MAP/microtubule affinity-regulating kinase 3

Details

Name

MAP/microtubule affinity-regulating kinase 3

Synonyms

• 2.7.11.1
• C-TAK1
• Cdc25C-associated protein kinase 1
• CTAK1
• ELKL motif kinase 2
• EMK-2
• EMK2
• Par-1a
• Protein kinase STK10
• Ser/Thr protein kinase PAR-1
• Serine/threonine-protein kinase p78

Gene Name

MARK3

Organism

Humans

Amino acid sequence

>lcl|BSEQ0051840|MAP/microtubule affinity-regulating kinase 3
MSTRTPLPTVNERDTENHTSHGDGRQEVTSRTSRSGARCRNSIASCADEQPHIGNYRLLK
TIGKGNFAKVKLARHILTGREVAIKIIDKTQLNPTSLQKLFREVRIMKILNHPNIVKLFE
VIETEKTLYLIMEYASGGEVFDYLVAHGRMKEKEARSKFRQIVSAVQYCHQKRIVHRDLK
AENLLLDADMNIKIADFGFSNEFTVGGKLDTFCGSPPYAAPELFQGKKYDGPEVDVWSLG
VILYTLVSGSLPFDGQNLKELRERVLRGKYRIPFYMSTDCENLLKRFLVLNPIKRGTLEQ
IMKDRWINAGHEEDELKPFVEPELDISDQKRIDIMVGMGYSQEEIQESLSKMKYDEITAT
YLLLGRKSSELDASDSSSSSNLSLAKVRPSSDLNNSTGQSPHHKVQRSVSSSQKQRRYSD
HAGPAIPSVVAYPKRSQTSTADSDLKEDGISSRKSSGSAVGGKGIAPASPMLGNASNPNK
ADIPERKKSSTVPSSNTASGGMTRRNTYVCSERTTADRHSVIQNGKENSTIPDQRTPVAS
THSISSAATPDRIRFPRGTASRSTFHGQPRERRTATYNGPPASPSLSHEATPLSQTRSRG
STNLFSKLTSKLTRRNMSFRFIKRLPTEYERNGRYEGSSRNVSAEQKDENKEAKPRSLRF
TWSMKTTSSMDPGDMMREIRKVLDANNCDYEQRERFLLFCVHGDGHAENLVQWEMEVCKL
PRLSLNGVRFKRISGTSIAFKNIASKIANELKL

Number of residues

753

Molecular Weight

84427.71

Theoretical pI

Not Available

GO Classification

Functions

ATP binding / protein serine/threonine kinase activity

Processes

establishment of cell polarity / MAPK cascade / microtubule cytoskeleton organization / negative regulation of hippo signaling

Components

cytosol / extracellular exosome / plasma membrane

General Function

Involved in the specific phosphorylation of microtubule-associated proteins for tau, MAP2 and MAP4. Phosphorylates CDC25C on 'Ser-216'. 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 (PubMed:16980613). Negatively regulates the Hippo signaling pathway and antagonizes the phosphorylation of LATS1. Cooperates with DLG5 to inhibit the kinase activity of STK3/MST2 toward LATS1 (PubMed:28087714).

Specific Function

Atp binding

Pfam Domain Function

• Pkinase (PF00069)
• KA1 (PF02149)
• UBA (PF00627)

Transmembrane Regions

Not Available

Cellular Location

Cell membrane

Gene sequence

>lcl|BSEQ0051841|MAP/microtubule affinity-regulating kinase 3 (MARK3)
ATGTCCACTAGGACCCCATTGCCAACGGTGAATGAACGAGACACTGAAAACCACACGTCA
CATGGAGATGGGCGTCAAGAAGTTACCTCTCGTACCAGCCGCTCAGGAGCTCGGTGTAGA
AACTCTATAGCCTCCTGTGCAGATGAACAACCTCACATCGGAAACTACAGACTGTTGAAA
ACAATCGGCAAGGGGAATTTTGCAAAAGTAAAATTGGCAAGACATATCCTTACAGGCAGA
GAGGTTGCAATAAAAATAATTGACAAAACTCAGTTGAATCCAACAAGTCTACAAAAGCTC
TTCAGAGAAGTAAGAATAATGAAGATTTTAAATCATCCCAATATAGTGAAGTTATTCGAA
GTCATTGAAACTGAAAAAACACTCTACCTAATCATGGAATATGCAAGTGGAGGTGAAGTA
TTTGACTATTTGGTTGCACATGGCAGGATGAAGGAAAAAGAAGCAAGATCTAAATTTAGA
CAGATTGTGTCTGCAGTTCAATACTGCCATCAGAAACGGATCGTACATCGAGACCTCAAG
GCTGAAAATCTATTGTTAGATGCCGATATGAACATTAAAATAGCAGATTTCGGTTTTAGC
AATGAATTTACTGTTGGCGGTAAACTCGACACGTTTTGTGGCAGTCCTCCATACGCAGCA
CCTGAGCTCTTCCAGGGCAAGAAATATGACGGGCCAGAAGTGGATGTGTGGAGTCTGGGG
GTCATTTTATACACACTAGTCAGTGGCTCACTTCCCTTTGATGGGCAAAACCTAAAGGAA
CTGAGAGAGAGAGTATTAAGAGGGAAATACAGAATTCCCTTCTACATGTCTACAGACTGT
GAAAACCTTCTCAAACGTTTCCTGGTGCTAAATCCAATTAAACGCGGCACTCTAGAGCAA
ATCATGAAGGACAGGTGGATCAATGCAGGGCATGAAGAAGATGAACTCAAACCATTTGTT
GAACCAGAGCTAGACATCTCAGACCAAAAAAGAATAGATATTATGGTGGGAATGGGATAT
TCACAAGAAGAAATTCAAGAATCTCTTAGTAAGATGAAATACGATGAAATCACAGCTACA
TATTTGTTATTGGGGAGAAAATCTTCAGAGCTGGATGCTAGTGATTCCAGTTCTAGCAGC
AATCTTTCACTTGCTAAGGTTAGGCCGAGCAGTGATCTCAACAACAGTACTGGCCAGTCT
CCTCACCACAAAGTGCAGAGAAGTGTTTCTTCAAGCCAAAAGCAAAGACGCTACAGTGAC
CATGCTGGACCAGCTATTCCTTCTGTTGTGGCGTATCCGAAAAGGAGTCAGACCAGCACT
GCAGATAGTGACCTCAAAGAAGATGGAATTTCCTCCCGGAAATCAAGTGGCAGTGCTGTT
GGAGGAAAGGGAATTGCTCCAGCCAGTCCCATGCTTGGGAATGCAAGTAATCCTAATAAG
GCGGATATTCCTGAACGCAAGAAAAGCTCCACTGTCCCTAGTAGTAACACAGCATCTGGT
GGAATGACACGACGAAATACTTATGTTTGCAGTGAGAGAACTACAGCTGATAGACACTCA
GTGATTCAGAATGGCAAAGAAAACAGCACTATTCCTGATCAGAGAACTCCAGTTGCTTCA
ACACACAGTATCAGTAGTGCAGCCACCCCAGATCGAATCCGCTTCCCAAGAGGCACTGCC
AGTCGTAGCACTTTCCACGGCCAGCCCCGGGAACGGCGAACCGCAACATATAATGGCCCT
CCTGCCTCTCCCAGCCTGTCCCATGAAGCCACACCATTGTCCCAGACTCGAAGCCGAGGC
TCCACTAATCTCTTTAGTAAATTAACTTCAAAACTCACAAGGAGAAACATGTCATTCAGG
TTTATCAAAAGGCTTCCAACTGAATATGAGAGGAACGGGAGATATGAGGGCTCAAGTCGC
AATGTATCTGCTGAGCAAAAAGATGAAAACAAAGAAGCAAAGCCTCGATCCCTACGCTTC
ACCTGGAGCATGAAAACCACTAGTTCAATGGATCCCGGGGACATGATGCGGGAAATCCGC
AAAGTGTTGGACGCCAATAACTGCGACTATGAGCAGAGGGAGCGCTTCTTGCTCTTCTGC
GTCCACGGAGATGGGCACGCGGAGAACCTCGTGCAGTGGGAAATGGAAGTGTGCAAGCTG
CCAAGACTGTCTCTGAACGGGGTCCGGTTTAAGCGGATATCGGGGACATCCATAGCCTTC
AAAAATATTGCTTCCAAAATTGCCAATGAGCTAAAGCTGTAA

Chromosome Location

14

Locus

14q32.32-q32.33

External Identifiers

Resource	Link
UniProtKB ID	P27448
UniProtKB Entry Name	MARK3_HUMAN
HGNC ID	HGNC:6897

General References

1. Peng CY, Graves PR, Ogg S, Thoma RS, Byrnes MJ 3rd, Wu Z, Stephenson MT, Piwnica-Worms H: C-TAK1 protein kinase phosphorylates human Cdc25C on serine 216 and promotes 14-3-3 protein binding. Cell Growth Differ. 1998 Mar;9(3):197-208. [Article]
2. 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]
3. Heilig R, Eckenberg R, Petit JL, Fonknechten N, Da Silva C, Cattolico L, Levy M, Barbe V, de Berardinis V, Ureta-Vidal A, Pelletier E, Vico V, Anthouard V, Rowen L, Madan A, Qin S, Sun H, Du H, Pepin K, Artiguenave F, Robert C, Cruaud C, Bruls T, Jaillon O, Friedlander L, Samson G, Brottier P, Cure S, Segurens B, Aniere F, Samain S, Crespeau H, Abbasi N, Aiach N, Boscus D, Dickhoff R, Dors M, Dubois I, Friedman C, Gouyvenoux M, James R, Madan A, Mairey-Estrada B, Mangenot S, Martins N, Menard M, Oztas S, Ratcliffe A, Shaffer T, Trask B, Vacherie B, Bellemere C, Belser C, Besnard-Gonnet M, Bartol-Mavel D, Boutard M, Briez-Silla S, Combette S, Dufosse-Laurent V, Ferron C, Lechaplais C, Louesse C, Muselet D, Magdelenat G, Pateau E, Petit E, Sirvain-Trukniewicz P, Trybou A, Vega-Czarny N, Bataille E, Bluet E, Bordelais I, Dubois M, Dumont C, Guerin T, Haffray S, Hammadi R, Muanga J, Pellouin V, Robert D, Wunderle E, Gauguet G, Roy A, Sainte-Marthe L, Verdier J, Verdier-Discala C, Hillier L, Fulton L, McPherson J, Matsuda F, Wilson R, Scarpelli C, Gyapay G, Wincker P, Saurin W, Quetier F, Waterston R, Hood L, Weissenbach J: The DNA sequence and analysis of human chromosome 14. Nature. 2003 Feb 6;421(6923):601-7. Epub 2003 Jan 1. [Article]
4. 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]
5. 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]
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. 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]
8. 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]
9. 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]
10. 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]
11. 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]
12. 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]
13. 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]
14. 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]
15. 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]
16. 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]
17. 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]
18. Kwan J, Sczaniecka A, Heidary Arash E, Nguyen L, Chen CC, Ratkovic S, Klezovitch O, Attisano L, McNeill H, Emili A, Vasioukhin V: DLG5 connects cell polarity and Hippo signaling protein networks by linking PAR-1 with MST1/2. Genes Dev. 2016 Dec 15;30(24):2696-2709. doi: 10.1101/gad.284539.116. [Article]
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Drug Relations

Drug Relations

DrugBank ID	Name	Drug group	Pharmacological action?	Actions	Details
DB12010	Fostamatinib	approved, investigational	unknown	inhibitor	Details