ALAS2

C-terminus is a mobile self-inhibitory loop which interferes directly with active site.

Catalyzes the pyridoxal 5'-phosphate (PLP)-dependent condensation of succinyl-CoA and glycine to form aminolevulinic acid (ALA), with CoA and CO2 as by-products (PubMed:14643893, PubMed:21252495, PubMed:21309041, PubMed:21653323, PubMed:32499479). Contributes significantly to heme formation during erythropoiesis (PubMed:2050125).

Isoform 3

Catalyzes the pyridoxal 5'-phosphate (PLP)-dependent condensation of succinyl-CoA and glycine to form aminolevulinic acid (ALA), with CoA and CO2 as by-products (PubMed:14643893). Catalytic activity is 75-85% of isoform 1 activity (PubMed:14643893).

Isoform 4

Catalyzes the pyridoxal 5'-phosphate (PLP)-dependent condensation of succinyl-CoA and glycine to form aminolevulinic acid (ALA), with CoA and CO2 as by-products (PubMed:14643893). Catalytic activity is 65-75% of isoform 1 activity (PubMed:14643893).

Anemia, sideroblastic, 1

SIDBA1

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.

None

The disease is caused by variants affecting the gene represented in this entry.

Erythropoietic protoporphyria, X-linked dominant

XLDPT

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.

None

The disease is caused by variants 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).

Porphyrin-containing compound metabolism; protoporphyrin-IX biosynthesis; 5-aminolevulinate from glycine: step 1/1.

Belongs to the class-II pyridoxal-phosphate-dependent aminotransferase family.

Isoform 1

Erythroid-specific.

Isoform 2

Erythroid-specific.

Isoform 3

Erythroid-specific.

Isoform 4

Erythroid-specific.

• Mitochondrion inner membrane
• Peripheral membrane protein
• Localizes to the matrix side of the mitochondrion inner membrane.
• Isoform 4
• Mitochondrion inner membrane
• Peripheral membrane protein
• Localizes to the matrix side of the mitochondrion inner membrane.

ALASE, ASB, ALAS2, ALAS-E, 5-aminolevulinic acid synthase 2, Delta-ALA synthase 2, Delta-aminolevulinate synthase 2

• entrezGene:212
• omim:301300
• swissprot:P22557

Proteins

Metabolism

64633Da