MAP/microtubule affinity-regulating kinase 4

Details

Name
MAP/microtubule affinity-regulating kinase 4
Synonyms
  • 2.7.11.1
  • KIAA1860
  • MAP/microtubule affinity-regulating kinase-like 1
  • MARKL1
Gene Name
MARK4
Organism
Humans
Amino acid sequence
>lcl|BSEQ0051842|MAP/microtubule affinity-regulating kinase 4
MSSRTVLAPGNDRNSDTHGTLGSGRSSDKGPSWSSRSLGARCRNSIASCPEEQPHVGNYR
LLRTIGKGNFAKVKLARHILTGREVAIKIIDKTQLNPSSLQKLFREVRIMKGLNHPNIVK
LFEVIETEKTLYLVMEYASAGEVFDYLVSHGRMKEKEARAKFRQIVSAVHYCHQKNIVHR
DLKAENLLLDAEANIKIADFGFSNEFTLGSKLDTFCGSPPYAAPELFQGKKYDGPEVDIW
SLGVILYTLVSGSLPFDGHNLKELRERVLRGKYRVPFYMSTDCESILRRFLVLNPAKRCT
LEQIMKDKWINIGYEGEELKPYTEPEEDFGDTKRIEVMVGMGYTREEIKESLTSQKYNEV
TATYLLLGRKTEEGGDRGAPGLALARVRAPSDTTNGTSSSKGTSHSKGQRSSSSTYHRQR
RHSDFCGPSPAPLHPKRSPTSTGEAELKEERLPGRKASCSTAGSGSRGLPPSSPMVSSAH
NPNKAEIPERRKDSTSTPNNLPPSMMTRRNTYVCTERPGAERPSLLPNGKENSSGTPRVP
PASPSSHSLAPPSGERSRLARGSTIRSTFHGGQVRDRRAGGGGGGGVQNGPPASPTLAHE
AAPLPAGRPRPTTNLFTKLTSKLTRRVADEPERIGGPEVTSCHLPWDQTETAPRLLRFPW
SVKLTSSRPPEALMAALRQATAAARCRCRQPQPFLLACLHGGAGGPEPLSHFEVEVCQLP
RPGLRGVLFRRVAGTALAFRTLVTRISNDLEL
Number of residues
752
Molecular Weight
82518.895
Theoretical pI
Not Available
GO Classification
Functions
ATP binding / gamma-tubulin binding / microtubule binding / protein serine/threonine kinase activity / tau-protein kinase activity / ubiquitin binding
Processes
cell cycle / cell division / ciliary basal body-plasma membrane docking / establishment of cell polarity / microtubule bundle formation / microtubule cytoskeleton organization / nervous system development / positive regulation of programmed cell death / protein phosphorylation
Components
centrosome / ciliary basal body / cytosol / microtubule cytoskeleton / microtubule organizing center / neuron projection
General Function
Serine/threonine-protein kinase (PubMed:15009667, PubMed:14594945, PubMed:23666762, PubMed:23184942). Phosphorylates the microtubule-associated protein MAPT (PubMed:14594945, PubMed:23666762). Also phosphorylates the microtubule-associated proteins MAP2 and MAP4 (PubMed:14594945). Involved in regulation of the microtubule network, causing reorganization of microtubules into bundles (PubMed:14594945, PubMed:25123532). Required for the initiation of axoneme extension during cilium assembly (PubMed:23400999). Regulates the centrosomal location of ODF2 and phosphorylates ODF2 in vitro (PubMed:23400999). Plays a role in cell cycle progression, specifically in the G1/S checkpoint (PubMed:25123532). Reduces neuronal cell survival (PubMed:15009667). Plays a role in energy homeostasis by regulating satiety and metabolic rate (By similarity). Promotes adipogenesis by activating JNK1 and inhibiting the p38MAPK pathway, and triggers apoptosis by activating the JNK1 pathway (By similarity). Phosphorylates mTORC1 complex member RPTOR and acts as a negative regulator of the mTORC1 complex, probably due to disruption of the interaction between phosphorylated RPTOR and the RRAGA/RRAGC heterodimer which is required for mTORC1 activation (PubMed:23184942).
Specific Function
Atp binding
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0051843|MAP/microtubule affinity-regulating kinase 4 (MARK4)
ATGTCTTCGCGGACGGTGCTGGCCCCGGGCAACGATCGGAACTCGGACACGCATGGCACC
TTGGGCAGTGGCCGCTCCTCGGACAAAGGCCCGTCCTGGTCCAGCCGCTCACTGGGTGCC
CGTTGCCGGAACTCCATCGCCTCCTGTCCCGAGGAGCAGCCCCACGTGGGCAACTACCGC
CTGCTGAGGACCATTGGGAAGGGCAACTTTGCCAAAGTCAAGCTGGCTCGGCACATCCTC
ACTGGTCGGGAGGTTGCCATCAAGATTATCGACAAAACCCAGCTGAATCCCAGCAGCCTG
CAGAAGCTGTTCCGAGAAGTCCGCATCATGAAGGGCCTAAACCACCCCAACATCGTGAAG
CTCTTTGAGGTGATTGAGACTGAGAAGACGCTGTACCTGGTGATGGAGTACGCAAGTGCT
GGAGAAGTGTTTGACTACCTCGTGTCGCATGGCCGCATGAAGGAGAAGGAAGCTCGAGCC
AAGTTCCGACAGATTGTTTCGGCTGTGCACTATTGTCACCAGAAAAATATTGTACACAGG
GACCTGAAGGCTGAGAACCTCTTGCTGGATGCCGAGGCCAACATCAAGATTGCTGACTTT
GGCTTCAGCAACGAGTTCACGCTGGGATCGAAGCTGGACACGTTCTGCGGGAGCCCCCCA
TATGCCGCCCCGGAGCTGTTTCAGGGCAAGAAGTACGACGGGCCGGAGGTGGACATCTGG
AGCCTGGGAGTCATCCTGTACACCCTCGTCAGCGGCTCCCTGCCCTTCGACGGGCACAAC
CTCAAGGAGCTGCGGGAGCGAGTACTCAGAGGGAAGTACCGGGTCCCTTTCTACATGTCA
ACAGACTGTGAGAGCATCCTGCGGAGATTTTTGGTGCTGAACCCAGCTAAACGCTGTACT
CTCGAGCAAATCATGAAAGACAAATGGATCAACATCGGCTATGAGGGTGAGGAGTTGAAG
CCATACACAGAGCCCGAGGAGGACTTCGGGGACACCAAGAGAATTGAGGTGATGGTGGGT
ATGGGCTACACACGGGAAGAAATCAAAGAGTCCTTGACCAGCCAGAAGTACAACGAAGTG
ACCGCCACCTACCTCCTGCTGGGCAGGAAGACTGAGGAGGGTGGGGACCGGGGCGCCCCA
GGGCTGGCCCTGGCACGGGTGCGGGCGCCCAGCGACACCACCAACGGAACAAGTTCCAGC
AAAGGCACCAGCCACAGCAAAGGGCAGCGGAGTTCCTCTTCCACCTACCACCGCCAGCGC
AGGCATAGCGATTTCTGTGGCCCATCCCCTGCACCCCTGCACCCCAAACGCAGCCCGACG
AGCACGGGGGAGGCGGAGCTGAAGGAGGAGCGGCTGCCAGGCCGGAAGGCGAGCTGCAGC
ACCGCGGGGAGTGGGAGTCGAGGGCTGCCCCCCTCCAGCCCCATGGTCAGCAGCGCCCAC
AACCCCAACAAGGCAGAGATCCCAGAGCGGCGGAAGGACAGCACGAGCACCCCCAACAAC
CTCCCTCCTAGCATGATGACCCGCAGAAACACCTACGTTTGCACAGAACGCCCGGGGGCT
GAGCGCCCGTCACTGTTGCCAAATGGGAAAGAAAACAGCTCAGGCACCCCACGGGTGCCC
CCTGCCTCCCCCTCCAGTCACAGCCTGGCACCCCCATCAGGGGAGCGGAGCCGCCTGGCA
CGCGGTTCCACCATCCGCAGCACCTTCCATGGTGGCCAGGTCCGGGACCGGCGGGCAGGG
GGTGGGGGTGGTGGGGGTGTGCAGAATGGGCCCCCTGCCTCTCCCACACTGGCCCATGAG
GCTGCACCCCTGCCCGCCGGGCGGCCCCGCCCCACCACCAACCTCTTCACCAAGCTGACC
TCCAAACTGACCCGAAGGGTCGCAGACGAACCTGAGAGAATCGGGGGACCTGAGGTCACA
AGTTGCCATCTACCTTGGGATCAAACGGAAACCGCCCCCCGGCTGCTCCGATTCCCCTGG
AGTGTGAAGCTGACCAGCTCGCGCCCTCCTGAGGCCCTGATGGCAGCTCTGCGCCAGGCC
ACAGCAGCCGCCCGCTGCCGCTGCCGCCAGCCACAGCCGTTCCTGCTGGCCTGCCTGCAC
GGGGGTGCGGGCGGGCCCGAGCCCCTGTCCCACTTCGAAGTGGAGGTCTGCCAGCTGCCC
CGGCCAGGCTTGCGGGGAGTTCTCTTCCGCCGTGTGGCGGGCACCGCCCTGGCCTTCCGC
ACCCTCGTCACCCGCATCTCCAACGACCTCGAGCTCTGA
Chromosome Location
19
Locus
19q13.32
External Identifiers
ResourceLink
UniProtKB IDQ96L34
UniProtKB Entry NameMARK4_HUMAN
HGNC IDHGNC:13538
General References
  1. Kato T, Satoh S, Okabe H, Kitahara O, Ono K, Kihara C, Tanaka T, Tsunoda T, Yamaoka Y, Nakamura Y, Furukawa Y: Isolation of a novel human gene, MARKL1, homologous to MARK3 and its involvement in hepatocellular carcinogenesis. Neoplasia. 2001 Jan-Feb;3(1):4-9. [Article]
  2. Trinczek B, Brajenovic M, Ebneth A, Drewes G: MARK4 is a novel microtubule-associated proteins/microtubule affinity-regulating kinase that binds to the cellular microtubule network and to centrosomes. J Biol Chem. 2004 Feb 13;279(7):5915-23. doi: 10.1074/jbc.M304528200. Epub 2003 Nov 1. [Article]
  3. Schneider A, Laage R, von Ahsen O, Fischer A, Rossner M, Scheek S, Grunewald S, Kuner R, Weber D, Kruger C, Klaussner B, Gotz B, Hiemisch H, Newrzella D, Martin-Villalba A, Bach A, Schwaninger M: Identification of regulated genes during permanent focal cerebral ischaemia: characterization of the protein kinase 9b5/MARKL1/MARK4. J Neurochem. 2004 Mar;88(5):1114-26. [Article]
  4. Nagase T, Nakayama M, Nakajima D, Kikuno R, Ohara O: Prediction of the coding sequences of unidentified human genes. XX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. DNA Res. 2001 Apr 27;8(2):85-95. [Article]
  5. 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]
  6. Lizcano JM, Goransson O, Toth R, Deak M, Morrice NA, Boudeau J, Hawley SA, Udd L, Makela TP, Hardie DG, Alessi DR: LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR-1. EMBO J. 2004 Feb 25;23(4):833-43. Epub 2004 Feb 19. [Article]
  7. Al-Hakim AK, Zagorska A, Chapman L, Deak M, Peggie M, Alessi DR: Control of AMPK-related kinases by USP9X and atypical Lys(29)/Lys(33)-linked polyubiquitin chains. Biochem J. 2008 Apr 15;411(2):249-60. doi: 10.1042/BJ20080067. [Article]
  8. 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]
  9. Li L, Guan KL: Microtubule-associated protein/microtubule affinity-regulating kinase 4 (MARK4) is a negative regulator of the mammalian target of rapamycin complex 1 (mTORC1). J Biol Chem. 2013 Jan 4;288(1):703-8. doi: 10.1074/jbc.C112.396903. Epub 2012 Nov 26. [Article]
  10. Kuhns S, Schmidt KN, Reymann J, Gilbert DF, Neuner A, Hub B, Carvalho R, Wiedemann P, Zentgraf H, Erfle H, Klingmuller U, Boutros M, Pereira G: The microtubule affinity regulating kinase MARK4 promotes axoneme extension during early ciliogenesis. J Cell Biol. 2013 Feb 18;200(4):505-22. doi: 10.1083/jcb.201206013. Epub 2013 Feb 11. [Article]
  11. 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]
  12. Gu GJ, Lund H, Wu D, Blokzijl A, Classon C, von Euler G, Landegren U, Sunnemark D, Kamali-Moghaddam M: Role of individual MARK isoforms in phosphorylation of tau at Ser(2)(6)(2) in Alzheimer's disease. Neuromolecular Med. 2013 Sep;15(3):458-69. doi: 10.1007/s12017-013-8232-3. Epub 2013 May 12. [Article]
  13. Rovina D, Fontana L, Monti L, Novielli C, Panini N, Sirchia SM, Erba E, Magnani I, Larizza L: Microtubule-associated protein/microtubule affinity-regulating kinase 4 (MARK4) plays a role in cell cycle progression and cytoskeletal dynamics. Eur J Cell Biol. 2014 Aug-Sep;93(8-9):355-65. doi: 10.1016/j.ejcb.2014.07.004. Epub 2014 Jul 24. [Article]
  14. 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