Human Gene LATS1 (uc003qmu.2)
  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 

Page IndexSequence and LinksUniProtKB CommentsPrimersGenetic AssociationsMalaCards
CTDGene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein Structure
Other SpeciesGO AnnotationsmRNA DescriptionsPathwaysOther NamesModel Information
Methods
Data last updated at UCSC: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr6:149,979,289-150,039,392)mRNA (may differ from genome)Protein (1130 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
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MGIneXtProtOMIMPubMedReactomeUniProtKB
WikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  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.

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): LATS1
CDC HuGE Published Literature: LATS1

-  MalaCards Disease Associations
  MalaCards Gene Search: LATS1
Diseases sorted by gene-association score: tetraploidy (26), soft tissue sarcoma (14), wilson-turner syndrome (6)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 7.12 RPKM in Cervix - Endocervix
Total median expression: 219.70 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -240.10548-0.438 Picture PostScript Text
3' UTR -894.843576-0.250 Picture PostScript Text

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.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR000961 - AGC-kinase_C
IPR011009 - Kinase-like_dom
IPR017892 - Pkinase_C
IPR000719 - Prot_kinase_cat_dom
IPR002290 - Ser/Thr_dual-sp_kinase_dom
IPR008271 - Ser/Thr_kinase_AS
IPR009060 - UBA-like
IPR000449 - UBA/transl_elong_EF1B_N
IPR015940 - UBA/transl_elong_EF1B_N_euk

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.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologGenome BrowserGenome BrowserGenome BrowserNo ortholog
Gene Details  Gene DetailsGene Details 
Gene Sorter  Gene SorterGene Sorter 
  EnsemblFlyBaseWormBase 
  Protein SequenceProtein SequenceProtein Sequence 
  AlignmentAlignmentAlignment 

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000166 nucleotide binding
GO:0000287 magnesium ion binding
GO:0004672 protein kinase activity
GO:0004674 protein serine/threonine kinase activity
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0016301 kinase activity
GO:0016740 transferase activity
GO:0019901 protein kinase binding
GO:0030331 estrogen receptor binding
GO:0046872 metal ion binding

Biological Process:
GO:0000082 G1/S transition of mitotic cell cycle
GO:0000086 G2/M transition of mitotic cell cycle
GO:0000278 mitotic cell cycle
GO:0000819 sister chromatid segregation
GO:0001827 inner cell mass cell fate commitment
GO:0001828 inner cell mass cellular morphogenesis
GO:0006468 protein phosphorylation
GO:0007049 cell cycle
GO:0009755 hormone-mediated signaling pathway
GO:0016310 phosphorylation
GO:0030216 keratinocyte differentiation
GO:0030833 regulation of actin filament polymerization
GO:0033138 positive regulation of peptidyl-serine phosphorylation
GO:0033146 regulation of intracellular estrogen receptor signaling pathway
GO:0034613 cellular protein localization
GO:0035329 hippo signaling
GO:0043065 positive regulation of apoptotic process
GO:0043254 regulation of protein complex assembly
GO:0045736 negative regulation of cyclin-dependent protein serine/threonine kinase activity
GO:0046620 regulation of organ growth
GO:0051220 cytoplasmic sequestering of protein
GO:0051301 cell division
GO:0060644 mammary gland epithelial cell differentiation
GO:0090090 negative regulation of canonical Wnt signaling pathway
GO:2000058 regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process

Cellular Component:
GO:0000922 spindle pole
GO:0005737 cytoplasm
GO:0005815 microtubule organizing center
GO:0005829 cytosol
GO:0005856 cytoskeleton


-  Descriptions from all associated GenBank mRNAs
  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

-  Other Names for This Gene
  Alternate Gene Symbols: LATS1_HUMAN, NM_004690, NP_004681, O95835, Q6PKD0, uc003qmu.1, WARTS
UCSC ID: uc003qmu.2
RefSeq Accession: NM_004690
Protein: O95835 (aka LATS1_HUMAN or LTS1_HUMAN)
CCDS: CCDS34551.1

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_004690.3
exon count: 8CDS single in 3' UTR: no RNA size: 7533
ORF size: 3393CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 6461.00frame shift in genome: no % Coverage: 99.79
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.