Type: functioning gene, 8 exons.

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.

Not known; paralogs according to Ensembl: LATS1, ROCK1, ROCK2.

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.

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.

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.

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).

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).

No data.

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 rs55842804	Greenman 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 AP	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
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	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
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 rs45523141	Greenman 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 rs56116059	Greenman 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

NCBI CancerChromosomes database: Over 500 investigations on 13q11 and over 1000 on 13q12.
The Cancer genome anatomy project: 209 investigations on 13q11 found.