Serine/threonine-protein kinase MARK1

Details

Name
Serine/threonine-protein kinase MARK1
Synonyms
  • 2.7.11.1
  • KIAA1477
  • MAP/microtubule affinity-regulating kinase 1
  • MARK
  • Par-1c
  • PAR1 homolog c
  • Par1c
Gene Name
MARK1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0051836|Serine/threonine-protein kinase MARK1
MSARTPLPTVNERDTENHTSVDGYTEPHIQPTKSSSRQNIPRCRNSITSATDEQPHIGNY
RLQKTIGKGNFAKVKLARHVLTGREVAVKIIDKTQLNPTSLQKLFREVRIMKILNHPNIV
KLFEVIETEKTLYLVMEYASGGEVFDYLVAHGRMKEKEARAKFRQIVSAVQYCHQKYIVH
RDLKAENLLLDGDMNIKIADFGFSNEFTVGNKLDTFCGSPPYAAPELFQGKKYDGPEVDV
WSLGVILYTLVSGSLPFDGQNLKELRERVLRGKYRIPFYMSTDCENLLKKLLVLNPIKRG
SLEQIMKDRWMNVGHEEEELKPYTEPDPDFNDTKRIDIMVTMGFARDEINDALINQKYDE
VMATYILLGRKPPEFEGGESLSSGNLCQRSRPSSDLNNSTLQSPAHLKVQRSISANQKQR
RFSDHAGPSIPPAVSYTKRPQANSVESEQKEEWDKDVARKLGSTTVGSKSEMTASPLVGP
ERKKSSTIPSNNVYSGGSMARRNTYVCERTTDRYVALQNGKDSSLTEMSVSSISSAGSSV
ASAVPSARPRHQKSMSTSGHPIKVTLPTIKDGSEAYRPGTTQRVPAASPSAHSISTATPD
RTRFPRGSSSRSTFHGEQLRERRSVAYNGPPASPSHETGAFAHARRGTSTGIISKITSKF
VRRDPSEGEASGRTDTSRSTSGEPKERDKEEGKDSKPRSLRFTWSMKTTSSMDPNDMMRE
IRKVLDANNCDYEQKERFLLFCVHGDARQDSLVQWEMEVCKLPRLSLNGVRFKRISGTSI
AFKNIASKIANELKL
Number of residues
795
Molecular Weight
89001.84
Theoretical pI
Not Available
GO Classification
Functions
ATP binding / magnesium ion binding / phosphatidic acid binding / phosphatidylinositol-4,5-bisphosphate binding / phosphatidylserine binding / protein serine/threonine kinase activity / tau-protein kinase activity
Processes
cytoskeleton organization / establishment of cell polarity / intracellular signal transduction / microtubule cytoskeleton organization / neuron migration / protein phosphorylation / Wnt signaling pathway
Components
cytoplasm / cytoskeleton / microtubule cytoskeleton / plasma membrane
General Function
Serine/threonine-protein kinase involved in cell polarity and microtubule dynamics regulation. Phosphorylates DCX, MAP2, MAP4 and MAPT/TAU. Involved in cell polarity by phosphorylating the microtubule-associated proteins MAP2, MAP4 and MAPT/TAU at KXGS motifs, causing detachment from microtubules, and their disassembly. Involved in the regulation of neuronal migration through its dual activities in regulating cellular polarity and microtubule dynamics, possibly by phosphorylating and regulating DCX. Also acts as a positive regulator of the Wnt signaling pathway, probably by mediating phosphorylation of dishevelled proteins (DVL1, DVL2 and/or DVL3).
Specific Function
Atp binding
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0051837|Serine/threonine-protein kinase MARK1 (MARK1)
ATGTCGGCCCGGACGCCATTGCCGACGGTGAACGAGCGGGACACGGAAAATCATACATCT
GTGGATGGATATACTGAACCACACATCCAGCCTACCAAGTCGAGTAGCAGACAGAACATC
CCCCGGTGTAGAAACTCCATTACGTCAGCAACAGATGAACAGCCTCACATTGGAAATTAC
CGTTTACAAAAAACAATAGGGAAGGGAAATTTTGCCAAAGTCAAATTGGCAAGACACGTT
CTAACTGGTAGAGAGGTTGCTGTGAAAATAATAGACAAAACTCAGCTAAATCCTACCAGT
CTACAAAAGTTATTTCGAGAAGTACGAATAATGAAGATACTGAATCATCCTAATATAGTA
AAATTGTTTGAAGTTATTGAAACAGAGAAGACTCTCTATTTAGTCATGGAATACGCGAGT
GGGGGTGAAGTATTTGATTACTTAGTTGCCCATGGAAGAATGAAAGAGAAAGAGGCCCGT
GCAAAATTTAGGCAGATTGTATCTGCTGTACAGTATTGTCATCAAAAGTACATTGTTCAC
CGTGATCTTAAGGCTGAAAACCTTCTCCTTGATGGTGATATGAATATTAAAATTGCTGAC
TTTGGTTTTAGTAATGAATTTACAGTTGGGAACAAATTGGACACATTTTGTGGAAGCCCA
CCCTATGCTGCTCCCGAGCTTTTCCAAGGAAAGAAGTATGATGGGCCTGAAGTGGATGTG
TGGAGTCTGGGCGTCATTCTCTATACATTAGTCAGTGGCTCCTTGCCTTTCGATGGCCAG
AATTTAAAGGAACTGCGAGAGCGAGTTTTACGAGGGAAGTACCGTATTCCCTTCTATATG
TCCACAGACTGTGAAAATCTTCTGAAGAAATTATTAGTCCTGAATCCAATAAAGAGAGGC
AGCTTGGAACAAATAATGAAAGATCGATGGATGAATGTTGGTCATGAAGAGGAAGAACTA
AAGCCATATACTGAGCCTGATCCGGATTTCAATGACACAAAAAGAATAGACATTATGGTC
ACCATGGGCTTTGCACGAGATGAAATAAATGATGCCTTAATAAATCAGAAGTATGATGAA
GTTATGGCTACTTATATTCTTCTAGGTAGAAAACCACCTGAATTTGAAGGTGGTGAATCG
TTATCCAGTGGAAACTTGTGTCAGAGGTCCCGGCCCAGTAGTGACTTAAACAACAGCACT
CTTCAGTCCCCTGCTCACCTGAAGGTCCAGAGAAGTATCTCAGCAAATCAGAAGCAGCGG
CGTTTCAGTGATCATGCTGGTCCATCCATTCCTCCTGCTGTATCATATACCAAAAGACCT
CAGGCTAACAGTGTGGAAAGTGAACAGAAAGAGGAGTGGGACAAAGATGTGGCTCGAAAA
CTTGGCAGCACAACAGTTGGATCAAAAAGCGAGATGACTGCAAGCCCTCTTGTAGGGCCA
GAGAGGAAAAAATCTTCAACTATTCCAAGTAACAATGTGTATTCTGGAGGTAGCATGGCA
AGAAGGAATACATATGTCTGTGAAAGGACCACAGATCGATACGTAGCATTGCAGAATGGA
AAAGACAGCAGCCTTACGGAGATGTCTGTGAGTAGCATATCTTCTGCAGGCTCTTCTGTG
GCCTCTGCTGTCCCCTCAGCACGACCCCGCCACCAGAAGTCCATGTCCACTTCTGGTCAT
CCTATTAAAGTCACACTGCCAACCATTAAAGACGGCTCTGAAGCTTACCGGCCTGGTACA
ACCCAGAGAGTGCCTGCTGCTTCCCCATCTGCTCACAGTATTAGTACTGCGACTCCAGAC
CGGACCCGTTTTCCCCGAGGGAGCTCAAGCCGAAGCACTTTCCATGGTGAACAGCTCCGG
GAGCGACGCAGCGTTGCTTATAATGGGCCACCTGCTTCACCATCCCATGAAACGGGTGCA
TTTGCACATGCCAGAAGGGGAACGTCAACTGGTATAATAAGCAAAATCACATCCAAATTT
GTTCGCAGGGATCCAAGTGAAGGCGAAGCCAGTGGCAGAACCGACACCTCAAGAAGTACA
TCAGGGGAACCAAAAGAAAGAGACAAGGAAGAGGGTAAAGATTCTAAGCCGCGTTCTTTG
CGGTTCACATGGAGTATGAAGACCACTAGTTCAATGGACCCTAATGACATGATGAGAGAA
ATCCGAAAAGTGTTAGATGCAAATAACTGTGATTATGAGCAAAAAGAGAGATTTTTGCTT
TTCTGTGTCCATGGAGACGCTAGACAGGATAGCCTCGTGCAGTGGGAGATGGAAGTCTGC
AAGTTGCCACGACTGTCACTTAATGGGGTTCGCTTCAAGCGAATATCTGGGACATCTATT
GCCTTTAAGAACATTGCATCAAAAATAGCAAATGAGCTTAAGCTGTAA
Chromosome Location
1
Locus
1q41
External Identifiers
ResourceLink
UniProtKB IDQ9P0L2
UniProtKB Entry NameMARK1_HUMAN
HGNC IDHGNC:6896
General References
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  2. Nagase T, Kikuno R, Ishikawa K, Hirosawa M, Ohara O: Prediction of the coding sequences of unidentified human genes. XVII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. DNA Res. 2000 Apr 28;7(2):143-50. [Article]
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  6. Drewes G, Ebneth A, Preuss U, Mandelkow EM, Mandelkow E: MARK, a novel family of protein kinases that phosphorylate microtubule-associated proteins and trigger microtubule disruption. Cell. 1997 Apr 18;89(2):297-308. [Article]
  7. Chin JY, Knowles RB, Schneider A, Drewes G, Mandelkow EM, Hyman BT: Microtubule-affinity regulating kinase (MARK) is tightly associated with neurofibrillary tangles in Alzheimer brain: a fluorescence resonance energy transfer study. J Neuropathol Exp Neurol. 2000 Nov;59(11):966-71. [Article]
  8. Sun TQ, Lu B, Feng JJ, Reinhard C, Jan YN, Fantl WJ, Williams LT: PAR-1 is a Dishevelled-associated kinase and a positive regulator of Wnt signalling. Nat Cell Biol. 2001 Jul;3(7):628-36. [Article]
  9. Kojima Y, Miyoshi H, Clevers HC, Oshima M, Aoki M, Taketo MM: Suppression of tubulin polymerization by the LKB1-microtubule-associated protein/microtubule affinity-regulating kinase signaling. J Biol Chem. 2007 Aug 10;282(32):23532-40. Epub 2007 Jun 15. [Article]
  10. Maussion G, Carayol J, Lepagnol-Bestel AM, Tores F, Loe-Mie Y, Milbreta U, Rousseau F, Fontaine K, Renaud J, Moalic JM, Philippi A, Chedotal A, Gorwood P, Ramoz N, Hager J, Simonneau M: Convergent evidence identifying MAP/microtubule affinity-regulating kinase 1 (MARK1) as a susceptibility gene for autism. Hum Mol Genet. 2008 Aug 15;17(16):2541-51. doi: 10.1093/hmg/ddn154. Epub 2008 May 20. [Article]
  11. 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. [Article]
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  15. Matenia D, Mandelkow EM: The tau of MARK: a polarized view of the cytoskeleton. Trends Biochem Sci. 2009 Jul;34(7):332-42. doi: 10.1016/j.tibs.2009.03.008. Epub 2009 Jun 24. [Article]
  16. Marx A, Nugoor C, Panneerselvam S, Mandelkow E: Structure and function of polarity-inducing kinase family MARK/Par-1 within the branch of AMPK/Snf1-related kinases. FASEB J. 2010 Jun;24(6):1637-48. doi: 10.1096/fj.09-148064. Epub 2010 Jan 13. [Article]
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  18. 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]
  19. 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]
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  21. Moravcevic K, Mendrola JM, Schmitz KR, Wang YH, Slochower D, Janmey PA, Lemmon MA: Kinase associated-1 domains drive MARK/PAR1 kinases to membrane targets by binding acidic phospholipids. Cell. 2010 Dec 10;143(6):966-77. doi: 10.1016/j.cell.2010.11.028. [Article]
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails