InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: ALAS2

Summary

InnateDB Protein

IDBP-72060.7

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

ALAS2

Protein Name

aminolevulinate, delta-, synthase 2

Synonyms

ALAS-E; ALASE; ANH1; ASB; XLDPP; XLEPP; XLSA;

Species

Homo sapiens

Ensembl Protein

ENSP00000337131

InnateDB Gene

IDBG-72056 (ALAS2)

Protein Structure

UniProt Annotation

Function

Subcellular Localization

Mitochondrion matrix {ECO:0000269PubMed:14643893}.

Disease Associations

Anemia, 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:0000269PubMed:10029606, ECO:0000269PubMed:10577279, ECO:0000269PubMed:12031592, ECO:0000269PubMed:12393718, ECO:0000269PubMed:1570328, ECO:0000269PubMed:21252495, ECO:0000269PubMed:21309041, ECO:0000269PubMed:8107717, ECO:0000269PubMed:9858242}. Note=The disease is caused by mutations affecting the gene represented in this entry.Erythropoietic 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:0000269PubMed: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:0000269PubMed:21309041}.

Tissue Specificity

Erythroid specific.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 4 experimentally validated interaction(s) in this database.
They are also associated with 1 interaction(s) predicted by orthology.

Experimentally validated
Total	4 [view]
Protein-Protein	4 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	1 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003870	5-aminolevulinate synthase activity
GO:0005515	protein binding
GO:0016594	glycine binding
GO:0030170	pyridoxal phosphate binding
GO:0050662	coenzyme binding

Biological Process

GO:0001666	response to hypoxia
GO:0006778	porphyrin-containing compound metabolic process
GO:0006782	protoporphyrinogen IX biosynthetic process
GO:0006783	heme biosynthetic process
GO:0006879	cellular iron ion homeostasis
GO:0008152	metabolic process
GO:0009058	biosynthetic process
GO:0030218	erythrocyte differentiation
GO:0032364	oxygen homeostasis
GO:0033014	tetrapyrrole biosynthetic process
GO:0042541	hemoglobin biosynthetic process
GO:0044281	small molecule metabolic process

Cellular Component

GO:0005739	mitochondrion
GO:0005743	mitochondrial inner membrane
GO:0005759	mitochondrial matrix

Protein Structure and Domains

PDB ID

InterPro

IPR000192 Aminotransferase class V domain
IPR000277 Cys/Met metabolism, pyridoxal phosphate-dependent enzyme
IPR004839 Aminotransferase, class I/classII
IPR010961 Tetrapyrrole biosynthesis, 5-aminolevulinic acid synthase
IPR015118 5-aminolevulinate synthase presequence
IPR015424 Pyridoxal phosphate-dependent transferase

PFAM

PF00266
PF01053
PF00155
PF09029

PRINTS

PIRSF

PIRSF001434

SMART

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt

P22557