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Identification
HMDB Protein ID HMDBP01499
Secondary Accession Numbers
  • 6795
Name Serine/threonine-protein kinase LATS1
Synonyms
  1. Large tumor suppressor homolog 1
  2. WARTS protein kinase
  3. h-warts
Gene Name LATS1
Protein Type Unknown
Biological Properties
General Function Involved in ATP binding
Specific 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 MST1/MST2, 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
Pathways Not Available
Reactions Not Available
GO Classification
Function
binding
catalytic activity
transferase activity
transferase activity, transferring phosphorus-containing groups
kinase activity
nucleoside binding
purine nucleoside binding
adenyl nucleotide binding
adenyl ribonucleotide binding
atp binding
protein kinase activity
protein serine/threonine kinase activity
Process
phosphorus metabolic process
phosphate metabolic process
metabolic process
cellular metabolic process
protein amino acid phosphorylation
phosphorylation
Cellular Location
  1. Cytoplasm
  2. cytoskeleton
  3. centrosome
Gene Properties
Chromosome Location Chromosome:6
Locus 6q25.1
SNPs LATS1
Gene Sequence
>3393 bp
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
Protein Properties
Number of Residues 1130
Molecular Weight 126868.8
Theoretical pI 9.0
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • None
Protein Sequence
>Serine/threonine-protein kinase LATS1
MKRSEKPEGYRQMRPKTFPASNYTVSSRQMLQEIRESLRNLSKPSDAAKAEHNMSKMSTE
DPRQVRNPPKFGTHHKALQEIRNSLLPFANETNSSRSTSEVNPQMLQDLQAAGFDEDMVI
QALQKTNNRSIEAAIEFISKMSYQDPRREQMAAAAARPINASMKPGNVQQSVNRKQSWKG
SKESLVPQRHGPPLGESVAYHSESPNSQTDVGRPLSGSGISAFVQAHPSNGQRVNPPPPP
QVRSVTPPPPPRGQTPPPRGTTPPPPSWEPNSQTKRYSGNMEYVISRISPVPPGAWQEGY
PPPPLNTSPMNPPNQGQRGISSVPVGRQPIIMQSSSKFNFPSGRPGMQNGTGQTDFMIHQ
NVVPAGTVNRQPPPPYPLTAANGQSPSALQTGGSAAPSSYTNGSIPQSMMVPNRNSHNME
LYNISVPGLQTNWPQSSSAPAQSSPSSGHEIPTWQPNIPVRSNSFNNPLGNRASHSANSQ
PSATTVTAITPAPIQQPVKSMRVLKPELQTALAPTHPSWIPQPIQTVQPSPFPEGTASNV
TVMPPVAEAPNYQGPPPPYPKHLLHQNPSVPPYESISKPSKEDQPSLPKEDESEKSYENV
DSGDKEKKQITTSPITVRKNKKDEERRESRIQSYSPQAFKFFMEQHVENVLKSHQQRLHR
KKQLENEMMRVGLSQDAQDQMRKMLCQKESNYIRLKRAKMDKSMFVKIKTLGIGAFGEVC
LARKVDTKALYATKTLRKKDVLLRNQVAHVKAERDILAEADNEWVVRLYYSFQDKDNLYF
VMDYIPGGDMMSLLIRMGIFPESLARFYIAELTCAVESVHKMGFIHRDIKPDNILIDRDG
HIKLTDFGLCTGFRWTHDSKYYQSGDHPRQDSMDFSNEWGDPSSCRCGDRLKPLERRAAR
QHQRCLAHSLVGTPNYIAPEVLLRTGYTQLCDWWSVGVILFEMLVGQPPFLAQTPLETQM
KVINWQTSLHIPPQAKLSPEASDLIIKLCRGPEDRLGKNGADEIKAHPFFKTIDFSSDLR
QQSASYIPKITHPTDTSNFDPVDPDKLWSDDNEEENVNDTLNGWYKNGKHPEHAFYEFTF
RRFFDDNGYPYNYPKPIEYEYINSQGSEQQSDEDDQNTGSEIKNRDLVYV
GenBank ID Protein 4324434
UniProtKB/Swiss-Prot ID O95835
UniProtKB/Swiss-Prot Entry Name LATS1_HUMAN
PDB IDs Not Available
GenBank Gene ID AF104413
GeneCard ID LATS1
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
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  2. 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. [PubMed:18669648 ]
  3. 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. [PubMed:19690332 ]
  4. 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. [PubMed:18691976 ]
  5. 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. [PubMed:19369195 ]
  6. Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villen J, Li J, Cohn MA, Cantley LC, Gygi SP: Large-scale characterization of HeLa cell nuclear phosphoproteins. Proc Natl Acad Sci U S A. 2004 Aug 17;101(33):12130-5. Epub 2004 Aug 9. [PubMed:15302935 ]
  7. 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. [PubMed:19413330 ]
  8. 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. [PubMed:17525332 ]
  9. Wang Y, Du D, Fang L, Yang G, Zhang C, Zeng R, Ullrich A, Lottspeich F, Chen Z: Tyrosine phosphorylated Par3 regulates epithelial tight junction assembly promoted by EGFR signaling. EMBO J. 2006 Nov 1;25(21):5058-70. Epub 2006 Oct 19. [PubMed:17053785 ]
  10. 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. [PubMed:17344846 ]
  11. 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. [PubMed:15688006 ]
  12. 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. [PubMed:18158288 ]
  13. 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. [PubMed:19739119 ]
  14. 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. [PubMed:9988268 ]
  15. 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. [PubMed:10518011 ]
  16. 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. [PubMed:10831611 ]
  17. 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. [PubMed:15122335 ]
  18. 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. [PubMed:15220930 ]