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 27-MAR-2024, entry version 213. 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 WWC1; WWC2 AND WWC3. RX PubMed=24682284; DOI=10.1093/molbev/msu115; RA Wennmann D.O., Schmitz J., Wehr M.C., Krahn M.P., Koschmal N., RA Gromnitza S., Schulze U., Weide T., Chekuri A., Skryabin B.V., Gerke V., RA Pavenstadt H., Duning K., Kremerskothen J.; RT "Evolutionary and Molecular Facts Link the WWC Protein Family to Hippo RT Signaling."; RL Mol. Biol. Evol. 31:1710-1723(2014). RN [22] 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 [23] 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 [24] 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 [25] 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). Interacts CC with WWC1, WWC2 and WWC3 (via their WW domains) (PubMed:24682284). 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:24682284, ECO:0000269|PubMed:28068668, CC ECO:0000269|PubMed:28087714, ECO:0000269|PubMed:28169360, CC 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="https://atlasgeneticsoncology.org/gene/41127/LATS1"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 448. DR CORUM; O95835; -. DR DIP; DIP-31516N; -. DR IntAct; O95835; 66. DR MINT; O95835; -. DR STRING; 9606.ENSP00000437550; -. DR BindingDB; O95835; -. DR ChEMBL; CHEMBL6167; -. DR DrugBank; DB12010; Fostamatinib. DR DrugCentral; O95835; -. DR GuidetoPHARMACOLOGY; 1515; -. DR MoonProt; O95835; -. DR GlyGen; O95835; 4 sites, 1 O-linked glycan (4 sites). DR iPTMnet; O95835; -. DR PhosphoSitePlus; O95835; -. DR BioMuta; LATS1; -. DR CPTAC; CPTAC-3110; -. DR CPTAC; CPTAC-3111; -. DR EPD; O95835; -. DR jPOST; O95835; -. DR MassIVE; O95835; -. DR MaxQB; O95835; -. DR PaxDb; 9606-ENSP00000437550; -. DR PeptideAtlas; O95835; -. DR ProteomicsDB; 51081; -. [O95835-1] DR ProteomicsDB; 51082; -. [O95835-2] DR Pumba; O95835; -. DR Antibodypedia; 33280; 503 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 AGR; HGNC:6514; -. 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; MPFANEP; -. DR OrthoDB; 5348633at2759; -. 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; 25 hits in 1204 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 183 other cell types or tissues. DR ExpressionAtlas; O95835; baseline and differential. DR GO; GO:0005813; C:centrosome; IEA:UniProtKB-SubCell. DR GO; GO:0005829; C:cytosol; TAS:Reactome. 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: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: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; cd21778; MobB_LATS1; 1. DR CDD; cd05625; STKc_LATS1; 1. DR CDD; cd14397; UBA_LATS1; 1. DR Gene3D; 1.10.8.10; DNA helicase RuvA subunit, C-terminal domain; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 2. DR InterPro; IPR000961; AGC-kinase_C. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR049761; LATS1-like_MobB. DR InterPro; IPR042706; LATS1_STKc. DR InterPro; IPR017892; Pkinase_C. 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; SERINE/THREONINE-PROTEIN KINASE; 1. DR PANTHER; PTHR24356:SF138; SERINE_THREONINE-PROTEIN KINASE LATS1; 1. DR Pfam; PF00069; Pkinase; 2. DR Pfam; PF00433; Pkinase_C; 1. DR Pfam; PF00627; UBA; 1. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR SUPFAM; SSF46934; UBA-like; 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. DR Genevisible; O95835; HS. 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 //