GWL_MOUSE
ID GWL_MOUSE Reviewed; 865 AA.
AC Q8C0P0; A2AQY2; Q3MIA9; Q5RJW0; Q6NXX9; Q8BVF3; Q9CZH9; Q9D9V0;
DT 05-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 03-MAY-2011, sequence version 2.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Serine/threonine-protein kinase greatwall;
DE Short=GW;
DE Short=GWL;
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;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Cerebellum, Embryo, and Testis;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 194-865 (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Egg, and Embryonic germ cell;
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 [5]
RP FUNCTION.
RX PubMed=21156286; DOI=10.1016/j.ccr.2010.10.028;
RA Manchado E., Guillamot M., de Carcer G., Eguren M., Trickey M.,
RA Garcia-Higuera I., Moreno S., Yamano H., Canamero M., Malumbres M.;
RT "Targeting mitotic exit leads to tumor regression in vivo: Modulation by
RT Cdk1, Mastl, and the PP2A/B55alpha,delta phosphatase.";
RL Cancer Cell 18:641-654(2010).
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 (By similarity).
CC {ECO:0000250, ECO:0000269|PubMed:21156286}.
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 -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, microtubule organizing
CC center, centrosome {ECO:0000250}. Nucleus. Note=During interphase is
CC mainly nuclear, upon nuclear envelope breakdown localizes at the
CC cytoplasm and during mitosis at the centrosomes. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8C0P0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8C0P0-2; Sequence=VSP_014576, VSP_014577;
CC -!- PTM: Phosphorylation at Thr-727 by CDK1 during M phase activates its
CC kinase activity. Maximum phosphorylation occurs in prometaphase (By
CC similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH86483.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAB24595.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAC37239.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK006448; BAB24595.1; ALT_INIT; mRNA.
DR EMBL; AK012597; BAB28343.2; -; mRNA.
DR EMBL; AK030140; BAC26804.1; -; mRNA.
DR EMBL; AK078365; BAC37239.1; ALT_SEQ; mRNA.
DR EMBL; AL845257; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466542; EDL08150.1; -; Genomic_DNA.
DR EMBL; BC066834; AAH66834.1; -; mRNA.
DR EMBL; BC086483; AAH86483.1; ALT_INIT; mRNA.
DR EMBL; BC103779; AAI03780.1; -; mRNA.
DR CCDS; CCDS15727.1; -. [Q8C0P0-1]
DR RefSeq; NP_080255.3; NM_025979.4. [Q8C0P0-1]
DR AlphaFoldDB; Q8C0P0; -.
DR SMR; Q8C0P0; -.
DR BioGRID; 211955; 1.
DR STRING; 10090.ENSMUSP00000028119; -.
DR iPTMnet; Q8C0P0; -.
DR PhosphoSitePlus; Q8C0P0; -.
DR EPD; Q8C0P0; -.
DR jPOST; Q8C0P0; -.
DR MaxQB; Q8C0P0; -.
DR PaxDb; Q8C0P0; -.
DR PeptideAtlas; Q8C0P0; -.
DR PRIDE; Q8C0P0; -.
DR ProteomicsDB; 271116; -. [Q8C0P0-1]
DR ProteomicsDB; 271117; -. [Q8C0P0-2]
DR Antibodypedia; 12704; 359 antibodies from 32 providers.
DR DNASU; 67121; -.
DR Ensembl; ENSMUST00000028119; ENSMUSP00000028119; ENSMUSG00000026779. [Q8C0P0-1]
DR GeneID; 67121; -.
DR KEGG; mmu:67121; -.
DR UCSC; uc008iob.2; mouse. [Q8C0P0-1]
DR UCSC; uc008ioc.1; mouse. [Q8C0P0-2]
DR CTD; 84930; -.
DR MGI; MGI:1914371; Mastl.
DR VEuPathDB; HostDB:ENSMUSG00000026779; -.
DR eggNOG; KOG0606; Eukaryota.
DR GeneTree; ENSGT00940000157002; -.
DR HOGENOM; CLU_016048_0_0_1; -.
DR InParanoid; Q8C0P0; -.
DR OMA; STSHTPY; -.
DR OrthoDB; 878671at2759; -.
DR PhylomeDB; Q8C0P0; -.
DR TreeFam; TF313149; -.
DR Reactome; R-MMU-2465910; MASTL Facilitates Mitotic Progression.
DR BioGRID-ORCS; 67121; 23 hits in 76 CRISPR screens.
DR ChiTaRS; Lrp6; mouse.
DR PRO; PR:Q8C0P0; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q8C0P0; protein.
DR Bgee; ENSMUSG00000026779; Expressed in animal zygote and 192 other tissues.
DR Genevisible; Q8C0P0; MM.
DR GO; GO:0005813; C:centrosome; ISS:UniProtKB.
DR GO; GO:0032154; C:cleavage furrow; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016301; F:kinase activity; ISO:MGI.
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; ISS: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; IMP:MGI.
DR GO; GO:0000086; P:G2/M transition of mitotic cell cycle; ISS:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0000278; P:mitotic cell cycle; ISS:UniProtKB.
DR GO; GO:0032515; P:negative regulation of phosphoprotein phosphatase activity; ISS:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:1904668; P:positive regulation of ubiquitin protein ligase activity; IMP:MGI.
DR GO; GO:0051726; P:regulation of cell cycle; ISO:MGI.
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 2: Evidence at transcript level;
KW Acetylation; Alternative splicing; ATP-binding; Cell cycle; Cell division;
KW Cytoplasm; Cytoskeleton; Kinase; Mitosis; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW Transferase.
FT CHAIN 1..865
FT /note="Serine/threonine-protein kinase greatwall"
FT /id="PRO_0000086316"
FT DOMAIN 34..821
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 822..865
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT ACT_SITE 155
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 40..48
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 61
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:0000250|UniProtKB:Q96GX5"
FT MOD_RES 206
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q96GX5"
FT MOD_RES 221
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q96GX5"
FT MOD_RES 362
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96GX5"
FT MOD_RES 442
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96GX5"
FT MOD_RES 508
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q96GX5"
FT MOD_RES 545
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96GX5"
FT MOD_RES 619
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96GX5"
FT MOD_RES 644
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96GX5"
FT MOD_RES 655
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96GX5"
FT MOD_RES 708
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q96GX5"
FT MOD_RES 711
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96GX5"
FT MOD_RES 727
FT /note="Phosphothreonine; by CDK1"
FT /evidence="ECO:0000250|UniProtKB:Q96GX5"
FT MOD_RES 861
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96GX5"
FT MOD_RES 864
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96GX5"
FT VAR_SEQ 327..348
FT /note="STESSGCAMSWNAVEMLYAKST -> VSSKYSSLKLIYTRNQ (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_014576"
FT VAR_SEQ 349..865
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_014577"
FT CONFLICT 37
FT /note="V -> E (in Ref. 1; BAC37239)"
FT /evidence="ECO:0000305"
FT CONFLICT 62
FT /note="V -> G (in Ref. 1; BAC37239)"
FT /evidence="ECO:0000305"
FT CONFLICT 69
FT /note="I -> V (in Ref. 1; BAC26804)"
FT /evidence="ECO:0000305"
FT CONFLICT 79
FT /note="A -> S (in Ref. 1; BAC37239)"
FT /evidence="ECO:0000305"
FT CONFLICT 104
FT /note="N -> I (in Ref. 1; BAC37239)"
FT /evidence="ECO:0000305"
FT CONFLICT 118
FT /note="K -> Q (in Ref. 1; BAC37239)"
FT /evidence="ECO:0000305"
FT CONFLICT 222
FT /note="P -> S (in Ref. 4; AAI03780)"
FT /evidence="ECO:0000305"
FT CONFLICT 247
FT /note="F -> L (in Ref. 1; BAB24595)"
FT /evidence="ECO:0000305"
FT CONFLICT 314
FT /note="E -> G (in Ref. 4; AAI03780)"
FT /evidence="ECO:0000305"
FT CONFLICT 323
FT /note="R -> T (in Ref. 1; BAC37239)"
FT /evidence="ECO:0000305"
FT CONFLICT 376
FT /note="N -> D (in Ref. 1; BAB28343)"
FT /evidence="ECO:0000305"
FT CONFLICT 455
FT /note="T -> S (in Ref. 4; AAI03780)"
FT /evidence="ECO:0000305"
FT CONFLICT 529
FT /note="C -> R (in Ref. 2; AAH66834/AAH86483)"
FT /evidence="ECO:0000305"
FT CONFLICT 672
FT /note="C -> Y (in Ref. 2; AAH66834/AAH86483)"
FT /evidence="ECO:0000305"
FT CONFLICT 699
FT /note="Q -> R (in Ref. 4; AAI03780)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 865 AA; 95975 MW; 59C228B1E1D5CDC4 CRC64;
MESASASEEN EGGAAIEECV SRIPVPRPPS IEEFTIVKPI SRGAFGKVYL GQKGGKLYAV
KVVKKADMIN KNMTHQVQAE RDALALSKSP FVVHLYYSLQ SASNIYLIME YLIGGDVKSL
LHIYGYFDEE MAIKYISEVA LALDYLHRHG IIHRDLKPDN MLISNEGHIK LTDFGLSKVT
LNRDINMMDI LTTPSMSKPK QDYSRTPGQV LSLISSLGFF TPVGEKDQDS ANMFSAPKSA
AQLSRGFICP MSVDQKEPTS YSSKLLKSCF ETLSSNPEIP VKCLTSNLLQ CRKRLGTSST
SSQSHTFVSS VESECHSNPK WERDCQSTES SGCAMSWNAV EMLYAKSTSA IKTKTELELA
LSPIHDSSAI PAAGSNQVTL PRKCFREISW EARDPDNENM TIDKGQSGFC QSSQRSVNSS
ATSEEHLGKR NYKRNFHLVD SSPCQEIMQS KKNCTEYEAN KERQGCRANQ STGLTTEVQN
LKLSGCESQQ LDYANKENIV TYLTDRQTPE KLHIPTIAKN LMSELDEDCE LSSKKDCLSS
NSVCSDEDRA LKTTCVDSDS SFPGVSMMES SLEIQALEPD KSIRDYSFEE PNTEDLFVLP
KCQENSLPQD DCHACIQDSS QVSAHPSKAP KALTSKINVV AFRSFNSHIN ASTNSEPSKI
SITSLDAMDI SCDYSGSYPM AVSPTEKGRH YTSHQTPNQV KLGTSYRTPK SVRRGAAPVD
DGRILGTPDY LAPELLLGTA HGPAVDWWAL GVCLFEFLTG IPPFNDETPQ QVFQNILKRD
IPWPEGEEKL SDNAQSAMDM LLTIDDSKRA GMRELKQHPL FSEVDWENLQ HQTMPFVPQP
DDETDTSYFE ARNNAQHLTI SGFSL
