Mitogen-activated protein kinase kinase kinase 9

Details

Name
Mitogen-activated protein kinase kinase kinase 9
Synonyms
  • 2.7.11.25
  • Mixed lineage kinase 1
  • MLK1
  • PRKE1
Gene Name
MAP3K9
Organism
Humans
Amino acid sequence
>lcl|BSEQ0008328|Mitogen-activated protein kinase kinase kinase 9
MEPSRALLGCLASAAAAAPPGEDGAGAGAEEEEEEEEEAAAAVGPGELGCDAPLPYWTAV
FEYEAAGEDELTLRLGDVVEVLSKDSQVSGDEGWWTGQLNQRVGIFPSNYVTPRSAFSSR
CQPGGEDPSCYPPIQLLEIDFAELTLEEIIGIGGFGKVYRAFWIGDEVAVKAARHDPDED
ISQTIENVRQEAKLFAMLKHPNIIALRGVCLKEPNLCLVMEFARGGPLNRVLSGKRIPPD
ILVNWAVQIARGMNYLHDEAIVPIIHRDLKSSNILILQKVENGDLSNKILKITDFGLARE
WHRTTKMSAAGTYAWMAPEVIRASMFSKGSDVWSYGVLLWELLTGEVPFRGIDGLAVAYG
VAMNKLALPIPSTCPEPFAKLMEDCWNPDPHSRPSFTNILDQLTTIEESGFFEMPKDSFH
CLQDNWKHEIQEMFDQLRAKEKELRTWEEELTRAALQQKNQEELLRRREQELAEREIDIL
ERELNIIIHQLCQEKPRVKKRKGKFRKSRLKLKDGNRISLPSDFQHKFTVQASPTMDKRK
SLINSRSSPPASPTIIPRLRAIQLTPGESSKTWGRSSVVPKEEGEEEEKRAPKKKGRTWG
PGTLGQKELASGDEGSPQRREKANGLSTPSESPHFHLGLKSLVDGYKQWSSSAPNLVKGP
RSSPALPGFTSLMEMEDEDSEGPGSGESRLQHSPSQSYLCIPFPRGEDGDGPSSDGIHEE
PTPVNSATSTPQLTPTNSLKRGGAHHRRCEVALLGCGAVLAATGLGFDLLEAGKCQLLPL
EEPEPPAREEKKRREGLFQRSSRPRRSTSPPSRKLFKKEEPMLLLGDPSASLTLLSLSSI
SECNSTRSLLRSDSDEIVVYEMPVSPVEAPPLSPCTHNPLVNVRVERFKRDPNQSLTPTH
VTLTTPSQPSSHRRTPSDGALKPETLLASRSPSSNGLSPSPGAGMLKTPSPSRDPGEFPR
LPDPNVVFPPTPRRWNTQQDSTLERPKTLEFLPRPRPSANRQRLDPWWFVSPSHARSTSP
ANSSSTETPSNLDSCFASSSSTVEERPGLPALLPFQAGPLPPTERTLLDLDAEGQSQDST
VPLCRAELNTHRPAPYEIQQEFWS
Number of residues
1104
Molecular Weight
121893.235
Theoretical pI
5.65
GO Classification
Functions
ATP binding / JUN kinase kinase kinase activity / MAP kinase kinase activity / protein homodimerization activity / protein serine/threonine kinase activity / protein tyrosine kinase activity
Processes
activation of JNKK activity / activation of JUN kinase activity / apoptotic process / positive regulation of apoptotic process / protein autophosphorylation / protein phosphorylation / regulation of transcription, DNA-templated / transcription, DNA-templated
Components
intracellular
General Function
Protein tyrosine kinase activity
Specific Function
Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. Plays an important role in the cascades of cellular responses evoked by changes in the environment. Once activated, acts as an upstream activator of the MKK/JNK signal transduction cascade through the phosphorylation of MAP2K4/MKK4 and MAP2K7/MKK7 which in turn activate the JNKs. The MKK/JNK signaling pathway regulates stress response via activator protein-1 (JUN) and GATA4 transcription factors. Plays also a role in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Not Available
Gene sequence
>lcl|BSEQ0013054|Mitogen-activated protein kinase kinase kinase 9 (MAP3K9)
ATGGAGCCCTCCAGAGCGCTTCTCGGCTGCCTAGCGAGCGCCGCCGCTGCCGCCCCGCCG
GGGGAGGATGGAGCAGGGGCCGGGGCCGAGGAGGAGGAGGAGGAGGAGGAGGAGGCGGCG
GCGGCGGTGGGCCCCGGGGAGCTGGGCTGCGACGCGCCGCTGCCCTACTGGACGGCCGTG
TTCGAGTACGAGGCGGCGGGCGAGGACGAGCTGACCCTGCGGCTGGGCGACGTGGTGGAG
GTGCTGTCCAAGGACTCGCAGGTGTCCGGCGACGAGGGCTGGTGGACCGGGCAGCTGAAC
CAGCGGGTGGGCATCTTCCCCAGCAACTACGTGACCCCGCGCAGCGCCTTCTCCAGCCGC
TGCCAGCCCGGCGGCGAGGACCCCAGTTGCTACCCGCCCATTCAGTTGTTAGAAATTGAT
TTTGCGGAGCTCACCTTGGAAGAGATTATTGGCATCGGGGGCTTTGGGAAGGTCTATCGT
GCTTTCTGGATAGGGGATGAGGTTGCTGTGAAAGCAGCTCGCCACGACCCTGATGAGGAC
ATCAGCCAGACCATAGAGAATGTTCGCCAAGAGGCCAAGCTCTTCGCCATGCTGAAGCAC
CCCAACATCATTGCCCTAAGAGGGGTATGTCTGAAGGAGCCCAACCTCTGCTTGGTCATG
GAGTTTGCTCGTGGAGGACCTTTGAATAGAGTGTTATCTGGGAAAAGGATTCCCCCAGAC
ATCCTGGTGAATTGGGCTGTGCAGATTGCCAGAGGGATGAACTACTTACATGATGAGGCA
ATTGTTCCCATCATCCACCGCGACCTTAAGTCCAGCAACATATTGATCCTCCAGAAGGTG
GAGAATGGAGACCTGAGCAACAAGATTCTGAAGATCACTGATTTTGGCCTGGCTCGGGAA
TGGCACCGAACCACCAAGATGAGTGCGGCAGGGACGTATGCTTGGATGGCACCCGAAGTC
ATCCGGGCCTCCATGTTTTCCAAAGGCAGTGATGTGTGGAGCTATGGGGTGCTACTTTGG
GAGTTGCTGACTGGTGAGGTGCCCTTTCGAGGCATTGATGGCTTAGCAGTCGCTTATGGA
GTGGCCATGAACAAACTCGCCCTTCCTATTCCTTCTACGTGCCCAGAACCTTTTGCCAAA
CTCATGGAAGACTGCTGGAATCCTGATCCCCACTCACGACCATCTTTCACGAATATCCTG
GACCAGCTAACCACCATAGAGGAGTCTGGTTTCTTTGAAATGCCCAAGGACTCCTTCCAC
TGCCTGCAGGACAACTGGAAACACGAGATTCAGGAGATGTTTGACCAACTCAGGGCCAAA
GAAAAGGAACTTCGCACCTGGGAGGAGGAGCTGACGCGGGCTGCACTGCAGCAGAAGAAC
CAGGAGGAACTGCTGCGGCGTCGGGAGCAGGAGCTGGCCGAGCGGGAGATTGACATCCTG
GAACGGGAGCTCAACATCATCATCCACCAGCTGTGCCAGGAGAAGCCCCGGGTGAAGAAA
CGCAAGGGCAAGTTCAGGAAGAGCCGGCTGAAGCTCAAGGATGGCAACCGCATCAGCCTC
CCTTCTGATTTCCAGCACAAGTTCACGGTGCAGGCCTCCCCTACCATGGATAAAAGGAAG
AGTCTTATCAACAGCCGCTCCAGTCCTCCTGCAAGCCCCACCATCATTCCTCGCCTTCGA
GCCATCCAGTTGACACCAGGTGAAAGCAGCAAAACCTGGGGCAGGAGCTCAGTCGTCCCA
AAGGAGGAAGGGGAGGAGGAGGAGAAGAGGGCCCCAAAGAAGAAGGGACGGACGTGGGGG
CCAGGGACGCTTGGTCAGAAGGAGCTTGCCTCGGGAGATGAAGGATCCCCTCAGAGACGT
GAGAAAGCTAATGGTTTAAGTACCCCATCAGAATCTCCACATTTCCACTTGGGCCTCAAG
TCCCTGGTAGATGGATATAAGCAGTGGTCGTCCAGTGCCCCCAACCTGGTGAAGGGCCCA
AGGAGTAGCCCGGCCCTGCCAGGGTTCACCAGCCTTATGGAGATGGAGGATGAGGACAGT
GAAGGCCCAGGGAGTGGAGAGAGTCGCCTACAGCATTCACCCAGCCAGTCCTACCTCTGT
ATCCCATTCCCTCGTGGAGAGGATGGCGATGGCCCCTCCAGTGATGGAATCCATGAGGAG
CCCACCCCAGTCAACTCGGCCACGAGTACCCCTCAGCTGACGCCAACCAACAGCCTCAAG
CGGGGCGGTGCCCACCACCGCCGCTGCGAGGTGGCTCTGCTCGGCTGTGGGGCTGTTCTG
GCAGCCACAGGCCTAGGGTTTGACTTGCTGGAAGCTGGCAAGTGCCAGCTGCTTCCCCTG
GAGGAGCCTGAGCCACCAGCCCGGGAGGAGAAGAAAAGACGGGAGGGTCTTTTTCAGAGG
TCCAGCCGTCCTCGTCGGAGCACCAGCCCCCCATCCCGAAAGCTTTTCAAGAAGGAGGAG
CCCATGCTGTTGCTAGGAGACCCCTCTGCCTCCCTGACGCTGCTCTCCCTCTCCTCCATC
TCCGAGTGCAACTCCACACGCTCCCTGCTGCGCTCCGACAGCGATGAAATTGTCGTGTAT
GAGATGCCAGTCAGCCCAGTCGAGGCCCCTCCCCTGAGTCCATGTACCCACAACCCCCTG
GTCAATGTCCGAGTAGAGCGCTTCAAACGAGATCCTAACCAATCTCTGACTCCCACCCAT
GTCACCCTCACCACCCCCTCGCAGCCCAGCAGTCACCGGCGGACTCCTTCTGATGGGGCC
CTTAAGCCAGAGACTCTCCTAGCCAGCAGGAGCCCCTCCAGCAATGGGTTGAGCCCCAGT
CCTGGAGCAGGAATGTTGAAAACCCCCAGTCCCAGCCGAGACCCAGGTGAATTCCCCCGT
CTCCCTGACCCCAATGTGGTCTTCCCCCCAACCCCAAGGCGCTGGAACACTCAGCAGGAC
TCTACCTTGGAGAGACCCAAGACTCTGGAGTTTCTGCCTCGGCCGCGTCCTTCTGCCAAC
CGGCAACGGCTGGACCCTTGGTGGTTTGTGTCCCCCAGCCATGCCCGCAGCACCTCCCCA
GCCAACAGCTCCAGCACAGAGACGCCCAGCAACCTGGACTCCTGCTTTGCTAGCAGTAGC
AGCACTGTAGAGGAGCGGCCTGGACTTCCAGCCCTGCTCCCGTTCCAGGCAGGGCCGCTG
CCCCCGACTGAGCGGACGCTCCTGGACCTGGATGCAGAGGGGCAGAGTCAGGACAGCACC
GTGCCGCTGTGCAGAGCGGAACTGAACACACACAGGCCTGCCCCTTATGAGATCCAGCAG
GAGTTCTGGTCTTAG
Chromosome Location
14
Locus
14q24.3-q31
External Identifiers
ResourceLink
UniProtKB IDP80192
UniProtKB Entry NameM3K9_HUMAN
GenBank Protein ID33591094
GenBank Gene IDAY327900
HGNC IDHGNC:6861
General References
  1. Durkin JT, Holskin BP, Kopec KK, Reed MS, Spais CM, Steffy BM, Gessner G, Angeles TS, Pohl J, Ator MA, Meyer SL: Phosphoregulation of mixed-lineage kinase 1 activity by multiple phosphorylation in the activation loop. Biochemistry. 2004 Dec 28;43(51):16348-55. [Article]
  2. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  3. Dorow DS, Devereux L, Dietzsch E, De Kretser T: Identification of a new family of human epithelial protein kinases containing two leucine/isoleucine-zipper domains. Eur J Biochem. 1993 Apr 15;213(2):701-10. [Article]
  4. Maroney AC, Finn JP, Connors TJ, Durkin JT, Angeles T, Gessner G, Xu Z, Meyer SL, Savage MJ, Greene LA, Scott RW, Vaught JL: Cep-1347 (KT7515), a semisynthetic inhibitor of the mixed lineage kinase family. J Biol Chem. 2001 Jul 6;276(27):25302-8. Epub 2001 Apr 26. [Article]
  5. Xu Z, Maroney AC, Dobrzanski P, Kukekov NV, Greene LA: The MLK family mediates c-Jun N-terminal kinase activation in neuronal apoptosis. Mol Cell Biol. 2001 Jul;21(14):4713-24. [Article]
  6. Murakata C, Kaneko M, Gessner G, Angeles TS, Ator MA, O'Kane TM, McKenna BA, Thomas BA, Mathiasen JR, Saporito MS, Bozyczko-Coyne D, Hudkins RL: Mixed lineage kinase activity of indolocarbazole analogues. Bioorg Med Chem Lett. 2002 Jan 21;12(2):147-50. [Article]
  7. Chen J, Guo L, Peiffer DA, Zhou L, Chan OT, Bibikova M, Wickham-Garcia E, Lu SH, Zhan Q, Wang-Rodriguez J, Jiang W, Fan JB: Genomic profiling of 766 cancer-related genes in archived esophageal normal and carcinoma tissues. Int J Cancer. 2008 May 15;122(10):2249-54. doi: 10.1002/ijc.23397. [Article]
  8. 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]
  9. Hudkins RL, Diebold JL, Tao M, Josef KA, Park CH, Angeles TS, Aimone LD, Husten J, Ator MA, Meyer SL, Holskin BP, Durkin JT, Fedorov AA, Fedorov EV, Almo SC, Mathiasen JR, Bozyczko-Coyne D, Saporito MS, Scott RW, Mallamo JP: Mixed-lineage kinase 1 and mixed-lineage kinase 3 subtype-selective dihydronaphthyl[3,4-a]pyrrolo[3,4-c]carbazole-5-ones: optimization, mixed-lineage kinase 1 crystallography, and oral in vivo activity in 1-methyl-4-phenyltetrahydropyridine models. J Med Chem. 2008 Sep 25;51(18):5680-9. doi: 10.1021/jm8005838. Epub 2008 Aug 21. [Article]
  10. 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
DB0870312-(2-hydroxyethyl)-2-(1-methylethoxy)-13,14-dihydronaphtho[2,1-a]pyrrolo[3,4-c]carbazol-5(12H)-oneexperimentalunknownDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails