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FLASH GENE
Symbol LATS1 contributors: mct/pgu - updated : 18-04-2016
HGNC name LATS, large tumor suppressor, homolog 1 (Drosophila)
HGNC id 6514
Location 6q25.1      Physical location : 149.982.050 - 150.039.392
Synonym name
  • WTS/large tumor-suppressor 1 mitotic kinase
  • LATS homolog 1
  • WARTS protein kinase
  • Synonym symbol(s) LATS, WARTS, WTS
    EC.number 2.7.11.1
    DNA
    TYPE functioning gene
    STRUCTURE 60.10 kb     8 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    4 - 2743 - 690 retina 2008 18158288
    LATS1S
    8 - 7533 170 1130 retina 2008 18158288
    LATS1L
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivepharynx   highly
    Reproductivefemale systemovary  highly
     female systembreastmammary gland  
    Respiratoryrespiratory tractlarynx  highly
    Visualeyeretina  moderately
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose  highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal
    Text ubiquitous
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N-terminal region binding CDC2 to form a complex showing reduced H1 histone kinase activity and 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
  • an UBA domain
  • eleven tyrosine kinase catalytic domains
  • C-terminal kinase domain binds to its own N-terminal region, suggesting potential negative regulation through interference with complex formation via intramolecular binding
  • HOMOLOGY
    interspecies ortholog to yeast, Dbf2
    homolog to Drosophila lats
    Homologene
    FAMILY
  • Ndr/LATS subfamily of AGC (protein kinase A/PKG/PKC) kinases
  • CATEGORY tumor suppressor , signaling , receptor membrane serine/threonine
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
    intracellular,nucleus,chromatin/chromosome
    text localizes to the centrosomes throughout interphase but migrates to the mitotic apparatus, including spindle pole bodies, mitotic spindle, and midbody, during mitosis
    basic FUNCTION
  • playing a role in tumorigenesis and specific endocrine dysfunction
  • may be playing a role in the control of tumor development, by negatively regulating cell proliferation and modulating cell survival
  • controlling with LATS2 cell proliferation by negatively regulating different cell cycle check points
  • plays a crucial role in the prevention of tumor formation by controlling mitosis progression
  • may act as negative key regulators of the cell cycle
  • putative serine/threonine kinase that localizes to the mitotic apparatus and complexes with cell cycle controller CDC2 kinase in early mitosis
  • tumor suppressor which plays a critical role in maintenance of ploidy through its actions in both mitotic progression and the G1 tetraploidy checkpoint
  • playing a role in mitotic exit and having abilities to induce G2 arrest and promote cytokinesis
  • role of LATS1 in controlling PLK1 at the G2 DNA damage checkpoint
  • central player of the emerging Hippo signaling pathway, which plays important roles in organ size control, tumorigenesis, and stem cell differentiation
  • CELLULAR PROCESS cell cycle, division, mitosis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • CDC2/LATS1 in early mitosis
  • INTERACTION
    DNA
    RNA
    small molecule cofactor,
  • Mg2+
  • protein
  • CDC2 (negative egulator of CDC2)
  • zyxin (ZYX, to control mitosis progression by forming a regulatory complex or mitotic apparatus)
  • MOBKL1A
  • MOBKL1B
  • interacts with MOB1A, a protein whose homologue in budding yeast associates with kinases involved in mitotic exit
  • can negatively regulate transcription regulation and transformation functions of YAP1 by inhibiting its nuclear translocation via phosphorylation of multiple sites in YAP1
  • interacting with the protein/discs-large protein/zonula (PDZ) domain of HTRA2 and promoting its protease activity
  • substrate for HTRA2 protease activity, thus it is not only a regulator but also a downstream target of this protease
  • LATS1 and LATS2 are novel HSP90AA1 clients and HSP90AA1 inhibitors can disrupt the LATS tumor suppressor pathway in cancer cells
  • NPHP4 inhibited LATS1-mediated phosphorylation of the Yes-associated protein (YAP1) and WWTR1, leading to derepression of these protooncogenic transcriptional regulators
  • phosphorylate Aurora B (AURKB)
  • PPP1R12A is a new substrate for LATS1 (LATS1 directly and preferentially phosphorylated serine 445 (S445) of PPP1R12A)
  • WWP1 is essential for LATS1 stability and negatively regulate LATS1 by promoting LATS1 degradation through polyubiquitination and the 26S proteasome pathway
  • disruption of the actin cytoskeleton promotes NF2-LATS1 interactions, which implicates NF2 in actin-mediated regulation of Hippo signaling
  • 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
  • NEDD4 directly interacts with LATS1, leading to ubiquitination and decreased levels of LATS1 and, thus, increased YAP1 localization in the nucleus
  • LATS1, LATS2 can synergize with F-actin perturbations by phosphorylating free AMOT130 to keep it from associating with F-actin
  • AJUBa recruits LATS1 to junctions in a tension-dependent manner
  • PTPN14 and WWC1 can induce the LATS1 activation independently and cooperatively
  • PARD3 promotes the interaction between PPP1CA and LATS1 to induce LATS1 dephosphorylation and inactivation, therefore leading to dephosphorylation and activation of TAZ
  • LMO3 promotes hepatocellular carcinoma invasion, metastasis and anoikis inhibition by directly interacting with LATS1 and suppressing Hippo signaling
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    by promoter hypermethylation-mediated in astrocytoma
    tumoral     --low  
    of LATS1 and LATS2 by promoter hypermethylation is associated with a biologically aggressive phenotype in breast cancer
    tumoral germinal mutation      
    N-terminally truncated LATS1 induced LATS2 downregulation and YAP1 protein accumulation, leading to chromosomal instability and tumorigenesis
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerlung 
    may serve as a novel therapeutic target of non-small-cell lung cancer
    cancerbrain 
    useful target for astrocytoma therapy
    cancerreproductivebreast
    promising therapeutic strategy in which developed drugs targeting WWP1 cause activation of LATS1 in suppressing
    ANIMAL & CELL MODELS