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
Functions
ATP binding / magnesium ion binding / MAP kinase kinase kinase activity / poly(A) RNA binding / protein serine/threonine kinase activity
Processes
activation 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 stress
Components
cytoplasm / 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
ResourceLink
UniProtKB IDQ9NYL2
UniProtKB Entry NameMLTK_HUMAN
General References
  1. 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]
  2. 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]
  3. 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]
  4. 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]
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  8. 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]
  9. 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]
  10. 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]
  11. 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]
  12. 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]
  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]
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  20. 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]
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB01254Dasatinibapproved, investigationalunknownbinderDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails