Mitogen-activated protein kinase kinase kinase 11

Details

Name
Mitogen-activated protein kinase kinase kinase 11
Synonyms
  • 2.7.11.25
  • Mixed lineage kinase 3
  • MLK3
  • PTK1
  • SPRK
  • Src-homology 3 domain-containing proline-rich kinase
Gene Name
MAP3K11
Organism
Humans
Amino acid sequence
>lcl|BSEQ0051804|Mitogen-activated protein kinase kinase kinase 11
MEPLKSLFLKSPLGSWNGSGSGGGGGGGGGRPEGSPKAAGYANPVWTALFDYEPSGQDEL
ALRKGDRVEVLSRDAAISGDEGWWAGQVGGQVGIFPSNYVSRGGGPPPCEVASFQELRLE
EVIGIGGFGKVYRGSWRGELVAVKAARQDPDEDISVTAESVRQEARLFAMLAHPNIIALK
AVCLEEPNLCLVMEYAAGGPLSRALAGRRVPPHVLVNWAVQIARGMHYLHCEALVPVIHR
DLKSNNILLLQPIESDDMEHKTLKITDFGLAREWHKTTQMSAAGTYAWMAPEVIKASTFS
KGSDVWSFGVLLWELLTGEVPYRGIDCLAVAYGVAVNKLTLPIPSTCPEPFAQLMADCWA
QDPHRRPDFASILQQLEALEAQVLREMPRDSFHSMQEGWKREIQGLFDELRAKEKELLSR
EEELTRAAREQRSQAEQLRRREHLLAQWELEVFERELTLLLQQVDRERPHVRRRRGTFKR
SKLRARDGGERISMPLDFKHRITVQASPGLDRRRNVFEVGPGDSPTFPRFRAIQLEPAEP
GQAWGRQSPRRLEDSSNGERRACWAWGPSSPKPGEAQNGRRRSRMDEATWYLDSDDSSPL
GSPSTPPALNGNPPRPSLEPEEPKRPVPAERGSSSGTPKLIQRALLRGTALLASLGLGRD
LQPPGGPGRERGESPTTPPTPTPAPCPTEPPPSPLICFSLKTPDSPPTPAPLLLDLGIPV
GQRSAKSPRREEEPRGGTVSPPPGTSRSAPGTPGTPRSPPLGLISRPRPSPLRSRIDPWS
FVSAGPRPSPLPSPQPAPRRAPWTLFPDSDPFWDSPPANPFQGGPQDCRAQTKDMGAQAP
WVPEAGP
Number of residues
847
Molecular Weight
92687.03
Theoretical pI
Not Available
GO Classification
Functions
ATP binding / identical protein binding / JUN kinase kinase kinase activity / mitogen-activated protein kinase kinase binding / mitogen-activated protein kinase kinase kinase binding / protein homodimerization activity / protein kinase activity / protein serine/threonine kinase activity / Rac GTPase binding
Processes
activation of JUN kinase activity / activation of MAPK activity / cell death / cell proliferation / JNK cascade / microtubule-based process / positive regulation of apoptotic process / positive regulation of JNK cascade / positive regulation of JUN kinase activity / positive regulation of neuron apoptotic process / protein autophosphorylation / protein phosphorylation
Components
centrosome / cytoplasm / membrane / microtubule
General Function
Activates the JUN N-terminal pathway. Required for serum-stimulated cell proliferation and for mitogen and cytokine activation of MAPK14 (p38), MAPK3 (ERK) and MAPK8 (JNK1) through phosphorylation and activation of MAP2K4/MKK4 and MAP2K7/MKK7. Plays a role in mitogen-stimulated phosphorylation and activation of BRAF, but does not phosphorylate BRAF directly. Influences microtubule organization during the cell cycle.
Specific Function
Atp binding
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0051805|Mitogen-activated protein kinase kinase kinase 11 (MAP3K11)
ATGGAGCCCTTGAAGAGCCTCTTCCTCAAGAGCCCTCTAGGGTCATGGAATGGCAGTGGC
AGCGGGGGTGGTGGGGGCGGTGGAGGAGGCCGGCCTGAGGGGTCTCCAAAGGCAGCGGGT
TATGCCAACCCGGTGTGGACAGCCCTGTTCGACTACGAGCCCAGTGGGCAGGATGAGCTG
GCCCTGAGGAAGGGTGACCGTGTGGAGGTGCTGTCCCGGGACGCAGCCATCTCAGGAGAC
GAGGGCTGGTGGGCGGGCCAGGTGGGTGGCCAGGTGGGCATCTTCCCGTCCAACTATGTG
TCTCGGGGTGGCGGCCCGCCCCCCTGCGAGGTGGCCAGCTTCCAGGAGCTGCGGCTGGAG
GAGGTGATCGGCATTGGAGGCTTTGGCAAGGTGTACAGGGGCAGCTGGCGAGGTGAGCTG
GTGGCTGTGAAGGCAGCTCGCCAGGACCCCGATGAGGACATCAGTGTGACAGCCGAGAGC
GTTCGCCAGGAGGCCCGGCTCTTCGCCATGCTGGCACACCCCAACATCATTGCCCTCAAG
GCTGTGTGCCTGGAGGAGCCCAACCTGTGCCTGGTGATGGAGTATGCAGCCGGTGGGCCC
CTCAGCCGAGCTCTGGCCGGGCGGCGCGTGCCTCCCCATGTGCTGGTCAACTGGGCTGTG
CAGATTGCCCGTGGGATGCACTACCTGCACTGCGAGGCCCTGGTGCCCGTCATCCACCGT
GATCTCAAGTCCAACAACATTTTGCTGCTGCAGCCCATTGAGAGTGACGACATGGAGCAC
AAGACCCTGAAGATCACCGACTTTGGCCTGGCCCGAGAGTGGCACAAAACCACACAAATG
AGTGCCGCGGGCACCTACGCCTGGATGGCTCCTGAGGTTATCAAGGCCTCCACCTTCTCT
AAGGGCAGTGACGTCTGGAGTTTTGGGGTGCTGCTGTGGGAACTGCTGACCGGGGAGGTG
CCATACCGTGGCATTGACTGCCTTGCTGTGGCCTATGGCGTAGCTGTTAACAAGCTCACA
CTGCCCATCCCATCCACCTGCCCCGAGCCCTTCGCACAGCTTATGGCCGACTGCTGGGCG
CAGGACCCCCACCGCAGGCCCGACTTCGCCTCCATCCTGCAGCAGTTGGAGGCGCTGGAG
GCACAGGTCCTACGGGAAATGCCGCGGGACTCCTTCCATTCCATGCAGGAAGGCTGGAAG
CGCGAGATCCAGGGTCTCTTCGACGAGCTGCGAGCCAAGGAAAAGGAACTACTGAGCCGC
GAGGAGGAGCTGACGCGAGCGGCGCGCGAGCAGCGGTCACAGGCGGAGCAGCTGCGGCGG
CGCGAGCACCTGCTGGCCCAGTGGGAGCTAGAGGTGTTCGAGCGCGAGCTGACGCTGCTG
CTGCAGCAGGTGGACCGCGAGCGACCGCACGTGCGCCGCCGCCGCGGGACATTCAAGCGC
AGCAAGCTCCGGGCGCGCGACGGCGGCGAGCGTATCAGCATGCCACTCGACTTCAAGCAC
CGCATCACCGTGCAGGCCTCACCCGGCCTTGACCGGAGGAGAAACGTCTTCGAGGTCGGG
CCTGGGGATTCGCCCACCTTTCCCCGGTTCCGAGCCATCCAGTTGGAGCCTGCAGAGCCA
GGCCAGGCATGGGGCCGCCAGTCCCCCCGACGTCTGGAGGACTCAAGCAATGGAGAGCGG
CGAGCATGCTGGGCTTGGGGTCCCAGTTCCCCCAAGCCTGGGGAAGCCCAGAATGGGAGG
AGAAGGTCCCGCATGGACGAAGCCACATGGTACCTGGATTCAGATGACTCATCCCCCTTA
GGATCTCCTTCCACACCCCCAGCACTCAATGGTAACCCCCCGCGGCCTAGCCTGGAGCCC
GAGGAGCCCAAGAGGCCTGTCCCCGCAGAGCGCGGTAGCAGCTCTGGGACGCCCAAGCTG
ATCCAGCGGGCGCTGCTGCGCGGCACCGCCCTGCTCGCCTCGCTGGGCCTTGGCCGCGAC
CTGCAGCCGCCGGGAGGCCCAGGACGCGAGCGCGGGGAGTCCCCGACAACACCCCCCACG
CCAACGCCCGCGCCCTGCCCGACCGAGCCGCCCCCTTCCCCGCTCATCTGCTTCTCGCTC
AAGACGCCCGACTCCCCGCCCACTCCTGCACCCCTGTTGCTGGACCTGGGTATCCCTGTG
GGCCAGCGGTCAGCCAAGAGCCCCCGACGTGAGGAGGAGCCCCGCGGAGGCACTGTCTCA
CCCCCACCGGGGACATCACGCTCTGCTCCTGGCACCCCAGGCACCCCACGTTCACCACCC
CTGGGCCTCATCAGCCGACCTCGGCCCTCGCCCCTTCGCAGCCGCATTGATCCCTGGAGC
TTTGTGTCAGCTGGGCCACGGCCTTCTCCCCTGCCATCACCACAGCCTGCACCCCGCCGA
GCACCCTGGACCTTGTTCCCGGACTCAGACCCCTTCTGGGACTCCCCACCTGCCAACCCC
TTCCAGGGGGGCCCCCAGGACTGCAGGGCACAGACCAAAGACATGGGTGCCCAGGCCCCG
TGGGTGCCGGAAGCGGGGCCTTGA
Chromosome Location
11
Locus
11q13.1
External Identifiers
ResourceLink
UniProtKB IDQ16584
UniProtKB Entry NameM3K11_HUMAN
HGNC IDHGNC:6850
General References
  1. Gallo KA, Mark MR, Scadden DT, Wang Z, Gu Q, Godowski PJ: Identification and characterization of SPRK, a novel src-homology 3 domain-containing proline-rich kinase with serine/threonine kinase activity. J Biol Chem. 1994 May 27;269(21):15092-100. [Article]
  2. Ing YL, Leung IW, Heng HH, Tsui LC, Lassam NJ: MLK-3: identification of a widely-expressed protein kinase bearing an SH3 domain and a leucine zipper-basic region domain. Oncogene. 1994 Jun;9(6):1745-50. [Article]
  3. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
  4. Taylor TD, Noguchi H, Totoki Y, Toyoda A, Kuroki Y, Dewar K, Lloyd C, Itoh T, Takeda T, Kim DW, She X, Barlow KF, Bloom T, Bruford E, Chang JL, Cuomo CA, Eichler E, FitzGerald MG, Jaffe DB, LaButti K, Nicol R, Park HS, Seaman C, Sougnez C, Yang X, Zimmer AR, Zody MC, Birren BW, Nusbaum C, Fujiyama A, Hattori M, Rogers J, Lander ES, Sakaki Y: Human chromosome 11 DNA sequence and analysis including novel gene identification. Nature. 2006 Mar 23;440(7083):497-500. [Article]
  5. 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]
  6. Tibbles LA, Ing YL, Kiefer F, Chan J, Iscove N, Woodgett JR, Lassam NJ: MLK-3 activates the SAPK/JNK and p38/RK pathways via SEK1 and MKK3/6. EMBO J. 1996 Dec 16;15(24):7026-35. [Article]
  7. Leung IW, Lassam N: Dimerization via tandem leucine zippers is essential for the activation of the mitogen-activated protein kinase kinase kinase, MLK-3. J Biol Chem. 1998 Dec 4;273(49):32408-15. [Article]
  8. Leung IW, Lassam N: The kinase activation loop is the key to mixed lineage kinase-3 activation via both autophosphorylation and hematopoietic progenitor kinase 1 phosphorylation. J Biol Chem. 2001 Jan 19;276(3):1961-7. Epub 2000 Oct 26. [Article]
  9. Vacratsis PO, Phinney BS, Gage DA, Gallo KA: Identification of in vivo phosphorylation sites of MLK3 by mass spectrometry and phosphopeptide mapping. Biochemistry. 2002 Apr 30;41(17):5613-24. [Article]
  10. Swenson KI, Winkler KE, Means AR: A new identity for MLK3 as an NIMA-related, cell cycle-regulated kinase that is localized near centrosomes and influences microtubule organization. Mol Biol Cell. 2003 Jan;14(1):156-72. [Article]
  11. Chadee DN, Kyriakis JM: MLK3 is required for mitogen activation of B-Raf, ERK and cell proliferation. Nat Cell Biol. 2004 Aug;6(8):770-6. Epub 2004 Jul 18. [Article]
  12. Beausoleil SA, Villen J, Gerber SA, Rush J, Gygi SP: A probability-based approach for high-throughput protein phosphorylation analysis and site localization. Nat Biotechnol. 2006 Oct;24(10):1285-92. Epub 2006 Sep 10. [Article]
  13. 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]
  14. 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]
  15. 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]
  16. 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]
  17. 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]
  18. 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]
  19. 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