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UniProtKB/Swiss-Prot entry P45985


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name MP2K4_HUMAN
Primary accession number P45985
Secondary accession number Q5U0B8
Integrated into Swiss-Prot on November 1, 1995
Sequence was last modified on November 1, 1995 (Sequence version 1)
Annotations were last modified on    June 16, 2009 (Entry version 93)
Name and origin of the protein
Protein name Dual specificity mitogen-activated protein kinase kinase 4
Synonyms MAP kinase kinase 4
EC 2.7.12.2
JNK-activating kinase 1
c-Jun N-terminal kinase kinase 1
JNKK
SAPK/ERK kinase 1
SEK1
Gene name
Name: MAP2K4
Synonyms: JNKK1, MKK4, PRKMK4, SERK1
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [MRNA].
DOI=10.1126/science.7716521; PubMed=7716521 [NCBI, ExPASy, EBI, Israel, Japan]
Lin A., Minden A., Martinetto H., Claret F.-X., Lange-Carter C., Mercurio F., Johnson G.L., Karin M.;
"Identification of a dual specificity kinase that activates the Jun kinases and p38-Mpk2.";
Science 268:286-290(1995).
[2]
NUCLEOTIDE SEQUENCE [MRNA].
TISSUE=Brain;
DOI=10.1126/science.7839144; PubMed=7839144 [NCBI, ExPASy, EBI, Israel, Japan]
Derijard B., Raingeaud J., Barrett T., Wu I.-H., Han J., Ulevitch R.J., Davis R.J.;
"Independent human MAP-kinase signal transduction pathways defined by MEK and MKK isoforms.";
Science 267:682-685(1995).
[3]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
PubMed=9622070 [NCBI, ExPASy, EBI, Israel, Japan]
Su G.H., Hilgers W., Shekher M.C., Tang D.J., Yeo C.J., Hruban R.H., Kern S.E.;
"Alterations in pancreatic, biliary, and breast carcinomas support MKK4 as a genetically targeted tumor suppressor gene.";
Cancer Res. 58:2339-2342(1998).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.;
"Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
[5]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
NIEHS SNPs program;
Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
[6]
CLEAVAGE BY ANTHRAX LETHAL FACTOR.
DOI=10.1042/0264-6021:3520739; PubMed=11104681 [NCBI, ExPASy, EBI, Israel, Japan]
Vitale G., Bernardi L., Napolitani G., Mock M., Montecucco C.;
"Susceptibility of mitogen-activated protein kinase kinase family members to proteolysis by anthrax lethal factor.";
Biochem. J. 352:739-745(2000).
[7]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-90, AND MASS SPECTROMETRY.
DOI=10.1073/pnas.0805139105; PubMed=18669648 [NCBI, ExPASy, EBI, Israel, Japan]
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.;
"A quantitative atlas of mitotic phosphorylation.";
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
[8]
IDENTIFICATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
Colinge J., Superti-Furga G., Bennett K.L.;
Submitted (OCT-2008) to UniProtKB.
[9]
VARIANTS [LARGE SCALE ANALYSIS] LEU-142; TRP-154; ILE-234; ASN-251 AND THR-279.
DOI=10.1038/nature05610; PubMed=17344846 [NCBI, ExPASy, EBI, Israel, Japan]
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.;
"Patterns of somatic mutation in human cancer genomes.";
Nature 446:153-158(2007).
Comments
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
U17743; AAC50127.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
L36870; AAC41719.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF070090; AAC24130.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF070080; AAC24130.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF070081; AAC24130.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF070082; AAC24130.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF070083; AAC24130.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF070084; AAC24130.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF070085; AAC24130.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF070086; AAC24130.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF070087; AAC24130.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF070088; AAC24130.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF070089; AAC24130.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BT019676; AAV38482.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
DQ015703; AAY22176.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
IPI IPI00024674; -.
PIR I38901; I38901.
RefSeq NP_003001.1; -.
UniGene Hs.514681
3D structure databases
HSSP Q13153; 1F3M. [HSSP ENTRY / PDB]
ModBase P45985.
Protein-protein interaction databases
IntAct P45985; 5.
PTM databases
PhosphoSite P45985; -.
Enzyme and pathway databases
BRENDA 2.7.12.2; 247.
Pathway_Interaction_DB anthraxpathway; Cellular roles of Anthrax toxin.
ceramidepathway; Ceramide signaling pathway.
ephrinbrevpathway; Ephrin B reverse signaling.
faspathway; FAS signaling pathway (CD95).
fcer1pathway; Fc-epsilon receptor I signaling in mast cells.
il6_7pathway; IL6-mediated signaling events.
tcrjnkpathway; JNK signaling in the CD4+ TCR pathway.
ar_tf_pathway; Regulation of Androgen receptor activity.
p38alphabetapathway; Regulation of p38-alpha and p38-beta.
met_pathway; Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met).
trail_pathway; TRAIL signaling pathway.
lymphangiogenesis_pathway; VEGFR3 signaling in lymphatic endothelium.
Organism-specific databases
GeneCards GC17P011864; -.
H-InvDB HIX0027148; -.
HGNC HGNC:6844; MAP2K4.
GenAtlas MAP2K4.
HPA CAB007751; -.
MIM 601335; gene. [NCBI / EBI]
PharmGKB PA30589; -.
Gene expression databases
ArrayExpress P45985; -.
Bgee P45985; -.
CleanEx HS_MAP2K4; -.
Ontologies
GO
GO:0005524; Molecular function: ATP binding (inferred from electronic annotation from UniProtKB-KW).
GO:0005515; Molecular function: protein binding (inferred from physical interaction from IntAct).
GO:0004674; Molecular function: protein serine/threonine kinase activity (inferred from electronic annotation from UniProtKB-KW).
GO:0004713; Molecular function: protein tyrosine kinase activity (inferred from electronic annotation from UniProtKB-KW).
GO:0007254; Biological process: JNK cascade (traceable author statement from ProtInc).
GO:0006468; Biological process: protein amino acid phosphorylation (inferred from electronic annotation from InterPro).
QuickGo view.
Family and domain databases
InterPro IPR000719; Prot_kinase_core.
IPR017441; Protein_kinase_ATP_BS.
IPR017442; Se/Thr_pkinase-rel.
IPR008271; Ser_thr_pkin_AS.
IPR002290; Ser_thr_pkinase.
Graphical view of domain structure.
Pfam PF00069; Pkinase; 1.
Pfam graphical view of domain structure.
ProDom PD000001; Prot_kinase; 1.
[Domain structure / List of seq. sharing at least 1 domain]
SMART SM00220; S_TKc; 1.
SMART graphical view of domain structure.
PROSITE PS00107; PROTEIN_KINASE_ATP; 1.
PS50011; PROTEIN_KINASE_DOM; 1.
PS00108; PROTEIN_KINASE_ST; 1.
PROSITE graphical view of domain structure (profiles).
Proteomic databases
PRIDE P45985; -.
Genome annotation databases
Ensembl ENSG00000065559; Homo sapiens. [Contig view]
GeneID 6416; -.
KEGG hsa:6416; -.
NMPDR fig|9606.3.peg.13149; -.
Phylogenomic databases
HOGENOM P45985; -.
HOVERGEN P45985; -.
OMA P45985; NILMDRR.
Other
NextBio 24922; -.
PMAP-CutDB P45985; -.
SOURCE MAP2K4; Homo sapiens.
ProtoNet P45985.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
ATP-binding; Kinase; Nucleotide-binding; Phosphoprotein; Polymorphism; Serine/threonine-protein kinase; Transferase; Tyrosine-protein kinase.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom   To Length Description FTId
CHAIN   1   399  399     Dual specificity mitogen-activated protein kinase kinase 4. PRO_0000086381
DOMAIN   102   367  266     Protein kinase. 
NP_BIND   108   116  9     ATP (By similarity). 
COMPBIAS   5    19  15     Gly/Ser-rich. 
ACT_SITE   229   229        Proton acceptor (By similarity). 
BINDING   131   131        ATP (By similarity). 
SITE   45    46  2     Cleavage; by anthrax lethal factor. 
SITE   58    59  2     Cleavage; by anthrax lethal factor. 
MOD_RES   90    90        Phosphoserine. 
VARIANT   142   142  1     Q -> L (in a lung squamous cell carcinoma sample; somatic mutation). VAR_040818 
VARIANT   154   154  1     R -> W (in a colorectal adenocarcinoma sample; somatic mutation). VAR_040819 
VARIANT   234   234  1     N -> I (in an ovarian serous carcinoma sample; somatic mutation). VAR_040820 
VARIANT   251   251  1     S -> N (in a metastatic melanoma sample; somatic mutation). VAR_040821 
VARIANT   279   279  1     A -> T (in a colorectal adenocarcinoma sample; somatic mutation). VAR_040822 
Sequence information
Length: 399 AA [This is the length of the unprocessed precursor] Molecular weight: 44288 Da [This is the MW of the unprocessed precursor] CRC64: A472537F2F26770B [This is a checksum on the sequence]
        10         20         30         40         50         60 
MAAPSPSGGG GSGGGSGSGT PGPVGSPAPG HPAVSSMQGK RKALKLNFAN PPFKSTARFT 

        70         80         90        100        110        120 
LNPNPTGVQN PHIERLRTHS IESSGKLKIS PEQHWDFTAE DLKDLGEIGR GAYGSVNKMV 

       130        140        150        160        170        180 
HKPSGQIMAV KRIRSTVDEK EQKQLLMDLD VVMRSSDCPY IVQFYGALFR EGDCWICMEL 

       190        200        210        220        230        240 
MSTSFDKFYK YVYSVLDDVI PEEILGKITL ATVKALNHLK ENLKIIHRDI KPSNILLDRS 

       250        260        270        280        290        300 
GNIKLCDFGI SGQLVDSIAK TRDAGCRPYM APERIDPSAS RQGYDVRSDV WSLGITLYEL 

       310        320        330        340        350        360 
ATGRFPYPKW NSVFDQLTQV VKGDPPQLSN SEEREFSPSF INFVNLCLTK DESKRPKYKE 

       370        380        390 
LLKHPFILMY EERAVEVACY VCKILDQMPA TPSSPMYVD 

P45985 in FASTA format

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