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LATS2 (LATS, large tumor suppressor, homolog 2 (Drosophila))

Written2010-01Damjan Glavač, Mojca Stražišar
Department of Molecular genetics, Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia

(Note : for Links provided by Atlas : click)

Identity

Alias_namesLATS (large tumor suppressor, Drosophila) homolog 2
LATS, large tumor suppressor, homolog 2 (Drosophila)
Other aliasKPM
FLJ13161
EC 2.7.11.1
HGNC (Hugo) LATS2
LocusID (NCBI) 26524
Atlas_Id 41128
Location 13q12.11  [Link to chromosome band 13q12]
Location_base_pair Starts at 21547176 and ends at 21635722 bp from pter ( according to hg19-Feb_2009)  [Mapping LATS2.png]
Local_order Chromosome 13; orientation: negative.
 
  UBA: ubiquitin-associated domain, PK: protein kinase domain, AGC: AGC-C terminal domain, Nu-B: NB-nucleotide binding domain.
Fusion genes
(updated 2016)
LATS2 (13q12.11) / TXN (9q31.3)PSPC1 (13q12.11) / LATS2 (13q12.11)

DNA/RNA

Note Type: functioning gene, 8 exons.
 
  Filled blocks: coding exons, white blocks: non-coding exons, line: intron region, Ex: exon, In: intron, bp: base pair, kb: kilobase.
Description Yabuta et al. (2000) mapped the human LATS2 gene to 13q11-q12 (FISH); gene with protein product. Gene encodes a serine/threonine protein kinase belonging to the LATS tumor suppressor family.
Pseudogene Not known; paralogs according to Ensembl: LATS1, ROCK1, ROCK2.

Protein

Note LATS2 is a nuclear protein of approximately 120 kDa and 1088 AA. The protein localizes to centrosomes during interphase, and early and late metaphase. It interacts with the centrosomal proteins aurora-A and Ajuba and is required for accumulation of gamma-tubulin and spindle formation at the onset of mitosis. It also interacts with a negative regulator of TP53 and may function in a positive feedback loop with TP53 that responds to cytoskeleton damage. Additionally, it can function as a co-repressor of androgen-responsive gene expression.
 
  UBA: ubiquitin-associated domain, STK: serin/threonin kinase domain, AGC: AGC- C terminal domain, Ab: ATP-binding domain, AA: amino acid, P-Ser: phosphorylated serine, P-Thr: phosphorylated threonine, ATP-b: ATP binding site, Pa: proton acceptor.
Description LATS2 protein is a serine/threonine protein kinase, 1088 AA; 120kDa; cofactor is magnesium. Subunit interacts and is phosphorylated by STK6. LATS2 binds to AR and interacts to JUB during mitosis. Complex regulates spindle apparatus organisation through gamma-tubulin recruitment to the centrosome. Protein is auto-phosphorylated and phosphorylated during M- and G1/S- phase of cell cycle; phosphorylated and activated by STK3.
Expression Expressed at high levels in heart and skeletal muscle and at lower levels in all other tissues examined. Gene is found in cDNA libraries from the following tissue types: b-cell, bone, bone marrow, brain, cartilage, cerebrum, colon, ear, embryonic tissue, eye, foetus, gastrointestinal tract, heart, kidney, liver, lung, lymph node, lympho-reticular, mammary gland, muscle, nervous, ovary, pancreas, pancreatic islet, peripheral nervous system, placenta, pooled tissue, prostate, skin, spleen, stem cell, stomach, t-cell, testis, uncharacterized tissue, uterus, vascular.
Localisation Cytoplasm, nucleus, spindle pole, centrosome; co-localizes with STK6 at the centrosomes during interphase, early pro-phase and cytokinesis. Migrates to spindle poles during mitosis, and to the mid-body during cytokinesis. S83 of Lats2 is a phosphorylation target of Aurora-A and the phosphorylation plays a role of the centrosomal localization of Lats2 (Toji et al., 2004).
Function Protein product involved in: G1/S transition of mitotic cell cycle, hormone-mediated signalling pathway; negative regulation of Cyclin-dependent protein kinase activity; protein amino acid phosphorylation; protein kinase cascade; centrosome localisation; ATP binding; Mg-ion binding, nucleotide binding, protein serine/threonine kinase activity; protein tyrosine kinase activity; transferase activity; negative regulation of androgen receptor activity. LATS2 is a tumour suppressor that plays critical role in centrosome duplication, maintenance of mitotic fidelity and genomic stability. Negatively regulates G1/S transition by down-regulating cyclin E/CDK2 kinase activity.
LATS2 is involved in conserved Hippo signalling pathway (Zhang et al., 2008; Hergovich et al., 2009). LATS2 has an essential role in the integrity of processes that govern centrosome duplication, mitotic fidelity and genomic stability (McPherson et al., 2004). Components of the pathway bring LATS2 in contact with MST1 and MST2 kinase, which phosphorylates and activates LATS2. Functionally, pathway with LATS2 included is involved in cell proliferation, apoptosis, and cell migration. Involvement in apoptosis has been demonstrated in lung cancer cells where LATS2 has been shown to induce apoptosis through down regulation of BCL-2 and BCL-XL (BCL2L1) anti-apoptotic proteins (Ke et al., 2004).
LATS2 has been reported to inhibit cell growth by causing G1/S and/or G2/M cycle arrest (Li et al., 2003; Kamikubo et al., 2003). LATS2 binds MDM2 and with inhibiting its E3 ligase activity activates TP53. In turn TP53 rapidly and selectively up-regulates LATS2 expression in G2/M cells, defining positive feedback loop. Therefore LATS2-MDM2-TP53 constitutes a novel checkpoint pathway critical for maintenance of proper chromosome number (Aylon et al., 2007). LATS2 is also associated with Ajuba in LATS2-Ajuba complex that regulates organization of the spindle apparatus through recruitment of γ-tubulin to the centrosome (Abe et al., 2006).
In vitro over expression of LATS2 was seen to cause G1/S arrest through the inhibition of CDK2 activity (Li et al., 2003). Complete LATS2 knock-out cells exhibit an acceleration of exit from mitosis and marked down-regulation of critical mitotic regulators, proving its role in coordinating accurate cytokinesis completion, governing the stabilization of other regulators of mitosis (Yabuta at al., 2007). Study of LATS2 knock-out cells and transient co-expression of LATS2, YAP and TP73 showed that LATS2 contributes to the stability of YAP2 (YAP1) and TP73, which is dependant on the kinase function leading to the conclusion that LATS2 is involved in the fate of TP73 through YAP2 (Kawahara et al., 2008).

Mutations

 
  Position of alterations marked on the exons; length and position of the coding region described according to the exons.
Germinal No data.
Somatic Mutations are rare and mostly found in cancerous tissue. More frequently hypermethylation of the LATS2 promoter and or down-regulation of the expression is related to different kind of cancers (lung, breast, hepatocellular, leukaemias, testicular, astrocytomas, retinoblastoma, head and neck).
When polymorphism is noted or when dbSNP entrance number is provided, alterations are listed as polymorphisms; references are those when the alteration was first published.
1-59_70delT polymorphism Strazisar M, Mlakar V, Glavac D. LATS2 tumour specific mutations and down-regulation of the gene in non-small cell carcinoma. Lung Cancer. 2009; 64(3): 257-62
119G>A (G40E) in lung adenocarcinoma cell line   Greenman C, Stephens P, Smith R, et al. Patterns of somatic mutation in human cancer genomes. Nature. 2007 Mar 8; 446(7132): 153-8.
1-203G/T

polymorphism

Strazisar M, Mlakar V, Glavac D. LATS2 tumour specific mutations and down-regulation of the gene in non-small cell carcinoma. Lung Cancer. 2009; 64(3): 257-62
272C>T (S91L)dbSNP rs55842804Greenman C, Stephens P, Smith R, et al. Patterns of somatic mutation in human cancer genomes. Nature. 2007 Mar 8; 446(7132): 153-8.
ins 472_479 APpolymorphismStrazisar M, Mlakar V, Glavac D. LATS2 tumour specific mutations and down-regulation of the gene in non-small cell carcinoma. Lung Cancer. 2009; 64(3): 257-62
del 472_479 APAPAPAP Strazisar M, Mlakar V, Glavac D. LATS2 tumour specific mutations and down-regulation of the gene in non-small cell carcinoma. Lung Cancer. 2009; 64(3): 257-62
971C>T (A324V) dbSNP rs558614 Yabuta N, Fujii T, Copeland NG, et al. Structure, expression, and chromosome mapping of LATS2, a mammalian homologue of the Drosophila tumor suppressor gene lats/warts. Genomics. 2000 Jan 15; 63(2): 263-70.
1087G>A (G363S) dbSNP rs2770928 
1899+145A/G polymorphismStrazisar M, Mlakar V, Glavac D. LATS2 tumour specific mutations and down-regulation of the gene in non-small cell carcinoma. Lung Cancer. 2009; 64(3): 257-62

2133C>T (V711V)

  
2395A>G (I799V)

dbSNP rs35368391 

Greenman C, Stephens P, Smith R, et al. Patterns of somatic mutation in human cancer genomes. Nature. 2007 Mar 8; 446(7132): 153-8.
2775G>A (V925V) in lung adenocarcinoma cell line  Sanger
2859C>A (C953Ter) in ovary mucinous carcinoma (not specified) Sanger
2892C>T (A964A)  Strazisar M, Mlakar V, Glavac D. LATS2 tumour specific mutations and down-regulation of the gene in non-small cell carcinoma. Lung Cancer. 2009; 64(3): 257-62
3041C>G (A1014G)dbSNP rs45523141Greenman C, Stephens P, Smith R, et al. Patterns of somatic mutation in human cancer genomes. Nature. 2007 Mar 8; 446(7132): 153-8.
3074T>C (L1025P)dbSNP rs56116059Greenman C, Stephens P, Smith R, et al. Patterns of somatic mutation in human cancer genomes. Nature. 2007 Mar 8; 446(7132): 153-8.
3219C>A (S1073R) Strazisar M, Mlakar V, Glavac D. LATS2 tumour specific mutations and down-regulation of the gene in non-small cell carcinoma. Lung Cancer. 2009; 64(3): 257-62

Implicated in

Note
  
Entity Various cancers
Note Loss of LATS2 in mice is lethal. Knockout of the gene in mice embryonic fibroblasts induces mitotic defects, genomic instability and loss of contact inhibition (McPherson et al., 2004; Yabuta et al., 2007). Over-expression of LATS2 inhibits tumour formation in mice, or reduces cell growth in human tumour cell lines (Yang et al., 2001; Xia et al., 2002; Li et al., 2003) and on the other hand mutations and/or reduced expression (either methylation or miRNA regulation or unknown) have been observed in variety of human cancers; leukaemia (Jimenez-Velasco et al., 2005), astrocytomas (Jiang et al., 2006), prostate (Powzaniuk et al., 2004), breast (Takahashi et al., 2005), lung (Strazisar et al., 2009), head and neck (Steinmann et al., 2009), retinoblastoma (Chaktaborty et al., 2007), oesophageal (Lee et al., 2009), hepatocellular (Chen et al., 2005) and possibly also colon (Sivarajasingham et al., 2003) cancer. Frequent LOH of the gene has been observed in breast, ovary and liver cancer (Lee et al., 1988; Sato et al., 1991; Wang and Roger, 1988).
  
  
Entity Breast cancer
Note Reduced expression of LATS2 mRNA is associated with biologically aggressive phenotypes of breast cancer, indicating that the reduced function of LATS2 can lead to accelerated cell proliferation and have as a result higher incidence of distant metastases (Takahashi et al., 2005). LATS2 mRNA levels were in 2007 discovered to be clinically useful for the prediction of response to epirubicin plus cyclophosphamide treatment in breast cancer patients (Takahashi et al., 2007).
  
  
Entity Acute lymphoblastic leukaemia
Prognosis Down regulation mainly by aberrant promoter methylation of LATS2 is also associated with poor prognosis in acute lymphoblastic leukaemia (Jimenez-Velasco et al., 2005).
  
  
Entity Testicular and prostate tumours
Note In testicular germ cell tumours miRNAs (miR-372 and miR-373) were implicated in neutralization of TP53-mediated CDK inhibition, through direct inhibition of the expression of LATS2 (Voorhoeve et al., 2006). It has been also shown that LATS2 is down regulated in human testicular cancer cells (Vorhoeve et al., 2006; Duale et al., 2007). LATS2 functions also as negative regulator of AR (androgen receptor), which plays an essential role in the development and maintenance of the male reproductive system and in prostate cancer. It has been shown that expression of LATS2 is lower in human prostate tumours, and suggested to contribute to the development of prostate cancer through regulation AR-mediated transcription (Powzaniuk et al., 2004).
  
  
Entity Astrocytomas
Note Methylation of LATS2 and down regulation was detected in astrocytomas and proposed as a useful target for astrocytomas therapy by Jiang et al. (2006).
  
  
Entity Oesophageal squamous cell carcinoma
Note Frequent polymorphic changes but rare tumour specific mutations of the LATS2 gene were found in oesophageal squamous cell carcinoma, indicating LATS2 is inactivated in only small parts of oesophageal tumours (Ishizaki et al., 2002).
  
  
Entity Non-small cell lung cancer
Note Down regulation of LATS2 have been found in non-small cell lung cancer and mutations discovered have been related mostly to squamous lung cell carcinomas (Strazisar et al., 2009a; Strazisar et al., 2009b).
  

Breakpoints

Note Data about all observed breakpoints found at the approximate/distal location of LATS2, but no mentioning of the gene itself:
NCBI CancerChromosomes database: Over 500 investigations on 13q11 and over 1000 on 13q12.
The Cancer genome anatomy project: 209 investigations on 13q11 found.

Bibliography

LATS2-Ajuba complex regulates gamma-tubulin recruitment to centrosomes and spindle organization during mitosis.
Abe Y, Ohsugi M, Haraguchi K, Fujimoto J, Yamamoto T.
FEBS Lett. 2006 Feb 6;580(3):782-8. Epub 2006 Jan 9.
PMID 16413547
 
A positive feedback loop between the p53 and Lats2 tumor suppressors prevents tetraploidization.
Aylon Y, Michael D, Shmueli A, Yabuta N, Nojima H, Oren M.
Genes Dev. 2006 Oct 1;20(19):2687-700.
PMID 17015431
 
Silencing of the Lats2 tumor suppressor overrides a p53-dependent oncogenic stress checkpoint and enables mutant H-Ras-driven cell transformation.
Aylon Y, Yabuta N, Besserglick H, Buganim Y, Rotter V, Nojima H, Oren M.
Oncogene. 2009 Dec 17;28(50):4469-79. Epub 2009 Oct 26.
PMID 19855428
 
Pharmacogenomic profile of soy isoflavone concentrate in the prostate of Nrf2 deficient and wild-type mice.
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J Pharm Sci. 2008 Oct;97(10):4528-45.
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Identification of genes associated with tumorigenesis of retinoblastoma by microarray analysis.
Chakraborty S, Khare S, Dorairaj SK, Prabhakaran VC, Prakash DR, Kumar A.
Genomics. 2007 Sep;90(3):344-53. Epub 2007 Jun 29.
PMID 17604597
 
The Ste20-like kinase Mst2 activates the human large tumor suppressor kinase Lats1.
Chan EH, Nousiainen M, Chalamalasetty RB, Schafer A, Nigg EA, Sillje HH.
Oncogene. 2005 Mar 17;24(12):2076-86.
PMID 15688006
 
Molecular genetic evidence supporting a novel human hepatocellular carcinoma tumor suppressor locus at 13q12.11.
Chen CF, Yeh SH, Chen DS, Chen PJ, Jou YS.
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PMID 16075462
 
Comparative expression of zebrafish lats1 and lats2 and their implication in gastrulation movements.
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Molecular characterization of human homologs of yeast MOB1.
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Gene-expression profiling and array-based CGH classify CD4+CD56+ hematodermic neoplasm and cutaneous myelomonocytic leukemia as distinct disease entities.
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Mol Cancer. 2007 Aug 21;6:53.
PMID 17711579
 
Combined translocation with ZNF198-FGFR1 gene fusion and deletion of potential tumor suppressors in a myeloproliferative disorder.
Etienne A, Gelsi-Boyer V, Carbuccia N, Adelaide J, Barba G, La Starza R, Murati A, Eclache V, Birg F, Birnbaum D, Mozziconacci MJ, Mecucci C, Chaffanet M.
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Fbw7 regulates the activity of endoreduplication mediators and the p53 pathway to prevent drug-induced polyploidy.
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Oncogene. 2008 Jul 24;27(32):4411-21. Epub 2008 Apr 7.
PMID 18391985
 
Mdm2 exerts pro-apoptotic activities by antagonizing insulin-like growth factor-I-mediated survival.
Froment P, Dupont J, Christophe-Marine J.
Cell Cycle. 2008 Oct;7(19):3098-103. Epub 2008 Oct 18.
PMID 18802403
 
Patterns of somatic mutation in human cancer genomes.
Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, Davies H, Teague J, Butler A, Stevens C, Edkins S, O'Meara S, Vastrik I, Schmidt EE, Avis T, Barthorpe S, Bhamra G, Buck G, Choudhury B, Clements J, Cole J, Dicks E, Forbes S, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jenkinson A, Jones D, Menzies A, Mironenko T, Perry J, Raine K, Richardson D, Shepherd R, Small A, Tofts C, Varian J, Webb T, West S, Widaa S, Yates A, Cahill DP, Louis DN, Goldstraw P, Nicholson AG, Brasseur F, Looijenga L, Weber BL, Chiew YE, DeFazio A, Greaves MF, Green AR, Campbell P, Birney E, Easton DF, Chenevix-Trench G, Tan MH, Khoo SK, Teh BT, Yuen ST, Leung SY, Wooster R, Futreal PA, Stratton MR.
Nature. 2007 Mar 8;446(7132):153-8.
PMID 17344846
 
Mammalian NDR/LATS protein kinases in hippo tumor suppressor signaling.
Hergovich A, Hemmings BA.
Biofactors. 2009 Jul-Aug;35(4):338-45. (REVIEW)
PMID 19484742
 
Molecular cloning of a novel human protein kinase, kpm, that is homologous to warts/lats, a Drosophila tumor suppressor.
Hori T, Takaori-Kondo A, Kamikubo Y, Uchiyama T.
Oncogene. 2000 Jun 22;19(27):3101-9.
PMID 10871863
 
TTK/hMps1 mediates the p53-dependent postmitotic checkpoint by phosphorylating p53 at Thr18.
Huang YF, Chang MD, Shieh SY.
Mol Cell Biol. 2009 Jun;29(11):2935-44. Epub 2009 Mar 30.
PMID 19332559
 
Frequent polymorphic changes but rare tumor specific mutations of the LATS2 gene on 13q11-12 in esophageal squamous cell carcinoma.
Ishizaki K, Fujimoto J, Kumimoto H, Nishimoto Y, Shimada Y, Shinoda M, Yamamoto T.
Int J Oncol. 2002 Nov;21(5):1053-7.
PMID 12370754
 
Promoter hypermethylation-mediated down-regulation of LATS1 and LATS2 in human astrocytoma.
Jiang Z, Li X, Hu J, Zhou W, Jiang Y, Li G, Lu D.
Neurosci Res. 2006 Dec;56(4):450-8. Epub 2006 Oct 17.
PMID 17049657
 
Downregulation of the large tumor suppressor 2 (LATS2/KPM) gene is associated with poor prognosis in acute lymphoblastic leukemia.
Jimenez-Velasco A, Roman-Gomez J, Agirre X, Barrios M, Navarro G, Vazquez I, Prosper F, Torres A, Heiniger A.
Leukemia. 2005 Dec;19(12):2347-50.
PMID 16208412
 
Inhibition of cell growth by conditional expression of kpm, a human homologue of Drosophila warts/lats tumor suppressor.
Kamikubo Y, Takaori-Kondo A, Uchiyama T, Hori T.
J Biol Chem. 2003 May 16;278(20):17609-14. Epub 2003 Mar 5.
PMID 12624101
 
Kpm/Lats2 is linked to chemosensitivity of leukemic cells through the stabilization of p73.
Kawahara M, Hori T, Chonabayashi K, Oka T, Sudol M, Uchiyama T.
Blood. 2008 Nov 1;112(9):3856-66. Epub 2008 Jun 18.
PMID 18565851
 
Putative tumor suppressor Lats2 induces apoptosis through downregulation of Bcl-2 and Bcl-x(L).
Ke H, Pei J, Ni Z, Xia H, Qi H, Woods T, Kelekar A, Tao W.
Exp Cell Res. 2004 Aug 15;298(2):329-38.
PMID 15265683
 
[Aurora kinases and cancer]
Kimura M, Okano Y.
Gan To Kagaku Ryoho. 2005 Jan;32(1):1-5. (REVIEW)
PMID 15675572
 
MicroRNA-373 (miR-373) post-transcriptionally regulates large tumor suppressor, homolog 2 (LATS2) and stimulates proliferation in human esophageal cancer.
Lee KH, Goan YG, Hsiao M, Lee CH, Jian SH, Lin JT, Chen YL, Lu PJ.
Exp Cell Res. 2009 Sep 10;315(15):2529-38. Epub 2009 Jun 6.
PMID 19501585
 
Lats2, a putative tumor suppressor, inhibits G1/S transition.
Li Y, Pei J, Xia H, Ke H, Wang H, Tao W.
Oncogene. 2003 Jul 10;22(28):4398-405.
PMID 12853976
 
Lats2 is a negative regulator of myocyte size in the heart.
Matsui Y, Nakano N, Shao D, Gao S, Luo W, Hong C, Zhai P, Holle E, Yu X, Yabuta N, Tao W, Wagner T, Nojima H, Sadoshima J.
Circ Res. 2008 Nov 21;103(11):1309-18. Epub 2008 Oct 16.
PMID 18927464
 
Lats2/Kpm is required for embryonic development, proliferation control and genomic integrity.
McPherson JP, Tamblyn L, Elia A, Migon E, Shehabeldin A, Matysiak-Zablocki E, Lemmers B, Salmena L, Hakem A, Fish J, Kassam F, Squire J, Bruneau BG, Hande MP, Hakem R.
EMBO J. 2004 Sep 15;23(18):3677-88. Epub 2004 Sep 2.
PMID 15343267
 
Integrated genomic profiling of chronic lymphocytic leukemia identifies subtypes of deletion 13q14.
Ouillette P, Erba H, Kujawski L, Kaminski M, Shedden K, Malek SN.
Cancer Res. 2008 Feb 15;68(4):1012-21.
PMID 18281475
 
The LATS2/KPM tumor suppressor is a negative regulator of the androgen receptor.
Powzaniuk M, McElwee-Witmer S, Vogel RL, Hayami T, Rutledge SJ, Chen F, Harada S, Schmidt A, Rodan GA, Freedman LP, Bai C.
Mol Endocrinol. 2004 Aug;18(8):2011-23. Epub 2004 May 6.
PMID 15131260
 
Frequent hypermethylation of MST1 and MST2 in soft tissue sarcoma.
Seidel C, Schagdarsurengin U, Blumke K, Wurl P, Pfeifer GP, Hauptmann S, Taubert H, Dammann R.
Mol Carcinog. 2007 Oct;46(10):865-71.
PMID 17538946
 
Identifying a region of interest in site- and stage-specific colon cancer on chromosome 13.
Sivarajasingham NS, Baker R, Tilsed JV, Greenman J, Monson JR, Cawkwell L.
Ann Surg Oncol. 2003 Nov;10(9):1095-9.
PMID 14597449
 
Frequent promoter hypermethylation of tumor-related genes in head and neck squamous cell carcinoma.
Steinmann K, Sandner A, Schagdarsurengin U, Dammann RH.
Oncol Rep. 2009 Dec;22(6):1519-26.
PMID 19885608
 
The expression of COX-2, hTERT, MDM2, LATS2 and S100A2 in different types of non-small cell lung cancer (NSCLC).
Strazisar M, Mlakar V, Glavac D.
Cell Mol Biol Lett. 2009b;14(3):442-56. Epub 2009 Feb 23.
PMID 19238334
 
Low LATS2 mRNA level can predict favorable response to epirubicin plus cyclophosphamide, but not to docetaxel, in breast cancers.
Takahashi Y, Miyoshi Y, Morimoto K, Taguchi T, Tamaki Y, Noguchi S.
J Cancer Res Clin Oncol. 2007 Aug;133(8):501-9. Epub 2007 Feb 13.
PMID 17297610
 
The centrosomal protein Lats2 is a phosphorylation target of Aurora-A kinase.
Toji S, Yabuta N, Hosomi T, Nishihara S, Kobayashi T, Suzuki S, Tamai K, Nojima H.
Genes Cells. 2004 May;9(5):383-97.
PMID 15147269
 
Identification of LATS transcriptional targets in HeLa cells using whole human genome oligonucleotide microarray.
Visser S, Yang X.
Gene. 2010 Jan 1;449(1-2):22-9. Epub 2009 Sep 30.
PMID 19799973
 
A genetic screen implicates miRNA-372 and miRNA-373 as oncogenes in testicular germ cell tumors.
Voorhoeve PM, le Sage C, Schrier M, Gillis AJ, Stoop H, Nagel R, Liu YP, van Duijse J, Drost J, Griekspoor A, Zlotorynski E, Yabuta N, De Vita G, Nojima H, Looijenga LH, Agami R.
Adv Exp Med Biol. 2007;604:17-46.
PMID 17695719
 
Structure, expression, and chromosome mapping of LATS2, a mammalian homologue of the Drosophila tumor suppressor gene lats/warts.
Yabuta N, Fujii T, Copeland NG, Gilbert DJ, Jenkins NA, Nishiguchi H, Endo Y, Toji S, Tanaka H, Nishimune Y, Nojima H.
Genomics. 2000 Jan 15;63(2):263-70.
PMID 10673337
 
Lats2 is an essential mitotic regulator required for the coordination of cell division.
Yabuta N, Okada N, Ito A, Hosomi T, Nishihara S, Sasayama Y, Fujimori A, Okuzaki D, Zhao H, Ikawa M, Okabe M, Nojima H.
J Biol Chem. 2007 Jun 29;282(26):19259-71. Epub 2007 May 3.
PMID 17478426
 
Negative regulation of YAP by LATS1 underscores evolutionary conservation of the Drosophila Hippo pathway.
Zhang J, Smolen GA, Haber DA.
Cancer Res. 2008 Apr 15;68(8):2789-94.
PMID 18413746
 
Transcriptional output of the Salvador/warts/hippo pathway is controlled in distinct fashions in Drosophila melanogaster and mammalian cell lines.
Zhang X, Milton CC, Humbert PO, Harvey KF.
Cancer Res. 2009 Aug 1;69(15):6033-41. Epub 2009 Jul 7.
PMID 19584286
 
Mst out and HCC in.
Zhao B, Lei Q, Guan KL.
Cancer Cell. 2009 Nov 6;16(5):363-4.
PMID 19878866
 

Citation

This paper should be referenced as such :
Glavač , D ; Stražišar, M
LATS2 (LATS, large tumor suppressor, homolog 2 (Drosophila))
Atlas Genet Cytogenet Oncol Haematol. 2010;14(10):979-985.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/LATS2ID41128ch13q12.html


External links

Nomenclature
HGNC (Hugo)LATS2   6515
Cards
AtlasLATS2ID41128ch13q12
Entrez_Gene (NCBI)LATS2  26524  large tumor suppressor kinase 2
AliasesKPM
GeneCards (Weizmann)LATS2
Ensembl hg19 (Hinxton)ENSG00000150457 [Gene_View]  chr13:21547176-21635722 [Contig_View]  LATS2 [Vega]
Ensembl hg38 (Hinxton)ENSG00000150457 [Gene_View]  chr13:21547176-21635722 [Contig_View]  LATS2 [Vega]
ICGC DataPortalENSG00000150457
TCGA cBioPortalLATS2
AceView (NCBI)LATS2
Genatlas (Paris)LATS2
WikiGenes26524
SOURCE (Princeton)LATS2
Genetics Home Reference (NIH)LATS2
Genomic and cartography
GoldenPath hg19 (UCSC)LATS2  -     chr13:21547176-21635722 -  13q12.11   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)LATS2  -     13q12.11   [Description]    (hg38-Dec_2013)
EnsemblLATS2 - 13q12.11 [CytoView hg19]  LATS2 - 13q12.11 [CytoView hg38]
Mapping of homologs : NCBILATS2 [Mapview hg19]  LATS2 [Mapview hg38]
OMIM604861   
Gene and transcription
Genbank (Entrez)AB028019 AB209897 AF207547 AK123520 AK314235
RefSeq transcript (Entrez)NM_014572
RefSeq genomic (Entrez)NC_000013 NC_018924 NT_024524 NW_004929388
Consensus coding sequences : CCDS (NCBI)LATS2
Cluster EST : UnigeneHs.78960 [ NCBI ]
CGAP (NCI)Hs.78960
Alternative Splicing GalleryENSG00000150457
Gene ExpressionLATS2 [ NCBI-GEO ]   LATS2 [ EBI - ARRAY_EXPRESS ]   LATS2 [ SEEK ]   LATS2 [ MEM ]
Gene Expression Viewer (FireBrowse)LATS2 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)26524
GTEX Portal (Tissue expression)LATS2
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9NRM7   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ9NRM7  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ9NRM7
Splice isoforms : SwissVarQ9NRM7
Catalytic activity : Enzyme2.7.11.1 [ Enzyme-Expasy ]   2.7.11.12.7.11.1 [ IntEnz-EBI ]   2.7.11.1 [ BRENDA ]   2.7.11.1 [ KEGG ]   
PhosPhoSitePlusQ9NRM7
Domaine pattern : Prosite (Expaxy)AGC_KINASE_CTER (PS51285)    PROTEIN_KINASE_ATP (PS00107)    PROTEIN_KINASE_DOM (PS50011)    PROTEIN_KINASE_ST (PS00108)    UBA (PS50030)   
Domains : Interpro (EBI)AGC-kinase_C    Kinase-like_dom    LATS2    Prot_kinase_dom    Protein_kinase_ATP_BS    Ser/Thr_dual-sp_kinase    Ser/Thr_kinase_AS    UBA    UBA-like   
Domain families : Pfam (Sanger)Pkinase (PF00069)   
Domain families : Pfam (NCBI)pfam00069   
Domain families : Smart (EMBL)S_TK_X (SM00133)  S_TKc (SM00220)  
Conserved Domain (NCBI)LATS2
DMDM Disease mutations26524
Blocks (Seattle)LATS2
PDB (SRS)4ZRI   
PDB (PDBSum)4ZRI   
PDB (IMB)4ZRI   
PDB (RSDB)4ZRI   
Structural Biology KnowledgeBase4ZRI   
SCOP (Structural Classification of Proteins)4ZRI   
CATH (Classification of proteins structures)4ZRI   
SuperfamilyQ9NRM7
Human Protein AtlasENSG00000150457
Peptide AtlasQ9NRM7
HPRD07277
IPIIPI00016690   
Protein Interaction databases
DIP (DOE-UCLA)Q9NRM7
IntAct (EBI)Q9NRM7
FunCoupENSG00000150457
BioGRIDLATS2
STRING (EMBL)LATS2
ZODIACLATS2
Ontologies - Pathways
QuickGOQ9NRM7
Ontology : AmiGOG1/S transition of mitotic cell cycle  spindle pole  inner cell mass cell fate commitment  inner cell mass cellular morphogenesis  protein serine/threonine kinase activity  protein serine/threonine kinase activity  protein binding  ATP binding  nucleus  nucleus  cytoplasm  microtubule organizing center  cytosol  protein phosphorylation  mitotic nuclear division  hormone-mediated signaling pathway  peptidyl-serine phosphorylation  keratinocyte differentiation  cellular protein localization  hippo signaling  hippo signaling  intracellular signal transduction  positive regulation of apoptotic process  negative regulation of cyclin-dependent protein serine/threonine kinase activity  regulation of organ growth  metal ion binding  cell division  negative regulation of canonical Wnt signaling pathway  
Ontology : EGO-EBIG1/S transition of mitotic cell cycle  spindle pole  inner cell mass cell fate commitment  inner cell mass cellular morphogenesis  protein serine/threonine kinase activity  protein serine/threonine kinase activity  protein binding  ATP binding  nucleus  nucleus  cytoplasm  microtubule organizing center  cytosol  protein phosphorylation  mitotic nuclear division  hormone-mediated signaling pathway  peptidyl-serine phosphorylation  keratinocyte differentiation  cellular protein localization  hippo signaling  hippo signaling  intracellular signal transduction  positive regulation of apoptotic process  negative regulation of cyclin-dependent protein serine/threonine kinase activity  regulation of organ growth  metal ion binding  cell division  negative regulation of canonical Wnt signaling pathway  
Pathways : KEGGHippo signaling pathway   
REACTOMEQ9NRM7 [protein]
REACTOME Pathways2028269 [pathway]   
NDEx NetworkLATS2
Atlas of Cancer Signalling NetworkLATS2
Wikipedia pathwaysLATS2
Orthology - Evolution
OrthoDB26524
GeneTree (enSembl)ENSG00000150457
Phylogenetic Trees/Animal Genes : TreeFamLATS2
HOVERGENQ9NRM7
HOGENOMQ9NRM7
Homologs : HomoloGeneLATS2
Homology/Alignments : Family Browser (UCSC)LATS2
Gene fusions - Rearrangements
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerLATS2 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)LATS2
dbVarLATS2
ClinVarLATS2
1000_GenomesLATS2 
Exome Variant ServerLATS2
ExAC (Exome Aggregation Consortium)LATS2 (select the gene name)
Genetic variants : HAPMAP26524
Genomic Variants (DGV)LATS2 [DGVbeta]
DECIPHER (Syndromes)13:21547176-21635722  ENSG00000150457
CONAN: Copy Number AnalysisLATS2 
Mutations
ICGC Data PortalLATS2 
TCGA Data PortalLATS2 
Broad Tumor PortalLATS2
OASIS PortalLATS2 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICLATS2  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDLATS2
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch LATS2
DgiDB (Drug Gene Interaction Database)LATS2
DoCM (Curated mutations)LATS2 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)LATS2 (select a term)
intoGenLATS2
NCG5 (London)LATS2
Cancer3DLATS2(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM604861   
Orphanet
MedgenLATS2
Genetic Testing Registry LATS2
NextProtQ9NRM7 [Medical]
TSGene26524
GENETestsLATS2
Huge Navigator LATS2 [HugePedia]
snp3D : Map Gene to Disease26524
BioCentury BCIQLATS2
ClinGenLATS2
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD26524
Chemical/Pharm GKB GenePA30302
Clinical trialLATS2
Miscellaneous
canSAR (ICR)LATS2 (select the gene name)
Other databaseCGAP (The Cancer Genome Anatomy Project)
Probes
Litterature
PubMed87 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineLATS2
EVEXLATS2
GoPubMedLATS2
iHOPLATS2
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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