Mitogen-activated protein kinase kinase kinase 2

Details

Name
Mitogen-activated protein kinase kinase kinase 2
Synonyms
  • 2.7.11.25
  • MAPK/ERK kinase kinase 2
  • MAPKKK2
  • MEK kinase 2
  • MEKK 2
  • MEKK2
Gene Name
MAP3K2
Organism
Humans
Amino acid sequence
>lcl|BSEQ0008596|Mitogen-activated protein kinase kinase kinase 2
MDDQQALNSIMQDLAVLHKASRPALSLQETRKAKSSSPKKQNDVRVKFEHRGEKRILQFP
RPVKLEDLRSKAKIAFGQSMDLHYTNNELVIPLTTQDDLDKAVELLDRSIHMKSLKILLV
INGSTQATNLEPLPSLEDLDNTVFGAERKKRLSIIGPTSRDRSSPPPGYIPDELHQVARN
GSFTSINSEGEFIPESMDQMLDPLSLSSPENSGSGSCPSLDSPLDGESYPKSRMPRAQSY
PDNHQEFSDYDNPIFEKFGKGGTYPRRYHVSYHHQEYNDGRKTFPRARRTQGTSLRSPVS
FSPTDHSLSTSSGSSIFTPEYDDSRIRRRGSDIDNPTLTVMDISPPSRSPRAPTNWRLGK
LLGQGAFGRVYLCYDVDTGRELAVKQVQFDPDSPETSKEVNALECEIQLLKNLLHERIVQ
YYGCLRDPQEKTLSIFMEYMPGGSIKDQLKAYGALTENVTRKYTRQILEGVHYLHSNMIV
HRDIKGANILRDSTGNVKLGDFGASKRLQTICLSGTGMKSVTGTPYWMSPEVISGEGYGR
KADIWSVACTVVEMLTEKPPWAEFEAMAAIFKIATQPTNPKLPPHVSDYTRDFLKRIFVE
AKLRPSADELLRHMFVHYH
Number of residues
619
Molecular Weight
69740.21
Theoretical pI
Not Available
GO Classification
Functions
ATP binding / MAP kinase kinase kinase activity / metal ion binding / protein kinase activity / protein kinase binding / protein serine/threonine kinase activity
Processes
activation of JUN kinase activity / activation of MAPK activity / cellular response to mechanical stimulus / positive regulation of transcription, DNA-templated / protein phosphorylation
Components
cytoplasm / cytosol / nucleoplasm
General Function
Protein serine/threonine kinase activity
Specific Function
Component of a protein kinase signal transduction cascade. Regulates the JNK and ERK5 pathways by phosphorylating and activating MAP2K5 and MAP2K7 (By similarity). Plays a role in caveolae kiss-and-run dynamics.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0013293|Mitogen-activated protein kinase kinase kinase 2 (MAP3K2)
ATGGATGATCAGCAAGCTTTGAACTCAATCATGCAAGATTTGGCTGTCCTTCATAAGGCC
AGTCGACCAGCATTATCCTTGCAGGAAACCAGAAAAGCAAAATCTTCATCACCAAAAAAA
CAGAATGATGTCCGAGTCAAATTTGAACATAGAGGAGAAAAAAGAATCCTTCAGTTCCCC
AGACCAGTTAAACTGGAAGATCTGAGATCTAAAGCTAAAATTGCCTTTGGACAGTCTATG
GATCTACATTATACCAATAACGAGTTGGTAATTCCATTAACTACTCAAGATGACTTGGAC
AAAGCTGTGGAACTGCTGGATCGTAGTATTCATATGAAGAGCCTCAAGATATTACTTGTA
ATAAATGGAAGTACACAGGCTACTAATTTAGAACCATTGCCATCACTAGAAGATTTGGAT
AATACAGTATTTGGAGCAGAGAGGAAAAAACGGCTATCTATAATAGGTCCTACTAGTAGA
GATAGAAGTTCTCCTCCCCCAGGTTACATTCCAGATGAATTACACCAGGTTGCCCGGAAT
GGGTCATTCACTAGTATCAACAGTGAAGGAGAGTTCATTCCAGAGAGCATGGACCAAATG
CTGGATCCATTATCTTTAAGCAGCCCTGAAAATTCTGGCTCAGGAAGTTGTCCATCACTT
GATAGTCCTTTGGATGGAGAGAGCTATCCAAAATCACGAATGCCTAGGGCTCAGAGCTAC
CCAGATAATCATCAGGAATTTTCAGACTATGATAACCCTATCTTTGAGAAATTTGGAAAA
GGAGGAACATATCCAAGAAGGTATCATGTTTCATATCATCATCAAGAGTATAATGATGGT
CGTAAAACTTTTCCAAGAGCTAGAAGGACCCAGGGGACCAGCTTACGGTCTCCTGTGAGT
TTCAGTCCTACTGATCATTCCTTAAGCACTAGTAGTGGAAGCAGTATCTTTACCCCAGAG
TATGATGATAGTCGAATAAGAAGAAGGGGAAGTGACATAGACAATCCTACTTTGACCGTA
ATGGACATCAGCCCACCCAGCCGTTCACCTCGAGCTCCGACCAACTGGAGATTGGGCAAA
CTGCTTGGCCAAGGAGCCTTTGGAAGGGTCTACCTCTGTTATGATGTTGATACAGGAAGA
GAATTGGCTGTTAAGCAAGTTCAATTTGACCCCGATAGTCCTGAGACCAGCAAGGAAGTA
AATGCACTTGAGTGTGAAATTCAGTTGCTGAAAAACTTGCTACATGAGCGAATTGTTCAG
TATTATGGCTGTTTGAGGGATCCCCAGGAAAAAACACTTTCCATATTTATGGAATATATG
CCAGGGGGTTCAATTAAGGACCAATTAAAAGCATATGGCGCTCTTACTGAGAATGTGACT
AGGAAATACACCCGTCAGATTCTGGAGGGTGTCCATTATTTGCACAGTAATATGATTGTC
CATAGAGATATCAAAGGCGCAAATATCCTGCGAGATTCAACAGGCAACGTCAAACTAGGA
GATTTTGGGGCCAGCAAACGGCTTCAGACCATCTGTCTCTCAGGGACAGGAATGAAGTCT
GTCACGGGCACACCATACTGGATGAGCCCTGAAGTCATCAGTGGAGAAGGCTATGGAAGA
AAAGCAGACATCTGGAGTGTTGCATGTACTGTGGTAGAAATGCTAACTGAAAAGCCGCCT
TGGGCTGAATTTGAAGCAATGGCTGCCATCTTTAAAATCGCCACTCAGCCAACAAACCCA
AAGCTGCCACCTCATGTCTCAGACTATACTCGAGATTTCCTCAAACGGATTTTTGTAGAG
GCCAAACTGAGACCTTCAGCTGATGAACTCTTAAGGCACATGTTTGTGCATTATCACTAG
Chromosome Location
2
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDQ9Y2U5
UniProtKB Entry NameM3K2_HUMAN
HGNC IDHGNC:6854
General References
  1. 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. [PubMed:15815621]
  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. [PubMed:15489334]
  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. [PubMed:14702039]
  4. Cheng J, Yang J, Xia Y, Karin M, Su B: Synergistic interaction of MEK kinase 2, c-Jun N-terminal kinase (JNK) kinase 2, and JNK1 results in efficient and specific JNK1 activation. Mol Cell Biol. 2000 Apr;20(7):2334-42. [PubMed:10713157]
  5. Raviv Z, Kalie E, Seger R: MEK5 and ERK5 are localized in the nuclei of resting as well as stimulated cells, while MEKK2 translocates from the cytosol to the nucleus upon stimulation. J Cell Sci. 2004 Apr 1;117(Pt 9):1773-84. Epub 2004 Mar 16. [PubMed:15075238]
  6. Pelkmans L, Zerial M: Kinase-regulated quantal assemblies and kiss-and-run recycling of caveolae. Nature. 2005 Jul 7;436(7047):128-33. [PubMed:16001074]
  7. Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M: Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell. 2006 Nov 3;127(3):635-48. [PubMed:17081983]
  8. Winsauer G, Resch U, Hofer-Warbinek R, Schichl YM, de Martin R: XIAP regulates bi-phasic NF-kappaB induction involving physical interaction and ubiquitination of MEKK2. Cell Signal. 2008 Nov;20(11):2107-12. doi: 10.1016/j.cellsig.2008.08.004. Epub 2008 Aug 13. [PubMed:18761086]
  9. 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]
  10. Zahedi RP, Lewandrowski U, Wiesner J, Wortelkamp S, Moebius J, Schutz C, Walter U, Gambaryan S, Sickmann A: Phosphoproteome of resting human platelets. J Proteome Res. 2008 Feb;7(2):526-34. Epub 2007 Dec 19. [PubMed:18088087]
  11. 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]
  12. Enomoto A, Kido N, Ito M, Morita A, Matsumoto Y, Takamatsu N, Hosoi Y, Miyagawa K: Negative regulation of MEKK1/2 signaling by serine-threonine kinase 38 (STK38). Oncogene. 2008 Mar 20;27(13):1930-8. Epub 2007 Oct 1. [PubMed:17906693]
  13. 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]
  14. 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]
  15. 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]
  16. 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. [PubMed:20068231]
  17. 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. [PubMed:21406692]
  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. [PubMed:24275569]
  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. [PubMed:17344846]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB06616BosutinibapprovedunknowninhibitorDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails