MARK3_HUMAN
ID MARK3_HUMAN Reviewed; 753 AA.
AC P27448; A0A0A0MQR8; A0A0A0MST9; A0A0A0MT23; O60219; Q86TT8; Q8TB41; Q8WX83;
AC Q96RG1; Q9UMY9; Q9UN34;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 28-MAR-2018, sequence version 5.
DT 03-AUG-2022, entry version 214.
DE RecName: Full=MAP/microtubule affinity-regulating kinase 3;
DE EC=2.7.11.1;
DE AltName: Full=C-TAK1;
DE Short=cTAK1;
DE AltName: Full=Cdc25C-associated protein kinase 1;
DE AltName: Full=ELKL motif kinase 2;
DE Short=EMK-2;
DE AltName: Full=Protein kinase STK10;
DE AltName: Full=Ser/Thr protein kinase PAR-1;
DE Short=Par-1a;
DE AltName: Full=Serine/threonine-protein kinase p78;
GN Name=MARK3; Synonyms=CTAK1, EMK2;
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]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), AND VARIANT GLY-443.
RC TISSUE=Cervix carcinoma;
RX PubMed=9543386;
RA Peng C.Y., Graves P.R., Ogg S., Thoma R.S., Byrnes M.J. III, Wu Z.,
RA Stephenson M.T., Piwnica-Worms H.;
RT "C-TAK1 protein kinase phosphorylates human Cdc25C on serine 216 and
RT promotes 14-3-3 protein binding.";
RL Cell Growth Differ. 9:197-208(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND VARIANT GLY-443.
RC TISSUE=Monocyte;
RA Waggoner S.N., Stephen R., Farrar W.L., Howard O.M.Z.;
RT "Human serine/threonine protein kinase cTAK1/Kp78/Mark3: Identification of
RT a novel splice variant and a larger 5'UTR.";
RL Submitted (JUN-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4).
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 [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Drewes G.;
RT "Characterization of an alternatively spliced form of MARK3 from human
RT brain.";
RL Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5).
RC TISSUE=Pancreas;
RA Maheshwari K.K., Som S., Parsa I.;
RL Submitted (JAN-1992) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 7), AND VARIANT PHE-410.
RC TISSUE=Neuroblastoma;
RA Li W.B., Gruber C., Jessee J., Polayes D.;
RT "Full-length cDNA libraries and normalization.";
RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Cervix;
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 [10]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 300-752 (ISOFORM 6).
RC TISSUE=Urinary bladder;
RA Reynolds C.H., Patel U.A., Anderton B.H.;
RT "Homo sapiens mRNA partial sequence for a protein kinase, STK10, similar to
RT p78/C-TAK1.";
RL Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP PHOSPHORYLATION AT THR-564.
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 [12]
RP ACTIVITY REGULATION, PHOSPHORYLATION AT THR-211, AND MUTAGENESIS OF
RP THR-211.
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 [13]
RP FUNCTION.
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 [14]
RP INTERACTION WITH YWHAB; YWHAG; YWHAQ AND YWHAZ.
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 [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-549, AND IDENTIFICATION BY
RP 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 [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-383; SER-400; SER-469;
RP THR-549; SER-598 AND SER-643, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT
RP SER-384 (ISOFORM 5), PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-407
RP (ISOFORM 6), AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP 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 [17]
RP IDENTIFICATION BY MASS 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 [18]
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 [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-42; SER-383; SER-469 AND
RP SER-643, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE 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 [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [21]
RP SUBCELLULAR LOCATION.
RX PubMed=21145462; DOI=10.1016/j.cell.2010.11.028;
RA Moravcevic K., Mendrola J.M., Schmitz K.R., Wang Y.H., Slochower D.,
RA Janmey P.A., Lemmon M.A.;
RT "Kinase associated-1 domains drive MARK/PAR1 kinases to membrane targets by
RT binding acidic phospholipids.";
RL Cell 143:966-977(2010).
RN [22]
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 [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-469, AND IDENTIFICATION BY
RP 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 [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-376; SER-380; SER-419;
RP SER-469; SER-540; THR-549; SER-583 AND SER-601, AND IDENTIFICATION BY MASS
RP 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 [25]
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 [26]
RP FUNCTION, AND INTERACTION WITH STK3; STK4 AND DLG5.
RX PubMed=28087714; DOI=10.1101/gad.284539.116;
RA Kwan J., Sczaniecka A., Arash E.H., Nguyen L., Chen C.C., Ratkovic S.,
RA Klezovitch O., Attisano L., McNeill H., Emili A., Vasioukhin V.;
RT "DLG5 connects cell polarity and Hippo signaling protein networks by
RT linking PAR-1 with MST1/2.";
RL Genes Dev. 30:2696-2709(2016).
RN [27]
RP VARIANTS [LARGE SCALE ANALYSIS] ALA-429 AND GLY-443.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
RN [28]
RP VARIANT VIPB GLY-570, AND INVOLVEMENT IN VIPB.
RX PubMed=29771303; DOI=10.1093/hmg/ddy180;
RA Ansar M., Chung H., Waryah Y.M., Makrythanasis P., Falconnet E., Rao A.R.,
RA Guipponi M., Narsani A.K., Fingerhut R., Santoni F.A., Ranza E.,
RA Waryah A.M., Bellen H.J., Antonarakis S.E.;
RT "Visual impairment and progressive phthisis bulbi caused by recessive
RT pathogenic variant in MARK3.";
RL Hum. Mol. Genet. 27:2703-2711(2018).
CC -!- FUNCTION: Serine/threonine-protein kinase (PubMed:23666762). Involved
CC in the specific phosphorylation of microtubule-associated proteins for
CC MAP2 and MAP4. Phosphorylates the microtubule-associated protein
CC MAPT/TAU (PubMed:23666762). Phosphorylates CDC25C on 'Ser-216'.
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 (PubMed:16980613).
CC Negatively regulates the Hippo signaling pathway and antagonizes the
CC phosphorylation of LATS1. Cooperates with DLG5 to inhibit the kinase
CC activity of STK3/MST2 toward LATS1 (PubMed:28087714).
CC {ECO:0000269|PubMed:16980613, ECO:0000269|PubMed:23666762,
CC ECO:0000269|PubMed:28087714}.
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 -!- 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;
CC -!- ACTIVITY REGULATION: Activated by phosphorylation on Thr-211. Inhibited
CC by phosphorylation on Thr-564. {ECO:0000269|PubMed:14976552}.
CC -!- SUBUNIT: Interacts with MAPT/TAU (PubMed:23666762). Interacts with DLG5
CC (via coiled-coil domain). Interacts with STK3/MST2 and STK4/MST1 in the
CC presence of DLG5 (PubMed:28087714). Interacts with YWHAB, YWHAG, YWHAQ
CC and YWHAZ (PubMed:16959763). {ECO:0000269|PubMed:16959763,
CC ECO:0000269|PubMed:23666762, ECO:0000269|PubMed:28087714}.
CC -!- INTERACTION:
CC P27448; Q8WXK3: ASB13; NbExp=2; IntAct=EBI-707595, EBI-707573;
CC P27448; P31947: SFN; NbExp=2; IntAct=EBI-707595, EBI-476295;
CC P27448; Q15560: TCEA2; NbExp=2; IntAct=EBI-707595, EBI-710310;
CC P27448; P31946: YWHAB; NbExp=5; IntAct=EBI-707595, EBI-359815;
CC P27448; P61981: YWHAG; NbExp=4; IntAct=EBI-707595, EBI-359832;
CC P27448; Q04917: YWHAH; NbExp=6; IntAct=EBI-707595, EBI-306940;
CC P27448; P63104: YWHAZ; NbExp=12; IntAct=EBI-707595, EBI-347088;
CC P27448; Q6S8E0: ORF9b; Xeno; NbExp=2; IntAct=EBI-707595, EBI-25489144;
CC P27448; Q8BHN0: Ppm1l; Xeno; NbExp=3; IntAct=EBI-707595, EBI-7970002;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:21145462};
CC Peripheral membrane protein {ECO:0000269|PubMed:21145462}. Cell
CC projection, dendrite {ECO:0000269|PubMed:23666762}. Cytoplasm
CC {ECO:0000269|PubMed:23666762}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=7;
CC Name=1;
CC IsoId=P27448-5; Sequence=Displayed;
CC Name=2; Synonyms=CTAK75a;
CC IsoId=P27448-2; Sequence=VSP_041582, VSP_004944;
CC Name=3;
CC IsoId=P27448-3; Sequence=VSP_004944;
CC Name=4;
CC IsoId=P27448-4; Sequence=VSP_004945;
CC Name=5; Synonyms=p58;
CC IsoId=P27448-6; Sequence=VSP_004943, VSP_004944;
CC Name=6;
CC IsoId=P27448-7; Sequence=VSP_041582, VSP_004943;
CC Name=7;
CC IsoId=P27448-8; Sequence=VSP_043197, VSP_043198;
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- PTM: Phosphorylated at Thr-211 by STK11/LKB1 in complex with STE20-
CC related adapter-alpha (STRADA) pseudo kinase and CAB39. Phosphorylation
CC at Thr-564 by PRKCZ/aPKC inhibits the kinase activity.
CC {ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:15084291}.
CC -!- DISEASE: Visual impairment and progressive phthisis bulbi (VIPB)
CC [MIM:618283]: An autosomal recessive, progressive disease characterized
CC by poor vision at birth and development of bilateral phthisis bulbi by
CC adulthood. {ECO:0000269|PubMed:29771303}. Note=The disease may be
CC caused by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. SNF1 subfamily. {ECO:0000305}.
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DR EMBL; U64205; AAC15093.1; -; mRNA.
DR EMBL; AF159295; AAD48007.1; -; mRNA.
DR EMBL; AF387637; AAK82367.1; -; mRNA.
DR EMBL; AF465413; AAL69982.1; -; mRNA.
DR EMBL; M80359; AAA59991.1; -; mRNA.
DR EMBL; BX161395; CAD61882.1; -; mRNA.
DR EMBL; AL133367; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; KF456011; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471061; EAW81813.1; -; Genomic_DNA.
DR EMBL; CH471061; EAW81815.1; -; Genomic_DNA.
DR EMBL; CH471061; EAW81817.1; -; Genomic_DNA.
DR EMBL; BC024773; AAH24773.1; -; mRNA.
DR EMBL; AF170723; AAD51631.1; -; mRNA.
DR CCDS; CCDS41993.1; -. [P27448-3]
DR CCDS; CCDS45165.1; -. [P27448-5]
DR CCDS; CCDS45166.1; -. [P27448-4]
DR CCDS; CCDS45167.1; -. [P27448-8]
DR CCDS; CCDS55947.1; -. [P27448-6]
DR PIR; S27966; S27966.
DR RefSeq; NP_001122390.2; NM_001128918.2. [P27448-5]
DR RefSeq; NP_001122391.2; NM_001128919.2. [P27448-4]
DR RefSeq; NP_001122392.2; NM_001128920.2. [P27448-6]
DR RefSeq; NP_001122393.2; NM_001128921.2. [P27448-8]
DR RefSeq; NP_002367.5; NM_002376.6. [P27448-3]
DR PDB; 2QNJ; X-ray; 2.70 A; A/B=48-370.
DR PDB; 3FE3; X-ray; 1.90 A; A/B=41-367.
DR PDB; 7P1L; X-ray; 1.95 A; A/B=48-366.
DR PDBsum; 2QNJ; -.
DR PDBsum; 3FE3; -.
DR PDBsum; 7P1L; -.
DR AlphaFoldDB; P27448; -.
DR BMRB; P27448; -.
DR SMR; P27448; -.
DR BioGRID; 110310; 187.
DR DIP; DIP-34637N; -.
DR IntAct; P27448; 109.
DR MINT; P27448; -.
DR STRING; 9606.ENSP00000411397; -.
DR BindingDB; P27448; -.
DR ChEMBL; CHEMBL5600; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; P27448; -.
DR GuidetoPHARMACOLOGY; 2099; -.
DR GlyGen; P27448; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P27448; -.
DR MetOSite; P27448; -.
DR PhosphoSitePlus; P27448; -.
DR BioMuta; MARK3; -.
DR DMDM; 341941142; -.
DR EPD; P27448; -.
DR jPOST; P27448; -.
DR MassIVE; P27448; -.
DR MaxQB; P27448; -.
DR PaxDb; P27448; -.
DR PeptideAtlas; P27448; -.
DR PRIDE; P27448; -.
DR ProteomicsDB; 54386; -. [P27448-5]
DR ProteomicsDB; 54387; -. [P27448-2]
DR ProteomicsDB; 54388; -. [P27448-3]
DR ProteomicsDB; 54389; -. [P27448-4]
DR ProteomicsDB; 54390; -. [P27448-6]
DR ProteomicsDB; 54391; -. [P27448-7]
DR ProteomicsDB; 54392; -. [P27448-8]
DR Antibodypedia; 6515; 496 antibodies from 37 providers.
DR DNASU; 4140; -.
DR Ensembl; ENST00000216288.11; ENSP00000216288.7; ENSG00000075413.19. [P27448-6]
DR Ensembl; ENST00000303622.13; ENSP00000303698.9; ENSG00000075413.19. [P27448-3]
DR Ensembl; ENST00000416682.6; ENSP00000408092.2; ENSG00000075413.19. [P27448-2]
DR Ensembl; ENST00000429436.7; ENSP00000411397.2; ENSG00000075413.19. [P27448-5]
DR Ensembl; ENST00000440884.7; ENSP00000402104.3; ENSG00000075413.19. [P27448-8]
DR Ensembl; ENST00000553942.5; ENSP00000450772.1; ENSG00000075413.19. [P27448-4]
DR GeneID; 4140; -.
DR KEGG; hsa:4140; -.
DR MANE-Select; ENST00000429436.7; ENSP00000411397.2; NM_001128918.3; NP_001122390.2.
DR UCSC; uc001ymw.5; human. [P27448-5]
DR UCSC; uc001ymy.5; human.
DR UCSC; uc001ymz.5; human.
DR UCSC; uc001yna.5; human.
DR CTD; 4140; -.
DR DisGeNET; 4140; -.
DR GeneCards; MARK3; -.
DR HGNC; HGNC:6897; MARK3.
DR HPA; ENSG00000075413; Low tissue specificity.
DR MalaCards; MARK3; -.
DR MIM; 602678; gene.
DR MIM; 618283; phenotype.
DR neXtProt; NX_P27448; -.
DR OpenTargets; ENSG00000075413; -.
DR PharmGKB; PA30640; -.
DR VEuPathDB; HostDB:ENSG00000075413; -.
DR eggNOG; KOG0586; Eukaryota.
DR GeneTree; ENSGT00940000154862; -.
DR InParanoid; P27448; -.
DR OMA; AKFRQGC; -.
DR TreeFam; TF315213; -.
DR PathwayCommons; P27448; -.
DR Reactome; R-HSA-5673000; RAF activation.
DR Reactome; R-HSA-5674135; MAP2K and MAPK activation.
DR Reactome; R-HSA-5675221; Negative regulation of MAPK pathway.
DR Reactome; R-HSA-6802946; Signaling by moderate kinase activity BRAF mutants.
DR Reactome; R-HSA-6802948; Signaling by high-kinase activity BRAF mutants.
DR Reactome; R-HSA-6802952; Signaling by BRAF and RAF1 fusions.
DR Reactome; R-HSA-6802955; Paradoxical activation of RAF signaling by kinase inactive BRAF.
DR Reactome; R-HSA-9649948; Signaling downstream of RAS mutants.
DR Reactome; R-HSA-9656223; Signaling by RAF1 mutants.
DR SignaLink; P27448; -.
DR SIGNOR; P27448; -.
DR BioGRID-ORCS; 4140; 28 hits in 1124 CRISPR screens.
DR ChiTaRS; MARK3; human.
DR EvolutionaryTrace; P27448; -.
DR GeneWiki; MARK3; -.
DR GenomeRNAi; 4140; -.
DR Pharos; P27448; Tchem.
DR PRO; PR:P27448; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; P27448; protein.
DR Bgee; ENSG00000075413; Expressed in cerebellar hemisphere and 203 other tissues.
DR ExpressionAtlas; P27448; baseline and differential.
DR Genevisible; P27448; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0030425; C:dendrite; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
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:0048156; F:tau protein binding; NAS:ARUK-UCL.
DR GO; GO:0050321; F:tau-protein kinase activity; IMP:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0000226; P:microtubule cytoskeleton organization; IBA:GO_Central.
DR GO; GO:0035331; P:negative regulation of hippo signaling; IDA:UniProtKB.
DR GO; GO:0036289; P:peptidyl-serine autophosphorylation; IDA:ARUK-UCL.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:ARUK-UCL.
DR GO; GO:0032092; P:positive regulation of protein binding; IDA:ARUK-UCL.
DR GO; GO:0006468; P:protein phosphorylation; IMP:UniProtKB.
DR InterPro; IPR028375; KA1/Ssp2_C.
DR InterPro; IPR001772; KA1_dom.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR033628; MARK3.
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 PANTHER; PTHR24346:SF1; PTHR24346:SF1; 2.
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 splicing; ATP-binding; Cell membrane;
KW Cell projection; Cytoplasm; Disease variant; Kinase; Membrane;
KW Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..753
FT /note="MAP/microtubule affinity-regulating kinase 3"
FT /id="PRO_0000086304"
FT DOMAIN 56..307
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 326..365
FT /note="UBA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00212"
FT DOMAIN 704..753
FT /note="KA1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00565"
FT REGION 1..36
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 370..600
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 632..655
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 14..28
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 370..418
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 488..548
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 578..600
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 178
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 62..70
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 85
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 42
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 211
FT /note="Phosphothreonine; by LKB1"
FT /evidence="ECO:0000269|PubMed:14976552"
FT MOD_RES 368
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q03141"
FT MOD_RES 374
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q03141"
FT MOD_RES 376
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 380
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 383
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195"
FT MOD_RES 400
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976"
FT MOD_RES 419
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 469
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 540
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 543
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q03141"
FT MOD_RES 549
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18220336,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:23186163"
FT MOD_RES 564
FT /note="Phosphothreonine; by PKC/PRKCZ"
FT /evidence="ECO:0000250"
FT MOD_RES 583
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 598
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976"
FT MOD_RES 601
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 643
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195"
FT VAR_SEQ 161
FT /note="Q -> QGCQAGQTIKVQVSFDLLSLMFTF (in isoform 2 and
FT isoform 6)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_041582"
FT VAR_SEQ 179..257
FT /note="Missing (in isoform 7)"
FT /evidence="ECO:0000303|Ref.6"
FT /id="VSP_043197"
FT VAR_SEQ 371..386
FT /note="Missing (in isoform 5 and isoform 6)"
FT /evidence="ECO:0000303|Ref.10, ECO:0000303|Ref.5"
FT /id="VSP_004943"
FT VAR_SEQ 615..638
FT /note="Missing (in isoform 2, isoform 3 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:9543386, ECO:0000303|Ref.2,
FT ECO:0000303|Ref.5"
FT /id="VSP_004944"
FT VAR_SEQ 615..623
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:11433294"
FT /id="VSP_004945"
FT VAR_SEQ 624..638
FT /note="Missing (in isoform 7)"
FT /evidence="ECO:0000303|Ref.6"
FT /id="VSP_043198"
FT VARIANT 410
FT /note="S -> F (in dbSNP:rs10137161)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_080189"
FT VARIANT 429
FT /note="V -> A"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040765"
FT VARIANT 443
FT /note="S -> G (in dbSNP:rs56305318)"
FT /evidence="ECO:0000269|PubMed:17344846,
FT ECO:0000269|PubMed:9543386, ECO:0000269|Ref.2"
FT /id="VAR_046763"
FT VARIANT 570
FT /note="R -> G (in VIPB; dbSNP:rs376395495)"
FT /evidence="ECO:0000269|PubMed:29771303"
FT /id="VAR_080778"
FT MUTAGEN 211
FT /note="T->A: Prevents phosphorylation and activation by
FT STK11/LKB1 complex."
FT /evidence="ECO:0000269|PubMed:14976552"
FT CONFLICT 125
FT /note="E -> Q (in Ref. 5; AAA59991)"
FT /evidence="ECO:0000305"
FT CONFLICT 139
FT /note="E -> K (in Ref. 4; AAL69982 and 5; AAA59991)"
FT /evidence="ECO:0000305"
FT CONFLICT 149
FT /note="R -> K (in Ref. 2; AAD48007)"
FT /evidence="ECO:0000305"
FT CONFLICT 425
FT /note="A -> G (in Ref. 5; AAA59991)"
FT /evidence="ECO:0000305"
FT CONFLICT 456
FT /note="S -> T (in Ref. 5; AAA59991)"
FT /evidence="ECO:0000305"
FT CONFLICT 516
FT /note="A -> D (in Ref. 5; AAA59991)"
FT /evidence="ECO:0000305"
FT CONFLICT 603
FT /note="N -> T (in Ref. 5; AAA59991)"
FT /evidence="ECO:0000305"
FT CONFLICT 645
FT /note="E -> K (in Ref. 5; AAA59991)"
FT /evidence="ECO:0000305"
FT STRAND 56..64
FT /evidence="ECO:0007829|PDB:3FE3"
FT STRAND 66..75
FT /evidence="ECO:0007829|PDB:3FE3"
FT TURN 76..78
FT /evidence="ECO:0007829|PDB:3FE3"
FT STRAND 81..88
FT /evidence="ECO:0007829|PDB:3FE3"
FT HELIX 89..91
FT /evidence="ECO:0007829|PDB:3FE3"
FT HELIX 94..109
FT /evidence="ECO:0007829|PDB:3FE3"
FT STRAND 118..123
FT /evidence="ECO:0007829|PDB:3FE3"
FT STRAND 125..132
FT /evidence="ECO:0007829|PDB:3FE3"
FT HELIX 140..147
FT /evidence="ECO:0007829|PDB:3FE3"
FT HELIX 152..171
FT /evidence="ECO:0007829|PDB:3FE3"
FT HELIX 181..183
FT /evidence="ECO:0007829|PDB:3FE3"
FT STRAND 184..186
FT /evidence="ECO:0007829|PDB:3FE3"
FT STRAND 192..194
FT /evidence="ECO:0007829|PDB:3FE3"
FT HELIX 201..203
FT /evidence="ECO:0007829|PDB:3FE3"
FT STRAND 204..206
FT /evidence="ECO:0007829|PDB:3FE3"
FT HELIX 208..210
FT /evidence="ECO:0007829|PDB:3FE3"
FT STRAND 213..215
FT /evidence="ECO:0007829|PDB:3FE3"
FT HELIX 216..218
FT /evidence="ECO:0007829|PDB:3FE3"
FT HELIX 221..225
FT /evidence="ECO:0007829|PDB:3FE3"
FT HELIX 232..248
FT /evidence="ECO:0007829|PDB:3FE3"
FT HELIX 258..267
FT /evidence="ECO:0007829|PDB:3FE3"
FT HELIX 278..287
FT /evidence="ECO:0007829|PDB:3FE3"
FT TURN 292..294
FT /evidence="ECO:0007829|PDB:3FE3"
FT HELIX 298..301
FT /evidence="ECO:0007829|PDB:3FE3"
FT TURN 305..310
FT /evidence="ECO:0007829|PDB:3FE3"
FT HELIX 329..337
FT /evidence="ECO:0007829|PDB:3FE3"
FT HELIX 342..350
FT /evidence="ECO:0007829|PDB:3FE3"
FT HELIX 356..364
FT /evidence="ECO:0007829|PDB:3FE3"
FT MOD_RES P27448-6:384
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976"
FT MOD_RES P27448-7:407
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976"
SQ SEQUENCE 753 AA; 84429 MW; B50B3C145E896B0B CRC64;
MSTRTPLPTV NERDTENHTS HGDGRQEVTS RTSRSGARCR NSIASCADEQ PHIGNYRLLK
TIGKGNFAKV KLARHILTGR EVAIKIIDKT QLNPTSLQKL FREVRIMKIL NHPNIVKLFE
VIETEKTLYL IMEYASGGEV FDYLVAHGRM KEKEARSKFR QIVSAVQYCH QKRIVHRDLK
AENLLLDADM NIKIADFGFS NEFTVGGKLD TFCGSPPYAA PELFQGKKYD GPEVDVWSLG
VILYTLVSGS LPFDGQNLKE LRERVLRGKY RIPFYMSTDC ENLLKRFLVL NPIKRGTLEQ
IMKDRWINAG HEEDELKPFV EPELDISDQK RIDIMVGMGY SQEEIQESLS KMKYDEITAT
YLLLGRKSSE LDASDSSSSS NLSLAKVRPS SDLNNSTGQS PHHKVQRSVS SSQKQRRYSD
HAGPAIPSVV AYPKRSQTST ADSDLKEDGI SSRKSSGSAV GGKGIAPASP MLGNASNPNK
ADIPERKKSS TVPSSNTASG GMTRRNTYVC SERTTADRHS VIQNGKENST IPDQRTPVAS
THSISSAATP DRIRFPRGTA SRSTFHGQPR ERRTATYNGP PASPSLSHEA TPLSQTRSRG
STNLFSKLTS KLTRRNMSFR FIKRLPTEYE RNGRYEGSSR NVSAEQKDEN KEAKPRSLRF
TWSMKTTSSM DPGDMMREIR KVLDANNCDY EQRERFLLFC VHGDGHAENL VQWEMEVCKL
PRLSLNGVRF KRISGTSIAF KNIASKIANE LKL
