Serine/threonine-protein kinase LATS1
Details
- Name
- Serine/threonine-protein kinase LATS1
- Synonyms
- 2.7.11.1
- h-warts
- Large tumor suppressor homolog 1
- WARTS
- WARTS protein kinase
- Gene Name
- LATS1
- Organism
- Humans
- Amino acid sequence
>lcl|BSEQ0051788|Serine/threonine-protein kinase LATS1 MKRSEKPEGYRQMRPKTFPASNYTVSSRQMLQEIRESLRNLSKPSDAAKAEHNMSKMSTE DPRQVRNPPKFGTHHKALQEIRNSLLPFANETNSSRSTSEVNPQMLQDLQAAGFDEDMVI QALQKTNNRSIEAAIEFISKMSYQDPRREQMAAAAARPINASMKPGNVQQSVNRKQSWKG SKESLVPQRHGPPLGESVAYHSESPNSQTDVGRPLSGSGISAFVQAHPSNGQRVNPPPPP QVRSVTPPPPPRGQTPPPRGTTPPPPSWEPNSQTKRYSGNMEYVISRISPVPPGAWQEGY PPPPLNTSPMNPPNQGQRGISSVPVGRQPIIMQSSSKFNFPSGRPGMQNGTGQTDFMIHQ NVVPAGTVNRQPPPPYPLTAANGQSPSALQTGGSAAPSSYTNGSIPQSMMVPNRNSHNME LYNISVPGLQTNWPQSSSAPAQSSPSSGHEIPTWQPNIPVRSNSFNNPLGNRASHSANSQ PSATTVTAITPAPIQQPVKSMRVLKPELQTALAPTHPSWIPQPIQTVQPSPFPEGTASNV TVMPPVAEAPNYQGPPPPYPKHLLHQNPSVPPYESISKPSKEDQPSLPKEDESEKSYENV DSGDKEKKQITTSPITVRKNKKDEERRESRIQSYSPQAFKFFMEQHVENVLKSHQQRLHR KKQLENEMMRVGLSQDAQDQMRKMLCQKESNYIRLKRAKMDKSMFVKIKTLGIGAFGEVC LARKVDTKALYATKTLRKKDVLLRNQVAHVKAERDILAEADNEWVVRLYYSFQDKDNLYF VMDYIPGGDMMSLLIRMGIFPESLARFYIAELTCAVESVHKMGFIHRDIKPDNILIDRDG HIKLTDFGLCTGFRWTHDSKYYQSGDHPRQDSMDFSNEWGDPSSCRCGDRLKPLERRAAR QHQRCLAHSLVGTPNYIAPEVLLRTGYTQLCDWWSVGVILFEMLVGQPPFLAQTPLETQM KVINWQTSLHIPPQAKLSPEASDLIIKLCRGPEDRLGKNGADEIKAHPFFKTIDFSSDLR QQSASYIPKITHPTDTSNFDPVDPDKLWSDDNEEENVNDTLNGWYKNGKHPEHAFYEFTF RRFFDDNGYPYNYPKPIEYEYINSQGSEQQSDEDDQNTGSEIKNRDLVYV
- Number of residues
- 1130
- Molecular Weight
- 126868.825
- Theoretical pI
- Not Available
- GO Classification
- FunctionsATP binding / estrogen receptor binding / magnesium ion binding / protein kinase binding / protein serine/threonine kinase activityProcessescell division / cellular protein localization / cytoplasmic sequestering of protein / G1/S transition of mitotic cell cycle / G2/M transition of mitotic cell cycle / hippo signaling / hormone-mediated signaling pathway / inner cell mass cell fate commitment / inner cell mass cellular morphogenesis / keratinocyte differentiation / mammary gland epithelial cell differentiation / negative regulation of canonical Wnt signaling pathway / negative regulation of cyclin-dependent protein serine/threonine kinase activity / positive regulation of apoptotic process / positive regulation of peptidyl-serine phosphorylation / protein phosphorylation / regulation of actin filament polymerization / regulation of intracellular estrogen receptor signaling pathway / regulation of organ growth / regulation of protein complex assembly / regulation of ubiquitin-dependent protein catabolic process / sister chromatid segregationComponentscytosol / microtubule organizing center / spindle pole
- General Function
- Negative regulator of YAP1 in the Hippo signaling pathway that plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS1 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. Acts as a tumor suppressor which plays a critical role in maintenance of ploidy through its actions in both mitotic progression and the G1 tetraploidy checkpoint. Negatively regulates G2/M transition by down-regulating CDK1 kinase activity. Involved in the control of p53 expression. Affects cytokinesis by regulating actin polymerization through negative modulation of LIMK1. May also play a role in endocrine function. Plays a role in mammary gland epithelial cells differentiation, both through the Hippo signaling pathway and the intracellular estrogen receptor signaling pathway by promoting the degradation of ESR1 (PubMed:28068668).
- Specific Function
- Atp binding
- Pfam Domain Function
- Transmembrane Regions
- Not Available
- Cellular Location
- Cytoplasm
- Gene sequence
>lcl|BSEQ0051789|Serine/threonine-protein kinase LATS1 (LATS1) ATGAAGAGGAGTGAAAAGCCAGAAGGATATAGACAAATGAGGCCTAAGACCTTTCCTGCC AGTAACTATACTGTCAGTAGCCGGCAAATGTTACAAGAAATTCGGGAATCCCTTAGGAAT TTATCTAAACCATCTGATGCTGCTAAGGCTGAGCATAACATGAGTAAAATGTCAACCGAA GATCCTCGACAAGTCAGAAATCCACCCAAATTTGGGACGCATCATAAAGCCTTGCAGGAA ATTCGAAACTCTCTGCTTCCATTTGCAAATGAAACAAATTCTTCTCGGAGTACTTCAGAA GTTAATCCACAAATGCTTCAAGACTTGCAAGCTGCTGGATTTGATGAGGATATGGTTATA CAAGCTCTTCAGAAAACTAACAACAGAAGTATAGAAGCAGCAATTGAATTCATTAGTAAA ATGAGTTACCAAGATCCTCGACGAGAGCAGATGGCTGCAGCAGCTGCCAGACCTATTAAT GCCAGCATGAAACCAGGGAATGTGCAGCAATCAGTTAACCGCAAACAGAGCTGGAAAGGT TCTAAAGAATCCTTAGTTCCTCAGAGGCATGGCCCGCCACTAGGAGAAAGTGTGGCCTAT CATTCTGAGAGTCCCAACTCACAGACAGATGTAGGAAGACCTTTGTCTGGATCTGGTATA TCAGCATTTGTTCAAGCTCACCCTAGCAACGGACAGAGAGTGAACCCCCCACCACCACCT CAAGTAAGGAGTGTTACTCCTCCACCACCTCCAAGAGGCCAGACTCCCCCTCCAAGAGGT ACAACTCCACCTCCCCCTTCATGGGAACCAAACTCTCAAACAAAGCGCTATTCTGGAAAC ATGGAATACGTAATCTCCCGAATCTCTCCTGTCCCACCTGGGGCATGGCAAGAGGGCTAT CCTCCACCACCTCTCAACACTTCCCCCATGAATCCTCCTAATCAAGGACAGAGAGGCATT AGTTCTGTTCCTGTTGGCAGACAACCAATCATCATGCAGAGTTCTAGCAAATTTAACTTT CCATCAGGGAGACCTGGAATGCAGAATGGTACTGGACAAACTGATTTCATGATACACCAA AATGTTGTCCCTGCTGGCACTGTGAATCGGCAGCCACCACCTCCATATCCTCTGACAGCA GCTAATGGACAAAGCCCTTCTGCTTTACAAACAGGGGGATCTGCTGCTCCTTCGTCATAT ACAAATGGAAGTATTCCTCAGTCTATGATGGTGCCAAACAGAAATAGTCATAACATGGAA CTATATAACATTAGTGTACCTGGACTGCAAACAAATTGGCCTCAGTCATCTTCTGCTCCA GCCCAGTCATCCCCGAGCAGTGGGCATGAAATCCCTACATGGCAACCTAACATACCAGTG AGGTCAAATTCTTTTAATAACCCATTAGGAAATAGAGCAAGTCACTCTGCTAATTCTCAG CCTTCTGCTACAACAGTCACTGCAATTACACCAGCTCCTATTCAACAGCCTGTGAAAAGT ATGCGTGTATTAAAACCAGAGCTACAGACTGCTTTAGCACCTACACACCCTTCTTGGATA CCACAGCCAATTCAAACTGTTCAACCCAGTCCTTTTCCTGAGGGAACCGCTTCAAATGTG ACTGTGATGCCACCTGTTGCTGAAGCTCCAAACTATCAAGGACCACCACCACCCTACCCA AAACATCTGCTGCACCAAAACCCATCTGTTCCTCCATACGAGTCAATCAGTAAGCCTAGC AAAGAGGATCAGCCAAGCTTGCCCAAGGAAGATGAGAGTGAAAAGAGTTATGAAAATGTT GATAGTGGGGATAAAGAAAAGAAACAGATTACAACTTCACCTATTACTGTTAGGAAAAAC AAGAAAGATGAAGAGCGAAGGGAATCTCGTATTCAAAGTTATTCTCCTCAAGCATTTAAA TTCTTTATGGAGCAACATGTAGAAAATGTACTCAAATCTCATCAGCAGCGTCTACATCGT AAAAAACAATTAGAGAATGAAATGATGCGGGTTGGATTATCTCAAGATGCCCAGGATCAA ATGAGAAAGATGCTTTGCCAAAAAGAATCTAATTACATCCGTCTTAAAAGGGCTAAAATG GACAAGTCTATGTTTGTGAAGATAAAGACACTAGGAATAGGAGCATTTGGTGAAGTCTGT CTAGCAAGAAAAGTAGATACTAAGGCTTTGTATGCAACAAAAACTCTTCGAAAGAAAGAT GTTCTTCTTCGAAATCAAGTCGCTCATGTTAAGGCTGAGAGAGATATCCTGGCTGAAGCT GACAATGAATGGGTAGTTCGTCTATATTATTCATTCCAAGATAAGGACAATTTATACTTT GTAATGGACTACATTCCTGGGGGTGATATGATGAGCCTATTAATTAGAATGGGCATCTTT CCAGAAAGTCTGGCACGATTCTACATAGCAGAACTTACCTGTGCAGTTGAAAGTGTTCAT AAAATGGGTTTTATTCATAGAGATATTAAACCTGATAATATTTTGATTGATCGTGATGGT CATATTAAATTGACTGACTTTGGCCTCTGCACTGGCTTCAGATGGACACACGATTCTAAG TACTATCAGAGTGGTGACCATCCACGGCAAGATAGCATGGATTTCAGTAATGAATGGGGG GATCCCTCAAGCTGTCGATGTGGAGACAGACTGAAGCCATTAGAGCGGAGAGCTGCACGC CAGCACCAGCGATGTCTAGCACATTCTTTGGTTGGGACTCCCAATTATATTGCACCTGAA GTGTTGCTACGAACAGGATACACACAGTTGTGTGATTGGTGGAGTGTTGGTGTTATTCTT TTTGAAATGTTGGTGGGACAACCTCCTTTCTTGGCACAAACACCATTAGAAACACAAATG AAGGTTATCAACTGGCAAACATCTCTTCACATTCCACCACAAGCTAAACTCAGTCCTGAA GCTTCTGATCTTATTATTAAACTTTGCCGAGGACCCGAAGATCGCTTAGGCAAGAATGGT GCTGATGAAATAAAAGCTCATCCATTTTTTAAAACAATTGACTTCTCCAGTGACCTGAGA CAGCAGTCTGCTTCATACATTCCTAAAATCACACACCCAACAGATACATCAAATTTTGAT CCTGTTGATCCTGATAAATTATGGAGTGATGATAACGAGGAAGAAAATGTAAATGACACT CTCAATGGATGGTATAAAAATGGAAAGCATCCTGAACATGCATTCTATGAATTTACCTTC CGAAGGTTTTTTGATGACAATGGCTACCCATATAATTATCCGAAGCCTATTGAATATGAA TACATTAATTCACAAGGCTCAGAGCAGCAGTCGGATGAAGATGATCAAAACACAGGCTCA GAGATTAAAAATCGCGATCTAGTATATGTTTAA
- Chromosome Location
- 6
- Locus
- 6q25.1
- External Identifiers
Resource Link UniProtKB ID O95835 UniProtKB Entry Name LATS1_HUMAN HGNC ID HGNC:6514 - General References
- Tao W, Zhang S, Turenchalk GS, Stewart RA, St John MA, Chen W, Xu T: Human homologue of the Drosophila melanogaster lats tumour suppressor modulates CDC2 activity. Nat Genet. 1999 Feb;21(2):177-81. [Article]
- Nishiyama Y, Hirota T, Morisaki T, Hara T, Marumoto T, Iida S, Makino K, Yamamoto H, Hiraoka T, Kitamura N, Saya H: A human homolog of Drosophila warts tumor suppressor, h-warts, localized to mitotic apparatus and specifically phosphorylated during mitosis. FEBS Lett. 1999 Oct 8;459(2):159-65. [Article]
- Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
- Hirota T, Morisaki T, Nishiyama Y, Marumoto T, Tada K, Hara T, Masuko N, Inagaki M, Hatakeyama K, Saya H: Zyxin, a regulator of actin filament assembly, targets the mitotic apparatus by interacting with h-warts/LATS1 tumor suppressor. J Cell Biol. 2000 May 29;149(5):1073-86. [Article]
- Brill LM, Salomon AR, Ficarro SB, Mukherji M, Stettler-Gill M, Peters EC: Robust phosphoproteomic profiling of tyrosine phosphorylation sites from human T cells using immobilized metal affinity chromatography and tandem mass spectrometry. Anal Chem. 2004 May 15;76(10):2763-72. [Article]
- Iida S, Hirota T, Morisaki T, Marumoto T, Hara T, Kuninaka S, Honda S, Kosai K, Kawasuji M, Pallas DC, Saya H: Tumor suppressor WARTS ensures genomic integrity by regulating both mitotic progression and G1 tetraploidy checkpoint function. Oncogene. 2004 Jul 8;23(31):5266-74. [Article]
- Yang X, Yu K, Hao Y, Li DM, Stewart R, Insogna KL, Xu T: LATS1 tumour suppressor affects cytokinesis by inhibiting LIMK1. Nat Cell Biol. 2004 Jul;6(7):609-17. Epub 2004 Jun 27. [Article]
- Chan EH, Nousiainen M, Chalamalasetty RB, Schafer A, Nigg EA, Sillje HH: The Ste20-like kinase Mst2 activates the human large tumor suppressor kinase Lats1. Oncogene. 2005 Mar 17;24(12):2076-86. [Article]
- Matsuoka S, Ballif BA, Smogorzewska A, McDonald ER 3rd, Hurov KE, Luo J, Bakalarski CE, Zhao Z, Solimini N, Lerenthal Y, Shiloh Y, Gygi SP, Elledge SJ: ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Science. 2007 May 25;316(5828):1160-6. [Article]
- Hao Y, Chun A, Cheung K, Rashidi B, Yang X: Tumor suppressor LATS1 is a negative regulator of oncogene YAP. J Biol Chem. 2008 Feb 29;283(9):5496-509. Epub 2007 Dec 24. [Article]
- Daub H, Olsen JV, Bairlein M, Gnad F, Oppermann FS, Korner R, Greff Z, Keri G, Stemmann O, Mann M: Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol Cell. 2008 Aug 8;31(3):438-48. doi: 10.1016/j.molcel.2008.07.007. [Article]
- Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [Article]
- Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501. doi: 10.1021/ac9004309. [Article]
- Oppermann FS, Gnad F, Olsen JV, Hornberger R, Greff Z, Keri G, Mann M, Daub H: Large-scale proteomics analysis of the human kinome. Mol Cell Proteomics. 2009 Jul;8(7):1751-64. doi: 10.1074/mcp.M800588-MCP200. Epub 2009 Apr 15. [Article]
- Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. [Article]
- Das Thakur M, Feng Y, Jagannathan R, Seppa MJ, Skeath JB, Longmore GD: Ajuba LIM proteins are negative regulators of the Hippo signaling pathway. Curr Biol. 2010 Apr 13;20(7):657-62. doi: 10.1016/j.cub.2010.02.035. Epub 2010 Mar 18. [Article]
- Chow A, Hao Y, Yang X: Molecular characterization of human homologs of yeast MOB1. Int J Cancer. 2010 May 1;126(9):2079-89. doi: 10.1002/ijc.24878. [Article]
- Humbert N, Navaratnam N, Augert A, Da Costa M, Martien S, Wang J, Martinez D, Abbadie C, Carling D, de Launoit Y, Gil J, Bernard D: Regulation of ploidy and senescence by the AMPK-related kinase NUAK1. EMBO J. 2010 Jan 20;29(2):376-86. doi: 10.1038/emboj.2009.342. Epub 2009 Nov 19. [Article]
- Zhou H, Di Palma S, Preisinger C, Peng M, Polat AN, Heck AJ, Mohammed S: Toward a comprehensive characterization of a human cancer cell phosphoproteome. J Proteome Res. 2013 Jan 4;12(1):260-71. doi: 10.1021/pr300630k. Epub 2012 Dec 18. [Article]
- Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [Article]
- Kwan J, Sczaniecka A, Heidary Arash E, Nguyen L, Chen CC, Ratkovic S, Klezovitch O, Attisano L, McNeill H, Emili A, Vasioukhin V: DLG5 connects cell polarity and Hippo signaling protein networks by linking PAR-1 with MST1/2. Genes Dev. 2016 Dec 15;30(24):2696-2709. doi: 10.1101/gad.284539.116. [Article]
- Britschgi A, Duss S, Kim S, Couto JP, Brinkhaus H, Koren S, De Silva D, Mertz KD, Kaup D, Varga Z, Voshol H, Vissieres A, Leroy C, Roloff T, Stadler MB, Scheel CH, Miraglia LJ, Orth AP, Bonamy GM, Reddy VA, Bentires-Alj M: The Hippo kinases LATS1 and 2 control human breast cell fate via crosstalk with ERalpha. Nature. 2017 Jan 26;541(7638):541-545. doi: 10.1038/nature20829. Epub 2017 Jan 9. [Article]
- Liu J, Li J, Li P, Wang Y, Liang Z, Jiang Y, Li J, Feng C, Wang R, Chen H, Zhou C, Zhang J, Yang J, Liu P: Loss of DLG5 promotes breast cancer malignancy by inhibiting the Hippo signaling pathway. Sci Rep. 2017 Feb 7;7:42125. doi: 10.1038/srep42125. [Article]
- 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: Patterns of somatic mutation in human cancer genomes. Nature. 2007 Mar 8;446(7132):153-8. [Article]