LATS2_HUMAN
ID LATS2_HUMAN Reviewed; 1088 AA.
AC Q9NRM7; B1AM47; Q9P2X1;
DT 27-SEP-2004, integrated into UniProtKB/Swiss-Prot.
DT 04-NOV-2008, sequence version 2.
DT 03-AUG-2022, entry version 194.
DE RecName: Full=Serine/threonine-protein kinase LATS2;
DE EC=2.7.11.1;
DE AltName: Full=Kinase phosphorylated during mitosis protein;
DE AltName: Full=Large tumor suppressor homolog 2;
DE AltName: Full=Serine/threonine-protein kinase kpm;
DE AltName: Full=Warts-like kinase;
GN Name=LATS2 {ECO:0000312|EMBL:BAA92381.1}; Synonyms=KPM;
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:AAF80561.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY,
RP AUTOPHOSPHORYLATION, AND MUTAGENESIS OF LYS-697.
RC TISSUE=Myeloid {ECO:0000312|EMBL:AAF80561.1};
RX PubMed=10871863; DOI=10.1038/sj.onc.1203659;
RA Hori T., Takaori-Kondo A., Kamikubo Y., Uchiyama T.;
RT "Molecular cloning of a novel human protein kinase, kpm, that is homologous
RT to warts/lats, a Drosophila tumor suppressor.";
RL Oncogene 19:3101-3109(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057823; DOI=10.1038/nature02379;
RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L.,
RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S.,
RA Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Andrews D.T., Ashwell R.I.S., Babbage A.K., Bagguley C.L.,
RA Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C.,
RA Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P.,
RA Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L.,
RA Frankish A.G., Frankland J., French L., Garner P., Garnett J.,
RA Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M.,
RA Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D.,
RA Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D.,
RA Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S.,
RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S.,
RA Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R.,
RA Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W.,
RA Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L.,
RA Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R.,
RA Rogers J., Ross M.T.;
RT "The DNA sequence and analysis of human chromosome 13.";
RL Nature 428:522-528(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5] {ECO:0000305, ECO:0000312|EMBL:BAA92381.1}
RP NUCLEOTIDE SEQUENCE [MRNA] OF 42-1088, TISSUE SPECIFICITY, AND VARIANT
RP VAL-324.
RC TISSUE=Testis {ECO:0000269|PubMed:10673337};
RX PubMed=10673337; DOI=10.1006/geno.1999.6065;
RA Yabuta N., Fujii T., Copeland N.G., Gilbert D.J., Jenkins N.A.,
RA Nishiguchi H., Endo Y., Toji S., Tanaka H., Nishimune Y., Nojima H.;
RT "Structure, expression, and chromosome mapping of LATS2, a mammalian
RT homologue of the Drosophila tumor suppressor gene lats/warts.";
RL Genomics 63:263-270(2000).
RN [6] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF LYS-697 AND SER-872.
RX PubMed=12853976; DOI=10.1038/sj.onc.1206603;
RA Li Y., Pei J., Xia H., Ke H., Wang H., Tao W.;
RT "Lats2, a putative tumor suppressor, inhibits G1/S transition.";
RL Oncogene 22:4398-4405(2003).
RN [7] {ECO:0000305}
RP SUBCELLULAR LOCATION, INTERACTION WITH AURKA, MUTAGENESIS OF SER-83, AND
RP PHOSPHORYLATION AT SER-83.
RX PubMed=15147269; DOI=10.1111/j.1356-9597.2004.00732.x;
RA Toji S., Yabuta N., Hosomi T., Nishihara S., Kobayashi T., Suzuki S.,
RA Tamai K., Nojima H.;
RT "The centrosomal protein Lats2 is a phosphorylation target of Aurora-A
RT kinase.";
RL Genes Cells 9:383-397(2004).
RN [8] {ECO:0000305}
RP FUNCTION, AND INTERACTION WITH AR.
RX PubMed=15131260; DOI=10.1210/me.2004-0065;
RA Powzaniuk M., McElwee-Witmer S., Vogel R.L., Hayami T., Rutledge S.J.,
RA Chen F., Harada S., Schmidt A., Rodan G.A., Freedman L.P., Bai C.;
RT "The LATS2/KPM tumor suppressor is a negative regulator of the androgen
RT receptor.";
RL Mol. Endocrinol. 18:2011-2023(2004).
RN [9]
RP PHOSPHORYLATION.
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 [10]
RP INTERACTION WITH AJUBA.
RX PubMed=16413547; DOI=10.1016/j.febslet.2005.12.096;
RA Abe Y., Ohsugi M., Haraguchi K., Fujimoto J., Yamamoto T.;
RT "LATS2-Ajuba complex regulates gamma-tubulin recruitment to centrosomes and
RT spindle organization during mitosis.";
RL FEBS Lett. 580:782-788(2006).
RN [11]
RP FUNCTION, AND INTERACTION WITH YAP1.
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 [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-279, AND IDENTIFICATION BY
RP 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 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 [14]
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 [15]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH SNAI1, AND PHOSPHORYLATION
RP AT THR-1041.
RX PubMed=21952048; DOI=10.1038/emboj.2011.357;
RA Zhang K., Rodriguez-Aznar E., Yabuta N., Owen R.J., Mingot J.M., Nojima H.,
RA Nieto M.A., Longmore G.D.;
RT "Lats2 kinase potentiates Snail1 activity by promoting nuclear retention
RT upon phosphorylation.";
RL EMBO J. 31:29-43(2012).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-380 AND SER-576, 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 [17]
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 [18]
RP PHOSPHORYLATION BY NUAK2.
RX PubMed=32845958; DOI=10.1084/jem.20191561;
RA Bonnard C., Navaratnam N., Ghosh K., Chan P.W., Tan T.T., Pomp O.,
RA Ng A.Y.J., Tohari S., Changede R., Carling D., Venkatesh B., Altunoglu U.,
RA Kayserili H., Reversade B.;
RT "A loss-of-function NUAK2 mutation in humans causes anencephaly due to
RT impaired Hippo-YAP signaling.";
RL J. Exp. Med. 217:0-0(2020).
RN [19]
RP VARIANTS [LARGE SCALE ANALYSIS] GLU-40; LEU-91; VAL-799; GLY-1014 AND
RP PRO-1025.
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 LATS2 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 centrosome duplication,
CC maintenance of mitotic fidelity and genomic stability. Negatively
CC regulates G1/S transition by down-regulating cyclin E/CDK2 kinase
CC activity. Negative regulator of the androgen receptor. Phosphorylates
CC SNAI1 in the nucleus leading to its nuclear retention and
CC stabilization, which enhances its epithelial-mesenchymal transition and
CC tumor cell invasion/migration activities. This tumor-promoting activity
CC is independent of its effects upon YAP1 or WWTR1/TAZ.
CC {ECO:0000269|PubMed:10871863, ECO:0000269|PubMed:12853976,
CC ECO:0000269|PubMed:15131260, ECO:0000269|PubMed:18158288,
CC ECO:0000269|PubMed:21952048}.
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:10871863};
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:10871863};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC -!- SUBUNIT: Interacts with and is phosphorylated by AURKA. Binds to AR.
CC Interacts with AJUBA during mitosis and this complex regulates
CC organization of the spindle apparatus through recruitment of gamma-
CC tubulin to the centrosome. Interacts (via PPxY motif) with YAP1 (via WW
CC domains). Interacts with MOB1A and MOB1B. Interacts with LIMD1, WTIP
CC and AJUBA. Interacts with SNAI1. {ECO:0000269|PubMed:15131260,
CC ECO:0000269|PubMed:15147269, ECO:0000269|PubMed:16413547,
CC ECO:0000269|PubMed:18158288, ECO:0000269|PubMed:19739119,
CC ECO:0000269|PubMed:20303269, ECO:0000269|PubMed:21952048}.
CC -!- INTERACTION:
CC Q9NRM7; Q96IF1: AJUBA; NbExp=6; IntAct=EBI-3506895, EBI-949782;
CC Q9NRM7; Q9Y4B6: DCAF1; NbExp=2; IntAct=EBI-3506895, EBI-1996353;
CC Q9NRM7; Q13643: FHL3; NbExp=4; IntAct=EBI-3506895, EBI-741101;
CC Q9NRM7; Q9H8S9: MOB1A; NbExp=4; IntAct=EBI-3506895, EBI-748229;
CC Q9NRM7; Q7L9L4: MOB1B; NbExp=5; IntAct=EBI-3506895, EBI-2558745;
CC Q9NRM7; O43255: SIAH2; NbExp=6; IntAct=EBI-3506895, EBI-948141;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, microtubule organizing
CC center, centrosome. Cytoplasm. Cytoplasm, cytoskeleton, spindle pole.
CC Nucleus. Note=Colocalizes with AURKA at the centrosomes during
CC interphase, early prophase and cytokinesis. Migrates to the spindle
CC poles during mitosis, and to the midbody during cytokinesis.
CC Translocates to the nucleus upon mitotic stress by nocodazole
CC treatment.
CC -!- TISSUE SPECIFICITY: Expressed at high levels in heart and skeletal
CC muscle and at lower levels in all other tissues examined.
CC {ECO:0000269|PubMed:10673337, ECO:0000269|PubMed:10871863}.
CC -!- PTM: Autophosphorylated and phosphorylated during M-phase and the G1/S-
CC phase of the cell cycle. Phosphorylated and activated by STK3/MST2.
CC Phosphorylation by NUAK2 may regulate its activity in phosphorylation
CC and inactivation YAP1 (PubMed:32845958). {ECO:0000269|PubMed:15147269,
CC ECO:0000269|PubMed:15688006, ECO:0000269|PubMed:21952048,
CC ECO:0000269|PubMed:32845958}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA92381.1; Type=Frameshift; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/LATS2ID41128ch13q12.html";
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DR EMBL; AF207547; AAF80561.1; -; mRNA.
DR EMBL; AK314235; BAG36905.1; -; mRNA.
DR EMBL; AL161613; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL356285; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471075; EAX08286.1; -; Genomic_DNA.
DR EMBL; AB028019; BAA92381.1; ALT_FRAME; mRNA.
DR CCDS; CCDS9294.1; -.
DR RefSeq; NP_055387.2; NM_014572.2.
DR RefSeq; XP_005266399.1; XM_005266342.1.
DR PDB; 4ZRI; X-ray; 2.70 A; C/D=68-99.
DR PDBsum; 4ZRI; -.
DR AlphaFoldDB; Q9NRM7; -.
DR SMR; Q9NRM7; -.
DR BioGRID; 117727; 228.
DR CORUM; Q9NRM7; -.
DR DIP; DIP-43883N; -.
DR ELM; Q9NRM7; -.
DR IntAct; Q9NRM7; 84.
DR MINT; Q9NRM7; -.
DR STRING; 9606.ENSP00000372035; -.
DR BindingDB; Q9NRM7; -.
DR ChEMBL; CHEMBL5907; -.
DR DrugCentral; Q9NRM7; -.
DR GlyGen; Q9NRM7; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9NRM7; -.
DR PhosphoSitePlus; Q9NRM7; -.
DR BioMuta; LATS2; -.
DR DMDM; 212276441; -.
DR EPD; Q9NRM7; -.
DR jPOST; Q9NRM7; -.
DR MassIVE; Q9NRM7; -.
DR MaxQB; Q9NRM7; -.
DR PaxDb; Q9NRM7; -.
DR PeptideAtlas; Q9NRM7; -.
DR PRIDE; Q9NRM7; -.
DR ProteomicsDB; 82392; -.
DR Antibodypedia; 22361; 323 antibodies from 31 providers.
DR DNASU; 26524; -.
DR Ensembl; ENST00000382592.5; ENSP00000372035.4; ENSG00000150457.9.
DR GeneID; 26524; -.
DR KEGG; hsa:26524; -.
DR MANE-Select; ENST00000382592.5; ENSP00000372035.4; NM_014572.3; NP_055387.2.
DR UCSC; uc001unr.6; human.
DR CTD; 26524; -.
DR DisGeNET; 26524; -.
DR GeneCards; LATS2; -.
DR HGNC; HGNC:6515; LATS2.
DR HPA; ENSG00000150457; Low tissue specificity.
DR MIM; 604861; gene.
DR neXtProt; NX_Q9NRM7; -.
DR OpenTargets; ENSG00000150457; -.
DR PharmGKB; PA30302; -.
DR VEuPathDB; HostDB:ENSG00000150457; -.
DR eggNOG; KOG0608; Eukaryota.
DR GeneTree; ENSGT00940000159161; -.
DR HOGENOM; CLU_004885_1_0_1; -.
DR InParanoid; Q9NRM7; -.
DR OMA; PRQYMDF; -.
DR OrthoDB; 759391at2759; -.
DR PhylomeDB; Q9NRM7; -.
DR TreeFam; TF351549; -.
DR PathwayCommons; Q9NRM7; -.
DR Reactome; R-HSA-2028269; Signaling by Hippo.
DR SignaLink; Q9NRM7; -.
DR SIGNOR; Q9NRM7; -.
DR BioGRID-ORCS; 26524; 29 hits in 1115 CRISPR screens.
DR ChiTaRS; LATS2; human.
DR GeneWiki; LATS2; -.
DR GenomeRNAi; 26524; -.
DR Pharos; Q9NRM7; Tchem.
DR PRO; PR:Q9NRM7; -.
DR Proteomes; UP000005640; Chromosome 13.
DR RNAct; Q9NRM7; protein.
DR Bgee; ENSG00000150457; Expressed in epithelial cell of pancreas and 194 other tissues.
DR ExpressionAtlas; Q9NRM7; baseline and differential.
DR Genevisible; Q9NRM7; HS.
DR GO; GO:0034451; C:centriolar satellite; IDA:HPA.
DR GO; GO:0005829; C:cytosol; IDA:FlyBase.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0000922; C:spindle pole; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
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:0060070; P:canonical Wnt signaling pathway; IEA:Ensembl.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0000082; P:G1/S 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; IDA: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; IDA:UniProtKB.
DR GO; GO:0030216; P:keratinocyte differentiation; IEA:Ensembl.
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:0008104; P:protein localization; IEA:Ensembl.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0046620; P:regulation of organ growth; IBA:GO_Central.
DR GO; GO:0017015; P:regulation of transforming growth factor beta receptor signaling pathway; ISS:UniProtKB.
DR InterPro; IPR000961; AGC-kinase_C.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR028742; LATS2.
DR InterPro; IPR017892; Pkinase_C.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR InterPro; IPR015940; UBA.
DR InterPro; IPR009060; UBA-like_sf.
DR PANTHER; PTHR24356:SF149; PTHR24356:SF149; 1.
DR Pfam; PF00069; Pkinase; 1.
DR Pfam; PF00433; Pkinase_C; 1.
DR SMART; SM00133; S_TK_X; 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; PS00107; PROTEIN_KINASE_ATP; 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; ATP-binding; Cell cycle; Cell division; Cytoplasm;
KW Cytoskeleton; Kinase; Magnesium; Metal-binding; Mitosis;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Tumor suppressor.
FT CHAIN 1..1088
FT /note="Serine/threonine-protein kinase LATS2"
FT /id="PRO_0000086234"
FT DOMAIN 98..139
FT /note="UBA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00212"
FT DOMAIN 668..973
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 974..1052
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT REGION 24..49
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 271..323
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 383..428
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 454..483
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 543..592
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 994..1022
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1056..1088
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 515..518
FT /note="PPxY motif"
FT COMPBIAS 26..42
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 464..478
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 551..571
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1062..1080
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 791
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P22612,
FT ECO:0000255|PROSITE-ProRule:PRU00159, ECO:0000255|PROSITE-
FT ProRule:PRU10027"
FT BINDING 674..782
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P22612,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 697
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000269|PubMed:10871863"
FT MOD_RES 83
FT /note="Phosphoserine; by AURKA"
FT /evidence="ECO:0000269|PubMed:15147269"
FT MOD_RES 279
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 380
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 576
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1041
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:21952048"
FT VARIANT 40
FT /note="G -> E (in a lung adenocarcinoma sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040669"
FT VARIANT 91
FT /note="S -> L (in dbSNP:rs55842804)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040670"
FT VARIANT 324
FT /note="A -> V (in dbSNP:rs558614)"
FT /evidence="ECO:0000269|PubMed:10673337"
FT /id="VAR_019789"
FT VARIANT 363
FT /note="G -> S (in dbSNP:rs2770928)"
FT /id="VAR_047077"
FT VARIANT 799
FT /note="I -> V (in dbSNP:rs35368391)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040671"
FT VARIANT 1014
FT /note="A -> G (in dbSNP:rs45523141)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040672"
FT VARIANT 1025
FT /note="L -> P (in dbSNP:rs56116059)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040673"
FT MUTAGEN 83
FT /note="S->C: Fails to localize at the centromere during
FT interphase."
FT /evidence="ECO:0000269|PubMed:15147269"
FT MUTAGEN 83
FT /note="S->E: Fails to localize at the centromere during
FT interphase."
FT /evidence="ECO:0000269|PubMed:15147269"
FT MUTAGEN 697
FT /note="K->A: Loss of kinase activity, autophosphorylation
FT and tumor suppressor activity."
FT /evidence="ECO:0000269|PubMed:10871863,
FT ECO:0000269|PubMed:12853976"
FT MUTAGEN 872
FT /note="S->A: Loss of tumor suppressor activity."
FT /evidence="ECO:0000269|PubMed:12853976"
FT CONFLICT 59..61
FT /note="RQQ -> SSK (in Ref. 5; BAA92381)"
FT /evidence="ECO:0000305"
FT CONFLICT 436
FT /note="T -> S (in Ref. 5; BAA92381)"
FT /evidence="ECO:0000305"
FT CONFLICT 711
FT /note="A -> V (in Ref. 1; AAF80561)"
FT /evidence="ECO:0000305"
FT CONFLICT 868
FT /note="C -> S (in Ref. 5; BAA92381)"
FT /evidence="ECO:0000305"
FT HELIX 74..84
FT /evidence="ECO:0007829|PDB:4ZRI"
FT HELIX 85..87
FT /evidence="ECO:0007829|PDB:4ZRI"
SQ SEQUENCE 1088 AA; 120136 MW; 2866F6B75637AD36 CRC64;
MRPKTFPATT YSGNSRQRLQ EIREGLKQPS KSSVQGLPAG PNSDTSLDAK VLGSKDATRQ
QQQMRATPKF GPYQKALREI RYSLLPFANE SGTSAAAEVN RQMLQELVNA GCDQEMAGRA
LKQTGSRSIE AALEYISKMG YLDPRNEQIV RVIKQTSPGK GLMPTPVTRR PSFEGTGDSF
ASYHQLSGTP YEGPSFGADG PTALEEMPRP YVDYLFPGVG PHGPGHQHQH PPKGYGASVE
AAGAHFPLQG AHYGRPHLLV PGEPLGYGVQ RSPSFQSKTP PETGGYASLP TKGQGGPPGA
GLAFPPPAAG LYVPHPHHKQ AGPAAHQLHV LGSRSQVFAS DSPPQSLLTP SRNSLNVDLY
ELGSTSVQQW PAATLARRDS LQKPGLEAPP RAHVAFRPDC PVPSRTNSFN SHQPRPGPPG
KAEPSLPAPN TVTAVTAAHI LHPVKSVRVL RPEPQTAVGP SHPAWVPAPA PAPAPAPAPA
AEGLDAKEEH ALALGGAGAF PLDVEYGGPD RRCPPPPYPK HLLLRSKSEQ YDLDSLCAGM
EQSLRAGPNE PEGGDKSRKS AKGDKGGKDK KQIQTSPVPV RKNSRDEEKR ESRIKSYSPY
AFKFFMEQHV ENVIKTYQQK VNRRLQLEQE MAKAGLCEAE QEQMRKILYQ KESNYNRLKR
AKMDKSMFVK IKTLGIGAFG EVCLACKVDT HALYAMKTLR KKDVLNRNQV AHVKAERDIL
AEADNEWVVK LYYSFQDKDS LYFVMDYIPG GDMMSLLIRM EVFPEHLARF YIAELTLAIE
SVHKMGFIHR DIKPDNILID LDGHIKLTDF GLCTGFRWTH NSKYYQKGSH VRQDSMEPSD
LWDDVSNCRC GDRLKTLEQR ARKQHQRCLA HSLVGTPNYI APEVLLRKGY TQLCDWWSVG
VILFEMLVGQ PPFLAPTPTE TQLKVINWEN TLHIPAQVKL SPEARDLITK LCCSADHRLG
RNGADDLKAH PFFSAIDFSS DIRKQPAPYV PTISHPMDTS NFDPVDEESP WNDASEGSTK
AWDTLTSPNN KHPEHAFYEF TFRRFFDDNG YPFRCPKPSG AEASQAESSD LESSDLVDQT
EGCQPVYV
