Serine/threonine-protein kinase MARK2

Details

Name
Serine/threonine-protein kinase MARK2
Synonyms
  • 2.7.11.1
  • ELKL motif kinase 1
  • EMK-1
  • EMK1
  • MAP/microtubule affinity-regulating kinase 2
  • Par-1b
  • PAR1 homolog
  • PAR1 homolog b
  • Par1b
Gene Name
MARK2
Organism
Humans
Amino acid sequence
>lcl|BSEQ0051838|Serine/threonine-protein kinase MARK2
MSSARTPLPTLNERDTEQPTLGHLDSKPSSKSNMIRGRNSATSADEQPHIGNYRLLKTIG
KGNFAKVKLARHILTGKEVAVKIIDKTQLNSSSLQKLFREVRIMKVLNHPNIVKLFEVIE
TEKTLYLVMEYASGGEVFDYLVAHGRMKEKEARAKFRQIVSAVQYCHQKFIVHRDLKAEN
LLLDADMNIKIADFGFSNEFTFGNKLDTFCGSPPYAAPELFQGKKYDGPEVDVWSLGVIL
YTLVSGSLPFDGQNLKELRERVLRGKYRIPFYMSTDCENLLKKFLILNPSKRGTLEQIMK
DRWMNVGHEDDELKPYVEPLPDYKDPRRTELMVSMGYTREEIQDSLVGQRYNEVMATYLL
LGYKSSELEGDTITLKPRPSADLTNSSAPSPSHKVQRSVSANPKQRRFSDQAAGPAIPTS
NSYSKKTQSNNAENKRPEEDRESGRKASSTAKVPASPLPGLERKKTTPTPSTNSVLSTST
NRSRNSPLLERASLGQASIQNGKDSLTMPGSRASTASASAAVSAARPRQHQKSMSASVHP
NKASGLPPTESNCEVPRPSTAPQRVPVASPSAHNISSSGGAPDRTNFPRGVSSRSTFHAG
QLRQVRDQQNLPYGVTPASPSGHSQGRRGASGSIFSKFTSKFVRRNLSFRFARRNLNEPE
SKDRVETLRPHVVGSGGNDKEKEEFREAKPRSLRFTWSMKTTSSMEPNEMMREIRKVLDA
NSCQSELHEKYMLLCMHGTPGHEDFVQWEMEVCKLPRLSLNGVRFKRISGTSMAFKNIAS
KIANELKL
Number of residues
788
Molecular Weight
87909.995
Theoretical pI
Not Available
GO Classification
Functions
ATP binding / cadherin binding / lipid binding / magnesium ion binding / protein kinase activator activity / protein serine/threonine kinase activity / RNA binding / tau-protein kinase activity
Processes
activation of protein kinase activity / autophagy of mitochondrion / establishment of cell polarity / establishment or maintenance of epithelial cell apical/basal polarity / intracellular signal transduction / microtubule cytoskeleton organization / mitochondrion localization / neuron migration / peptidyl-threonine phosphorylation / positive regulation of neuron projection development / protein autophosphorylation / protein phosphorylation / regulation of axonogenesis / regulation of cytoskeleton organization / Wnt signaling pathway
Components
actin filament / lateral plasma membrane / membrane / microtubule bundle / mitochondrion / nucleoplasm / plasma membrane
General Function
Serine/threonine-protein kinase involved in cell polarity and microtubule dynamics regulation. Phosphorylates CRTC2/TORC2, DCX, HDAC7, KIF13B, MAP2, MAP4, MAPT/TAU, and RAB11FIP2. Plays a key role in cell polarity by phosphorylating the microtubule-associated proteins MAP2, MAP4 and MAPT/TAU at KXGS motifs, causing detachment from microtubules, and their disassembly. Regulates epithelial cell polarity by phosphorylating RAB11FIP2. Involved in the regulation of neuronal migration through its dual activities in regulating cellular polarity and microtubule dynamics, possibly by phosphorylating and regulating DCX. Regulates axogenesis by phosphorylating KIF13B, promoting interaction between KIF13B and 14-3-3 and inhibiting microtubule-dependent accumulation of KIF13B. Also required for neurite outgrowth and establishment of neuronal polarity. Regulates localization and activity of some histone deacetylases by mediating phosphorylation of HDAC7, promoting subsequent interaction between HDAC7 and 14-3-3 and export from the nucleus. Also acts as a positive regulator of the Wnt signaling pathway, probably by mediating phosphorylation of dishevelled proteins (DVL1, DVL2 and/or DVL3). Modulates the developmental decision to build a columnar versus a hepatic epithelial cell apparently by promoting a switch from a direct to a transcytotic mode of apical protein delivery. Essential for the asymmetric development of membrane domains of polarized epithelial cells.
Specific Function
Atp binding
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0051839|Serine/threonine-protein kinase MARK2 (MARK2)
ATGTCCAGCGCTCGGACCCCCCTACCCACGCTGAACGAGAGGGACACGGAGCAGCCCACC
TTGGGACACCTTGACTCCAAGCCCAGCAGTAAGTCCAACATGATTCGGGGCCGCAACTCA
GCCACCTCTGCTGATGAGCAGCCCCACATTGGAAACTACCGGCTCCTCAAGACCATTGGC
AAGGGTAATTTTGCCAAGGTGAAGTTGGCCCGACACATCCTGACTGGGAAAGAGGTAGCT
GTGAAGATCATTGACAAGACTCAACTGAACTCCTCCAGCCTCCAGAAACTATTCCGCGAA
GTAAGAATAATGAAGGTTTTGAATCATCCCAACATAGTTAAATTATTTGAAGTGATTGAG
ACTGAGAAAACGCTCTACCTTGTCATGGAGTACGCTAGTGGCGGAGAGGTATTTGATTAC
CTAGTGGCTCATGGCAGGATGAAAGAAAAAGAGGCTCGAGCCAAATTCCGCCAGATAGTG
TCTGCTGTGCAGTACTGTCACCAGAAGTTTATTGTCCATAGAGACTTAAAGGCAGAAAAC
CTGCTCTTGGATGCTGATATGAACATCAAGATTGCAGACTTTGGCTTCAGCAATGAATTC
ACCTTTGGGAACAAGCTGGACACCTTCTGTGGCAGTCCCCCTTATGCTGCCCCAGAACTC
TTCCAGGGCAAAAAATATGATGGACCCGAGGTGGATGTGTGGAGCCTAGGAGTTATCCTC
TATACACTGGTCAGCGGATCCCTGCCTTTTGATGGACAGAACCTCAAGGAGCTGCGGGAA
CGGGTACTGAGGGGAAAATACCGTATTCCATTCTACATGTCCACGGACTGTGAAAACCTG
CTTAAGAAATTTCTCATTCTTAATCCCAGCAAGAGAGGCACTTTAGAGCAAATCATGAAA
GATCGATGGATGAATGTGGGTCACGAAGATGATGAACTAAAGCCTTACGTGGAGCCACTC
CCTGACTACAAGGACCCCCGGCGGACAGAGCTGATGGTGTCCATGGGTTATACACGGGAA
GAGATCCAGGACTCGCTGGTGGGCCAGAGATACAACGAGGTGATGGCCACCTATCTGCTC
CTGGGCTACAAGAGCTCCGAGCTGGAAGGCGACACCATCACCCTGAAACCCCGGCCTTCA
GCTGATCTGACCAATAGCAGCGCCCCATCCCCATCCCACAAGGTACAGCGCAGCGTGTCG
GCCAATCCCAAGCAGCGGCGCTTCAGCGACCAGGCAGCTGGTCCTGCCATTCCCACCTCT
AATTCTTACTCTAAGAAGACTCAGAGTAACAACGCAGAAAATAAGCGGCCTGAGGAGGAC
CGGGAGTCAGGGCGGAAAGCCAGCAGCACAGCCAAGGTGCCTGCCAGCCCCCTGCCCGGT
CTGGAGAGGAAGAAGACCACCCCAACCCCCTCCACGAACAGCGTCCTCTCCACCAGCACA
AATCGAAGCAGGAATTCCCCACTTTTGGAGCGGGCCAGCCTCGGCCAGGCCTCCATCCAG
AATGGCAAAGACAGCCTAACCATGCCAGGGTCCCGGGCCTCCACGGCTTCTGCTTCTGCC
GCAGTCTCTGCGGCCCGGCCCCGCCAGCACCAGAAATCCATGTCGGCCTCCGTGCACCCC
AACAAGGCCTCTGGGCTGCCCCCCACGGAGAGTAACTGTGAGGTGCCGCGGCCCAGCACA
GCCCCCCAGCGTGTCCCTGTTGCCTCCCCATCCGCCCACAACATCAGCAGCAGTGGTGGA
GCCCCAGACCGAACTAACTTCCCCCGGGGTGTGTCCAGCCGAAGCACCTTCCATGCTGGG
CAGCTCCGACAGGTGCGGGACCAGCAGAATTTGCCCTACGGTGTGACCCCAGCCTCTCCC
TCTGGCCACAGCCAGGGCCGGCGGGGGGCCTCTGGGAGCATCTTCAGCAAGTTCACCTCC
AAGTTTGTACGCAGAAATCTGTCTTTCAGGTTTGCCAGAAGGAACCTGAATGAACCTGAA
AGCAAAGACCGAGTGGAGACGCTCAGACCTCACGTGGTGGGCAGTGGCGGCAACGACAAA
GAAAAGGAAGAATTTCGGGAGGCCAAGCCCCGCTCCCTCCGCTTCACGTGGAGTATGAAG
ACCACGAGCTCCATGGAGCCCAACGAGATGATGCGGGAGATCCGCAAGGTGCTGGACGCG
AACAGCTGCCAGAGCGAGCTGCATGAGAAGTACATGCTGCTGTGCATGCACGGCACGCCG
GGCCACGAGGACTTCGTGCAGTGGGAGATGGAGGTGTGCAAACTGCCGCGGCTCTCTCTC
AACGGGGTTCGATTTAAGCGGATATCGGGCACCTCCATGGCCTTCAAAAACATTGCCTCC
AAAATAGCCAACGAGCTGAAGCTTTAA
Chromosome Location
11
Locus
11q13.1
External Identifiers
ResourceLink
UniProtKB IDQ7KZI7
UniProtKB Entry NameMARK2_HUMAN
HGNC IDHGNC:3332
General References
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  4. 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]
  5. Schultz SJ, Nigg EA: Identification of 21 novel human protein kinases, including 3 members of a family related to the cell cycle regulator nimA of Aspergillus nidulans. Cell Growth Differ. 1993 Oct;4(10):821-30. [Article]
  6. Biernat J, Wu YZ, Timm T, Zheng-Fischhofer Q, Mandelkow E, Meijer L, Mandelkow EM: Protein kinase MARK/PAR-1 is required for neurite outgrowth and establishment of neuronal polarity. Mol Biol Cell. 2002 Nov;13(11):4013-28. [Article]
  7. Hueso M, Beltran V, Moreso F, Ciriero E, Fulladosa X, Grinyo JM, Seron D, Navarro E: Splicing alterations in human renal allografts: detection of a new splice variant of protein kinase Par1/Emk1 whose expression is associated with an increase of inflammation in protocol biopsies of transplanted patients. Biochim Biophys Acta. 2004 May 24;1689(1):58-65. [Article]
  8. 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]
  9. Cohen D, Rodriguez-Boulan E, Musch A: Par-1 promotes a hepatic mode of apical protein trafficking in MDCK cells. Proc Natl Acad Sci U S A. 2004 Sep 21;101(38):13792-7. Epub 2004 Sep 13. [Article]
  10. Hurov JB, Watkins JL, Piwnica-Worms H: Atypical PKC phosphorylates PAR-1 kinases to regulate localization and activity. Curr Biol. 2004 Apr 20;14(8):736-41. [Article]
  11. Suzuki A, Hirata M, Kamimura K, Maniwa R, Yamanaka T, Mizuno K, Kishikawa M, Hirose H, Amano Y, Izumi N, Miwa Y, Ohno S: aPKC acts upstream of PAR-1b in both the establishment and maintenance of mammalian epithelial polarity. Curr Biol. 2004 Aug 24;14(16):1425-35. [Article]
  12. 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. [Article]
  13. Ducharme NA, Hales CM, Lapierre LA, Ham AJ, Oztan A, Apodaca G, Goldenring JR: MARK2/EMK1/Par-1Balpha phosphorylation of Rab11-family interacting protein 2 is necessary for the timely establishment of polarity in Madin-Darby canine kidney cells. Mol Biol Cell. 2006 Aug;17(8):3625-37. Epub 2006 Jun 14. [Article]
  14. Dequiedt F, Martin M, Von Blume J, Vertommen D, Lecomte E, Mari N, Heinen MF, Bachmann M, Twizere JC, Huang MC, Rider MH, Piwnica-Worms H, Seufferlein T, Kettmann R: New role for hPar-1 kinases EMK and C-TAK1 in regulating localization and activity of class IIa histone deacetylases. Mol Cell Biol. 2006 Oct;26(19):7086-102. [Article]
  15. Beausoleil SA, Villen J, Gerber SA, Rush J, Gygi SP: A probability-based approach for high-throughput protein phosphorylation analysis and site localization. Nat Biotechnol. 2006 Oct;24(10):1285-92. Epub 2006 Sep 10. [Article]
  16. Saadat I, Higashi H, Obuse C, Umeda M, Murata-Kamiya N, Saito Y, Lu H, Ohnishi N, Azuma T, Suzuki A, Ohno S, Hatakeyama M: Helicobacter pylori CagA targets PAR1/MARK kinase to disrupt epithelial cell polarity. Nature. 2007 May 17;447(7142):330-3. [Article]
  17. 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]
  18. 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. [Article]
  19. 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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  29. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [Article]
  30. 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]
  31. Sato Y, Akitsu M, Amano Y, Yamashita K, Ide M, Shimada K, Yamashita A, Hirano H, Arakawa N, Maki T, Hayashi I, Ohno S, Suzuki A: The novel PAR-1-binding protein MTCL1 has crucial roles in organizing microtubules in polarizing epithelial cells. J Cell Sci. 2013 Oct 15;126(Pt 20):4671-83. doi: 10.1242/jcs.127845. Epub 2013 Jul 31. [Article]
  32. 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]
  33. Nesic D, Miller MC, Quinkert ZT, Stein M, Chait BT, Stebbins CE: Helicobacter pylori CagA inhibits PAR1-MARK family kinases by mimicking host substrates. Nat Struct Mol Biol. 2010 Jan;17(1):130-2. doi: 10.1038/nsmb.1705. Epub 2009 Dec 6. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails