EIF2AK4

Protein identityUniProt · HPA

UniProt accession

Q9P2K8

Gene

EIF2AK4

Ensembl

ENSG00000128829

Chromosome

15

Canonical length

1649 aa

Protein class

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

Subcellular location

Cytosol

Quaternary structure

Homodimer

OverviewNCBI Gene

This gene encodes a member of a family of kinases that phosphorylate the alpha subunit of eukaryotic translation initiation factor-2 (EIF2), resulting in the downregulaton of protein synthesis. The encoded protein responds to amino acid deprivation by binding uncharged transfer RNAs. It may also be activated by glucose deprivation and viral infection. Mutations in this gene have been found in individuals suffering from autosomal recessive pulmonary venoocclusive-disease-2. [provided by RefSeq, Mar 2014]

Canonical amino-acid sequenceUniProt

1649 residues, UniProt reviewed canonical sequence.

>Q9P2K8|EIF2AK4
     1  MAGGRGAPGR GRDEPPESYP QRQDHELQAL EAIYGADFQD LRPDACGPVK EPPEINLVLY
    61  PQGLTGEEVY VKVDLRVKCP PTYPDVVPEI ELKNAKGLSN ESVNLLKSRL EELAKKHCGE
   121  VMIFELAYHV QSFLSEHNKP PPKSFHEEML ERRAQEEQQR LLEAKRKEEQ EQREILHEIQ
   181  RRKEEIKEEK KRKEMAKQER LEIASLSNQD HTSKKDPGGH RTAAILHGGS PDFVGNGKHR
   241  ANSSGRSRRE RQYSVCNSED SPGSCEILYF NMGSPDQLMV HKGKCIGSDE QLGKLVYNAL
   301  ETATGGFVLL YEWVLQWQKK MGPFLTSQEK EKIDKCKKQI QGTETEFNSL VKLSHPNVVR
   361  YLAMNLKEQD DSIVVDILVE HISGVSLAAH LSHSGPIPVH QLRRYTAQLL SGLDYLHSNS
   421  VVHKVLSASN VLVDAEGTVK ITDYSISKRL ADICKEDVFE QTRVRFSDNA LPYKTGKKGD
   481  VWRLGLLLLS LSQGQECGEY PVTIPSDLPA DFQDFLKKCV CLDDKERWSP QQLLKHSFIN
   541  PQPKMPLVEQ SPEDSEGQDY VETVIPSNRL PSAAFFSETQ RQFSRYFIEF EELQLLGKGA
   601  FGAVIKVQNK LDGCCYAVKR IPINPASRQF RRIKGEVTLL SRLHHENIVR YYNAWIERHE
   661  RPAGPGTPPP DSGPLAKDDR AARGQPASDT DGLDSVEAAA PPPILSSSVE WSTSGERSAS
   721  ARFPATGPGS SDDEDDDEDE HGGVFSQSFL PASDSESDII FDNEDENSKS QNQDEDCNEK
   781  NGCHESEPSV TTEAVHYLYI QMEYCEKSTL RDTIDQGLYR DTVRLWRLFR EILDGLAYIH
   841  EKGMIHRDLK PVNIFLDSDD HVKIGDFGLA TDHLAFSADS KQDDQTGDLI KSDPSGHLTG
   901  MVGTALYVSP EVQGSTKSAY NQKVDLFSLG IIFFEMSYHP MVTASERIFV LNQLRDPTSP
   961  KFPEDFDDGE HAKQKSVISW LLNHDPAKRP TATELLKSEL LPPPQMEESE LHEVLHHTLT
  1021  NVDGKAYRTM MAQIFSQRIS PAIDYTYDSD ILKGNFSIRT AKMQQHVCET IIRIFKRHGA
  1081  VQLCTPLLLP RNRQIYEHNE AALFMDHSGM LVMLPFDLRI PFARYVARNN ILNLKRYCIE
  1141  RVFRPRKLDR FHPKELLECA FDIVTSTTNS FLPTAEIIYT IYEIIQEFPA LQERNYSIYL
  1201  NHTMLLKAIL LHCGIPEDKL SQVYIILYDA VTEKLTRREV EAKFCNLSLS SNSLCRLYKF
  1261  IEQKGDLQDL MPTINSLIKQ KTGIAQLVKY GLKDLEEVVG LLKKLGIKLQ VLINLGLVYK
  1321  VQQHNGIIFQ FVAFIKRRQR AVPEILAAGG RYDLLIPQFR GPQALGPVPT AIGVSIAIDK
  1381  ISAAVLNMEE SVTISSCDLL VVSVGQMSMS RAINLTQKLW TAGITAEIMY DWSQSQEELQ
  1441  EYCRHHEITY VALVSDKEGS HVKVKSFEKE RQTEKRVLET ELVDHVLQKL RTKVTDERNG
  1501  REASDNLAVQ NLKGSFSNAS GLFEIHGATV VPIVSVLAPE KLSASTRRRY ETQVQTRLQT
  1561  SLANLHQKSS EIEILAVDLP KETILQFLSL EWDADEQAFN TTVKQLLSRL PKQRYLKLVC
  1621  DEIYNIKVEK KVSVLFLYSY RDDYYRILF

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against EIF2AK4 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

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.37

Highest tissue expression

29 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about EIF2AK4.

Disease | AllUniProt

Conditions EIF2AK4 is implicated in, by any mechanism.

• Pulmonary venoocclusive disease 2, autosomal recessive (PVOD2) MIM:234810

Disease | GeneticClinVar

80 pathogenic / likely-pathogenic of 589 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Familial pulmonary capillary hemangiomatosis
• Pulmonary arterial hypertension
• EIF2AK4-related disorder
• Pulmonary venoocclusive disease 1

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)

0.57

gnomAD pLI

0

gnomAD missense Z

2.67

DepMap mean gene effect

-0.09

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• adaptive immune response
• cellular response to amino acid starvation
• cellular response to cold
• cellular response to UV
• defense response to virus
• DNA damage checkpoint signaling
• GCN2-mediated signaling
• host-mediated suppression of viral genome replication
• learning
• long-term memory
• negative regulation of CREB transcription factor activity
• negative regulation of neuron differentiation
• negative regulation of translational initiation
• negative regulation of translational initiation in response to stress
• neuron projection extension
• positive regulation of adaptive immune response
• positive regulation of defense response to virus by host
• positive regulation of long-term synaptic potentiation
• protein autophosphorylation
• protein phosphorylation
• regulation of feeding behavior
• regulation of translational initiation
• response to amino acid starvation
• T cell activation involved in immune response
• positive regulation of translational initiation in response to starvation
• regulation of translational initiation by eIF2 alpha phosphorylation
• viral translation

Molecular functions

• ATP binding
• eukaryotic translation initiation factor 2alpha kinase activity
• protein kinase activity
• protein serine kinase activity
• protein serine/threonine kinase activity
• tRNA binding

Cellular components

• cytoplasm
• cytosol
• cytosolic ribosome
• nucleus

Protein domainsUniProt · Pfam · InterPro

• Protein kinase domain
• RWD domain
• Serine/threonine-protein kinase, active site
• Protein kinase-like domain superfamily
• Ubiquitin-conjugating enzyme/RWD-like
• Protein kinase, ATP binding site
• Anticodon-binding domain superfamily
• Class II Histidinyl-tRNA synthetase (HisRS)-like catalytic core domain
• Class II Aminoacyl-tRNA synthetase/Biotinyl protein ligase (BPL) and lipoyl protein ligase (LPL)
• Cell Cycle and Stress Response Kinase
• Protein kinase domain
• RWD domain
• Histidyl-tRNA synthetase
• eIF-2-alpha kinase Gcn2
• Histidyl tRNA synthetase-related domain
• Anticodon binding domain of tRNAs

KeywordsUniProt

• Acetylation
• Activator
• Adaptive immunity
• Antiviral defense
• ATP-binding
• Cell cycle
• Coiled coil
• Cytoplasm
• Growth arrest
• Host-virus interaction
• Immunity
• Kinase
• Neurogenesis
• Nucleotide-binding
• Phosphoprotein
• Repeat
• RNA-binding
• Serine/threonine-protein kinase
• Stress response
• Transferase
• Translation regulation
• tRNA-binding
• Activation of host autophagy by virus

InteractionsUniProt · HPA

Protein binding partners of EIF2AK4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• DNAJC3
• GCN1
• MAP3K20