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UniProtKB/Swiss-Prot entry P36507


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

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Entry information
Entry name MP2K2_HUMAN
Primary accession number P36507
Secondary accession numbers None
Integrated into Swiss-Prot on June 1, 1994
Sequence was last modified on June 1, 1994 (Sequence version 1)
Annotations were last modified on    June 16, 2009 (Entry version 112)
Name and origin of the protein
Protein name Dual specificity mitogen-activated protein kinase kinase 2
Synonyms MAP kinase kinase 2
MAPKK 2
EC 2.7.12.2
ERK activator kinase 2
MAPK/ERK kinase 2
MEK2
Gene name
Name: MAP2K2
Synonyms: MEK2, MKK2, PRKMK2
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].
PubMed=8388392 [NCBI, ExPASy, EBI, Israel, Japan]
Zheng C.-F., Guan K.-L.;
"Cloning and characterization of two distinct human extracellular signal-regulated kinase activator kinases, MEK1 and MEK2.";
J. Biol. Chem. 268:11435-11439(1993).
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Muscle, and Skin;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[3]
PROTEIN SEQUENCE OF 40-51; 53-61; 64-100; 102-112; 164-172; 194-205; 265-297; 362-371 AND 389-397, PHOSPHORYLATION AT THR-394, AND MASS SPECTROMETRY.
TISSUE=Colon carcinoma;
Bienvenut W.V., Zebisch A., Kolch W.;
Submitted (DEC-2008) to UniProtKB.
[4]
CLEAVAGE BY ANTHRAX LETHAL FACTOR.
DOI=10.1126/science.280.5364.734; PubMed=9563949 [NCBI, ExPASy, EBI, Israel, Japan]
Duesbery N.S., Webb C.P., Leppla S.H., Gordon V.M., Klimpel K.R., Copeland T.D., Ahn N.G., Oskarsson M.K., Fukasawa K., Paull K.D., Vande Woude G.F.;
"Proteolytic inactivation of MAP-kinase-kinase by anthrax lethal factor.";
Science 280:734-737(1998).
[5]
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).
[6]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-394, AND MASS SPECTROMETRY.
TISSUE=Epithelium;
DOI=10.1073/pnas.0404720101; PubMed=15302935 [NCBI, ExPASy, EBI, Israel, Japan]
Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P.;
"Large-scale characterization of HeLa cell nuclear phosphoproteins.";
Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004).
[7]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-23 AND THR-394, AND MASS SPECTROMETRY.
TISSUE=Epithelium;
DOI=10.1016/j.cell.2006.09.026; PubMed=17081983 [NCBI, ExPASy, EBI, Israel, Japan]
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.";
Cell 127:635-648(2006).
[8]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-396, AND MASS SPECTROMETRY.
TISSUE=Epithelium;
DOI=10.1038/nbt1240; PubMed=16964243 [NCBI, ExPASy, EBI, Israel, Japan]
Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
"A probability-based approach for high-throughput protein phosphorylation analysis and site localization.";
Nat. Biotechnol. 24:1285-1292(2006).
[9]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-226 AND THR-394, AND MASS SPECTROMETRY.
DOI=10.1074/mcp.T600062-MCP200; PubMed=17192257 [NCBI, ExPASy, EBI, Israel, Japan]
Wissing J., Jaensch L., Nimtz M., Dieterich G., Hornberger R., Keri G., Wehland J., Daub H.;
"Proteomics analysis of protein kinases by target class-selective prefractionation and tandem mass spectrometry.";
Mol. Cell. Proteomics 6:537-547(2007).
[10]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-396, AND MASS SPECTROMETRY.
DOI=10.2116/analsci.24.161; PubMed=18187866 [NCBI, ExPASy, EBI, Israel, Japan]
Imami K., Sugiyama N., Kyono Y., Tomita M., Ishihama Y.;
"Automated phosphoproteome analysis for cultured cancer cells by two-dimensional nanoLC-MS using a calcined titania/C18 biphasic column.";
Anal. Sci. 24:161-166(2008).
[11]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-394 AND THR-396, AND MASS SPECTROMETRY.
TISSUE=Platelet;
DOI=10.1021/pr0704130; PubMed=18088087 [NCBI, ExPASy, EBI, Israel, Japan]
Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A.;
"Phosphoproteome of resting human platelets.";
J. Proteome Res. 7:526-534(2008).
[12]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-23; SER-293; SER-295 AND THR-396, AND MASS SPECTROMETRY.
DOI=10.1016/j.molcel.2008.07.007; PubMed=18691976 [NCBI, ExPASy, EBI, Israel, Japan]
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.;
"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle.";
Mol. Cell 31:438-448(2008).
[13]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-222; SER-226; THR-394 AND THR-396, 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).
[14]
IDENTIFICATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
Colinge J., Superti-Furga G., Bennett K.L.;
Submitted (OCT-2008) to UniProtKB.
[15]
VARIANT CFC SYNDROME CYS-57.
DOI=10.1126/science.1124642; PubMed=16439621 [NCBI, ExPASy, EBI, Israel, Japan]
Rodriguez-Viciana P., Tetsu O., Tidyman W.E., Estep A.L., Conger B.A., Cruz M.S., McCormick F., Rauen K.A.;
"Germline mutations in genes within the MAPK pathway cause cardio-facio-cutaneous syndrome.";
Science 311:1287-1290(2006).
Comments
  • FUNCTION: Catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in MAP kinases. Activates the ERK1 and ERK2 MAP kinases (By similarity).
  • CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
  • SUBUNIT: Interacts with MORG1 (By similarity).
  • INTERACTION:
    P10398:ARAF; NbExp=3; IntAct=EBI-1056930, EBI-365961;
  • PTM: MAPKK is itself dependent on Ser/Thr phosphorylation for activity catalyzed by MAP kinase kinase kinases (RAF or MEKK1).
  • DISEASE: Defects in MAP2K2 are a cause of cardiofaciocutaneous syndrome (CFC syndrome) [MIM:115150]; also known as cardio-facio-cutaneous syndrome. CFC syndrome is characterized by a distinctive facial appearance, heart defects and mental retardation. Heart defects include pulmonic stenosis, atrial septal defects and hypertrophic cardiomyopathy. Some affected individuals present with ectodermal abnormalities such as sparse, friable hair, hyperkeratotic skin lesions and a generalized ichthyosis-like condition. Typical facial features are similar to Noonan syndrome. They include high forehead with bitemporal constriction, hypoplastic supraorbital ridges, downslanting palpebral fissures, a depressed nasal bridge, and posteriorly angulated ears with prominent helices. The inheritance of CFC syndrome is autosomal dominant.
  • SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily.
  • SIMILARITY: Contains 1 protein kinase domain.
  • WEB RESOURCE: Name=GeneReviews; URL="http://www.genetests.org/query?gene=MAP2K2";.
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
L11285; -; NOT_ANNOTATED_CDS; mRNA.[EMBL / GenBank / DDBJ]
BC000471; AAH00471.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC018645; AAH18645.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
IPI IPI00003783; -.
PIR A46723; A46723.
RefSeq NP_109587.1; -.
UniGene Hs.465627
3D structure databases
PDB
1S9I; X-ray; 3.20 A; A/B=55-400.[ExPASy / RCSB / EBI]
PDBsum 1S9I; -.
ModBase P36507.
Protein-protein interaction databases
DIP DIP:29119N; -.
IntAct P36507; 11.
PTM databases
PhosphoSite P36507; -.
Enzyme and pathway databases
BRENDA 2.7.12.2; 247.
Pathway_Interaction_DB anthraxpathway; Cellular roles of Anthrax toxin.
ceramidepathway; Ceramide signaling pathway.
cd8tcrdownstreampathway; Downstream signaling in naive CD8+ T cells.
endothelinpathway; Endothelins.
fcer1pathway; Fc-epsilon receptor I signaling in mast cells.
il2_1pathway; IL2-mediated signaling events.
met_pathway; Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met).
kitpathway; Signaling events mediated by Stem cell factor receptor (c-Kit).
Reactome REACT_11061; Signalling by NGF.
REACT_498; Signaling by Insulin receptor.
2D gel databases
REPRODUCTION-2DPAGE IPI00003783; -.
Organism-specific databases
GeneCards GC19M004041; -.
H-InvDB HIX0014653; -.
HIX0033655; -.
HGNC HGNC:6842; MAP2K2.
GenAtlas MAP2K2.
HPA CAB003835; -.
MIM 115150; phenotype. [NCBI / EBI]
601263; gene. [NCBI / EBI]
Orphanet 1340; Cardiofaciocutaneous syndrome.
PharmGKB PA30587; -.
Gene expression databases
ArrayExpress P36507; -.
Bgee P36507; -.
CleanEx HS_MAP2K2; -.
GermOnline ENSG00000126934; Homo sapiens.
Ontologies
GO
GO:0005576; Cellular component: extracellular region (non-traceable author statement from UniProtKB).
GO:0005524; Molecular function: ATP binding (non-traceable author statement from UniProtKB).
GO:0005515; Molecular function: protein binding (inferred from physical interaction from IntAct).
GO:0004674; Molecular function: protein serine/threonine kinase activity (non-traceable author statement from UniProtKB).
GO:0004713; Molecular function: protein tyrosine kinase activity (inferred from electronic annotation from UniProtKB-KW).
GO:0006468; Biological process: protein amino acid phosphorylation (non-traceable author statement from UniProtKB).
GO:0007265; Biological process: Ras protein signal transduction (inferred from experiment from Reactome).
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
PeptideAtlas P36507; -.
PRIDE P36507; -.
Genome annotation databases
Ensembl ENSG00000126934; Homo sapiens. [Contig view]
GeneID 5605; -.
KEGG hsa:5605; -.
Phylogenomic databases
HOGENOM P36507; -.
HOVERGEN P36507; -.
OMA P36507; FEPICEL.
Other
NextBio 21780; -.
PMAP-CutDB P36507; -.
SOURCE MAP2K2; Homo sapiens.
ProtoNet P36507.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
3D-structure; ATP-binding; Direct protein sequencing; Disease mutation; Kinase; Nucleotide-binding; Phosphoprotein; 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   400  400     Dual specificity mitogen-activated protein kinase kinase 2. PRO_0000086372
DOMAIN   72   369  298     Protein kinase. 
NP_BIND   78    86  9     ATP (By similarity). 
COMPBIAS   266   315  50     Pro-rich. 
ACT_SITE   194   194        Proton acceptor (By similarity). 
BINDING   101   101        ATP (By similarity). 
SITE   10    11  2     Cleavage; by anthrax lethal factor. 
MOD_RES   23    23        Phosphoserine. 
MOD_RES   222   222        Phosphoserine; by RAF. 
MOD_RES   226   226        Phosphoserine. 
MOD_RES   293   293        Phosphoserine. 
MOD_RES   295   295        Phosphoserine. 
MOD_RES   394   394        Phosphothreonine. 
MOD_RES   396   396        Phosphothreonine. 
VARIANT   57    57  1     F -> C (in CFC syndrome). VAR_035095 
HELIX   69    71  3      
STRAND   72    80  9      
STRAND   85    91  7      
TURN   92    94  3      
STRAND   97   103  7      
HELIX   110   119  10      
HELIX   120   122  3      
STRAND   133   148  16      
HELIX   155   161  7      
STRAND   162   164  3      
HELIX   167   186  20      
HELIX   197   199  3      
STRAND   200   202  3      
STRAND   208   210  3      
HELIX   217   222  6      
HELIX   236   239  4      
HELIX   246   262  17      
HELIX   272   279  8      
HELIX   318   327  10      
TURN   335   337  3      
HELIX   340   349  10      
TURN   354   356  3      
HELIX   360   364  5      
HELIX   367   374  8      
HELIX   379   386  8      
Sequence information
Length: 400 AA [This is the length of the unprocessed precursor] Molecular weight: 44424 Da [This is the MW of the unprocessed precursor] CRC64: 3401D522515C30A5 [This is a checksum on the sequence]
        10         20         30         40         50         60 
MLARRKPVLP ALTINPTIAE GPSPTSEGAS EANLVDLQKK LEELELDEQQ KKRLEAFLTQ 

        70         80         90        100        110        120 
KAKVGELKDD DFERISELGA GNGGVVTKVQ HRPSGLIMAR KLIHLEIKPA IRNQIIRELQ 

       130        140        150        160        170        180 
VLHECNSPYI VGFYGAFYSD GEISICMEHM DGGSLDQVLK EAKRIPEEIL GKVSIAVLRG 

       190        200        210        220        230        240 
LAYLREKHQI MHRDVKPSNI LVNSRGEIKL CDFGVSGQLI DSMANSFVGT RSYMAPERLQ 

       250        260        270        280        290        300 
GTHYSVQSDI WSMGLSLVEL AVGRYPIPPP DAKELEAIFG RPVVDGEEGE PHSISPRPRP 

       310        320        330        340        350        360 
PGRPVSGHGM DSRPAMAIFE LLDYIVNEPP PKLPNGVFTP DFQEFVNKCL IKNPAERADL 

       370        380        390        400 
KMLTNHTFIK RSEVEEVDFA GWLCKTLRLN QPGTPTRTAV 

P36507 in FASTA format

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