MARK2_HUMAN
ID MARK2_HUMAN Reviewed; 788 AA.
AC Q7KZI7; Q15449; Q15524; Q5XGA3; Q68A18; Q96HB3; Q96RG0;
DT 12-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 12-APR-2005, sequence version 2.
DT 03-AUG-2022, entry version 180.
DE RecName: Full=Serine/threonine-protein kinase MARK2;
DE EC=2.7.11.1;
DE EC=2.7.11.26;
DE AltName: Full=ELKL motif kinase 1;
DE Short=EMK-1;
DE AltName: Full=MAP/microtubule affinity-regulating kinase 2;
DE AltName: Full=PAR1 homolog;
DE AltName: Full=PAR1 homolog b;
DE Short=Par-1b;
DE Short=Par1b;
GN Name=MARK2 {ECO:0000312|EMBL:AAH08771.2}; Synonyms=EMK1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1] {ECO:0000305, ECO:0000312|EMBL:CAA66229.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3), AND TISSUE SPECIFICITY.
RC TISSUE=Colon {ECO:0000312|EMBL:CAA66229.1};
RX PubMed=9730619; DOI=10.1159/000015046;
RA Espinosa L., Navarro E.;
RT "Human serine/threonine protein kinase EMK1: genome structure and cDNA
RT cloning of isoforms produced by alternative splicing.";
RL Cytogenet. Cell Genet. 81:278-282(1998).
RN [2] {ECO:0000305, ECO:0000312|EMBL:BAD37141.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5).
RC TISSUE=Kidney {ECO:0000312|EMBL:CAA66229.1};
RA Sugiyama A., Inoue H., Oka M.;
RL Submitted (AUG-2004) to the EMBL/GenBank/DDBJ databases.
RN [3] {ECO:0000305, ECO:0000312|EMBL:BAD37141.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 6).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [5] {ECO:0000305, ECO:0000312|EMBL:AAH08771.2}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 11-755 (ISOFORM 1).
RC TISSUE=Kidney {ECO:0000312|EMBL:AAH84540.1}, and
RC Placenta {ECO:0000312|EMBL:AAH08771.2};
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6] {ECO:0000305, ECO:0000312|EMBL:AAK82368.1}
RP NUCLEOTIDE SEQUENCE [MRNA] OF 28-788 (ISOFORM 4), AND FUNCTION.
RX PubMed=11433294; DOI=10.1038/35083016;
RA Sun T.-Q., Lu B., Feng J.-J., Reinhard C., Jan Y.N., Fantl W.J.,
RA Williams L.T.;
RT "PAR-1 is a Dishevelled-associated kinase and a positive regulator of Wnt
RT signalling.";
RL Nat. Cell Biol. 3:628-636(2001).
RN [7] {ECO:0000305, ECO:0000312|EMBL:CAA80914.1}
RP NUCLEOTIDE SEQUENCE [MRNA] OF 190-237.
RX PubMed=8274451;
RA Schultz S.J., Nigg E.A.;
RT "Identification of 21 novel human protein kinases, including 3 members of a
RT family related to the cell cycle regulator nimA of Aspergillus nidulans.";
RL Cell Growth Differ. 4:821-830(1993).
RN [8]
RP FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=12429843; DOI=10.1091/mbc.02-03-0046;
RA Biernat J., Wu Y.Z., Timm T., Zheng-Fischhofer Q., Mandelkow E., Meijer L.,
RA Mandelkow E.M.;
RT "Protein kinase MARK/PAR-1 is required for neurite outgrowth and
RT establishment of neuronal polarity.";
RL Mol. Biol. Cell 13:4013-4028(2002).
RN [9] {ECO:0000305}
RP FUNCTION, AND ALTERNATIVE PROMOTER USAGE.
RX PubMed=15158914; DOI=10.1016/j.bbadis.2004.01.008;
RA Hueso M., Beltran V., Moreso F., Ciriero E., Fulladosa X., Grinyo J.M.,
RA Seron D., Navarro E.;
RT "Splicing alterations in human renal allografts: detection of a new splice
RT variant of protein kinase Par1/Emk1 whose expression is associated with an
RT increase of inflammation in protocol biopsies of transplanted patients.";
RL Biochim. Biophys. Acta 1689:58-65(2004).
RN [10] {ECO:0000305}
RP FUNCTION, ACTIVITY REGULATION, PHOSPHORYLATION AT THR-208, AND MUTAGENESIS
RP OF THR-208.
RX PubMed=14976552; DOI=10.1038/sj.emboj.7600110;
RA Lizcano J.M., Goeransson O., Toth R., Deak M., Morrice N.A., Boudeau J.,
RA Hawley S.A., Udd L., Maekelae T.P., Hardie D.G., Alessi D.R.;
RT "LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily,
RT including MARK/PAR-1.";
RL EMBO J. 23:833-843(2004).
RN [11] {ECO:0000305}
RP FUNCTION.
RX PubMed=15365179; DOI=10.1073/pnas.0403684101;
RA Cohen D., Rodriguez-Boulan E., Musch A.;
RT "Par-1 promotes a hepatic mode of apical protein trafficking in MDCK
RT cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:13792-13797(2004).
RN [12]
RP PHOSPHORYLATION AT THR-596, MUTAGENESIS OF THR-596, AND SUBCELLULAR
RP LOCATION.
RX PubMed=15084291; DOI=10.1016/j.cub.2004.04.007;
RA Hurov J.B., Watkins J.L., Piwnica-Worms H.;
RT "Atypical PKC phosphorylates PAR-1 kinases to regulate localization and
RT activity.";
RL Curr. Biol. 14:736-741(2004).
RN [13] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT THR-596, MUTAGENESIS OF
RP THR-596, AND INTERACTION WITH YWHAZ.
RX PubMed=15324659; DOI=10.1016/j.cub.2004.08.021;
RA Suzuki A., Hirata M., Kamimura K., Maniwa R., Yamanaka T., Mizuno K.,
RA Kishikawa M., Hirose H., Amano Y., Izumi N., Miwa Y., Ohno S.;
RT "aPKC acts upstream of PAR-1b in both the establishment and maintenance of
RT mammalian epithelial polarity.";
RL Curr. Biol. 14:1425-1435(2004).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-486, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [15]
RP FUNCTION IN PHOSPHORYLATION OF RAB11FIP2.
RX PubMed=16775013; DOI=10.1091/mbc.e05-08-0736;
RA Ducharme N.A., Hales C.M., Lapierre L.A., Ham A.J., Oztan A., Apodaca G.,
RA Goldenring J.R.;
RT "MARK2/EMK1/Par-1Balpha phosphorylation of Rab11-family interacting protein
RT 2 is necessary for the timely establishment of polarity in Madin-Darby
RT canine kidney cells.";
RL Mol. Biol. Cell 17:3625-3637(2006).
RN [16]
RP FUNCTION IN PHOSPHORYLATION OF HDAC7.
RX PubMed=16980613; DOI=10.1128/mcb.00231-06;
RA Dequiedt F., Martin M., Von Blume J., Vertommen D., Lecomte E., Mari N.,
RA Heinen M.F., Bachmann M., Twizere J.C., Huang M.C., Rider M.H.,
RA Piwnica-Worms H., Seufferlein T., Kettmann R.;
RT "New role for hPar-1 kinases EMK and C-TAK1 in regulating localization and
RT activity of class IIa histone deacetylases.";
RL Mol. Cell. Biol. 26:7086-7102(2006).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-456, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein phosphorylation
RT analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [18]
RP INTERACTION WITH H.PYLORI CAGA (MICROBIAL INFECTION).
RX PubMed=17507984; DOI=10.1038/nature05765;
RA Saadat I., Higashi H., Obuse C., Umeda M., Murata-Kamiya N., Saito Y.,
RA Lu H., Ohnishi N., Azuma T., Suzuki A., Ohno S., Hatakeyama M.;
RT "Helicobacter pylori CagA targets PAR1/MARK kinase to disrupt epithelial
RT cell polarity.";
RL Nature 447:330-333(2007).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-456 AND SER-486, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-456, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-409; SER-456; SER-486 AND
RP SER-493, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [22]
RP FUNCTION IN PHOSPHORYLATION OF CRTC2.
RX PubMed=18626018; DOI=10.1073/pnas.0800796105;
RA Jansson D., Ng A.C., Fu A., Depatie C., Al Azzabi M., Screaton R.A.;
RT "Glucose controls CREB activity in islet cells via regulated
RT phosphorylation of TORC2.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10161-10166(2008).
RN [23]
RP DOMAIN UBA.
RX PubMed=16396636; DOI=10.1042/bj20051844;
RA Jaleel M., Villa F., Deak M., Toth R., Prescott A.R., Van Aalten D.M.,
RA Alessi D.R.;
RT "The ubiquitin-associated domain of AMPK-related kinases regulates
RT conformation and LKB1-mediated phosphorylation and activation.";
RL Biochem. J. 394:545-555(2006).
RN [24]
RP INTERACTION WITH YWHAB; YWHAG AND YWHAQ.
RX PubMed=16959763; DOI=10.1074/mcp.m600147-mcp200;
RA Angrand P.O., Segura I., Voelkel P., Ghidelli S., Terry R., Brajenovic M.,
RA Vintersten K., Klein R., Superti-Furga G., Drewes G., Kuster B.,
RA Bouwmeester T., Acker-Palmer A.;
RT "Transgenic mouse proteomics identifies new 14-3-3-associated proteins
RT involved in cytoskeletal rearrangements and cell signaling.";
RL Mol. Cell. Proteomics 5:2211-2227(2006).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-569, PHOSPHORYLATION [LARGE
RP SCALE ANALYSIS] AT SER-376 (ISOFORMS 13 AND 14), PHOSPHORYLATION [LARGE
RP SCALE ANALYSIS] AT SER-409 (ISOFORMS 15 AND 16), AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [26]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [27]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-208; SER-409; SER-456;
RP SER-486 AND SER-722, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-376
RP (ISOFORMS 13 AND 14), PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-409
RP (ISOFORMS 15 AND 16), AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [28]
RP FUNCTION IN PHOSPHORYLATION OF KIF13B.
RX PubMed=20194617; DOI=10.1128/mcb.01181-09;
RA Yoshimura Y., Terabayashi T., Miki H.;
RT "Par1b/MARK2 phosphorylates kinesin-like motor protein GAKIN/KIF13B to
RT regulate axon formation.";
RL Mol. Cell. Biol. 30:2206-2219(2010).
RN [29]
RP REVIEW.
RX PubMed=19559622; DOI=10.1016/j.tibs.2009.03.008;
RA Matenia D., Mandelkow E.M.;
RT "The tau of MARK: a polarized view of the cytoskeleton.";
RL Trends Biochem. Sci. 34:332-342(2009).
RN [30]
RP REVIEW.
RX PubMed=20071654; DOI=10.1096/fj.09-148064;
RA Marx A., Nugoor C., Panneerselvam S., Mandelkow E.;
RT "Structure and function of polarity-inducing kinase family MARK/Par-1
RT within the branch of AMPK/Snf1-related kinases.";
RL FASEB J. 24:1637-1648(2010).
RN [31]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [32]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [33]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-40; SER-486 AND SER-619, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [34]
RP INTERACTION WITH MTCL1, AND SUBCELLULAR LOCATION.
RX PubMed=23902687; DOI=10.1242/jcs.127845;
RA Sato Y., Akitsu M., Amano Y., Yamashita K., Ide M., Shimada K.,
RA Yamashita A., Hirano H., Arakawa N., Maki T., Hayashi I., Ohno S.,
RA Suzuki A.;
RT "The novel PAR-1-binding protein MTCL1 has crucial roles in organizing
RT microtubules in polarizing epithelial cells.";
RL J. Cell Sci. 126:4671-4683(2013).
RN [35]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-40; SER-456; THR-467;
RP SER-486; SER-569; SER-571; SER-592; THR-596 AND SER-619, AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [36]
RP FUNCTION, INTERACTION WITH MAPT, AND SUBCELLULAR LOCATION.
RX PubMed=23666762; DOI=10.1007/s12017-013-8232-3;
RA Gu G.J., Lund H., Wu D., Blokzijl A., Classon C., von Euler G.,
RA Landegren U., Sunnemark D., Kamali-Moghaddam M.;
RT "Role of individual MARK isoforms in phosphorylation of tau at Ser262 in
RT Alzheimer's disease.";
RL NeuroMolecular Med. 15:458-469(2013).
RN [37]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 49-363 IN COMPLEX WITH H.PYLORI
RP CAGA PEPTIDE INHIBITOR.
RX PubMed=19966800; DOI=10.1038/nsmb.1705;
RA Nesic D., Miller M.C., Quinkert Z.T., Stein M., Chait B.T., Stebbins C.E.;
RT "Helicobacter pylori CagA inhibits PAR1-MARK family kinases by mimicking
RT host substrates.";
RL Nat. Struct. Mol. Biol. 17:130-132(2010).
CC -!- FUNCTION: Serine/threonine-protein kinase (PubMed:23666762). Involved
CC in cell polarity and microtubule dynamics regulation. Phosphorylates
CC CRTC2/TORC2, DCX, HDAC7, KIF13B, MAP2, MAP4 and RAB11FIP2.
CC Phosphorylates the microtubule-associated protein MAPT/TAU
CC (PubMed:23666762). Plays a key role in cell polarity by phosphorylating
CC the microtubule-associated proteins MAP2, MAP4 and MAPT/TAU at KXGS
CC motifs, causing detachment from microtubules, and their disassembly.
CC Regulates epithelial cell polarity by phosphorylating RAB11FIP2.
CC Involved in the regulation of neuronal migration through its dual
CC activities in regulating cellular polarity and microtubule dynamics,
CC possibly by phosphorylating and regulating DCX. Regulates axogenesis by
CC phosphorylating KIF13B, promoting interaction between KIF13B and 14-3-3
CC and inhibiting microtubule-dependent accumulation of KIF13B. Also
CC required for neurite outgrowth and establishment of neuronal polarity.
CC Regulates localization and activity of some histone deacetylases by
CC mediating phosphorylation of HDAC7, promoting subsequent interaction
CC between HDAC7 and 14-3-3 and export from the nucleus. Also acts as a
CC positive regulator of the Wnt signaling pathway, probably by mediating
CC phosphorylation of dishevelled proteins (DVL1, DVL2 and/or DVL3).
CC Modulates the developmental decision to build a columnar versus a
CC hepatic epithelial cell apparently by promoting a switch from a direct
CC to a transcytotic mode of apical protein delivery. Essential for the
CC asymmetric development of membrane domains of polarized epithelial
CC cells. {ECO:0000269|PubMed:11433294, ECO:0000269|PubMed:12429843,
CC ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:15158914,
CC ECO:0000269|PubMed:15324659, ECO:0000269|PubMed:15365179,
CC ECO:0000269|PubMed:16775013, ECO:0000269|PubMed:16980613,
CC ECO:0000269|PubMed:18626018, ECO:0000269|PubMed:20194617,
CC ECO:0000269|PubMed:23666762}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC Evidence={ECO:0000269|PubMed:14976552};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1; Evidence={ECO:0000269|PubMed:14976552};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[tau protein] = ADP + H(+) + O-phospho-L-seryl-
CC [tau protein]; Xref=Rhea:RHEA:12801, Rhea:RHEA-COMP:13701, Rhea:RHEA-
CC COMP:13702, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.26;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[tau protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[tau protein]; Xref=Rhea:RHEA:53904, Rhea:RHEA-COMP:13703,
CC Rhea:RHEA-COMP:13704, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.26;
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC -!- ACTIVITY REGULATION: Inhibited by PAK5; inhibition is independent of
CC the kinase activity of PAK5 (By similarity). Activated by
CC phosphorylation on Thr-208. Inhibited by phosphorylation at Ser-212 and
CC Thr-596. Inhibited by hymenialdisine. Specifically inhibited by the
CC H.pylori CagA peptide FPLKRHDKVDDLSK that mimics host substrates and
CC binds to the kinase substrate-binding site. {ECO:0000250,
CC ECO:0000269|PubMed:12429843, ECO:0000269|PubMed:14976552}.
CC -!- SUBUNIT: Homodimer. Interacts with PAK5; leading to inhibit the protein
CC kinase activity (By similarity). Interacts with MAPT/TAU
CC (PubMed:23666762). Interacts with MTCL1 isoform 1; the interaction is
CC direct and increases MARK2 microtubule-binding ability
CC (PubMed:23902687). Interacts (when phosphorylated at Thr-596) with
CC YWHAZ (PubMed:15324659). Interacts with YWHAB, YWHAG and YWHAQ
CC (PubMed:16959763). {ECO:0000250|UniProtKB:O08679,
CC ECO:0000269|PubMed:15324659, ECO:0000269|PubMed:16959763,
CC ECO:0000269|PubMed:23666762, ECO:0000269|PubMed:23902687}.
CC -!- SUBUNIT: (Microbial infection) In case of infection, interacts with
CC H.pylori CagA, leading to inhibit kinase activity and junctional and
CC polarity defects. {ECO:0000269|PubMed:17507984,
CC ECO:0000269|PubMed:19966800}.
CC -!- INTERACTION:
CC Q7KZI7; Q9BYG4: PARD6G; NbExp=2; IntAct=EBI-516560, EBI-295417;
CC Q7KZI7; P31946: YWHAB; NbExp=4; IntAct=EBI-516560, EBI-359815;
CC Q7KZI7; P61981: YWHAG; NbExp=4; IntAct=EBI-516560, EBI-359832;
CC Q7KZI7; Q04917: YWHAH; NbExp=10; IntAct=EBI-516560, EBI-306940;
CC Q7KZI7; P63104: YWHAZ; NbExp=8; IntAct=EBI-516560, EBI-347088;
CC Q7KZI7; P55980: cagA; Xeno; NbExp=4; IntAct=EBI-516560, EBI-528104;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Peripheral membrane protein.
CC Cytoplasm. Lateral cell membrane. Cytoplasm, cytoskeleton. Cell
CC projection, dendrite {ECO:0000269|PubMed:23666762}. Cytoplasm
CC {ECO:0000269|PubMed:23666762}. Note=Phosphorylation at Thr-596 by
CC PRKCZ/aPKC and subsequent interaction with 14-3-3 protein YWHAZ
CC promotes relocation from the cell membrane to the cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative promoter usage, Alternative splicing; Named isoforms=16;
CC Name=1 {ECO:0000305}; Synonyms=Alpha;
CC IsoId=Q7KZI7-1; Sequence=Displayed;
CC Name=2 {ECO:0000269|PubMed:9730619};
CC IsoId=Q7KZI7-2; Sequence=VSP_051705, VSP_051706;
CC Name=3 {ECO:0000269|PubMed:9730619};
CC IsoId=Q7KZI7-3; Sequence=VSP_051705, VSP_051707;
CC Name=4 {ECO:0000269|PubMed:11433294}; Synonyms=Par-1Balpha
CC {ECO:0000269|PubMed:11433294};
CC IsoId=Q7KZI7-4; Sequence=VSP_051706, VSP_051707;
CC Name=5;
CC IsoId=Q7KZI7-5; Sequence=VSP_051706, VSP_051708;
CC Name=6 {ECO:0000305}; Synonyms=Beta;
CC IsoId=Q7KZI7-6; Sequence=VSP_051705;
CC Name=7 {ECO:0000305};
CC IsoId=Q7KZI7-7; Sequence=VSP_051705, VSP_051706, VSP_051707;
CC Name=8 {ECO:0000305};
CC IsoId=Q7KZI7-8; Sequence=VSP_051707;
CC Name=9 {ECO:0000305};
CC IsoId=Q7KZI7-9; Sequence=VSP_051706;
CC Name=10 {ECO:0000305};
CC IsoId=Q7KZI7-10; Sequence=VSP_051705, VSP_051706, VSP_051708;
CC Name=11 {ECO:0000305};
CC IsoId=Q7KZI7-11; Sequence=VSP_051708;
CC Name=12 {ECO:0000305};
CC IsoId=Q7KZI7-12; Sequence=VSP_051705, VSP_051708;
CC Name=13;
CC IsoId=Q7KZI7-13; Sequence=VSP_051705, VSP_039872, VSP_051706,
CC VSP_051707;
CC Name=14;
CC IsoId=Q7KZI7-14; Sequence=VSP_051705, VSP_039872, VSP_051707;
CC Name=15;
CC IsoId=Q7KZI7-15; Sequence=VSP_039872, VSP_051706, VSP_041853;
CC Name=16;
CC IsoId=Q7KZI7-16; Sequence=VSP_039872, VSP_051706, VSP_051707;
CC -!- TISSUE SPECIFICITY: High levels of expression in heart, brain, skeletal
CC muscle and pancreas, lower levels observed in lung, liver and kidney.
CC {ECO:0000269|PubMed:9730619}.
CC -!- DOMAIN: The UBA domain does not seem to bind ubiquitin and ubiquitin-
CC like and might play a role in regulating the enzyme conformation and
CC localization. Activation of the kinase activity following
CC phosphorylation at Thr-208 is accompanied by a conformational change
CC that alters the orientation of the UBA domain with respect to the
CC catalytic domain. {ECO:0000269|PubMed:16396636}.
CC -!- DOMAIN: The KA1 domain mediates binding to phospholipids and targeting
CC to membranes. {ECO:0000250}.
CC -!- PTM: Autophosphorylated. Phosphorylated at Thr-208 by STK11/LKB1 in
CC complex with STE20-related adapter-alpha (STRADA) pseudo kinase and
CC CAB39. Phosphorylation at Thr-208 by TAOK1 activates the kinase
CC activity, leading to phosphorylation and detachment of MAPT/TAU from
CC microtubules. Phosphorylation at Ser-212 by GSK3-beta (GSK3B) inhibits
CC the kinase activity. Phosphorylation by CaMK1 promotes activity and is
CC required to promote neurite outgrowth. Phosphorylation at Thr-596 by
CC PRKCZ/aPKC in polarized epithelial cells inhibits the kinase activity
CC and promotes binding to 14-3-3 protein YWHAZ, leading to relocation
CC from cell membrane to cytoplasm. {ECO:0000269|PubMed:14976552,
CC ECO:0000269|PubMed:15084291, ECO:0000269|PubMed:15324659}.
CC -!- MISCELLANEOUS: [Isoform 1]: Produced by alternative promoter usage.
CC -!- MISCELLANEOUS: [Isoform 2]: Produced by alternative splicing of isoform
CC 6. {ECO:0000269|PubMed:9730619}.
CC -!- MISCELLANEOUS: [Isoform 3]: Produced by alternative splicing of isoform
CC 6. {ECO:0000269|PubMed:9730619}.
CC -!- MISCELLANEOUS: [Isoform 4]: Produced by alternative splicing of isoform
CC 1. {ECO:0000269|PubMed:11433294}.
CC -!- MISCELLANEOUS: [Isoform 5]: Produced by alternative splicing of isoform
CC 1. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 6]: Produced by alternative promoter usage.
CC {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 7]: Produced by alternative splicing of isoform
CC 6. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 8]: Produced by alternative splicing of isoform
CC 1. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 9]: Produced by alternative splicing of isoform
CC 1. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 10]: Produced by alternative splicing of
CC isoform 6. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 11]: Produced by alternative splicing of
CC isoform 1. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 12]: Produced by alternative splicing of
CC isoform 6. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 13]: Produced by alternative splicing of
CC isoform 6. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 14]: Produced by alternative splicing of
CC isoform 6. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 15]: Produced by alternative splicing of
CC isoform 1. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 16]: Produced by alternative splicing of
CC isoform 1. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. SNF1 subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAK82368.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; X97630; CAA66229.1; -; mRNA.
DR EMBL; AB188493; BAD37141.1; -; mRNA.
DR EMBL; BT007342; AAP36006.1; -; mRNA.
DR EMBL; AP003780; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC008771; AAH08771.2; -; mRNA.
DR EMBL; BC084540; AAH84540.1; -; mRNA.
DR EMBL; AF387638; AAK82368.1; ALT_INIT; mRNA.
DR EMBL; Z25427; CAA80914.1; -; mRNA.
DR CCDS; CCDS41665.1; -. [Q7KZI7-14]
DR CCDS; CCDS53649.1; -. [Q7KZI7-1]
DR CCDS; CCDS53650.1; -. [Q7KZI7-5]
DR CCDS; CCDS53651.1; -. [Q7KZI7-15]
DR CCDS; CCDS8051.2; -. [Q7KZI7-16]
DR PIR; G01025; G01025.
DR PIR; I38217; I38217.
DR RefSeq; NP_001034558.2; NM_001039469.2. [Q7KZI7-1]
DR RefSeq; NP_001156768.1; NM_001163296.1. [Q7KZI7-5]
DR RefSeq; NP_001156769.1; NM_001163297.1. [Q7KZI7-15]
DR RefSeq; NP_004945.4; NM_004954.4. [Q7KZI7-16]
DR RefSeq; NP_059672.2; NM_017490.3. [Q7KZI7-14]
DR PDB; 3IEC; X-ray; 2.20 A; A/B/C/D=49-363.
DR PDB; 5EAK; X-ray; 2.80 A; A/B=39-364.
DR PDB; 5KZ7; X-ray; 3.20 A; A/B=39-364.
DR PDB; 5KZ8; X-ray; 3.21 A; A/B=39-364.
DR PDBsum; 3IEC; -.
DR PDBsum; 5EAK; -.
DR PDBsum; 5KZ7; -.
DR PDBsum; 5KZ8; -.
DR AlphaFoldDB; Q7KZI7; -.
DR SASBDB; Q7KZI7; -.
DR SMR; Q7KZI7; -.
DR BioGRID; 108326; 227.
DR CORUM; Q7KZI7; -.
DR DIP; DIP-31321N; -.
DR IntAct; Q7KZI7; 96.
DR MINT; Q7KZI7; -.
DR STRING; 9606.ENSP00000385751; -.
DR BindingDB; Q7KZI7; -.
DR ChEMBL; CHEMBL3831; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; Q7KZI7; -.
DR GlyGen; Q7KZI7; 3 sites, 1 O-linked glycan (1 site).
DR iPTMnet; Q7KZI7; -.
DR PhosphoSitePlus; Q7KZI7; -.
DR BioMuta; MARK2; -.
DR DMDM; 62510922; -.
DR EPD; Q7KZI7; -.
DR jPOST; Q7KZI7; -.
DR MassIVE; Q7KZI7; -.
DR MaxQB; Q7KZI7; -.
DR PaxDb; Q7KZI7; -.
DR PeptideAtlas; Q7KZI7; -.
DR PRIDE; Q7KZI7; -.
DR ProteomicsDB; 68707; -. [Q7KZI7-1]
DR ProteomicsDB; 68708; -. [Q7KZI7-10]
DR ProteomicsDB; 68709; -. [Q7KZI7-11]
DR ProteomicsDB; 68710; -. [Q7KZI7-12]
DR ProteomicsDB; 68711; -. [Q7KZI7-13]
DR ProteomicsDB; 68712; -. [Q7KZI7-14]
DR ProteomicsDB; 68713; -. [Q7KZI7-15]
DR ProteomicsDB; 68714; -. [Q7KZI7-16]
DR ProteomicsDB; 68715; -. [Q7KZI7-2]
DR ProteomicsDB; 68716; -. [Q7KZI7-3]
DR ProteomicsDB; 68717; -. [Q7KZI7-4]
DR ProteomicsDB; 68718; -. [Q7KZI7-5]
DR ProteomicsDB; 68719; -. [Q7KZI7-6]
DR ProteomicsDB; 68720; -. [Q7KZI7-7]
DR ProteomicsDB; 68721; -. [Q7KZI7-8]
DR ProteomicsDB; 68722; -. [Q7KZI7-9]
DR Antibodypedia; 15193; 488 antibodies from 41 providers.
DR DNASU; 2011; -.
DR Ensembl; ENST00000350490.11; ENSP00000294247.9; ENSG00000072518.22. [Q7KZI7-15]
DR Ensembl; ENST00000361128.9; ENSP00000355091.5; ENSG00000072518.22. [Q7KZI7-5]
DR Ensembl; ENST00000402010.8; ENSP00000385751.2; ENSG00000072518.22. [Q7KZI7-1]
DR Ensembl; ENST00000408948.7; ENSP00000386128.3; ENSG00000072518.22. [Q7KZI7-13]
DR Ensembl; ENST00000508192.5; ENSP00000425765.1; ENSG00000072518.22. [Q7KZI7-16]
DR Ensembl; ENST00000509502.6; ENSP00000423974.2; ENSG00000072518.22. [Q7KZI7-14]
DR Ensembl; ENST00000513765.7; ENSP00000421075.3; ENSG00000072518.22. [Q7KZI7-8]
DR GeneID; 2011; -.
DR KEGG; hsa:2011; -.
DR MANE-Select; ENST00000402010.8; ENSP00000385751.2; NM_001039469.3; NP_001034558.2.
DR UCSC; uc001nxv.5; human. [Q7KZI7-1]
DR CTD; 2011; -.
DR DisGeNET; 2011; -.
DR GeneCards; MARK2; -.
DR HGNC; HGNC:3332; MARK2.
DR HPA; ENSG00000072518; Low tissue specificity.
DR MIM; 600526; gene.
DR neXtProt; NX_Q7KZI7; -.
DR OpenTargets; ENSG00000072518; -.
DR PharmGKB; PA35047; -.
DR VEuPathDB; HostDB:ENSG00000072518; -.
DR eggNOG; KOG0586; Eukaryota.
DR GeneTree; ENSGT00940000155031; -.
DR HOGENOM; CLU_000288_157_5_1; -.
DR InParanoid; Q7KZI7; -.
DR OMA; MSASMHP; -.
DR OrthoDB; 1127668at2759; -.
DR PhylomeDB; Q7KZI7; -.
DR TreeFam; TF315213; -.
DR PathwayCommons; Q7KZI7; -.
DR SignaLink; Q7KZI7; -.
DR SIGNOR; Q7KZI7; -.
DR BioGRID-ORCS; 2011; 140 hits in 1129 CRISPR screens.
DR ChiTaRS; MARK2; human.
DR EvolutionaryTrace; Q7KZI7; -.
DR GeneWiki; MARK2; -.
DR GenomeRNAi; 2011; -.
DR Pharos; Q7KZI7; Tchem.
DR PRO; PR:Q7KZI7; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q7KZI7; protein.
DR Bgee; ENSG00000072518; Expressed in lower esophagus mucosa and 111 other tissues.
DR ExpressionAtlas; Q7KZI7; baseline and differential.
DR Genevisible; Q7KZI7; HS.
DR GO; GO:0005884; C:actin filament; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0030425; C:dendrite; IDA:UniProtKB.
DR GO; GO:0016328; C:lateral plasma membrane; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IMP:UniProtKB.
DR GO; GO:0097427; C:microtubule bundle; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; NAS:ParkinsonsUK-UCL.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0045296; F:cadherin binding; HDA:BHF-UCL.
DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR GO; GO:0030295; F:protein kinase activator activity; TAS:ParkinsonsUK-UCL.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0048156; F:tau protein binding; ISS:ARUK-UCL.
DR GO; GO:0050321; F:tau-protein kinase activity; IMP:UniProtKB.
DR GO; GO:0032147; P:activation of protein kinase activity; TAS:ParkinsonsUK-UCL.
DR GO; GO:0000422; P:autophagy of mitochondrion; NAS:ParkinsonsUK-UCL.
DR GO; GO:0061564; P:axon development; ISS:ARUK-UCL.
DR GO; GO:0030010; P:establishment of cell polarity; IDA:UniProtKB.
DR GO; GO:0071963; P:establishment or maintenance of cell polarity regulating cell shape; ISS:ARUK-UCL.
DR GO; GO:0045197; P:establishment or maintenance of epithelial cell apical/basal polarity; IDA:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IDA:UniProtKB.
DR GO; GO:0000226; P:microtubule cytoskeleton organization; IBA:GO_Central.
DR GO; GO:0051646; P:mitochondrion localization; NAS:ParkinsonsUK-UCL.
DR GO; GO:0001764; P:neuron migration; ISS:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:ARUK-UCL.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; TAS:ParkinsonsUK-UCL.
DR GO; GO:0010976; P:positive regulation of neuron projection development; IDA:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; ISS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0050770; P:regulation of axonogenesis; IMP:UniProtKB.
DR GO; GO:0051493; P:regulation of cytoskeleton organization; ISS:UniProtKB.
DR GO; GO:1904526; P:regulation of microtubule binding; ISS:ARUK-UCL.
DR GO; GO:0070507; P:regulation of microtubule cytoskeleton organization; IDA:ARUK-UCL.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR InterPro; IPR028375; KA1/Ssp2_C.
DR InterPro; IPR001772; KA1_dom.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR InterPro; IPR015940; UBA.
DR Pfam; PF02149; KA1; 1.
DR Pfam; PF00069; Pkinase; 1.
DR Pfam; PF00627; UBA; 1.
DR SMART; SM00220; S_TKc; 1.
DR SMART; SM00165; UBA; 1.
DR SUPFAM; SSF103243; SSF103243; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50032; KA1; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR PROSITE; PS50030; UBA; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative promoter usage; Alternative splicing;
KW ATP-binding; Cell membrane; Cell projection; Cytoplasm; Cytoskeleton;
KW Developmental protein; Differentiation; Kinase; Lipid-binding; Magnesium;
KW Membrane; Metal-binding; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Transferase;
KW Wnt signaling pathway.
FT CHAIN 1..788
FT /note="Serine/threonine-protein kinase MARK2"
FT /id="PRO_0000086301"
FT DOMAIN 53..304
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 323..362
FT /note="UBA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00212"
FT DOMAIN 739..788
FT /note="KA1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00565"
FT REGION 1..46
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 373..632
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 378..407
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 414..430
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 431..447
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 465..632
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 175
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q9H0K1,
FT ECO:0000255|PROSITE-ProRule:PRU00159, ECO:0000255|PROSITE-
FT ProRule:PRU10027"
FT BINDING 59..67
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9H0K1,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 82
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:O08678,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 40
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 58
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:O08679"
FT MOD_RES 91
FT /note="Phosphoserine; by CaMK1"
FT /evidence="ECO:0000250|UniProtKB:O08679"
FT MOD_RES 92
FT /note="Phosphoserine; by CaMK1"
FT /evidence="ECO:0000250|UniProtKB:O08679"
FT MOD_RES 93
FT /note="Phosphoserine; by CaMK1"
FT /evidence="ECO:0000250|UniProtKB:O08679"
FT MOD_RES 208
FT /note="Phosphothreonine; by LKB1 and TAOK1"
FT /evidence="ECO:0000269|PubMed:14976552,
FT ECO:0007744|PubMed:19369195"
FT MOD_RES 212
FT /note="Phosphoserine; by GSK3-beta"
FT /evidence="ECO:0000250|UniProtKB:O08679"
FT MOD_RES 274
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:O08679"
FT MOD_RES 275
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:O08679"
FT MOD_RES 294
FT /note="Phosphothreonine; by CaMK1"
FT /evidence="ECO:0000250|UniProtKB:O08679"
FT MOD_RES 409
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195"
FT MOD_RES 456
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:18088087, ECO:0007744|PubMed:18220336,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 467
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 486
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18220336, ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 493
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976"
FT MOD_RES 569
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 571
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 592
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 596
FT /note="Phosphothreonine; by PKC/PRKCZ"
FT /evidence="ECO:0000269|PubMed:15084291,
FT ECO:0000269|PubMed:15324659, ECO:0007744|PubMed:23186163"
FT MOD_RES 619
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 722
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT VAR_SEQ 1..33
FT /note="Missing (in isoform 2, isoform 3, isoform 6, isoform
FT 7, isoform 10, isoform 12, isoform 13 and isoform 14)"
FT /evidence="ECO:0000303|PubMed:9730619, ECO:0000303|Ref.3"
FT /id="VSP_051705"
FT VAR_SEQ 412
FT /note="Missing (in isoform 13, isoform 14, isoform 15 and
FT isoform 16)"
FT /evidence="ECO:0000305"
FT /id="VSP_039872"
FT VAR_SEQ 505..558
FT /note="Missing (in isoform 2, isoform 4, isoform 5, isoform
FT 7, isoform 9, isoform 10, isoform 13, isoform 15 and
FT isoform 16)"
FT /evidence="ECO:0000303|PubMed:11433294,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:9730619,
FT ECO:0000303|Ref.2"
FT /id="VSP_051706"
FT VAR_SEQ 644..652
FT /note="Missing (in isoform 3, isoform 4, isoform 7, isoform
FT 8, isoform 13, isoform 14 and isoform 16)"
FT /evidence="ECO:0000303|PubMed:11433294,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:9730619"
FT /id="VSP_051707"
FT VAR_SEQ 645..668
FT /note="Missing (in isoform 15)"
FT /evidence="ECO:0000305"
FT /id="VSP_041853"
FT VAR_SEQ 654..668
FT /note="Missing (in isoform 5, isoform 11, isoform 10 and
FT isoform 12)"
FT /evidence="ECO:0000303|PubMed:11433294,
FT ECO:0000303|PubMed:9730619, ECO:0000303|Ref.2"
FT /id="VSP_051708"
FT MUTAGEN 208
FT /note="T->A: Prevents phosphorylation and activation by
FT STK11/LKB1 complex."
FT /evidence="ECO:0000269|PubMed:14976552"
FT MUTAGEN 596
FT /note="T->A: Loss of membrane dissociation and binding to
FT YWHAZ."
FT /evidence="ECO:0000269|PubMed:15084291,
FT ECO:0000269|PubMed:15324659"
FT CONFLICT 192
FT /note="A -> G (in Ref. 7; CAA80914)"
FT /evidence="ECO:0000305"
FT CONFLICT 236
FT /note="L -> C (in Ref. 7; CAA80914)"
FT /evidence="ECO:0000305"
FT CONFLICT 389..390
FT /note="PS -> QF (in Ref. 1; CAA66229)"
FT /evidence="ECO:0000305"
FT STRAND 53..60
FT /evidence="ECO:0007829|PDB:3IEC"
FT STRAND 66..72
FT /evidence="ECO:0007829|PDB:3IEC"
FT TURN 73..75
FT /evidence="ECO:0007829|PDB:3IEC"
FT STRAND 78..86
FT /evidence="ECO:0007829|PDB:3IEC"
FT HELIX 91..106
FT /evidence="ECO:0007829|PDB:3IEC"
FT STRAND 115..120
FT /evidence="ECO:0007829|PDB:3IEC"
FT STRAND 122..129
FT /evidence="ECO:0007829|PDB:3IEC"
FT HELIX 137..144
FT /evidence="ECO:0007829|PDB:3IEC"
FT HELIX 149..168
FT /evidence="ECO:0007829|PDB:3IEC"
FT HELIX 178..180
FT /evidence="ECO:0007829|PDB:3IEC"
FT STRAND 181..183
FT /evidence="ECO:0007829|PDB:3IEC"
FT STRAND 189..191
FT /evidence="ECO:0007829|PDB:3IEC"
FT HELIX 213..215
FT /evidence="ECO:0007829|PDB:3IEC"
FT HELIX 218..221
FT /evidence="ECO:0007829|PDB:3IEC"
FT HELIX 228..245
FT /evidence="ECO:0007829|PDB:3IEC"
FT HELIX 255..264
FT /evidence="ECO:0007829|PDB:3IEC"
FT HELIX 275..284
FT /evidence="ECO:0007829|PDB:3IEC"
FT HELIX 289..291
FT /evidence="ECO:0007829|PDB:3IEC"
FT HELIX 295..299
FT /evidence="ECO:0007829|PDB:3IEC"
FT HELIX 302..305
FT /evidence="ECO:0007829|PDB:3IEC"
FT STRAND 309..311
FT /evidence="ECO:0007829|PDB:5KZ7"
FT HELIX 326..334
FT /evidence="ECO:0007829|PDB:3IEC"
FT HELIX 339..347
FT /evidence="ECO:0007829|PDB:3IEC"
FT HELIX 353..361
FT /evidence="ECO:0007829|PDB:3IEC"
FT MOD_RES Q7KZI7-13:376
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19369195"
FT MOD_RES Q7KZI7-14:376
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19369195"
FT MOD_RES Q7KZI7-15:409
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19369195"
FT MOD_RES Q7KZI7-16:409
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19369195"
SQ SEQUENCE 788 AA; 87911 MW; F307BF4DDB543A70 CRC64;
MSSARTPLPT LNERDTEQPT LGHLDSKPSS KSNMIRGRNS ATSADEQPHI GNYRLLKTIG
KGNFAKVKLA RHILTGKEVA VKIIDKTQLN SSSLQKLFRE VRIMKVLNHP NIVKLFEVIE
TEKTLYLVME YASGGEVFDY LVAHGRMKEK EARAKFRQIV SAVQYCHQKF IVHRDLKAEN
LLLDADMNIK IADFGFSNEF TFGNKLDTFC GSPPYAAPEL FQGKKYDGPE VDVWSLGVIL
YTLVSGSLPF DGQNLKELRE RVLRGKYRIP FYMSTDCENL LKKFLILNPS KRGTLEQIMK
DRWMNVGHED DELKPYVEPL PDYKDPRRTE LMVSMGYTRE EIQDSLVGQR YNEVMATYLL
LGYKSSELEG DTITLKPRPS ADLTNSSAPS PSHKVQRSVS ANPKQRRFSD QAAGPAIPTS
NSYSKKTQSN NAENKRPEED RESGRKASST AKVPASPLPG LERKKTTPTP STNSVLSTST
NRSRNSPLLE RASLGQASIQ NGKDSLTMPG SRASTASASA AVSAARPRQH QKSMSASVHP
NKASGLPPTE SNCEVPRPST APQRVPVASP SAHNISSSGG APDRTNFPRG VSSRSTFHAG
QLRQVRDQQN LPYGVTPASP SGHSQGRRGA SGSIFSKFTS KFVRRNLSFR FARRNLNEPE
SKDRVETLRP HVVGSGGNDK EKEEFREAKP RSLRFTWSMK TTSSMEPNEM MREIRKVLDA
NSCQSELHEK YMLLCMHGTP GHEDFVQWEM EVCKLPRLSL NGVRFKRISG TSMAFKNIAS
KIANELKL
