CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-011926
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Mitogen-activated protein kinase kinase kinase kinase 2 
Protein Synonyms/Alias
 B lymphocyte serine/threonine-protein kinase; Germinal center kinase; GC kinase; MAPK/ERK kinase kinase kinase 2; MEK kinase kinase 2; MEKKK 2; Rab8-interacting protein 
Gene Name
 MAP4K2 
Gene Synonyms/Alias
 GCK; RAB8IP 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
32GTYGDVYKARDTVTSubiquitination[1, 2, 3]
45TSELAAVKIVKLDPGubiquitination[3]
48LAAVKIVKLDPGDDIubiquitination[3]
336EIQFHQVKFGAPRRKubiquitination[3]
403DDTMGTIKRAPFLGPubiquitination[3]
591RRFALSTKIPDTKGCubiquitination[3]
596STKIPDTKGCLQCRVubiquitination[3]
Reference
 [1] 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]
 [2] 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]
 [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] 
Functional Description
 Serine/threonine-protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Acts as a MAPK kinase kinase kinase (MAP4K) and is an upstream activator of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway and to a lesser extend of the p38 MAPKs signaling pathway. Required for the efficient activation of JNKs by TRAF6-dependent stimuli, including pathogen-associated molecular patterns (PAMPs) such as polyinosine-polycytidine (poly(IC)), lipopolysaccharides (LPS), lipid A, peptidoglycan (PGN), or bacterial flagellin. To a lesser degree, IL-1 and engagement of CD40 also stimulate MAP4K2-mediated JNKs activation. The requirement for MAP4K2/GCK is most pronounced for LPS signaling, and extends to LPS stimulation of c-Jun phosphorylation and induction of IL-8. Enhances MAP3K1 oligomerization, which may relieve N-terminal mediated MAP3K1 autoinhibition and lead to activation following autophosphorylation. Mediates also the SAP/JNK signaling pathway and the p38 MAPKs signaling pathway through activation of the MAP3Ks MAP3K10/MLK2 and MAP3K11/MLK3. May play a role in the regulation of vesicle targeting or fusion. regulation of vesicle targeting or fusion. 
Sequence Annotation
 DOMAIN 16 273 Protein kinase.
 DOMAIN 482 793 CNH.
 NP_BIND 22 30 ATP (By similarity).
 REGION 294 314 PEST1.
 REGION 344 360 PEST2.
 REGION 405 448 PEST3.
 ACT_SITE 136 136 Proton acceptor (By similarity).
 BINDING 45 45 ATP (By similarity).
 MOD_RES 394 394 Phosphoserine.  
Keyword
 ATP-binding; Cell membrane; Complete proteome; Cytoplasm; Golgi apparatus; Immunity; Innate immunity; Kinase; Membrane; Nucleotide-binding; Phosphoprotein; Reference proteome; Serine/threonine-protein kinase; Stress response; Transferase; Ubl conjugation. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 820 AA 
Protein Sequence
MALLRDVSLQ DPRDRFELLQ RVGAGTYGDV YKARDTVTSE LAAVKIVKLD PGDDISSLQQ 60
EITILRECRH PNVVAYIGSY LRNDRLWICM EFCGGGSLQE IYHATGPLEE RQIAYVCREA 120
LKGLHHLHSQ GKIHRDIKGA NLLLTLQGDV KLADFGVSGE LTASVAKRRS FIGTPYWMAP 180
EVAAVERKGG YNELCDVWAL GITAIELGEL QPPLFHLHPM RALMLMSKSS FQPPKLRDKT 240
RWTQNFHHFL KLALTKNPKK RPTAEKLLQH PFTTQQLPRA LLTQLLDKAS DPHLGTPSPE 300
DCELETYDMF PDTIHSRGQH GPAERTPSEI QFHQVKFGAP RRKETDPLNE PWEEEWTLLG 360
KEELSGSLLQ SVQEALEERS LTIRSASEFQ ELDSPDDTMG TIKRAPFLGP LPTDPPAEEP 420
LSSPPGTLPP PPSGPNSSPL LPTAWATMKQ REDPERSSCH GLPPTPKVHM GACFSKVFNG 480
CPLRIHAAVT WIHPVTRDQF LVVGAEEGIY TLNLHELHED TLEKLISHRC SWLYCVNNVL 540
LSLSGKSTHI WAHDLPGLFE QRRLQQQVPL SIPTNRLTQR IIPRRFALST KIPDTKGCLQ 600
CRVVRNPYTG ATFLLAALPT SLLLLQWYEP LQKFLLLKNF SSPLPSPAGM LEPLVLDGKE 660
LPQVCVGAEG PEGPGCRVLF HVLPLEAGLT PDILIPPEGI PGSAQQVIQV DRDTILVSFE 720
RCVRIVNMQG EPTATLAPEL TFDFPIETVV CLQDSVLAFW SHGMQGRSLD TNEVTQEITD 780
ETRIFRVLGA HRDIILESIP TDNPEAHSNL YILTGHQSTY 820 
Gene Ontology
 GO:0016323; C:basolateral plasma membrane; IEA:UniProtKB-SubCell.
 GO:0000139; C:Golgi membrane; TAS:ProtInc.
 GO:0005524; F:ATP binding; IDA:UniProtKB.
 GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
 GO:0005083; F:small GTPase regulator activity; IEA:InterPro.
 GO:0007257; P:activation of JUN kinase activity; IDA:UniProtKB.
 GO:0006955; P:immune response; TAS:ProtInc.
 GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
 GO:0046330; P:positive regulation of JNK cascade; IDA:UniProtKB.
 GO:0006903; P:vesicle targeting; NAS:UniProtKB. 
Interpro
 IPR001180; Citron.
 IPR011009; Kinase-like_dom.
 IPR021160; MAPKKKK.
 IPR000719; Prot_kinase_cat_dom.
 IPR017441; Protein_kinase_ATP_BS.
 IPR002290; Ser/Thr_dual-sp_kinase_dom. 
Pfam
 PF00780; CNH
 PF00069; Pkinase 
SMART
 SM00036; CNH
 SM00220; S_TKc 
PROSITE
 PS50219; CNH
 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00108; PROTEIN_KINASE_ST 
PRINTS