UniProt Accession

 EF2K_HUMAN; O00418; Q8N588 

Genbank Protein ID

 U93850; AC009034; BC032665 

Genbank Nucleotide ID

 AAB58270.1; AAH32665.1 

Protein Name

 Eukaryotic elongation factor 2 kinase 

Protein Synonyms/Alias

 eEF-2 kinase; eEF-2K; Calcium/calmodulin-dependent eukaryotic elongation factor 2 kinase 

Gene Name

 EEF2K 

Gene Synonyms/Alias

  

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
65	KYYSNLTKSERYSSS	ubiquitination	[1, 2]
162	FLHAQQWKGASNYVA	ubiquitination	[1, 2]
238	YIEGKYIKYNSNSGF	ubiquitination	[1, 2, 3]
341	DAVNQNTKLLQSAKT	ubiquitination	[1, 2, 3, 4, 5, 6, 7]
347	TKLLQSAKTILRGTE	ubiquitination	[1, 2, 3, 6, 7]
447	DSGYPSEKRGELDDP	ubiquitination	[4]
485	SGRVCVEKWNLLNSS	ubiquitination	[3, 5, 8, 9]
517	NALDLEKKIGKSILG	ubiquitination	[3]
603	KGFDYLLKAAEAGDR	ubiquitination	[1, 2, 3, 4, 7, 9]
705	EAAMEAMKGRLANQY	ubiquitination	[7]

Reference

 [1] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [2] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [3] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [4] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [5] Proteome-wide identification of ubiquitylation sites by conjugation of engineered lysine-less ubiquitin.
 Oshikawa K, Matsumoto M, Oyamada K, Nakayama KI.
 J Proteome Res. 2012 Feb 3;11(2):796-807. [PMID: 22053931]
 [6] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [7] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [8] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
 [9] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302] 

Functional Description

 Threonine kinase that regulates protein synthesis by controlling the rate of peptide chain elongation. Upon activation by a variety of upstream kinases including AMPK or TRPM7, phosphorylates the elongation factor EEF2 at a single site, renders it unable to bind ribosomes and thus inactive. In turn, the rate of protein synthesis is reduced. 

Sequence Annotation

 DOMAIN 116 326 Alpha-type protein kinase.
 NP_BIND 296 302 ATP (By similarity).
 REGION 594 610 Calmodulin-binding (Potential).
 REGION 610 627 Pseudosubstrate/autoinhibitory domain
 MOD_RES 18 18 Phosphoserine.
 MOD_RES 27 27 Phosphoserine (By similarity).
 MOD_RES 31 31 Phosphoserine (By similarity).
 MOD_RES 61 61 Phosphoserine; by autocatalysis.
 MOD_RES 66 66 Phosphoserine; by autocatalysis.
 MOD_RES 71 71 Phosphoserine (By similarity).
 MOD_RES 78 78 Phosphoserine; by autocatalysis and
 MOD_RES 348 348 Phosphothreonine; by autocatalysis.
 MOD_RES 353 353 Phosphothreonine; by autocatalysis.
 MOD_RES 359 359 Phosphoserine; by MAPK13 and CDK1.
 MOD_RES 366 366 Phosphoserine; by autocatalysis, RPS6KA1
 MOD_RES 398 398 Phosphoserine; by AMPK.
 MOD_RES 445 445 Phosphoserine; by autocatalysis.
 MOD_RES 470 470 Phosphoserine.
 MOD_RES 474 474 Phosphoserine; by autocatalysis.
 MOD_RES 477 477 Phosphoserine.
 MOD_RES 491 491 Phosphoserine; by autocatalysis.
 MOD_RES 500 500 Phosphoserine; by PKA (By similarity).  

Keyword

 ATP-binding; Calcium; Calmodulin-binding; Complete proteome; Kinase; Nucleotide-binding; Phosphoprotein; Polymorphism; Reference proteome; Serine/threonine-protein kinase; Transferase. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 725 AA 

Protein Sequence

Gene Ontology

 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0005509; F:calcium ion binding; IEA:InterPro.
 GO:0005516; F:calmodulin binding; IDA:UniProtKB.
 GO:0004686; F:elongation factor-2 kinase activity; IDA:UniProtKB.
 GO:0008135; F:translation factor activity, nucleic acid binding; TAS:ProtInc.
 GO:0008286; P:insulin receptor signaling pathway; TAS:Reactome.
 GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
 GO:0031952; P:regulation of protein autophosphorylation; IEA:Compara.
 GO:0006414; P:translational elongation; TAS:ProtInc. 

Interpro

 IPR017400; Elongation_factor_2_kinase.
 IPR011009; Kinase-like_dom.
 IPR004166; MHCK_EF2_kinase.
 IPR006597; Sel1-like.
 IPR011990; TPR-like_helical. 

Pfam

 PF02816; Alpha_kinase
 PF08238; Sel1 

SMART

 SM00811; Alpha_kinase 

PROSITE

 PS51158; ALPHA_KINASE 

PRINTS