EKS-HOS-00329

Eukaryotic Protein Kinase & Protein Phosphatase Database

Tag

Content

EKPD ID

EKS-HOS-00329

Classification

Group/Family	Score	E-Value	Start	End	Domain Length
STE/STE20	333.9	3.3E-99	16	272	257

Status

Reviewed

Ensembl Protein

ENSP00000366567

UniProt Accession

Q12851;

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

MAP4K2; GCK, RAB8IP;

Ensembl Information

Ensembl Gene ID	Ensembl Protein ID	Ensembl Transcript ID
ENSG00000168067	ENSP00000404534	ENST00000444560
ENSG00000168067	ENSP00000413167	ENST00000433890
ENSG00000168067	ENSP00000366567	ENST00000377350
ENSG00000168067	ENSP00000400594	ENST00000435926
ENSG00000168067	ENSP00000403563	ENST00000439069
ENSG00000168067	ENSP00000403410	ENST00000424945
ENSG00000168067	ENSP00000294066	ENST00000294066

Organism

Homo sapiens

Functional Description

Serine/threonine-protein kinase which acts as anessential 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.

Protein Length

812

Protein Sequence
(FASTA)

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

LSSPPGPNSS PLLPTAWATM KQREDPERSS CHGLPPTPKV HMGACFSKVF NGCPLRIHAA 480

VTWIHPVTRD QFLVVGAEEG IYTLNLHELH EDTLEKLISH RCSWLYCVNN VLLSLSGKST 540

HIWAHDLPGL FEQRRLQQQV PLSIPTNRLT QRIIPRRFAL STKIPDTKGC LQCRVVRNPY 600

TGATFLLAAL PTSLLLLQWY EPLQKFLLLK NFSSPLPSPA GMLEPLVLDG KELPQVCVGA 660

EGPEGPGCRV LFHVLPLEAG LTPDILIPPE GIPGSAQQVI QVDRDTILVS FERCVRIVNM 720

QGEPTATLAP ELTFDFPIET VVCLQDSVLA FWSHGMQGRS LDTNEVTQEI TDETRIFRVL 780

GAHRDIILES IPTDNPEAHS NLYILTGHQS TY 812

Nucleotide Sequence
(FASTA)

ATGGCGCTGC TGCGGGATGT GTCGCTGCAG GACCCGCGGG ACCGCTTCGA GCTGCTGCAG 60

CGCGTGGGGG CCGGGACCTA TGGCGACGTC TACAAGGCCC GCGACACGGT CACGTCCGAA 120

CTGGCCGCCG TGAAGATAGT CAAGCTAGAC CCAGGGGACG ACATCAGCTC CCTCCAGCAG 180

GAAATCACCA TCCTGCGTGA GTGCCGCCAC CCCAATGTGG TGGCCTACAT TGGCAGCTAC 240

CTCAGGAATG ACCGCTTGTG GATCTGCATG GAGTTCTGCG GAGGGGGCTC CCTGCAGGAG 300

ATTTACCATG CCACTGGGCC CCTGGAGGAG CGGCAGATTG CCTACGTCTG CCGAGAGGCA 360

CTGAAGGGGC TCCACCACCT GCATTCTCAG GGGAAGATCC ACAGAGACAT CAAGGGAGCC 420

AACCTTCTCC TCACTCTCCA GGGAGATGTC AAACTGGCTG ACTTTGGGGT GTCAGGCGAG 480

CTGACAGCGT CTGTGGCCAA GAGGAGGTCT TTCATTGGGA CTCCCTACTG GATGGCTCCC 540

GAGGTGGCTG CTGTGGAGCG CAAAGGTGGC TACAATGAGC TATGTGACGT CTGGGCCCTG 600

GGCATCACTG CCATTGAGCT GGGCGAGCTG CAGCCCCCTC TGTTCCACCT GCACCCCATG 660

AGGGCCCTGA TGCTCATGTC GAAGAGCAGC TTCCAGCCGC CCAAACTGAG AGATAAGACT 720

CGCTGGACCC AGAATTTCCA CCACTTTCTC AAACTGGCCC TGACCAAGAA TCCTAAGAAG 780

AGGCCGACAG CAGAGAAGCT CCTGCAGCAC CCGTTCACGA CTCAGCAGCT CCCTCGGGCC 840

CTCCTCACAC AGCTGCTGGA CAAAGCCAGT GACCCTCATC TGGGGACCCC CTCCCCTGAG 900

GACTGTGAGC TGGAGACCTA TGACATGTTT CCAGACACCA TTCACTCCCG GGGGCAGCAC 960

GGCCCAGCCG AGAGGACCCC CTCGGAGATC CAGTTTCACC AGGTGAAATT TGGCGCCCCA 1020

CGCAGGAAGG AAACTGACCC ACTGAATGAG CCGTGGGAGG AAGAGTGGAC ACTACTGGGA 1080

AAGGAAGAGT TGAGTGGGAG CCTGCTGCAG TCGGTCCAGG AGGCCCTGGA GGAAAGGAGT 1140

CTGACTATTC GGTCAGCCTC AGAATTCCAG GAGCTGGACT CCCCAGACGA TACCATGGGA 1200

ACCATCAAGC GGGCCCCGTT CCTAGGGCCA CTCCCCACTG ACCCTCCAGC AGAGGAGCCT 1260

CTGTCCAGTC CCCCAGGCCC CAACAGCTCC CCACTGCTGC CCACGGCCTG GGCCACCATG 1320

AAGCAGCGGG AGGATCCTGA GAGGTCATCC TGCCACGGGC TCCCCCCAAC TCCCAAGGTG 1380

CATATGGGCG CCTGCTTCTC CAAGGTCTTC AATGGCTGCC CCCTGCGGAT CCACGCTGCT 1440

GTCACCTGGA TTCACCCTGT TACTCGGGAC CAGTTCCTGG TGGTAGGGGC CGAGGAAGGC 1500

ATCTACACAC TCAACCTGCA TGAACTGCAT GAGGATACGC TGGAGAAGCT GATTTCACAT 1560

CGCTGCTCCT GGCTCTACTG CGTGAACAAC GTGCTGCTGT CACTCTCAGG GAAATCCACG 1620

CACATCTGGG CCCATGACCT CCCAGGCCTG TTTGAGCAGC GGAGGCTACA GCAACAGGTT 1680

CCCCTCTCCA TCCCCACCAA CCGCCTCACC CAGCGCATCA TCCCCAGGCG CTTTGCTCTG 1740

TCCACCAAGA TTCCTGACAC CAAAGGCTGC TTGCAGTGTC GTGTGGTGCG GAACCCCTAC 1800

ACGGGTGCCA CCTTCCTGCT GGCCGCCCTG CCCACCAGCC TGCTCCTGCT GCAGTGGTAT 1860

GAGCCGCTGC AGAAGTTTCT GCTGCTGAAG AACTTCTCCA GCCCTCTGCC CAGCCCAGCT 1920

GGGATGCTGG AGCCGCTGGT GCTGGATGGG AAGGAGCTGC CGCAGGTGTG TGTTGGGGCC 1980

GAGGGGCCTG AGGGGCCCGG CTGCCGCGTC CTGTTCCATG TCCTGCCCCT GGAGGCTGGC 2040

CTGACGCCCG ACATCCTCAT CCCACCTGAG GGGATCCCAG GCTCGGCCCA GCAGGTGATC 2100

CAGGTGGACA GGGACACAAT CCTAGTCAGC TTTGAACGCT GTGTGAGGAT TGTCAACATG 2160

CAGGGCGAGC CCACGGCCAC ACTGGCACCT GAGCTGACCT TTGATTTCCC CATCGAGACT 2220

GTGGTGTGCC TGCAGGACAG TGTGCTGGCC TTCTGGAGCC ATGGGATGCA AGGCCGAAGC 2280

CTGGATACCA ATGAGGTGAC CCAGGAGATC ACAGATGAAA CAAGGATCTT CCGAGTGCTT 2340

GGGGCCCACA GAGACATCAT CCTGGAGAGC ATTCCCACTG ACAACCCAGA GGCGCACAGC 2400

AACCTCTACA TCCTCACGGG CCACCAGAGC ACCTACTAA 2439

Domain Profile

S: 1     yelleeigkGalgkvylarekktgelvaikkinlekqekleelqkeisvlkklkhpnive  60

         +ell+++g G++g+vy+ar++ t+el+a+k+++l+  +++++lq+ei++l++++hpn+v+

Q: 16    FELLQRVGAGTYGDVYKARDTVTSELAAVKIVKLDPGDDISSLQQEITILRECRHPNVVA  75

         899*********************************************************

S: 61    ylesflkeeelwlvmeylagGslsdlvkeelkselkEeqiayilrevlkaLeylHskkvi  120

         y++s+l++++lw++me++ gGsl+++++   + +l+E+qiay++re+lk+L++lHs+++i

Q: 76    YIGSYLRNDRLWICMEFCGGGSLQEIYH--ATGPLEERQIAYVCREALKGLHHLHSQGKI  133

         ****************************..9*****************************

S: 121   HrdikakniLlteegeVkLsdfgvaaqlektrkkrktvvgtpywmAPEviaqe.ekgYde  179

         Hrdik++n+Llt +g+VkL+dfgv+ +l+++++kr++++gtpywmAPEv a+e + gY+e

Q: 134   HRDIKGANLLLTLQGDVKLADFGVSGELTASVAKRRSFIGTPYWMAPEVAAVErKGGYNE  193

         ****************************************************98889***

S: 180   kaDiwslGItaielaegepPfkdleplkallkilkne..ppklkskkkfskefkefvekc  237

          +D+w+lGItaiel e +pP+++l+p++al++++k++  ppkl++k++++++f++f++ +

Q: 194   LCDVWALGITAIELGELQPPLFHLHPMRALMLMSKSSfqPPKLRDKTRWTQNFHHFLKLA  253

         **********************************99988*********************

S: 238   lqknpekRpsasellkhkF  256

         l+knp+kRp+a++ll+h+F

Q: 254   LTKNPKKRPTAEKLLQHPF  272

         ******************9

Domain Sequence
(FASTA)

FELLQRVGAG TYGDVYKARD TVTSELAAVK IVKLDPGDDI SSLQQEITIL RECRHPNVVA 60

YIGSYLRNDR LWICMEFCGG GSLQEIYHAT GPLEERQIAY VCREALKGLH HLHSQGKIHR 120

DIKGANLLLT LQGDVKLADF GVSGELTASV AKRRSFIGTP YWMAPEVAAV ERKGGYNELC 180

DVWALGITAI ELGELQPPLF HLHPMRALML MSKSSFQPPK LRDKTRWTQN FHHFLKLALT 240

KNPKKRPTAE KLLQHPF 257

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

Ensembl

Orthology

Ortholog group

Ailuropoda melanoleuca"; ?>Bos taurus"; ?>Callithrix jacchus"; ?>Canis familiaris"; ?>Cavia porcellus"; ?>Dipodomys ordii"; ?>Equus caballus"; ?>Felis catus"; ?>Gasterosteus aculeatus"; ?>Gorilla gorilla"; ?>Ictidomys tridecemlineatus"; ?>Mus musculus"; ?>Myotis lucifugus"; ?>Otolemur garnettii"; ?>Pan troglodytes"; ?>Pongo abelii"; ?>Pteropus vampyrus"; ?>Rattus norvegicus"; ?>Sus scrofa"; ?>Tetraodon nigroviridis"; ?>Xenopus tropicalis"; ?>Xiphophorus maculatus"; ?>

Gene Ontology

GO:0016323	; C:basolateral plasma membrane
GO:0000139	; C:Golgi membrane
GO:0005524	; F:ATP binding
GO:0004674	; F:protein serine/threonine kinase activity
GO:0005083	; F:small GTPase regulator activity
GO:0007257	; P:activation of JUN kinase activity
GO:0006955	; P:immune response
GO:0045087	; P:innate immune response
GO:0046330	; P:positive regulation of JNK cascade
GO:0006903	; P:vesicle targeting

KEGG

hsa:5871

;

InterPros

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; 1.
PF00069	; Pkinase; 1.

SMARTs

SM00036	; CNH; 1.
SM00220	; S_TKc; 1.

Prosites

PS50219	; CNH; 1.
PS00107	; PROTEIN_KINASE_ATP; 1.
PS50011	; PROTEIN_KINASE_DOM; 1.
PS00108	; PROTEIN_KINASE_ST; FALSE_NEG.

Prints

Created Date

20-Feb-2013