Description: Homo sapiens large tumor suppressor kinase 1 (LATS1), transcript variant 1, mRNA. RefSeq Summary (NM_004690): 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 H1 histone 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. [provided by RefSeq, Apr 2017]. Transcript (Including UTRs) Position: hg19 chr6:149,979,289-150,039,392 Size: 60,104 Total Exon Count: 8 Strand: - Coding Region Position: hg19 chr6:149,982,865-150,023,262 Size: 40,398 Coding Exon Count: 7
ID:LATS1_HUMAN DESCRIPTION: RecName: Full=Serine/threonine-protein kinase LATS1; EC=2.7.11.1; AltName: Full=Large tumor suppressor homolog 1; AltName: Full=WARTS protein kinase; Short=h-warts; 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. CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. COFACTOR: Magnesium. SUBUNIT: Complexes with CDK1 in early mitosis. LATS1-associated CDK1 has no mitotic cyclin partner and no apparent kinase activity. Binds phosphorylated ZYX, locating this protein to the mitotic spindle and suggesting a role for actin regulatory proteins during mitosis. Binds to and colocalizes with LIMK1 at the actomyosin contractile ring during cytokinesis. Interacts (via PPxY motif 2) with YAP1 (via WW domains). Interacts with MOB1A and MOB1B. Interacts with LIMD1, WTIP and AJUBA. INTERACTION: P06493:CDK1; NbExp=2; IntAct=EBI-444209, EBI-444308; P53667:LIMK1; NbExp=5; IntAct=EBI-444209, EBI-444403; Q9H8S9:MOB1A; NbExp=2; IntAct=EBI-444209, EBI-748229; Q7L9L4:MOB1B; NbExp=2; IntAct=EBI-444209, EBI-2558745; Q9GZV5:WWTR1; NbExp=4; IntAct=EBI-444209, EBI-747743; Q15942:ZYX; NbExp=10; IntAct=EBI-444209, EBI-444225; SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, centrosome. Note=Localizes to the centrosomes throughout interphase but migrates to the mitotic apparatus, including spindle pole bodies, mitotic spindle, and midbody, during mitosis. TISSUE SPECIFICITY: Expressed in all adult tissues examined except for lung and kidney. PTM: Autophosphorylated and phosphorylated during M-phase of the cell cycle. Phosphorylated by STK3/MST2 at Ser-909 and Thr-1079, which results in its activation. Phosphorylated upon DNA damage, probably by ATM or ATR. Phosphorylation at Ser-464 by NUAK1 and NUAK2 leads to decreased protein level and is required to regulate cellular senescence and cellular ploidy. SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. SIMILARITY: Contains 1 AGC-kinase C-terminal domain. SIMILARITY: Contains 1 protein kinase domain. SIMILARITY: Contains 1 UBA domain.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
Pfam Domains: PF00069 - Protein kinase domain PF00627 - UBA/TS-N domain PF07714 - Protein tyrosine kinase
SCOP Domains: 46934 - UBA-like 56112 - Protein kinase-like (PK-like)
ModBase Predicted Comparative 3D Structure on O95835
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
AB209426 - Homo sapiens mRNA for LATS homolog 1 variant protein. JD526851 - Sequence 507875 from Patent EP1572962. AF164041 - Homo sapiens WARTS protein kinase (WARTS) mRNA, complete cds. JD201957 - Sequence 182981 from Patent EP1572962. JD093363 - Sequence 74387 from Patent EP1572962. AF104413 - Homo sapiens large tumor suppressor 1 (LATS1) mRNA, complete cds. JD528003 - Sequence 509027 from Patent EP1572962. AK310422 - Homo sapiens cDNA, FLJ17464. JD289500 - Sequence 270524 from Patent EP1572962. JD221088 - Sequence 202112 from Patent EP1572962. BC002767 - Homo sapiens LATS, large tumor suppressor, homolog 1 (Drosophila), mRNA (cDNA clone MGC:3608 IMAGE:3632571), complete cds. KJ901942 - Synthetic construct Homo sapiens clone ccsbBroadEn_11336 LATS1 gene, encodes complete protein. KJ905371 - Synthetic construct Homo sapiens clone ccsbBroadEn_14930 LATS1 gene, encodes complete protein. JD114984 - Sequence 96008 from Patent EP1572962. JD274456 - Sequence 255480 from Patent EP1572962. CU678182 - Synthetic construct Homo sapiens gateway clone IMAGE:100023044 5' read LATS1 mRNA. JD064325 - Sequence 45349 from Patent EP1572962. AF119846 - Homo sapiens PRO1474 mRNA, complete cds. BC015665 - Homo sapiens LATS, large tumor suppressor, homolog 1 (Drosophila), mRNA (cDNA clone IMAGE:4550430), complete cds. JD357771 - Sequence 338795 from Patent EP1572962. JD315146 - Sequence 296170 from Patent EP1572962. KJ901941 - Synthetic construct Homo sapiens clone ccsbBroadEn_11335 LATS1 gene, encodes complete protein. HQ257893 - Synthetic construct Homo sapiens clone IMAGE:100072202 Unknown protein gene, encodes complete protein. JD236425 - Sequence 217449 from Patent EP1572962. JD233229 - Sequence 214253 from Patent EP1572962. JD079914 - Sequence 60938 from Patent EP1572962. JD257547 - Sequence 238571 from Patent EP1572962.
Biochemical and Signaling Pathways
Reactome (by CSHL, EBI, and GO)
Protein O95835 (Reactome details) participates in the following event(s):
R-HSA-2028626 Phosphorylated MOB1A proteins associate with LATS proteins R-HSA-2038398 KIBRA (WWC1) binds LATS proteins R-HSA-2059926 NPHP4 protein binds LATS proteins R-HSA-2028598 Phosphorylation of YAP by LATS1 R-HSA-2060328 Phosphorylation of WWTR1 (TAZ) by LATS1 R-HSA-2028555 Phosphorylation of LATS1 and 2 by p-STK4 (p-MST1) R-HSA-2028589 Phosphorylation of LATS1 and 2 by p-STK3 (p-MST2) R-HSA-2028673 Phosphorylation of LATS1 and 2 by p-STK3 (MST2)/N R-HSA-2028679 Phosphorylation of LATS1 and 2 by p-STK4(MST1)/N R-HSA-2028269 Signaling by Hippo R-HSA-162582 Signal Transduction