MGP Database

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MGP000112

UniProt Annotations

Entry Information
Gene Name5'-aminolevulinate synthase 2
Protein EntryHEM0_HUMAN
UniProt IDP22557
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=4; Name=1; IsoId=P22557-1; Sequence=Displayed; Name=2; Synonyms=Delta4; IsoId=P22557-2; Sequence=VSP_042852; Note=Constitutes 35-45% of erythrocytes ALAS2 mRNAs. Catalytic activity is 70% of isoform 1 activity.; Name=3; Synonyms=F143M; IsoId=P22557-3; Sequence=VSP_042851, VSP_042853; Note=Catalytic activity is 80% of isoform 1 activity.; Name=4; IsoId=P22557-4; Sequence=VSP_047330, VSP_042852;
Catalytic ActivitySuccinyl-CoA + glycine = 5-aminolevulinate + CoA + CO(2). {ECO:0000269|PubMed:14643893}.
CofactorName=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
DiseaseAnemia, sideroblastic, X-linked (XLSA) [MIM:300751]: A form of sideroblastic anemia that shows a variable hematologic response to pharmacologic doses of pyridoxine. Sideroblastic anemia is characterized by anemia of varying severity, hypochromic peripheral erythrocytes, systemic iron overload secondary to chronic ineffective erythropoiesis, and the presence of bone marrow ringed sideroblasts. Sideroblasts are characterized by iron-loaded mitochondria clustered around the nucleus. {ECO:0000269|PubMed:10029606, ECO:0000269|PubMed:10577279, ECO:0000269|PubMed:12031592, ECO:0000269|PubMed:12393718, ECO:0000269|PubMed:1570328, ECO:0000269|PubMed:19731322, ECO:0000269|PubMed:21252495, ECO:0000269|PubMed:21309041, ECO:0000269|PubMed:8107717, ECO:0000269|PubMed:9858242}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseaseErythropoietic protoporphyria, X-linked dominant (XLDPT) [MIM:300752]: A form of porphyria. Porphyrias are inherited defects in the biosynthesis of heme, resulting in the accumulation and increased excretion of porphyrins or porphyrin precursors. They are classified as erythropoietic or hepatic, depending on whether the enzyme deficiency occurs in red blood cells or in the liver. XLDPT is characterized biochemically by a high proportion of zinc-protoporphyrin in erythrocytes, in which a mismatch between protoporphyrin production and the heme requirement of differentiating erythroid cells leads to overproduction of protoporphyrin in amounts sufficient to cause photosensitivity and liver disease. {ECO:0000269|PubMed:18760763}. Note=The disease is caused by mutations affecting the gene represented in this entry. Gain of function mutations in ALS2 are responsible for XLDPT, but they can also be a possible aggravating factor in congenital erythropoietic porphyria and other erythropoietic disorders caused by mutations in other genes (PubMed:21309041). {ECO:0000269|PubMed:21309041}.
MiscellaneousThere are two delta-ALA synthases in vertebrates: an erythroid- specific form and one (housekeeping) which is expressed in all tissues.
PathwayPorphyrin-containing compound metabolism; protoporphyrin- IX biosynthesis; 5-aminolevulinate from glycine: step 1/1.
Sequence CautionSequence=CAA39795.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};
SimilarityBelongs to the class-II pyridoxal-phosphate-dependent aminotransferase family. {ECO:0000305}.
Subcellular LocationMitochondrion matrix {ECO:0000269|PubMed:14643893}.
SubunitHomodimer. Interacts with SUCLA2. {ECO:0000269|PubMed:14643893}.
Tissue SpecificityErythroid specific.
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