PMYT1_HUMAN
ID PMYT1_HUMAN Reviewed; 499 AA.
AC Q99640; B3KUN8; B4DXD4; D3DUA4; F8W164; I3L1V2; O14731; Q7LE24; Q8TCM9;
DT 23-NOV-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 03-AUG-2022, entry version 194.
DE RecName: Full=Membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase;
DE EC=2.7.11.1;
DE AltName: Full=Myt1 kinase;
GN Name=PKMYT1; Synonyms=MYT1;
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 1), AND ACTIVITY REGULATION.
RX PubMed=9268380; DOI=10.1074/jbc.272.35.22300;
RA Booher R.N., Holman P.S., Fattaey A.;
RT "Human Myt1 is a cell cycle-regulated kinase that inhibits Cdc2 but not
RT Cdk2 activity.";
RL J. Biol. Chem. 272:22300-22306(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=9001210; DOI=10.1128/mcb.17.2.571;
RA Liu F., Stanton J.J., Wu Z., Piwnica-Worms H.;
RT "The human Myt1 kinase preferentially phosphorylates Cdc2 on threonine 14
RT and localizes to the endoplasmic reticulum and Golgi complex.";
RL Mol. Cell. Biol. 17:571-583(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2; 3 AND 4).
RC TISSUE=Testis, and Thyroid;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS CYS-140; ARG-417 AND
RP ALA-445.
RG NIEHS SNPs program;
RL Submitted (OCT-2002) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [6]
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 403-499 (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [8]
RP INTERACTION WITH PIN1.
RX PubMed=9499405; DOI=10.1101/gad.12.5.706;
RA Shen M., Stukenberg P.T., Kirschner M.W., Lu K.P.;
RT "The essential mitotic peptidyl-prolyl isomerase Pin1 binds and regulates
RT mitosis-specific phosphoproteins.";
RL Genes Dev. 12:706-720(1998).
RN [9]
RP PHOSPHORYLATION, COMPONENT OF CDC2-CCNB1 COMPLEX, INTERACTION WITH PIN1,
RP AND MUTAGENESIS OF ASP-251.
RX PubMed=10504341; DOI=10.1242/jcs.112.19.3361;
RA Wells N.J., Watanabe N., Tokusumi T., Jiang W., Verdecia M.A., Hunter T.;
RT "The C-terminal domain of the Cdc2 inhibitory kinase Myt1 interacts with
RT Cdc2 complexes and is required for inhibition of G(2)/M progression.";
RL J. Cell Sci. 112:3361-3371(1999).
RN [10]
RP FUNCTION, AND MUTAGENESIS OF ASN-238 AND 486-ARG--LEU-488.
RX PubMed=10373560; DOI=10.1128/mcb.19.7.5113;
RA Liu F., Rothblum-Oviatt C., Ryan C.E., Piwnica-Worms H.;
RT "Overproduction of human Myt1 kinase induces a G2 cell cycle delay by
RT interfering with the intracellular trafficking of Cdc2-cyclin B1
RT complexes.";
RL Mol. Cell. Biol. 19:5113-5123(1999).
RN [11]
RP PHOSPHORYLATION AT SER-426 AND THR-495.
RX PubMed=12738781; DOI=10.1074/jbc.c300126200;
RA Nakajima H., Toyoshima-Morimoto F., Taniguchi E., Nishida E.;
RT "Identification of a consensus motif for Plk (Polo-like kinase)
RT phosphorylation reveals Myt1 as a Plk1 substrate.";
RL J. Biol. Chem. 278:25277-25280(2003).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-17; SER-94; SER-469 AND
RP THR-495, 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 [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-120; SER-469 AND SER-473, AND
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 [14]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, PHOSPHORYLATION [LARGE SCALE
RP ANALYSIS] AT THR-17 AND SER-160, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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 [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-40; SER-94; SER-120; SER-143;
RP SER-469 AND SER-482, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=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 [16]
RP VARIANTS [LARGE SCALE ANALYSIS] GLN-103; CYS-140; HIS-246 AND LYS-351.
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).
CC -!- FUNCTION: Acts as a negative regulator of entry into mitosis (G2 to M
CC transition) by phosphorylation of the CDK1 kinase specifically when
CC CDK1 is complexed to cyclins. Mediates phosphorylation of CDK1
CC predominantly on 'Thr-14'. Also involved in Golgi fragmentation. May be
CC involved in phosphorylation of CDK1 on 'Tyr-15' to a lesser degree,
CC however tyrosine kinase activity is unclear and may be indirect. May be
CC a downstream target of Notch signaling pathway during eye development.
CC {ECO:0000269|PubMed:10373560, ECO:0000269|PubMed:9001210}.
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: Negatively regulated by hyperphosphorylation
CC during mitosis. The hyperphosphorylated form does not associate with
CC CCNB1-CDC2 complexes. The PLK1 protein kinase may be required for
CC mitotic phosphorylation. {ECO:0000269|PubMed:9268380}.
CC -!- SUBUNIT: Interacts with CDC2-CCNB1 complex. Can also interact with PIN1
CC when phosphorylated by CDC2-CCNB1. {ECO:0000269|PubMed:10504341,
CC ECO:0000269|PubMed:9499405}.
CC -!- INTERACTION:
CC Q99640; P14635: CCNB1; NbExp=6; IntAct=EBI-495308, EBI-495332;
CC Q99640; P06493: CDK1; NbExp=7; IntAct=EBI-495308, EBI-444308;
CC Q99640-2; O95870: ABHD16A; NbExp=3; IntAct=EBI-12257782, EBI-348517;
CC Q99640-2; P07766: CD3E; NbExp=3; IntAct=EBI-12257782, EBI-1211297;
CC Q99640-2; P11912: CD79A; NbExp=3; IntAct=EBI-12257782, EBI-7797864;
CC Q99640-2; P56748: CLDN8; NbExp=3; IntAct=EBI-12257782, EBI-10215641;
CC Q99640-2; Q9GZR5: ELOVL4; NbExp=3; IntAct=EBI-12257782, EBI-18535450;
CC Q99640-2; Q969F0: FATE1; NbExp=3; IntAct=EBI-12257782, EBI-743099;
CC Q99640-2; Q9H400: LIME1; NbExp=3; IntAct=EBI-12257782, EBI-2830566;
CC Q99640-2; Q8N386: LRRC25; NbExp=3; IntAct=EBI-12257782, EBI-11304917;
CC Q99640-2; Q5SR56: MFSD14B; NbExp=3; IntAct=EBI-12257782, EBI-373355;
CC Q99640-2; Q6N075: MFSD5; NbExp=3; IntAct=EBI-12257782, EBI-3920969;
CC Q99640-2; Q86VR2: RETREG3; NbExp=3; IntAct=EBI-12257782, EBI-10192441;
CC Q99640-2; Q14973: SLC10A1; NbExp=3; IntAct=EBI-12257782, EBI-3923031;
CC Q99640-2; Q8IWU4: SLC30A8; NbExp=3; IntAct=EBI-12257782, EBI-10262251;
CC Q99640-2; Q96IK0: TMEM101; NbExp=3; IntAct=EBI-12257782, EBI-3922699;
CC Q99640-2; Q8NBD8: TMEM229B; NbExp=3; IntAct=EBI-12257782, EBI-12195227;
CC Q99640-2; Q9Y320: TMX2; NbExp=3; IntAct=EBI-12257782, EBI-6447886;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:9001210}; Peripheral membrane protein
CC {ECO:0000269|PubMed:9001210}. Golgi apparatus membrane
CC {ECO:0000269|PubMed:9001210}; Peripheral membrane protein
CC {ECO:0000269|PubMed:9001210}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q99640-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q99640-2; Sequence=VSP_045699;
CC Name=3;
CC IsoId=Q99640-3; Sequence=VSP_046846;
CC Name=4;
CC IsoId=Q99640-4; Sequence=VSP_046847;
CC -!- DOMAIN: The membrane-association motif is essential for the
CC localization to membrane of Golgi stack. According to some authors, it
CC is a transmembrane domain; the existence of a transmembrane region is
CC however unproven.
CC -!- PTM: Autophosphorylated. Phosphorylated by CDC2-CCNB1 complexes on
CC undefined serine and threonine residues. The phosphorylation by CDC2-
CC CCNB1 complexes may inhibit the catalytic activity.
CC {ECO:0000269|PubMed:10504341, ECO:0000269|PubMed:12738781}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein
CC kinase family. WEE1 subfamily. {ECO:0000255|PROSITE-ProRule:PRU00159}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAD28540.1; Type=Miscellaneous discrepancy; Note=Chimeric cDNA.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/pkmyt1/";
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DR EMBL; AF014118; AAB71843.1; -; mRNA.
DR EMBL; U56816; AAC50949.1; -; mRNA.
DR EMBL; AK097642; BAG53500.1; -; mRNA.
DR EMBL; AK098452; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AK301926; BAG63346.1; -; mRNA.
DR EMBL; AF549406; AAN40703.1; -; Genomic_DNA.
DR EMBL; AC004233; AAC04478.1; -; Genomic_DNA.
DR EMBL; AC004235; AAC04477.1; -; Genomic_DNA.
DR EMBL; CH471112; EAW85439.1; -; Genomic_DNA.
DR EMBL; CH471112; EAW85440.1; -; Genomic_DNA.
DR EMBL; AL713779; CAD28540.1; ALT_SEQ; mRNA.
DR CCDS; CCDS10486.1; -. [Q99640-1]
DR CCDS; CCDS45391.1; -. [Q99640-2]
DR CCDS; CCDS58414.1; -. [Q99640-3]
DR CCDS; CCDS58415.1; -. [Q99640-4]
DR RefSeq; NP_001245379.1; NM_001258450.1. [Q99640-4]
DR RefSeq; NP_001245380.1; NM_001258451.1. [Q99640-3]
DR RefSeq; NP_004194.3; NM_004203.4. [Q99640-1]
DR RefSeq; NP_872629.1; NM_182687.2. [Q99640-2]
DR RefSeq; XP_011521036.1; XM_011522734.2. [Q99640-1]
DR RefSeq; XP_011521037.1; XM_011522735.2. [Q99640-3]
DR RefSeq; XP_011521038.1; XM_011522736.2. [Q99640-3]
DR PDB; 3P1A; X-ray; 1.70 A; A=75-362.
DR PDB; 5VCV; X-ray; 1.92 A; A=75-362.
DR PDB; 5VCW; X-ray; 2.25 A; A/B=75-362.
DR PDB; 5VCX; X-ray; 2.70 A; A=75-362.
DR PDB; 5VCY; X-ray; 1.56 A; A=75-362.
DR PDB; 5VCZ; X-ray; 1.50 A; A=75-362.
DR PDB; 5VD0; X-ray; 2.13 A; A=75-362.
DR PDB; 5VD1; X-ray; 1.70 A; A=75-362.
DR PDB; 5VD3; X-ray; 1.80 A; A=75-362.
DR PDBsum; 3P1A; -.
DR PDBsum; 5VCV; -.
DR PDBsum; 5VCW; -.
DR PDBsum; 5VCX; -.
DR PDBsum; 5VCY; -.
DR PDBsum; 5VCZ; -.
DR PDBsum; 5VD0; -.
DR PDBsum; 5VD1; -.
DR PDBsum; 5VD3; -.
DR AlphaFoldDB; Q99640; -.
DR SMR; Q99640; -.
DR BioGRID; 114544; 136.
DR ELM; Q99640; -.
DR IntAct; Q99640; 44.
DR MINT; Q99640; -.
DR STRING; 9606.ENSP00000262300; -.
DR BindingDB; Q99640; -.
DR ChEMBL; CHEMBL3984; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; Q99640; -.
DR GuidetoPHARMACOLOGY; 2167; -.
DR iPTMnet; Q99640; -.
DR PhosphoSitePlus; Q99640; -.
DR BioMuta; PKMYT1; -.
DR DMDM; 55976573; -.
DR EPD; Q99640; -.
DR jPOST; Q99640; -.
DR MassIVE; Q99640; -.
DR MaxQB; Q99640; -.
DR PaxDb; Q99640; -.
DR PeptideAtlas; Q99640; -.
DR PRIDE; Q99640; -.
DR ProteomicsDB; 29565; -.
DR ProteomicsDB; 46754; -.
DR ProteomicsDB; 5428; -.
DR ProteomicsDB; 78372; -. [Q99640-1]
DR Antibodypedia; 23946; 528 antibodies from 34 providers.
DR DNASU; 9088; -.
DR Ensembl; ENST00000262300.13; ENSP00000262300.8; ENSG00000127564.17. [Q99640-1]
DR Ensembl; ENST00000440027.6; ENSP00000397739.2; ENSG00000127564.17. [Q99640-2]
DR Ensembl; ENST00000573944.5; ENSP00000459123.1; ENSG00000127564.17. [Q99640-3]
DR Ensembl; ENST00000574385.5; ENSP00000458943.1; ENSG00000127564.17. [Q99640-3]
DR Ensembl; ENST00000574730.5; ENSP00000460868.1; ENSG00000127564.17. [Q99640-4]
DR GeneID; 9088; -.
DR KEGG; hsa:9088; -.
DR MANE-Select; ENST00000262300.13; ENSP00000262300.8; NM_004203.5; NP_004194.3.
DR UCSC; uc002csm.4; human. [Q99640-1]
DR CTD; 9088; -.
DR DisGeNET; 9088; -.
DR GeneCards; PKMYT1; -.
DR HGNC; HGNC:29650; PKMYT1.
DR HPA; ENSG00000127564; Tissue enhanced (bone marrow, testis).
DR MIM; 602474; gene.
DR neXtProt; NX_Q99640; -.
DR OpenTargets; ENSG00000127564; -.
DR PharmGKB; PA385; -.
DR VEuPathDB; HostDB:ENSG00000127564; -.
DR eggNOG; KOG0601; Eukaryota.
DR GeneTree; ENSGT00940000159427; -.
DR InParanoid; Q99640; -.
DR OMA; PCTPPKD; -.
DR OrthoDB; 1063695at2759; -.
DR PhylomeDB; Q99640; -.
DR TreeFam; TF101087; -.
DR PathwayCommons; Q99640; -.
DR Reactome; R-HSA-156711; Polo-like kinase mediated events.
DR Reactome; R-HSA-69273; Cyclin A/B1/B2 associated events during G2/M transition.
DR Reactome; R-HSA-69478; G2/M DNA replication checkpoint.
DR SignaLink; Q99640; -.
DR SIGNOR; Q99640; -.
DR BioGRID-ORCS; 9088; 786 hits in 1115 CRISPR screens.
DR ChiTaRS; PKMYT1; human.
DR EvolutionaryTrace; Q99640; -.
DR GeneWiki; PKMYT1; -.
DR GenomeRNAi; 9088; -.
DR Pharos; Q99640; Tchem.
DR PRO; PR:Q99640; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q99640; protein.
DR Bgee; ENSG00000127564; Expressed in right testis and 112 other tissues.
DR ExpressionAtlas; Q99640; baseline and differential.
DR Genevisible; Q99640; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005783; C:endoplasmic reticulum; TAS:ProtInc.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016301; F:kinase activity; IDA:HGNC-UCL.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004672; F:protein kinase activity; IBA:GO_Central.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0000086; P:G2/M transition of mitotic cell cycle; TAS:Reactome.
DR GO; GO:0051321; P:meiotic cell cycle; IBA:GO_Central.
DR GO; GO:0000278; P:mitotic cell cycle; TAS:ProtInc.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR GO; GO:0000079; P:regulation of cyclin-dependent protein serine/threonine kinase activity; TAS:ProtInc.
DR GO; GO:0007088; P:regulation of mitotic nuclear division; TAS:ProtInc.
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; IPR016235; Tyr/Thr_kinase_Cdc2_inhib.
DR Pfam; PF00069; Pkinase; 1.
DR PIRSF; PIRSF000567; TYPK_Myt1; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; ATP-binding; Cell cycle;
KW Endoplasmic reticulum; Golgi apparatus; Kinase; Magnesium; Membrane;
KW Metal-binding; Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..499
FT /note="Membrane-associated tyrosine- and threonine-specific
FT cdc2-inhibitory kinase"
FT /id="PRO_0000086573"
FT DOMAIN 110..359
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..29
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 42..72
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 398..499
FT /note="Interaction with PIN1"
FT REGION 437..499
FT /note="Interaction with CDC2-CCNB1"
FT REGION 451..485
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 382..398
FT /note="Membrane-association motif"
FT COMPBIAS 11..26
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 48..62
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 233
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 116..124
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 139
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 238
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 251
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 17
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:20068231"
FT MOD_RES 40
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 94
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 120
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 143
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 160
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 426
FT /note="Phosphoserine; by PLK1"
FT /evidence="ECO:0000269|PubMed:12738781"
FT MOD_RES 469
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:23186163"
FT MOD_RES 473
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 482
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 495
FT /note="Phosphothreonine; by PLK1"
FT /evidence="ECO:0000269|PubMed:12738781,
FT ECO:0007744|PubMed:18691976"
FT VAR_SEQ 1..9
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_046846"
FT VAR_SEQ 5..73
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_046847"
FT VAR_SEQ 439..499
FT /note="SLSPEAVLARTVGSTSTPRSRCTPRDALDLSDINSEPPRGSFPSFEPRNLLS
FT LFEDTLDPT -> GHPPCLACPPAGLHSPLRLSWPGLWGAPPPPGAGAHPGMPWT (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_045699"
FT VARIANT 103
FT /note="E -> Q (in dbSNP:rs55834293)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041034"
FT VARIANT 140
FT /note="R -> C (in dbSNP:rs4149796)"
FT /evidence="ECO:0000269|PubMed:17344846, ECO:0000269|Ref.4"
FT /id="VAR_019928"
FT VARIANT 246
FT /note="R -> H (in dbSNP:rs35192104)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041035"
FT VARIANT 351
FT /note="E -> K (in dbSNP:rs56382954)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041036"
FT VARIANT 417
FT /note="P -> R (in dbSNP:rs4149800)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_019929"
FT VARIANT 445
FT /note="V -> A (in dbSNP:rs10546)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_019930"
FT MUTAGEN 238
FT /note="N->A: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:10373560"
FT MUTAGEN 251
FT /note="D->A: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:10504341"
FT MUTAGEN 486..488
FT /note="RNL->AAA: Loss of CDC2-CCNB1 interaction."
FT /evidence="ECO:0000269|PubMed:10373560"
FT CONFLICT 131
FT /note="E -> A (in Ref. 4; BAG53500)"
FT /evidence="ECO:0000305"
FT CONFLICT 415
FT /note="G -> D (in Ref. 1; AAB71843)"
FT /evidence="ECO:0000305"
FT CONFLICT 427
FT /note="L -> F (in Ref. 1; AAB71843)"
FT /evidence="ECO:0000305"
FT CONFLICT 491
FT /note="L -> M (in Ref. 1; AAB71843)"
FT /evidence="ECO:0000305"
FT STRAND 84..87
FT /evidence="ECO:0007829|PDB:5VD1"
FT STRAND 101..103
FT /evidence="ECO:0007829|PDB:5VCZ"
FT HELIX 105..109
FT /evidence="ECO:0007829|PDB:5VCZ"
FT STRAND 110..119
FT /evidence="ECO:0007829|PDB:5VCZ"
FT STRAND 122..129
FT /evidence="ECO:0007829|PDB:5VCZ"
FT TURN 130..132
FT /evidence="ECO:0007829|PDB:5VCZ"
FT STRAND 135..144
FT /evidence="ECO:0007829|PDB:5VCZ"
FT HELIX 148..164
FT /evidence="ECO:0007829|PDB:5VCZ"
FT STRAND 173..179
FT /evidence="ECO:0007829|PDB:5VCZ"
FT STRAND 182..188
FT /evidence="ECO:0007829|PDB:5VCZ"
FT HELIX 194..201
FT /evidence="ECO:0007829|PDB:5VCZ"
FT HELIX 207..226
FT /evidence="ECO:0007829|PDB:5VCZ"
FT HELIX 236..238
FT /evidence="ECO:0007829|PDB:5VCZ"
FT STRAND 239..241
FT /evidence="ECO:0007829|PDB:5VCZ"
FT HELIX 243..245
FT /evidence="ECO:0007829|PDB:5VCZ"
FT STRAND 247..249
FT /evidence="ECO:0007829|PDB:5VCZ"
FT HELIX 252..254
FT /evidence="ECO:0007829|PDB:5VD0"
FT STRAND 256..259
FT /evidence="ECO:0007829|PDB:5VCZ"
FT STRAND 261..263
FT /evidence="ECO:0007829|PDB:5VCZ"
FT TURN 271..273
FT /evidence="ECO:0007829|PDB:5VCZ"
FT HELIX 276..280
FT /evidence="ECO:0007829|PDB:5VCZ"
FT HELIX 286..301
FT /evidence="ECO:0007829|PDB:5VCZ"
FT HELIX 309..315
FT /evidence="ECO:0007829|PDB:5VCZ"
FT TURN 316..318
FT /evidence="ECO:0007829|PDB:5VCZ"
FT HELIX 322..325
FT /evidence="ECO:0007829|PDB:5VCZ"
FT HELIX 330..339
FT /evidence="ECO:0007829|PDB:5VCZ"
FT TURN 344..346
FT /evidence="ECO:0007829|PDB:5VCZ"
FT HELIX 350..354
FT /evidence="ECO:0007829|PDB:5VCZ"
FT HELIX 357..359
FT /evidence="ECO:0007829|PDB:5VCZ"
SQ SEQUENCE 499 AA; 54521 MW; 4DF28A5965265567 CRC64;
MLERPPALAM PMPTEGTPPP LSGTPIPVPA YFRHAEPGFS LKRPRGLSRS LPPPPPAKGS
IPISRLFPPR TPGWHQLQPR RVSFRGEASE TLQSPGYDPS RPESFFQQSF QRLSRLGHGS
YGEVFKVRSK EDGRLYAVKR SMSPFRGPKD RARKLAEVGS HEKVGQHPCC VRLEQAWEEG
GILYLQTELC GPSLQQHCEA WGASLPEAQV WGYLRDTLLA LAHLHSQGLV HLDVKPANIF
LGPRGRCKLG DFGLLVELGT AGAGEVQEGD PRYMAPELLQ GSYGTAADVF SLGLTILEVA
CNMELPHGGE GWQQLRQGYL PPEFTAGLSS ELRSVLVMML EPDPKLRATA EALLALPVLR
QPRAWGVLWC MAAEALSRGW ALWQALLALL CWLWHGLAHP ASWLQPLGPP ATPPGSPPCS
LLLDSSLSSN WDDDSLGPSL SPEAVLARTV GSTSTPRSRC TPRDALDLSD INSEPPRGSF
PSFEPRNLLS LFEDTLDPT
