LATS1

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LATS1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4ZRK, 5BRK, 5B5W
Identifiers
Aliases	LATS1, WARTS, wts, large tumor suppressor kinase 1
External IDs	OMIM: 603473; MGI: 1333883; HomoloGene: 55843; GeneCards: LATS1; OMA:LATS1 - orthologs
Gene location (Human) Chr. Chromosome 6 (human) Band 6q25.1 Start 149,658,153 bp End 149,718,105 bp
Gene location (Mouse) Chr. Chromosome 10 (mouse) Band 10|10 A1 Start 7,556,978 bp End 7,592,224 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in germinal epithelium tibia mucosa of paranasal sinus gingival epithelium epithelium of nasopharynx parietal pleura visceral pleura seminal vesicula retinal pigment epithelium palpebral conjunctiva Top expressed in genital tubercle tail of embryo uterus ganglionic eminence ventricular zone ovary lens jejunum granulocyte ileum More reference expression data BioGPS More reference expression data
Gene ontology Molecular function nucleotide binding protein binding protein kinase binding protein kinase activity kinase activity transferase activity metal ion binding magnesium ion binding protein serine/threonine kinase activity ATP binding estrogen receptor binding Cellular component microtubule organizing center spindle pole cytoplasm cytoskeleton cytosol Biological process cell cycle phosphorylation G2/M transition of mitotic cell cycle regulation of actin filament polymerization inner cell mass cell fate commitment keratinocyte differentiation negative regulation of cyclin-dependent protein serine/threonine kinase activity regulation of organ growth regulation of protein-containing complex assembly cytoplasmic sequestering of protein sister chromatid segregation positive regulation of apoptotic process negative regulation of canonical Wnt signaling pathway inner cell mass cellular morphogenesis cell division positive regulation of peptidyl-serine phosphorylation hippo signaling protein phosphorylation hormone-mediated signaling pathway regulation of intracellular estrogen receptor signaling pathway mammary gland epithelial cell differentiation regulation of ubiquitin-dependent protein catabolic process mitotic cell cycle G1/S transition of mitotic cell cycle peptidyl-serine phosphorylation intracellular signal transduction Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 9113 16798 Ensembl ENSG00000131023 ENSMUSG00000040021 UniProt O95835 Q6PJG3 Q8BYR2 RefSeq (mRNA) NM_001270519 NM_004690 NM_001350339 NM_001350340 NM_001350392 NM_010690 RefSeq (protein) NP_001257448 NP_004681 NP_001337268 NP_001337269 NP_001337321 NP_034820 Location (UCSC) Chr 6: 149.66 – 149.72 Mb Chr 10: 7.56 – 7.59 Mb PubMed search
Wikidata
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Large tumor suppressor kinase 1 (LATS1) is an enzyme that in humans is encoded by the LATS1 gene.

It has been associated with the Hippo signaling pathway, where it phosphorylates YAP and TAZ to inactivate their function.

The protein encoded by this gene is a putative serine/threonine kinase that localizes to the mitotic apparatus and complexes with cell cycle controller CDC2 kinase in early mitosis. The protein is phosphorylated in a cell-cycle dependent manner, with late prophase phosphorylation remaining through metaphase. The N-terminal region of the protein binds CDC2 to form a complex showing reduced histone H1 kinase activity, indicating a role as a negative regulator of CDC2/cyclin A. In addition, the C-terminal kinase domain binds to its own N-terminal region, suggesting potential negative regulation through interference with complex formation via intramolecular binding. Biochemical and genetic data suggest a role as a tumor suppressor. This is supported by studies in knockout mice showing development of soft-tissue sarcomas, ovarian stromal cell tumors and a high sensitivity to carcinogenic treatments.

Interactions

LATS1 has been shown to interact with Zyxin and Cdk1.

References

1. ^ a b c GRCh38: Ensembl release 89: ENSG00000131023 – Ensembl, May 2017
2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000040021 – 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. ^ a b Tao W, Zhang S, Turenchalk GS, Stewart RA, St John MA, Chen W, Xu T (February 1999). "Human homologue of the Drosophila melanogaster lats tumour suppressor modulates CDC2 activity". Nat Genet. 21 (2): 177–81. doi:10.1038/5960. PMID 9988268. S2CID 32090556.
6. ^ Iida S, Hirota T, Morisaki T, Marumoto T, Hara T, Kuninaka S, Honda S, Kosai K, Kawasuji M, Pallas DC, Saya H (July 2004). "Tumor suppressor WARTS ensures genomic integrity by regulating both mitotic progression and G1 tetraploidy checkpoint function". Oncogene. 23 (31): 5266–74. doi:10.1038/sj.onc.1207623. PMID 15122335. S2CID 25545351.
7. ^ a b "Entrez Gene: LATS1 LATS, large tumor suppressor, homolog 1 (Drosophila)".
8. ^ Hao Y, Chun A, Cheung K, Rashidi B, Yang X (February 2008). "Tumor suppressor LATS1 is a negative regulator of oncogene YAP". J. Biol. Chem. 283 (9): 5496–509. doi:10.1074/jbc.M709037200. PMID 18158288.
9. ^ Hirota T, Morisaki T, Nishiyama Y, Marumoto T, Tada K, Hara T, Masuko N, Inagaki M, Hatakeyama K, Saya H (May 2000). "Zyxin, a regulator of actin filament assembly, targets the mitotic apparatus by interacting with h-warts/LATS1 tumor suppressor". J. Cell Biol. 149 (5): 1073–86. doi:10.1083/jcb.149.5.1073. ISSN 0021-9525. PMC 2174824. PMID 10831611.

Further reading

• Xu T, Wang W, Zhang S, et al. (1995). "Identifying tumor suppressors in genetic mosaics: the Drosophila lats gene encodes a putative protein kinase". Development. 121 (4): 1053–63. doi:10.1242/dev.121.4.1053. PMID 7743921.
• St John MA, Tao W, Fei X, et al. (1999). "Mice deficient of Lats1 develop soft-tissue sarcomas, ovarian tumours and pituitary dysfunction". Nat. Genet. 21 (2): 182–6. doi:10.1038/5965. PMID 9988269. S2CID 11882936.
• Nishiyama Y, Hirota T, Morisaki T, et al. (1999). "A human homolog of Drosophila warts tumor suppressor, h-warts, localized to mitotic apparatus and specifically phosphorylated during mitosis". FEBS Lett. 459 (2): 159–65. doi:10.1016/S0014-5793(99)01224-7. PMID 10518011. S2CID 22292346.
• Hirota T, Morisaki T, Nishiyama Y, et al. (2000). "Zyxin, a regulator of actin filament assembly, targets the mitotic apparatus by interacting with h-warts/LATS1 tumor suppressor". J. Cell Biol. 149 (5): 1073–86. doi:10.1083/jcb.149.5.1073. PMC 2174824. PMID 10831611.
• Morisaki T, Hirota T, Iida S, et al. (2002). "WARTS tumor suppressor is phosphorylated by Cdc2/cyclin B at spindle poles during mitosis". FEBS Lett. 529 (2–3): 319–24. doi:10.1016/S0014-5793(02)03360-4. PMID 12372621. S2CID 45272429.
• Hisaoka M, Tanaka A, Hashimoto H (2002). "Molecular alterations of h-warts/LATS1 tumor suppressor in human soft tissue sarcoma". Lab. Invest. 82 (10): 1427–35. doi:10.1097/01.lab.0000032381.68634.ca. PMID 12379777. S2CID 34100799.
• 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.
• Kamikubo Y, Takaori-Kondo A, Uchiyama T, Hori T (2003). "Inhibition of cell growth by conditional expression of kpm, a human homologue of Drosophila warts/lats tumor suppressor". J. Biol. Chem. 278 (20): 17609–14. doi:10.1074/jbc.M211974200. hdl:2433/148480. PMID 12624101.
• Brill LM, Salomon AR, Ficarro SB, et al. (2004). "Robust phosphoproteomic profiling of tyrosine phosphorylation sites from human T cells using immobilized metal affinity chromatography and tandem mass spectrometry". Anal. Chem. 76 (10): 2763–72. doi:10.1021/ac035352d. PMID 15144186.
• Yang X, Yu K, Hao Y, et al. (2004). "LATS1 tumour suppressor affects cytokinesis by inhibiting LIMK1". Nat. Cell Biol. 6 (7): 609–17. doi:10.1038/ncb1140. PMID 15220930. S2CID 20493738.
• Beausoleil SA, Jedrychowski M, Schwartz D, et al. (2004). "Large-scale characterization of HeLa cell nuclear phosphoproteins". Proc. Natl. Acad. Sci. U.S.A. 101 (33): 12130–5. Bibcode:2004PNAS..10112130B. doi:10.1073/pnas.0404720101. PMC 514446. PMID 15302935.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
• 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. S2CID 23415582.
• Kuninaka S, Nomura M, Hirota T, et al. (2005). "The tumor suppressor WARTS activates the Omi / HtrA2-dependent pathway of cell death". Oncogene. 24 (34): 5287–98. doi:10.1038/sj.onc.1208682. PMID 16007220. S2CID 25678521.
• Bothos J, Tuttle RL, Ottey M, et al. (2005). "Human LATS1 is a mitotic exit network kinase". Cancer Res. 65 (15): 6568–75. doi:10.1158/0008-5472.CAN-05-0862. PMID 16061636.
• 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.

v t e Signaling pathway: Hippo signaling pathway
Receptor	FAT4
Adaptor protein	NF2 FRMD6 SAV1 MOBKL1A MOBKL1B
Kinase	MST1 LATS1 LATS2 STK3
Transcription factor	YAP1 TAZ
Other/unknown	RASSF1

v t e Kinases: Serine/threonine-specific protein kinases (EC 2.7.11-12)
Serine/threonine-specific protein kinases (EC 2.7.11.1-EC 2.7.11.20) Non-specific serine/threonine protein kinases (EC 2.7.11.1) LATS1 LATS2 MAST1 MAST2 STK38 STK38L CIT ROCK1 SGK SGK2 SGK3 Protein kinase B AKT1 AKT2 AKT3 Ataxia telangiectasia mutated mTOR EIF-2 kinases PKR HRI EIF2AK3 EIF2AK4 Wee1 WEE1 Pyruvate dehydrogenase kinase (EC 2.7.11.2) PDK1 PDK2 PDK3 PDK4 Dephospho-(reductase kinase) kinase (EC 2.7.11.3) AMP-activated protein kinase α PRKAA1 PRKAA2 β PRKAB1 PRKAB2 γ PRKAG1 PRKAG2 PRKAG3 3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring) kinase (EC 2.7.11.4) BCKDK BCKDHA BCKDHB (isocitrate dehydrogenase (NADP+)) kinase (EC 2.7.11.5) IDH2 IDH3A IDH3B IDH3G (tyrosine 3-monooxygenase) kinase (EC 2.7.11.6) STK4 Myosin-heavy-chain kinase (EC 2.7.11.7) Aurora kinase Aurora A kinase Aurora B kinase Aurora C kinase Fas-activated serine/threonine kinase (EC 2.7.11.8) FASTK STK10 Goodpasture-antigen-binding protein kinase (EC 2.7.11.9) - IκB kinase (EC 2.7.11.10) CHUK IKK2 TBK1 IKBKE IKBKG IKBKAP cAMP-dependent protein kinase (EC 2.7.11.11) Protein kinase A PRKACG PRKACB PRKACA PRKY cGMP-dependent protein kinase (EC 2.7.11.12) Protein kinase G PRKG1 Protein kinase C (EC 2.7.11.13) Protein kinase C Protein kinase Cζ PKC alpha PRKCB1 PRKCD PRKCE PRKCH PRKCG PRKCI PRKCQ Protein kinase N1 PKN2 PKN3 Rhodopsin kinase (EC 2.7.11.14) Rhodopsin kinase Beta adrenergic receptor kinase (EC 2.7.11.15) Beta adrenergic receptor kinase Beta adrenergic receptor kinase-2 G-protein coupled receptor kinases (EC 2.7.11.16) GRK4 GRK5 GRK6 Ca2+/calmodulin-dependent (EC 2.7.11.17) BRSK2 CAMK1 CAMK1A CAMK1B CAMK1D CAMK1G CAMK2 CAMK2A CAMK2B CAMK2D CAMK2G CAMK4 MLCK CASK CHEK1 CHEK2 DAPK1 DAPK2 DAPK3 STK11 MAPKAPK2 MAPKAPK3 MAPKAPK5 MARK1 MARK2 MARK3 MARK4 MELK MKNK1 MKNK2 NUAK1 NUAK2 OBSCN PASK PHKG1 PHKG2 PIM1 PIM2 PKD1 PRKD2 PRKD3 PSKH1 SNF1LK2 KIAA0999 STK40 SNF1LK SNRK SPEG TSSK2 Kalirin TRIB1 TRIB2 TRIB3 TRIO Titin DCLK1 Myosin light-chain kinase (EC 2.7.11.18) MYLK MYLK2 MYLK3 MYLK4 Phosphorylase kinase (EC 2.7.11.19) PHKA1 PHKA2 PHKB PHKG1 PHKG2 Elongation factor 2 kinase (EC 2.7.11.20) EEF2K STK19 Polo kinase (EC 2.7.11.21) PLK1 PLK2 PLK3 PLK4
Serine/threonine-specific protein kinases (EC 2.7.11.21-EC 2.7.11.30) Polo kinase (EC 2.7.11.21) PLK1 PLK2 PLK3 PLK4 Cyclin-dependent kinase (EC 2.7.11.22) CDK1 CDK2 CDKL2 CDK3 CDK4 CDK5 CDKL5 CDK6 CDK7 CDK8 CDK9 CDK10 CDK12 CDC2L5 PCTK1 PCTK2 PCTK3 PFTK1 CDC2L1 (RNA-polymerase)-subunit kinase (EC 2.7.11.23) RPS6KA5 RPS6KA4 P70S6 kinase P70-S6 Kinase 1 RPS6KB2 RPS6KA2 RPS6KA3 RPS6KA1 RPS6KC1 Mitogen-activated protein kinase (EC 2.7.11.24) Extracellular signal-regulated MAPK1 MAPK3 MAPK4 MAPK6 MAPK7 MAPK12 MAPK15 C-Jun N-terminal MAPK8 MAPK9 MAPK10 P38 mitogen-activated protein MAPK11 MAPK13 MAPK14 MAP3K (EC 2.7.11.25) MAP kinase kinase kinases MAP3K1 MAP3K2 MAP3K3 MAP3K4 MAP3K5 MAP3K6 MAP3K7 MAP3K8 RAFs ARAF BRAF KSR1 KSR2 MLKs MAP3K12 MAP3K13 MAP3K9 MAP3K10 MAP3K11 MAP3K7 ZAK CDC7 MAP3K14 Tau-protein kinase (EC 2.7.11.26) TPK1 TTK GSK-3 (acetyl-CoA carboxylase) kinase (EC 2.7.11.27) - Tropomyosin kinase (EC 2.7.11.28) - Low-density-lipoprotein receptor kinase (EC 2.7.11.29) - Receptor protein serine/threonine kinase (EC 2.7.11.30) Bone morphogenetic protein receptors BMPR1 BMPR1A BMPR1B BMPR2 ACVR1 ACVR1B ACVR1C ACVR2A ACVR2B ACVRL1 Anti-Müllerian hormone receptor
Dual-specificity kinases (EC 2.7.12) MAP2K MAP2K1 MAP2K2 MAP2K3 MAP2K4 MAP2K5 MAP2K6 MAP2K7

v t e Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Diffusion-limited enzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics
Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list) EC7 Translocases (list)

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