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UniProtKB/Swiss-Prot entry Q9Y2U5


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

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Entry information
Entry name M3K2_HUMAN
Primary accession number Q9Y2U5
Secondary accession numbers Q53QL9 Q53S75 Q59GZ6 Q8NC32 Q9NYK3
Integrated into Swiss-Prot on May 30, 2000
Sequence was last modified on May 16, 2006 (Sequence version 2)
Annotations were last modified on    June 16, 2009 (Entry version 100)
Name and origin of the protein
Protein name Mitogen-activated protein kinase kinase kinase 2
Synonyms EC 2.7.11.25
MAPK/ERK kinase kinase 2
MEK kinase 2
MEKK 2
Gene name
Name: MAP3K2
Synonyms: MAPKKK2, MEKK2
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].
Su B., Yang J.H., Xia Y., Karin M.;
"MEKK2 is involved in transducing T-cell co-stimulatory signals to the JNK cascade.";
Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases.
[2]
NUCLEOTIDE SEQUENCE [MRNA].
TISSUE=T-cell;
Wang C., Lo H.;
"Cloning of human MEKK2b cDNA.";
Submitted (FEB-2000) to the EMBL/GenBank/DDBJ databases.
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Brain;
Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F.;
Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
DOI=10.1038/nature03466; PubMed=15815621 [NCBI, ExPASy, EBI, Israel, Japan]
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.;
"Generation and annotation of the DNA sequences of human chromosomes 2 and 4.";
Nature 434:724-731(2005).
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 180-619.
TISSUE=Teratocarcinoma;
DOI=10.1038/ng1285; PubMed=14702039 [NCBI, ExPASy, EBI, Israel, Japan]
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
"Complete sequencing and characterization of 21,243 full-length human cDNAs.";
Nat. Genet. 36:40-45(2004).
[6]
FUNCTION, AND INTERACTION WITH MAP2K7 AND MAPK8.
DOI=10.1128/MCB.20.7.2334-2342.2000; PubMed=10713157 [NCBI, ExPASy, EBI, Israel, Japan]
Cheng J., Yang J., Xia Y., Karin M., Su B.;
"Synergistic interaction of MEK kinase 2, c-Jun N-terminal kinase (JNK) kinase 2, and JNK1 results in efficient and specific JNK1 activation.";
Mol. Cell. Biol. 20:2334-2342(2000).
[7]
SUBCELLULAR LOCATION.
DOI=10.1242/jcs.01040; PubMed=15075238 [NCBI, ExPASy, EBI, Israel, Japan]
Raviv Z., Kalie E., Seger R.;
"MEK5 and ERK5 are localized in the nuclei of resting as well as stimulated cells, while MEKK2 translocates from the cytosol to the nucleus upon stimulation.";
J. Cell Sci. 117:1773-1784(2004).
[8]
FUNCTION.
DOI=10.1038/nature03866; PubMed=16001074 [NCBI, ExPASy, EBI, Israel, Japan]
Pelkmans L., Zerial M.;
"Kinase-regulated quantal assemblies and kiss-and-run recycling of caveolae.";
Nature 436:128-133(2005).
[9]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-164, 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 SER-164, 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).
[11]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-163; SER-164 AND SER-297, AND MASS SPECTROMETRY.
DOI=10.1021/pr0705441; PubMed=18220336 [NCBI, ExPASy, EBI, Israel, Japan]
Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis.";
J. Proteome Res. 7:1346-1351(2008).
[12]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-153; SER-239; SER-331; SER-344 AND SER-349, 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-153; SER-159 AND SER-164, 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]
STRUCTURE BY NMR OF 43-132.
RIKEN structural genomics initiative (RSGI);
"Solution structure of the PB1 domain of human protein kinase MEKK2B.";
Submitted (NOV-2005) to the PDB data bank.
[15]
VARIANTS [LARGE SCALE ANALYSIS] VAL-110; ILE-112 AND GLY-140.
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
AF111105; AAD28547.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF239798; AAF63496.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AB208963; BAD92200.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AC068282; AAY15043.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AC110926; AAY15070.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AK075004; BAC11348.1; ALT_INIT; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
IPI IPI00513803; -.
RefSeq NP_006600.3; -.
UniGene Hs.145605
3D structure databases
PDB
2CU1; NMR; -; A=43-132.[ExPASy / RCSB / EBI]
2NPT; X-ray; 1.75 A; B/D=26-123.[ExPASy / RCSB / EBI]
Detailed list of linked structures.
PDBsum 2CU1; -.
2NPT; -.
ModBase Q9Y2U5.
Protein-protein interaction databases
IntAct Q9Y2U5; 5.
PTM databases
PhosphoSite Q9Y2U5; -.
Enzyme and pathway databases
BRENDA 2.7.11.25; 247.
2.7.12.2; 247.
Pathway_Interaction_DB mapktrkpathway; Trk receptor signaling mediated by the MAPK pathway.
Organism-specific databases
GeneCards GC02M127780; -.
H-InvDB HIX0002433; -.
HGNC HGNC:6854; MAP3K2.
GenAtlas MAP3K2.
MIM 609487; gene. [NCBI / EBI]
PharmGKB PA30598; -.
Gene expression databases
ArrayExpress Q9Y2U5; -.
Bgee Q9Y2U5; -.
CleanEx HS_MAP3K2; -.
GermOnline ENSG00000169967; Homo sapiens.
Ontologies
GO
GO:0005737; Cellular component: cytoplasm (inferred from electronic annotation from UniProtKB-SubCell).
GO:0005634; Cellular component: nucleus (inferred from electronic annotation from UniProtKB-SubCell).
GO:0005524; Molecular function: ATP binding (inferred from electronic annotation from UniProtKB-KW).
GO:0000287; Molecular function: magnesium ion binding (inferred from electronic annotation from UniProtKB-KW).
GO:0004709; Molecular function: MAP kinase kinase kinase activity (inferred from electronic annotation from EC).
GO:0007257; Biological process: activation of JUN kinase activity (traceable author statement from ProtInc).
QuickGo view.
Family and domain databases
InterPro IPR015748; MAPKKK3.
IPR000270; OPR_PB1.
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.
PANTHER PTHR22986:SF64; MAPKKK3; 1.
Pfam PF00564; PB1; 1.
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 SM00666; PB1; 1.
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; FALSE_NEG.
PROSITE graphical view of domain structure (profiles).
Proteomic databases
PRIDE Q9Y2U5; -.
Genome annotation databases
Ensembl ENSG00000169967; Homo sapiens. [Contig view]
GeneID 10746; -.
KEGG hsa:10746; -.
NMPDR fig|9606.3.peg.18599; -.
Phylogenomic databases
HOGENOM Q9Y2U5; -.
HOVERGEN Q9Y2U5; -.
Other
NextBio 40805; -.
SOURCE MAP3K2; Homo sapiens.
ProtoNet Q9Y2U5.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
3D-structure; ATP-binding; Cytoplasm; Kinase; Magnesium; Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Serine/threonine-protein kinase; Transferase.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom   To Length Description FTId
CHAIN   1   619  619     Mitogen-activated protein kinase kinase kinase 2. PRO_0000086243
DOMAIN   43   122  80     OPR. 
DOMAIN   357   617  261     Protein kinase. 
NP_BIND   362   371  10     ATP (By similarity). 
ACT_SITE   483   483        Proton acceptor (By similarity). 
BINDING   385   385        ATP (By similarity). 
MOD_RES   153   153        Phosphoserine. 
MOD_RES   159   159        Phosphoserine. 
MOD_RES   163   163        Phosphoserine. 
MOD_RES   164   164        Phosphoserine. 
MOD_RES   239   239        Phosphoserine. 
MOD_RES   297   297        Phosphoserine. 
MOD_RES   304   304        Phosphothreonine (By similarity). 
MOD_RES   331   331        Phosphoserine. 
MOD_RES   344   344        Phosphoserine. 
MOD_RES   349   349        Phosphoserine. 
MOD_RES   524   524        Phosphothreonine (By similarity). 
VARIANT   110   110  1     I -> V. VAR_040682 
VARIANT   112   112  1     M -> I (in a lung large cell carcinoma sample; somatic mutation). VAR_040683 
VARIANT   140   140  1     D -> G. VAR_040684 
CONFLICT   1     1        M -> GTR (in Ref. 3; BAD92200). 
CONFLICT   103   103        V -> L (in Ref. 1; AAD28547 and 2; AAF63496). 
CONFLICT   198   198        D -> E (in Ref. 1; AAD28547 and 2; AAF63496). 
CONFLICT   225   225        D -> G (in Ref. 1; AAD28547). 
CONFLICT   275   277        QEY -> KD (in Ref. 1; AAD28547). 
CONFLICT   293   296        TSLR -> NQLT (in Ref. 1; AAD28547 and 2; AAF63496). 
CONFLICT   413   413        L -> F (in Ref. 1; AAD28547). 
CONFLICT   459   459        V -> G (in Ref. 1; AAD28547). 
CONFLICT   480   480        V -> L (in Ref. 1; AAD28547). 
CONFLICT   536   536        E -> Q (in Ref. 1; AAD28547 and 2; AAF63496). 
CONFLICT   579   579        N -> S (in Ref. 5; BAC11348). 
STRAND   44    50  7      
STRAND   53    59  7      
HELIX   65    76  12      
STRAND   80    86  7      
STRAND   89    92  4      
HELIX   96   108  13      
STRAND   114   121  8      
Sequence information
Length: 619 AA [This is the length of the unprocessed precursor] Molecular weight: 69741 Da [This is the MW of the unprocessed precursor] CRC64: E034580D349F097F [This is a checksum on the sequence]
        10         20         30         40         50         60 
MDDQQALNSI MQDLAVLHKA SRPALSLQET RKAKSSSPKK QNDVRVKFEH RGEKRILQFP 

        70         80         90        100        110        120 
RPVKLEDLRS KAKIAFGQSM DLHYTNNELV IPLTTQDDLD KAVELLDRSI HMKSLKILLV 

       130        140        150        160        170        180 
INGSTQATNL EPLPSLEDLD NTVFGAERKK RLSIIGPTSR DRSSPPPGYI PDELHQVARN 

       190        200        210        220        230        240 
GSFTSINSEG EFIPESMDQM LDPLSLSSPE NSGSGSCPSL DSPLDGESYP KSRMPRAQSY 

       250        260        270        280        290        300 
PDNHQEFSDY DNPIFEKFGK GGTYPRRYHV SYHHQEYNDG RKTFPRARRT QGTSLRSPVS 

       310        320        330        340        350        360 
FSPTDHSLST SSGSSIFTPE YDDSRIRRRG SDIDNPTLTV MDISPPSRSP RAPTNWRLGK 

       370        380        390        400        410        420 
LLGQGAFGRV YLCYDVDTGR ELAVKQVQFD PDSPETSKEV NALECEIQLL KNLLHERIVQ 

       430        440        450        460        470        480 
YYGCLRDPQE KTLSIFMEYM PGGSIKDQLK AYGALTENVT RKYTRQILEG VHYLHSNMIV 

       490        500        510        520        530        540 
HRDIKGANIL RDSTGNVKLG DFGASKRLQT ICLSGTGMKS VTGTPYWMSP EVISGEGYGR 

       550        560        570        580        590        600 
KADIWSVACT VVEMLTEKPP WAEFEAMAAI FKIATQPTNP KLPPHVSDYT RDFLKRIFVE 

       610 
AKLRPSADEL LRHMFVHYH 

Q9Y2U5 in FASTA format

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