Hmdb loader
Survey
Identification
HMDB Protein ID HMDBP01495
Secondary Accession Numbers
  • 6791
Name Mitogen-activated protein kinase kinase kinase kinase 4
Synonyms
  1. HPK/GCK-like kinase HGK
  2. MAPK/ERK kinase kinase kinase 4
  3. MEK kinase kinase 4
  4. MEKKK 4
  5. Nck-interacting kinase
Gene Name MAP4K4
Protein Type Unknown
Biological Properties
General Function Involved in small GTPase regulator activity
Specific 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
Pathways Not Available
Reactions Not Available
GO Classification
Function
small gtpase regulator activity
binding
catalytic activity
transferase activity
transferase activity, transferring phosphorus-containing groups
kinase activity
nucleoside binding
purine nucleoside binding
adenyl nucleotide binding
adenyl ribonucleotide binding
atp binding
enzyme regulator activity
protein kinase activity
protein serine/threonine kinase activity
nucleoside-triphosphatase regulator activity
gtpase regulator activity
Process
phosphorus metabolic process
phosphate metabolic process
metabolic process
cellular metabolic process
protein amino acid phosphorylation
phosphorylation
Cellular Location Not Available
Gene Properties
Chromosome Location Chromosome:2
Locus 2q11.2-q12
SNPs MAP4K4
Gene Sequence
>3720 bp
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
GTAGAAAGTGAGCCGGCCATGACCCCATCCAAGGAGGGCACTCTAATCGTCCGCCGGACT
CAGTCCGCTAGTAGCACACTCCAGAAACACAAATCTTCCTCCTCCTTTACACCTTTTATA
GACCCCAGATTACTACAGATTTCTCCATCTAGCGGAACAACAGTGACATCTGTGGTGGGA
TTTTCCTGTGATGGGATGAGACCAGAAGCCATAAGGCAAGATCCTACCCGGAAAGGCTCA
GTGGTCAATGTGAATCCTACCAACACTAGGCCACAGAGTGACACCCCGGAGATTCGTAAA
TACAAGAAGAGGTTTAACTCTGAGATTCTGTGTGCTGCCTTATGGGGAGTGAATTTGCTA
GTGGGTACAGAGAGTGGCCTGATGCTGCTGGACAGAAGTGGCCAAGGGAAGGTCTATCCT
CTTATCAACCGAAGACGATTTCAACAAATGGACGTACTTGAGGGCTTGAATGTCTTGGTG
ACAATATCTGGCAAAAAGGATAAGTTACGTGTCTACTATTTGTCCTGGTTAAGAAATAAA
ATACTTCACAATGATCCAGAAGTTGAGAAGAAGCAGGGATGGACAACCGTAGGGGATTTG
GAAGGATGTGTACATTATAAAGTTGTAAAATATGAAAGAATCAAATTTCTGGTGATTGCT
TTGAAGAGTTCTGTGGAAGTCTATGCGTGGGCACCAAAGCCATATCACAAATTTATGGCC
TTTAAGTCATTTGGAGAATTGGTACATAAGCCATTACTGGTGGATCTCACTGTTGAGGAA
GGCCAGAGGTTGAAAGTGATCTATGGATCCTGTGCTGGATTCCATGCTGTTGATGTGGAT
TCAGGATCAGTCTATGACATTTATCTACCAACACATATCCAGTGTAGCATCAAACCCCAT
GCAATCATCATCCTCCCCAATACAGATGGAATGGAGCTTCTGGTGTGCTATGAAGATGAG
GGGGTTTATGTAAACACATATGGAAGGATCACCAAGGATGTAGTTCTACAGTGGGGAGAG
ATGCCTACATCAGTAGCATATATTCGATCCAATCAGACAATGGGCTGGGGAGAGAAGGCC
ATAGAGATCCGATCTGTGGAAACTGGTCACTTGGATGGTGTGTTCATGCACAAAAGGGCT
CAAAGACTAAAATTCTTGTGTGAACGCAATGACAAGGTGTTCTTTGCCTCTGTTCGGTCT
GGTGGCAGCAGTCAGGTTTATTTCATGACCTTAGGCAGGACTTCTCTTCTGAGCTGGTAG
Protein Properties
Number of Residues 1239
Molecular Weight 142099.8
Theoretical pI 7.49
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • None
Protein Sequence
>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
GenBank ID Protein 28207195
UniProtKB/Swiss-Prot ID O95819
UniProtKB/Swiss-Prot Entry Name M4K4_HUMAN
PDB IDs Not Available
GenBank Gene ID AY212247
GeneCard ID MAP4K4
GenAtlas ID MAP4K4
HGNC ID HGNC:6866
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. 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. [PubMed:19690332 ]
  3. 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 ]
  4. 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 ]
  5. Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villen J, Li J, Cohn MA, Cantley LC, Gygi SP: Large-scale characterization of HeLa cell nuclear phosphoproteins. Proc Natl Acad Sci U S A. 2004 Aug 17;101(33):12130-5. Epub 2004 Aug 9. [PubMed:15302935 ]
  6. Matsuoka S, Ballif BA, Smogorzewska A, McDonald ER 3rd, Hurov KE, Luo J, Bakalarski CE, Zhao Z, Solimini N, Lerenthal Y, Shiloh Y, Gygi SP, Elledge SJ: ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Science. 2007 May 25;316(5828):1160-6. [PubMed:17525332 ]
  7. 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. [PubMed:17974005 ]
  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. [PubMed:18220336 ]
  9. 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 ]
  10. Wissing J, Jansch 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. 2007 Mar;6(3):537-47. Epub 2006 Dec 27. [PubMed:17192257 ]
  11. 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. [PubMed:9734811 ]
  12. 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. [PubMed:9890973 ]
  13. 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. [PubMed:12612079 ]
  14. 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. [PubMed:12387898 ]