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FLASH GENE
Symbol LATS2 contributors: mct/npt/pgu - updated : 29-10-2013
HGNC name LATS, large tumor suppressor, homolog 2 (Drosophila)
HGNC id 6515
Location 13q12.11      Physical location : 21.547.177 - 21.635.722
Synonym name
  • warts-like kinase
  • serine/threonine kinase KPM
  • Synonym symbol(s) FLJ13161, KPM
    EC.number 2.7.11.1
    DNA
    TYPE functioning gene
    STRUCTURE 88.55 kb     8 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Binding site
    MAPPING cloned Y linked N status provisional
    Physical map
    LOC387901 13 LOC387901 ZNF198 13q11-q12 zinc finger protein 198 LOC144845 13q12.11 hypothetical protein BC008631 GJA3 13q11 gap junction protein, alpha 3, 46kDa (connexin 46) LOC390378 13 similar to peptidylprolyl isomerase A GJB2 13q11-q12.1 gap junction protein, beta 2, 26kDa (connexin 26) GJB6 13q12.1 gap junction protein, beta 6 (connexin 30) CRYL1 13q11 crystallin, lambda 1 TG737 13q12.1 crystallin, lambda 1 IL17D 13q12.11 interleukin 17D LOC221143 13q12.11 hypothetical protein LOC221143 XPO4 13q11 exportin 4 LOC390379 13 similar to Heterogeneous nuclear ribonucleoprotein A1 (Helix-destabilizing protein) (Single-strand binding protein) (hnRNP core protein A1) (HDP) LOC387902 13 similar to protein 40kD LATS2 13q11-q12 LATS, large tumor suppressor, homolog 2 (Drosophila) LOC338870 13q12.11 similar to ribosomal protein S12 LOC390380 13 similar to chromosome 9 open reading frame 12; 1,3,4,5,6-pentakisphosphate 2-kinase SAP18 13q12.11 sin3-associated polypeptide, 18kDa C13orf3 13q11 chromosome 13 open reading frame 3 MRP63 13p11.1-q11 mitochondrial ribosomal protein 63 LOC387903 13 LOC387903 ESTRRA 13q12.11 estrogen-related receptor alpha pseudogene LOC387904 13 similar to hypothetical protein GPRK6P 13pter-q21 G protein-coupled receptor kinase 6 pseudogene LOC387905 13 LOC387905 FLJ25952 13q12.11 hypothetical protein FLJ25952 LOC387906 13 similar to RIKEN cDNA 5033406L14 LOC390382 13 similar to histone 1, H2bc; H2B histone family, member S FLJ34588 13q12.11 Smhs2 homolog (rat) LOC387907 13 similar to bA271B5.1 (similar to ribosomal protein S7) FGF9 13q11-q12 fibroblast growth factor 9 (glia-activating factor)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    8 - 5558 120 1048 - 2003 12853976
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart    
    Digestiveliver   highly Homo sapiens
    Hearing/Equilibriumear   highly
    Lymphoid/Immunespleen   highly
    Nervousbrain    
    Reproductivemale systemprostate   
    Urinarykidney    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow   
    Connectivebone   
    Epithelialbarrier lining   
    Lymphoid    
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Digestivehepatocyte Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N-terminal non-kinase regions are distinct except for LATS conserved domains 1 and 2 (LCD1 and LCD2), which may be important for LATS1/2-specific functions
  • a PAPA repeat with seven copies of the dipeptide proline-alanine, may be involved in protein-protein interactions
  • a kinase domain with presence, also in DMPK, of two negative pockets in the peptide binding groove provides an explanation for the substrate preference
  • a C-terminal serine/threonine kinase domain
  • HOMOLOGY
    interspecies homolog to Drosophila LATS large tumor suppressor 2
    homolog to Drosophila loss of the lats/warts
    ortholog to murine Lats2
    homolog to C.elegans T20F10.1
    intraspecies homolog to CDC42BP (myotonic DMPK-like)
    Homologene
    FAMILY
  • LATS tumor suppressor family
  • Dbf2 kinase family
  • CATEGORY enzyme , tumor suppressor , receptor membrane serine/threonine
    SUBCELLULAR LOCALIZATION     plasma membrane,junction,tight
        intracellular
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,nucleus,chromatin/chromosome
    text
  • cytoplasmic during interphase, while it becomes localized to the mitotic apparatus during mitosis
  • co-localizing with AURKA at the centrosomes during the cell cycle
  • LATS2, AMOTL2, and YAP1 all localize to tight junctions, raising the possibility that clustering of Hippo pathway components at tight junctions might function to trigger LATS2 activation and growth inhibition in response to increased cell density
  • basic FUNCTION
  • playing a role in suppressing tumor development and regulating cell proliferation
  • functioning as a modulator of AR by inhibiting androgen-regulated gene expression
  • may play a role in AR-mediated transcription and contribute to the development of prostate cancer
  • implicated in regulation of the cell cycle and apoptosis
  • affects both growth and death of cardiac myocytes, but it primarily regulates the size of the heart and acts as an endogenous negative regulator of cardiac hypertrophy
  • may potentially involve in Hippo pathway regulating the fat reduction by inhibiting adipocyte differentiation and growth
  • coordinate the cell cycle, cell proliferation, and cell death, promotes the stabilization of TP53 by inactivating MDM2
  • functions as part of the Hippo pathway to promote contact inhibition of growth and tumor suppression by phosphorylating and inhibiting the transcriptional co-activator YAP1
  • Aurora A-LATS1/2-Aurora B axis might be a novel pathway that regulates accurate mitotic progression by ensuring the proper mitotic localization of LATS2
  • acts as a positive modulator of SNAI1 protein level and potentiates its EMT activity
  • CELLULAR PROCESS cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
  • Aurora A-LATS1/2-Aurora B axis might be a novel pathway that regulates accurate mitotic progression
  • a component
  • component of the Hippo tumor-suppressive signaling pathway
  • WWC1-Aurora-LATS2 protein complexes form a novel axis that regulates precise mitosis
  • INTERACTION
    DNA
    RNA
    small molecule nucleotide,
  • ATP
  • protein
  • phosphorylation target of Aurora-A kinase (AURKA)(and this phosphorylation plays a role of the centrosomal localization of LATS2)
  • AR-interacting protein
  • LATS1 and LATS2 are novel HSP90AA1 clients and HSP90AA1 inhibitors can disrupt the LATS tumor suppressor pathway in cancer cells
  • AMOT activate LATS2 through a novel conserved domain that binds and activates LATS2
  • binding between WWC1 and LATS2 requires the N-terminal 86 AAs of WWC1 and the PPPY motif and AAs 667788 in LATS2
  • interacting with FOXP3 (LATS2 induction required binding of FOXP3 to a specific sequence in the LATS2 promoter, and this interaction contributed to FOXP3-mediated growth inhibition of tumor cells)
  • LATS2 kinase is a novel regulator of SNAI1 protein level, subcellular localization, and thus, activity
  • LATS2 modulates ESR1-regulated gene transcription, through direct and/or indirect interactions with ESR1
  • involved in phosphorylation of AMOT130, which is a key feature that enables it to inhibit YAP1-dependent signaling and cell growth
  • AMOT is a direct substrate of LATS1/LATS2 mediating functions of the Hippo pathway in endothelial cell migration and angiogenesis
  • LATS1, LATS2 can synergize with F-actin perturbations by phosphorylating free AMOT130 to keep it from associating with F-actin
  • cell & other
    REGULATION
    activated by activated by the MST2 kinase
    repressed by tristetraprolin (TTP) (overexpression of TTP reduced the expression level of LATS2)
    Phosphorylated by AURKA (Aurora A was demonstrated to phosphorylate LATSs2 on serine 380 (S380) during mitosis)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    in prostate cancer
    tumoral     --low  
    by promoter hypermethylation-mediated in astrocytoma
    tumoral       loss of function
    is one of the key mechanisms for constitutive activation of YAP1, which induces deregulation of malignant mesothelioma cell proliferation
    tumoral     --low  
    of LATS1 and LATS2 by promoter hypermethylation is associated with a biologically aggressive phenotype in breast cancer
    tumoral     --low  
    in breast and prostate cancer and acts as an important tumor suppressor relay between the FOXP3 and HIPPO pathways which are widely implicated in cancer (
    constitutional     --over  
    reduced left ventricular systolic and diastolic function without affecting baseline levels of myocardial apoptosis
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerbrain 
    useful target for astrocytoma therapy
    ANIMAL & CELL MODELS