ID:HEM0_HUMAN DESCRIPTION: RecName: Full=5-aminolevulinate synthase, erythroid-specific, mitochondrial; Short=ALAS-E; EC=2.3.1.37; AltName: Full=5-aminolevulinic acid synthase 2; AltName: Full=Delta-ALA synthase 2; AltName: Full=Delta-aminolevulinate synthase 2; Flags: Precursor; CATALYTIC ACTIVITY: Succinyl-CoA + glycine = 5-aminolevulinate + CoA + CO(2). COFACTOR: Pyridoxal phosphate. PATHWAY: Porphyrin metabolism; protoporphyrin-IX biosynthesis; 5- aminolevulinate from glycine: step 1/1. SUBUNIT: Homodimer. Interacts with SUCLA2. SUBCELLULAR LOCATION: Mitochondrion matrix. TISSUE SPECIFICITY: Erythroid specific. DISEASE: Defects in ALAS2 are a cause of anemia sideroblastic X- linked (XLSA) [MIM:300751]. 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. XLSA shows a variable hematologic response to pharmacologic doses of pyridoxine. DISEASE: Defects in ALAS2 are the cause of erythropoietic protoporphyria X-linked dominant (XLDPT) [MIM:300752]. 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 a form of porphyria 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. Note=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). MISCELLANEOUS: There are two delta-ALA synthases in vertebrates: an erythroid- specific form and one (housekeeping) which is expressed in all tissues. SIMILARITY: Belongs to the class-II pyridoxal-phosphate-dependent aminotransferase family. SEQUENCE CAUTION: Sequence=CAA39795.1; Type=Erroneous initiation; WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/ALAS2";
Protein Domain and Structure Information
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