Full text data of MARK3
MARK3
(CTAK1, EMK2)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
MAP/microtubule affinity-regulating kinase 3; 2.7.11.1 (C-TAK1; cTAK1; Cdc25C-associated protein kinase 1; ELKL motif kinase 2; EMK-2; Protein kinase STK10; Ser/Thr protein kinase PAR-1; Par-1a; Serine/threonine-protein kinase p78)
MAP/microtubule affinity-regulating kinase 3; 2.7.11.1 (C-TAK1; cTAK1; Cdc25C-associated protein kinase 1; ELKL motif kinase 2; EMK-2; Protein kinase STK10; Ser/Thr protein kinase PAR-1; Par-1a; Serine/threonine-protein kinase p78)
UniProt
P27448
ID MARK3_HUMAN Reviewed; 753 AA.
AC P27448; O60219; Q86TT8; Q8TB41; Q8WX83; Q96RG1; Q9UMY9; Q9UN34;
read moreDT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 4.
DT 22-JAN-2014, entry version 144.
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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:
RT Identification of 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
RT Wnt 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).
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.,
RA Sun H., Du H., Pepin K., Artiguenave F., Robert C., Cruaud C.,
RA Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P.,
RA Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N.,
RA Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C.,
RA Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S.,
RA Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B.,
RA Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M.,
RA Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S.,
RA Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D.,
RA Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A.,
RA 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.,
RA Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J.,
RA Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W.,
RA Quetier F., 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 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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
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,
RT similar to p78/C-TAK1.";
RL Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases.
RN [10]
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
RT and activity.";
RL Curr. Biol. 14:736-741(2004).
RN [11]
RP ENZYME 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.,
RA Boudeau J., Hawley S.A., Udd L., Maekelae T.P., Hardie D.G.,
RA Alessi D.R.;
RT "LKB1 is a master kinase that activates 13 kinases of the AMPK
RT subfamily, including MARK/PAR-1.";
RL EMBO J. 23:833-843(2004).
RN [12]
RP FUNCTION.
RX PubMed=16980613; DOI=10.1128/MCB.00231-06;
RA Dequiedt F., Martin M., Von Blume J., Vertommen D., Lecomte E.,
RA Mari N., Heinen M.F., Bachmann M., Twizere J.C., Huang M.C.,
RA Rider M.H., Piwnica-Worms H., Seufferlein T., Kettmann R.;
RT "New role for hPar-1 kinases EMK and C-TAK1 in regulating localization
RT and activity of class IIa histone deacetylases.";
RL Mol. Cell. Biol. 26:7086-7102(2006).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-549, AND MASS
RP SPECTROMETRY.
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.,
RA Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for
RT efficient phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-383; SER-400; SER-469;
RP THR-549; SER-598 AND SER-643, PHOSPHORYLATION [LARGE SCALE ANALYSIS]
RP AT SER-384 (ISOFORM 5), PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT
RP SER-407 (ISOFORM 6), AND MASS SPECTROMETRY.
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
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [15]
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 [16]
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.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-42; SER-383; SER-469 AND
RP SER-643, AND MASS SPECTROMETRY.
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 [18]
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 [19]
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
RT targets by binding acidic phospholipids.";
RL Cell 143:966-977(2010).
RN [20]
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.,
RA Buerckstuemmer T., 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 [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-469, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [22]
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.,
RA Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S.,
RA O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S.,
RA Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E.,
RA Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J.,
RA Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K.,
RA Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T.,
RA West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P.,
RA Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E.,
RA DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E.,
RA Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T.,
RA Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
CC -!- FUNCTION: Involved in the specific phosphorylation of microtubule-
CC associated proteins for tau, MAP2 and MAP4. Phosphorylates CDC25C
CC on 'Ser-216'. Regulates localization and activity of some histone
CC deacetylases by mediating phosphorylation of HDAC7, promoting
CC subsequent interaction between HDAC7 and 14-3-3 and export from
CC the nucleus.
CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
CC -!- ENZYME REGULATION: Activated by phosphorylation on Thr-211.
CC Inhibited by phosphorylation on Thr-564.
CC -!- INTERACTION:
CC Q8WXK3:ASB13; NbExp=2; IntAct=EBI-707595, EBI-707573;
CC Q8BHN0:Ppm1l (xeno); NbExp=3; IntAct=EBI-707595, EBI-7970002;
CC P31947:SFN; NbExp=2; IntAct=EBI-707595, EBI-476295;
CC Q15560:TCEA2; NbExp=2; IntAct=EBI-707595, EBI-710310;
CC P31946:YWHAB; NbExp=4; IntAct=EBI-707595, EBI-359815;
CC P61981:YWHAG; NbExp=2; IntAct=EBI-707595, EBI-359832;
CC Q04917:YWHAH; NbExp=4; IntAct=EBI-707595, EBI-306940;
CC P63104:YWHAZ; NbExp=9; IntAct=EBI-707595, EBI-347088;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Peripheral membrane protein.
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 Note=Contains a phosphoserine at position 384;
CC Name=6;
CC IsoId=P27448-7; Sequence=VSP_041582, VSP_004943;
CC Note=Contains a phosphoserine at position 407;
CC Name=7;
CC IsoId=P27448-8; Sequence=VSP_043197, VSP_043198;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- PTM: Phosphorylated at Thr-211 by STK11/LKB1 in complex with
CC STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39.
CC Phosphorylation at Thr-564 by PRKCZ/aPKC inhibits the kinase
CC activity.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK
CC Ser/Thr protein kinase family. SNF1 subfamily.
CC -!- SIMILARITY: Contains 1 KA1 (kinase-associated) domain.
CC -!- SIMILARITY: Contains 1 protein kinase domain.
CC -!- SIMILARITY: Contains 1 UBA domain.
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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; BC024773; AAH24773.1; -; mRNA.
DR EMBL; AF170723; AAD51631.1; -; mRNA.
DR PIR; S27966; S27966.
DR RefSeq; NP_001122390.1; NM_001128918.1.
DR RefSeq; NP_001122391.1; NM_001128919.1.
DR RefSeq; NP_001122392.1; NM_001128920.1.
DR RefSeq; NP_001122393.1; NM_001128921.1.
DR RefSeq; NP_002367.4; NM_002376.5.
DR UniGene; Hs.35828; -.
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 PDBsum; 2QNJ; -.
DR PDBsum; 3FE3; -.
DR ProteinModelPortal; P27448; -.
DR SMR; P27448; 18-366, 657-753.
DR DIP; DIP-34637N; -.
DR IntAct; P27448; 38.
DR MINT; MINT-272697; -.
DR STRING; 9606.ENSP00000411397; -.
DR ChEMBL; CHEMBL5600; -.
DR GuidetoPHARMACOLOGY; 2099; -.
DR PhosphoSite; P27448; -.
DR DMDM; 281185502; -.
DR PaxDb; P27448; -.
DR PRIDE; P27448; -.
DR DNASU; 4140; -.
DR Ensembl; ENST00000216288; ENSP00000216288; ENSG00000075413.
DR Ensembl; ENST00000303622; ENSP00000303698; ENSG00000075413.
DR Ensembl; ENST00000416682; ENSP00000408092; ENSG00000075413.
DR Ensembl; ENST00000429436; ENSP00000411397; ENSG00000075413.
DR Ensembl; ENST00000440884; ENSP00000402104; ENSG00000075413.
DR Ensembl; ENST00000553942; ENSP00000450772; ENSG00000075413.
DR GeneID; 4140; -.
DR KEGG; hsa:4140; -.
DR UCSC; uc001ymz.4; human.
DR CTD; 4140; -.
DR GeneCards; GC14P103851; -.
DR HGNC; HGNC:6897; MARK3.
DR HPA; HPA024652; -.
DR MIM; 602678; gene.
DR neXtProt; NX_P27448; -.
DR PharmGKB; PA30640; -.
DR eggNOG; COG0515; -.
DR HOGENOM; HOG000233025; -.
DR HOVERGEN; HBG052453; -.
DR InParanoid; P27448; -.
DR KO; K08798; -.
DR SignaLink; P27448; -.
DR ChiTaRS; MARK3; human.
DR EvolutionaryTrace; P27448; -.
DR GeneWiki; MARK3; -.
DR GenomeRNAi; 4140; -.
DR NextBio; 16260; -.
DR PRO; PR:P27448; -.
DR ArrayExpress; P27448; -.
DR Bgee; P27448; -.
DR CleanEx; HS_MARK3; -.
DR Genevestigator; P27448; -.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR InterPro; IPR028375; KA1/Ssp2_C.
DR InterPro; IPR001772; KA1_dom.
DR InterPro; IPR011009; Kinase-like_dom.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR002290; Ser/Thr_dual-sp_kinase_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR InterPro; IPR015940; UBA/transl_elong_EF1B_N_euk.
DR Pfam; PF02149; KA1; 1.
DR Pfam; PF00069; Pkinase; 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 Complete proteome; Kinase; Membrane; Nucleotide-binding;
KW Phosphoprotein; Polymorphism; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1 753 MAP/microtubule affinity-regulating
FT kinase 3.
FT /FTId=PRO_0000086304.
FT DOMAIN 56 307 Protein kinase.
FT DOMAIN 326 365 UBA.
FT DOMAIN 704 753 KA1.
FT NP_BIND 62 70 ATP (By similarity).
FT ACT_SITE 178 178 Proton acceptor (By similarity).
FT BINDING 85 85 ATP (By similarity).
FT MOD_RES 42 42 Phosphoserine.
FT MOD_RES 211 211 Phosphothreonine; by LKB1.
FT MOD_RES 383 383 Phosphoserine.
FT MOD_RES 400 400 Phosphoserine.
FT MOD_RES 469 469 Phosphoserine.
FT MOD_RES 549 549 Phosphothreonine.
FT MOD_RES 564 564 Phosphothreonine; by PKC/PRKCZ (By
FT similarity).
FT MOD_RES 598 598 Phosphoserine.
FT MOD_RES 643 643 Phosphoserine.
FT VAR_SEQ 161 161 Q -> QGCQAGQTIKVQVSFDLLSLMFTF (in isoform
FT 2 and isoform 6).
FT /FTId=VSP_041582.
FT VAR_SEQ 179 257 Missing (in isoform 7).
FT /FTId=VSP_043197.
FT VAR_SEQ 371 386 Missing (in isoform 5 and isoform 6).
FT /FTId=VSP_004943.
FT VAR_SEQ 615 638 Missing (in isoform 2, isoform 3 and
FT isoform 5).
FT /FTId=VSP_004944.
FT VAR_SEQ 615 623 Missing (in isoform 4).
FT /FTId=VSP_004945.
FT VAR_SEQ 624 638 Missing (in isoform 7).
FT /FTId=VSP_043198.
FT VARIANT 429 429 V -> A.
FT /FTId=VAR_040765.
FT VARIANT 443 443 S -> G (in dbSNP:rs56305318).
FT /FTId=VAR_046763.
FT MUTAGEN 211 211 T->A: Prevents phosphorylation and
FT activation by STK11/LKB1 complex.
FT CONFLICT 125 125 E -> Q (in Ref. 5; AAA59991).
FT CONFLICT 139 139 E -> K (in Ref. 4; AAL69982 and 5;
FT AAA59991).
FT CONFLICT 149 149 R -> K (in Ref. 2; AAD48007).
FT CONFLICT 410 410 F -> S (in Ref. 1; AAC15093, 2; AAD48007,
FT 3; AAK82367, 4; AAL69982, 5; AAA59991, 7;
FT AAH24773 and 8; AAD51631).
FT CONFLICT 425 425 A -> G (in Ref. 5; AAA59991).
FT CONFLICT 456 456 S -> T (in Ref. 5; AAA59991).
FT CONFLICT 516 516 A -> D (in Ref. 5; AAA59991).
FT CONFLICT 603 603 N -> T (in Ref. 5; AAA59991).
FT CONFLICT 645 645 E -> K (in Ref. 5; AAA59991).
FT STRAND 56 64
FT STRAND 66 75
FT TURN 76 78
FT STRAND 81 88
FT HELIX 89 91
FT HELIX 94 109
FT STRAND 118 123
FT STRAND 125 132
FT HELIX 140 147
FT HELIX 152 171
FT HELIX 181 183
FT STRAND 184 186
FT STRAND 192 194
FT HELIX 201 203
FT STRAND 204 206
FT HELIX 208 210
FT STRAND 213 215
FT HELIX 216 218
FT HELIX 221 225
FT HELIX 232 248
FT HELIX 258 267
FT HELIX 278 287
FT TURN 292 294
FT HELIX 298 301
FT TURN 305 310
FT HELIX 329 337
FT HELIX 342 350
FT HELIX 356 364
SQ SEQUENCE 753 AA; 84489 MW; 0CA50C58A4A49D93 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 PHHKVQRSVF 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
//
ID MARK3_HUMAN Reviewed; 753 AA.
AC P27448; O60219; Q86TT8; Q8TB41; Q8WX83; Q96RG1; Q9UMY9; Q9UN34;
read moreDT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 4.
DT 22-JAN-2014, entry version 144.
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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:
RT Identification of 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
RT Wnt 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).
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.,
RA Sun H., Du H., Pepin K., Artiguenave F., Robert C., Cruaud C.,
RA Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P.,
RA Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N.,
RA Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C.,
RA Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S.,
RA Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B.,
RA Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M.,
RA Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S.,
RA Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D.,
RA Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A.,
RA 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.,
RA Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J.,
RA Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W.,
RA Quetier F., 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 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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
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,
RT similar to p78/C-TAK1.";
RL Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases.
RN [10]
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
RT and activity.";
RL Curr. Biol. 14:736-741(2004).
RN [11]
RP ENZYME 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.,
RA Boudeau J., Hawley S.A., Udd L., Maekelae T.P., Hardie D.G.,
RA Alessi D.R.;
RT "LKB1 is a master kinase that activates 13 kinases of the AMPK
RT subfamily, including MARK/PAR-1.";
RL EMBO J. 23:833-843(2004).
RN [12]
RP FUNCTION.
RX PubMed=16980613; DOI=10.1128/MCB.00231-06;
RA Dequiedt F., Martin M., Von Blume J., Vertommen D., Lecomte E.,
RA Mari N., Heinen M.F., Bachmann M., Twizere J.C., Huang M.C.,
RA Rider M.H., Piwnica-Worms H., Seufferlein T., Kettmann R.;
RT "New role for hPar-1 kinases EMK and C-TAK1 in regulating localization
RT and activity of class IIa histone deacetylases.";
RL Mol. Cell. Biol. 26:7086-7102(2006).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-549, AND MASS
RP SPECTROMETRY.
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.,
RA Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for
RT efficient phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-383; SER-400; SER-469;
RP THR-549; SER-598 AND SER-643, PHOSPHORYLATION [LARGE SCALE ANALYSIS]
RP AT SER-384 (ISOFORM 5), PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT
RP SER-407 (ISOFORM 6), AND MASS SPECTROMETRY.
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
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [15]
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 [16]
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.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-42; SER-383; SER-469 AND
RP SER-643, AND MASS SPECTROMETRY.
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 [18]
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 [19]
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
RT targets by binding acidic phospholipids.";
RL Cell 143:966-977(2010).
RN [20]
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.,
RA Buerckstuemmer T., 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 [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-469, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [22]
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.,
RA Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S.,
RA O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S.,
RA Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E.,
RA Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J.,
RA Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K.,
RA Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T.,
RA West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P.,
RA Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E.,
RA DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E.,
RA Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T.,
RA Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
CC -!- FUNCTION: Involved in the specific phosphorylation of microtubule-
CC associated proteins for tau, MAP2 and MAP4. Phosphorylates CDC25C
CC on 'Ser-216'. Regulates localization and activity of some histone
CC deacetylases by mediating phosphorylation of HDAC7, promoting
CC subsequent interaction between HDAC7 and 14-3-3 and export from
CC the nucleus.
CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
CC -!- ENZYME REGULATION: Activated by phosphorylation on Thr-211.
CC Inhibited by phosphorylation on Thr-564.
CC -!- INTERACTION:
CC Q8WXK3:ASB13; NbExp=2; IntAct=EBI-707595, EBI-707573;
CC Q8BHN0:Ppm1l (xeno); NbExp=3; IntAct=EBI-707595, EBI-7970002;
CC P31947:SFN; NbExp=2; IntAct=EBI-707595, EBI-476295;
CC Q15560:TCEA2; NbExp=2; IntAct=EBI-707595, EBI-710310;
CC P31946:YWHAB; NbExp=4; IntAct=EBI-707595, EBI-359815;
CC P61981:YWHAG; NbExp=2; IntAct=EBI-707595, EBI-359832;
CC Q04917:YWHAH; NbExp=4; IntAct=EBI-707595, EBI-306940;
CC P63104:YWHAZ; NbExp=9; IntAct=EBI-707595, EBI-347088;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Peripheral membrane protein.
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 Note=Contains a phosphoserine at position 384;
CC Name=6;
CC IsoId=P27448-7; Sequence=VSP_041582, VSP_004943;
CC Note=Contains a phosphoserine at position 407;
CC Name=7;
CC IsoId=P27448-8; Sequence=VSP_043197, VSP_043198;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- PTM: Phosphorylated at Thr-211 by STK11/LKB1 in complex with
CC STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39.
CC Phosphorylation at Thr-564 by PRKCZ/aPKC inhibits the kinase
CC activity.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK
CC Ser/Thr protein kinase family. SNF1 subfamily.
CC -!- SIMILARITY: Contains 1 KA1 (kinase-associated) domain.
CC -!- SIMILARITY: Contains 1 protein kinase domain.
CC -!- SIMILARITY: Contains 1 UBA domain.
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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; BC024773; AAH24773.1; -; mRNA.
DR EMBL; AF170723; AAD51631.1; -; mRNA.
DR PIR; S27966; S27966.
DR RefSeq; NP_001122390.1; NM_001128918.1.
DR RefSeq; NP_001122391.1; NM_001128919.1.
DR RefSeq; NP_001122392.1; NM_001128920.1.
DR RefSeq; NP_001122393.1; NM_001128921.1.
DR RefSeq; NP_002367.4; NM_002376.5.
DR UniGene; Hs.35828; -.
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 PDBsum; 2QNJ; -.
DR PDBsum; 3FE3; -.
DR ProteinModelPortal; P27448; -.
DR SMR; P27448; 18-366, 657-753.
DR DIP; DIP-34637N; -.
DR IntAct; P27448; 38.
DR MINT; MINT-272697; -.
DR STRING; 9606.ENSP00000411397; -.
DR ChEMBL; CHEMBL5600; -.
DR GuidetoPHARMACOLOGY; 2099; -.
DR PhosphoSite; P27448; -.
DR DMDM; 281185502; -.
DR PaxDb; P27448; -.
DR PRIDE; P27448; -.
DR DNASU; 4140; -.
DR Ensembl; ENST00000216288; ENSP00000216288; ENSG00000075413.
DR Ensembl; ENST00000303622; ENSP00000303698; ENSG00000075413.
DR Ensembl; ENST00000416682; ENSP00000408092; ENSG00000075413.
DR Ensembl; ENST00000429436; ENSP00000411397; ENSG00000075413.
DR Ensembl; ENST00000440884; ENSP00000402104; ENSG00000075413.
DR Ensembl; ENST00000553942; ENSP00000450772; ENSG00000075413.
DR GeneID; 4140; -.
DR KEGG; hsa:4140; -.
DR UCSC; uc001ymz.4; human.
DR CTD; 4140; -.
DR GeneCards; GC14P103851; -.
DR HGNC; HGNC:6897; MARK3.
DR HPA; HPA024652; -.
DR MIM; 602678; gene.
DR neXtProt; NX_P27448; -.
DR PharmGKB; PA30640; -.
DR eggNOG; COG0515; -.
DR HOGENOM; HOG000233025; -.
DR HOVERGEN; HBG052453; -.
DR InParanoid; P27448; -.
DR KO; K08798; -.
DR SignaLink; P27448; -.
DR ChiTaRS; MARK3; human.
DR EvolutionaryTrace; P27448; -.
DR GeneWiki; MARK3; -.
DR GenomeRNAi; 4140; -.
DR NextBio; 16260; -.
DR PRO; PR:P27448; -.
DR ArrayExpress; P27448; -.
DR Bgee; P27448; -.
DR CleanEx; HS_MARK3; -.
DR Genevestigator; P27448; -.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR InterPro; IPR028375; KA1/Ssp2_C.
DR InterPro; IPR001772; KA1_dom.
DR InterPro; IPR011009; Kinase-like_dom.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR002290; Ser/Thr_dual-sp_kinase_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR InterPro; IPR015940; UBA/transl_elong_EF1B_N_euk.
DR Pfam; PF02149; KA1; 1.
DR Pfam; PF00069; Pkinase; 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 Complete proteome; Kinase; Membrane; Nucleotide-binding;
KW Phosphoprotein; Polymorphism; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1 753 MAP/microtubule affinity-regulating
FT kinase 3.
FT /FTId=PRO_0000086304.
FT DOMAIN 56 307 Protein kinase.
FT DOMAIN 326 365 UBA.
FT DOMAIN 704 753 KA1.
FT NP_BIND 62 70 ATP (By similarity).
FT ACT_SITE 178 178 Proton acceptor (By similarity).
FT BINDING 85 85 ATP (By similarity).
FT MOD_RES 42 42 Phosphoserine.
FT MOD_RES 211 211 Phosphothreonine; by LKB1.
FT MOD_RES 383 383 Phosphoserine.
FT MOD_RES 400 400 Phosphoserine.
FT MOD_RES 469 469 Phosphoserine.
FT MOD_RES 549 549 Phosphothreonine.
FT MOD_RES 564 564 Phosphothreonine; by PKC/PRKCZ (By
FT similarity).
FT MOD_RES 598 598 Phosphoserine.
FT MOD_RES 643 643 Phosphoserine.
FT VAR_SEQ 161 161 Q -> QGCQAGQTIKVQVSFDLLSLMFTF (in isoform
FT 2 and isoform 6).
FT /FTId=VSP_041582.
FT VAR_SEQ 179 257 Missing (in isoform 7).
FT /FTId=VSP_043197.
FT VAR_SEQ 371 386 Missing (in isoform 5 and isoform 6).
FT /FTId=VSP_004943.
FT VAR_SEQ 615 638 Missing (in isoform 2, isoform 3 and
FT isoform 5).
FT /FTId=VSP_004944.
FT VAR_SEQ 615 623 Missing (in isoform 4).
FT /FTId=VSP_004945.
FT VAR_SEQ 624 638 Missing (in isoform 7).
FT /FTId=VSP_043198.
FT VARIANT 429 429 V -> A.
FT /FTId=VAR_040765.
FT VARIANT 443 443 S -> G (in dbSNP:rs56305318).
FT /FTId=VAR_046763.
FT MUTAGEN 211 211 T->A: Prevents phosphorylation and
FT activation by STK11/LKB1 complex.
FT CONFLICT 125 125 E -> Q (in Ref. 5; AAA59991).
FT CONFLICT 139 139 E -> K (in Ref. 4; AAL69982 and 5;
FT AAA59991).
FT CONFLICT 149 149 R -> K (in Ref. 2; AAD48007).
FT CONFLICT 410 410 F -> S (in Ref. 1; AAC15093, 2; AAD48007,
FT 3; AAK82367, 4; AAL69982, 5; AAA59991, 7;
FT AAH24773 and 8; AAD51631).
FT CONFLICT 425 425 A -> G (in Ref. 5; AAA59991).
FT CONFLICT 456 456 S -> T (in Ref. 5; AAA59991).
FT CONFLICT 516 516 A -> D (in Ref. 5; AAA59991).
FT CONFLICT 603 603 N -> T (in Ref. 5; AAA59991).
FT CONFLICT 645 645 E -> K (in Ref. 5; AAA59991).
FT STRAND 56 64
FT STRAND 66 75
FT TURN 76 78
FT STRAND 81 88
FT HELIX 89 91
FT HELIX 94 109
FT STRAND 118 123
FT STRAND 125 132
FT HELIX 140 147
FT HELIX 152 171
FT HELIX 181 183
FT STRAND 184 186
FT STRAND 192 194
FT HELIX 201 203
FT STRAND 204 206
FT HELIX 208 210
FT STRAND 213 215
FT HELIX 216 218
FT HELIX 221 225
FT HELIX 232 248
FT HELIX 258 267
FT HELIX 278 287
FT TURN 292 294
FT HELIX 298 301
FT TURN 305 310
FT HELIX 329 337
FT HELIX 342 350
FT HELIX 356 364
SQ SEQUENCE 753 AA; 84489 MW; 0CA50C58A4A49D93 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 PHHKVQRSVF 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
//
MIM
602678
*RECORD*
*FIELD* NO
602678
*FIELD* TI
*602678 MAP/MICROTUBULE AFFINITY-REGULATING KINASE 3; MARK3
;;MICROTUBULE-ASSOCIATED PROTEIN/MICROTUBULE AFFINITY-REGULATING KINASE
read more3;;
CDC25C-ASSOCIATED PROTEIN KINASE 1; CTAK1;;
PAR1, C. ELEGANS, HOMOLOG OF, A; PAR1A
*FIELD* TX
CLONING
MARK proteins are involved in the specific phosphorylation of
microtubule-associated proteins for tau (157140), MAP2 (157130), and
MAP4 (157132). MARK3 was originally identified as a marker (KP78) that
was induced by treatment with DNA damaging agents, and loss of MARK3 was
found with carcinogenesis in the pancreas (Parsa, 1988). MARK3 may be
involved in cell cycle regulation, and alterations in the MARK3 gene may
lead to carcinogenesis.
Peng et al. (1998) cloned a full-length HeLa cell cDNA encoding MARK3,
which they called CTAK1. By Northern blot analysis, CTAK1 was expressed
as 3.1- and 3.8-kb transcripts in all human tissues examined; an
additional 3.0-kb transcript was observed in heart. The predicted
729-amino acid CTAK1 protein belongs to the AMPK (e.g., 602739)
subfamily of protein kinases. Members of this subfamily are
characterized by a conserved N-terminal kinase domain, a divergent
C-terminal region, and a conserved region of about 40 amino acids at
their extreme C-termini, which end with an ELKL
(glutamate-leucine-lysine-leucine) domain. CTAK1 protein from HeLa cell
lysates resolved as a doublet of approximately 78 and 80 kD in Western
blot and immunoprecipitation analyses. Indirect immunofluorescence
detected CTAK1 in the cytoplasm but not the nucleus of HeLa cells. The
authors demonstrated that CTAK1 binds to CDC25C (157680) and
phosphorylates CDC25C on serine-216 in vitro and in vivo.
Using Western blot analysis, Lennerz et al. (2010) found that Par1a was
expressed at variable levels in all mouse tissues examined. Database
analysis suggested the presence of 5 Par1a splice variants encoding
proteins of 659 to 753 amino acids.
BIOCHEMICAL FEATURES
Muller et al. (2001) showed that KSR1 (601132) translocates from the
cytoplasm to the cell surface in response to growth factor treatment and
that this process is regulated by CTAK1. CTAK1 constitutively associates
with mammalian KSR1 and phosphorylates ser392 to confer 14-3-3 binding
and cytoplasmic sequestration of KSR1 in unstimulated cells. In response
to signal activation, the phosphorylation state of ser392 is reduced,
allowing the KSR1 complex to colocalize with activated RAS and RAF1
(164760) at the plasma membrane, thereby facilitating the
phosphorylation reactions required for the activation of MEK and MAPK
(see 176872).
MAPPING
Ono et al. (1997) used fluorescence in situ hybridization to map the
MARK3 gene to 14q32.3.
ANIMAL MODEL
Lennerz et al. (2010) obtained Par1a -/- mice at less than mendelian
ratios. Those that survived were viable and developed normally, but
became hypermetabolic and showed reduced body weight, adiposity, and
hypofertility compared with wildtype. Par1a -/- mice on a high-fat diet
exhibited profound resistance to development of glucose intolerance,
weight gain, and hepatic steatosis. Upon short-term starvation, livers
of Par1a -/- mice exhibited defects in both glycogen storage and glucose
mobilization, with depletion of lipid and glycogen stores, upregulation
of glycogen synthase (GYS1; 138570), and activation of autophagy. This
phenotype partly overlapped that displayed by Par1b -/- mice. Double
knockout of Par1a and Par1b in mice was embryonic lethal. At least 1
allele of either Par1a or Par1b was necessary for viability, but mice
expressing only 1 Par1 allele were not healthy, and a high proportion
died shortly after birth.
*FIELD* RF
1. Lennerz, J. K.; Hurov, J. B.; White, L. S.; Lewandowski, K. T.;
Prior, J. L.; Planer, G. J.; Gereau, R. W., IV; Piwnica-Worms, D.;
Schmidt, R. E.; Piwnica-Worms, H.: Loss of Par-1a/MARK3/C-TAK1 kinase
leads to reduced adiposity, resistance to hepatic steatosis, and defective
gluconeogenesis. Molec. Cell. Biol. 30: 5043-5056, 2010.
2. Muller, J.; Ory, S.; Copeland, T.; Piwnica-Worms, H.; Morrison,
D. K.: C-TAK1 regulates Ras signaling by phosphorylating the MAPK
scaffold, KSR1. Molec. Cell 8: 983-993, 2001.
3. Ono, T.; Kawabe, T.; Sonta, S.; Okamoto, T.: Assignment of MARK3
alias KP78 to human chromosome band 14q32.3 by in situ hybridization. Cytogenet.
Cell Genet. 79: 101-102, 1997.
4. Parsa, I.: Loss of Mr 78,000 marker in chemically induced transplantable
carcinomas and primary carcinoma of human pancreas. Cancer Res. 48:
2265-2272, 1988.
5. Peng, C.-Y.; Graves, P. R.; Ogg, S.; Thoma, R. S.; Byrnes, M. J.,
III; Wu, Z.; Stephenson, M. T.; Piwnica-Worms, H.: C-TAK1 protein
kinase phosphorylates human Cdc25C on serine 216 and promotes 14-3-3
protein binding. Cell Growth Differ. 9: 197-208, 1998.
*FIELD* CN
Patricia A. Hartz - updated: 11/15/2011
Stylianos E. Antonarakis - updated: 1/2/2002
Patti M. Sherman - updated: 6/25/1998
*FIELD* CD
Victor A. McKusick: 6/2/1998
*FIELD* ED
mgross: 02/08/2012
terry: 11/15/2011
alopez: 2/4/2009
mgross: 1/2/2002
dkim: 10/28/1998
dholmes: 7/2/1998
carol: 6/25/1998
psherman: 6/25/1998
psherman: 6/4/1998
carol: 6/3/1998
*RECORD*
*FIELD* NO
602678
*FIELD* TI
*602678 MAP/MICROTUBULE AFFINITY-REGULATING KINASE 3; MARK3
;;MICROTUBULE-ASSOCIATED PROTEIN/MICROTUBULE AFFINITY-REGULATING KINASE
read more3;;
CDC25C-ASSOCIATED PROTEIN KINASE 1; CTAK1;;
PAR1, C. ELEGANS, HOMOLOG OF, A; PAR1A
*FIELD* TX
CLONING
MARK proteins are involved in the specific phosphorylation of
microtubule-associated proteins for tau (157140), MAP2 (157130), and
MAP4 (157132). MARK3 was originally identified as a marker (KP78) that
was induced by treatment with DNA damaging agents, and loss of MARK3 was
found with carcinogenesis in the pancreas (Parsa, 1988). MARK3 may be
involved in cell cycle regulation, and alterations in the MARK3 gene may
lead to carcinogenesis.
Peng et al. (1998) cloned a full-length HeLa cell cDNA encoding MARK3,
which they called CTAK1. By Northern blot analysis, CTAK1 was expressed
as 3.1- and 3.8-kb transcripts in all human tissues examined; an
additional 3.0-kb transcript was observed in heart. The predicted
729-amino acid CTAK1 protein belongs to the AMPK (e.g., 602739)
subfamily of protein kinases. Members of this subfamily are
characterized by a conserved N-terminal kinase domain, a divergent
C-terminal region, and a conserved region of about 40 amino acids at
their extreme C-termini, which end with an ELKL
(glutamate-leucine-lysine-leucine) domain. CTAK1 protein from HeLa cell
lysates resolved as a doublet of approximately 78 and 80 kD in Western
blot and immunoprecipitation analyses. Indirect immunofluorescence
detected CTAK1 in the cytoplasm but not the nucleus of HeLa cells. The
authors demonstrated that CTAK1 binds to CDC25C (157680) and
phosphorylates CDC25C on serine-216 in vitro and in vivo.
Using Western blot analysis, Lennerz et al. (2010) found that Par1a was
expressed at variable levels in all mouse tissues examined. Database
analysis suggested the presence of 5 Par1a splice variants encoding
proteins of 659 to 753 amino acids.
BIOCHEMICAL FEATURES
Muller et al. (2001) showed that KSR1 (601132) translocates from the
cytoplasm to the cell surface in response to growth factor treatment and
that this process is regulated by CTAK1. CTAK1 constitutively associates
with mammalian KSR1 and phosphorylates ser392 to confer 14-3-3 binding
and cytoplasmic sequestration of KSR1 in unstimulated cells. In response
to signal activation, the phosphorylation state of ser392 is reduced,
allowing the KSR1 complex to colocalize with activated RAS and RAF1
(164760) at the plasma membrane, thereby facilitating the
phosphorylation reactions required for the activation of MEK and MAPK
(see 176872).
MAPPING
Ono et al. (1997) used fluorescence in situ hybridization to map the
MARK3 gene to 14q32.3.
ANIMAL MODEL
Lennerz et al. (2010) obtained Par1a -/- mice at less than mendelian
ratios. Those that survived were viable and developed normally, but
became hypermetabolic and showed reduced body weight, adiposity, and
hypofertility compared with wildtype. Par1a -/- mice on a high-fat diet
exhibited profound resistance to development of glucose intolerance,
weight gain, and hepatic steatosis. Upon short-term starvation, livers
of Par1a -/- mice exhibited defects in both glycogen storage and glucose
mobilization, with depletion of lipid and glycogen stores, upregulation
of glycogen synthase (GYS1; 138570), and activation of autophagy. This
phenotype partly overlapped that displayed by Par1b -/- mice. Double
knockout of Par1a and Par1b in mice was embryonic lethal. At least 1
allele of either Par1a or Par1b was necessary for viability, but mice
expressing only 1 Par1 allele were not healthy, and a high proportion
died shortly after birth.
*FIELD* RF
1. Lennerz, J. K.; Hurov, J. B.; White, L. S.; Lewandowski, K. T.;
Prior, J. L.; Planer, G. J.; Gereau, R. W., IV; Piwnica-Worms, D.;
Schmidt, R. E.; Piwnica-Worms, H.: Loss of Par-1a/MARK3/C-TAK1 kinase
leads to reduced adiposity, resistance to hepatic steatosis, and defective
gluconeogenesis. Molec. Cell. Biol. 30: 5043-5056, 2010.
2. Muller, J.; Ory, S.; Copeland, T.; Piwnica-Worms, H.; Morrison,
D. K.: C-TAK1 regulates Ras signaling by phosphorylating the MAPK
scaffold, KSR1. Molec. Cell 8: 983-993, 2001.
3. Ono, T.; Kawabe, T.; Sonta, S.; Okamoto, T.: Assignment of MARK3
alias KP78 to human chromosome band 14q32.3 by in situ hybridization. Cytogenet.
Cell Genet. 79: 101-102, 1997.
4. Parsa, I.: Loss of Mr 78,000 marker in chemically induced transplantable
carcinomas and primary carcinoma of human pancreas. Cancer Res. 48:
2265-2272, 1988.
5. Peng, C.-Y.; Graves, P. R.; Ogg, S.; Thoma, R. S.; Byrnes, M. J.,
III; Wu, Z.; Stephenson, M. T.; Piwnica-Worms, H.: C-TAK1 protein
kinase phosphorylates human Cdc25C on serine 216 and promotes 14-3-3
protein binding. Cell Growth Differ. 9: 197-208, 1998.
*FIELD* CN
Patricia A. Hartz - updated: 11/15/2011
Stylianos E. Antonarakis - updated: 1/2/2002
Patti M. Sherman - updated: 6/25/1998
*FIELD* CD
Victor A. McKusick: 6/2/1998
*FIELD* ED
mgross: 02/08/2012
terry: 11/15/2011
alopez: 2/4/2009
mgross: 1/2/2002
dkim: 10/28/1998
dholmes: 7/2/1998
carol: 6/25/1998
psherman: 6/25/1998
psherman: 6/4/1998
carol: 6/3/1998