UniProtKB - Q9P2K8 (E2AK4_HUMAN)
eIF-2-alpha kinase GCN2
EIF2AK4
Functioni
Metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) in response to low amino acid availability (PubMed:25329545).
Plays a role as an activator of the integrated stress response (ISR) required for adaptation to amino acid starvation (By similarity).
EIF2S1/eIF-2-alpha phosphorylation in response to stress converts EIF2S1/eIF-2-alpha into a global protein synthesis inhibitor, leading to a global attenuation of cap-dependent translation, and thus to a reduced overall utilization of amino acids, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activator ATF4, and hence allowing ATF4-mediated reprogramming of amino acid biosynthetic gene expression to alleviate nutrient depletion (By similarity).
Binds uncharged tRNAs (By similarity).
Required for the translational induction of protein kinase PRKCH following amino acid starvation (By similarity).
Involved in cell cycle arrest by promoting cyclin D1 mRNA translation repression after the unfolded protein response pathway (UPR) activation or cell cycle inhibitor CDKN1A/p21 mRNA translation activation in response to amino acid deprivation (PubMed:26102367).
Plays a role in the consolidation of synaptic plasticity, learning as well as formation of long-term memory (By similarity).
Plays a role in neurite outgrowth inhibition (By similarity).
Plays a proapoptotic role in response to glucose deprivation (By similarity).
Promotes global cellular protein synthesis repression in response to UV irradiation independently of the stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) and p38 MAPK signaling pathways (By similarity).
Plays a role in the antiviral response against alphavirus infection; impairs early viral mRNA translation of the incoming genomic virus RNA, thus preventing alphavirus replication (By similarity).
By similarity2 Publications(Microbial infection) Plays a role in modulating the adaptive immune response to yellow fever virus infection; promotes dendritic cells to initiate autophagy and antigene presentation to both CD4+ and CD8+ T-cells under amino acid starvation (PubMed:24310610).
1 PublicationCatalytic activityi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 619 | ATPPROSITE-ProRule annotation | 1 | |
Active sitei | 848 | Proton acceptorPROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 596 – 604 | ATPPROSITE-ProRule annotation | 9 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- eukaryotic translation initiation factor 2alpha kinase activity Source: UniProtKB
- protein kinase activity Source: GO_Central
- protein serine/threonine/tyrosine kinase activity Source: RHEA
- protein serine/threonine kinase activity Source: UniProtKB
- protein serine kinase activity Source: RHEA
- tRNA binding Source: UniProtKB
GO - Biological processi
- adaptive immune response Source: UniProtKB-KW
- cell cycle Source: UniProtKB-KW
- cellular response to amino acid starvation Source: UniProtKB
- cellular response to cold Source: UniProtKB
- cellular response to leucine starvation Source: UniProtKB
- cellular response to UV Source: UniProtKB
- defense response to virus Source: UniProtKB-KW
- DNA damage checkpoint signaling Source: InterPro
- eiF2alpha phosphorylation in response to endoplasmic reticulum stress Source: UniProtKB
- GCN2-mediated signaling Source: UniProtKB
- learning Source: UniProtKB
- long-term memory Source: UniProtKB
- negative regulation by host of viral genome replication Source: UniProtKB
- negative regulation of CREB transcription factor activity Source: UniProtKB
- negative regulation of neuron differentiation Source: UniProtKB
- negative regulation of translational initiation Source: UniProtKB
- negative regulation of translational initiation in response to stress Source: UniProtKB
- neuron projection extension Source: UniProtKB
- positive regulation of adaptive immune response Source: UniProtKB
- positive regulation of defense response to virus by host Source: UniProtKB
- positive regulation of long-term synaptic potentiation Source: UniProtKB
- positive regulation of protein phosphorylation Source: Ensembl
- positive regulation of translational initiation in response to starvation Source: UniProtKB
- protein autophosphorylation Source: UniProtKB
- protein phosphorylation Source: UniProtKB
- regulation of feeding behavior Source: UniProtKB
- regulation of translational initiation Source: UniProtKB
- regulation of translational initiation by eIF2 alpha phosphorylation Source: UniProtKB
- T cell activation involved in immune response Source: UniProtKB
- viral translation Source: UniProtKB
Keywordsi
Molecular function | Activator, Kinase, RNA-binding, Serine/threonine-protein kinase, Transferase, tRNA-binding |
Biological process | Activation of host autophagy by virus, Adaptive immunity, Antiviral defense, Cell cycle, Growth arrest, Host-virus interaction, Immunity, Neurogenesis, Stress response, Translation regulation |
Ligand | ATP-binding, Nucleotide-binding |
Enzyme and pathway databases
PathwayCommonsi | Q9P2K8 |
Reactomei | R-HSA-9633012, Response of EIF2AK4 (GCN2) to amino acid deficiency |
SignaLinki | Q9P2K8 |
SIGNORi | Q9P2K8 |
Names & Taxonomyi
Protein namesi | Recommended name: eIF-2-alpha kinase GCN2By similarity (EC:2.7.11.1By similarity)Alternative name(s): Eukaryotic translation initiation factor 2-alpha kinase 4Imported GCN2-like protein |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:19687, EIF2AK4 |
MIMi | 609280, gene |
neXtProti | NX_Q9P2K8 |
VEuPathDBi | HostDB:ENSG00000128829 |
Subcellular locationi
Cytoplasm and Cytosol
- Cytoplasm By similarity
Cytosol
- cytosol Source: GO_Central
- cytosolic ribosome Source: UniProtKB
Other locations
- polysome Source: UniProtKB
Keywords - Cellular componenti
CytoplasmPathology & Biotechi
Involvement in diseasei
Pulmonary venoocclusive disease 2, autosomal recessive (PVOD2)2 Publications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_070990 | 585 | R → Q in PVOD2. 1 PublicationCorresponds to variant dbSNP:rs587777106EnsemblClinVar. | 1 | |
Natural variantiVAR_070991 | 643 | L → R in PVOD2. 1 PublicationCorresponds to variant dbSNP:rs757852728EnsemblClinVar. | 1 |
Keywords - Diseasei
Disease variantOrganism-specific databases
DisGeNETi | 440275 |
MalaCardsi | EIF2AK4 |
MIMi | 234810, phenotype |
OpenTargetsi | ENSG00000128829 |
Orphaneti | 275777, Heritable pulmonary arterial hypertension 199241, Pulmonary capillary hemangiomatosis 31837, Pulmonary venoocclusive disease |
PharmGKBi | PA134947616 |
Miscellaneous databases
Pharosi | Q9P2K8, Tchem |
Chemistry databases
ChEMBLi | CHEMBL5358 |
DrugBanki | DB12010, Fostamatinib |
DrugCentrali | Q9P2K8 |
GuidetoPHARMACOLOGYi | 2018 |
Genetic variation databases
BioMutai | EIF2AK4 |
DMDMi | 296439368 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000085947 | 1 – 1649 | eIF-2-alpha kinase GCN2Add BLAST | 1649 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 230 | PhosphoserineCombined sources | 1 | |
Modified residuei | 667 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 871 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 899 | Phosphothreonine; by autocatalysisBy similarity | 1 | |
Modified residuei | 904 | Phosphothreonine; by autocatalysisBy similarity | 1 | |
Modified residuei | 1259 | N6-acetyllysineCombined sources | 1 |
Post-translational modificationi
Keywords - PTMi
Acetylation, PhosphoproteinProteomic databases
EPDi | Q9P2K8 |
jPOSTi | Q9P2K8 |
MassIVEi | Q9P2K8 |
MaxQBi | Q9P2K8 |
PaxDbi | Q9P2K8 |
PeptideAtlasi | Q9P2K8 |
PRIDEi | Q9P2K8 |
ProteomicsDBi | 83838 [Q9P2K8-1] 83839 [Q9P2K8-2] 83840 [Q9P2K8-3] |
PTM databases
iPTMneti | Q9P2K8 |
PhosphoSitePlusi | Q9P2K8 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000128829, Expressed in adenohypophysis and 217 other tissues |
ExpressionAtlasi | Q9P2K8, baseline and differential |
Genevisiblei | Q9P2K8, HS |
Organism-specific databases
HPAi | ENSG00000128829, Low tissue specificity |
Interactioni
Subunit structurei
Homodimer; homodimerization is important for kinase activation by uncharged tRNAs.
Interacts with GCN1; this interaction stimulates EIF2AK4/GCN2 kinase activity and is impaired by IMPACT upon a variety of stress conditions, such as amino acid depletion, UV-C irradiation, proteasome inhibitor treatment and glucose deprivation.
Interacts with DNAJC3; this interaction inhibits EIF2AK4/GCN2 kinase activity during endoplasmic reticulum (ER), hypothermic and amino acid-starving stress conditions.
By similarityProtein-protein interaction databases
BioGRIDi | 136426, 65 interactors |
IntActi | Q9P2K8, 32 interactors |
STRINGi | 9606.ENSP00000263791 |
Chemistry databases
BindingDBi | Q9P2K8 |
Miscellaneous databases
RNActi | Q9P2K8, protein |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | Q9P2K8 |
SMRi | Q9P2K8 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 25 – 137 | RWDPROSITE-ProRule annotationAdd BLAST | 113 | |
Domaini | 296 – 539 | Protein kinase 1PROSITE-ProRule annotationAdd BLAST | 244 | |
Domaini | 590 – 1001 | Protein kinase 2PROSITE-ProRule annotationAdd BLAST | 412 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 25 | DisorderedSequence analysisAdd BLAST | 25 | |
Regioni | 138 – 158 | DisorderedSequence analysisAdd BLAST | 21 | |
Regioni | 227 – 256 | DisorderedSequence analysisAdd BLAST | 30 | |
Regioni | 660 – 750 | DisorderedSequence analysisAdd BLAST | 91 | |
Regioni | 765 – 788 | DisorderedSequence analysisAdd BLAST | 24 | |
Regioni | 1022 – 1493 | Histidyl-tRNA synthetase-likeAdd BLAST | 472 |
Coiled coil
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Coiled coili | 146 – 205 | Sequence analysisAdd BLAST | 60 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 140 – 158 | Basic and acidic residuesSequence analysisAdd BLAST | 19 | |
Compositional biasi | 706 – 720 | Polar residuesSequence analysisAdd BLAST | 15 | |
Compositional biasi | 765 – 783 | Basic and acidic residuesSequence analysisAdd BLAST | 19 |
Domaini
Sequence similaritiesi
Keywords - Domaini
Coiled coil, RepeatPhylogenomic databases
eggNOGi | KOG1035, Eukaryota |
GeneTreei | ENSGT00940000156798 |
HOGENOMi | CLU_493107_0_0_1 |
InParanoidi | Q9P2K8 |
OMAi | GSEMIYE |
OrthoDBi | 64059at2759 |
PhylomeDBi | Q9P2K8 |
TreeFami | TF101512 |
Family and domain databases
Gene3Di | 3.10.110.10, 1 hit 3.30.930.10, 1 hit 3.40.50.800, 1 hit |
InterProi | View protein in InterPro IPR045864, aa-tRNA-synth_II/BPL/LPL IPR036621, Anticodon-bd_dom_sf IPR016255, Gcn2 IPR041715, HisRS-like_core IPR024435, HisRS-related_dom IPR011009, Kinase-like_dom_sf IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS IPR006575, RWD-domain IPR008271, Ser/Thr_kinase_AS IPR016135, UBQ-conjugating_enzyme/RWD |
Pfami | View protein in Pfam PF12745, HGTP_anticodon2, 1 hit PF00069, Pkinase, 3 hits PF05773, RWD, 1 hit PF13393, tRNA-synt_His, 1 hit |
PIRSFi | PIRSF000660, Ser/Thr_PK_GCN2, 1 hit |
SMARTi | View protein in SMART SM00591, RWD, 1 hit SM00220, S_TKc, 2 hits |
SUPFAMi | SSF54495, SSF54495, 1 hit SSF55681, SSF55681, 1 hit SSF56112, SSF56112, 2 hits |
PROSITEi | View protein in PROSITE PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 2 hits PS00108, PROTEIN_KINASE_ST, 1 hit PS50908, RWD, 1 hit |
s (3+)i Sequence
Sequence statusi: Complete.
This entry describes 3 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 3 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MAGGRGAPGR GRDEPPESYP QRQDHELQAL EAIYGADFQD LRPDACGPVK
60 70 80 90 100
EPPEINLVLY PQGLTGEEVY VKVDLRVKCP PTYPDVVPEI ELKNAKGLSN
110 120 130 140 150
ESVNLLKSRL EELAKKHCGE VMIFELAYHV QSFLSEHNKP PPKSFHEEML
160 170 180 190 200
ERRAQEEQQR LLEAKRKEEQ EQREILHEIQ RRKEEIKEEK KRKEMAKQER
210 220 230 240 250
LEIASLSNQD HTSKKDPGGH RTAAILHGGS PDFVGNGKHR ANSSGRSRRE
260 270 280 290 300
RQYSVCNSED SPGSCEILYF NMGSPDQLMV HKGKCIGSDE QLGKLVYNAL
310 320 330 340 350
ETATGGFVLL YEWVLQWQKK MGPFLTSQEK EKIDKCKKQI QGTETEFNSL
360 370 380 390 400
VKLSHPNVVR YLAMNLKEQD DSIVVDILVE HISGVSLAAH LSHSGPIPVH
410 420 430 440 450
QLRRYTAQLL SGLDYLHSNS VVHKVLSASN VLVDAEGTVK ITDYSISKRL
460 470 480 490 500
ADICKEDVFE QTRVRFSDNA LPYKTGKKGD VWRLGLLLLS LSQGQECGEY
510 520 530 540 550
PVTIPSDLPA DFQDFLKKCV CLDDKERWSP QQLLKHSFIN PQPKMPLVEQ
560 570 580 590 600
SPEDSEGQDY VETVIPSNRL PSAAFFSETQ RQFSRYFIEF EELQLLGKGA
610 620 630 640 650
FGAVIKVQNK LDGCCYAVKR IPINPASRQF RRIKGEVTLL SRLHHENIVR
660 670 680 690 700
YYNAWIERHE RPAGPGTPPP DSGPLAKDDR AARGQPASDT DGLDSVEAAA
710 720 730 740 750
PPPILSSSVE WSTSGERSAS ARFPATGPGS SDDEDDDEDE HGGVFSQSFL
760 770 780 790 800
PASDSESDII FDNEDENSKS QNQDEDCNEK NGCHESEPSV TTEAVHYLYI
810 820 830 840 850
QMEYCEKSTL RDTIDQGLYR DTVRLWRLFR EILDGLAYIH EKGMIHRDLK
860 870 880 890 900
PVNIFLDSDD HVKIGDFGLA TDHLAFSADS KQDDQTGDLI KSDPSGHLTG
910 920 930 940 950
MVGTALYVSP EVQGSTKSAY NQKVDLFSLG IIFFEMSYHP MVTASERIFV
960 970 980 990 1000
LNQLRDPTSP KFPEDFDDGE HAKQKSVISW LLNHDPAKRP TATELLKSEL
1010 1020 1030 1040 1050
LPPPQMEESE LHEVLHHTLT NVDGKAYRTM MAQIFSQRIS PAIDYTYDSD
1060 1070 1080 1090 1100
ILKGNFSIRT AKMQQHVCET IIRIFKRHGA VQLCTPLLLP RNRQIYEHNE
1110 1120 1130 1140 1150
AALFMDHSGM LVMLPFDLRI PFARYVARNN ILNLKRYCIE RVFRPRKLDR
1160 1170 1180 1190 1200
FHPKELLECA FDIVTSTTNS FLPTAEIIYT IYEIIQEFPA LQERNYSIYL
1210 1220 1230 1240 1250
NHTMLLKAIL LHCGIPEDKL SQVYIILYDA VTEKLTRREV EAKFCNLSLS
1260 1270 1280 1290 1300
SNSLCRLYKF IEQKGDLQDL MPTINSLIKQ KTGIAQLVKY GLKDLEEVVG
1310 1320 1330 1340 1350
LLKKLGIKLQ VLINLGLVYK VQQHNGIIFQ FVAFIKRRQR AVPEILAAGG
1360 1370 1380 1390 1400
RYDLLIPQFR GPQALGPVPT AIGVSIAIDK ISAAVLNMEE SVTISSCDLL
1410 1420 1430 1440 1450
VVSVGQMSMS RAINLTQKLW TAGITAEIMY DWSQSQEELQ EYCRHHEITY
1460 1470 1480 1490 1500
VALVSDKEGS HVKVKSFEKE RQTEKRVLET ELVDHVLQKL RTKVTDERNG
1510 1520 1530 1540 1550
REASDNLAVQ NLKGSFSNAS GLFEIHGATV VPIVSVLAPE KLSASTRRRY
1560 1570 1580 1590 1600
ETQVQTRLQT SLANLHQKSS EIEILAVDLP KETILQFLSL EWDADEQAFN
1610 1620 1630 1640
TTVKQLLSRL PKQRYLKLVC DEIYNIKVEK KVSVLFLYSY RDDYYRILF
Computationally mapped potential isoform sequencesi
There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketH0YME5 | H0YME5_HUMAN | Non-specific serine/threonine prote... | EIF2AK4 | 1,427 | Annotation score: | ||
H0YND8 | H0YND8_HUMAN | eIF-2-alpha kinase GCN2 | EIF2AK4 | 136 | Annotation score: | ||
H0YNY9 | H0YNY9_HUMAN | eIF-2-alpha kinase GCN2 | EIF2AK4 | 80 | Annotation score: |
Sequence cautioni
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 556 | E → G in BAA92576 (PubMed:10718198).Curated | 1 | |
Sequence conflicti | 556 | E → G in CAH10626 (PubMed:17974005).Curated | 1 | |
Sequence conflicti | 629 | Q → K in CAH10626 (PubMed:17974005).Curated | 1 | |
Sequence conflicti | 858 | S → F in BAB15625 (PubMed:14702039).Curated | 1 | |
Sequence conflicti | 1133 | N → I in CAB58360 (PubMed:10504407).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_040479 | 137 | H → R1 PublicationCorresponds to variant dbSNP:rs35509999Ensembl. | 1 | |
Natural variantiVAR_040480 | 166 | R → W1 PublicationCorresponds to variant dbSNP:rs34439704Ensembl. | 1 | |
Natural variantiVAR_040481 | 441 | I → L2 PublicationsCorresponds to variant dbSNP:rs2291627EnsemblClinVar. | 1 | |
Natural variantiVAR_070990 | 585 | R → Q in PVOD2. 1 PublicationCorresponds to variant dbSNP:rs587777106EnsemblClinVar. | 1 | |
Natural variantiVAR_070991 | 643 | L → R in PVOD2. 1 PublicationCorresponds to variant dbSNP:rs757852728EnsemblClinVar. | 1 | |
Natural variantiVAR_040482 | 872 | D → V1 PublicationCorresponds to variant dbSNP:rs34665481Ensembl. | 1 | |
Natural variantiVAR_040483 | 939 | H → Y in a lung neuroendocrine carcinoma sample; somatic mutation. 1 Publication | 1 | |
Natural variantiVAR_040484 | 1060 | T → R1 PublicationCorresponds to variant dbSNP:rs55781333Ensembl. | 1 | |
Natural variantiVAR_040485 | 1306 | G → C2 PublicationsCorresponds to variant dbSNP:rs35602605EnsemblClinVar. | 1 | |
Natural variantiVAR_040486 | 1336 | K → R1 PublicationCorresponds to variant dbSNP:rs35480871EnsemblClinVar. | 1 | |
Natural variantiVAR_040487 | 1406 | Q → H1 PublicationCorresponds to variant dbSNP:rs55721315EnsemblClinVar. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_039185 | 608 – 616 | QNKLDGCCY → WYRVIPSPL in isoform 3. 1 Publication | 9 | |
Alternative sequenceiVSP_039186 | 617 – 1649 | Missing in isoform 3. 1 PublicationAdd BLAST | 1033 | |
Alternative sequenceiVSP_013038 | 774 – 801 | Missing in isoform 2. CuratedAdd BLAST | 28 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AC012377 Genomic DNA No translation available. AC025168 Genomic DNA No translation available. BC009350 mRNA Translation: AAH09350.2 BC078179 mRNA Translation: AAH78179.1 AB037759 mRNA Translation: BAA92576.1 Sequence problems. AL137627 mRNA Translation: CAB70849.1 AL157497 mRNA Translation: CAB75678.1 AL832907 mRNA Translation: CAH10626.1 AK027011 mRNA Translation: BAB15625.1 Different initiation. AJ243428 mRNA Translation: CAB58360.1 |
CCDSi | CCDS42016.1 [Q9P2K8-1] |
PIRi | T46924 |
RefSeqi | NP_001013725.2, NM_001013703.3 [Q9P2K8-1] |
Genome annotation databases
Ensembli | ENST00000263791.10; ENSP00000263791.5; ENSG00000128829.12 ENST00000559624.5; ENSP00000453148.1; ENSG00000128829.12 [Q9P2K8-3] |
GeneIDi | 440275 |
KEGGi | hsa:440275 |
MANE-Selecti | ENST00000263791.10; ENSP00000263791.5; NM_001013703.4; NP_001013725.2 |
UCSCi | uc001zkl.4, human [Q9P2K8-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AC012377 Genomic DNA No translation available. AC025168 Genomic DNA No translation available. BC009350 mRNA Translation: AAH09350.2 BC078179 mRNA Translation: AAH78179.1 AB037759 mRNA Translation: BAA92576.1 Sequence problems. AL137627 mRNA Translation: CAB70849.1 AL157497 mRNA Translation: CAB75678.1 AL832907 mRNA Translation: CAH10626.1 AK027011 mRNA Translation: BAB15625.1 Different initiation. AJ243428 mRNA Translation: CAB58360.1 |
CCDSi | CCDS42016.1 [Q9P2K8-1] |
PIRi | T46924 |
RefSeqi | NP_001013725.2, NM_001013703.3 [Q9P2K8-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
6N3L | X-ray | 2.61 | A/B | 577-657 | [»] | |
A/B | 782-1013 | [»] | ||||
6N3N | X-ray | 3.01 | A | 577-1013 | [»] | |
6N3O | X-ray | 2.40 | A | 577-1013 | [»] | |
7E2K | X-ray | 2.04 | A | 17-139 | [»] | |
7E2M | X-ray | 2.35 | A/B/C/D/E/F | 17-139 | [»] | |
AlphaFoldDBi | Q9P2K8 | |||||
SMRi | Q9P2K8 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 136426, 65 interactors |
IntActi | Q9P2K8, 32 interactors |
STRINGi | 9606.ENSP00000263791 |
Chemistry databases
BindingDBi | Q9P2K8 |
ChEMBLi | CHEMBL5358 |
DrugBanki | DB12010, Fostamatinib |
DrugCentrali | Q9P2K8 |
GuidetoPHARMACOLOGYi | 2018 |
PTM databases
iPTMneti | Q9P2K8 |
PhosphoSitePlusi | Q9P2K8 |
Genetic variation databases
BioMutai | EIF2AK4 |
DMDMi | 296439368 |
Proteomic databases
EPDi | Q9P2K8 |
jPOSTi | Q9P2K8 |
MassIVEi | Q9P2K8 |
MaxQBi | Q9P2K8 |
PaxDbi | Q9P2K8 |
PeptideAtlasi | Q9P2K8 |
PRIDEi | Q9P2K8 |
ProteomicsDBi | 83838 [Q9P2K8-1] 83839 [Q9P2K8-2] 83840 [Q9P2K8-3] |
Protocols and materials databases
Antibodypediai | 22934, 420 antibodies from 36 providers |
DNASUi | 440275 |
Genome annotation databases
Ensembli | ENST00000263791.10; ENSP00000263791.5; ENSG00000128829.12 ENST00000559624.5; ENSP00000453148.1; ENSG00000128829.12 [Q9P2K8-3] |
GeneIDi | 440275 |
KEGGi | hsa:440275 |
MANE-Selecti | ENST00000263791.10; ENSP00000263791.5; NM_001013703.4; NP_001013725.2 |
UCSCi | uc001zkl.4, human [Q9P2K8-1] |
Organism-specific databases
CTDi | 440275 |
DisGeNETi | 440275 |
GeneCardsi | EIF2AK4 |
HGNCi | HGNC:19687, EIF2AK4 |
HPAi | ENSG00000128829, Low tissue specificity |
MalaCardsi | EIF2AK4 |
MIMi | 234810, phenotype 609280, gene |
neXtProti | NX_Q9P2K8 |
OpenTargetsi | ENSG00000128829 |
Orphaneti | 275777, Heritable pulmonary arterial hypertension 199241, Pulmonary capillary hemangiomatosis 31837, Pulmonary venoocclusive disease |
PharmGKBi | PA134947616 |
VEuPathDBi | HostDB:ENSG00000128829 |
HUGEi | Search... |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1035, Eukaryota |
GeneTreei | ENSGT00940000156798 |
HOGENOMi | CLU_493107_0_0_1 |
InParanoidi | Q9P2K8 |
OMAi | GSEMIYE |
OrthoDBi | 64059at2759 |
PhylomeDBi | Q9P2K8 |
TreeFami | TF101512 |
Enzyme and pathway databases
PathwayCommonsi | Q9P2K8 |
Reactomei | R-HSA-9633012, Response of EIF2AK4 (GCN2) to amino acid deficiency |
SignaLinki | Q9P2K8 |
SIGNORi | Q9P2K8 |
Miscellaneous databases
BioGRID-ORCSi | 440275, 64 hits in 1085 CRISPR screens |
ChiTaRSi | EIF2AK4, human |
GeneWikii | EIF2AK4 |
GenomeRNAii | 440275 |
Pharosi | Q9P2K8, Tchem |
PROi | PR:Q9P2K8 |
RNActi | Q9P2K8, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000128829, Expressed in adenohypophysis and 217 other tissues |
ExpressionAtlasi | Q9P2K8, baseline and differential |
Genevisiblei | Q9P2K8, HS |
Family and domain databases
Gene3Di | 3.10.110.10, 1 hit 3.30.930.10, 1 hit 3.40.50.800, 1 hit |
InterProi | View protein in InterPro IPR045864, aa-tRNA-synth_II/BPL/LPL IPR036621, Anticodon-bd_dom_sf IPR016255, Gcn2 IPR041715, HisRS-like_core IPR024435, HisRS-related_dom IPR011009, Kinase-like_dom_sf IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS IPR006575, RWD-domain IPR008271, Ser/Thr_kinase_AS IPR016135, UBQ-conjugating_enzyme/RWD |
Pfami | View protein in Pfam PF12745, HGTP_anticodon2, 1 hit PF00069, Pkinase, 3 hits PF05773, RWD, 1 hit PF13393, tRNA-synt_His, 1 hit |
PIRSFi | PIRSF000660, Ser/Thr_PK_GCN2, 1 hit |
SMARTi | View protein in SMART SM00591, RWD, 1 hit SM00220, S_TKc, 2 hits |
SUPFAMi | SSF54495, SSF54495, 1 hit SSF55681, SSF55681, 1 hit SSF56112, SSF56112, 2 hits |
PROSITEi | View protein in PROSITE PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 2 hits PS00108, PROTEIN_KINASE_ST, 1 hit PS50908, RWD, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | E2AK4_HUMAN | |
Accessioni | Q9P2K8Primary (citable) accession number: Q9P2K8 Secondary accession number(s): C9JEC4 Q9UJ56 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | March 15, 2005 |
Last sequence update: | May 18, 2010 | |
Last modified: | May 25, 2022 | |
This is version 184 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human and mouse protein kinases
Human and mouse protein kinases: classification and index - Human chromosome 15
Human chromosome 15: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families