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Protein Page:
GCK (human)
p Phosphorylation
ac Acetylation
me Methylation
m1 Mono-methylation
m2 Di-methylation
m3 Tri-methylation
ub Ubiquitination
sm Sumoylation
ne Neddylation
gl O-GlcNAc
ga O-GalNAc
pa Palmitoylation
ad Adenylylation
sn S-Nitrosylation
ca Caspase cleavage
sc Succinylation

Overview
GCK 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. Interacts with TRAF2, TRAF6, MAP3K1/MEKK1 and MAP3K11/MLK3. Interacts with RAB8A. Highly expressed in germinal center but not mantle zone B-cells. Also expressed in lung, brain and placenta and at lower levels in other tissues examined. The tumor necrosis factor (TNF), as well as endotoxins and proinflammatory stimuli such as polyinosine- polycytidine (poly(IC)), lipopolysaccharides (LPS), peptidoglycan (PGN), flagellin, or lipid A activate MAP4K2 by promoting its autophosphorylation. Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily. Note: This description may include information from UniProtKB.
Protein type: Kinase, protein; EC 2.7.11.1; Protein kinase, Ser/Thr (non-receptor); Protein kinase, STE; Motility/polarity/chemotaxis; STE group; STE20 family; KHS subfamily
Cellular Component: Golgi membrane; basolateral plasma membrane
Molecular Function: protein serine/threonine kinase activity; protein binding; mitogen-activated protein kinase kinase kinase binding; ATP binding; small GTPase regulator activity
Biological Process: vesicle targeting; activation of MAPKKK activity; positive regulation of JNK cascade; JNK cascade; innate immune response; immune response; protein amino acid phosphorylation; activation of JNK activity
Reference #:  Q12851 (UniProtKB)
Alt. Names/Synonyms: B lymphocyte serine/threonine protein kinase; B lymphocyte serine/threonine-protein kinase; BL44; GC kinase; GCK; Germinal center kinase; germinal centre kinase (GC kinase); M4K2; MAP4K2; MAPK/ERK kinase kinase kinase 2; MEK kinase kinase 2; MEKKK 2; Mitogen-activated protein kinase kinase kinase kinase 2; Rab8 interacting protein; Rab8-interacting protein; RAB8IP
Gene Symbols: MAP4K2
Molecular weight: 91,556 Da
Basal Isoelectric point: 5.91  Predict pI for various phosphorylation states
CST Pathways:  SAPK/JNK Signaling Cascades
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
Select Structure to View Below

GCK

Protein Structure Not Found.


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Modification Sites and Domains Show Modification Legend
Click here to view phosphorylation modifications only

Modification Sites in Parent Protein, Orthologs, and Isoforms Show Modification Legend
 

Show Multiple Sequence Alignment


 SS 

SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.


 MS 

MS: The number of records in which this modification site was assigned using ONLY proteomic discovery-mode mass spectrometry.


       human

 
0 2 S8-p MALLRDVsLQDPRDR
0 1 Y27-p QRVGAGTyGDVYkAR
0 1 K32-ub GTyGDVYkARDTVTS
0 9 S170-p ASVAKRRsFIGtPYW
0 3 T174-p KRRsFIGtPYWMAPE
0 1 S227-p MRALMLMsKSSFQPP
0 1 S298-p DPHLGTPsPEDCELE
0 1 T306-p PEDCELEtyDMFPDT
0 4 Y307-p EDCELEtyDMFPDTI
0 8 T326-p QHGPAERtPsEIQFH
0 69 S328-p GPAERtPsEIQFHQV
0 1 S385-p ERSLTIRsASEFQEL
0 12 S394-p SEFQELDsPDDTMGT
0 3 T574-p QVPLSIPtNRLtQRI
0 4 T578-p SIPtNRLtQRIIPRR
0 1 T819-p ILTGHQStY______
  mouse

 
S8 MALLRDVSLQDPRDR
Y27 QRVGAGTYGDVYKAR
K32 GTYGDVYKARDTVTS
S170 ASVAKRRSFIGTPYW
T174 KRRSFIGTPYWMAPE
S227 MRALMLMSKSSFQPP
S298 DPHLGTLSPEDSELE
T306 PEDSELETHDMFPDT
H307 EDSELETHDMFPDTI
T326-p HHGPAERtPsEIQFH
S328-p GPAERtPsEIQFHQV
P385 ERSLTIRPALELQEL
S394-p LELQELDsPDDAIGT
T575 QAPLSIPTNRITQRI
T579 SIPTNRITQRIIPRR
S820 ILTGHQSSY______
  rat

 
S8 MALLRDVSLQDPRDR
Y27 QRVGAGTYGDVYKAR
K32 GTYGDVYKARDTVTS
S170 ASVAKRRSFIGTPYW
T174 KRRSFIGTPYWMAPE
S227 MRALMLMSKSSFQPP
S298 DPHLGTLSPEDSELE
T306 PEDSELETHDMFPDT
H307 EDSELETHDMFPDTI
T326 HHGPAERTPSEIQFH
S328 GPAERTPSEIQFHQV
P385 ERSLTIRPAIELQEL
S394 IELQELDSPDDAIGT
T575 QAPLSIPTNRITQRI
T579 SIPTNRITQRIIPRR
S820 ILTGHQSSY______
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