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Protein

5-aminolevulinate synthase, erythroid-specific, mitochondrial

Gene

ALAS2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Miscellaneous

There are two delta-ALA synthases in vertebrates: an erythroid- specific form and one (housekeeping) which is expressed in all tissues.

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

<p>This subsection of the ‘Function’ section provides information relevant to cofactors. A cofactor is any non-protein substance required for a protein to be catalytically active. Some cofactors are inorganic, such as the metal atoms zinc, iron, and copper in various oxidation states. Others, such as most vitamins, are organic.<p><a href='/help/cofactor' target='_top'>More...</a></p>Cofactori

pyridoxal 5'-phosphate

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section describes the metabolic pathway(s) associated with a protein.<p><a href='/help/pathway' target='_top'>More...</a></p>Pathwayi: protoporphyrin-IX biosynthesis

This protein is involved in step 1 of the subpathway that synthesizes 5-aminolevulinate from glycine.
Proteins known to be involved in this subpathway in this organism are:
  1. 5-aminolevulinate synthase, erythroid-specific, mitochondrial (ALAS2), 5-aminolevulinate synthase, nonspecific, mitochondrial (ALAS1), 5-aminolevulinate synthase (ALAS1)
This subpathway is part of the pathway protoporphyrin-IX biosynthesis, which is itself part of Porphyrin-containing compound metabolism.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes 5-aminolevulinate from glycine, the pathway protoporphyrin-IX biosynthesis and in Porphyrin-containing compound metabolism.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Function’ section describes the interaction between a single amino acid and another chemical entity. Priority is given to the annotation of physiological ligands.<p><a href='/help/binding' target='_top'>More...</a></p>Binding sitei163SubstrateBy similarity1
Binding sitei280SubstrateBy similarity1
Binding sitei299SubstrateBy similarity1
Binding sitei332Pyridoxal phosphateBy similarity1
Binding sitei360Pyridoxal phosphateBy similarity1
Binding sitei388Pyridoxal phosphateBy similarity1
<p>This subsection of the ‘Function’ section is used for enzymes and indicates the residues directly involved in catalysis.<p><a href='/help/act_site' target='_top'>More...</a></p>Active sitei391By similarity1
Binding sitei420Pyridoxal phosphate; shared with dimeric partnerBy similarity1
Binding sitei421Pyridoxal phosphate; shared with dimeric partnerBy similarity1
Binding sitei508SubstrateBy similarity1

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionAcyltransferase, Transferase
Biological processHeme biosynthesis
LigandPyridoxal phosphate

Enzyme and pathway databases

BioCyc Collection of Pathway/Genome Databases

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BioCyci
MetaCyc:HS08311-MONOMER

BRENDA Comprehensive Enzyme Information System

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BRENDAi
2.3.1.37 2681

Reactome - a knowledgebase of biological pathways and processes

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Reactomei
R-HSA-189451 Heme biosynthesis

SIGNOR Signaling Network Open Resource

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SIGNORi
P22557

UniPathway: a resource for the exploration and annotation of metabolic pathways

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UniPathwayi
UPA00251;UER00375

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
5-aminolevulinate synthase, erythroid-specific, mitochondrial (EC:2.3.1.37)
Short name:
ALAS-E
Alternative name(s):
5-aminolevulinic acid synthase 2
Delta-ALA synthase 2
Delta-aminolevulinate synthase 2
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:ALAS2
Synonyms:ALASE, ASB
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">proteome</a> can consist of several components. <br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome X

Organism-specific databases

Eukaryotic Pathogen Database Resources

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EuPathDBi
HostDB:ENSG00000158578.18

Human Gene Nomenclature Database

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HGNCi
HGNC:397 ALAS2

Online Mendelian Inheritance in Man (OMIM)

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MIMi
301300 gene

neXtProt; the human protein knowledge platform

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neXtProti
NX_P22557

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Mitochondrion

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the ‘Pathology and Biotech’ section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

Anemia, sideroblastic, 1 (SIDBA1)10 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:300751
Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_066232156K → E in SIDBA1; significantly reduced activity. 1 Publication1
Natural variantiVAR_018604159D → Y in SIDBA1. 1 PublicationCorresponds to variant dbSNP:rs137852308EnsemblClinVar.1
Natural variantiVAR_072328165F → L in SIDBA1. 1 PublicationCorresponds to variant dbSNP:rs137852301EnsemblClinVar.1
Natural variantiVAR_072329170R → C in SIDBA1. 1 Publication1
Natural variantiVAR_066233170R → H in SIDBA1; significantly increased thermosensitivity. 1 Publication1
Natural variantiVAR_012334199Y → H in SIDBA1. 1 PublicationCorresponds to variant dbSNP:rs137852310EnsemblClinVar.1
Natural variantiVAR_012335204R → Q in SIDBA1; 15% to 35% activity of wild-type. 1 PublicationCorresponds to variant dbSNP:rs1338391423Ensembl.1
Natural variantiVAR_066234218R → H in SIDBA1; significantly increased thermosensitivity. 1 PublicationCorresponds to variant dbSNP:rs185504937Ensembl.1
Natural variantiVAR_066235242E → K in SIDBA1; significantly reduced activity. 1 Publication1
Natural variantiVAR_066236263D → N in SIDBA1; significantly reduced activity. 1 Publication1
Natural variantiVAR_072330301V → A in SIDBA1. 1 Publication1
Natural variantiVAR_066237339P → L in SIDBA1; significantly reduced activity. 1 Publication1
Natural variantiVAR_066238375R → C in SIDBA1; significantly reduced activity. 1 Publication1
Natural variantiVAR_000562388T → S in SIDBA1. 1 PublicationCorresponds to variant dbSNP:rs137852300EnsemblClinVar.1
Natural variantiVAR_000563411R → C in SIDBA1; 12% to 25% activity of wild-type. 3 PublicationsCorresponds to variant dbSNP:rs137852305EnsemblClinVar.1
Natural variantiVAR_066239411R → H in SIDBA1; significantly reduced activity. 1 Publication1
Natural variantiVAR_012336448R → Q in SIDBA1. 1 Publication1
Natural variantiVAR_012337452R → C in SIDBA1. 2 PublicationsCorresponds to variant dbSNP:rs137852311EnsemblClinVar.1
Natural variantiVAR_066240452R → G in SIDBA1; does not affect activity. 2 Publications1
Natural variantiVAR_066241452R → H in SIDBA1. 1 PublicationCorresponds to variant dbSNP:rs863223904EnsemblClinVar.1
Natural variantiVAR_000564476I → N in SIDBA1. 1 PublicationCorresponds to variant dbSNP:rs137852299EnsemblClinVar.1
Natural variantiVAR_072331517R → G in SIDBA1. 1 Publication1
Natural variantiVAR_066242520P → L in SIDBA1. 2 PublicationsCorresponds to variant dbSNP:rs201062903EnsemblClinVar.1
Natural variantiVAR_018605560R → H in SIDBA1. 1 PublicationCorresponds to variant dbSNP:rs892041887Ensembl.1
Natural variantiVAR_066243572R → H in SIDBA1; does not affect activity. 1 Publication1
Erythropoietic protoporphyria, X-linked dominant (XLDPT)1 Publication
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).1 Publication
Disease descriptionA 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.
See also OMIM:300752

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNET

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DisGeNETi
212

GeneReviews a resource of expert-authored, peer-reviewed disease descriptions.

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GeneReviewsi
ALAS2

MalaCards human disease database

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MalaCardsi
ALAS2
MIMi300751 phenotype
300752 phenotype

Open Targets

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OpenTargetsi
ENSG00000158578

Orphanet; a database dedicated to information on rare diseases and orphan drugs

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Orphaneti
443197 X-linked erythropoietic protoporphyria
75563 X-linked sideroblastic anemia

The Pharmacogenetics and Pharmacogenomics Knowledge Base

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PharmGKBi
PA24689

Chemistry databases

Drug and drug target database

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DrugBanki
DB00145 Glycine
DB00114 Pyridoxal Phosphate

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

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BioMutai
ALAS2

Domain mapping of disease mutations (DMDM)

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DMDMi
20141346

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section describes the extent of a transit peptide.<p><a href='/help/transit' target='_top'>More...</a></p>Transit peptidei1 – 49Mitochondrion1 PublicationAdd BLAST49
<p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_000000122350 – 5875-aminolevulinate synthase, erythroid-specific, mitochondrialAdd BLAST538

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei391N6-(pyridoxal phosphate)lysineBy similarity1

Proteomic databases

MaxQB - The MaxQuant DataBase

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MaxQBi
P22557

PaxDb, a database of protein abundance averages across all three domains of life

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PaxDbi
P22557

PeptideAtlas

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PeptideAtlasi
P22557

PRoteomics IDEntifications database

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PRIDEi
P22557

ProteomicsDB human proteome resource

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ProteomicsDBi
54000
54001 [P22557-2]
54002 [P22557-3]

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

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iPTMneti
P22557

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

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PhosphoSitePlusi
P22557

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the ‘Expression’ section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified ‘at protein level’. <br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

Erythroid specific.

Gene expression databases

Bgee dataBase for Gene Expression Evolution

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Bgeei
ENSG00000158578 Expressed in 111 organ(s), highest expression level in bone marrow

CleanEx database of gene expression profiles

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CleanExi
HS_ALAS2

ExpressionAtlas, Differential and Baseline Expression

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ExpressionAtlasi
P22557 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

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Genevisiblei
P22557 HS

Organism-specific databases

Human Protein Atlas

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HPAi
HPA001638

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Homodimer. Interacts with SUCLA2.1 Publication

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

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BioGridi
106714, 3 interactors

Protein interaction database and analysis system

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IntActi
P22557, 2 interactors

STRING: functional protein association networks

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STRINGi
9606.ENSP00000332369

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

3D structure databases

Select the link destinations:

Protein Data Bank Europe

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PDBei

Protein Data Bank RCSB

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RCSB PDBi

Protein Data Bank Japan

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PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
6HRHX-ray2.30A/B143-587[»]

Protein Model Portal of the PSI-Nature Structural Biology Knowledgebase

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ProteinModelPortali
P22557

SWISS-MODEL Repository - a database of annotated 3D protein structure models

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SMRi
P22557

Database of comparative protein structure models

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ModBasei
Search...

MobiDB: a database of protein disorder and mobility annotations

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MobiDBi
Search...

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Keywords - Domaini

Transit peptide

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

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eggNOGi
KOG1360 Eukaryota
COG0156 LUCA

Ensembl GeneTree

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GeneTreei
ENSGT00940000159912

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

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HOGENOMi
HOG000221020

The HOVERGEN Database of Homologous Vertebrate Genes

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HOVERGENi
HBG005954

InParanoid: Eukaryotic Ortholog Groups

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InParanoidi
P22557

KEGG Orthology (KO)

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KOi
K00643

Identification of Orthologs from Complete Genome Data

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OMAi
CPVMGKA

Database of Orthologous Groups

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OrthoDBi
930001at2759

Database for complete collections of gene phylogenies

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PhylomeDBi
P22557

TreeFam database of animal gene trees

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TreeFami
TF300724

Family and domain databases

Gene3D Structural and Functional Annotation of Protein Families

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Gene3Di
3.40.640.10, 1 hit
3.90.1150.10, 1 hit

Integrated resource of protein families, domains and functional sites

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InterProi
View protein in InterPro
IPR010961 4pyrrol_synth_NH2levulA_synth
IPR015118 5aminolev_synth_preseq
IPR001917 Aminotrans_II_pyridoxalP_BS
IPR004839 Aminotransferase_I/II
IPR015424 PyrdxlP-dep_Trfase
IPR015422 PyrdxlP-dep_Trfase_dom1
IPR015421 PyrdxlP-dep_Trfase_major

Pfam protein domain database

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Pfami
View protein in Pfam
PF00155 Aminotran_1_2, 1 hit
PF09029 Preseq_ALAS, 1 hit

Superfamily database of structural and functional annotation

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SUPFAMi
SSF53383 SSF53383, 1 hit

TIGRFAMs; a protein family database

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TIGRFAMsi
TIGR01821 5aminolev_synth, 1 hit

PROSITE; a protein domain and family database

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PROSITEi
View protein in PROSITE
PS00599 AA_TRANSFER_CLASS_2, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>.<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (4+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 4 <p>This subsection of the ‘Sequence’ section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 4 described isoforms and 5 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: P22557-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MVTAAMLLQC CPVLARGPTS LLGKVVKTHQ FLFGIGRCPI LATQGPNCSQ
60 70 80 90 100
IHLKATKAGG DSPSWAKGHC PFMLSELQDG KSKIVQKAAP EVQEDVKAFK
110 120 130 140 150
TDLPSSLVSV SLRKPFSGPQ EQEQISGKVT HLIQNNMPGN YVFSYDQFFR
160 170 180 190 200
DKIMEKKQDH TYRVFKTVNR WADAYPFAQH FSEASVASKD VSVWCSNDYL
210 220 230 240 250
GMSRHPQVLQ ATQETLQRHG AGAGGTRNIS GTSKFHVELE QELAELHQKD
260 270 280 290 300
SALLFSSCFV ANDSTLFTLA KILPGCEIYS DAGNHASMIQ GIRNSGAAKF
310 320 330 340 350
VFRHNDPDHL KKLLEKSNPK IPKIVAFETV HSMDGAICPL EELCDVSHQY
360 370 380 390 400
GALTFVDEVH AVGLYGSRGA GIGERDGIMH KIDIISGTLG KAFGCVGGYI
410 420 430 440 450
ASTRDLVDMV RSYAAGFIFT TSLPPMVLSG ALESVRLLKG EEGQALRRAH
460 470 480 490 500
QRNVKHMRQL LMDRGLPVIP CPSHIIPIRV GNAALNSKLC DLLLSKHGIY
510 520 530 540 550
VQAINYPTVP RGEELLRLAP SPHHSPQMME DFVEKLLLAW TAVGLPLQDV
560 570 580
SVAACNFCRR PVHFELMSEW ERSYFGNMGP QYVTTYA
Length:587
Mass (Da):64,633
Last modified:January 23, 2002 - v2
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:iFD821BE245C440B5
GO
Isoform 2 (identifier: P22557-2) [UniParc]FASTAAdd to basket
Also known as: Delta4

The sequence of this isoform differs from the canonical sequence as follows:
     102-138: Missing.

Note: Constitutes 35-45% of erythrocytes ALAS2 mRNAs. Catalytic activity is 70% of isoform 1 activity.
Show »
Length:550
Mass (Da):60,589
Checksum:iBB28A593D343264F
GO
Isoform 3 (identifier: P22557-3) [UniParc]FASTAAdd to basket
Also known as: F143M

The sequence of this isoform differs from the canonical sequence as follows:
     1-142: Missing.
     143-143: F → M

Note: Catalytic activity is 80% of isoform 1 activity.
Show »
Length:445
Mass (Da):49,395
Checksum:i3304747E4DE0CC2E
GO
Isoform 4 (identifier: P22557-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MRGGEVALGWNKKKRLFCEDFRFKM
     102-138: Missing.

Show »
Length:574
Mass (Da):63,487
Checksum:i7F5E13D5F36738CD
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A2R8Y6R4A0A2R8Y6R4_HUMAN
5-aminolevulinate synthase, erythro...
ALAS2
141Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A0A2R8Y6N3A0A2R8Y6N3_HUMAN
5-aminolevulinate synthase, erythro...
ALAS2
276Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A0A2R8Y782A0A2R8Y782_HUMAN
5-aminolevulinate synthase, erythro...
ALAS2
165Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
H0Y6R3H0Y6R3_HUMAN
5-aminolevulinate synthase, erythro...
ALAS2
197Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A0A2R8Y836A0A2R8Y836_HUMAN
5-aminolevulinate synthase, erythro...
ALAS2
170Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

<p>This subsection of the ‘Sequence’ section reports difference(s) between the protein sequence shown in the UniProtKB entry and other available protein sequences derived from the same gene.<p><a href='/help/sequence_caution' target='_top'>More...</a></p>Sequence cautioni

The sequence CAA39795 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti182S → F in CAA39795 (PubMed:2263504).Curated1
Sequence conflicti221A → V in AAH30230 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_066232156K → E in SIDBA1; significantly reduced activity. 1 Publication1
Natural variantiVAR_018604159D → Y in SIDBA1. 1 PublicationCorresponds to variant dbSNP:rs137852308EnsemblClinVar.1
Natural variantiVAR_072328165F → L in SIDBA1. 1 PublicationCorresponds to variant dbSNP:rs137852301EnsemblClinVar.1
Natural variantiVAR_072329170R → C in SIDBA1. 1 Publication1
Natural variantiVAR_066233170R → H in SIDBA1; significantly increased thermosensitivity. 1 Publication1
Natural variantiVAR_012334199Y → H in SIDBA1. 1 PublicationCorresponds to variant dbSNP:rs137852310EnsemblClinVar.1
Natural variantiVAR_012335204R → Q in SIDBA1; 15% to 35% activity of wild-type. 1 PublicationCorresponds to variant dbSNP:rs1338391423Ensembl.1
Natural variantiVAR_066234218R → H in SIDBA1; significantly increased thermosensitivity. 1 PublicationCorresponds to variant dbSNP:rs185504937Ensembl.1
Natural variantiVAR_066235242E → K in SIDBA1; significantly reduced activity. 1 Publication1
Natural variantiVAR_066236263D → N in SIDBA1; significantly reduced activity. 1 Publication1
Natural variantiVAR_072330301V → A in SIDBA1. 1 Publication1
Natural variantiVAR_066237339P → L in SIDBA1; significantly reduced activity. 1 Publication1
Natural variantiVAR_066238375R → C in SIDBA1; significantly reduced activity. 1 Publication1
Natural variantiVAR_000562388T → S in SIDBA1. 1 PublicationCorresponds to variant dbSNP:rs137852300EnsemblClinVar.1
Natural variantiVAR_000563411R → C in SIDBA1; 12% to 25% activity of wild-type. 3 PublicationsCorresponds to variant dbSNP:rs137852305EnsemblClinVar.1
Natural variantiVAR_066239411R → H in SIDBA1; significantly reduced activity. 1 Publication1
Natural variantiVAR_012336448R → Q in SIDBA1. 1 Publication1
Natural variantiVAR_012337452R → C in SIDBA1. 2 PublicationsCorresponds to variant dbSNP:rs137852311EnsemblClinVar.1
Natural variantiVAR_066240452R → G in SIDBA1; does not affect activity. 2 Publications1
Natural variantiVAR_066241452R → H in SIDBA1. 1 PublicationCorresponds to variant dbSNP:rs863223904EnsemblClinVar.1
Natural variantiVAR_000564476I → N in SIDBA1. 1 PublicationCorresponds to variant dbSNP:rs137852299EnsemblClinVar.1
Natural variantiVAR_072331517R → G in SIDBA1. 1 Publication1
Natural variantiVAR_066242520P → L in SIDBA1. 2 PublicationsCorresponds to variant dbSNP:rs201062903EnsemblClinVar.1
Natural variantiVAR_018605560R → H in SIDBA1. 1 PublicationCorresponds to variant dbSNP:rs892041887Ensembl.1
Natural variantiVAR_066243572R → H in SIDBA1; does not affect activity. 1 Publication1
Natural variantiVAR_066244586Y → F Rare variant found in a congenital erythropoietic porphyria patient that also carries UROS mutations R-73 and Q-248; increased enzyme activity. 1 PublicationCorresponds to variant dbSNP:rs139596860EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting. The information stored in this subsection is used to automatically construct alternative protein sequence(s) for display.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_0428511 – 142Missing in isoform 3. CuratedAdd BLAST142
Alternative sequenceiVSP_0473301M → MRGGEVALGWNKKKRLFCED FRFKM in isoform 4. 1 Publication1
Alternative sequenceiVSP_042852102 – 138Missing in isoform 2 and isoform 4. 2 PublicationsAdd BLAST37
Alternative sequenceiVSP_042853143F → M in isoform 3. Curated1

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...
EMBLi

GenBank nucleotide sequence database

More...
GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...
DDBJi
Links Updated
X56352 mRNA Translation: CAA39795.1 Different initiation.
X60364 mRNA Translation: CAA42916.1
AF068624 Genomic DNA Translation: AAC39838.1
AK290565 mRNA Translation: BAF83254.1
AK291589 mRNA Translation: BAF84278.1
AK313118 mRNA Translation: BAG35939.1
Z83821 Genomic DNA No translation available.
AL020991 Genomic DNA No translation available.
CH471154 Genomic DNA Translation: EAW93211.1
CH471154 Genomic DNA Translation: EAW93213.1
BC030230 mRNA Translation: AAH30230.2

The Consensus CDS (CCDS) project

More...
CCDSi
CCDS14366.1 [P22557-1]
CCDS35303.1 [P22557-2]
CCDS43960.1 [P22557-4]

Protein sequence database of the Protein Information Resource

More...
PIRi
S16347 SYHUAE

NCBI Reference Sequences

More...
RefSeqi
NP_000023.2, NM_000032.4 [P22557-1]
NP_001033056.1, NM_001037967.3 [P22557-2]
NP_001033057.1, NM_001037968.3 [P22557-4]

UniGene gene-oriented nucleotide sequence clusters

More...
UniGenei
Hs.522666
Hs.555936

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...
Ensembli
ENST00000330807; ENSP00000332369; ENSG00000158578 [P22557-1]
ENST00000335854; ENSP00000337131; ENSG00000158578 [P22557-2]
ENST00000396198; ENSP00000379501; ENSG00000158578 [P22557-4]
ENST00000650242; ENSP00000497236; ENSG00000158578 [P22557-1]

Database of genes from NCBI RefSeq genomes

More...
GeneIDi
212

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...
KEGGi
hsa:212

UCSC genome browser

More...
UCSCi
uc004dua.4 human [P22557-1]

Keywords - Coding sequence diversityi

Alternative splicing

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X56352 mRNA Translation: CAA39795.1 Different initiation.
X60364 mRNA Translation: CAA42916.1
AF068624 Genomic DNA Translation: AAC39838.1
AK290565 mRNA Translation: BAF83254.1
AK291589 mRNA Translation: BAF84278.1
AK313118 mRNA Translation: BAG35939.1
Z83821 Genomic DNA No translation available.
AL020991 Genomic DNA No translation available.
CH471154 Genomic DNA Translation: EAW93211.1
CH471154 Genomic DNA Translation: EAW93213.1
BC030230 mRNA Translation: AAH30230.2
CCDSiCCDS14366.1 [P22557-1]
CCDS35303.1 [P22557-2]
CCDS43960.1 [P22557-4]
PIRiS16347 SYHUAE
RefSeqiNP_000023.2, NM_000032.4 [P22557-1]
NP_001033056.1, NM_001037967.3 [P22557-2]
NP_001033057.1, NM_001037968.3 [P22557-4]
UniGeneiHs.522666
Hs.555936

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
6HRHX-ray2.30A/B143-587[»]
ProteinModelPortaliP22557
SMRiP22557
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106714, 3 interactors
IntActiP22557, 2 interactors
STRINGi9606.ENSP00000332369

Chemistry databases

DrugBankiDB00145 Glycine
DB00114 Pyridoxal Phosphate

PTM databases

iPTMnetiP22557
PhosphoSitePlusiP22557

Polymorphism and mutation databases

BioMutaiALAS2
DMDMi20141346

Proteomic databases

MaxQBiP22557
PaxDbiP22557
PeptideAtlasiP22557
PRIDEiP22557
ProteomicsDBi54000
54001 [P22557-2]
54002 [P22557-3]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000330807; ENSP00000332369; ENSG00000158578 [P22557-1]
ENST00000335854; ENSP00000337131; ENSG00000158578 [P22557-2]
ENST00000396198; ENSP00000379501; ENSG00000158578 [P22557-4]
ENST00000650242; ENSP00000497236; ENSG00000158578 [P22557-1]
GeneIDi212
KEGGihsa:212
UCSCiuc004dua.4 human [P22557-1]

Organism-specific databases

Comparative Toxicogenomics Database

More...
CTDi
212
DisGeNETi212
EuPathDBiHostDB:ENSG00000158578.18

GeneCards: human genes, protein and diseases

More...
GeneCardsi
ALAS2
GeneReviewsiALAS2
HGNCiHGNC:397 ALAS2
HPAiHPA001638
MalaCardsiALAS2
MIMi300751 phenotype
300752 phenotype
301300 gene
neXtProtiNX_P22557
OpenTargetsiENSG00000158578
Orphaneti443197 X-linked erythropoietic protoporphyria
75563 X-linked sideroblastic anemia
PharmGKBiPA24689

GenAtlas: human gene database

More...
GenAtlasi
Search...

Phylogenomic databases

eggNOGiKOG1360 Eukaryota
COG0156 LUCA
GeneTreeiENSGT00940000159912
HOGENOMiHOG000221020
HOVERGENiHBG005954
InParanoidiP22557
KOiK00643
OMAiCPVMGKA
OrthoDBi930001at2759
PhylomeDBiP22557
TreeFamiTF300724

Enzyme and pathway databases

UniPathwayi
UPA00251;UER00375

BioCyciMetaCyc:HS08311-MONOMER
BRENDAi2.3.1.37 2681
ReactomeiR-HSA-189451 Heme biosynthesis
SIGNORiP22557

Miscellaneous databases

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

More...
ChiTaRSi
ALAS2 human

The Gene Wiki collection of pages on human genes and proteins

More...
GeneWikii
ALAS2

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

More...
GenomeRNAii
212

Protein Ontology

More...
PROi
PR:P22557

The Stanford Online Universal Resource for Clones and ESTs

More...
SOURCEi
Search...

Gene expression databases

BgeeiENSG00000158578 Expressed in 111 organ(s), highest expression level in bone marrow
CleanExiHS_ALAS2
ExpressionAtlasiP22557 baseline and differential
GenevisibleiP22557 HS

Family and domain databases

Gene3Di3.40.640.10, 1 hit
3.90.1150.10, 1 hit
InterProiView protein in InterPro
IPR010961 4pyrrol_synth_NH2levulA_synth
IPR015118 5aminolev_synth_preseq
IPR001917 Aminotrans_II_pyridoxalP_BS
IPR004839 Aminotransferase_I/II
IPR015424 PyrdxlP-dep_Trfase
IPR015422 PyrdxlP-dep_Trfase_dom1
IPR015421 PyrdxlP-dep_Trfase_major
PfamiView protein in Pfam
PF00155 Aminotran_1_2, 1 hit
PF09029 Preseq_ALAS, 1 hit
SUPFAMiSSF53383 SSF53383, 1 hit
TIGRFAMsiTIGR01821 5aminolev_synth, 1 hit
PROSITEiView protein in PROSITE
PS00599 AA_TRANSFER_CLASS_2, 1 hit

ProtoNet; Automatic hierarchical classification of proteins

More...
ProtoNeti
Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the ‘Entry information’ section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiHEM0_HUMAN
<p>This subsection of the ‘Entry information’ section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called ‘Primary (citable) accession number’.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: P22557
Secondary accession number(s): A8K3F0
, A8K6C4, Q13735, Q5JZF5, Q8N6H3
<p>This subsection of the ‘Entry information’ section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification (‘Last modified’). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: January 23, 2002
Last modified: January 16, 2019
This is version 196 of the entry and version 2 of the sequence. See complete history.
<p>This subsection of the ‘Entry information’ section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome X
    Human chromosome X: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  7. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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