GWL_HUMAN
ID GWL_HUMAN Reviewed; 879 AA.
AC Q96GX5; Q5T8D5; Q5T8D7; Q8NCD6; Q96SJ5;
DT 05-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 182.
DE RecName: Full=Serine/threonine-protein kinase greatwall;
DE Short=GW;
DE Short=GWL;
DE Short=hGWL;
DE EC=2.7.11.1;
DE AltName: Full=Microtubule-associated serine/threonine-protein kinase-like;
DE Short=MAST-L;
GN Name=MASTL; Synonyms=GW, GWL, THC2;
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 [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
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 [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-631, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein phosphorylation
RT analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-370, 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 [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-370; SER-657 AND SER-878, AND
RP 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 [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-293; SER-370; SER-552;
RP SER-556; THR-722; SER-725; THR-741; SER-875 AND SER-878, AND IDENTIFICATION
RP 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 [8]
RP FUNCTION.
RX PubMed=19680222; DOI=10.1038/emboj.2009.228;
RA Vigneron S., Brioudes E., Burgess A., Labbe J.C., Lorca T., Castro A.;
RT "Greatwall maintains mitosis through regulation of PP2A.";
RL EMBO J. 28:2786-2793(2009).
RN [9]
RP SUBCELLULAR LOCATION, AND CHARACTERIZATION OF VARIANT ASP-167.
RX PubMed=19460416; DOI=10.1016/j.exphem.2009.05.005;
RA Johnson H.J., Gandhi M.J., Shafizadeh E., Langer N.B., Pierce E.L.,
RA Paw B.H., Gilligan D.M., Drachman J.G.;
RT "In vivo inactivation of MASTL kinase results in thrombocytopenia.";
RL Exp. Hematol. 37:901-908(2009).
RN [10]
RP FUNCTION.
RX PubMed=19793917; DOI=10.1091/mbc.e09-07-0643;
RA Castilho P.V., Williams B.C., Mochida S., Zhao Y., Goldberg M.L.;
RT "The M phase kinase Greatwall (Gwl) promotes inactivation of PP2A/B55delta,
RT a phosphatase directed against CDK phosphosites.";
RL Mol. Biol. Cell 20:4777-4789(2009).
RN [11]
RP 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 [12]
RP FUNCTION, SUBCELLULAR LOCATION, AND PHOSPHORYLATION.
RX PubMed=20818157; DOI=10.4161/cc.9.17.12832;
RA Voets E., Wolthuis R.M.F.;
RT "MASTL is the human orthologue of Greatwall kinase that facilitates mitotic
RT entry, anaphase and cytokinesis.";
RL Cell Cycle 9:3591-3601(2010).
RN [13]
RP FUNCTION, SUBCELLULAR LOCATION, AND PHOSPHORYLATION.
RX PubMed=20538976; DOI=10.1073/pnas.0914191107;
RA Burgess A., Vigneron S., Brioudes E., Labbe J.-C., Lorca T., Castro A.;
RT "Loss of human Greatwall results in G2 arrest and multiple mitotic defects
RT due to deregulation of the cyclin B-Cdc2/PP2A balance.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:12564-12569(2010).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-207; THR-222; SER-370;
RP SER-631; SER-668; SER-875 AND SER-878, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [15]
RP CATALYTIC ACTIVITY, AND MUTAGENESIS OF LYS-72.
RX PubMed=21164014; DOI=10.1126/science.1197048;
RA Gharbi-Ayachi A., Labbe J.C., Burgess A., Vigneron S., Strub J.M.,
RA Brioudes E., Van-Dorsselaer A., Castro A., Lorca T.;
RT "The substrate of Greatwall kinase, Arpp19, controls mitosis by inhibiting
RT protein phosphatase 2A.";
RL Science 330:1673-1677(2010).
RN [16]
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 [17]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-370; SER-453; THR-519;
RP SER-657 AND SER-878, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP 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 [19]
RP VARIANT ASP-167, FUNCTION, AND POSSIBLE INVOLVEMENT IN THROMBOCYTOPENIA.
RX PubMed=12890928; DOI=10.1159/000071812;
RA Gandhi M.J., Cummings C.L., Drachman J.G.;
RT "FLJ14813 missense mutation: a candidate for autosomal dominant
RT thrombocytopenia on human chromosome 10.";
RL Hum. Hered. 55:66-70(2003).
RN [20]
RP VARIANTS [LARGE SCALE ANALYSIS] LYS-337; ILE-610 AND ALA-620.
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: Serine/threonine kinase that plays a key role in M phase by
CC acting as a regulator of mitosis entry and maintenance. Acts by
CC promoting the inactivation of protein phosphatase 2A (PP2A) during M
CC phase: does not directly inhibit PP2A but acts by mediating
CC phosphorylation and subsequent activation of ARPP19 and ENSA at 'Ser-
CC 62' and 'Ser-67', respectively. ARPP19 and ENSA are phosphatase
CC inhibitors that specifically inhibit the PPP2R2D (PR55-delta) subunit
CC of PP2A. Inactivation of PP2A during M phase is essential to keep
CC cyclin-B1-CDK1 activity high. Following DNA damage, it is also involved
CC in checkpoint recovery by being inhibited. Phosphorylates histone
CC protein in vitro; however such activity is unsure in vivo. May be
CC involved in megakaryocyte differentiation.
CC {ECO:0000269|PubMed:12890928, ECO:0000269|PubMed:19680222,
CC ECO:0000269|PubMed:19793917, ECO:0000269|PubMed:20538976,
CC ECO:0000269|PubMed:20818157}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC Evidence={ECO:0000269|PubMed:21164014};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1; Evidence={ECO:0000269|PubMed:21164014};
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, microtubule organizing
CC center, centrosome {ECO:0000269|PubMed:20818157}. Nucleus
CC {ECO:0000269|PubMed:19460416, ECO:0000269|PubMed:20818157}. Cleavage
CC furrow {ECO:0000269|PubMed:20818157}. Note=During interphase is mainly
CC nuclear, upon nuclear envelope breakdown localizes at the cytoplasm and
CC during mitosis at the centrosomes. Upon mitotic exit moves to the
CC cleavage furrow. {ECO:0000269|PubMed:20818157}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q96GX5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96GX5-2; Sequence=VSP_014574, VSP_014575;
CC Name=3;
CC IsoId=Q96GX5-3; Sequence=VSP_014574;
CC -!- PTM: Phosphorylation at Thr-741 by CDK1 during M phase activates its
CC kinase activity (By similarity). Maximum phosphorylation occurs in
CC prometaphase. {ECO:0000250, ECO:0000269|PubMed:20538976,
CC ECO:0000269|PubMed:20818157}.
CC -!- DISEASE: Note=Defects in MASTL may play a role in the pathogenesis of
CC thrombocytopenia, a disorder defined by reduced number of platelets in
CC circulating blood, resulting in the potential for increased bleeding
CC and decreased ability for clotting. {ECO:0000269|PubMed:12890928}.
CC -!- MISCELLANEOUS: Reduced levels of MASTL by RNAi causes mitotic
CC abnormalities that consist of delay in G(2) phase and slow chromosome
CC condensation. Cells that enter and progress through mitosis often fail
CC to completely separate their sister chromatids in anaphase leading to
CC the formation of 4N G(1) cells subsequent to failure of cytokinesis
CC (PubMed:20818157 and PubMed:20538976).
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. {ECO:0000305}.
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DR EMBL; AK027719; BAB55321.1; -; mRNA.
DR EMBL; AK074804; BAC11218.1; -; mRNA.
DR EMBL; AL160291; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC009107; AAH09107.1; -; mRNA.
DR CCDS; CCDS53502.1; -. [Q96GX5-1]
DR CCDS; CCDS53503.1; -. [Q96GX5-2]
DR CCDS; CCDS7153.1; -. [Q96GX5-3]
DR RefSeq; NP_001165774.1; NM_001172303.2. [Q96GX5-1]
DR RefSeq; NP_001165775.1; NM_001172304.2. [Q96GX5-2]
DR RefSeq; NP_116233.2; NM_032844.4. [Q96GX5-3]
DR PDB; 5LOH; X-ray; 3.10 A; A/B=1-194, A/B=740-879.
DR PDBsum; 5LOH; -.
DR AlphaFoldDB; Q96GX5; -.
DR SMR; Q96GX5; -.
DR BioGRID; 124364; 50.
DR IntAct; Q96GX5; 25.
DR MINT; Q96GX5; -.
DR STRING; 9606.ENSP00000365107; -.
DR ChEMBL; CHEMBL4105826; -.
DR GlyGen; Q96GX5; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q96GX5; -.
DR PhosphoSitePlus; Q96GX5; -.
DR BioMuta; MASTL; -.
DR DMDM; 68565604; -.
DR EPD; Q96GX5; -.
DR jPOST; Q96GX5; -.
DR MassIVE; Q96GX5; -.
DR MaxQB; Q96GX5; -.
DR PaxDb; Q96GX5; -.
DR PeptideAtlas; Q96GX5; -.
DR PRIDE; Q96GX5; -.
DR ProteomicsDB; 76677; -. [Q96GX5-1]
DR ProteomicsDB; 76678; -. [Q96GX5-2]
DR ProteomicsDB; 76679; -. [Q96GX5-3]
DR Antibodypedia; 12704; 359 antibodies from 32 providers.
DR DNASU; 84930; -.
DR Ensembl; ENST00000342386.10; ENSP00000343446.5; ENSG00000120539.15. [Q96GX5-2]
DR Ensembl; ENST00000375940.9; ENSP00000365107.5; ENSG00000120539.15. [Q96GX5-1]
DR Ensembl; ENST00000375946.8; ENSP00000365113.4; ENSG00000120539.15. [Q96GX5-3]
DR GeneID; 84930; -.
DR KEGG; hsa:84930; -.
DR MANE-Select; ENST00000375940.9; ENSP00000365107.5; NM_001172303.3; NP_001165774.1.
DR UCSC; uc001itl.3; human. [Q96GX5-1]
DR CTD; 84930; -.
DR DisGeNET; 84930; -.
DR GeneCards; MASTL; -.
DR HGNC; HGNC:19042; MASTL.
DR HPA; ENSG00000120539; Low tissue specificity.
DR MalaCards; MASTL; -.
DR MIM; 608221; gene.
DR neXtProt; NX_Q96GX5; -.
DR OpenTargets; ENSG00000120539; -.
DR Orphanet; 168629; Autosomal thrombocytopenia with normal platelets.
DR PharmGKB; PA134943781; -.
DR VEuPathDB; HostDB:ENSG00000120539; -.
DR eggNOG; KOG0606; Eukaryota.
DR GeneTree; ENSGT00940000157002; -.
DR HOGENOM; CLU_016048_0_0_1; -.
DR InParanoid; Q96GX5; -.
DR OMA; STSHTPY; -.
DR OrthoDB; 878671at2759; -.
DR PhylomeDB; Q96GX5; -.
DR TreeFam; TF313149; -.
DR PathwayCommons; Q96GX5; -.
DR Reactome; R-HSA-2465910; MASTL Facilitates Mitotic Progression.
DR SignaLink; Q96GX5; -.
DR SIGNOR; Q96GX5; -.
DR BioGRID-ORCS; 84930; 739 hits in 1063 CRISPR screens.
DR ChiTaRS; MASTL; human.
DR GeneWiki; MASTL; -.
DR GenomeRNAi; 84930; -.
DR Pharos; Q96GX5; Tbio.
DR PRO; PR:Q96GX5; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q96GX5; protein.
DR Bgee; ENSG00000120539; Expressed in secondary oocyte and 151 other tissues.
DR ExpressionAtlas; Q96GX5; baseline and differential.
DR Genevisible; Q96GX5; HS.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0032154; C:cleavage furrow; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016301; F:kinase activity; IDA:UniProtKB.
DR GO; GO:0051721; F:protein phosphatase 2A binding; ISS:UniProtKB.
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:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISS:UniProtKB.
DR GO; GO:0007147; P:female meiosis II; IEA:Ensembl.
DR GO; GO:0000086; P:G2/M transition of mitotic cell cycle; IMP:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0000278; P:mitotic cell cycle; IMP:UniProtKB.
DR GO; GO:0032515; P:negative regulation of phosphoprotein phosphatase activity; IMP:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:1904668; P:positive regulation of ubiquitin protein ligase activity; IEA:Ensembl.
DR GO; GO:0051726; P:regulation of cell cycle; IMP:UniProtKB.
DR CDD; cd05610; STKc_MASTL; 1.
DR InterPro; IPR000961; AGC-kinase_C.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR037638; MASTL_STKc.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 2.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS51285; AGC_KINASE_CTER; 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 Cell division; Cytoplasm; Cytoskeleton; Disease variant; Kinase; Mitosis;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..879
FT /note="Serine/threonine-protein kinase greatwall"
FT /id="PRO_0000086315"
FT DOMAIN 35..835
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 836..879
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT REGION 1..23
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 566..632
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 700..728
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 566..588
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 700..720
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 156
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 41..49
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 62
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT MOD_RES 207
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 222
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 293
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 370
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18220336,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 453
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 519
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 552
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 556
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 631
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:20068231"
FT MOD_RES 657
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 668
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 722
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 725
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 741
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 875
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231"
FT MOD_RES 878
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT VAR_SEQ 708
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_014574"
FT VAR_SEQ 756..793
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_014575"
FT VARIANT 167
FT /note="E -> D (found in a large family with autosomal
FT dominant thrombocytopenia; unknown pathological
FT significance; no effect on nuclear localization;
FT dbSNP:rs28941470)"
FT /evidence="ECO:0000269|PubMed:12890928,
FT ECO:0000269|PubMed:19460416"
FT /id="VAR_022838"
FT VARIANT 337
FT /note="T -> K (in dbSNP:rs36121140)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040792"
FT VARIANT 606
FT /note="D -> Y (in dbSNP:rs35413630)"
FT /id="VAR_057103"
FT VARIANT 610
FT /note="V -> I (in dbSNP:rs35571315)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040793"
FT VARIANT 620
FT /note="P -> A (in dbSNP:rs3802526)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_022839"
FT MUTAGEN 72
FT /note="K->M: Hyperactive form."
FT /evidence="ECO:0000269|PubMed:21164014"
FT CONFLICT 634
FT /note="K -> E (in Ref. 1; BAC11218)"
FT /evidence="ECO:0000305"
FT CONFLICT 685
FT /note="C -> R (in Ref. 1; BAB55321)"
FT /evidence="ECO:0000305"
FT CONFLICT 731
FT /note="A -> P (in Ref. 1; BAC11218)"
FT /evidence="ECO:0000305"
FT CONFLICT 865
FT /note="A -> T (in Ref. 1; BAB55321)"
FT /evidence="ECO:0000305"
FT HELIX 32..34
FT /evidence="ECO:0007829|PDB:5LOH"
FT STRAND 35..40
FT /evidence="ECO:0007829|PDB:5LOH"
FT STRAND 48..56
FT /evidence="ECO:0007829|PDB:5LOH"
FT STRAND 58..65
FT /evidence="ECO:0007829|PDB:5LOH"
FT TURN 66..68
FT /evidence="ECO:0007829|PDB:5LOH"
FT STRAND 96..98
FT /evidence="ECO:0007829|PDB:5LOH"
FT STRAND 103..111
FT /evidence="ECO:0007829|PDB:5LOH"
FT HELIX 118..125
FT /evidence="ECO:0007829|PDB:5LOH"
FT HELIX 130..149
FT /evidence="ECO:0007829|PDB:5LOH"
FT TURN 159..161
FT /evidence="ECO:0007829|PDB:5LOH"
FT STRAND 162..164
FT /evidence="ECO:0007829|PDB:5LOH"
FT STRAND 170..172
FT /evidence="ECO:0007829|PDB:5LOH"
FT STRAND 174..177
FT /evidence="ECO:0007829|PDB:5LOH"
FT HELIX 200..203
FT /evidence="ECO:0007829|PDB:5LOH"
SQ SEQUENCE 879 AA; 97319 MW; E6533029D1CE58B4 CRC64;
MDPTAGSKKE PGGGAATEEG VNRIAVPKPP SIEEFSIVKP ISRGAFGKVY LGQKGGKLYA
VKVVKKADMI NKNMTHQVQA ERDALALSKS PFIVHLYYSL QSANNVYLVM EYLIGGDVKS
LLHIYGYFDE EMAVKYISEV ALALDYLHRH GIIHRDLKPD NMLISNEGHI KLTDFGLSKV
TLNRDINMMD ILTTPSMAKP RQDYSRTPGQ VLSLISSLGF NTPIAEKNQD PANILSACLS
ETSQLSQGLV CPMSVDQKDT TPYSSKLLKS CLETVASNPG MPVKCLTSNL LQSRKRLATS
SASSQSHTFI SSVESECHSS PKWEKDCQES DEALGPTMMS WNAVEKLCAK SANAIETKGF
NKKDLELALS PIHNSSALPT TGRSCVNLAK KCFSGEVSWE AVELDVNNIN MDTDTSQLGF
HQSNQWAVDS GGISEEHLGK RSLKRNFELV DSSPCKKIIQ NKKTCVEYKH NEMTNCYTNQ
NTGLTVEVQD LKLSVHKSQQ NDCANKENIV NSFTDKQQTP EKLPIPMIAK NLMCELDEDC
EKNSKRDYLS SSFLCSDDDR ASKNISMNSD SSFPGISIME SPLESQPLDS DRSIKESSFE
ESNIEDPLIV TPDCQEKTSP KGVENPAVQE SNQKMLGPPL EVLKTLASKR NAVAFRSFNS
HINASNNSEP SRMNMTSLDA MDISCAYSGS YPMAITPTQK RRSCMPHQQT PNQIKSGTPY
RTPKSVRRGV APVDDGRILG TPDYLAPELL LGRAHGPAVD WWALGVCLFE FLTGIPPFND
ETPQQVFQNI LKRDIPWPEG EEKLSDNAQS AVEILLTIDD TKRAGMKELK RHPLFSDVDW
ENLQHQTMPF IPQPDDETDT SYFEARNTAQ HLTVSGFSL
