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

Functions

ATP binding / estrogen receptor binding / magnesium ion binding / protein kinase binding / protein serine/threonine kinase activity

Processes

cell 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 segregation

Components

cytosol / 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

• Pkinase (PF00069)
• UBA (PF00627)

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

1. 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]
2. 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]
3. 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]
4. 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]
5. 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]
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7. 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]
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10. 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]
11. 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]
12. 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]
13. 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]
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Drug Relations

Drug Relations

DrugBank ID	Name	Drug group	Pharmacological action?	Actions	Details
DB12010	Fostamatinib	approved, investigational	unknown	inhibitor	Details