Mitogen-activated protein kinase kinase kinase MLT
Details
- Name
- Mitogen-activated protein kinase kinase kinase MLT
- Synonyms
- 2.7.11.25
- HCCS-4
- Human cervical cancer suppressor gene 4 protein
- Leucine zipper- and sterile alpha motif-containing kinase
- Mixed lineage kinase-related kinase
- MLK-like mitogen-activated protein triple kinase
- MLK-related kinase
- MLTK
- MRK
- Sterile alpha motif- and leucine zipper-containing kinase AZK
- Gene Name
- ZAK
- Organism
- Humans
- Amino acid sequence
>lcl|BSEQ0009622|Mitogen-activated protein kinase kinase kinase MLT MSSLGASFVQIKFDDLQFFENCGGGSFGSVYRAKWISQDKEVAVKKLLKIEKEAEILSVL SHRNIIQFYGVILEPPNYGIVTEYASLGSLYDYINSNRSEEMDMDHIMTWATDVAKGMHY LHMEAPVKVIHRDLKSRNVVIAADGVLKICDFGASRFHNHTTHMSLVGTFPWMAPEVIQS LPVSETCDTYSYGVVLWEMLTREVPFKGLEGLQVAWLVVEKNERLTIPSSCPRSFAELLH QCWEADAKKRPSFKQIISILESMSNDTSLPDKCNSFLHNKAEWRCEIEATLERLKKLERD LSFKEQELKERERRLKMWEQKLTEQSNTPLLPSFEIGAWTEDDVYCWVQQLVRKGDSSAE MSVYASLFKENNITGKRLLLLEEEDLKDMGIVSKGHIIHFKSAIEKLTHDYINLFHFPPL IKDSGGEPEENEEKIVNLELVFGFHLKPGTGPQDCKWKMYMEMDGDEIAITYIKDVTFNT NLPDAEILKMTKPPFVMEKWIVGIAKSQTVECTVTYESDVRTPKSTKHVHSIQWSRTKPQ DEVKAVQLAIQTLFTNSDGNPGSRSDSSADCQWLDTLRMRQIASNTSLQRSQSNPILGSP FFSHFDGQDSYAAAVRRPQVPIKYQQITPVNQSRSSSPTQYGLTKNFSSLHLNSRDSGFS SGNTDTSSERGRYSDRSRNKYGRGSISLNSSPRGRYSGKSQHSTPSRGRYPGKFYRVSQS ALNPHQSPDFKRSPRDLHQPNTIPGMPLHPETDSRASEEDSKVSEGGWTKVEYRKKPHRP SPAKTNKERARGDHRGWRNF
- Number of residues
- 800
- Molecular Weight
- 91154.315
- Theoretical pI
- Not Available
- GO Classification
- FunctionsATP binding / magnesium ion binding / MAP kinase kinase kinase activity / poly(A) RNA binding / protein serine/threonine kinase activityProcessesactivation of JUN kinase activity / activation of MAPKK activity / cell cycle arrest / cell cycle checkpoint / cell death / cell differentiation / cell proliferation / cytoskeleton organization / DNA damage checkpoint / intracellular signal transduction / positive regulation of apoptotic process / protein phosphorylation / response to radiation / response to stressComponentscytoplasm / nucleus
- General Function
- Protein serine/threonine kinase activity
- Specific Function
- Stress-activated component of a protein kinase signal transduction cascade. Regulates the JNK and p38 pathways. Pro-apoptotic. Role in regulation of S and G2 cell cycle checkpoint by direct phosphorylation of CHEK2. Isoform 1, but not isoform 2, causes cell shrinkage and disruption of actin stress fibers. Isoform 1 may have role in neoplastic cell transformation and cancer development. Isoform 1, but not isoform 2, phosphorylates histone H3 at 'Ser-28'.
- Pfam Domain Function
- Transmembrane Regions
- Not Available
- Cellular Location
- Cytoplasm
- Gene sequence
>lcl|BSEQ0020889|Mitogen-activated protein kinase kinase kinase MLT (ZAK) ATGTCGTCTCTCGGTGCCTCCTTTGTGCAAATTAAATTTGATGACTTGCAGTTTTTTGAA AACTGCGGTGGAGGAAGTTTTGGGAGTGTTTATCGAGCCAAATGGATATCACAGGACAAG GAGGTGGCTGTAAAGAAGCTCCTCAAAATAGAGAAAGAGGCAGAAATACTCAGTGTCCTC AGTCACAGAAACATCATCCAGTTTTATGGAGTAATTCTTGAACCTCCCAACTATGGCATT GTCACAGAATATGCTTCTCTGGGATCACTCTATGATTACATTAACAGTAACAGAAGTGAG GAGATGGATATGGATCACATTATGACCTGGGCCACTGATGTAGCCAAAGGAATGCATTAT TTACATATGGAGGCTCCTGTCAAGGTGATTCACAGAGACCTCAAGTCAAGAAACGTTGTT ATAGCTGCTGATGGAGTATTGAAGATCTGTGACTTTGGTGCCTCTCGGTTCCATAACCAT ACAACACACATGTCCTTGGTTGGAACTTTCCCATGGATGGCTCCAGAAGTTATCCAGAGT CTCCCTGTGTCAGAAACTTGTGACACATATTCCTATGGTGTGGTTCTCTGGGAGATGCTA ACAAGGGAGGTCCCCTTTAAAGGTTTGGAAGGATTACAAGTAGCTTGGCTTGTAGTGGAA AAAAACGAGAGATTAACCATTCCAAGCAGTTGCCCCAGAAGTTTTGCTGAACTGTTACAT CAGTGTTGGGAAGCTGATGCCAAGAAACGGCCATCATTCAAGCAAATCATTTCAATCCTG GAGTCCATGTCAAATGACACGAGCCTTCCTGACAAGTGTAACTCATTCCTACACAACAAG GCGGAGTGGAGGTGCGAAATTGAGGCAACTCTTGAGAGGCTAAAGAAACTAGAGCGTGAT CTCAGCTTTAAGGAGCAGGAGCTTAAAGAACGAGAAAGACGTTTAAAGATGTGGGAGCAA AAGCTGACAGAGCAGTCCAACACCCCGCTGCTGCCTTCCTTTGAGATTGGTGCATGGACG GAAGACGATGTGTATTGTTGGGTTCAGCAGCTCGTCAGAAAAGGTGACTCTTCAGCAGAG ATGAGTGTATATGCAAGCTTGTTTAAAGAAAACAACATTACAGGGAAGCGGCTGCTGCTG CTGGAGGAAGAAGACCTGAAAGACATGGGCATTGTCTCCAAGGGGCATATCATTCACTTC AAGTCAGCCATTGAGAAATTAACCCATGATTACATAAATTTGTTTCACTTCCCACCACTA ATTAAGGACTCAGGAGGTGAACCTGAAGAAAATGAGGAAAAAATAGTGAACCTGGAACTG GTTTTTGGTTTTCACTTGAAACCAGGAACTGGCCCACAGGATTGTAAGTGGAAAATGTAT ATGGAGATGGATGGGGATGAAATTGCAATAACCTACATAAAAGATGTGACATTCAACACT AACCTACCTGATGCGGAGATTTTAAAGATGACAAAGCCACCATTTGTAATGGAGAAGTGG ATTGTAGGAATAGCAAAAAGTCAGACTGTGGAGTGCACTGTCACATATGAGAGTGATGTT AGAACTCCAAAAAGCACTAAACATGTCCATTCGATTCAGTGGAGTAGAACAAAACCTCAG GATGAAGTGAAAGCAGTCCAACTTGCCATTCAGACATTATTCACCAATTCAGATGGCAAC CCTGGAAGCAGGTCCGACTCAAGTGCTGATTGCCAGTGGTTAGATACTCTGAGGATGCGG CAGATTGCATCCAACACTTCTTTACAGCGTTCCCAGAGCAATCCTATTCTGGGGTCACCG TTCTTCTCACACTTTGATGGCCAGGATTCCTACGCTGCTGCTGTGAGACGGCCCCAGGTG CCCATTAAGTATCAACAGATTACACCTGTGAACCAGTCCAGAAGCTCGTCTCCTACTCAG TATGGACTGACCAAAAACTTCTCTTCCCTACATCTCAACTCTAGGGACAGTGGCTTTTCC AGTGGCAATACTGACACCTCTTCAGAGAGGGGTCGATACTCAGACAGAAGCAGGAACAAA TATGGACGTGGTAGTATATCACTCAATTCTTCTCCTAGAGGAAGATACAGTGGAAAGAGT CAGCATTCCACTCCTTCAAGAGGAAGATACCCTGGAAAGTTCTACAGGGTTTCTCAGTCA GCACTCAATCCTCACCAGTCGCCTGACTTCAAGAGAAGCCCCAGGGACCTCCACCAACCC AACACCATACCAGGGATGCCTTTGCACCCTGAGACTGACTCAAGAGCCAGTGAAGAGGAC AGCAAAGTCAGCGAAGGGGGCTGGACAAAAGTGGAATACCGGAAAAAGCCCCACAGGCCA TCTCCCGCCAAAACCAATAAAGAGAGAGCCAGAGGGGACCACCGTGGATGGAGAAACTTT TGA
- Chromosome Location
- 2
- Locus
- Not Available
- External Identifiers
Resource Link UniProtKB ID Q9NYL2 UniProtKB Entry Name MLTK_HUMAN - General References
- Liu TC, Huang CJ, Chu YC, Wei CC, Chou CC, Chou MY, Chou CK, Yang JJ: Cloning and expression of ZAK, a mixed lineage kinase-like protein containing a leucine-zipper and a sterile-alpha motif. Biochem Biophys Res Commun. 2000 Aug 11;274(3):811-6. [Article]
- Gotoh I, Adachi M, Nishida E: Identification and characterization of a novel MAP kinase kinase kinase, MLTK. J Biol Chem. 2001 Feb 9;276(6):4276-86. Epub 2000 Oct 19. [Article]
- Bloem LJ, Pickard TR, Acton S, Donoghue M, Beavis RC, Knierman MD, Wang X: Tissue distribution and functional expression of a cDNA encoding a novel mixed lineage kinase. J Mol Cell Cardiol. 2001 Sep;33(9):1739-50. [Article]
- Gross EA, Callow MG, Waldbaum L, Thomas S, Ruggieri R: MRK, a mixed lineage kinase-related molecule that plays a role in gamma-radiation-induced cell cycle arrest. J Biol Chem. 2002 Apr 19;277(16):13873-82. Epub 2002 Feb 8. [Article]
- 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]
- 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. [Article]
- 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]
- Yang JJ: A novel zinc finger protein, ZZaPK, interacts with ZAK and stimulates the ZAK-expressing cells re-entering the cell cycle. Biochem Biophys Res Commun. 2003 Jan 31;301(1):71-7. [Article]
- Takahashi M, Gotoh Y, Isagawa T, Nishimura T, Goyama E, Kim HS, Mukai H, Ono Y: Regulation of a mitogen-activated protein kinase kinase kinase, MLTK by PKN. J Biochem. 2003 Feb;133(2):181-7. [Article]
- Cho YY, Bode AM, Mizuno H, Choi BY, Choi HS, Dong Z: A novel role for mixed-lineage kinase-like mitogen-activated protein triple kinase alpha in neoplastic cell transformation and tumor development. Cancer Res. 2004 Jun 1;64(11):3855-64. [Article]
- Tosti E, Waldbaum L, Warshaw G, Gross EA, Ruggieri R: The stress kinase MRK contributes to regulation of DNA damage checkpoints through a p38gamma-independent pathway. J Biol Chem. 2004 Nov 12;279(46):47652-60. Epub 2004 Sep 1. [Article]
- Choi HS, Choi BY, Cho YY, Zhu F, Bode AM, Dong Z: Phosphorylation of Ser28 in histone H3 mediated by mixed lineage kinase-like mitogen-activated protein triple kinase alpha. J Biol Chem. 2005 Apr 8;280(14):13545-53. Epub 2005 Jan 31. [Article]
- 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]
- 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]
- Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501. doi: 10.1021/ac9004309. [Article]
- 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]
- 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]
- 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. [Article]
- 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. [Article]
- 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]
- 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]