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Identification
HMDB Protein ID HMDBP01134
Secondary Accession Numbers
  • 6430
Name Mitogen-activated protein kinase kinase kinase 1
Synonyms
  1. MAPK/ERK kinase kinase 1
  2. MEK kinase 1
  3. MEKK 1
Gene Name MAP3K1
Protein Type Unknown
Biological Properties
General Function Involved in magnesium ion binding
Specific Function Component of a protein kinase signal transduction cascade. Activates the ERK and JNK kinase pathways by phosphorylation of MAP2K1 and MAP2K4. Activates CHUK and IKBKB, the central protein kinases of the NF-kappa-B pathway
Pathways
  • Intracellular Signalling Through Adenosine Receptor A2a and Adenosine
  • Intracellular Signalling Through Adenosine Receptor A2b and Adenosine
Reactions Not Available
GO Classification
Function
ion binding
cation binding
metal ion binding
binding
catalytic activity
transition metal ion binding
zinc ion binding
transferase activity
transferase activity, transferring phosphorus-containing groups
kinase activity
nucleoside binding
purine nucleoside binding
adenyl nucleotide binding
adenyl ribonucleotide binding
atp binding
magnesium ion binding
protein binding
protein kinase activity
protein serine/threonine kinase activity
receptor signaling protein serine/threonine kinase activity
map kinase kinase kinase activity
Process
phosphorus metabolic process
phosphate metabolic process
metabolic process
signaling process
signal transmission
cellular metabolic process
protein amino acid phosphorylation
phosphorylation
signal transmission via phosphorylation event
intracellular protein kinase cascade
mapkkk cascade
Cellular Location Not Available
Gene Properties
Chromosome Location Chromosome:5
Locus 5q11.2
SNPs MAP3K1
Gene Sequence
>4539 bp
ATGGCGGCGGCGGCGGGGAATCGCGCCTCGTCGTCGGGATTCCCGGGCGCCAGGGCTACG
AGCCCTGAGGCAGGCGGCGGCGGAGGAGCCCTCAAGGCGAGCAGCGCGCCCGCGGCTGCC
GCGGGACTGCTGCGGGAGGCGGGCAGCGGGGGCCGCGAGCGGGCGGACTGGCGGCGGCGG
CAGCTGCGCAAAGTGCGGAGTGTGGAGCTGGACCAGCTGCCTGAGCAGCCGCTCTTCCTT
GCCGCCTCACCGCCGGCCTCCTCGACTTCCCCGTCGCCGGAGCCCGCGGACGCAGCGGGG
AGTGGGACCGGCTTCCAGCCTGTGGCGGTGCCGCCGCCCCACGGAGCCGCGAGCCGCGGC
GGCGCCCACCTTACCGAGTCGGTGGCGGCGCCGGACAGCGGCGCCTCGAGTCCCGCAGCG
GCCGAGCCCGGGGAGAAGCGGGCGCCCGCCGCCGAGCCGTCTCCTGCAGCGGCCCCCGCC
GGTCGTGAGATGGAGAATAAAGAAACTCTCAAAGGGTTGCACAAGATGGATGATCGTCCA
GAGGAACGAATGATCAGGGAGAAACTGAAGGCAACCTGTATGCCAGCCTGGAAGCACGAA
TGGTTGGAAAGGAGAAATAGGCGAGGGCCTGTGGTGGTAAAACCAATCCCAGTTAAAGGA
GATGGATCTGAAATGAATCACTTAGCAGCTGAGTCTCCAGGAGAGGTCCAGGCAAGTGCG
GCTTCACCAGCTTCCAAAGGCCGACGCAGTCCTTCTCCTGGCAACTCCCCATCAGGTCGC
ACAGTGAAATCAGAATCTCCAGGAGTAAGGAGAAAAAGAGTTTCCCCAGTGCCTTTTCAG
AGTGGCAGAATCACACCACCCCGAAGAGCCCCTTCACCAGATGGCTTCTCACCATATAGC
CCTGAGGAAACAAACCGCCGTGTTAACAAAGTGATGCGGGCCAGACTGTACTTACTGCAG
CAGATAGGGCCTAACTCTTTCCTGATTGGAGGAGACAGCCCAGACAATAAATACCGGGTG
TTTATTGGGCCTCAGAACTGCAGCTGTGCACGTGGAACATTCTGTATTCATCTGCTATTT
GTGATGCTCCGGGTGTTTCAACTAGAACCTTCAGACCCAATGTTATGGAGAAAAACTTTA
AAGAATTTTGAGGTTGAGAGTTTGTTCCAGAAATATCACAGTAGGCGTAGCTCAAGGATC
AAAGCTCCATCTCGTAACACCATCCAGAAGTTTGTTTCACGCATGTCAAATTCTCATACA
TTGTCATCATCTAGTACTTCTACGTCTAGTTCAGAAAACAGCATAAAGGATGAAGAGGAA
CAGATGTGTCCTATTTGCTTGTTGGGCATGCTTGATGAAGAAAGTCTTACAGTGTGTGAA
GACGGCTGCAGGAACAAGCTGCACCACCACTGCATGTCAATTTGGGCAGAAGAGTGTAGA
AGAAATAGAGAACCTTTAATATGTCCCCTTTGTAGATCTAAGTGGAGATCTCATGATTTC
TACAGCCACGAGTTGTCAAGTCCTGTGGATTCCCCTTCTTCCCTCAGAGCTGCACAGCAG
CAAACCGTACAGCAGCAGCCTTTGGCTGGATCACGAAGGAATCAAGAGAGCAATTTTAAC
CTTACTCATTATGGAACTCAGCAAATCCCTCCTGCTTACAAAGATTTAGCTGAGCCATGG
ATTCAGGTGTTTGGAATGGAACTCGTTGGCTGCTTATTTTCTAGAAACTGGAATGTGAGA
GAGATGGCCCTCAGGCGTCTTTCCCATGATGTCAGTGGGGCCCTGCTGTTGGCAAATGGG
GAGAGCACTGGAAATTCTGGGGGCAGCAGTGGAAGCAGCCCGAGTGGGGGAGCCACCAGT
GGGTCTTCCCAGACCAGTATCTCAGGAGATGTGGTGGAGGCATGCTGCAGCGTTCTGTCA
ATGGTCTGTGCTGACCCTGTCTACAAAGTGTACGTTGCTGCTTTAAAAACATTGAGAGCC
ATGCTGGTATATACTCCTTGCCACAGTTTAGCGGAAAGAATCAAACTTCAGAGACTTCTC
CAGCCAGTTGTAGACACCATCCTAGTCAAATGTGCAGATGCCAATAGCCGCACAAGTCAG
CTGTCCATATCAACACTGTTGGAACTGTGCAAAGGCCAAGCAGGAGAGTTGGCAGTTGGC
AGAGAAATACTAAAAGCTGGATCCATTGGTATTGGTGGTGTTGATTATGTCTTAAATTGT
ATTCTTGGAAACCAAACTGAATCAAACAATTGGCAAGAACTTCTTGGCCGCCTTTGTCTT
ATAGATAGACTGTTGTTGGAATTTCCTGCTGAATTTTATCCTCATATTGTCAGTACTGAT
GTTTCACAAGCTGAGCCTGTTGAAATCAGGTATAAGAAGCTGCTGTCCCTCTTAACCTTT
GCTTTGCAGTCCATTGATAATTCCCACTCAATGGTTGGCAAACTTTCCAGAAGGATCTAC
TTGAGTTCTGCAAGAATGGTTACTACAGTACCCCATGTGTTTTCAAAACTGTTAGAAATG
CTGAGTGTTTCCAGTTCCACTCACTTCACCAGGATGCGTCGCCGTTTGATGGCTATTGCA
GATGAGGTGGAAATTGCCGAAGCCATCCAGTTGGGCGTAGAAGACACTTTGGATGGTCAA
CAGGACAGCTTCTTGCAGGCATCTGTTCCCAACAACTATCTGGAAACCACAGAGAACAGT
TCCCCTGAGTGCACAGTCCATTTAGAGAAAACTGGAAAAGGATTATGTGCTACAAAATTG
AGTGCCAGTTCAGAGGACATTTCTGAGAGACTGGCCAGCATTTCAGTAGGACCTTCTAGT
TCAACAACAACAACAACAACAACAACAGAGCAACCAAAGCCAATGGTTCAAACAAAAGGC
AGACCCCACAGTCAGTGTTTGAACTCCTCTCCTTTATCTCATCATTCCCAATTAATGTTT
CCAGCCTTGTCAACCCCTTCTTCTTCTACCCCATCTGTACCAGCTGGCACTGCAACAGAT
GTCTCTAAGCATAGACTTCAGGGATTCATTCCCTGCAGAATACCTTCTGCATCTCCTCAA
ACACAGCGCAAGTTTTCTCTACAATTCCACAGAAACTGTCCTGAAAACAAAGACTCAGAT
AAACTTTCCCCAGTCTTTACTCAGTCAAGACCCTTGCCCTCCAGTAACATACACAGGCCA
AAGCCATCTAGACCTACCCCAGGTAATACAAGTAAACAGGGAGATCCCTCAAAAAATAGC
ATGACACTTGATCTGAACAGTAGTTCCAAATGTGATGACAGCTTTGGCTGTAGCAGCAAT
AGTAGTAATGCTGTTATACCCAGTGACGAGACAGTGTTCACCCCAGTAGAGGAGAAATGC
AGATTAGATGTCAATACAGAGCTCAACTCCAGTATTGAGGACCTTCTTGAAGCATCTATG
CCTTCAAGTGATACAACAGTAACTTTTAAGTCAGAAGTTGCTGTCCTGTCTCCTGAAAAG
GCTGAAAATGATGATACCTACAAAGATGATGTGAATCATAATCAAAAGTGCAAAGAGAAG
ATGGAAGCTGAAGAAGAAGAAGCTTTAGCAATTGCCATGGCAATGTCAGCGTCTCAGGAT
GCCCTCCCCATAGTTCCTCAGCTGCAGGTTGAAAATGGAGAAGATATCATCATTATTCAA
CAGGATACACCAGAGACTCTACCAGGACATACCAAAGCAAAACAACCGTATAGAGAAGAC
ACTGAATGGCTGAAAGGTCAACAGATAGGCCTTGGAGCATTTTCTTCTTGTTATCAGGCT
CAAGATGTGGGAACTGGAACTTTAATGGCTGTTAAACAGGTGACTTATGTCAGAAACACA
TCTTCTGAGCAAGAAGAAGTAGTAGAAGCACTAAGAGAAGAGATAAGAATGATGAGCCAT
CTGAATCATCCAAACATCATTAGGATGTTGGGAGCCACGTGTGAGAAGAGCAATTACAAT
CTCTTCATTGAATGGATGGCAGGGGGATCGGTGGCTCATTTGCTGAGTAAATATGGAGCC
TTCAAAGAATCAGTAGTTATTAACTACACTGAACAGTTACTCCGTGGCCTTTCGTATCTC
CATGAAAACCAAATCATTCACAGAGATGTCAAAGGTGCCAATTTGCTAATTGACAGCACT
GGTCAGAGACTAAGAATTGCAGATTTTGGAGCTGCAGCCAGGTTGGCATCAAAAGGAACT
GGTGCAGGAGAGTTTCAGGGACAATTACTGGGGACAATTGCATTTATGGCACCTGAGGTA
CTAAGAGGTCAACAGTATGGAAGGAGCTGTGATGTATGGAGTGTTGGCTGTGCTATTATA
GAAATGGCTTGTGCAAAACCACCATGGAATGCAGAAAAACACTCCAATCATCTTGCTTTG
ATATTTAAGATTGCTAGTGCAACTACTGCTCCATCGATCCCTTCACATTTGTCTCCTGGT
TTACGAGATGTGGCTCTTCGTTGTTTAGAACTTCAACCTCAGGACAGACCTCCATCAAGA
GAGCTACTGAAGCATCCAGTCTTTCGTACTACATGGTAG
Protein Properties
Number of Residues 1512
Molecular Weight 164468.3
Theoretical pI 7.77
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • None
Protein Sequence
>Mitogen-activated protein kinase kinase kinase 1
MAAAAGNRASSSGFPGARATSPEAGGGGGALKASSAPAAAAGLLREAGSGGRERADWRRR
QLRKVRSVELDQLPEQPLFLAASPPASSTSPSPEPADAAGSGTGFQPVAVPPPHGAASRG
GAHLTESVAAPDSGASSPAAAEPGEKRAPAAEPSPAAAPAGREMENKETLKGLHKMDDRP
EERMIREKLKATCMPAWKHEWLERRNRRGPVVVKPIPVKGDGSEMNHLAAESPGEVQASA
ASPASKGRRSPSPGNSPSGRTVKSESPGVRRKRVSPVPFQSGRITPPRRAPSPDGFSPYS
PEETNRRVNKVMRARLYLLQQIGPNSFLIGGDSPDNKYRVFIGPQNCSCARGTFCIHLLF
VMLRVFQLEPSDPMLWRKTLKNFEVESLFQKYHSRRSSRIKAPSRNTIQKFVSRMSNSHT
LSSSSTSTSSSENSIKDEEEQMCPICLLGMLDEESLTVCEDGCRNKLHHHCMSIWAEECR
RNREPLICPLCRSKWRSHDFYSHELSSPVDSPSSLRAAQQQTVQQQPLAGSRRNQESNFN
LTHYGTQQIPPAYKDLAEPWIQVFGMELVGCLFSRNWNVREMALRRLSHDVSGALLLANG
ESTGNSGGSSGSSPSGGATSGSSQTSISGDVVEACCSVLSMVCADPVYKVYVAALKTLRA
MLVYTPCHSLAERIKLQRLLQPVVDTILVKCADANSRTSQLSISTLLELCKGQAGELAVG
REILKAGSIGIGGVDYVLNCILGNQTESNNWQELLGRLCLIDRLLLEFPAEFYPHIVSTD
VSQAEPVEIRYKKLLSLLTFALQSIDNSHSMVGKLSRRIYLSSARMVTTVPHVFSKLLEM
LSVSSSTHFTRMRRRLMAIADEVEIAEAIQLGVEDTLDGQQDSFLQASVPNNYLETTENS
SPECTVHLEKTGKGLCATKLSASSEDISERLASISVGPSSSTTTTTTTTEQPKPMVQTKG
RPHSQCLNSSPLSHHSQLMFPALSTPSSSTPSVPAGTATDVSKHRLQGFIPCRIPSASPQ
TQRKFSLQFHRNCPENKDSDKLSPVFTQSRPLPSSNIHRPKPSRPTPGNTSKQGDPSKNS
MTLDLNSSSKCDDSFGCSSNSSNAVIPSDETVFTPVEEKCRLDVNTELNSSIEDLLEASM
PSSDTTVTFKSEVAVLSPEKAENDDTYKDDVNHNQKCKEKMEAEEEEALAIAMAMSASQD
ALPIVPQLQVENGEDIIIIQQDTPETLPGHTKAKQPYREDTEWLKGQQIGLGAFSSCYQA
QDVGTGTLMAVKQVTYVRNTSSEQEEVVEALREEIRMMSHLNHPNIIRMLGATCEKSNYN
LFIEWMAGGSVAHLLSKYGAFKESVVINYTEQLLRGLSYLHENQIIHRDVKGANLLIDST
GQRLRIADFGAAARLASKGTGAGEFQGQLLGTIAFMAPEVLRGQQYGRSCDVWSVGCAII
EMACAKPPWNAEKHSNHLALIFKIASATTAPSIPSHLSPGLRDVALRCLELQPQDRPPSR
ELLKHPVFRTTW
GenBank ID Protein 153945765
UniProtKB/Swiss-Prot ID Q13233
UniProtKB/Swiss-Prot Entry Name M3K1_HUMAN
PDB IDs Not Available
GenBank Gene ID NM_005921.1
GeneCard ID MAP3K1
GenAtlas ID MAP3K1
HGNC ID HGNC:6848
References
General References
  1. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [PubMed:18669648 ]
  2. Daub H, Olsen JV, Bairlein M, Gnad F, Oppermann FS, 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. 2008 Aug 8;31(3):438-48. doi: 10.1016/j.molcel.2008.07.007. [PubMed:18691976 ]
  3. Oppermann FS, Gnad F, Olsen JV, Hornberger R, Greff Z, Keri G, Mann M, Daub H: Large-scale proteomics analysis of the human kinome. Mol Cell Proteomics. 2009 Jul;8(7):1751-64. doi: 10.1074/mcp.M800588-MCP200. Epub 2009 Apr 15. [PubMed:19369195 ]
  4. 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. 2008 Jan;24(1):161-6. [PubMed:18187866 ]
  5. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501. doi: 10.1021/ac9004309. [PubMed:19413330 ]
  6. Cantin GT, Yi W, Lu B, Park SK, Xu T, Lee JD, Yates JR 3rd: Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis. J Proteome Res. 2008 Mar;7(3):1346-51. doi: 10.1021/pr0705441. Epub 2008 Jan 26. [PubMed:18220336 ]
  7. Schmutz J, Martin J, Terry A, Couronne O, Grimwood J, Lowry S, Gordon LA, Scott D, Xie G, Huang W, Hellsten U, Tran-Gyamfi M, She X, Prabhakar S, Aerts A, Altherr M, Bajorek E, Black S, Branscomb E, Caoile C, Challacombe JF, Chan YM, Denys M, Detter JC, Escobar J, Flowers D, Fotopulos D, Glavina T, Gomez M, Gonzales E, Goodstein D, Grigoriev I, Groza M, Hammon N, Hawkins T, Haydu L, Israni S, Jett J, Kadner K, Kimball H, Kobayashi A, Lopez F, Lou Y, Martinez D, Medina C, Morgan J, Nandkeshwar R, Noonan JP, Pitluck S, Pollard M, Predki P, Priest J, Ramirez L, Retterer J, Rodriguez A, Rogers S, Salamov A, Salazar A, Thayer N, Tice H, Tsai M, Ustaszewska A, Vo N, Wheeler J, Wu K, Yang J, Dickson M, Cheng JF, Eichler EE, Olsen A, Pennacchio LA, Rokhsar DS, Richardson P, Lucas SM, Myers RM, Rubin EM: The DNA sequence and comparative analysis of human chromosome 5. Nature. 2004 Sep 16;431(7006):268-74. [PubMed:15372022 ]
  8. Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, Davies H, Teague J, Butler A, Stevens C, Edkins S, O'Meara S, Vastrik I, Schmidt EE, 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 DP, Louis DN, Goldstraw P, Nicholson AG, Brasseur F, Looijenga L, Weber BL, Chiew YE, DeFazio A, Greaves MF, Green AR, Campbell P, Birney E, Easton DF, Chenevix-Trench G, Tan MH, Khoo SK, Teh BT, Yuen ST, Leung SY, Wooster R, Futreal PA, Stratton MR: Patterns of somatic mutation in human cancer genomes. Nature. 2007 Mar 8;446(7132):153-8. [PubMed:17344846 ]
  9. Xia Y, Wu Z, Su B, Murray B, Karin M: JNKK1 organizes a MAP kinase module through specific and sequential interactions with upstream and downstream components mediated by its amino-terminal extension. Genes Dev. 1998 Nov 1;12(21):3369-81. [PubMed:9808624 ]
  10. Vinik BS, Kay ES, Fiedorek FT Jr: Mapping of the MEK kinase gene (Mekk) to mouse chromosome 13 and human chromosome 5. Mamm Genome. 1995 Nov;6(11):782-3. [PubMed:8597633 ]
  11. Rui HL, Fan E, Zhou HM, Xu Z, Zhang Y, Lin SC: SUMO-1 modification of the C-terminal KVEKVD of Axin is required for JNK activation but has no effect on Wnt signaling. J Biol Chem. 2002 Nov 8;277(45):42981-6. Epub 2002 Sep 9. [PubMed:12223491 ]
  12. Wong CK, Luo W, Deng Y, Zou H, Ye Z, Lin SC: The DIX domain protein coiled-coil-DIX1 inhibits c-Jun N-terminal kinase activation by Axin and dishevelled through distinct mechanisms. J Biol Chem. 2004 Sep 17;279(38):39366-73. Epub 2004 Jul 15. [PubMed:15262978 ]
  13. Enomoto A, Kido N, Ito M, Morita A, Matsumoto Y, Takamatsu N, Hosoi Y, Miyagawa K: Negative regulation of MEKK1/2 signaling by serine-threonine kinase 38 (STK38). Oncogene. 2008 Mar 20;27(13):1930-8. Epub 2007 Oct 1. [PubMed:17906693 ]