LATS1_HUMAN
ID LATS1_HUMAN Reviewed; 1130 AA.
AC O95835; Q6PKD0;
DT 27-SEP-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 204.
DE RecName: Full=Serine/threonine-protein kinase LATS1;
DE EC=2.7.11.1 {ECO:0000269|PubMed:10518011, ECO:0000269|PubMed:15122335};
DE AltName: Full=Large tumor suppressor homolog 1;
DE AltName: Full=WARTS protein kinase;
DE Short=h-warts;
GN Name=LATS1 {ECO:0000312|EMBL:AAD16882.1};
GN Synonyms=WARTS {ECO:0000312|EMBL:AAD50272.1};
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] {ECO:0000305, ECO:0000312|EMBL:AAD16882.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PHOSPHORYLATION, AND INTERACTION
RP WITH CDK1.
RC TISSUE=Fetal brain {ECO:0000312|EMBL:AAD16882.1};
RX PubMed=9988268; DOI=10.1038/5960;
RA Tao W., Zhang S., Turenchalk G.S., Stewart R.A., St John M.A., Chen W.,
RA Xu T.;
RT "Human homologue of the Drosophila melanogaster lats tumour suppressor
RT modulates CDC2 activity.";
RL Nat. Genet. 21:177-181(1999).
RN [2] {ECO:0000305, ECO:0000312|EMBL:AAD50272.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY,
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND PHOSPHORYLATION.
RX PubMed=10518011; DOI=10.1016/s0014-5793(99)01224-7;
RA Nishiyama Y., Hirota T., Morisaki T., Hara T., Marumoto T., Iida S.,
RA Makino K., Yamamoto H., Hiraoka T., Kitamura N., Saya H.;
RT "A human homolog of Drosophila warts tumor suppressor, h-warts, localized
RT to mitotic apparatus and specifically phosphorylated during mitosis.";
RL FEBS Lett. 459:159-165(1999).
RN [3] {ECO:0000305, ECO:0000312|EMBL:AAH02767.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Endometrium {ECO:0000312|EMBL:AAH02767.1};
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] {ECO:0000305}
RP FUNCTION, AND INTERACTION WITH ZYX.
RX PubMed=10831611; DOI=10.1083/jcb.149.5.1073;
RA Hirota T., Morisaki T., Nishiyama Y., Marumoto T., Tada K., Hara T.,
RA Masuko N., Inagaki M., Hatakeyama K., Saya H.;
RT "Zyxin, a regulator of actin filament assembly, targets the mitotic
RT apparatus by interacting with h-warts/LATS1 tumor suppressor.";
RL J. Cell Biol. 149:1073-1086(2000).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=15144186; DOI=10.1021/ac035352d;
RA Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M.,
RA Peters E.C.;
RT "Robust phosphoproteomic profiling of tyrosine phosphorylation sites from
RT human T cells using immobilized metal affinity chromatography and tandem
RT mass spectrometry.";
RL Anal. Chem. 76:2763-2772(2004).
RN [6] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION, AND MUTAGENESIS OF
RP LYS-734.
RX PubMed=15122335; DOI=10.1038/sj.onc.1207623;
RA Iida S., Hirota T., Morisaki T., Marumoto T., Hara T., Kuninaka S.,
RA Honda S., Kosai K., Kawasuji M., Pallas D.C., Saya H.;
RT "Tumor suppressor WARTS ensures genomic integrity by regulating both
RT mitotic progression and G1 tetraploidy checkpoint function.";
RL Oncogene 23:5266-5274(2004).
RN [7] {ECO:0000305}
RP FUNCTION, AND INTERACTION WITH LIMK1.
RX PubMed=15220930; DOI=10.1038/ncb1140;
RA Yang X., Yu K., Hao Y., Li D.-M., Stewart R.A., Insogna K.L., Xu T.;
RT "LATS1 tumour suppressor affects cytokinesis by inhibiting LIMK1.";
RL Nat. Cell Biol. 6:609-617(2004).
RN [8]
RP PHOSPHORYLATION AT SER-909 AND THR-1079.
RX PubMed=15688006; DOI=10.1038/sj.onc.1208445;
RA Chan E.H.Y., Nousiainen M., Chalamalasetty R.B., Schaefer A., Nigg E.A.,
RA Sillje H.H.W.;
RT "The Ste20-like kinase Mst2 activates the human large tumor suppressor
RT kinase Lats1.";
RL Oncogene 24:2076-2086(2005).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-674, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E.,
RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y.,
RA Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [10]
RP FUNCTION, INTERACTION WITH YAP1, AND MUTAGENESIS OF TYR-559.
RX PubMed=18158288; DOI=10.1074/jbc.m709037200;
RA Hao Y., Chun A., Cheung K., Rashidi B., Yang X.;
RT "Tumor suppressor LATS1 is a negative regulator of oncogene YAP.";
RL J. Biol. Chem. 283:5496-5509(2008).
RN [11]
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 [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-246; SER-278 AND SER-464, 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 [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [14]
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 [15]
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 [16]
RP INTERACTION WITH LIMD1; WTIP AND AJUBA.
RX PubMed=20303269; DOI=10.1016/j.cub.2010.02.035;
RA Das Thakur M., Feng Y., Jagannathan R., Seppa M.J., Skeath J.B.,
RA Longmore G.D.;
RT "Ajuba LIM proteins are negative regulators of the Hippo signaling
RT pathway.";
RL Curr. Biol. 20:657-662(2010).
RN [17]
RP INTERACTION WITH MOB1A AND MOB1B.
RX PubMed=19739119; DOI=10.1002/ijc.24878;
RA Chow A., Hao Y., Yang X.;
RT "Molecular characterization of human homologs of yeast MOB1.";
RL Int. J. Cancer 126:2079-2089(2010).
RN [18]
RP FUNCTION, PHOSPHORYLATION AT SER-464, AND MUTAGENESIS OF SER-464.
RX PubMed=19927127; DOI=10.1038/emboj.2009.342;
RA Humbert N., Navaratnam N., Augert A., Da Costa M., Martien S., Wang J.,
RA Martinez D., Abbadie C., Carling D., de Launoit Y., Gil J., Bernard D.;
RT "Regulation of ploidy and senescence by the AMPK-related kinase NUAK1.";
RL EMBO J. 29:376-386(2010).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-246; SER-464 AND SER-613, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [21]
RP INTERACTION WITH STK3, AND PHOSPHORYLATION AT THR-1079.
RX PubMed=28087714; DOI=10.1101/gad.284539.116;
RA Kwan J., Sczaniecka A., Arash E.H., Nguyen L., Chen C.C., Ratkovic S.,
RA Klezovitch O., Attisano L., McNeill H., Emili A., Vasioukhin V.;
RT "DLG5 connects cell polarity and Hippo signaling protein networks by
RT linking PAR-1 with MST1/2.";
RL Genes Dev. 30:2696-2709(2016).
RN [22]
RP FUNCTION, AND INTERACTION WITH DCAF13; ESR1 AND DCAF1.
RX PubMed=28068668; DOI=10.1038/nature20829;
RA Britschgi A., Duss S., Kim S., Couto J.P., Brinkhaus H., Koren S.,
RA De Silva D., Mertz K.D., Kaup D., Varga Z., Voshol H., Vissieres A.,
RA Leroy C., Roloff T., Stadler M.B., Scheel C.H., Miraglia L.J., Orth A.P.,
RA Bonamy G.M., Reddy V.A., Bentires-Alj M.;
RT "The Hippo kinases LATS1 and 2 control human breast cell fate via crosstalk
RT with ERalpha.";
RL Nature 541:541-545(2017).
RN [23]
RP INTERACTION WITH SCRIB.
RX PubMed=28169360; DOI=10.1038/srep42125;
RA Liu J., Li J., Li P., Wang Y., Liang Z., Jiang Y., Li J., Feng C., Wang R.,
RA Chen H., Zhou C., Zhang J., Yang J., Liu P.;
RT "Loss of DLG5 promotes breast cancer malignancy by inhibiting the Hippo
RT signaling pathway.";
RL Sci. Rep. 7:42125-42125(2017).
RN [24]
RP VARIANTS [LARGE SCALE ANALYSIS] TRP-96; GLY-204; GLN-237; TRP-370; SER-531;
RP LEU-641; ILE-669; PRO-806 AND SER-1000.
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: Negative regulator of YAP1 in the Hippo signaling pathway
CC that plays a pivotal role in organ size control and tumor suppression
CC by restricting proliferation and promoting apoptosis. The core of this
CC pathway is composed of a kinase cascade wherein STK3/MST2 and
CC STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates
CC and activates LATS1/2 in complex with its regulatory protein MOB1,
CC which in turn phosphorylates and inactivates YAP1 oncoprotein and
CC WWTR1/TAZ. Phosphorylation of YAP1 by LATS1 inhibits its translocation
CC into the nucleus to regulate cellular genes important for cell
CC proliferation, cell death, and cell migration. Acts as a tumor
CC suppressor which plays a critical role in maintenance of ploidy through
CC its actions in both mitotic progression and the G1 tetraploidy
CC checkpoint. Negatively regulates G2/M transition by down-regulating
CC CDK1 kinase activity. Involved in the control of p53 expression.
CC Affects cytokinesis by regulating actin polymerization through negative
CC modulation of LIMK1. May also play a role in endocrine function. Plays
CC a role in mammary gland epithelial cell differentiation, both through
CC the Hippo signaling pathway and the intracellular estrogen receptor
CC signaling pathway by promoting the degradation of ESR1
CC (PubMed:28068668). {ECO:0000269|PubMed:10518011,
CC ECO:0000269|PubMed:10831611, ECO:0000269|PubMed:15122335,
CC ECO:0000269|PubMed:15220930, ECO:0000269|PubMed:18158288,
CC ECO:0000269|PubMed:19927127, ECO:0000269|PubMed:28068668}.
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:10518011, ECO:0000269|PubMed:15122335};
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:10518011,
CC ECO:0000269|PubMed:15122335};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC -!- SUBUNIT: Complexes with CDK1 in early mitosis (PubMed:9988268). LATS1-
CC associated CDK1 has no mitotic cyclin partner and no apparent kinase
CC activity (PubMed:9988268). Binds phosphorylated ZYX, locating this
CC protein to the mitotic spindle and suggesting a role for actin
CC regulatory proteins during mitosis (PubMed:10831611). Binds to and
CC colocalizes with LIMK1 at the actomyosin contractile ring during
CC cytokinesis (PubMed:15220930). Interacts (via PPxY motif 2) with YAP1
CC (via WW domains) (PubMed:18158288). Interacts with MOB1A and MOB1B
CC (PubMed:19739119). Interacts with LIMD1, WTIP and AJUBA
CC (PubMed:20303269). Interacts with ESR1, DCAF1 and DCAF13; probably
CC recruits DCAF1 and DCAF13 to ESR1 to promote ESR1 ubiquitination and
CC ubiquitin-mediated proteasomal degradation (PubMed:28068668). Interacts
CC with STK3/MST2; this interaction is inhibited in the presence of DLG5
CC (PubMed:28087714). Interacts with SCRIB in the presence of DLG5
CC (PubMed:28169360). Interacts with WWTR1/TAZ (By similarity).
CC {ECO:0000250|UniProtKB:Q8BYR2, ECO:0000269|PubMed:10831611,
CC ECO:0000269|PubMed:15220930, ECO:0000269|PubMed:18158288,
CC ECO:0000269|PubMed:19739119, ECO:0000269|PubMed:20303269,
CC ECO:0000269|PubMed:28068668, ECO:0000269|PubMed:28087714,
CC ECO:0000269|PubMed:28169360, ECO:0000269|PubMed:9988268}.
CC -!- INTERACTION:
CC O95835; P06493: CDK1; NbExp=3; IntAct=EBI-444209, EBI-444308;
CC O95835; P24941: CDK2; NbExp=4; IntAct=EBI-444209, EBI-375096;
CC O95835; Q9Y4B6: DCAF1; NbExp=4; IntAct=EBI-444209, EBI-1996353;
CC O95835; P03372: ESR1; NbExp=2; IntAct=EBI-444209, EBI-78473;
CC O95835; P53667: LIMK1; NbExp=5; IntAct=EBI-444209, EBI-444403;
CC O95835; Q9H8S9: MOB1A; NbExp=9; IntAct=EBI-444209, EBI-748229;
CC O95835; Q7L9L4: MOB1B; NbExp=7; IntAct=EBI-444209, EBI-2558745;
CC O95835; P35240: NF2; NbExp=4; IntAct=EBI-444209, EBI-1014472;
CC O95835; O60285: NUAK1; NbExp=2; IntAct=EBI-444209, EBI-1046789;
CC O95835; O43255: SIAH2; NbExp=2; IntAct=EBI-444209, EBI-948141;
CC O95835; Q15831: STK11; NbExp=2; IntAct=EBI-444209, EBI-306838;
CC O95835; Q9GZV5: WWTR1; NbExp=5; IntAct=EBI-444209, EBI-747743;
CC O95835; P46937: YAP1; NbExp=10; IntAct=EBI-444209, EBI-1044059;
CC O95835; Q15942: ZYX; NbExp=10; IntAct=EBI-444209, EBI-444225;
CC O95835; P46662: Nf2; Xeno; NbExp=5; IntAct=EBI-444209, EBI-644586;
CC O95835-2; O15145: ARPC3; NbExp=3; IntAct=EBI-17978514, EBI-351829;
CC O95835-2; Q9UHD9: UBQLN2; NbExp=3; IntAct=EBI-17978514, EBI-947187;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, microtubule organizing
CC center, centrosome {ECO:0000269|PubMed:10518011}. Cytoplasm,
CC cytoskeleton, spindle {ECO:0000269|PubMed:10518011}. Midbody
CC {ECO:0000269|PubMed:10518011}. Cytoplasm, cytoskeleton, microtubule
CC organizing center, spindle pole body {ECO:0000269|PubMed:10518011}.
CC Note=Localizes to the centrosomes throughout interphase but migrates to
CC the mitotic apparatus, including spindle pole bodies, mitotic spindle,
CC and midbody, during mitosis. {ECO:0000269|PubMed:10518011}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1 {ECO:0000269|PubMed:9988268};
CC IsoId=O95835-1; Sequence=Displayed;
CC Name=2 {ECO:0000305};
CC IsoId=O95835-2; Sequence=VSP_051604, VSP_051605;
CC -!- TISSUE SPECIFICITY: Expressed in all adult tissues examined except for
CC lung and kidney. {ECO:0000269|PubMed:10518011}.
CC -!- PTM: Autophosphorylated and phosphorylated during M-phase of the cell
CC cycle (PubMed:9988268, PubMed:10518011, PubMed:15122335).
CC Phosphorylated by STK3/MST2 at Ser-909 and Thr-1079, which results in
CC its activation (PubMed:15688006). Phosphorylation at Ser-464 by NUAK1
CC and NUAK2 leads to decreased protein level and is required to regulate
CC cellular senescence and cellular ploidy (PubMed:19927127).
CC {ECO:0000269|PubMed:10518011, ECO:0000269|PubMed:15122335,
CC ECO:0000269|PubMed:15688006, ECO:0000269|PubMed:19927127,
CC ECO:0000269|PubMed:9988268}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/LATS1ID41127ch6q25.html";
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DR EMBL; AF104413; AAD16882.1; -; mRNA.
DR EMBL; AF164041; AAD50272.1; -; mRNA.
DR EMBL; BC002767; AAH02767.1; -; mRNA.
DR CCDS; CCDS34551.1; -. [O95835-1]
DR CCDS; CCDS59040.1; -. [O95835-2]
DR RefSeq; NP_001257448.1; NM_001270519.1. [O95835-2]
DR RefSeq; NP_004681.1; NM_004690.3. [O95835-1]
DR PDB; 4ZRK; X-ray; 2.32 A; E/F/G/H=69-100.
DR PDB; 5B5W; X-ray; 2.96 A; U=622-704.
DR PDB; 5BRK; X-ray; 2.30 A; B=602-704.
DR PDB; 7LWH; X-ray; 1.61 A; B=69-91.
DR PDBsum; 4ZRK; -.
DR PDBsum; 5B5W; -.
DR PDBsum; 5BRK; -.
DR PDBsum; 7LWH; -.
DR AlphaFoldDB; O95835; -.
DR SMR; O95835; -.
DR BioGRID; 114563; 248.
DR CORUM; O95835; -.
DR DIP; DIP-31516N; -.
DR IntAct; O95835; 63.
DR MINT; O95835; -.
DR STRING; 9606.ENSP00000437550; -.
DR BindingDB; O95835; -.
DR ChEMBL; CHEMBL6167; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; O95835; -.
DR iPTMnet; O95835; -.
DR PhosphoSitePlus; O95835; -.
DR BioMuta; LATS1; -.
DR EPD; O95835; -.
DR jPOST; O95835; -.
DR MassIVE; O95835; -.
DR MaxQB; O95835; -.
DR PaxDb; O95835; -.
DR PeptideAtlas; O95835; -.
DR PRIDE; O95835; -.
DR ProteomicsDB; 51081; -. [O95835-1]
DR ProteomicsDB; 51082; -. [O95835-2]
DR Antibodypedia; 33280; 409 antibodies from 32 providers.
DR DNASU; 9113; -.
DR Ensembl; ENST00000253339.9; ENSP00000253339.5; ENSG00000131023.13. [O95835-1]
DR Ensembl; ENST00000392273.7; ENSP00000444678.1; ENSG00000131023.13. [O95835-2]
DR Ensembl; ENST00000543571.6; ENSP00000437550.1; ENSG00000131023.13. [O95835-1]
DR GeneID; 9113; -.
DR KEGG; hsa:9113; -.
DR MANE-Select; ENST00000543571.6; ENSP00000437550.1; NM_004690.4; NP_004681.1.
DR UCSC; uc003qmu.2; human. [O95835-1]
DR CTD; 9113; -.
DR DisGeNET; 9113; -.
DR GeneCards; LATS1; -.
DR HGNC; HGNC:6514; LATS1.
DR HPA; ENSG00000131023; Low tissue specificity.
DR MIM; 603473; gene.
DR neXtProt; NX_O95835; -.
DR OpenTargets; ENSG00000131023; -.
DR PharmGKB; PA30301; -.
DR VEuPathDB; HostDB:ENSG00000131023; -.
DR eggNOG; KOG0608; Eukaryota.
DR GeneTree; ENSGT00940000157684; -.
DR HOGENOM; CLU_004885_0_0_1; -.
DR InParanoid; O95835; -.
DR OMA; YQSGDHA; -.
DR OrthoDB; 759391at2759; -.
DR PhylomeDB; O95835; -.
DR TreeFam; TF351549; -.
DR PathwayCommons; O95835; -.
DR Reactome; R-HSA-2028269; Signaling by Hippo.
DR SignaLink; O95835; -.
DR SIGNOR; O95835; -.
DR BioGRID-ORCS; 9113; 23 hits in 1120 CRISPR screens.
DR ChiTaRS; LATS1; human.
DR GeneWiki; LATS1; -.
DR GenomeRNAi; 9113; -.
DR Pharos; O95835; Tchem.
DR PRO; PR:O95835; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; O95835; protein.
DR Bgee; ENSG00000131023; Expressed in germinal epithelium of ovary and 181 other tissues.
DR ExpressionAtlas; O95835; baseline and differential.
DR Genevisible; O95835; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005815; C:microtubule organizing center; IEA:UniProtKB-SubCell.
DR GO; GO:0030496; C:midbody; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0000922; C:spindle pole; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR GO; GO:0030331; F:nuclear estrogen receptor binding; IPI:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; IPI: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:0051220; P:cytoplasmic sequestering of protein; IMP:BHF-UCL.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; IBA:GO_Central.
DR GO; GO:0000086; P:G2/M transition of mitotic cell cycle; IDA:UniProtKB.
DR GO; GO:0035329; P:hippo signaling; IDA:BHF-UCL.
DR GO; GO:0009755; P:hormone-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0001827; P:inner cell mass cell fate commitment; IEA:Ensembl.
DR GO; GO:0001828; P:inner cell mass cellular morphogenesis; IEA:Ensembl.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0030216; P:keratinocyte differentiation; IEA:Ensembl.
DR GO; GO:0060644; P:mammary gland epithelial cell differentiation; IMP:UniProtKB.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IMP:BHF-UCL.
DR GO; GO:0045736; P:negative regulation of cyclin-dependent protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:1900181; P:negative regulation of protein localization to nucleus; ISS:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IBA:GO_Central.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IDA:BHF-UCL.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0030833; P:regulation of actin filament polymerization; IDA:UniProtKB.
DR GO; GO:0033146; P:regulation of intracellular estrogen receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0046620; P:regulation of organ growth; IBA:GO_Central.
DR GO; GO:0043254; P:regulation of protein-containing complex assembly; IMP:BHF-UCL.
DR GO; GO:0017015; P:regulation of transforming growth factor beta receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:2000058; P:regulation of ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR GO; GO:0000819; P:sister chromatid segregation; IDA:UniProtKB.
DR CDD; cd05625; STKc_LATS1; 1.
DR InterPro; IPR000961; AGC-kinase_C.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR028741; LATS1.
DR InterPro; IPR042706; LATS1_STKc.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR InterPro; IPR015940; UBA.
DR InterPro; IPR009060; UBA-like_sf.
DR PANTHER; PTHR24356:SF138; PTHR24356:SF138; 1.
DR Pfam; PF00069; Pkinase; 1.
DR Pfam; PF00627; UBA; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF46934; SSF46934; 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.
DR PROSITE; PS50030; UBA; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Cell cycle; Cell division;
KW Cytoplasm; Cytoskeleton; Kinase; Magnesium; Metal-binding; Mitosis;
KW Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Tumor suppressor.
FT CHAIN 1..1130
FT /note="Serine/threonine-protein kinase LATS1"
FT /id="PRO_0000086232"
FT DOMAIN 100..141
FT /note="UBA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00212"
FT DOMAIN 705..1010
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 1011..1090
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT REGION 1..71
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 149..276
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 294..321
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 365..405
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 432..484
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 515..631
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 526..655
FT /note="Interaction with YAP1"
FT /evidence="ECO:0000269|PubMed:18158288"
FT REGION 1104..1130
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 373..376
FT /note="PPxY motif 1"
FT MOTIF 556..559
FT /note="PPxY motif 2"
FT COMPBIAS 17..38
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 39..59
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 163..183
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 200..215
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 232..270
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 295..310
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 381..405
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 515..537
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 549..565
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 583..631
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 828
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P22612,
FT ECO:0000255|PROSITE-ProRule:PRU00159, ECO:0000255|PROSITE-
FT ProRule:PRU10027"
FT BINDING 711..719
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P22612,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 734
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000269|PubMed:15122335"
FT MOD_RES 246
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 278
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 464
FT /note="Phosphoserine; by NUAK1 and NUAK2"
FT /evidence="ECO:0000269|PubMed:19927127,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:23186163"
FT MOD_RES 613
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 674
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17525332"
FT MOD_RES 909
FT /note="Phosphoserine; by STK3/MST2"
FT /evidence="ECO:0000269|PubMed:15688006"
FT MOD_RES 1079
FT /note="Phosphothreonine; by STK3/MST2"
FT /evidence="ECO:0000269|PubMed:15688006,
FT ECO:0000269|PubMed:28087714"
FT VAR_SEQ 672..690
FT /note="GLSQDAQDQMRKMLCQKES -> KPFKMSIFILNHLFAWCLF (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_051604"
FT VAR_SEQ 691..1130
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_051605"
FT VARIANT 96
FT /note="R -> W (in dbSNP:rs55945045)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040660"
FT VARIANT 204
FT /note="S -> G (in dbSNP:rs34793526)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040661"
FT VARIANT 237
FT /note="P -> Q (in dbSNP:rs56149740)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040662"
FT VARIANT 370
FT /note="R -> W (in dbSNP:rs56348064)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040663"
FT VARIANT 531
FT /note="P -> S (in dbSNP:rs55874734)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040664"
FT VARIANT 641
FT /note="F -> L (in dbSNP:rs35163691)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040665"
FT VARIANT 669
FT /note="M -> I (in a lung adenocarcinoma sample; somatic
FT mutation; dbSNP:rs1390558952)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040666"
FT VARIANT 806
FT /note="R -> P (in a lung large cell carcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040667"
FT VARIANT 1000
FT /note="G -> S (in dbSNP:rs56412005)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040668"
FT MUTAGEN 464
FT /note="S->A: Abolishes phosphorylation by NUAK1 and NUAK2."
FT /evidence="ECO:0000269|PubMed:19927127"
FT MUTAGEN 559
FT /note="Y->F: Loss of interaction with YAP1."
FT /evidence="ECO:0000269|PubMed:18158288"
FT MUTAGEN 734
FT /note="K->A: Loss of kinase activity, autophosphorylation,
FT increased ploidy, prolonged duration of mitosis and lack of
FT p53 expression."
FT /evidence="ECO:0000269|PubMed:15122335"
FT HELIX 72..74
FT /evidence="ECO:0007829|PDB:7LWH"
FT HELIX 75..85
FT /evidence="ECO:0007829|PDB:7LWH"
FT HELIX 86..88
FT /evidence="ECO:0007829|PDB:7LWH"
FT HELIX 637..671
FT /evidence="ECO:0007829|PDB:5BRK"
FT HELIX 675..697
FT /evidence="ECO:0007829|PDB:5BRK"
SQ SEQUENCE 1130 AA; 126870 MW; 11CFBCD8FD87DCD8 CRC64;
MKRSEKPEGY RQMRPKTFPA SNYTVSSRQM LQEIRESLRN LSKPSDAAKA EHNMSKMSTE
DPRQVRNPPK FGTHHKALQE IRNSLLPFAN ETNSSRSTSE VNPQMLQDLQ AAGFDEDMVI
QALQKTNNRS IEAAIEFISK MSYQDPRREQ MAAAAARPIN ASMKPGNVQQ SVNRKQSWKG
SKESLVPQRH GPPLGESVAY HSESPNSQTD VGRPLSGSGI SAFVQAHPSN GQRVNPPPPP
QVRSVTPPPP PRGQTPPPRG TTPPPPSWEP NSQTKRYSGN MEYVISRISP VPPGAWQEGY
PPPPLNTSPM NPPNQGQRGI SSVPVGRQPI IMQSSSKFNF PSGRPGMQNG TGQTDFMIHQ
NVVPAGTVNR QPPPPYPLTA ANGQSPSALQ TGGSAAPSSY TNGSIPQSMM VPNRNSHNME
LYNISVPGLQ TNWPQSSSAP AQSSPSSGHE IPTWQPNIPV RSNSFNNPLG NRASHSANSQ
PSATTVTAIT PAPIQQPVKS MRVLKPELQT ALAPTHPSWI PQPIQTVQPS PFPEGTASNV
TVMPPVAEAP NYQGPPPPYP KHLLHQNPSV PPYESISKPS KEDQPSLPKE DESEKSYENV
DSGDKEKKQI TTSPITVRKN KKDEERRESR IQSYSPQAFK FFMEQHVENV LKSHQQRLHR
KKQLENEMMR VGLSQDAQDQ MRKMLCQKES NYIRLKRAKM DKSMFVKIKT LGIGAFGEVC
LARKVDTKAL YATKTLRKKD VLLRNQVAHV KAERDILAEA DNEWVVRLYY SFQDKDNLYF
VMDYIPGGDM MSLLIRMGIF PESLARFYIA ELTCAVESVH KMGFIHRDIK PDNILIDRDG
HIKLTDFGLC TGFRWTHDSK YYQSGDHPRQ DSMDFSNEWG DPSSCRCGDR LKPLERRAAR
QHQRCLAHSL VGTPNYIAPE VLLRTGYTQL CDWWSVGVIL FEMLVGQPPF LAQTPLETQM
KVINWQTSLH IPPQAKLSPE ASDLIIKLCR GPEDRLGKNG ADEIKAHPFF KTIDFSSDLR
QQSASYIPKI THPTDTSNFD PVDPDKLWSD DNEEENVNDT LNGWYKNGKH PEHAFYEFTF
RRFFDDNGYP YNYPKPIEYE YINSQGSEQQ SDEDDQNTGS EIKNRDLVYV
