LATS2

Large tumor suppressor kinase 2 (LATS2) is an enzyme that in humans is encoded by the LATS2 gene. This gene encodes a serine/threonine protein kinase belonging to the LATS tumor suppressor family and participates in the Hippo signaling pathway where it inactivates the effector proteins, YAP and WWTR1 (TAZ). 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 p53 and may function in a positive feedback loop with p53 that responds to cytoskeleton damage. Additionally, it can function as a corepressor of androgen-responsive gene expression.

Protein-coding gene in the species Homo sapiens

LATS2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4ZRI
Identifiers
Aliases	LATS2, KPM, large tumor suppressor kinase 2
External IDs	OMIM: 604861; MGI: 1354386; HomoloGene: 56678; GeneCards: LATS2; OMA:LATS2 - orthologs
Gene location (Human) Chr. Chromosome 13 (human)[1] Band 13q12.11 Start 20,973,036 bp[1] End 21,061,586 bp[1]
Gene location (Mouse) Chr. Chromosome 14 (mouse)[2] Band 14|14 C3 Start 57,927,119 bp[2] End 57,995,845 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in pancreatic epithelial cell myocardium of left ventricle visceral pleura parietal pleura tibialis anterior muscle tibia germinal epithelium cardiac muscle tissue of right atrium lower lobe of lung amniotic fluid Top expressed in ascending aorta aortic valve external carotid artery sciatic nerve cardiac muscle tissue of left ventricle internal carotid artery spermatid left lung lobe plantaris muscle carotid body More reference expression data BioGPS More reference expression data
Gene ontology Molecular function transferase activity nucleotide binding protein kinase activity metal ion binding kinase activity protein binding ATP binding protein serine/threonine kinase activity Cellular component spindle pole microtubule organizing center cytoskeleton nucleus cytoplasm cytosol Biological process intracellular signal transduction phosphorylation negative regulation of cyclin-dependent protein serine/threonine kinase activity cell division protein phosphorylation peptidyl-serine phosphorylation hormone-mediated signaling pathway positive regulation of apoptotic process cell cycle G1/S transition of mitotic cell cycle hippo signaling regulation of organ growth negative regulation of canonical Wnt signaling pathway inner cell mass cell fate commitment inner cell mass cellular morphogenesis keratinocyte differentiation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 26524 50523 Ensembl ENSG00000150457 ENSMUSG00000021959 UniProt Q9NRM7 Q7TSJ6 RefSeq (mRNA) NM_014572 NM_015771 NM_153382 RefSeq (protein) NP_055387 NP_056586 NP_700431 Location (UCSC) Chr 13: 20.97 – 21.06 Mb Chr 14: 57.93 – 58 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Large tumor suppressor kinase 2 (LATS2) is an enzyme that in humans is encoded by the LATS2 gene.^[5][6]

This gene encodes a serine/threonine protein kinase belonging to the LATS tumor suppressor family and participates in the Hippo signaling pathway where it inactivates the effector proteins, YAP and WWTR1 (TAZ). 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 p53 and may function in a positive feedback loop with p53 that responds to cytoskeleton damage. Additionally, it can function as a corepressor of androgen-responsive gene expression.^[6]

References

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1. ^ ^{a b c} GRCh38: Ensembl release 89: ENSG00000150457 – Ensembl, May 2017
2. ^ ^{a b c} GRCm38: Ensembl release 89: ENSMUSG00000021959 – Ensembl, May 2017
3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. ^ Yabuta N, Fujii T, Copeland NG, Gilbert DJ, Jenkins NA, Nishiguchi H, Endo Y, Toji S, Tanaka H, Nishimune Y, Nojima H (Apr 2000). "Structure, expression, and chromosome mapping of LATS2, a mammalian homologue of the Drosophila tumor suppressor gene lats/warts". Genomics. 63 (2): 263–70. doi:10.1006/geno.1999.6065. PMID 10673337.
6. ^ ^{a b} "Entrez Gene: LATS2 LATS, large tumor suppressor, homolog 2 (Drosophila)".

Further reading

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• Hori T, Takaori-Kondo A, Kamikubo Y, Uchiyama T (2000). "Molecular cloning of a novel human protein kinase, kpm, that is homologous to warts/lats, a Drosophila tumor suppressor". Oncogene. 19 (27): 3101–9. doi:10.1038/sj.onc.1203659. PMID 10871863.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Li Y, Pei J, Xia H, et al. (2003). "Lats2, a putative tumor suppressor, inhibits G1/S transition". Oncogene. 22 (28): 4398–405. doi:10.1038/sj.onc.1206603. PMID 12853976.
• Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
• Powzaniuk M, McElwee-Witmer S, Vogel RL, et al. (2005). "The LATS2/KPM tumor suppressor is a negative regulator of the androgen receptor". Mol. Endocrinol. 18 (8): 2011–23. doi:10.1210/me.2004-0065. PMID 15131260.
• Toji S, Yabuta N, Hosomi T, et al. (2005). "The centrosomal protein Lats2 is a phosphorylation target of Aurora-A kinase". Genes Cells. 9 (5): 383–97. doi:10.1111/j.1356-9597.2004.00732.x. PMID 15147269.
• Ke H, Pei J, Ni Z, et al. (2004). "Putative tumor suppressor Lats2 induces apoptosis through downregulation of Bcl-2 and Bcl-x(L)". Exp. Cell Res. 298 (2): 329–38. doi:10.1016/j.yexcr.2004.04.031. PMID 15265683.
• Chan EH, Nousiainen M, Chalamalasetty RB, et al. (2005). "The Ste20-like kinase Mst2 activates the human large tumor suppressor kinase Lats1". Oncogene. 24 (12): 2076–86. doi:10.1038/sj.onc.1208445. PMID 15688006. S2CID 27285160.
• Takahashi Y, Miyoshi Y, Takahata C, et al. (2005). "Down-regulation of LATS1 and LATS2 mRNA expression by promoter hypermethylation and its association with biologically aggressive phenotype in human breast cancers". Clin. Cancer Res. 11 (4): 1380–5. doi:10.1158/1078-0432.CCR-04-1773. PMID 15746036.
• Abe Y, Ohsugi M, Haraguchi K, et al. (2006). "LATS2-Ajuba complex regulates gamma-tubulin recruitment to centrosomes and spindle organization during mitosis". FEBS Lett. 580 (3): 782–8. Bibcode:2006FEBSL.580..782A. doi:10.1016/j.febslet.2005.12.096. PMID 16413547.
• Voorhoeve PM, le Sage C, Schrier M, et al. (2006). "A genetic screen implicates miRNA-372 and miRNA-373 as oncogenes in testicular germ cell tumors". Cell. 124 (6): 1169–81. doi:10.1016/j.cell.2006.02.037. PMID 16564011.
• Aylon Y, Michael D, Shmueli A, et al. (2007). "A positive feedback loop between the p53 and Lats2 tumor suppressors prevents tetraploidization". Genes Dev. 20 (19): 2687–700. doi:10.1101/gad.1447006. PMC 1578695. PMID 17015431.
• Jiang Z, Li X, Hu J, et al. (2007). "Promoter hypermethylation-mediated down-regulation of LATS1 and LATS2 in human astrocytoma". Neurosci. Res. 56 (4): 450–8. doi:10.1016/j.neures.2006.09.006. PMID 17049657. S2CID 22763208.

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