Mitogen-activated protein kinase kinase kinase 1

Details

Name
Mitogen-activated protein kinase kinase kinase 1
Synonyms
  • 2.7.11.25
  • MAPK/ERK kinase kinase 1
  • MAPKKK1
  • MEK kinase 1
  • MEKK
  • MEKK 1
  • MEKK1
Gene Name
MAP3K1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0017097|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
Number of residues
1512
Molecular Weight
164468.265
Theoretical pI
8.09
GO Classification
Functions
ATP binding / JUN kinase kinase kinase activity / MAP kinase kinase kinase activity / protein kinase activity / protein kinase binding / zinc ion binding
Processes
activation of JUN kinase activity / activation of protein kinase activity / apoptotic mitochondrial changes / cellular response to mechanical stimulus / epithelial cell morphogenesis / eyelid development in camera-type eye / Fc-epsilon receptor signaling pathway / innate immune response / MyD88-dependent toll-like receptor signaling pathway / positive regulation of actin filament polymerization / protein phosphorylation / regulation of apoptotic process / regulation of cell migration / regulation of mitotic cell cycle / stress-activated MAPK cascade / toll-like receptor 10 signaling pathway / toll-like receptor 2 signaling pathway / toll-like receptor 4 signaling pathway / toll-like receptor 5 signaling pathway / toll-like receptor 9 signaling pathway / toll-like receptor signaling pathway / toll-like receptor TLR1 / toll-like receptor TLR6 / transforming growth factor beta receptor signaling pathway / wound healing
Components
cytoplasm / cytosol
General Function
Zinc 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.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Not Available
Gene sequence
>lcl|BSEQ0017098|Mitogen-activated protein kinase kinase kinase 1 (MAP3K1)
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
Chromosome Location
5
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDQ13233
UniProtKB Entry NameM3K1_HUMAN
GenBank Gene IDAF042838
GenAtlas IDMAP3K1
HGNC IDHGNC:6848
General References
  1. 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. [Article]
  2. 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. [Article]
  3. 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. [Article]
  4. 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. [Article]
  5. 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. [Article]
  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. [Article]
  7. 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. [Article]
  8. 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. [Article]
  9. 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. [Article]
  10. 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. [Article]
  11. 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. [Article]
  12. 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. [Article]
  13. Pearlman A, Loke J, Le Caignec C, White S, Chin L, Friedman A, Warr N, Willan J, Brauer D, Farmer C, Brooks E, Oddoux C, Riley B, Shajahan S, Camerino G, Homfray T, Crosby AH, Couper J, David A, Greenfield A, Sinclair A, Ostrer H: Mutations in MAP3K1 cause 46,XY disorders of sex development and implicate a common signal transduction pathway in human testis determination. Am J Hum Genet. 2010 Dec 10;87(6):898-904. doi: 10.1016/j.ajhg.2010.11.003. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB06061AZD-8330investigationalunknownDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails
DB11967Binimetinibapproved, investigationalyesinhibitorDetails