DegronMD - Q9P2K8(EIF2AK4)

FUNCTION: 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). {ECO:0000250|UniProtKB:P15442, ECO:0000250|UniProtKB:Q9QZ05, ECO:0000269|PubMed:25329545, ECO:0000269|PubMed:26102367}.; FUNCTION: (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). {ECO:0000269|PubMed:24310610}. View more >>

GO - Biological processes (BP): View more >>

GO - Molecular function (MF): View more >>

GO - Cellular component (CC): View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.C79Y	TCGA-A7-A6VV	BRCA	TCGA	PPTY	ITCH	80:83	Mutation rewiring degron network	0.3056
p.C79Y	DO50015	BRCA	ICGC	PPTY	ITCH	80:83	Mutation rewiring degron network	0.3056
p.Y70S	TCGA-AA-3532	COAD	TCGA	PPTY	ITCH	80:83	Mutation rewiring degron network	0.0556
p.Y70S	DO8930	COAD	ICGC	PPTY	ITCH	80:83	Mutation rewiring degron network	0.0556
p.V87A	DO225167	BRCA	ICGC	PPTY	ITCH	80:83	Mutation rewiring degron network	0.2222
p.T82A	DO50813	LIRI	ICGC	PPTY	ITCH	80:83	Mutation altering degron motif	0.6028
p.H177L	DO45261	LIRI	ICGC	QREILHEIQ	DEG_APCC_DBOX_1	172:180	Mutation altering degron motif	0.6202
p.D74N	SIDM01021	Glioblastoma	GDSC	PPTY	ITCH	80:83	Mutation rewiring degron network	0.1667
p.D74N	ACH-002223	Brain Cancer	CCLE	PPTY	ITCH	80:83	Mutation rewiring degron network	0.1667
p.D74N	D-245MG	central nervous system	COSMIC	PPTY	ITCH	80:83	Mutation rewiring degron network	0.1667
p.E89Q	SIDM00751	Non-Small Cell Lung Carcinoma	GDSC	PPTY	ITCH	80:83	Mutation rewiring degron network	0.1667
p.E89Q	ACH-000892	Lung Cancer	CCLE	PPTY	ITCH	80:83	Mutation rewiring degron network	0.1667
p.L92F	ACH-000946	Endometrial/Uterine Cancer	CCLE	PPTY	ITCH	80:83	Mutation rewiring degron network	0.0833

DegronMD: protein-targeted degradation, mutation and drug response to degrons

EIF2AK4

UniProt ID: Q9P2K8

Entrez ID: 440275

Protein name: eIF-2-alpha kinase GCN2 (EC 2.7.11.1) (Eukaryotic translation initiation factor 2-alpha kinase 4) (GCN2-like protein)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for EIF2AK4 in