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Identification
HMDB Protein ID HMDBP08747
Secondary Accession Numbers
  • 14470
Name Mitogen-activated protein kinase kinase kinase 11
Synonyms
  1. Mixed lineage kinase 3
  2. Src-homology 3 domain-containing proline-rich kinase
Gene Name MAP3K11
Protein Type Unknown
Biological Properties
General Function Involved in protein kinase activity
Specific 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). Plays a role in mitogen-stimulated phosphorylation and activation of BRAF, but does not phosphorylate BRAF directly. Influences microtubule organization during the cell cycle
Pathways Not Available
Reactions Not Available
GO Classification
Function
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
protein kinase activity
protein serine/threonine kinase activity
Process
phosphorus metabolic process
phosphate metabolic process
metabolic process
cellular metabolic process
protein amino acid phosphorylation
phosphorylation
Cellular Location
  1. Cytoplasm
  2. cytoskeleton
  3. centrosome
Gene Properties
Chromosome Location Chromosome:1
Locus 11q13.1-q13.3
SNPs MAP3K11
Gene Sequence
>2544 bp
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
Protein Properties
Number of Residues 847
Molecular Weight 92687.0
Theoretical pI 8.21
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • None
Protein Sequence
>Mitogen-activated protein kinase kinase kinase 11
MEPLKSLFLKSPLGSWNGSGSGGGGGGGGGRPEGSPKAAGYANPVWTALFDYEPSGQDEL
ALRKGDRVEVLSRDAAISGDEGWWAGQVGGQVGIFPSNYVSRGGGPPPCEVASFQELRLE
EVIGIGGFGKVYRGSWRGELVAVKAARQDPDEDISVTAESVRQEARLFAMLAHPNIIALK
AVCLEEPNLCLVMEYAAGGPLSRALAGRRVPPHVLVNWAVQIARGMHYLHCEALVPVIHR
DLKSNNILLLQPIESDDMEHKTLKITDFGLAREWHKTTQMSAAGTYAWMAPEVIKASTFS
KGSDVWSFGVLLWELLTGEVPYRGIDCLAVAYGVAVNKLTLPIPSTCPEPFAQLMADCWA
QDPHRRPDFASILQQLEALEAQVLREMPRDSFHSMQEGWKREIQGLFDELRAKEKELLSR
EEELTRAAREQRSQAEQLRRREHLLAQWELEVFERELTLLLQQVDRERPHVRRRRGTFKR
SKLRARDGGERISMPLDFKHRITVQASPGLDRRRNVFEVGPGDSPTFPRFRAIQLEPAEP
GQAWGRQSPRRLEDSSNGERRACWAWGPSSPKPGEAQNGRRRSRMDEATWYLDSDDSSPL
GSPSTPPALNGNPPRPSLEPEEPKRPVPAERGSSSGTPKLIQRALLRGTALLASLGLGRD
LQPPGGPGRERGESPTTPPTPTPAPCPTEPPPSPLICFSLKTPDSPPTPAPLLLDLGIPV
GQRSAKSPRREEEPRGGTVSPPPGTSRSAPGTPGTPRSPPLGLISRPRPSPLRSRIDPWS
FVSAGPRPSPLPSPQPAPRRAPWTLFPDSDPFWDSPPANPFQGGPQDCRAQTKDMGAQAP
WVPEAGP
GenBank ID Protein 4505195
UniProtKB/Swiss-Prot ID Q16584
UniProtKB/Swiss-Prot Entry Name M3K11_HUMAN
PDB IDs Not Available
GenBank Gene ID NM_002419.3
GeneCard ID MAP3K11
GenAtlas ID MAP3K11
HGNC ID HGNC:6850
References
General References
  1. 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. [PubMed:15489334 ]
  2. 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 ]
  3. 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 ]
  4. 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 ]
  5. 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 ]
  6. Yu LR, Zhu Z, Chan KC, Issaq HJ, Dimitrov DS, Veenstra TD: Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra. J Proteome Res. 2007 Nov;6(11):4150-62. Epub 2007 Oct 9. [PubMed:17924679 ]
  7. 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. [PubMed:16964243 ]
  8. 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 ]
  9. 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 ]
  10. 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. [PubMed:8195146 ]
  11. 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. [PubMed:8183572 ]
  12. 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. [PubMed:9829970 ]
  13. 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. [PubMed:11053428 ]
  14. 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. [PubMed:11969422 ]
  15. 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. [PubMed:12529434 ]
  16. 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. [PubMed:15258589 ]