ALAS2

Protein identityUniProt · HPA

UniProt accession

P22557

Gene

ALAS2

Ensembl

ENSG00000158578

Chromosome

X

Canonical length

587 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Potential drug targets, Predicted intracellular proteins

Quaternary structure

Homodimer

OverviewNCBI Gene

The product of this gene specifies an erythroid-specific mitochondrially located enzyme. The encoded protein catalyzes the first step in the heme biosynthetic pathway. Defects in this gene cause X-linked pyridoxine-responsive sideroblastic anemia. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

587 residues, UniProt reviewed canonical sequence.

>P22557|ALAS2
     1  MVTAAMLLQC CPVLARGPTS LLGKVVKTHQ FLFGIGRCPI LATQGPNCSQ IHLKATKAGG
    61  DSPSWAKGHC PFMLSELQDG KSKIVQKAAP EVQEDVKAFK TDLPSSLVSV SLRKPFSGPQ
   121  EQEQISGKVT HLIQNNMPGN YVFSYDQFFR DKIMEKKQDH TYRVFKTVNR WADAYPFAQH
   181  FSEASVASKD VSVWCSNDYL GMSRHPQVLQ ATQETLQRHG AGAGGTRNIS GTSKFHVELE
   241  QELAELHQKD SALLFSSCFV ANDSTLFTLA KILPGCEIYS DAGNHASMIQ GIRNSGAAKF
   301  VFRHNDPDHL KKLLEKSNPK IPKIVAFETV HSMDGAICPL EELCDVSHQY GALTFVDEVH
   361  AVGLYGSRGA GIGERDGIMH KIDIISGTLG KAFGCVGGYI ASTRDLVDMV RSYAAGFIFT
   421  TSLPPMVLSG ALESVRLLKG EEGQALRRAH QRNVKHMRQL LMDRGLPVIP CPSHIIPIRV
   481  GNAALNSKLC DLLLSKHGIY VQAINYPTVP RGEELLRLAP SPHHSPQMME DFVEKLLLAW
   541  TAVGLPLQDV SVAACNFCRR PVHFELMSEW ERSYFGNMGP QYVTTYA

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ALAS2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Other membrane

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.34

Highest tissue expression

571 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ALAS2.

Disease | AllUniProt

Conditions ALAS2 is implicated in, by any mechanism.

• Anemia, sideroblastic, 1 (SIDBA1) MIM:300751
• Erythropoietic protoporphyria, X-linked dominant (XLDPT) MIM:300752

Disease | GeneticClinVar

50 pathogenic / likely-pathogenic of 415 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• X-linked sideroblastic anemia 1
• X-linked erythropoietic protoporphyria
• Sideroblastic anemia 1, late-onset
• See cases
• ALAS2-related disorder

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.18

gnomAD pLI

1

gnomAD missense Z

2.37

DepMap mean gene effect

0.07

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 2% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• erythrocyte development
• erythrocyte differentiation
• heme B biosynthetic process
• heme biosynthetic process
• hemoglobin biosynthetic process
• intracellular iron ion homeostasis
• intracellular oxygen homeostasis
• protoporphyrinogen IX biosynthetic process
• response to hypoxia

Molecular functions

• 5-aminolevulinate synthase activity
• pyridoxal phosphate binding

Cellular components

• mitochondrial inner membrane
• mitochondrial matrix
• mitochondrion

Protein domainsUniProt · Pfam · InterPro

• Aminotransferase, class-II, pyridoxal-phosphate binding site
• Aminotransferase, class I/classII, large domain
• Tetrapyrrole biosynthesis, 5-aminolevulinic acid synthase
• 5-aminolevulinate synthase presequence
• Pyridoxal phosphate-dependent transferase, major domain
• Pyridoxal phosphate-dependent transferase, small domain
• Pyridoxal phosphate-dependent transferase
• 8-amino-7-oxononanoate synthase class-II
• Aminotransferase class I and II
• 5-aminolevulinate synthase presequence

KeywordsUniProt

• Acyltransferase
• Heme biosynthesis
• Membrane
• Mitochondrion
• Mitochondrion inner membrane
• Pyridoxal phosphate
• Transferase
• Transit peptide

InteractionsUniProt · HPA

Protein binding partners of ALAS2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• SUCLA2