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UniProtKB/Swiss-Prot entry Q9Y6R4


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

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Entry information
Entry name M3K4_HUMAN
Primary accession number Q9Y6R4
Secondary accession number Q92612
Integrated into Swiss-Prot on May 30, 2000
Sequence was last modified on November 1, 1999 (Sequence version 1)
Annotations were last modified on    June 16, 2009 (Entry version 86)
Name and origin of the protein
Protein name Mitogen-activated protein kinase kinase kinase 4
Synonyms EC 2.7.11.25
MAPK/ERK kinase kinase 4
MEK kinase 4
MEKK 4
MAP three kinase 1
Gene name
Name: MAP3K4
Synonyms: KIAA0213, MAPKKK4, MEKK4, MTK1
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], FUNCTION, TISSUE SPECIFICITY, ALTERNATIVE SPLICING, AND MUTAGENESIS OF LYS-1371.
TISSUE=Fetal liver, and Skeletal muscle;
DOI=10.1093/emboj/16.16.4973; PubMed=9305639 [NCBI, ExPASy, EBI, Israel, Japan]
Takekawa M., Posas F., Saito H.;
"A human homolog of the yeast Ssk2/Ssk22 MAP kinase kinase kinases, MTK1, mediates stress-induced activation of the p38 and JNK pathways.";
EMBO J. 16:4973-4982(1997).
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B).
TISSUE=Bone marrow;
DOI=10.1093/dnares/3.5.321; PubMed=9039502 [NCBI, ExPASy, EBI, Israel, Japan]
Nagase T., Seki N., Ishikawa K., Ohira M., Kawarabayasi Y., Ohara O., Tanaka A., Kotani H., Miyajima N., Nomura N.;
"Prediction of the coding sequences of unidentified human genes. VI. The coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of cDNA clones from cell line KG-1 and brain.";
DNA Res. 3:321-329(1996).
[3]
SEQUENCE REVISION.
Ohara O., Nagase T., Kikuno R., Nomura N.;
Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
[4]
FUNCTION, ENZYME REGULATION, INTERACTION WITH GADD45 AND MAP2K6, AND MUTAGENESIS OF LYS-1371.
DOI=10.1128/MCB.22.13.4544-4555.2002; PubMed=12052864 [NCBI, ExPASy, EBI, Israel, Japan]
Mita H., Tsutsui J., Takekawa M., Witten E.A., Saito H.;
"Regulation of MTK1/MEKK4 kinase activity by its N-terminal autoinhibitory domain and GADD45 binding.";
Mol. Cell. Biol. 22:4544-4555(2002).
[5]
INTERACTION WITH AXIN1 AND DIXDC1.
DOI=10.1074/jbc.M404598200; PubMed=15262978 [NCBI, ExPASy, EBI, Israel, Japan]
Wong C.K., Luo W., Deng Y., Zou H., Ye Z., Lin S.-C.;
"The DIX domain protein coiled-coil-DIX1 inhibits c-Jun N-terminal kinase activation by Axin and dishevelled through distinct mechanisms.";
J. Biol. Chem. 279:39366-39373(2004).
[6]
IDENTIFICATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
Colinge J., Superti-Furga G., Bennett K.L.;
Submitted (OCT-2008) to UniProtKB.
[7]
VARIANTS [LARGE SCALE ANALYSIS] THR-294; ILE-335; HIS-566; HIS-584; PRO-906; GLN-1412 AND VAL-1491.
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
AF002715; AAB68804.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
D86968; BAA13204.2; ALT_INIT; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
IPI IPI00186536; -.
IPI00386260; -.
PIR T03022; T03022.
RefSeq NP_005913.2; -.
NP_006715.2; -.
UniGene Hs.390428
3D structure databases
HSSP P24941; 1H0U. [HSSP ENTRY / PDB]
ModBase Q9Y6R4.
Protein-protein interaction databases
IntAct Q9Y6R4; 9.
PTM databases
PhosphoSite Q9Y6R4; -.
Enzyme and pathway databases
BRENDA 2.7.11.25; 247.
2.7.12.2; 247.
Pathway_Interaction_DB p38_mkk3_6pathway; p38 MAPK signaling pathway.
Organism-specific databases
GeneCards GC06P161383; -.
H-InvDB HIX0006350; -.
HIX0019122; -.
HGNC HGNC:6856; MAP3K4.
GenAtlas MAP3K4.
HPA HPA007625; -.
MIM 602425; gene. [NCBI / EBI]
PharmGKB PA30600; -.
HUGE KIAA0213.
Gene expression databases
ArrayExpress Q9Y6R4; -.
Bgee Q9Y6R4; -.
CleanEx HS_MAP3K4; -.
Ontologies
GO
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 (traceable author statement from ProtInc).
GO:0000186; Biological process: activation of MAPKK activity (traceable author statement from ProtInc).
GO:0007254; Biological process: JNK cascade (traceable author statement from ProtInc).
QuickGo view.
Family and domain databases
InterPro IPR015747; MAPKKK4.
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:SF60; MAPKKK4; 1.
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 Q9Y6R4; -.
Genome annotation databases
Ensembl ENSG00000085511; Homo sapiens. [Contig view]
GeneID 4216; -.
KEGG hsa:4216; -.
Phylogenomic databases
HOGENOM Q9Y6R4; -.
HOVERGEN Q9Y6R4; -.
Other
NextBio 16627; -.
SOURCE MAP3K4; Homo sapiens.
ProtoNet Q9Y6R4.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
Alternative splicing; ATP-binding; Kinase; Magnesium; Metal-binding; Nucleotide-binding; 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   1607  1607     Mitogen-activated protein kinase kinase kinase 4. PRO_0000086247
DOMAIN   1342   1600  259     Protein kinase. 
NP_BIND   1348   1356  9     ATP (By similarity). 
COMPBIAS   4      7  4     Poly-Ala. 
COMPBIAS   25     38  14     Poly-Pro. 
COMPBIAS   1190   1201  12     Poly-Ala. 
ACT_SITE   1462   1462        Proton acceptor (By similarity). 
BINDING   1371   1371        ATP (By similarity). 
MOD_RES   499    499        Phosphoserine (By similarity). 
MOD_RES   1504   1504        Phosphothreonine (By similarity). 
VAR_SEQ   1175   1223        Missing (in isoform B). VSP_004884
VARIANT   294    294  1     I -> T. VAR_040686 
VARIANT   335    335  1     V -> I. VAR_040687 
VARIANT   566    566  1     R -> H. VAR_040688 
VARIANT   584    584  1     Q -> H. VAR_040689 
VARIANT   906    906  1     H -> P. VAR_040690 
VARIANT   1412   1412  1     E -> Q (in an ovarian serous carcinoma sample; somatic mutation). VAR_040691 
VARIANT   1491   1491  1     A -> V. VAR_040692 
MUTAGEN   1371   1371        K->R: Loss of activity. 
CONFLICT   791    791        I -> R (in Ref. 2; BAA13204). 
Sequence information
Length: 1607 AA [This is the length of the unprocessed precursor] Molecular weight: 181552 Da [This is the MW of the unprocessed precursor] CRC64: 24BC4597730B5287 [This is a checksum on the sequence]
        10         20         30         40         50         60 
MREAAAALVP PPAFAVTPAA AMEEPPPPPP PPPPPPEPET ESEPECCLAA RQEGTLGDSA 

        70         80         90        100        110        120 
CKSPESDLED FSDETNTENL YGTSPPSTPR QMKRMSTKHQ RNNVGRPASR SNLKEKMNAP 

       130        140        150        160        170        180 
NQPPHKDTGK TVENVEEYSY KQEKKIRAAL RTTERDHKKN VQCSFMLDSV GGSLPKKSIP 

       190        200        210        220        230        240 
DVDLNKPYLS LGCSNAKLPV SVPMPIARPA RQTSRTDCPA DRLKFFETLR LLLKLTSVSK 

       250        260        270        280        290        300 
KKDREQRGQE NTSGFWLNRS NELIWLELQA WHAGRTINDQ DFFLYTARQA IPDIINEILT 

       310        320        330        340        350        360 
FKVDYGSFAF VRDRAGFNGT SVEGQCKATP GTKIVGYSTH HEHLQRQRVS FEQVKRIMEL 

       370        380        390        400        410        420 
LEYIEALYPS LQALQKDYEK YAAKDFQDRV QALCLWLNIT KDLNQKLRIM GTVLGIKNLS 

       430        440        450        460        470        480 
DIGWPVFEIP SPRPSKGNEP EYEGDDTEGE LKELESSTDE SEEEQISDPR VPEIRQPIDN 

       490        500        510        520        530        540 
SFDIQSRDCI SKKLERLESE DDSLGWGAPD WSTEAGFSRH CLTSIYRPFV DKALKQMGLR 

       550        560        570        580        590        600 
KLILRLHKLM DGSLQRARIA LVKNDRPVEF SEFPDPMWGS DYVQLSRTPP SSEEKCSAVS 

       610        620        630        640        650        660 
WEELKAMDLP SFEPAFLVLC RVLLNVIHEC LKLRLEQRPA GEPSLLSIKQ LVRECKEVLK 

       670        680        690        700        710        720 
GGLLMKQYYQ FMLQEVLEDL EKPDCNIDAF EEDLHKMLMV YFDYMRSWIQ MLQQLPQASH 

       730        740        750        760        770        780 
SLKNLLEEEW NFTKEITHYI RGGEAQAGKL FCDIAGMLLK STGSFLEFGL QESCAEFWTS 

       790        800        810        820        830        840 
ADDSSASDEI IRSVIEISRA LKELFHEARE RASKALGFAK MLRKDLEIAA EFRLSAPVRD 

       850        860        870        880        890        900 
LLDVLKSKQY VKVQIPGLEN LQMFVPDTLA EEKSIILQLL NAAAGKDCSK DSDDVLIDAY 

       910        920        930        940        950        960 
LLLTKHGDRA RDSEDSWGTW EAQPVKVVPQ VETVDTLRSM QVDNLLLVVM QSAHLTIQRK 

       970        980        990       1000       1010       1020 
AFQQSIEGLM TLCQEQTSSQ PVIAKALQQL KNDALELCNR ISNAIDRVDH MFTSEFDAEV 

      1030       1040       1050       1060       1070       1080 
DESESVTLQQ YYREAMIQGY NFGFEYHKEV VRLMSGEFRQ KIGDKYISFA RKWMNYVLTK 

      1090       1100       1110       1120       1130       1140 
CESGRGTRPR WATQGFDFLQ AIEPAFISAL PEDDFLSLQA LMNECIGHVI GKPHSPVTGL 

      1150       1160       1170       1180       1190       1200 
YLAIHRNSPR PMKVPRCHSD PPNPHLIIPT PEGFSTRSMP SDARSHGSPA AAAAAAAAVA 

      1210       1220       1230       1240       1250       1260 
ASRPSPSGGD SVLPKSISSA HDTRGSSVPE NDRLASIAAE LQFRSLSRHS SPTEERDEPA 

      1270       1280       1290       1300       1310       1320 
YPRGDSSGST RRSWELRTLI SQSKDTASKL GPIEAIQKSV RLFEEKRYRE MRRKNIIGQV 

      1330       1340       1350       1360       1370       1380 
CDTPKSYDNV MHVGLRKVTF KWQRGNKIGE GQYGKVYTCI SVDTGELMAM KEIRFQPNDH 

      1390       1400       1410       1420       1430       1440 
KTIKETADEL KIFEGIKHPN LVRYFGVELH REEMYIFMEY CDEGTLEEVS RLGLQEHVIR 

      1450       1460       1470       1480       1490       1500 
LYSKQITIAI NVLHEHGIVH RDIKGANIFL TSSGLIKLGD FGCSVKLKNN AQTMPGEVNS 

      1510       1520       1530       1540       1550       1560 
TLGTAAYMAP EVITRAKGEG HGRAADIWSL GCVVIEMVTG KRPWHEYEHN FQIMYKVGMG 

      1570       1580       1590       1600 
HKPPIPERLS PEGKDFLSHC LESDPKMRWT ASQLLDHSFV KVCTDEE 

Q9Y6R4 in FASTA format

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