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FLASH GENE
Symbol TES contributors: mct/npt/pgu - updated : 10-02-2021
HGNC name testin LIM domain protein
HGNC id 14620
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheart     Homo sapiens
cell lineage lymphoblastoid cells
cell lines cancer cell lines but not in hematological malignancies cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a PET domain in the N-terminus
  • four phosphorylation sites
  • one glycosylation site
  • one cytochrome C heme binding site
  • three cysteine-rich LIM/double zinc finger motifs (LIM domains) at the C terminus (LIM3 domain lacking the FPPPP motif, binds to the EVH1 domain of ENAH, but not to those of VASP or EVL)(Boeda 2007)
  • HOMOLOGY
    interspecies homolog to murine Testin
    intraspecies homolog to SOX9
    Homologene
    FAMILY
  • prickle/espinas/testin family
  • CATEGORY adhesion , transcription factor
    SUBCELLULAR LOCALIZATION     plasma membrane,junction
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    text
  • putative tumor suppressor and localizes to the cytoplasm as a component of focal adhesions and cell contacts
  • locates in the cytoplasm along stress fibers being recruited to focal adhesions
  • basic FUNCTION
  • transcriptional regulation through protein-protein interactions
  • actin-binding protein mainly located at focal adhesions (Rotter 2005)
  • atypical EVH1 binding partner and regulator specific to a single ENAH/VASP family member (Boeda 2008)
  • plays a role in cell spreading and motility as well as cytoskeletal organisation, e.g. actin stress fibre assembly
  • has different conformational states in different cellular compartments, and a "closed" conformational state of TES may be involved in nucleolar localization (
  • novel protein partner of the CASR that regulates receptor-mediated Rho signalling, and supports CASR-dependent activation of Rho kinase
  • involved in endothelial cell (EC) functions relevant to atherosclerosis
  • focal adhesion protein testin is a modular scaffold and tumour suppressor
  • testin region (amino acids 52-233) harbouring the PET domain interacts with the C-terminal LIM1-2 domains
  • participate in the processes of tumor growth, angiogenesis, and metastasis
  • expression of testin protein level correlates positively with percentage of cells in G1 phase, while overexpression can induce apoptosis and decreased colony forming ability
  • TES serves likely as a crucial regulator of the hypertrophic reaction by hindering the calcineurin-dependent pathway in the heart
  • CELLULAR PROCESS nucleotide, transcription, regulation
    cell organization/biogenesis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • specific ENAH interacting partner
  • interaction between TES and spectrin is mediated by a LIM (Lin-11, Isl-1 and Mec3) domain of TES and by the alpha10 repeat of alphaII-spectrin (Rotter 2005)
  • interaction between TES and EVL (co-localization of these two proteins at focal adhesions) (Rotter 2005)
  • SRY and NR5A1 co-operate to activate the human SOX9 homologous TES, a process dependent on phosphorylated NR5A1
  • SOX9 activates TES, augmented by NR5A1, suggesting a mechanism for maintenance of SOX9 expression by auto-regulation
  • interplay between the CASR and testin in the regulation of CASR-mediated Rho signalling with possible effects on the cytoskeleton
  • TES directly interacted with calcineurin and suppressed its downstream signalling pathway
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral       loss of function
    by hypermethylation in ovarian carcinoma
    tumoral   amplification    
    with MET oncogene in gastric cancer
    constitutional     --low  
    association between reduced TES expression and coronary artery disease
    tumoral   LOH    
    in primary gastric cancer
    tumoral     --low  
    is the most frequently methylated and silenced gene yet reported in childhood acute lymphoblastic leukaemia
    constitutional     --low  
    associate with loss by cells epithelial morphology and gain migratory and invasive properties of mesenchymal cells
    tumoral       loss of function
    in human endometrial carcinoma
    tumoral     --other  
    is aberrantly methylated in ALL
    Susceptibility
    Variant & Polymorphism
    Candidate gene best candidate tumor suppressor gene at 7q31
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerreproductiveuterus
    restoration of TESTIN to be a novel therapeutic strategy for endometrial carcinoma
    cancerhemopathy 
    re-expression of TESTIN has anti-leukaemia effects which point to novel therapeutic opportunities for childhood ALL
    ANIMAL & CELL MODELS