E2AK4_HUMAN - dbPTM
E2AK4_HUMAN - PTM Information in dbPTM
Basic Information of Protein
UniProt ID E2AK4_HUMAN
UniProt AC Q9P2K8
Protein Name eIF-2-alpha kinase GCN2 {ECO:0000250|UniProtKB:Q9QZ05}
Gene Name EIF2AK4 {ECO:0000312|HGNC:HGNC:19687}
Organism Homo sapiens (Human).
Sequence Length 1649
Subcellular Localization Cytoplasm .
Protein Description Metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (eIF-2-alpha/EIF2S1) on 'Ser-52' in response to low amino acid availability. [PubMed: 25329545 Plays a role as an activator of the integrated stress response (ISR) required for adapatation to amino acid starvation. Converts phosphorylated eIF-2-alpha/EIF2S1 either to a competitive inhibitor of the translation initiation factor eIF-2B, leading to a global protein synthesis repression, and thus to a reduced overall utilization of amino acids, or to a translational initiation activation of specific mRNAs, such as the transcriptional activator ATF4, and hence allowing ATF4-mediated reprogramming of amino acid biosynthetic gene expression to alleviate nutrient depletion. Binds uncharged tRNAs (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]
Protein Sequence MAGGRGAPGRGRDEPPESYPQRQDHELQALEAIYGADFQDLRPDACGPVKEPPEINLVLYPQGLTGEEVYVKVDLRVKCPPTYPDVVPEIELKNAKGLSNESVNLLKSRLEELAKKHCGEVMIFELAYHVQSFLSEHNKPPPKSFHEEMLERRAQEEQQRLLEAKRKEEQEQREILHEIQRRKEEIKEEKKRKEMAKQERLEIASLSNQDHTSKKDPGGHRTAAILHGGSPDFVGNGKHRANSSGRSRRERQYSVCNSEDSPGSCEILYFNMGSPDQLMVHKGKCIGSDEQLGKLVYNALETATGGFVLLYEWVLQWQKKMGPFLTSQEKEKIDKCKKQIQGTETEFNSLVKLSHPNVVRYLAMNLKEQDDSIVVDILVEHISGVSLAAHLSHSGPIPVHQLRRYTAQLLSGLDYLHSNSVVHKVLSASNVLVDAEGTVKITDYSISKRLADICKEDVFEQTRVRFSDNALPYKTGKKGDVWRLGLLLLSLSQGQECGEYPVTIPSDLPADFQDFLKKCVCLDDKERWSPQQLLKHSFINPQPKMPLVEQSPEDSEGQDYVETVIPSNRLPSAAFFSETQRQFSRYFIEFEELQLLGKGAFGAVIKVQNKLDGCCYAVKRIPINPASRQFRRIKGEVTLLSRLHHENIVRYYNAWIERHERPAGPGTPPPDSGPLAKDDRAARGQPASDTDGLDSVEAAAPPPILSSSVEWSTSGERSASARFPATGPGSSDDEDDDEDEHGGVFSQSFLPASDSESDIIFDNEDENSKSQNQDEDCNEKNGCHESEPSVTTEAVHYLYIQMEYCEKSTLRDTIDQGLYRDTVRLWRLFREILDGLAYIHEKGMIHRDLKPVNIFLDSDDHVKIGDFGLATDHLAFSADSKQDDQTGDLIKSDPSGHLTGMVGTALYVSPEVQGSTKSAYNQKVDLFSLGIIFFEMSYHPMVTASERIFVLNQLRDPTSPKFPEDFDDGEHAKQKSVISWLLNHDPAKRPTATELLKSELLPPPQMEESELHEVLHHTLTNVDGKAYRTMMAQIFSQRISPAIDYTYDSDILKGNFSIRTAKMQQHVCETIIRIFKRHGAVQLCTPLLLPRNRQIYEHNEAALFMDHSGMLVMLPFDLRIPFARYVARNNILNLKRYCIERVFRPRKLDRFHPKELLECAFDIVTSTTNSFLPTAEIIYTIYEIIQEFPALQERNYSIYLNHTMLLKAILLHCGIPEDKLSQVYIILYDAVTEKLTRREVEAKFCNLSLSSNSLCRLYKFIEQKGDLQDLMPTINSLIKQKTGIAQLVKYGLKDLEEVVGLLKKLGIKLQVLINLGLVYKVQQHNGIIFQFVAFIKRRQRAVPEILAAGGRYDLLIPQFRGPQALGPVPTAIGVSIAIDKISAAVLNMEESVTISSCDLLVVSVGQMSMSRAINLTQKLWTAGITAEIMYDWSQSQEELQEYCRHHEITYVALVSDKEGSHVKVKSFEKERQTEKRVLETELVDHVLQKLRTKVTDERNGREASDNLAVQNLKGSFSNASGLFEIHGATVVPIVSVLAPEKLSASTRRRYETQVQTRLQTSLANLHQKSSEIEILAVDLPKETILQFLSLEWDADEQAFNTTVKQLLSRLPKQRYLKLVCDEIYNIKVEKKVSVLFLYSYRDDYYRILF
Overview of Protein Modification Sites with Functional and Structural Information
Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations Modification Substrate Peptides
&
Secondary Structure		 ASA (%) Reference Orthologous
Protein Cluster
5Methylation---MAGGRGAPGRGR
---CCCCCCCCCCCC		36.86-
102PhosphorylationAKGLSNESVNLLKSR
CCCCCHHHHHHHHHH		22.1325159151
205PhosphorylationQERLEIASLSNQDHT
HHHHHHHHHCCCCCC		37.6829255136
207PhosphorylationRLEIASLSNQDHTSK
HHHHHHHCCCCCCCC		29.9229255136
212PhosphorylationSLSNQDHTSKKDPGG
HHCCCCCCCCCCCCC		51.0028555341
213PhosphorylationLSNQDHTSKKDPGGH
HCCCCCCCCCCCCCC		34.0025627689
222PhosphorylationKDPGGHRTAAILHGG
CCCCCCCEEEEECCC		18.1123403867
230PhosphorylationAAILHGGSPDFVGNG
EEEECCCCCCCCCCC		26.3623401153
238AcetylationPDFVGNGKHRANSSG
CCCCCCCCCCCCCCC		33.6425953088
253PhosphorylationRSRRERQYSVCNSED
CCHHHHHEEECCCCC		14.8627273156
254PhosphorylationSRRERQYSVCNSEDS
CHHHHHEEECCCCCC		16.3222322096
258PhosphorylationRQYSVCNSEDSPGSC
HHEEECCCCCCCCCE		37.3423898821
261PhosphorylationSVCNSEDSPGSCEIL
EECCCCCCCCCEEEE		27.4022322096
264PhosphorylationNSEDSPGSCEILYFN
CCCCCCCCEEEEEEE		16.3823898821
269PhosphorylationPGSCEILYFNMGSPD
CCCEEEEEEECCCCC		9.8922322096
274PhosphorylationILYFNMGSPDQLMVH
EEEEECCCCCCEEEE		17.9723898821
327PhosphorylationKMGPFLTSQEKEKID
HHCCCCCHHHHHHHH		38.1925627689
405PhosphorylationPVHQLRRYTAQLLSG
CHHHHHHHHHHHHHC		10.4521406692
406PhosphorylationVHQLRRYTAQLLSGL
HHHHHHHHHHHHHCC		13.2021406692
411PhosphorylationRYTAQLLSGLDYLHS
HHHHHHHHCCCHHCC		45.9921406692
415PhosphorylationQLLSGLDYLHSNSVV
HHHHCCCHHCCCCHH		16.0321406692
418PhosphorylationSGLDYLHSNSVVHKV
HCCCHHCCCCHHHHH		28.3621406692
420PhosphorylationLDYLHSNSVVHKVLS
CCHHCCCCHHHHHHC		28.6521406692
467PhosphorylationEQTRVRFSDNALPYK
HHHCEECCCCCCCCC		21.2825159151
473PhosphorylationFSDNALPYKTGKKGD
CCCCCCCCCCCCCCC		23.2522210691
474UbiquitinationSDNALPYKTGKKGDV
CCCCCCCCCCCCCCH		49.1929967540
490PhosphorylationRLGLLLLSLSQGQEC
HHHHHHHHHHCCCCC		26.4126503514
492PhosphorylationGLLLLSLSQGQECGE
HHHHHHHHCCCCCCC		28.9626503514
500PhosphorylationQGQECGEYPVTIPSD
CCCCCCCCCCCCCCC		6.5726503514
503PhosphorylationECGEYPVTIPSDLPA
CCCCCCCCCCCCCCC		23.7526503514
551PhosphorylationKMPLVEQSPEDSEGQ
CCCCCCCCCCCCCCC		19.4220363803
555PhosphorylationVEQSPEDSEGQDYVE
CCCCCCCCCCCCCEE		41.8019664995
560PhosphorylationEDSEGQDYVETVIPS
CCCCCCCCEEEEECC		7.7218691976
572PhosphorylationIPSNRLPSAAFFSET
ECCCCCCCHHHCHHH		36.5025106551
606AcetylationGAFGAVIKVQNKLDG
CCCCEEEEEECCCCC		31.0418585335
610UbiquitinationAVIKVQNKLDGCCYA
EEEEEECCCCCCEEE		30.7529967540
619UbiquitinationDGCCYAVKRIPINPA
CCCEEEEEECCCCHH		36.12-
634UbiquitinationSRQFRRIKGEVTLLS
HHHHHHHCCEEEHHH		47.40-
667PhosphorylationERPAGPGTPPPDSGP
CCCCCCCCCCCCCCC		35.4429255136
672PhosphorylationPGTPPPDSGPLAKDD
CCCCCCCCCCCCCCC		48.3523927012
688PhosphorylationAARGQPASDTDGLDS
HHCCCCCCCCCCCCC		47.9630624053
690PhosphorylationRGQPASDTDGLDSVE
CCCCCCCCCCCCCCH		29.4830624053
695PhosphorylationSDTDGLDSVEAAAPP
CCCCCCCCCHHCCCC		27.2230624053
770PhosphorylationNEDENSKSQNQDEDC
CCCCCCCCCCCCCCC		33.9025159151
838PhosphorylationEILDGLAYIHEKGMI
HHHHHHHHHHHCCCC		14.0920068231
850UbiquitinationGMIHRDLKPVNIFLD
CCCCCCCCCEEEEEC		51.7329967540
871PhosphorylationIGDFGLATDHLAFSA
ECCCCCCCCEEEEEC		29.0623186163
881UbiquitinationLAFSADSKQDDQTGD
EEEECCCCCCCCCCC		59.2932015554
892PhosphorylationQTGDLIKSDPSGHLT
CCCCCCCCCCCCCCE		48.0030576142
895PhosphorylationDLIKSDPSGHLTGMV
CCCCCCCCCCCEECE		43.7830576142
899PhosphorylationSDPSGHLTGMVGTAL
CCCCCCCEECEEEEE		19.9830576142
904PhosphorylationHLTGMVGTALYVSPE
CCEECEEEEEEECHH		11.3330576142
928PhosphorylationNQKVDLFSLGIIFFE
HCCCCEEEEEEEEEE		32.74-
959PhosphorylationNQLRDPTSPKFPEDF
CCCCCCCCCCCCCCC		31.3328985074
976PhosphorylationGEHAKQKSVISWLLN
CHHHHHHHHHHHHHC		23.3823898821
979PhosphorylationAKQKSVISWLLNHDP
HHHHHHHHHHHCCCC		14.9823898821
988AcetylationLLNHDPAKRPTATEL
HHCCCCCCCCCHHHH		65.3825953088
991PhosphorylationHDPAKRPTATELLKS
CCCCCCCCHHHHHHH		50.6921406692
993PhosphorylationPAKRPTATELLKSEL
CCCCCCHHHHHHHCC		29.6421406692
1040PhosphorylationQIFSQRISPAIDYTY
HHHHCCCCCCCCEEC		15.5220068231
1045PhosphorylationRISPAIDYTYDSDIL
CCCCCCCEECCCCHH		10.9020068231
1046PhosphorylationISPAIDYTYDSDILK
CCCCCCEECCCCHHC		19.6620068231
1047PhosphorylationSPAIDYTYDSDILKG
CCCCCEECCCCHHCC		13.7620068231
1049PhosphorylationAIDYTYDSDILKGNF
CCCEECCCCHHCCCC		19.0120068231
1085PhosphorylationHGAVQLCTPLLLPRN
CCCHHHCCCCCCCCC		26.0928464451
1135MethylationRNNILNLKRYCIERV
HCCCHHHHHHHHHHH		40.00-
1135UbiquitinationRNNILNLKRYCIERV
HCCCHHHHHHHHHHH		40.00-
1196PhosphorylationPALQERNYSIYLNHT
HHHHHCCCHHHHCHH		11.5821406692
1197PhosphorylationALQERNYSIYLNHTM
HHHHCCCHHHHCHHH		14.3321406692
1199PhosphorylationQERNYSIYLNHTMLL
HHCCCHHHHCHHHHH		8.7721406692
1203PhosphorylationYSIYLNHTMLLKAIL
CHHHHCHHHHHHHHH		14.4021406692
1221PhosphorylationGIPEDKLSQVYIILY
CCCHHHHHHEEEEHH		24.2820068231
1259MalonylationNSLCRLYKFIEQKGD
HHHHHHHHHHHHCCC		44.4526320211
1259AcetylationNSLCRLYKFIEQKGD
HHHHHHHHHHHHCCC		44.4519608861
1276PhosphorylationDLMPTINSLIKQKTG
HHHHHHHHHHHHHHH		27.8524719451
1489UbiquitinationLVDHVLQKLRTKVTD
HHHHHHHHHHHHCCC		35.4629967540
1515PhosphorylationAVQNLKGSFSNASGL
EEECCCCCCCCCCCC		24.7424173317
1517PhosphorylationQNLKGSFSNASGLFE
ECCCCCCCCCCCCEE		32.9324173317
1520PhosphorylationKGSFSNASGLFEIHG
CCCCCCCCCCEEECC		40.0324173317
1543PhosphorylationVLAPEKLSASTRRRY
EECHHHCCHHHHHHH		31.1026270265
1545PhosphorylationAPEKLSASTRRRYET
CHHHCCHHHHHHHHH		21.0426270265
1546PhosphorylationPEKLSASTRRRYETQ
HHHCCHHHHHHHHHH		28.1026270265
1627UbiquitinationCDEIYNIKVEKKVSV
HHHHHCCEEEECEEE		40.4829967540
1639PhosphorylationVSVLFLYSYRDDYYR
EEEEEEEECCCCCEE		18.8124719451
Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)
Modified Location Modified Residue Modification Type of Upstream Proteins Gene Name of Upstream Proteins UniProt AC of Upstream Proteins Sources
-KUbiquitinationE3 ubiquitin ligaseNEDD4LQ96PU5
PMID:25589675
Functions of PTM Sites
Modified Location Modified Residue Modification Function Reference
899TPhosphorylation

-
Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Modified Location Modification Variant Position
(Distance <= 10) 		Residue Change SAP Related Disease Reference

Oops, there are no SNP-PTM records of E2AK4_HUMAN !!
Protein-Protein Interaction
Interacting Protein Gene Name Interaction Type PPI Reference Domain-Domain Interactions
Drug and Disease Associations
Kegg Disease
There are no disease associations of PTM sites.
OMIM Disease
234810Pulmonary venoocclusive disease 2, autosomal recessive (PVOD2)
Kegg Drug
There are no disease associations of PTM sites.
DrugBank
There are no disease associations of PTM sites.
Regulatory Network of E2AK4_HUMAN

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Related Literatures of Post-Translational Modification
Acetylation
ReferencePubMed
"Lysine acetylation targets protein complexes and co-regulates majorcellular functions.";
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.,Olsen J.V., Mann M.;
Science 325:834-840(2009).
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-1259, AND MASS SPECTROMETRY.
Phosphorylation
ReferencePubMed
"Large-scale proteomics analysis of the human kinome.";
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,Mann M., Daub H.;
Mol. Cell. Proteomics 8:1751-1764(2009).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-551; SER-555 ANDTHR-667, AND MASS SPECTROMETRY.
"A quantitative atlas of mitotic phosphorylation.";
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,Elledge S.J., Gygi S.P.;
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-230, AND MASSSPECTROMETRY.
"Kinase-selective enrichment enables quantitative phosphoproteomics ofthe kinome across the cell cycle.";
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,Greff Z., Keri G., Stemmann O., Mann M.;
Mol. Cell 31:438-448(2008).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-230; SER-551; SER-555AND THR-667, AND MASS SPECTROMETRY.
"Proteomics analysis of protein kinases by target class-selectiveprefractionation and tandem mass spectrometry.";
Wissing J., Jaensch L., Nimtz M., Dieterich G., Hornberger R.,Keri G., Wehland J., Daub H.;
Mol. Cell. Proteomics 6:537-547(2007).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-667, AND MASSSPECTROMETRY.
"Global, in vivo, and site-specific phosphorylation dynamics insignaling networks.";
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,Mann M.;
Cell 127:635-648(2006).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-667, AND MASSSPECTROMETRY.

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