Seroatlas · Human Serome Atlas

EIF2AK3

Eukaryotic translation initiation factor 2-alpha kinase 3

Also known as: E2AK3_HUMAN, PEK, PERK

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession: Q9NZJ5
Gene: EIF2AK3
Ensembl: ENSG00000172071
Chromosome: 2
Canonical length: 1116 aa
Protein class: Disease related genes, Enzymes, Human disease related genes, Potential drug targets, Predicted intracellular proteins, Predicted membrane proteins
Quaternary structure: Homotetramer

OverviewNCBI Gene

The protein encoded by this gene phosphorylates the alpha subunit of eukaryotic translation-initiation factor 2, leading to its inactivation, and thus to a rapid reduction of translational initiation and repression of global protein synthesis. This protein is thought to modulate mitochondrial function. It is a type I membrane protein located in the endoplasmic reticulum (ER), where it is induced by ER stress caused by malfolded proteins. Mutations in this gene are associated with Wolcott-Rallison syndrome. [provided by RefSeq, Sep 2015]

Canonical amino-acid sequenceUniProt

1116 residues, UniProt reviewed canonical sequence.

>Q9NZJ5|EIF2AK3
     1  MERAISPGLL VRALLLLLLL LGLAARTVAA GRARGLPAPT AEAAFGLGAA AAPTSATRVP
    61  AAGAVAAAEV TVEDAEALPA AAGEQEPRGP EPDDETELRP RGRSLVIIST LDGRIAALDP
   121  ENHGKKQWDL DVGSGSLVSS SLSKPEVFGN KMIIPSLDGA LFQWDQDRES METVPFTVES
   181  LLESSYKFGD DVVLVGGKSL TTYGLSAYSG KVRYICSALG CRQWDSDEME QEEDILLLQR
   241  TQKTVRAVGP RSGNEKWNFS VGHFELRYIP DMETRAGFIE STFKPNENTE ESKIISDVEE
   301  QEAAIMDIVI KVSVADWKVM AFSKKGGHLE WEYQFCTPIA SAWLLKDGKV IPISLFDDTS
   361  YTSNDDVLED EEDIVEAARG ATENSVYLGM YRGQLYLQSS VRISEKFPSS PKALESVTNE
   421  NAIIPLPTIK WKPLIHSPSR TPVLVGSDEF DKCLSNDKFS HEEYSNGALS ILQYPYDNGY
   481  YLPYYKRERN KRSTQITVRF LDNPHYNKNI RKKDPVLLLH WWKEIVATIL FCIIATTFIV
   541  RRLFHPHPHR QRKESETQCQ TENKYDSVSG EANDSSWNDI KNSGYISRYL TDFEPIQCLG
   601  RGGFGVVFEA KNKVDDCNYA IKRIRLPNRE LAREKVMREV KALAKLEHPG IVRYFNAWLE
   661  APPEKWQEKM DEIWLKDEST DWPLSSPSPM DAPSVKIRRM DPFATKEHIE IIAPSPQRSR
   721  SFSVGISCDQ TSSSESQFSP LEFSGMDHED ISESVDAAYN LQDSCLTDCD VEDGTMDGND
   781  EGHSFELCPS EASPYVRSRE RTSSSIVFED SGCDNASSKE EPKTNRLHIG NHCANKLTAF
   841  KPTSSKSSSE ATLSISPPRP TTLSLDLTKN TTEKLQPSSP KVYLYIQMQL CRKENLKDWM
   901  NGRCTIEERE RSVCLHIFLQ IAEAVEFLHS KGLMHRDLKP SNIFFTMDDV VKVGDFGLVT
   961  AMDQDEEEQT VLTPMPAYAR HTGQVGTKLY MSPEQIHGNS YSHKVDIFSL GLILFELLYP
  1021  FSTQMERVRT LTDVRNLKFP PLFTQKYPCE YVMVQDMLSP SPMERPEAIN IIENAVFEDL
  1081  DFPGKTVLRQ RSRSLSSSGT KHSRQSNNSH SPLPSN

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against EIF2AK3 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: 1
Mean surface accessibility (rSASA): 0.46
Highest tissue expression: 20 nTPM

Expression across tissuesHPA

Tissue

pancreas: 20 nTPM
salivary gland: 12 nTPM
stomach: 11 nTPM
duodenum: 5.3 nTPM
appendix: 4.9 nTPM
adrenal gland: 4.8 nTPM

Single-cell type

plasma cells: 941 nCPM
b-cells: 452 nCPM
epididymal principal cells: 450 nCPM
monocytes: 407 nCPM
pancreatic acinar cells: 395 nCPM
salivary acinar cells: 297 nCPM

Immune cell

naive B-cell: 1.8 nTPM
memory B-cell: 1.2 nTPM
plasmacytoid DC: 1.1 nTPM
T-reg: 0.7 nTPM
memory CD8 T-cell: 0.6 nTPM
MAIT T-cell: 0.4 nTPM

Brain region

white matter: 5.8 nTPM
cerebellum: 5.4 nTPM
hypothalamus: 5.1 nTPM
spinal cord: 5 nTPM
choroid plexus: 4.8 nTPM
cerebral cortex: 4.7 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about EIF2AK3.

Disease | AllUniProt

Conditions EIF2AK3 is implicated in, by any mechanism.

Wolcott-Rallison syndrome (WRS) MIM:226980

Disease | GeneticClinVar

110 pathogenic / likely-pathogenic of 1,045 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

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): 0.45
gnomAD pLI: 0
gnomAD missense Z: 2.03
DepMap mean gene effect: -0.08
DepMap dependency class: selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 6% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of EIF2AK3 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads EIF2AK3 as an antibody target. Whether an autoantibody or antibody against EIF2AK3 could matter depends on whether native EIF2AK3 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

EIF2AK3 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.

Annotation status

The present source text does not explicitly label EIF2AK3 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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