Mitogen-activated protein kinase kinase kinase kinase 4

Details

Name
Mitogen-activated protein kinase kinase kinase kinase 4
Synonyms
  • 2.7.11.1
  • HGK
  • HPK/GCK-like kinase HGK
  • KIAA0687
  • MAPK/ERK kinase kinase kinase 4
  • MEK kinase kinase 4
  • MEKKK 4
  • Nck-interacting kinase
  • NIK
Gene Name
MAP4K4
Organism
Humans
Amino acid sequence
>lcl|BSEQ0051824|Mitogen-activated protein kinase kinase kinase kinase 4
MANDSPAKSLVDIDLSSLRDPAGIFELVEVVGNGTYGQVYKGRHVKTGQLAAIKVMDVTE
DEEEEIKLEINMLKKYSHHRNIATYYGAFIKKSPPGHDDQLWLVMEFCGAGSITDLVKNT
KGNTLKEDWIAYISREILRGLAHLHIHHVIHRDIKGQNVLLTENAEVKLVDFGVSAQLDR
TVGRRNTFIGTPYWMAPEVIACDENPDATYDYRSDLWSCGITAIEMAEGAPPLCDMHPMR
ALFLIPRNPPPRLKSKKWSKKFFSFIEGCLVKNYMQRPSTEQLLKHPFIRDQPNERQVRI
QLKDHIDRTRKKRGEKDETEYEYSGSEEEEEEVPEQEGEPSSIVNVPGESTLRRDFLRLQ
QENKERSEALRRQQLLQEQQLREQEEYKRQLLAERQKRIEQQKEQRRRLEEQQRREREAR
RQQEREQRRREQEEKRRLEELERRRKEEEERRRAEEEKRRVEREQEYIRRQLEEEQRHLE
VLQQQLLQEQAMLLECRWREMEEHRQAERLQRQLQQEQAYLLSLQHDHRRPHPQHSQQPP
PPQQERSKPSFHAPEPKAHYEPADRAREVEDRFRKTNHSSPEAQSKQTGRVLEPPVPSRS
ESFSNGNSESVHPALQRPAEPQVPVRTTSRSPVLSRRDSPLQGSGQQNSQAGQRNSTSIE
PRLLWERVEKLVPRPGSGSSSGSSNSGSQPGSHPGSQSGSGERFRVRSSSKSEGSPSQRL
ENAVKKPEDKKEVFRPLKPADLTALAKELRAVEDVRPPHKVTDYSSSSEESGTTDEEDDD
VEQEGADESTSGPEDTRAASSLNLSNGETESVKTMIVHDDVESEPAMTPSKEGTLIVRQT
QSASSTLQKHKSSSSFTPFIDPRLLQISPSSGTTVTSVVGFSCDGMRPEAIRQDPTRKGS
VVNVNPTNTRPQSDTPEIRKYKKRFNSEILCAALWGVNLLVGTESGLMLLDRSGQGKVYP
LINRRRFQQMDVLEGLNVLVTISGKKDKLRVYYLSWLRNKILHNDPEVEKKQGWTTVGDL
EGCVHYKVVKYERIKFLVIALKSSVEVYAWAPKPYHKFMAFKSFGELVHKPLLVDLTVEE
GQRLKVIYGSCAGFHAVDVDSGSVYDIYLPTHIQCSIKPHAIIILPNTDGMELLVCYEDE
GVYVNTYGRITKDVVLQWGEMPTSVAYIRSNQTMGWGEKAIEIRSVETGHLDGVFMHKRA
QRLKFLCERNDKVFFASVRSGGSSQVYFMTLGRTSLLSW
Number of residues
1239
Molecular Weight
142099.84
Theoretical pI
Not Available
GO Classification
Functions
ATP binding / creatine kinase activity / MAP kinase kinase kinase kinase activity / protein serine/threonine kinase activity
Processes
intracellular signal transduction / negative regulation of apoptotic process / negative regulation of insulin secretion involved in cellular response to glucose stimulus / negative regulation of neuron projection regeneration / neuron projection morphogenesis / protein phosphorylation / regulation of JNK cascade / regulation of mitotic cell cycle
Components
cytoplasm
General Function
Serine/threonine kinase that may play a role in the response to environmental stress and cytokines such as TNF-alpha. Appears to act upstream of the JUN N-terminal pathway. Phosphorylates SMAD1 on Thr-322.
Specific Function
Atp binding
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0051825|Mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4)
ATGGCGAACGACTCCCCTGCAAAAAGTCTGGTGGACATCGACCTCTCCTCCCTGCGGGAT
CCTGCTGGGATTTTTGAGCTGGTGGAAGTGGTTGGAAATGGCACCTATGGACAAGTCTAT
AAGGGTCGACATGTTAAAACGGGTCAGTTGGCAGCCATCAAAGTTATGGATGTCACTGAG
GATGAAGAGGAAGAAATCAAACTGGAGATAAATATGCTAAAGAAATACTCTCATCACAGA
AACATTGCAACATATTATGGTGCTTTCATCAAAAAGAGCCCTCCAGGACATGATGACCAA
CTCTGGCTTGTTATGGAGTTCTGTGGGGCTGGGTCCATTACAGACCTTGTGAAGAACACC
AAAGGGAACACACTCAAAGAAGACTGGATCGCTTACATCTCCAGAGAAATCCTGAGGGGA
CTGGCACATCTTCACATTCATCATGTGATTCACCGGGATATCAAGGGCCAGAATGTGTTG
CTGACTGAGAATGCAGAGGTGAAACTTGTTGACTTTGGTGTGAGTGCTCAGCTGGACAGG
ACTGTGGGGCGGAGAAATACGTTCATAGGCACTCCCTACTGGATGGCTCCTGAGGTCATC
GCCTGTGATGAGAACCCAGATGCCACCTATGATTACAGAAGTGATCTTTGGTCTTGTGGC
ATTACAGCCATTGAGATGGCAGAAGGTGCTCCCCCTCTCTGTGACATGCATCCAATGAGA
GCACTGTTTCTCATTCCCAGAAACCCTCCTCCCCGGCTGAAGTCAAAAAAATGGTCGAAG
AAGTTTTTTAGTTTTATAGAAGGGTGCCTGGTGAAGAATTACATGCAGCGGCCCTCTACA
GAGCAGCTTTTGAAACATCCTTTTATAAGGGATCAGCCAAATGAAAGGCAAGTTAGAATC
CAGCTTAAGGATCATATAGATCGTACCAGGAAGAAGAGAGGCGAGAAAGATGAAACTGAG
TATGAGTACAGTGGGAGTGAGGAAGAAGAGGAGGAAGTGCCTGAACAGGAAGGAGAGCCA
AGTTCCATTGTGAACGTGCCTGGTGAGTCTACTCTTCGCCGAGATTTCCTGAGACTGCAG
CAGGAGAACAAGGAACGTTCCGAGGCTCTTCGGAGACAACAGTTACTACAGGAGCAACAG
CTCCGGGAGCAGGAAGAATATAAAAGGCAACTGCTGGCAGAGAGACAGAAGCGGATTGAG
CAGCAGAAAGAACAGAGGCGACGGCTAGAAGAGCAACAAAGGAGAGAGCGGGAAGCTAGA
AGGCAGCAGGAACGTGAACAGCGAAGGAGAGAACAAGAAGAAAAGAGGCGTCTAGAGGAG
TTGGAGAGAAGGCGCAAAGAAGAAGAGGAGAGGAGACGGGCAGAAGAAGAAAAGAGGAGA
GTTGAAAGAGAACAGGAGTATATCAGGCGACAGCTAGAAGAGGAGCAGCGGCACTTGGAA
GTCCTTCAGCAGCAGCTGCTCCAGGAGCAGGCCATGTTACTGGAGTGCCGATGGCGGGAG
ATGGAGGAGCACCGGCAGGCAGAGAGGCTCCAGAGGCAGTTGCAACAAGAACAAGCATAT
CTCCTGTCTCTACAGCATGACCATAGGAGGCCGCACCCGCAGCACTCGCAGCAGCCGCCA
CCACCGCAGCAGGAAAGGAGCAAGCCAAGCTTCCATGCTCCCGAGCCCAAAGCCCACTAC
GAGCCTGCTGACCGAGCGCGAGAGGTGGAAGATAGATTTAGGAAAACTAACCACAGCTCC
CCTGAAGCCCAGTCTAAGCAGACAGGCAGAGTATTGGAGCCACCAGTGCCTTCCCGATCA
GAGTCTTTTTCCAATGGCAACTCCGAGTCTGTGCATCCCGCCCTGCAGAGACCAGCGGAG
CCACAGGTTCCTGTGAGAACAACATCTCGCTCCCCTGTTCTGTCCCGTCGAGATTCCCCA
CTGCAGGGCAGTGGGCAGCAGAATAGCCAGGCAGGACAGAGAAACTCCACCAGTATTGAG
CCCAGGCTTCTGTGGGAGAGAGTGGAGAAGCTGGTGCCCAGACCTGGCAGTGGCAGCTCC
TCAGGGTCCAGCAACTCAGGATCCCAGCCCGGGTCTCACCCTGGGTCTCAGAGTGGCTCC
GGGGAACGCTTCAGAGTGAGATCATCATCCAAGTCTGAAGGCTCTCCATCTCAGCGCCTG
GAAAATGCAGTGAAAAAACCTGAAGATAAAAAGGAAGTTTTCAGACCCCTCAAGCCTGCT
GATCTGACCGCACTGGCCAAAGAGCTTCGAGCAGTGGAAGATGTACGGCCACCTCACAAA
GTAACGGACTACTCCTCATCCAGTGAGGAGTCGGGGACGACGGATGAGGAGGACGACGAT
GTGGAGCAGGAAGGGGCTGACGAGTCCACCTCAGGACCAGAGGACACCAGAGCAGCGTCA
TCTCTGAATTTGAGCAATGGTGAAACGGAATCTGTGAAAACCATGATTGTCCATGATGAT
GTAGAAAGTGAGCCGGCCATGACCCCATCCAAGGAGGGCACTCTAATCGTCCGCCAGACT
CAGTCCGCTAGTAGCACACTCCAGAAACACAAATCTTCCTCCTCCTTTACACCTTTTATA
GACCCCAGATTACTACAGATTTCTCCATCTAGCGGAACAACAGTGACATCTGTGGTGGGA
TTTTCCTGTGATGGGATGAGACCAGAAGCCATAAGGCAAGATCCTACCCGGAAAGGCTCA
GTGGTCAATGTGAATCCTACCAACACTAGGCCACAGAGTGACACCCCGGAGATTCGTAAA
TACAAGAAGAGGTTTAACTCTGAGATTCTGTGTGCTGCCTTATGGGGAGTGAATTTGCTA
GTGGGTACAGAGAGTGGCCTGATGCTGCTGGACAGAAGTGGCCAAGGGAAGGTCTATCCT
CTTATCAACCGAAGACGATTTCAACAAATGGACGTACTTGAGGGCTTGAATGTCTTGGTG
ACAATATCTGGCAAAAAGGATAAGTTACGTGTCTACTATTTGTCCTGGTTAAGAAATAAA
ATACTTCACAATGATCCAGAAGTTGAGAAGAAGCAGGGATGGACAACCGTAGGGGATTTG
GAAGGATGTGTACATTATAAAGTTGTAAAATATGAAAGAATCAAATTTCTGGTGATTGCT
TTGAAGAGTTCTGTGGAAGTCTATGCGTGGGCACCAAAGCCATATCACAAATTTATGGCC
TTTAAGTCATTTGGAGAATTGGTACATAAGCCATTACTGGTGGATCTCACTGTTGAGGAA
GGCCAGAGGTTGAAAGTGATCTATGGATCCTGTGCTGGATTCCATGCTGTTGATGTGGAT
TCAGGATCAGTCTATGACATTTATCTACCAACACATATCCAGTGTAGCATCAAACCCCAT
GCAATCATCATCCTCCCCAATACAGATGGAATGGAGCTTCTGGTGTGCTATGAAGATGAG
GGGGTTTATGTAAACACATATGGAAGGATCACCAAGGATGTAGTTCTACAGTGGGGAGAG
ATGCCTACATCAGTAGCATATATTCGATCCAATCAGACAATGGGCTGGGGAGAGAAGGCC
ATAGAGATCCGATCTGTGGAAACTGGTCACTTGGATGGTGTGTTCATGCACAAAAGGGCT
CAAAGACTAAAATTCTTGTGTGAACGCAATGACAAGGTGTTCTTTGCCTCTGTTCGGTCT
GGTGGCAGCAGTCAGGTTTATTTCATGACCTTAGGCAGGACTTCTCTTCTGAGCTGGTAG
Chromosome Location
2
Locus
2q11.2
External Identifiers
ResourceLink
UniProtKB IDO95819
UniProtKB Entry NameM4K4_HUMAN
HGNC IDHGNC:6866
General References
  1. Yao Z, Zhou G, Wang XS, Brown A, Diener K, Gan H, Tan TH: A novel human STE20-related protein kinase, HGK, that specifically activates the c-Jun N-terminal kinase signaling pathway. J Biol Chem. 1999 Jan 22;274(4):2118-25. [Article]
  2. Wright JH, Wang X, Manning G, LaMere BJ, Le P, Zhu S, Khatry D, Flanagan PM, Buckley SD, Whyte DB, Howlett AR, Bischoff JR, Lipson KE, Jallal B: The STE20 kinase HGK is broadly expressed in human tumor cells and can modulate cellular transformation, invasion, and adhesion. Mol Cell Biol. 2003 Mar;23(6):2068-82. [Article]
  3. Hillier LW, Graves TA, Fulton RS, Fulton LA, Pepin KH, Minx P, Wagner-McPherson C, Layman D, Wylie K, Sekhon M, Becker MC, Fewell GA, Delehaunty KD, Miner TL, Nash WE, 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 EA, 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 SS, Strong CM, Grewal N, Goyea E, Hou S, Levy A, Martinka S, Mead K, McLellan MD, Meyer R, Randall-Maher J, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Shah N, Swearengen-Shahid S, Snider J, Strong JT, Thompson J, Yoakum M, Leonard S, Pearman C, Trani L, Radionenko M, Waligorski JE, Wang C, Rock SM, Tin-Wollam AM, Maupin R, Latreille P, Wendl MC, Yang SP, Pohl C, Wallis JW, Spieth J, Bieri TA, Berkowicz N, Nelson JO, Osborne J, Ding L, Meyer R, Sabo A, Shotland Y, Sinha P, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Jones TA, She X, Ciccarelli FD, Izaurralde E, Taylor J, Schmutz J, Myers RM, Cox DR, Huang X, McPherson JD, Mardis ER, Clifton SW, Warren WC, Chinwalla AT, Eddy SR, Marra MA, Ovcharenko I, Furey TS, Miller W, Eichler EE, Bork P, Suyama M, Torrents D, Waterston RH, Wilson RK: Generation and annotation of the DNA sequences of human chromosomes 2 and 4. Nature. 2005 Apr 7;434(7034):724-31. [Article]
  4. Ishikawa K, Nagase T, Suyama M, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O: Prediction of the coding sequences of unidentified human genes. X. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro. DNA Res. 1998 Jun 30;5(3):169-76. [Article]
  5. Bechtel S, Rosenfelder H, Duda A, Schmidt CP, Ernst U, Wellenreuther R, Mehrle A, Schuster C, Bahr A, Blocker H, Heubner D, Hoerlein A, Michel G, Wedler H, Kohrer K, Ottenwalder B, Poustka A, Wiemann S, Schupp I: The full-ORF clone resource of the German cDNA Consortium. BMC Genomics. 2007 Oct 31;8:399. [Article]
  6. Luan Z, Zhang Y, Liu A, Man Y, Cheng L, Hu G: A novel GTP-binding protein hGBP3 interacts with NIK/HGK. FEBS Lett. 2002 Oct 23;530(1-3):233-8. [Article]
  7. Machida N, Umikawa M, Takei K, Sakima N, Myagmar BE, Taira K, Uezato H, Ogawa Y, Kariya K: Mitogen-activated protein kinase kinase kinase kinase 4 as a putative effector of Rap2 to activate the c-Jun N-terminal kinase. J Biol Chem. 2004 Apr 16;279(16):15711-4. Epub 2004 Feb 13. [Article]
  8. 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]
  9. 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]
  10. 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]
  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. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. [Article]
  13. Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller ML, Jensen LJ, Gnad F, Cox J, Jensen TS, Nigg EA, Brunak S, Mann M: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal. 2010 Jan 12;3(104):ra3. doi: 10.1126/scisignal.2000475. [Article]
  14. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [Article]
  15. Kaneko S, Chen X, Lu P, Yao X, Wright TG, Rajurkar M, Kariya K, Mao J, Ip YT, Xu L: Smad inhibition by the Ste20 kinase Misshapen. Proc Natl Acad Sci U S A. 2011 Jul 5;108(27):11127-32. doi: 10.1073/pnas.1104128108. Epub 2011 Jun 20. [Article]
  16. Rigbolt KT, Prokhorova TA, Akimov V, Henningsen J, Johansen PT, Kratchmarova I, Kassem M, Mann M, Olsen JV, Blagoev B: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci Signal. 2011 Mar 15;4(164):rs3. doi: 10.1126/scisignal.2001570. [Article]
  17. Van Damme P, Lasa M, Polevoda B, Gazquez C, Elosegui-Artola A, Kim DS, De Juan-Pardo E, Demeyer K, Hole K, Larrea E, Timmerman E, Prieto J, Arnesen T, Sherman F, Gevaert K, Aldabe R: N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB. Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12449-54. doi: 10.1073/pnas.1210303109. Epub 2012 Jul 18. [Article]
  18. Zhou H, Di Palma S, Preisinger C, Peng M, Polat AN, Heck AJ, Mohammed S: Toward a comprehensive characterization of a human cancer cell phosphoproteome. J Proteome Res. 2013 Jan 4;12(1):260-71. doi: 10.1021/pr300630k. Epub 2012 Dec 18. [Article]
  19. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [Article]
  20. 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]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails