to gain of function and cause X-linked dominant protoporphyria without anemia or iron overload.	Iron	125-129	5'-aminolevulinate synthase 2	Homo sapiens	28-33
18760763-1	2008	All reported mutations in ALAS2, which encodes the rate-regulating enzyme of erythroid heme biosynthesis, cause X-linked sideroblastic anemia.	Heme	87-91	5'-aminolevulinate synthase 2	Homo sapiens	26-31
18669654-3	2008	We show that SNCA and the heme metabolism genes ALAS2, FECH, and BLVRB form a block of tightly correlated gene expression in 113 samples of human blood, where SNCA naturally abounds (validated P = 1.6 x 10(-11), 1.8 x 10(-10), and 6.6 x 10(-5)).	Heme	26-30	5'-aminolevulinate synthase 2	Homo sapiens	48-53
19066423-0	2008	Multi-organ iron overload in an African-American man with ALAS2 R452S and SLC40A1 R561G.	Iron	12-16	5'-aminolevulinate synthase 2	Homo sapiens	58-63
19066423-1	2008	BACKGROUND: X-linked sideroblastic anemia (XLSA) is associated with iron overload and mutations in ALAS2, which encodes 5-aminolevulinate synthase.	Iron	68-72	5'-aminolevulinate synthase 2	Homo sapiens	12-41
19066423-1	2008	BACKGROUND: X-linked sideroblastic anemia (XLSA) is associated with iron overload and mutations in ALAS2, which encodes 5-aminolevulinate synthase.	Iron	68-72	5'-aminolevulinate synthase 2	Homo sapiens	43-47
19066423-10	2008	CONCLUSIONS: ALAS2 R452S largely explains this patient"s microcytic anemia and multi-organ iron overload and dysfunction.	Iron	91-95	5'-aminolevulinate synthase 2	Homo sapiens	13-18
17768398-6	2007	RT-PCR analysis reveals that N-CoR is required for induction by Ara-C of 5-aminolevulinate synthase (ALA-S2), a key enzyme involved in heme biosynthesis.	Heme	135-139	5'-aminolevulinate synthase 2	Homo sapiens	101-107
16935983-0	2006	A novel mutation, Ile289Thr, in the ALAS2 gene in a family with pyridoxine responsive sideroblastic anaemia.	ile289thr	18-27	5'-aminolevulinate synthase 2	Homo sapiens	36-41
17485548-8	2007	Based on the biochemical and clinical phenotype, we hypothesize that IRP2, less degraded by low heme, contributes to the repression of the erythroblasts ferritin and ALAS2, increasing mitochondrial iron.	Heme	96-100	5'-aminolevulinate synthase 2	Homo sapiens	166-171
17192398-2	2007	Here, we show that Abcb7 is essential for hematopoiesis and formally demonstrate that XLSA/A is due to partial loss of function mutations in Abcb7 that directly or indirectly inhibit heme biosynthesis.	Heme	183-187	5'-aminolevulinate synthase 2	Homo sapiens	86-90
16904069-1	2006	Erythroid-specific 5-aminolevulinate synthase (ALAS2) catalyzes the rate-limiting step in heme biosynthesis of erythroid cells.	Heme	90-94	5'-aminolevulinate synthase 2	Homo sapiens	47-52
16904069-2	2006	Here, we show that treatment of erythroid K562 cells with HDAC inhibitors sodium butyrate or Trichostatin A gave rise to a significant increase in ALAS2 gene transcripts, with a concurrent increase in acetylation level of histone H4 at the ALAS2 gene promoter.	Butyric Acid	74-89	5'-aminolevulinate synthase 2	Homo sapiens	147-152
16904069-2	2006	Here, we show that treatment of erythroid K562 cells with HDAC inhibitors sodium butyrate or Trichostatin A gave rise to a significant increase in ALAS2 gene transcripts, with a concurrent increase in acetylation level of histone H4 at the ALAS2 gene promoter.	Butyric Acid	74-89	5'-aminolevulinate synthase 2	Homo sapiens	240-245
16904069-2	2006	Here, we show that treatment of erythroid K562 cells with HDAC inhibitors sodium butyrate or Trichostatin A gave rise to a significant increase in ALAS2 gene transcripts, with a concurrent increase in acetylation level of histone H4 at the ALAS2 gene promoter.	trichostatin A	93-107	5'-aminolevulinate synthase 2	Homo sapiens	147-152
16904069-2	2006	Here, we show that treatment of erythroid K562 cells with HDAC inhibitors sodium butyrate or Trichostatin A gave rise to a significant increase in ALAS2 gene transcripts, with a concurrent increase in acetylation level of histone H4 at the ALAS2 gene promoter.	trichostatin A	93-107	5'-aminolevulinate synthase 2	Homo sapiens	240-245
16935983-0	2006	A novel mutation, Ile289Thr, in the ALAS2 gene in a family with pyridoxine responsive sideroblastic anaemia.	Pyridoxine	64-74	5'-aminolevulinate synthase 2	Homo sapiens	36-41
15498136-3	2004	The full length cDNA of ALAS2 gene was inserted into plasmid pDs-red2-N1, named pDs-red2-N1/ALAS2.	Palladium	61-64	5'-aminolevulinate synthase 2	Homo sapiens	24-29
16540354-0	2006	Disparate phenotypic expression of ALAS2 R452H (nt 1407 G --> A) in two brothers, one with severe sideroblastic anemia and iron overload, hepatic cirrhosis, and hepatocellular carcinoma.	Iron	126-130	5'-aminolevulinate synthase 2	Homo sapiens	35-40
16540354-3	2006	The proband"s brother, an ALAS2 R452H hemizygote, had mild anemia and mild iron overload.	Iron	75-79	5'-aminolevulinate synthase 2	Homo sapiens	26-31
16446107-1	2006	Mutations in aminolevulinate synthase 2 (ALAS2) are usually associated with sideroblastic anemia and iron overload.	Iron	101-105	5'-aminolevulinate synthase 2	Homo sapiens	41-46
16446107-2	2006	The objective of this study was to determine if "mild" mutations in ALAS2 might increase the severity of primary iron overload.	Iron	113-117	5'-aminolevulinate synthase 2	Homo sapiens	68-73
16446107-3	2006	Direct sequencing of the ALAS2 gene was performed on 24 subjects with primary hemochromatosis and one subject with sideroblastic anemia with severe iron overload.	Iron	148-152	5'-aminolevulinate synthase 2	Homo sapiens	25-30
16446107-10	2006	Thus, ALAS2 mutations might contribute to more severe iron loading in persons with primary hemochromatosis.	Iron	54-58	5'-aminolevulinate synthase 2	Homo sapiens	6-11
16343269-2	2006	An amino acid (AA) substitution for arginine at the 452 AA position of the ALAS2 protein is the most frequent mutation, which has been found in approximately one-quarter of patients with XLSA.	Arginine	36-44	5'-aminolevulinate synthase 2	Homo sapiens	75-80
16234850-5	2005	ALAS2 is expressed exclusively in erythroid cells and synthesizes heme specifically for haemoglobin.	Heme	66-70	5'-aminolevulinate synthase 2	Homo sapiens	0-5
16234850-6	2005	A database search for proteins potentially regulated by oxygen tension revealed that ALAS2 contained a sequence of amino acids (LXXLAP where L is leucine, X is any amino acid, A is alanine, and P is proline) not occurring in ALAS1, which may be hydroxylated under normoxic conditions (21% O2) and target the enzyme for ubiquitination and degradation by the proteasome.	Oxygen	56-62	5'-aminolevulinate synthase 2	Homo sapiens	85-90
16234850-6	2005	A database search for proteins potentially regulated by oxygen tension revealed that ALAS2 contained a sequence of amino acids (LXXLAP where L is leucine, X is any amino acid, A is alanine, and P is proline) not occurring in ALAS1, which may be hydroxylated under normoxic conditions (21% O2) and target the enzyme for ubiquitination and degradation by the proteasome.	Leucine	146-153	5'-aminolevulinate synthase 2	Homo sapiens	85-90
16234850-6	2005	A database search for proteins potentially regulated by oxygen tension revealed that ALAS2 contained a sequence of amino acids (LXXLAP where L is leucine, X is any amino acid, A is alanine, and P is proline) not occurring in ALAS1, which may be hydroxylated under normoxic conditions (21% O2) and target the enzyme for ubiquitination and degradation by the proteasome.	Alanine	181-188	5'-aminolevulinate synthase 2	Homo sapiens	85-90
16234850-6	2005	A database search for proteins potentially regulated by oxygen tension revealed that ALAS2 contained a sequence of amino acids (LXXLAP where L is leucine, X is any amino acid, A is alanine, and P is proline) not occurring in ALAS1, which may be hydroxylated under normoxic conditions (21% O2) and target the enzyme for ubiquitination and degradation by the proteasome.	Proline	199-206	5'-aminolevulinate synthase 2	Homo sapiens	85-90
16234850-6	2005	A database search for proteins potentially regulated by oxygen tension revealed that ALAS2 contained a sequence of amino acids (LXXLAP where L is leucine, X is any amino acid, A is alanine, and P is proline) not occurring in ALAS1, which may be hydroxylated under normoxic conditions (21% O2) and target the enzyme for ubiquitination and degradation by the proteasome.	Oxygen	289-291	5'-aminolevulinate synthase 2	Homo sapiens	85-90
16234850-7	2005	We examined protein turnover of ALAS2 in the presence of cycloheximide in K562 cells.	Cycloheximide	57-70	5'-aminolevulinate synthase 2	Homo sapiens	32-37
16234850-8	2005	Normoxic ALAS2 had a turnover time of approximately 36 h. Hypoxia (1% O2) and inhibition of the proteasome increased both the stability and the specific activity of ALAS2 (greater than 2- and 7-fold, respectively, over 72 h of treatment).	Oxygen	70-72	5'-aminolevulinate synthase 2	Homo sapiens	9-14
16234850-8	2005	Normoxic ALAS2 had a turnover time of approximately 36 h. Hypoxia (1% O2) and inhibition of the proteasome increased both the stability and the specific activity of ALAS2 (greater than 2- and 7-fold, respectively, over 72 h of treatment).	Oxygen	70-72	5'-aminolevulinate synthase 2	Homo sapiens	165-170
16234850-9	2005	Mutation of a key proline within the LXXLAP sequence of ALAS2 also stabilized the protein beyond 36 h under normoxic conditions.	Proline	18-25	5'-aminolevulinate synthase 2	Homo sapiens	56-61
15885606-0	2005	Iron overload in an African American woman with SS hemoglobinopathy and a promoter mutation in the X-linked erythroid-specific 5-aminolevulinate synthase (ALAS2) gene.	Iron	0-4	5'-aminolevulinate synthase 2	Homo sapiens	155-160
15885606-1	2005	We report the case of an African American woman with sickle cell anemia and iron overload incompletely explained by erythrocyte transfusion who is heterozygous for a promoter mutation in the X-linked erythroid-specific 5-aminolevulinate synthase gene (ALAS2): a C to G transversion at nucleotide -206 from the transcription start site, as defined by primer extension (-258 from the start ATG).	Iron	76-80	5'-aminolevulinate synthase 2	Homo sapiens	252-257
15885606-6	2005	We conclude that an ALAS2 promoter region mutation could partly account for iron overload in the present proband, and that this or other ALAS2 mutations could explain the occurrence of iron overload in other whites or blacks with or without anemia.	Iron	76-80	5'-aminolevulinate synthase 2	Homo sapiens	20-25
15885606-6	2005	We conclude that an ALAS2 promoter region mutation could partly account for iron overload in the present proband, and that this or other ALAS2 mutations could explain the occurrence of iron overload in other whites or blacks with or without anemia.	Iron	185-189	5'-aminolevulinate synthase 2	Homo sapiens	137-142
15885606-7	2005	The occurrence of anemia and iron overload may be discordant in women heterozygous for ALAS2 mutations.	Iron	29-33	5'-aminolevulinate synthase 2	Homo sapiens	87-92
15498136-3	2004	The full length cDNA of ALAS2 gene was inserted into plasmid pDs-red2-N1, named pDs-red2-N1/ALAS2.	Palladium	61-64	5'-aminolevulinate synthase 2	Homo sapiens	92-97
15498136-3	2004	The full length cDNA of ALAS2 gene was inserted into plasmid pDs-red2-N1, named pDs-red2-N1/ALAS2.	Palladium	80-83	5'-aminolevulinate synthase 2	Homo sapiens	24-29
15498136-3	2004	The full length cDNA of ALAS2 gene was inserted into plasmid pDs-red2-N1, named pDs-red2-N1/ALAS2.	Palladium	80-83	5'-aminolevulinate synthase 2	Homo sapiens	92-97
15498136-8	2004	The result showed that after the pDs-red2-N1/ALAS2 eukaryotic expression vector was digested by KpnI and BamHI, two fragments of 4 700 bp and 1 764 bp were displayed by electrophoresis on agarose gel.	Sepharose	188-195	5'-aminolevulinate synthase 2	Homo sapiens	45-50
14643893-0	2004	The major splice variant of human 5-aminolevulinate synthase-2 contributes significantly to erythroid heme biosynthesis.	erythroid heme	92-106	5'-aminolevulinate synthase 2	Homo sapiens	34-62
14643893-1	2004	The initial step of the heme biosynthetic pathway in erythroid cells is catalyzed by an erythroid-specific isoform of 5-aminolevulinate synthase-2 (ALAS2).	Heme	24-28	5'-aminolevulinate synthase 2	Homo sapiens	118-146
14643893-1	2004	The initial step of the heme biosynthetic pathway in erythroid cells is catalyzed by an erythroid-specific isoform of 5-aminolevulinate synthase-2 (ALAS2).	Heme	24-28	5'-aminolevulinate synthase 2	Homo sapiens	148-153
14643893-3	2004	We sought to characterize the contribution of this ALAS2 isoform to overall erythroid heme biosynthesis.	erythroid heme	76-90	5'-aminolevulinate synthase 2	Homo sapiens	51-56
14643893-7	2004	In contrast, in vitro studies show that the major splice variant (lacking exon 4-encoded sequence) produces a functional enzyme, albeit with slightly reduced activity and with affinity for the ATP-specific, beta subunit of succinyl CoA synthase, comparable to that of mature ALAS2.	Adenosine Triphosphate	193-196	5'-aminolevulinate synthase 2	Homo sapiens	275-280
14643893-9	2004	We conclude that the major splice isoform of ALAS2 is functional in vivo and could significantly contribute to erythroid heme biosynthesis and hemoglobin formation.	erythroid heme	111-125	5'-aminolevulinate synthase 2	Homo sapiens	45-50
12031592-7	2002	CONCLUSIONS: We identified a missense mutation in exon 5 of the ALAS2 gene in two brothers of a consanguineous marriage, who were clinically pyridoxine-responsive.	Pyridoxine	141-151	5'-aminolevulinate synthase 2	Homo sapiens	64-69
12531813-5	2003	In vitro analyses of recombinant Asp159Asn ALAS2 revealed that this mutation accounted for the pyridoxine-responsiveness of this disease.	Pyridoxine	95-105	5'-aminolevulinate synthase 2	Homo sapiens	43-48
12393745-1	2003	The erythroid-specific isoform of 5-aminolevulinate synthase (ALAS2) catalyzes the rate-limiting step in heme biosynthesis.	Heme	105-109	5'-aminolevulinate synthase 2	Homo sapiens	62-67
12393718-1	2002	X-linked sideroblastic anemia (XLSA) is caused by mutations in the erythroid-specific 5-aminolevulinic acid synthase (ALAS2) gene.	5-amino levulinic acid	86-107	5'-aminolevulinate synthase 2	Homo sapiens	118-123
12382202-3	2002	Initially, mutations in ALAS2 in X-linked sideroblastic anemia (XLSA) focused attention on the heme biosynthetic pathway as a primary cause of sideroblastic anemia.	Heme	95-99	5'-aminolevulinate synthase 2	Homo sapiens	24-29
12243984-2	2002	It does this via iron regulatory proteins (IRPs) which bind reversibly to the iron responsive elements (IREs) on the mRNA of transferrin receptor (TfR), erythroid 5-aminolaevulinic acid synthase (ALA-S2) and ferritin.	Iron	17-21	5'-aminolevulinate synthase 2	Homo sapiens	196-202
12243984-2	2002	It does this via iron regulatory proteins (IRPs) which bind reversibly to the iron responsive elements (IREs) on the mRNA of transferrin receptor (TfR), erythroid 5-aminolaevulinic acid synthase (ALA-S2) and ferritin.	Iron	78-82	5'-aminolevulinate synthase 2	Homo sapiens	196-202
11202048-14	2000	In the absence of iron, to be incorporated in the porphyrin formed in the last step of the synthesis, the mRNA of erythroid 5-aminolevulinate synthase (ALAS-2) is blocked by attachment of an iron-responsive element (IRE) binding cytosolic protein, and transcription of this key enzyme is inhibited.	Iron	18-22	5'-aminolevulinate synthase 2	Homo sapiens	152-158
11929048-2	2002	It has been shown that a deficiency of the erythroid-specific delta-aminolevulinate synthase (ALAS-E) activity is responsible for pyridoxine-responsive HSA in many patients, however, the pathogenesis of other types of HSA remains still unknown.	Pyridoxine	130-140	5'-aminolevulinate synthase 2	Homo sapiens	94-100
11566180-5	2001	In this study, we screened the specific genes expressed in the course of differentiation of HL-60 cells, and demonstrated that ASB-2, one of the ASB proteins, was rapidly induced by all-trans retinoic acid (ATRA).	Tretinoin	192-205	5'-aminolevulinate synthase 2	Homo sapiens	127-130
11566180-5	2001	In this study, we screened the specific genes expressed in the course of differentiation of HL-60 cells, and demonstrated that ASB-2, one of the ASB proteins, was rapidly induced by all-trans retinoic acid (ATRA).	Tretinoin	207-211	5'-aminolevulinate synthase 2	Homo sapiens	127-130
11110715-1	2000	X-linked sideroblastic anemia (XLSA) is caused by mutations in the erythroid-specific 5-aminolevulinic acid synthase (ALAS2) gene.	5-amino levulinic acid	86-107	5'-aminolevulinate synthase 2	Homo sapiens	118-123
11202048-14	2000	In the absence of iron, to be incorporated in the porphyrin formed in the last step of the synthesis, the mRNA of erythroid 5-aminolevulinate synthase (ALAS-2) is blocked by attachment of an iron-responsive element (IRE) binding cytosolic protein, and transcription of this key enzyme is inhibited.	Iron	191-195	5'-aminolevulinate synthase 2	Homo sapiens	152-158
11877024-5	2000	The mutation in the patients" ALAS2 gene was exon 5 A523G, causing threonine to alanine; and exon 3 T372C, leucine to proline.	Threonine	67-76	5'-aminolevulinate synthase 2	Homo sapiens	30-35
11877024-5	2000	The mutation in the patients" ALAS2 gene was exon 5 A523G, causing threonine to alanine; and exon 3 T372C, leucine to proline.	Alanine	80-87	5'-aminolevulinate synthase 2	Homo sapiens	30-35
11877024-5	2000	The mutation in the patients" ALAS2 gene was exon 5 A523G, causing threonine to alanine; and exon 3 T372C, leucine to proline.	Leucine	107-114	5'-aminolevulinate synthase 2	Homo sapiens	30-35
11877024-5	2000	The mutation in the patients" ALAS2 gene was exon 5 A523G, causing threonine to alanine; and exon 3 T372C, leucine to proline.	Proline	118-125	5'-aminolevulinate synthase 2	Homo sapiens	30-35
10522552-7	1999	Because the 5"-untranslated region of the erythroid-specific ALA-S2 mRNA contains the iron-responsive element, a cis-acting sequence responsible for translational induction of erythroid ALA-S2 by iron, the availability of iron controls protoporphyrin IX levels in hemoglobin-synthesizing cells.	Iron	86-90	5'-aminolevulinate synthase 2	Homo sapiens	61-67
11039663-1	2000	Erythroid 5-aminolevulinate synthase (ALAS-E) catalyzes the first step of heme biosynthesis in erythroid cells.	Heme	74-78	5'-aminolevulinate synthase 2	Homo sapiens	38-44
11039663-2	2000	Several lines of evidence suggest that the expression of ALAS-E is important for the process of erythroid differentiation, which requires a large amount of heme for hemoglobin production.	Heme	156-160	5'-aminolevulinate synthase 2	Homo sapiens	57-63
11039663-10	2000	These observations suggest that the mode of iron accumulation caused by the lack of ALAS-E is different in primitive and definitive erythroid cells.	Iron	44-48	5'-aminolevulinate synthase 2	Homo sapiens	84-90
11039663-11	2000	Thus ALAS-E, and hence heme supply, is necessary for erythroid cell differentiation and iron metabolism.	Iron	88-92	5'-aminolevulinate synthase 2	Homo sapiens	5-11
10727444-0	2000	Interaction between succinyl CoA synthetase and the heme-biosynthetic enzyme ALAS-E is disrupted in sideroblastic anemia.	Heme	52-56	5'-aminolevulinate synthase 2	Homo sapiens	77-83
10727444-7	2000	Because the D190V mutant was identified in a patient with pyridoxine-refractory X-linked sideroblastic anemia, our findings suggest that appropriate association of SCS-betaA and ALAS-E promotes efficient use of succinyl CoA by ALAS-E or helps translocate ALAS-E into mitochondria.	Pyridoxine	58-68	5'-aminolevulinate synthase 2	Homo sapiens	178-184
10727444-7	2000	Because the D190V mutant was identified in a patient with pyridoxine-refractory X-linked sideroblastic anemia, our findings suggest that appropriate association of SCS-betaA and ALAS-E promotes efficient use of succinyl CoA by ALAS-E or helps translocate ALAS-E into mitochondria.	Pyridoxine	58-68	5'-aminolevulinate synthase 2	Homo sapiens	227-233
10727444-7	2000	Because the D190V mutant was identified in a patient with pyridoxine-refractory X-linked sideroblastic anemia, our findings suggest that appropriate association of SCS-betaA and ALAS-E promotes efficient use of succinyl CoA by ALAS-E or helps translocate ALAS-E into mitochondria.	Pyridoxine	58-68	5'-aminolevulinate synthase 2	Homo sapiens	227-233
10727444-7	2000	Because the D190V mutant was identified in a patient with pyridoxine-refractory X-linked sideroblastic anemia, our findings suggest that appropriate association of SCS-betaA and ALAS-E promotes efficient use of succinyl CoA by ALAS-E or helps translocate ALAS-E into mitochondria.	succinyl-coenzyme A	211-223	5'-aminolevulinate synthase 2	Homo sapiens	178-184
10727444-7	2000	Because the D190V mutant was identified in a patient with pyridoxine-refractory X-linked sideroblastic anemia, our findings suggest that appropriate association of SCS-betaA and ALAS-E promotes efficient use of succinyl CoA by ALAS-E or helps translocate ALAS-E into mitochondria.	succinyl-coenzyme A	211-223	5'-aminolevulinate synthase 2	Homo sapiens	227-233
10727444-7	2000	Because the D190V mutant was identified in a patient with pyridoxine-refractory X-linked sideroblastic anemia, our findings suggest that appropriate association of SCS-betaA and ALAS-E promotes efficient use of succinyl CoA by ALAS-E or helps translocate ALAS-E into mitochondria.	succinyl-coenzyme A	211-223	5'-aminolevulinate synthase 2	Homo sapiens	227-233
10522552-7	1999	Because the 5"-untranslated region of the erythroid-specific ALA-S2 mRNA contains the iron-responsive element, a cis-acting sequence responsible for translational induction of erythroid ALA-S2 by iron, the availability of iron controls protoporphyrin IX levels in hemoglobin-synthesizing cells.	Iron	196-200	5'-aminolevulinate synthase 2	Homo sapiens	61-67
10522552-7	1999	Because the 5"-untranslated region of the erythroid-specific ALA-S2 mRNA contains the iron-responsive element, a cis-acting sequence responsible for translational induction of erythroid ALA-S2 by iron, the availability of iron controls protoporphyrin IX levels in hemoglobin-synthesizing cells.	Iron	196-200	5'-aminolevulinate synthase 2	Homo sapiens	61-67
10522552-7	1999	Because the 5"-untranslated region of the erythroid-specific ALA-S2 mRNA contains the iron-responsive element, a cis-acting sequence responsible for translational induction of erythroid ALA-S2 by iron, the availability of iron controls protoporphyrin IX levels in hemoglobin-synthesizing cells.	protoporphyrin IX	236-253	5'-aminolevulinate synthase 2	Homo sapiens	61-67
10577279-1	1999	A novel missense mutation, G663A, in exon 5 of the erythroid-specific delta-aminolevulinate synthase gene (ALAS2) was identified in a Japanese male with pyridoxine-responsive sideroblastic anemia.	Pyridoxine	153-163	5'-aminolevulinate synthase 2	Homo sapiens	107-112
10582344-3	1999	The key rate-controlling enzyme of the heme biosynthetic pathway is 5-aminolevulinate synthase (ALAS) and an erythroid-specific isoform (ALAS2) is up-regulated during erythropoiesis.	Heme	39-43	5'-aminolevulinate synthase 2	Homo sapiens	137-142
10582344-7	1999	Subsequent translation of the ALAS2 mRNA is dependent on an adequate iron supply.	Iron	69-73	5'-aminolevulinate synthase 2	Homo sapiens	30-35
10029606-0	1999	Four new mutations in the erythroid-specific 5-aminolevulinate synthase (ALAS2) gene causing X-linked sideroblastic anemia: increased pyridoxine responsiveness after removal of iron overload by phlebotomy and coinheritance of hereditary hemochromatosis.	Pyridoxine	134-144	5'-aminolevulinate synthase 2	Homo sapiens	73-78
10029606-0	1999	Four new mutations in the erythroid-specific 5-aminolevulinate synthase (ALAS2) gene causing X-linked sideroblastic anemia: increased pyridoxine responsiveness after removal of iron overload by phlebotomy and coinheritance of hereditary hemochromatosis.	Iron	177-181	5'-aminolevulinate synthase 2	Homo sapiens	73-78
9858242-0	1998	R411C mutation of the ALAS2 gene encodes a pyridoxine-responsive enzyme with low activity.	Pyridoxine	43-53	5'-aminolevulinate synthase 2	Homo sapiens	22-27
9858242-1	1998	A R411C missense mutation of the erythroid-specific delta-aminolaevulinate synthase (ALAS2) gene was identified in a pedigree with X-linked pyridoxine-responsive sideroblastic anaemia (XLSA).	Pyridoxine	140-150	5'-aminolevulinate synthase 2	Homo sapiens	85-90
9526800-2	1997	delta-Aminolevulinate synthase (ALAS) plays the key role to regulate heme biosynthesis in hepatocytes as well as in erythroid cells.	Heme	69-73	5'-aminolevulinate synthase 2	Homo sapiens	32-36
9688293-1	1998	DNA sequencing of the coding region of the erythroid 5-aminolaevulinate synthase (ALAS2) cDNA from a male with pyridoxine-responsive sideroblastic anaemia revealed a missense mutation, a G561T transversion in exon 5 of the gene.	Pyridoxine	111-121	5'-aminolevulinate synthase 2	Homo sapiens	82-87
9488633-1	1998	DNA sequencing of the coding region of the erythroid 5-aminolaevulinate synthase (ALAS2) cDNA from a male with pyridoxine-responsive sideroblastic anaemia revealed a missense mutation C1622G and a closely linked polymorphism C1612A in exon 10 of the gene.	Pyridoxine	111-121	5'-aminolevulinate synthase 2	Homo sapiens	82-87
9542324-1	1998	Pyridoxine-responsive, X-linked sideroblastic anaemia (XLSA) has been shown to be caused by missense mutations in the erythroid-specific ALA synthase gene, ALAS2.	Pyridoxine	0-10	5'-aminolevulinate synthase 2	Homo sapiens	23-60
9542324-1	1998	Pyridoxine-responsive, X-linked sideroblastic anaemia (XLSA) has been shown to be caused by missense mutations in the erythroid-specific ALA synthase gene, ALAS2.	Pyridoxine	0-10	5'-aminolevulinate synthase 2	Homo sapiens	156-161
9542324-7	1998	Mutations in the same gene which affect mitochondrial processing, terminate translation prematurely, or are thought to abolish function altogether cause an XLSA that is refractory to treatment with pyridoxine.	Pyridoxine	198-208	5'-aminolevulinate synthase 2	Homo sapiens	156-160
9526800-3	1997	In the liver, nonspecific (or housekeeping) isozyme of ALAS (ALAS-N) is expressed to be regulated by its end product, heme, in a negative feedback manner.	Heme	118-122	5'-aminolevulinate synthase 2	Homo sapiens	55-59
9526800-3	1997	In the liver, nonspecific (or housekeeping) isozyme of ALAS (ALAS-N) is expressed to be regulated by its end product, heme, in a negative feedback manner.	Heme	118-122	5'-aminolevulinate synthase 2	Homo sapiens	61-65
9526800-4	1997	The way to regulate ALAS-N in the liver is suitable to supply a constant level of heme for a family of drug metabolizing enzymes, cytochrome P-450 (CYP).	Heme	82-86	5'-aminolevulinate synthase 2	Homo sapiens	20-24
9526800-6	1997	Although heme regulates ALAS-N in a negative feedback manner even in erythroid cells, ALAS-E is upregulated by induced heme concentration.	Heme	9-13	5'-aminolevulinate synthase 2	Homo sapiens	24-28
9526800-6	1997	Although heme regulates ALAS-N in a negative feedback manner even in erythroid cells, ALAS-E is upregulated by induced heme concentration.	Heme	119-123	5'-aminolevulinate synthase 2	Homo sapiens	86-92
9526800-7	1997	ALAS-N in undifferentiated erythroid cells, therefore, is suggested to produce heme for CYP, whereas heme for accumulating hemoglobin (Hb) in cells undergoing differentiation is synthesized via ALAS-E.	Heme	79-83	5'-aminolevulinate synthase 2	Homo sapiens	0-4
9526800-7	1997	ALAS-N in undifferentiated erythroid cells, therefore, is suggested to produce heme for CYP, whereas heme for accumulating hemoglobin (Hb) in cells undergoing differentiation is synthesized via ALAS-E.	Heme	101-105	5'-aminolevulinate synthase 2	Homo sapiens	0-4
9526800-7	1997	ALAS-N in undifferentiated erythroid cells, therefore, is suggested to produce heme for CYP, whereas heme for accumulating hemoglobin (Hb) in cells undergoing differentiation is synthesized via ALAS-E.	Heme	101-105	5'-aminolevulinate synthase 2	Homo sapiens	194-200
9226183-1	1997	To elucidate how pyridoxine-refractory X-linked sideroblastic anemia (XLSA) develops, we analyzed the erythroid-specific 5-aminolevulinate synthase (ALAS-E) gene of a patient with the anemia.	Pyridoxine	17-27	5'-aminolevulinate synthase 2	Homo sapiens	149-155
9226183-6	1997	These results suggest that the mutation causing pyridoxine-refractory XLSA affects the processing of the ALAS-E precursor, thus provoking instability of the ALAS-E protein.	Pyridoxine	48-58	5'-aminolevulinate synthase 2	Homo sapiens	105-111
9226183-6	1997	These results suggest that the mutation causing pyridoxine-refractory XLSA affects the processing of the ALAS-E precursor, thus provoking instability of the ALAS-E protein.	Pyridoxine	48-58	5'-aminolevulinate synthase 2	Homo sapiens	157-163
9106619-0	1997	Protein tyrosine phosphatase-dependent activation of beta-globin and delta-aminolevulinic acid synthase genes in the camptothecin-induced IW32 erythroleukemia cell differentiation.	Camptothecin	117-129	5'-aminolevulinate synthase 2	Homo sapiens	69-103
9106619-6	1997	Camptothecin-induced expression of beta-globin or ALAS-E transcript levels was inhibited in the presence of cycloheximide or vanadate.	Camptothecin	0-12	5'-aminolevulinate synthase 2	Homo sapiens	50-56
9106619-6	1997	Camptothecin-induced expression of beta-globin or ALAS-E transcript levels was inhibited in the presence of cycloheximide or vanadate.	Cycloheximide	108-121	5'-aminolevulinate synthase 2	Homo sapiens	50-56
9106619-6	1997	Camptothecin-induced expression of beta-globin or ALAS-E transcript levels was inhibited in the presence of cycloheximide or vanadate.	Vanadates	125-133	5'-aminolevulinate synthase 2	Homo sapiens	50-56
9133617-1	1997	We examined the effect of hemin, TGF-beta1 and cytosine arabinoside (Ara-C) on the levels of mRNAs for the erythroid-specific 5-aminolevulinate synthase (ALAS-E) and gamma-globin in various human myelogenous leukemia cell lines.	Cytarabine	47-67	5'-aminolevulinate synthase 2	Homo sapiens	154-160
9133617-1	1997	We examined the effect of hemin, TGF-beta1 and cytosine arabinoside (Ara-C) on the levels of mRNAs for the erythroid-specific 5-aminolevulinate synthase (ALAS-E) and gamma-globin in various human myelogenous leukemia cell lines.	Cytarabine	69-74	5'-aminolevulinate synthase 2	Homo sapiens	154-160
9020366-1	1997	The coding region of the erythroid 5-aminolaevulinate synthetase gene (ALAS2) from a large pedigree with pyridoxine-responsive X-linked hereditary sideroblastic anaemia was examined for mutations.	Pyridoxine	105-115	5'-aminolevulinate synthase 2	Homo sapiens	71-76
7560104-1	1995	Missense mutations in the erythroid delta-aminolevulinate synthase (ALAS2) gene in two pyridoxine-responsive patients initially diagnosed with acquired refractory anemia and ringed sideroblasts.	Pyridoxine	87-97	5'-aminolevulinate synthase 2	Homo sapiens	68-73
9372069-5	1996	Speculation about their causes includes disturbed intracellular iron homeostasis involving iron-responsive factors involved in the translational control of ALAS2 and in certain nuclear and mitochondrial genes important for erythroid mitochondrial metabolism.	Iron	64-68	5'-aminolevulinate synthase 2	Homo sapiens	156-161
9372069-5	1996	Speculation about their causes includes disturbed intracellular iron homeostasis involving iron-responsive factors involved in the translational control of ALAS2 and in certain nuclear and mitochondrial genes important for erythroid mitochondrial metabolism.	Iron	91-95	5'-aminolevulinate synthase 2	Homo sapiens	156-161
7560104-5	1995	We report two unrelated cases of highly pyridoxine-responsive XLSA in geriatric patients previously diagnosed with refractory anemia and ringed sideroblasts.	Pyridoxine	40-50	5'-aminolevulinate synthase 2	Homo sapiens	62-66
7560104-12	1995	This late-onset form of XLSA can be distinguished from refractory anemia and ringed sideroblasts by microcytosis, pyridoxine-responsiveness, and ALAS2 mutations.	Pyridoxine	114-124	5'-aminolevulinate synthase 2	Homo sapiens	24-28
7560104-13	1995	These findings emphasize the need to consider all elderly patients with microcytic sideroblastic anemia as candidates for XLSA, especially if pyridoxine responsiveness is demonstrated.	Pyridoxine	142-152	5'-aminolevulinate synthase 2	Homo sapiens	122-126
7592563-1	1995	The erythroid-specific isozyme of 5-aminolevulinate synthase (ALAS2), the first and rate-limiting enzyme of heme biosynthesis, is expressed concomitantly with the differentiation and maturation of the erythroid cell in order to accommodate generation of the large amounts of heme required for hemoglobin production.	Heme	108-112	5'-aminolevulinate synthase 2	Homo sapiens	62-67
7616645-2	1995	delta-Aminolevulinate synthase (ALAS) plays the key role to regulate heme biosynthesis in the liver as well as in erythroid cells.	Heme	69-73	5'-aminolevulinate synthase 2	Homo sapiens	32-36
7616645-3	1995	In the liver, nonspecific (or housekeeping) isozyme of ALAS (ALAS-N) is expressed to be regulated by its end product, heme, in the negative feedback manner.	Heme	118-122	5'-aminolevulinate synthase 2	Homo sapiens	55-59
7616645-5	1995	For example, heme regulates ALAS-N and ALAS-E in the negative and in the positive feedback manner, respectively.	Heme	13-17	5'-aminolevulinate synthase 2	Homo sapiens	39-45
7592563-1	1995	The erythroid-specific isozyme of 5-aminolevulinate synthase (ALAS2), the first and rate-limiting enzyme of heme biosynthesis, is expressed concomitantly with the differentiation and maturation of the erythroid cell in order to accommodate generation of the large amounts of heme required for hemoglobin production.	Heme	275-279	5'-aminolevulinate synthase 2	Homo sapiens	62-67
7949148-2	1994	Almost 40 years later the enzymatic defect in XLSA was identified as the deficient activity of the erythroid-specific form of delta-aminolevulinate synthase (ALAS2), the first enzyme in the heme biosynthetic pathway.	Heme	190-194	5'-aminolevulinate synthase 2	Homo sapiens	158-163
34492704-10	2021	We further show that itaconyl-CoA is a competitive inhibitor of the erythroid-specific 5-aminolevulinate synthase (ALAS2), the first and rate-limiting step in heme synthesis.	Itaconyl-CoA	21-33	5'-aminolevulinate synthase 2	Homo sapiens	115-120
1301172-1	1992	We have identified a compound dinucleotide repeat within intron 7 of the human erythroid 5-aminolevulinate synthase (ALAS2) gene with a minimum of 9 alleles and heterozygosity of 78%.	Dinucleoside Phosphates	30-42	5'-aminolevulinate synthase 2	Homo sapiens	117-122
1301172-4	1992	As ALAS2 has recently been shown to be the defective locus in X-linked pyridoxine-responsive sideroblastic anemia (PRSA), the ALAS2 marker has allowed placement of the gene for PRSA into the multipoint linkage map of the X chromosome.	Pyridoxine	71-81	5'-aminolevulinate synthase 2	Homo sapiens	3-8
34490613-0	2022	Severe iron overload in a woman with homeostatic iron regulator (HFE) and a novel 5"-aminolevulinate synthase 2 (ALAS2) mutations: interactions of multiple genetic determinants.	Iron	7-11	5'-aminolevulinate synthase 2	Homo sapiens	82-111
34490613-0	2022	Severe iron overload in a woman with homeostatic iron regulator (HFE) and a novel 5"-aminolevulinate synthase 2 (ALAS2) mutations: interactions of multiple genetic determinants.	Iron	7-11	5'-aminolevulinate synthase 2	Homo sapiens	113-118
34492704-10	2021	We further show that itaconyl-CoA is a competitive inhibitor of the erythroid-specific 5-aminolevulinate synthase (ALAS2), the first and rate-limiting step in heme synthesis.	Aminolevulinic Acid	87-104	5'-aminolevulinate synthase 2	Homo sapiens	115-120
34492704-10	2021	We further show that itaconyl-CoA is a competitive inhibitor of the erythroid-specific 5-aminolevulinate synthase (ALAS2), the first and rate-limiting step in heme synthesis.	Heme	159-163	5'-aminolevulinate synthase 2	Homo sapiens	115-120
34492704-11	2021	These findings strongly support our hypothesis that the inhibition of heme synthesis observed in chronic inflammation is mediated not only by iron limitation, but also by limitation of tetrapyrrole synthesis at the point of ALAS2 catalysis by itaconate.	Heme	70-74	5'-aminolevulinate synthase 2	Homo sapiens	224-229
34492704-11	2021	These findings strongly support our hypothesis that the inhibition of heme synthesis observed in chronic inflammation is mediated not only by iron limitation, but also by limitation of tetrapyrrole synthesis at the point of ALAS2 catalysis by itaconate.	Tetrapyrroles	185-197	5'-aminolevulinate synthase 2	Homo sapiens	224-229
34492704-11	2021	These findings strongly support our hypothesis that the inhibition of heme synthesis observed in chronic inflammation is mediated not only by iron limitation, but also by limitation of tetrapyrrole synthesis at the point of ALAS2 catalysis by itaconate.	itaconic acid	243-252	5'-aminolevulinate synthase 2	Homo sapiens	224-229
34781359-4	2022	Here, we successfully generated active wild-type and mutant ALAS2 induced pluripotent stem cell (iPSC) lines from the peripheral blood cells of an affected mother and two daughters in a family with pyridoxine-resistant XLSA due to a heterozygous ALAS2 missense mutation (R227C).	Pyridoxine	198-208	5'-aminolevulinate synthase 2	Homo sapiens	60-65
34783528-2	2021	In the present work, we have systematically investigated the photochemical performance of the 2D beta-antimonene (beta-Sb) monolayer.	2d beta-antimonene	94-112	5'-aminolevulinate synthase 2	Homo sapiens	114-121
34783528-5	2021	Specifically, beta-Sb with single atom replacement has even superior that the reference catalysts IrO2(110) and Pt(111) with relatively low overpotential values for ORR and OER mechanisms.	iridium oxide	98-102	5'-aminolevulinate synthase 2	Homo sapiens	14-21
34783528-5	2021	Specifically, beta-Sb with single atom replacement has even superior that the reference catalysts IrO2(110) and Pt(111) with relatively low overpotential values for ORR and OER mechanisms.	Platinum	112-114	5'-aminolevulinate synthase 2	Homo sapiens	14-21
34783528-6	2021	The superior catalytic performance of beta-Sb has been described by its electronic structures, charge transfer mechanism, and suitable valence and conduction band edge positions versus normal hydrogen electrode.	Hydrogen	192-200	5'-aminolevulinate synthase 2	Homo sapiens	38-45
34783528-7	2021	Meanwhile, the low overpotential of multifunctional photocatalysts of the Bi@beta-Sb monolayer makes them show a remarkable performance in overall water splitting (0.06 V for HER, 0.25 V for OER, and 0.31 V for ORR).	Bismuth	74-76	5'-aminolevulinate synthase 2	Homo sapiens	77-84
34783528-7	2021	Meanwhile, the low overpotential of multifunctional photocatalysts of the Bi@beta-Sb monolayer makes them show a remarkable performance in overall water splitting (0.06 V for HER, 0.25 V for OER, and 0.31 V for ORR).	Water	147-152	5'-aminolevulinate synthase 2	Homo sapiens	77-84
34783528-8	2021	In general, the Bi@beta-Sb monolayer may be an excellent trifunctional catalyst that exhibits high activity toward all electrode reactions of hydrogen and oxygen.	Hydrogen	142-150	5'-aminolevulinate synthase 2	Homo sapiens	19-26
34783528-8	2021	In general, the Bi@beta-Sb monolayer may be an excellent trifunctional catalyst that exhibits high activity toward all electrode reactions of hydrogen and oxygen.	Oxygen	155-161	5'-aminolevulinate synthase 2	Homo sapiens	19-26
34781359-4	2022	Here, we successfully generated active wild-type and mutant ALAS2 induced pluripotent stem cell (iPSC) lines from the peripheral blood cells of an affected mother and two daughters in a family with pyridoxine-resistant XLSA due to a heterozygous ALAS2 missense mutation (R227C).	Pyridoxine	198-208	5'-aminolevulinate synthase 2	Homo sapiens	246-251
34781359-10	2022	Administration of a DNA demethylating agent, azacitidine, reactivated the silent wild-type ALAS2 allele in active mutant HPCs and ameliorated erythroid differentiation defects, suggesting that azacitidine is a potential novel therapeutic drug for female XLSA.	Azacitidine	45-56	5'-aminolevulinate synthase 2	Homo sapiens	91-96
34781359-10	2022	Administration of a DNA demethylating agent, azacitidine, reactivated the silent wild-type ALAS2 allele in active mutant HPCs and ameliorated erythroid differentiation defects, suggesting that azacitidine is a potential novel therapeutic drug for female XLSA.	Azacitidine	193-204	5'-aminolevulinate synthase 2	Homo sapiens	91-96
35054318-1	2022	Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are inherited disorders resulting from defects in two different enzymes of the heme biosynthetic pathway, i.e., ferrochelatase (FECH) and delta-aminolevulinic acid synthase-2 (ALAS2), respectively.	Heme	149-153	5'-aminolevulinate synthase 2	Homo sapiens	208-244
34940556-3	2021	In the bone marrow, heme synthesis is mainly controlled by intracellular labile iron by post-transcriptional regulation: translation of ALAS2 mRNA, the first and rate-limiting enzyme of the pathway, is inhibited when iron availability is low.	Heme	20-24	5'-aminolevulinate synthase 2	Homo sapiens	136-141
34940556-3	2021	In the bone marrow, heme synthesis is mainly controlled by intracellular labile iron by post-transcriptional regulation: translation of ALAS2 mRNA, the first and rate-limiting enzyme of the pathway, is inhibited when iron availability is low.	Iron	80-84	5'-aminolevulinate synthase 2	Homo sapiens	136-141
34940556-3	2021	In the bone marrow, heme synthesis is mainly controlled by intracellular labile iron by post-transcriptional regulation: translation of ALAS2 mRNA, the first and rate-limiting enzyme of the pathway, is inhibited when iron availability is low.	Iron	217-221	5'-aminolevulinate synthase 2	Homo sapiens	136-141
35054318-1	2022	Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are inherited disorders resulting from defects in two different enzymes of the heme biosynthetic pathway, i.e., ferrochelatase (FECH) and delta-aminolevulinic acid synthase-2 (ALAS2), respectively.	Heme	149-153	5'-aminolevulinate synthase 2	Homo sapiens	246-251
35054318-5	2022	The erythroid-specific ALAS2 catalyses the synthesis of delta-aminolevulinic acid (ALA), from the union of glycine and succinyl-coenzyme A, in the first step of the pathway in the erythron.	Aminolevulinic Acid	56-81	5'-aminolevulinate synthase 2	Homo sapiens	23-28
35054318-5	2022	The erythroid-specific ALAS2 catalyses the synthesis of delta-aminolevulinic acid (ALA), from the union of glycine and succinyl-coenzyme A, in the first step of the pathway in the erythron.	Aminolevulinic Acid	83-86	5'-aminolevulinate synthase 2	Homo sapiens	23-28
35054318-5	2022	The erythroid-specific ALAS2 catalyses the synthesis of delta-aminolevulinic acid (ALA), from the union of glycine and succinyl-coenzyme A, in the first step of the pathway in the erythron.	Glycine	107-114	5'-aminolevulinate synthase 2	Homo sapiens	23-28
35054318-5	2022	The erythroid-specific ALAS2 catalyses the synthesis of delta-aminolevulinic acid (ALA), from the union of glycine and succinyl-coenzyme A, in the first step of the pathway in the erythron.	succinyl-coenzyme A	119-138	5'-aminolevulinate synthase 2	Homo sapiens	23-28
35054318-6	2022	In XLP, ALAS2 activity increases, resulting in the amplified formation of ALA, and iron becomes the rate-limiting factor for heme synthesis in the erythroid tissue.	Aminolevulinic Acid	74-77	5'-aminolevulinate synthase 2	Homo sapiens	8-13
33596641-0	2021	A mutation in the iron-responsive element of ALAS2 is a modifier of disease severity in a patient suffering from CLPX associated erythropoietic protoporphyria.	Iron	18-22	5'-aminolevulinate synthase 2	Homo sapiens	45-50
33281618-0	2020	A Novel ALAS2 Missense Mutation in Two Brothers With Iron Overload and Associated Alterations in Serum Hepcidin/Erythroferrone Levels.	Iron	53-57	5'-aminolevulinate synthase 2	Homo sapiens	8-13
33659185-6	2021	The first and rate-limiting 5-aminolevulinate synthase 2 (ALAS2) enzyme controls heme synthesis and porphyrin production in erythroid cells, while iron availability modulates its expression through a post-transcriptional mechanism.	Heme	81-85	5'-aminolevulinate synthase 2	Homo sapiens	58-63
33659185-6	2021	The first and rate-limiting 5-aminolevulinate synthase 2 (ALAS2) enzyme controls heme synthesis and porphyrin production in erythroid cells, while iron availability modulates its expression through a post-transcriptional mechanism.	Iron	147-151	5'-aminolevulinate synthase 2	Homo sapiens	58-63
32678895-4	2020	One promising strategy to treat CEP is to reduce the erythroid production of porphyrins through substrate reduction therapy by inhibiting 5-aminolevulinate synthase 2 (ALAS2), the first and rate-limiting enzyme in the heme biosynthetic pathway.	Porphyrins	77-87	5'-aminolevulinate synthase 2	Homo sapiens	138-166
32678895-4	2020	One promising strategy to treat CEP is to reduce the erythroid production of porphyrins through substrate reduction therapy by inhibiting 5-aminolevulinate synthase 2 (ALAS2), the first and rate-limiting enzyme in the heme biosynthetic pathway.	Porphyrins	77-87	5'-aminolevulinate synthase 2	Homo sapiens	168-173
32678895-4	2020	One promising strategy to treat CEP is to reduce the erythroid production of porphyrins through substrate reduction therapy by inhibiting 5-aminolevulinate synthase 2 (ALAS2), the first and rate-limiting enzyme in the heme biosynthetic pathway.	Heme	218-222	5'-aminolevulinate synthase 2	Homo sapiens	138-166
32678895-4	2020	One promising strategy to treat CEP is to reduce the erythroid production of porphyrins through substrate reduction therapy by inhibiting 5-aminolevulinate synthase 2 (ALAS2), the first and rate-limiting enzyme in the heme biosynthetic pathway.	Heme	218-222	5'-aminolevulinate synthase 2	Homo sapiens	168-173
32678895-7	2020	Treatment of UROS-deficient erythroid cell lines and peripheral blood CD34+-derived erythroid cultures from a CEP patient with deferiprone inhibited iron-dependent protein ALAS2 and IRP2 expression and reduced porphyrin production.	Deferiprone	127-138	5'-aminolevulinate synthase 2	Homo sapiens	172-177
32678895-7	2020	Treatment of UROS-deficient erythroid cell lines and peripheral blood CD34+-derived erythroid cultures from a CEP patient with deferiprone inhibited iron-dependent protein ALAS2 and IRP2 expression and reduced porphyrin production.	Iron	149-153	5'-aminolevulinate synthase 2	Homo sapiens	172-177
33281618-7	2020	A novel pathogenic ALAS2 missense mutation (c.1382T>A, p.Leu461His) is described.	leu461his	57-66	5'-aminolevulinate synthase 2	Homo sapiens	19-24
32499479-3	2020	Here, we report the human ALAS2 crystal structure, revealing that its Ct-extension folds onto the catalytic core, sits atop the active site, and precludes binding of substrate succinyl-CoA.	succinyl-coenzyme A	176-188	5'-aminolevulinate synthase 2	Homo sapiens	26-31
33067979-5	2020	RESULTS: Compared with sh-NC group, knockdown of ALAS2 induced downregulation of BNIP3L mRNA and protein expression(P<0.01) and erythroid related transcription factors GATA1, Nrf2 expression, as well as reduction of ROS level(P<0.05).	Reactive Oxygen Species	216-219	5'-aminolevulinate synthase 2	Homo sapiens	49-54
32499479-7	2020	These fragments represent a starting point to develop ALAS2 inhibitors as substrate reduction therapy for porphyria disorders that accumulate toxic heme intermediates.	Heme	148-152	5'-aminolevulinate synthase 2	Homo sapiens	54-59
31823667-6	2020	Among them, the upregulated Bcl-associated X protein was related to "apoptosis," while the downregulated 5"-aminolevulinate synthase 2 (ALAS2) was related to both "glycine, serine, and threonine metabolism" and "porphyrin and chlorophyll metabolism" in pathway enrichment analysis.	Glycine	164-171	5'-aminolevulinate synthase 2	Homo sapiens	105-134
31823667-6	2020	Among them, the upregulated Bcl-associated X protein was related to "apoptosis," while the downregulated 5"-aminolevulinate synthase 2 (ALAS2) was related to both "glycine, serine, and threonine metabolism" and "porphyrin and chlorophyll metabolism" in pathway enrichment analysis.	Glycine	164-171	5'-aminolevulinate synthase 2	Homo sapiens	136-141
31823667-6	2020	Among them, the upregulated Bcl-associated X protein was related to "apoptosis," while the downregulated 5"-aminolevulinate synthase 2 (ALAS2) was related to both "glycine, serine, and threonine metabolism" and "porphyrin and chlorophyll metabolism" in pathway enrichment analysis.	cholecystokinin C-terminal flanking peptide	173-179	5'-aminolevulinate synthase 2	Homo sapiens	105-134
31823667-6	2020	Among them, the upregulated Bcl-associated X protein was related to "apoptosis," while the downregulated 5"-aminolevulinate synthase 2 (ALAS2) was related to both "glycine, serine, and threonine metabolism" and "porphyrin and chlorophyll metabolism" in pathway enrichment analysis.	cholecystokinin C-terminal flanking peptide	173-179	5'-aminolevulinate synthase 2	Homo sapiens	136-141
31823667-6	2020	Among them, the upregulated Bcl-associated X protein was related to "apoptosis," while the downregulated 5"-aminolevulinate synthase 2 (ALAS2) was related to both "glycine, serine, and threonine metabolism" and "porphyrin and chlorophyll metabolism" in pathway enrichment analysis.	glycyl-threonine	185-194	5'-aminolevulinate synthase 2	Homo sapiens	105-134
31823667-6	2020	Among them, the upregulated Bcl-associated X protein was related to "apoptosis," while the downregulated 5"-aminolevulinate synthase 2 (ALAS2) was related to both "glycine, serine, and threonine metabolism" and "porphyrin and chlorophyll metabolism" in pathway enrichment analysis.	glycyl-threonine	185-194	5'-aminolevulinate synthase 2	Homo sapiens	136-141
31823667-6	2020	Among them, the upregulated Bcl-associated X protein was related to "apoptosis," while the downregulated 5"-aminolevulinate synthase 2 (ALAS2) was related to both "glycine, serine, and threonine metabolism" and "porphyrin and chlorophyll metabolism" in pathway enrichment analysis.	Porphyrins	212-221	5'-aminolevulinate synthase 2	Homo sapiens	105-134
31823667-6	2020	Among them, the upregulated Bcl-associated X protein was related to "apoptosis," while the downregulated 5"-aminolevulinate synthase 2 (ALAS2) was related to both "glycine, serine, and threonine metabolism" and "porphyrin and chlorophyll metabolism" in pathway enrichment analysis.	Porphyrins	212-221	5'-aminolevulinate synthase 2	Homo sapiens	136-141
31823667-6	2020	Among them, the upregulated Bcl-associated X protein was related to "apoptosis," while the downregulated 5"-aminolevulinate synthase 2 (ALAS2) was related to both "glycine, serine, and threonine metabolism" and "porphyrin and chlorophyll metabolism" in pathway enrichment analysis.	Chlorophyll	226-237	5'-aminolevulinate synthase 2	Homo sapiens	105-134
31823667-6	2020	Among them, the upregulated Bcl-associated X protein was related to "apoptosis," while the downregulated 5"-aminolevulinate synthase 2 (ALAS2) was related to both "glycine, serine, and threonine metabolism" and "porphyrin and chlorophyll metabolism" in pathway enrichment analysis.	Chlorophyll	226-237	5'-aminolevulinate synthase 2	Homo sapiens	136-141
31823667-7	2020	CONCLUSIONS: ALAS2 and the metabolic pathways which were involved may play an important role in the development of epirubicin-induced cardiomyopathy.	Epirubicin	115-125	5'-aminolevulinate synthase 2	Homo sapiens	13-18
31823667-8	2020	ALAS2 may be useful as an early biomarker for epirubicin-induced cardiotoxicity detection.	Epirubicin	46-56	5'-aminolevulinate synthase 2	Homo sapiens	0-5
30098397-3	2019	The most prevalent form of CSA is X-linked sideroblastic anemia, caused by mutations in the erythroid-specific delta-aminolevulinate synthase (ALAS2), which is the first enzyme of the heme biosynthesis pathway in erythroid cells.	Heme	184-188	5'-aminolevulinate synthase 2	Homo sapiens	143-148
30737140-6	2019	In erythroid cells, ALAS2 is a gatekeeper of production of very large amounts of heme necessary for hemoglobin synthesis.	Heme	81-85	5'-aminolevulinate synthase 2	Homo sapiens	20-25
30737140-7	2019	The rate of ALAS2 synthesis is transiently increased during the period of active heme synthesis.	Heme	81-85	5'-aminolevulinate synthase 2	Homo sapiens	12-17
30737140-9	2019	ALAS2 mRNA translation is also regulated by the iron-responsive element (IRE)/iron regulatory proteins (IRP) binding system.	Iron	48-52	5'-aminolevulinate synthase 2	Homo sapiens	0-5
30737140-9	2019	ALAS2 mRNA translation is also regulated by the iron-responsive element (IRE)/iron regulatory proteins (IRP) binding system.	Iron	78-82	5'-aminolevulinate synthase 2	Homo sapiens	0-5
30737140-11	2019	Decreased ALAS2 activity results either directly from loss-of-function ALAS2 mutations as seen in X-linked sideroblastic anemia (XLSA) or from defect in the availability of one of its two mitochondrial substrates: glycine in SLC25A38 mutations and succinyl CoA in GLRX5 mutations.	Glycine	214-221	5'-aminolevulinate synthase 2	Homo sapiens	10-15
30737140-11	2019	Decreased ALAS2 activity results either directly from loss-of-function ALAS2 mutations as seen in X-linked sideroblastic anemia (XLSA) or from defect in the availability of one of its two mitochondrial substrates: glycine in SLC25A38 mutations and succinyl CoA in GLRX5 mutations.	succinyl-coenzyme A	248-260	5'-aminolevulinate synthase 2	Homo sapiens	10-15
31076252-6	2019	When iron is limited, iron response element binding protein 2 (IRP2) binds to the IRE of ALAS2 mRNA and suppresses its translation.	Iron	5-9	5'-aminolevulinate synthase 2	Homo sapiens	89-94
31076252-6	2019	When iron is limited, iron response element binding protein 2 (IRP2) binds to the IRE of ALAS2 mRNA and suppresses its translation.	Iron	22-26	5'-aminolevulinate synthase 2	Homo sapiens	89-94
31076252-7	2019	In this study, we demonstrated that iron deprivation increased the amount of ALAS2 mRNA as well as the ratio of ALAS2 to FECH mRNAs in cultured erythroleukemic K562 cells.	Iron	36-40	5'-aminolevulinate synthase 2	Homo sapiens	77-82
31076252-7	2019	In this study, we demonstrated that iron deprivation increased the amount of ALAS2 mRNA as well as the ratio of ALAS2 to FECH mRNAs in cultured erythroleukemic K562 cells.	Iron	36-40	5'-aminolevulinate synthase 2	Homo sapiens	112-117
31076252-9	2019	A comparable increase in the ratio of ALAS2 to FECH mRNAs was also found in EPP patients indicating an imbalance in heme biosynthesis.	Heme	116-120	5'-aminolevulinate synthase 2	Homo sapiens	38-43
31076252-10	2019	As iron cannot be completely missing from an organism, we assume that in EPP patients, a certain amount of ALAS2 mRNA is translated despite a partial deficiency of FECH.	Iron	3-7	5'-aminolevulinate synthase 2	Homo sapiens	107-112
31076252-11	2019	The increase in ALAS2 enzyme contributes to the accumulation in PPIX in the patients.	protoporphyrin IX	64-68	5'-aminolevulinate synthase 2	Homo sapiens	16-21
31395332-3	2019	Aminolevulinic acid synthase 2 (ALAS2), the rate limiting enzyme of the heme pathway in the erythron, is a therapeutic target in EPP because inhibiting enzyme function would reduce downstream production of protoporphyrin IX (PPIX), preventing accumulation of the toxic molecule and thereby ameliorating symptoms.	Heme	72-76	5'-aminolevulinate synthase 2	Homo sapiens	0-30
31395332-3	2019	Aminolevulinic acid synthase 2 (ALAS2), the rate limiting enzyme of the heme pathway in the erythron, is a therapeutic target in EPP because inhibiting enzyme function would reduce downstream production of protoporphyrin IX (PPIX), preventing accumulation of the toxic molecule and thereby ameliorating symptoms.	Heme	72-76	5'-aminolevulinate synthase 2	Homo sapiens	32-37
31395332-3	2019	Aminolevulinic acid synthase 2 (ALAS2), the rate limiting enzyme of the heme pathway in the erythron, is a therapeutic target in EPP because inhibiting enzyme function would reduce downstream production of protoporphyrin IX (PPIX), preventing accumulation of the toxic molecule and thereby ameliorating symptoms.	protoporphyrin IX	206-223	5'-aminolevulinate synthase 2	Homo sapiens	0-30
31395332-3	2019	Aminolevulinic acid synthase 2 (ALAS2), the rate limiting enzyme of the heme pathway in the erythron, is a therapeutic target in EPP because inhibiting enzyme function would reduce downstream production of protoporphyrin IX (PPIX), preventing accumulation of the toxic molecule and thereby ameliorating symptoms.	protoporphyrin IX	206-223	5'-aminolevulinate synthase 2	Homo sapiens	32-37
31395332-3	2019	Aminolevulinic acid synthase 2 (ALAS2), the rate limiting enzyme of the heme pathway in the erythron, is a therapeutic target in EPP because inhibiting enzyme function would reduce downstream production of protoporphyrin IX (PPIX), preventing accumulation of the toxic molecule and thereby ameliorating symptoms.	protoporphyrin IX	225-229	5'-aminolevulinate synthase 2	Homo sapiens	0-30
31395332-3	2019	Aminolevulinic acid synthase 2 (ALAS2), the rate limiting enzyme of the heme pathway in the erythron, is a therapeutic target in EPP because inhibiting enzyme function would reduce downstream production of protoporphyrin IX (PPIX), preventing accumulation of the toxic molecule and thereby ameliorating symptoms.	protoporphyrin IX	225-229	5'-aminolevulinate synthase 2	Homo sapiens	32-37
30765471-6	2019	In ABCB7-depleted cells, defective heme biosynthesis resulted from translational repression of ALAS2 by iron regulatory proteins and from decreased stability of the terminal enzyme ferrochelatase.	Heme	35-39	5'-aminolevulinate synthase 2	Homo sapiens	95-100
30765471-6	2019	In ABCB7-depleted cells, defective heme biosynthesis resulted from translational repression of ALAS2 by iron regulatory proteins and from decreased stability of the terminal enzyme ferrochelatase.	Iron	104-108	5'-aminolevulinate synthase 2	Homo sapiens	95-100
31059917-8	2019	B[a]P was positively correlated with an increased expression of a heme biosynthesis gene, ALAS2, which in turn, appears to promote concurrent increase of neutrophilic metamyelocyte and mature CD71low erythroid cells.	Heme	66-70	5'-aminolevulinate synthase 2	Homo sapiens	90-95
29991557-4	2018	Based upon the observation that 1 subunit of succinyl-CoA synthetase (SCS) physically interacts with the first enzyme of heme synthesis (5-aminolevulinate synthase 2, ALAS2) in erythroid cells, it has been posited that succinyl-CoA for ALA synthesis is provided by the adenosine triphosphate-dependent reverse SCS reaction.	Heme	121-125	5'-aminolevulinate synthase 2	Homo sapiens	167-172
30678654-6	2019	RESULTS: The five ALAS2 single nucleotide variants had from 1.3- to 1.9-fold increases in succinyl-CoA Vmax and 2- to 3-fold increases in thermostability suggesting that most could be gain-of-function modifiers of porphyria instead of causes.	succinyl-coenzyme A	90-102	5'-aminolevulinate synthase 2	Homo sapiens	18-23
30678654-8	2019	The five novel ALAS2 truncation mutations had increased Vmax values for both succinyl-CoA and glycine substrates (1.4 to 5.6-fold over wild-type), while the Kms for both substrates were only modestly changed.	succinyl-coenzyme A	77-89	5'-aminolevulinate synthase 2	Homo sapiens	15-20
30678654-8	2019	The five novel ALAS2 truncation mutations had increased Vmax values for both succinyl-CoA and glycine substrates (1.4 to 5.6-fold over wild-type), while the Kms for both substrates were only modestly changed.	Glycine	94-101	5'-aminolevulinate synthase 2	Homo sapiens	15-20
30678654-11	2019	A key region of the ALAS2 carboxyterminal region is identified by the truncation mutations studied here and the correlation of increased thermolability with activity suggests that increased molecular flexibility/active site openness is the mechanism of enhanced function of mutations in this region providing further insights into the role of the carboxyl-terminal region of ALAS2 in the regulation of erythroid heme synthesis.	Heme	412-416	5'-aminolevulinate synthase 2	Homo sapiens	20-25
30678654-11	2019	A key region of the ALAS2 carboxyterminal region is identified by the truncation mutations studied here and the correlation of increased thermolability with activity suggests that increased molecular flexibility/active site openness is the mechanism of enhanced function of mutations in this region providing further insights into the role of the carboxyl-terminal region of ALAS2 in the regulation of erythroid heme synthesis.	Heme	412-416	5'-aminolevulinate synthase 2	Homo sapiens	375-380
29929070-11	2018	Higher MMP-2 concentrations were detected for the groups that did not undergo demineralization treatment, and the lowest values for the ASB groups treated with CAPE.	caffeic acid phenethyl ester	160-164	5'-aminolevulinate synthase 2	Homo sapiens	136-139
29929070-15	2018	Immunoassay analysis showed that CAPE 0.1% reduced the MMP-2 concentration in the ASB adhesive without affecting bond strength to dentin.	caffeic acid phenethyl ester	33-37	5'-aminolevulinate synthase 2	Homo sapiens	82-85
30217463-1	2018	A previously disclosed protein kinase (PK) CK2-selective inhibitor 4-(2-amino-1,3-thiazol-5-yl)benzoic acid (ATB) and its selenium-containing counterpart (ASB) revealed remarkable room temperature phosphorescence when bound to the ATP pocket of the protein kinase CK2.	CHEMBL4166028	67-107	5'-aminolevulinate synthase 2	Homo sapiens	155-158
30217463-1	2018	A previously disclosed protein kinase (PK) CK2-selective inhibitor 4-(2-amino-1,3-thiazol-5-yl)benzoic acid (ATB) and its selenium-containing counterpart (ASB) revealed remarkable room temperature phosphorescence when bound to the ATP pocket of the protein kinase CK2.	atb	109-112	5'-aminolevulinate synthase 2	Homo sapiens	155-158
30217463-1	2018	A previously disclosed protein kinase (PK) CK2-selective inhibitor 4-(2-amino-1,3-thiazol-5-yl)benzoic acid (ATB) and its selenium-containing counterpart (ASB) revealed remarkable room temperature phosphorescence when bound to the ATP pocket of the protein kinase CK2.	Selenium	122-130	5'-aminolevulinate synthase 2	Homo sapiens	155-158
30217463-1	2018	A previously disclosed protein kinase (PK) CK2-selective inhibitor 4-(2-amino-1,3-thiazol-5-yl)benzoic acid (ATB) and its selenium-containing counterpart (ASB) revealed remarkable room temperature phosphorescence when bound to the ATP pocket of the protein kinase CK2.	Adenosine Triphosphate	231-234	5'-aminolevulinate synthase 2	Homo sapiens	155-158
29991557-4	2018	Based upon the observation that 1 subunit of succinyl-CoA synthetase (SCS) physically interacts with the first enzyme of heme synthesis (5-aminolevulinate synthase 2, ALAS2) in erythroid cells, it has been posited that succinyl-CoA for ALA synthesis is provided by the adenosine triphosphate-dependent reverse SCS reaction.	succinyl-coenzyme A	45-57	5'-aminolevulinate synthase 2	Homo sapiens	167-172
29991557-4	2018	Based upon the observation that 1 subunit of succinyl-CoA synthetase (SCS) physically interacts with the first enzyme of heme synthesis (5-aminolevulinate synthase 2, ALAS2) in erythroid cells, it has been posited that succinyl-CoA for ALA synthesis is provided by the adenosine triphosphate-dependent reverse SCS reaction.	Adenosine Triphosphate	269-291	5'-aminolevulinate synthase 2	Homo sapiens	167-172
29743399-0	2018	[Successful treatment of X-linked sideroblastic anemia with ALAS2 R452H mutation using vitamin B6].	Vitamin B 6	87-97	5'-aminolevulinate synthase 2	Homo sapiens	60-65
27838491-1	2017	Mutations in the C-terminus of human erythroid 5-aminolevulinate synthase (hALAS2), a pyridoxal 5"-phosphate (PLP)-dependent enzyme, are associated with two different blood disorders, X-linked sideroblastic anemia (XLSA) and X-linked protoporphyria (XLPP).	Pyridoxal Phosphate	86-108	5'-aminolevulinate synthase 2	Homo sapiens	75-81
30305500-3	2018	The most common form of CSA is X-linked sideroblastic anemia; it occurs because of mutations in the erythroid-specific delta-aminolevulinate synthase gene (ALAS2), which is the first enzyme of the heme biosynthesis pathway in erythroid cells.	Heme	197-201	5'-aminolevulinate synthase 2	Homo sapiens	156-161
28667034-0	2017	A Novel ALAS2 Mutation Resulting in Variable Phenotypes and Pyridoxine Response in a Family with X-linked Sideroblastic Anemia.	Pyridoxine	60-70	5'-aminolevulinate synthase 2	Homo sapiens	8-13
28667034-4	2017	We assume that this amino acid substitution affects the enzymatic activity of ALAS2 by affecting its interaction with the cofactor pyridoxal 5"-phosphate, since the patient was responsive to pyridoxine treatment.	Pyridoxal Phosphate	131-153	5'-aminolevulinate synthase 2	Homo sapiens	78-83
28667034-4	2017	We assume that this amino acid substitution affects the enzymatic activity of ALAS2 by affecting its interaction with the cofactor pyridoxal 5"-phosphate, since the patient was responsive to pyridoxine treatment.	Pyridoxine	191-201	5'-aminolevulinate synthase 2	Homo sapiens	78-83
28118224-6	2017	The treatment of hepatic porphyrias by an RNAi-targeting hepatic ALAS1 is actually tested and may lead to improve the management of acute attacks.In erythropoietic porphyrias, the key role of ALAS2 as a gate keeper of the heme and subsequently hemoglobin synthesis has been demonstrated.	Heme	222-226	5'-aminolevulinate synthase 2	Homo sapiens	192-197
27838491-4	2017	Isonicotinic acid hydrazide (isoniazid, INH), an antituberculosis agent, can cause sideroblastic anemia as a side-effect, by limiting PLP availability to hALAS2, via inhibition of pyridoxal kinase or reaction with pyridoxal to form pyridoxal isonicotinoyl hydrazone.	Isoniazid	0-27	5'-aminolevulinate synthase 2	Homo sapiens	154-160
27838491-4	2017	Isonicotinic acid hydrazide (isoniazid, INH), an antituberculosis agent, can cause sideroblastic anemia as a side-effect, by limiting PLP availability to hALAS2, via inhibition of pyridoxal kinase or reaction with pyridoxal to form pyridoxal isonicotinoyl hydrazone.	Isoniazid	29-38	5'-aminolevulinate synthase 2	Homo sapiens	154-160
27838491-7	2017	In addition, PLP and pyridoxamine 5"-phosphate (PMP) reversed the cellular inhibition of hALAS2 activity by INH.	pyridoxamine phosphate	21-46	5'-aminolevulinate synthase 2	Homo sapiens	89-95
27838491-7	2017	In addition, PLP and pyridoxamine 5"-phosphate (PMP) reversed the cellular inhibition of hALAS2 activity by INH.	pyridoxamine phosphate	48-51	5'-aminolevulinate synthase 2	Homo sapiens	89-95
28090037-6	2017	Treatment with rapamycin (100 nM) for 48 hours significantly increased %number of hemoglobin-producing cells, gamma-globin mRNA levels, erythroid specific 5-aminolevulinate synthase (ALAS2) mRNA levels, and heme content in K562 cells.	Sirolimus	15-24	5'-aminolevulinate synthase 2	Homo sapiens	183-188
26969896-5	2016	A more pronounced endogenous production of porphyrins concomitant to activation of ALAS2, the first and rate-limiting of the haem synthesis enzymes in erythroid cells, has also been reported.	Porphyrins	43-53	5'-aminolevulinate synthase 2	Homo sapiens	83-88
27247955-8	2016	The in vitro prokaryotic expression showed that the p.Leu406Phe and p.Tyr500Cys mutations reduced the ALAS2 specific activity (SA) to 14% and 7% of the control value, respectively.	sa	127-129	5'-aminolevulinate synthase 2	Homo sapiens	102-107
26698166-3	2016	To meet the intense demand for hemoglobin assembly in red blood cells, the cell type-specific factor GATA-1 activates transcription of Alas2, encoding the rate-limiting enzyme in heme biosynthesis, 5-aminolevulinic acid synthase-2 (ALAS-2).	Heme	179-183	5'-aminolevulinate synthase 2	Homo sapiens	135-140
26698166-3	2016	To meet the intense demand for hemoglobin assembly in red blood cells, the cell type-specific factor GATA-1 activates transcription of Alas2, encoding the rate-limiting enzyme in heme biosynthesis, 5-aminolevulinic acid synthase-2 (ALAS-2).	Heme	179-183	5'-aminolevulinate synthase 2	Homo sapiens	198-230
26698166-3	2016	To meet the intense demand for hemoglobin assembly in red blood cells, the cell type-specific factor GATA-1 activates transcription of Alas2, encoding the rate-limiting enzyme in heme biosynthesis, 5-aminolevulinic acid synthase-2 (ALAS-2).	Heme	179-183	5'-aminolevulinate synthase 2	Homo sapiens	232-238
26698166-5	2016	CRISPR/Cas9-mediated ablation of two Alas2 intronic cis elements strongly reduces GATA-1-induced Alas2 transcription, heme biosynthesis, and surprisingly, GATA-1 regulation of other vital constituents of the erythroid cell transcriptome.	Heme	118-122	5'-aminolevulinate synthase 2	Homo sapiens	37-42
26698166-6	2016	Bypassing ALAS-2 function in Alas2 cis element-mutant cells by providing its catalytic product 5-aminolevulinic acid rescues heme biosynthesis and the GATA-1-dependent genetic network.	5-amino levulinic acid	95-116	5'-aminolevulinate synthase 2	Homo sapiens	10-16
26698166-6	2016	Bypassing ALAS-2 function in Alas2 cis element-mutant cells by providing its catalytic product 5-aminolevulinic acid rescues heme biosynthesis and the GATA-1-dependent genetic network.	5-amino levulinic acid	95-116	5'-aminolevulinate synthase 2	Homo sapiens	29-34
26698166-6	2016	Bypassing ALAS-2 function in Alas2 cis element-mutant cells by providing its catalytic product 5-aminolevulinic acid rescues heme biosynthesis and the GATA-1-dependent genetic network.	Heme	125-129	5'-aminolevulinate synthase 2	Homo sapiens	10-16
26698166-6	2016	Bypassing ALAS-2 function in Alas2 cis element-mutant cells by providing its catalytic product 5-aminolevulinic acid rescues heme biosynthesis and the GATA-1-dependent genetic network.	Heme	125-129	5'-aminolevulinate synthase 2	Homo sapiens	29-34
25615817-1	2016	X-linked protoporphyria (XLP), a rare erythropoietic porphyria, results from terminal exon gain-of-function mutations in the ALAS2 gene causing increased ALAS2 activity and markedly increased erythrocyte protoporphyrin levels.	protoporphyrin IX	204-218	5'-aminolevulinate synthase 2	Homo sapiens	125-130
26605136-1	2015	5-Aminolevulinate synthase (ALAS) catalyzes the initial step of mammalian heme biosynthesis, the condensation between glycine and succinyl-CoA to produce CoA, CO2, and 5-aminolevulinate.	Heme	74-78	5'-aminolevulinate synthase 2	Homo sapiens	28-32
26702583-9	2016	Thus, Hspa9 depletion causes a mitochondrial ISC deficit, altering IRP1-IRE binding and FeCH stability, which consequently inhibits Alas2 translation, heme synthesis, and erythroid differentiation, i.e.: Hspa9-&gt;ISC-&gt;IRP/IRE-&gt;Alas2-&gt;heme synthesis-&gt;erythroid differentiation.	Heme	244-248	5'-aminolevulinate synthase 2	Homo sapiens	132-137
26487704-6	2016	Expression levels of 221 genes were associated with strength after adjustment for cofactors and for multiple statistical testing, including ALAS2 (rate-limiting enzyme in heme synthesis), PRF1 (perforin, a cytotoxic protein associated with inflammation), IGF1R, and IGF2BP2 (both insulin like growth factor related).	Heme	171-175	5'-aminolevulinate synthase 2	Homo sapiens	140-145
26703568-0	2015	MiR-218 Inhibits Erythroid Differentiation and Alters Iron Metabolism by Targeting ALAS2 in K562 Cells.	mir-218	0-7	5'-aminolevulinate synthase 2	Homo sapiens	83-88
26703568-2	2015	The regulatory function and potential role of miRNAs targeting the mRNA of the 5"-aminolevulinate synthase 2 (ALAS2) in erythropoiesis were investigated in order to identify miRNAs which play a role in erythroid iron metabolism and differentiation.	Iron	212-216	5'-aminolevulinate synthase 2	Homo sapiens	79-108
26703568-2	2015	The regulatory function and potential role of miRNAs targeting the mRNA of the 5"-aminolevulinate synthase 2 (ALAS2) in erythropoiesis were investigated in order to identify miRNAs which play a role in erythroid iron metabolism and differentiation.	Iron	212-216	5'-aminolevulinate synthase 2	Homo sapiens	110-115
26703568-5	2015	Overexpression of miR-218 repressed erythroid differentiation and altered iron metabolism in K562 cells similar to that seen in the ALAS2 knockdown in K562 cells.	mir-218	18-25	5'-aminolevulinate synthase 2	Homo sapiens	132-137
26703568-7	2015	Taken together, our results show that miR-218 inhibits erythroid differentiation and alters iron metabolism by targeting ALAS2 in K562 cells.	mir-218	38-45	5'-aminolevulinate synthase 2	Homo sapiens	121-126
26703568-7	2015	Taken together, our results show that miR-218 inhibits erythroid differentiation and alters iron metabolism by targeting ALAS2 in K562 cells.	Iron	92-96	5'-aminolevulinate synthase 2	Homo sapiens	121-126
26885114-0	2015	Delta-aminolevulinate synthase 2 polymorphism is associated with maximal oxygen uptake after Living-high exercise-high training-low in a male Chinese population.	Oxygen	73-79	5'-aminolevulinate synthase 2	Homo sapiens	0-32
26885114-9	2015	CONCLUSIONS: The compound dinucleotide repeat polymorphism in ALAS2 intron 7 correlated with response to HiHiLo training.	Dinucleoside Phosphates	26-38	5'-aminolevulinate synthase 2	Homo sapiens	62-67
26605136-1	2015	5-Aminolevulinate synthase (ALAS) catalyzes the initial step of mammalian heme biosynthesis, the condensation between glycine and succinyl-CoA to produce CoA, CO2, and 5-aminolevulinate.	Glycine	118-125	5'-aminolevulinate synthase 2	Homo sapiens	28-32
26605136-1	2015	5-Aminolevulinate synthase (ALAS) catalyzes the initial step of mammalian heme biosynthesis, the condensation between glycine and succinyl-CoA to produce CoA, CO2, and 5-aminolevulinate.	succinyl-coenzyme A	130-142	5'-aminolevulinate synthase 2	Homo sapiens	28-32
26605136-1	2015	5-Aminolevulinate synthase (ALAS) catalyzes the initial step of mammalian heme biosynthesis, the condensation between glycine and succinyl-CoA to produce CoA, CO2, and 5-aminolevulinate.	Coenzyme A	139-142	5'-aminolevulinate synthase 2	Homo sapiens	28-32
26605136-1	2015	5-Aminolevulinate synthase (ALAS) catalyzes the initial step of mammalian heme biosynthesis, the condensation between glycine and succinyl-CoA to produce CoA, CO2, and 5-aminolevulinate.	N2,N6-bis(4-(2-aminoethoxy)quinolin-2-yl)-4-((4-fluorobenzyl)oxy)pyridine-2,6-dicarboxamide	159-162	5'-aminolevulinate synthase 2	Homo sapiens	28-32
26605136-1	2015	5-Aminolevulinate synthase (ALAS) catalyzes the initial step of mammalian heme biosynthesis, the condensation between glycine and succinyl-CoA to produce CoA, CO2, and 5-aminolevulinate.	Aminolevulinic Acid	168-185	5'-aminolevulinate synthase 2	Homo sapiens	28-32
26605136-3	2015	Loss-of-function mutations in the analogous lysine of human erythroid ALAS (ALAS2) cause X-linked sideroblastic anemia.	Lysine	44-50	5'-aminolevulinate synthase 2	Homo sapiens	70-74
26605136-3	2015	Loss-of-function mutations in the analogous lysine of human erythroid ALAS (ALAS2) cause X-linked sideroblastic anemia.	Lysine	44-50	5'-aminolevulinate synthase 2	Homo sapiens	76-81
26231844-3	2015	We hypothesized that increased heme accumulation (through cardiac overexpression of ALAS2) leads to increased oxidative stress and cell death in the heart.	Heme	31-35	5'-aminolevulinate synthase 2	Homo sapiens	84-89
26300302-2	2015	Mutations in the C-terminal region of human erythroid-specific ALAS (hALAS2) are associated with X-linked protoporphyria (XLPP), a disease characterized by extreme photosensitivity, with elevated blood concentrations of free protoporphyrin IX and zinc protoporphyrin.	xlpp	122-126	5'-aminolevulinate synthase 2	Homo sapiens	69-75
26300302-2	2015	Mutations in the C-terminal region of human erythroid-specific ALAS (hALAS2) are associated with X-linked protoporphyria (XLPP), a disease characterized by extreme photosensitivity, with elevated blood concentrations of free protoporphyrin IX and zinc protoporphyrin.	protoporphyrin IX	225-242	5'-aminolevulinate synthase 2	Homo sapiens	69-75
26300302-2	2015	Mutations in the C-terminal region of human erythroid-specific ALAS (hALAS2) are associated with X-linked protoporphyria (XLPP), a disease characterized by extreme photosensitivity, with elevated blood concentrations of free protoporphyrin IX and zinc protoporphyrin.	zinc protoporphyrin	247-266	5'-aminolevulinate synthase 2	Homo sapiens	69-75
26300302-8	2015	We propose that (1) the XLPP mutations destabilize the succinyl-CoA-induced hALAS2 closed conformation and thus accelerate ALA release, (2) the extended C-terminus of wild-type mammalian ALAS2 provides a regulatory role that allows for allosteric modulation of activity, thereby controlling the rate of erythroid heme biosynthesis, and (3) this control is disrupted in XLPP, resulting in porphyrin accumulation.	succinyl-coenzyme A	55-67	5'-aminolevulinate synthase 2	Homo sapiens	76-82
26300302-8	2015	We propose that (1) the XLPP mutations destabilize the succinyl-CoA-induced hALAS2 closed conformation and thus accelerate ALA release, (2) the extended C-terminus of wild-type mammalian ALAS2 provides a regulatory role that allows for allosteric modulation of activity, thereby controlling the rate of erythroid heme biosynthesis, and (3) this control is disrupted in XLPP, resulting in porphyrin accumulation.	succinyl-coenzyme A	55-67	5'-aminolevulinate synthase 2	Homo sapiens	77-82
26300302-8	2015	We propose that (1) the XLPP mutations destabilize the succinyl-CoA-induced hALAS2 closed conformation and thus accelerate ALA release, (2) the extended C-terminus of wild-type mammalian ALAS2 provides a regulatory role that allows for allosteric modulation of activity, thereby controlling the rate of erythroid heme biosynthesis, and (3) this control is disrupted in XLPP, resulting in porphyrin accumulation.	Heme	313-317	5'-aminolevulinate synthase 2	Homo sapiens	76-82
26300302-8	2015	We propose that (1) the XLPP mutations destabilize the succinyl-CoA-induced hALAS2 closed conformation and thus accelerate ALA release, (2) the extended C-terminus of wild-type mammalian ALAS2 provides a regulatory role that allows for allosteric modulation of activity, thereby controlling the rate of erythroid heme biosynthesis, and (3) this control is disrupted in XLPP, resulting in porphyrin accumulation.	Heme	313-317	5'-aminolevulinate synthase 2	Homo sapiens	77-82
26300302-8	2015	We propose that (1) the XLPP mutations destabilize the succinyl-CoA-induced hALAS2 closed conformation and thus accelerate ALA release, (2) the extended C-terminus of wild-type mammalian ALAS2 provides a regulatory role that allows for allosteric modulation of activity, thereby controlling the rate of erythroid heme biosynthesis, and (3) this control is disrupted in XLPP, resulting in porphyrin accumulation.	Porphyrins	388-397	5'-aminolevulinate synthase 2	Homo sapiens	76-82
26300302-8	2015	We propose that (1) the XLPP mutations destabilize the succinyl-CoA-induced hALAS2 closed conformation and thus accelerate ALA release, (2) the extended C-terminus of wild-type mammalian ALAS2 provides a regulatory role that allows for allosteric modulation of activity, thereby controlling the rate of erythroid heme biosynthesis, and (3) this control is disrupted in XLPP, resulting in porphyrin accumulation.	Porphyrins	388-397	5'-aminolevulinate synthase 2	Homo sapiens	77-82
26231844-7	2015	We confirmed in cultured cardiomyoblasts that the increased oxidative stress and cell death observed with ALAS2 overexpression is mediated by increased heme accumulation.	Heme	152-156	5'-aminolevulinate synthase 2	Homo sapiens	106-111
26231844-8	2015	Furthermore, knockdown of ALAS2 in cultured cardiomyoblasts exposed to hypoxia reversed the increases in heme content and cell death.	Heme	105-109	5'-aminolevulinate synthase 2	Homo sapiens	26-31
26231844-9	2015	Administration of the mitochondrial antioxidant MitoTempo to ALAS2-overexpressing cardiomyoblasts normalized the elevated oxidative stress and cell death levels to baseline, indicating that the effects of increased ALAS2 and heme are through elevated mitochondrial oxidative stress.	MitoTEMPO	48-57	5'-aminolevulinate synthase 2	Homo sapiens	61-66
26231844-9	2015	Administration of the mitochondrial antioxidant MitoTempo to ALAS2-overexpressing cardiomyoblasts normalized the elevated oxidative stress and cell death levels to baseline, indicating that the effects of increased ALAS2 and heme are through elevated mitochondrial oxidative stress.	MitoTEMPO	48-57	5'-aminolevulinate synthase 2	Homo sapiens	215-220
25547425-10	2015	The patient responded well to treatment, showing the pyridoxine responsiveness of this novel ALAS2 mutation.	Pyridoxine	53-63	5'-aminolevulinate synthase 2	Homo sapiens	93-98
25972160-5	2015	Hypothesizing that iron restriction improved her symptoms by decreasing ALAS2 activity and subsequent porphyrin production, we treated the patient with off-label use of deferasirox to maintain iron deficiency, with successful results.	Iron	19-23	5'-aminolevulinate synthase 2	Homo sapiens	72-77
25972160-5	2015	Hypothesizing that iron restriction improved her symptoms by decreasing ALAS2 activity and subsequent porphyrin production, we treated the patient with off-label use of deferasirox to maintain iron deficiency, with successful results.	Deferasirox	169-180	5'-aminolevulinate synthase 2	Homo sapiens	72-77
25985931-11	2015	CONCLUSION: To our knowledge, the pyridoxine-effective mutation C471Y of ALAS2, the compound heterozygous mutation W87X, I143Pfs146X, and the homozygous mutation R134C of SLC25A38 were found for the first time.	Pyridoxine	34-44	5'-aminolevulinate synthase 2	Homo sapiens	73-78
25705881-5	2015	We determined that this mutation (Y365C) impairs binding of the essential cofactor pyridoxal 5"-phosphate to ALAS2, resulting in destabilization of the enzyme and consequent loss of function.	Pyridoxal Phosphate	83-105	5'-aminolevulinate synthase 2	Homo sapiens	109-114
24718052-4	2014	ALAS2 variants that cause high levels of PPIX accumulation provide a new means of targeted, and potentially enhanced, photosensitization.	protoporphyrin IX	41-45	5'-aminolevulinate synthase 2	Homo sapiens	0-5
25482442-2	2015	The mechanism of mammalian heme synthesis has been studied for many years; aminolevulinate synthase 2 (ALAS2), a heme synthetase, is associated with X-linked dominant protoporphyria in humans.	Heme	27-31	5'-aminolevulinate synthase 2	Homo sapiens	103-108
25179834-1	2015	The activity of the erythroid-specific isoenzyme of 5-aminolevulinic acid synthase (ALAS2), the first and rate-limiting enzyme in heme biosynthesis, is down-regulated during iron-deficiency.	Heme	130-134	5'-aminolevulinate synthase 2	Homo sapiens	84-89
25179834-10	2015	Furthermore, we hypothesize that EPP patients may benefit from a mild iron deficiency since it would limit PPIX production by restricting ALAS2 over-expression.	protoporphyrin IX	107-111	5'-aminolevulinate synthase 2	Homo sapiens	138-143
25450364-3	2014	ALAS2 is a mitochondrial enzyme, which utilizes glycine and succinyl-CoA to form 5-aminolevulinic acid (ALA), a crucial precursor in heme synthesis.	Glycine	48-55	5'-aminolevulinate synthase 2	Homo sapiens	0-5
25450364-3	2014	ALAS2 is a mitochondrial enzyme, which utilizes glycine and succinyl-CoA to form 5-aminolevulinic acid (ALA), a crucial precursor in heme synthesis.	succinyl-coenzyme A	60-72	5'-aminolevulinate synthase 2	Homo sapiens	0-5
25450364-3	2014	ALAS2 is a mitochondrial enzyme, which utilizes glycine and succinyl-CoA to form 5-aminolevulinic acid (ALA), a crucial precursor in heme synthesis.	5-amino levulinic acid	81-102	5'-aminolevulinate synthase 2	Homo sapiens	0-5
25450364-3	2014	ALAS2 is a mitochondrial enzyme, which utilizes glycine and succinyl-CoA to form 5-aminolevulinic acid (ALA), a crucial precursor in heme synthesis.	Heme	133-137	5'-aminolevulinate synthase 2	Homo sapiens	0-5
25450364-4	2014	Therefore, ALA supplementation could be an effective therapeutic strategy to restore heme synthesis in CSA caused by ALAS2 defects.	5-amino levulinic acid	11-14	5'-aminolevulinate synthase 2	Homo sapiens	117-122
25450364-4	2014	Therefore, ALA supplementation could be an effective therapeutic strategy to restore heme synthesis in CSA caused by ALAS2 defects.	Heme	85-89	5'-aminolevulinate synthase 2	Homo sapiens	117-122
25450364-15	2014	ALA may represent a novel therapeutic option for CSA treatment, particularly for cases harboring ALAS2 mutations.	5-amino levulinic acid	0-3	5'-aminolevulinate synthase 2	Homo sapiens	97-102
24718052-5	2014	In order to assess the prospective utility of ALAS2 variants in PPIX production for PDT, K562 human erythroleukemia cells and HeLa human cervical carcinoma cells were transfected with expression plasmids for ALAS2 variants with greater enzymatic activity than the wild-type enzyme.	protoporphyrin IX	64-68	5'-aminolevulinate synthase 2	Homo sapiens	46-51
24718052-6	2014	The levels of accumulated PPIX in ALAS2-expressing cells were analyzed using flow cytometry with fluorescence detection.	protoporphyrin IX	26-30	5'-aminolevulinate synthase 2	Homo sapiens	34-39
24718052-9	2014	Light treatments revealed that ALAS2 expression results in an increase in cell death in comparison to aminolevulinic acid (ALA) treatment producing a similar amount of PPIX.	protoporphyrin IX	168-172	5'-aminolevulinate synthase 2	Homo sapiens	31-36
24509859-6	2014	IRP1 attenuates protoporphyrin biosynthesis by binding to the 5"-iron response element (IRE) of alas2 mRNA, inhibiting its translation.	protoporphyrin IX	16-30	5'-aminolevulinate synthase 2	Homo sapiens	96-101
24509859-6	2014	IRP1 attenuates protoporphyrin biosynthesis by binding to the 5"-iron response element (IRE) of alas2 mRNA, inhibiting its translation.	Iron	65-69	5'-aminolevulinate synthase 2	Homo sapiens	96-101
23935018-1	2014	Erythroid-specific 5-aminolevulinate synthase (ALAS2) is the rate-limiting enzyme for heme biosynthesis in erythroid cells, and a missense mutation of the ALAS2 gene is associated with congenital sideroblastic anemia.	Heme	86-90	5'-aminolevulinate synthase 2	Homo sapiens	47-52
24166784-0	2014	X-linked sideroblastic anemia due to ALAS2 intron 1 enhancer element GATA-binding site mutations.	gata	69-73	5'-aminolevulinate synthase 2	Homo sapiens	37-42
24166784-2	2014	In affected males, it is uniformly associated with partial loss-of-function missense mutations in the erythroid-specific heme biosynthesis protein 5-aminolevulinate synthase 2 (ALAS2).	Heme	121-125	5'-aminolevulinate synthase 2	Homo sapiens	147-175
24166784-2	2014	In affected males, it is uniformly associated with partial loss-of-function missense mutations in the erythroid-specific heme biosynthesis protein 5-aminolevulinate synthase 2 (ALAS2).	Heme	121-125	5'-aminolevulinate synthase 2	Homo sapiens	177-182
23935018-1	2014	Erythroid-specific 5-aminolevulinate synthase (ALAS2) is the rate-limiting enzyme for heme biosynthesis in erythroid cells, and a missense mutation of the ALAS2 gene is associated with congenital sideroblastic anemia.	Heme	86-90	5'-aminolevulinate synthase 2	Homo sapiens	155-160
23935018-6	2014	Importantly, two mutations, each of which disrupts the GATA-binding site in the enhancer, were identified in unrelated male patients with congenital sideroblastic anemia, and the lower expression level of ALAS2 mRNA in bone marrow erythroblasts was confirmed in one of these patients.	gata	55-59	5'-aminolevulinate synthase 2	Homo sapiens	205-210
24606657-10	2014	Our findings emphasized the importance of gene based diagnosis of CSA, and CSA patient with ALAS2 mutation responded to pyridoxine treatment.	Pyridoxine	120-130	5'-aminolevulinate synthase 2	Homo sapiens	92-97