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FLASH GENE
Symbol TLN1 contributors: mct - updated : 27-03-2015
HGNC name talin 1
HGNC id 11845
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N terminal region containing elements required for localization of talin to cell-ECM junctions, and N-terminal talin head (47 kDa) contains a FERM domain composed of F1, F2, and F3 domains
  • a F0 subdomain is located N-terminus to F1, F0F1, and is essential for talin-induced activation of integrin alphaLbeta2 (LFA1) (
  • calpain cleavage site at both the N- and C-terminal regions of talin contributing to the regulation of ocal adhesions dynamics
  • F2 and F3 FERM subdomains contribute to binding (F3 domain has a phosphotyrosine-binding domain-like fold and binds to both the membrane proximal NPXY motif in beta3-integrin tails and the membrane proximal helix)
  • a membrane interaction site
  • in the central region of the rod, AAs 13591659 show significant homology to the gene MESDC1
  • a C-terminal calpain2 cleavage site important in focal adhesion dynamics (
  • a C terminal region containing binding sites for vinculin, actin, integrin beta, with a five-helix bundle linked to an helix responsible for dimerization, (I/LWEQ module is a conserved structural element that is critical for I/LWEQ module protein function)
  • secondary structure talin rod (220 kDa) is composed of 62 alpha-helices organized into a series of amphipathic helical bundles
    mono polymer dimer
    HOMOLOGY
    interspecies homolog to murine Tln1
    Homologene
    FAMILY
  • ezrin/moesin/radixin-like (ERM) family
  • I/LWEQ module superfamily
  • CATEGORY adaptor , adhesion , structural protein
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    text
  • co-localizes with SYNM within the costameres of human skeletal muscle cells
  • abundant in the cytosol, however, it mediates adhesion by associating with integrins in the plasma membrane where it forms a primary link between integrins and the actin cytoskeleton
  • was concentrated in peripheral focal adhesions
  • basic FUNCTION
  • cytoskeleton protein binding to vinculin and integrin
  • concentrating at points of cell adhesion (focal contacts), also substrate for calpa
  • n II
  • is the primary link between integrins and actin in dynamic focal adhesions in undifferentiated, motile cells
  • responding and participating in reorganization of membrane-cytoplasmic interactions
  • link the actin cytoskeleton to the extracellular environment through interactions with beta-integrins and actin
  • essential to integrin activation in platelets
  • required to support coupling of surface-associated fibronectin to the actin cytoskeleton through C-terminal region
  • serves as an essential link between integrins and the actin cytoskeleton in several similar, but functionally distinct, adhesion complexes, including focal adhesions, costameres, and intercalated disks
  • provides a direct link between the integrin family of cell adhesion molecules and the actin cytoskeleton
  • through conserved dimerization motif in the I/LWEQ module, plays an essential role as a component of focal adhesions and, by extension, the other I/LWEQ module proteins in other multicomponent assemblies involved in cell adhesion and vesicle trafficking
  • TLN1, TLN2 are crucial for skeletal muscle development, where they regulate myoblast fusion, sarcomere assembly and the maintenance of myotendinous junctions (MTJs)
  • key integrin coactivator
  • not required for follicular B-cell maturation in the spleen or homeostatic humoral immunity but is critical for integrin-dependent B lymphocyte emigration to lymph nodes and optimal immunity against T-dependent antigens
  • endothelial cell TLN1 is essential for embryonic angiogenesis
  • cytoskeletal protein that binds to integrin beta cytoplasmic tails and regulates integrin activation
  • recruits and activates focal adhesion proteins required for proliferation via the C terminus of its rod domain
  • new function for talin, which is to link integrin adhesions with cell cycle progression
  • adaptor proteins that connect the integrin family of cell adhesion receptors to cytoskeletal actin
  • plays a key role in cell adhesion and spreading
  • dimeric adaptor protein that associates with the integrin family of cell adhesion molecules in cell-extracellular matrix junctions (focal adhesions)
  • TLN1 and RAP1A are critical for resorptive function, and their selective inhibition in mature osteoclasts retards pathological bone loss
  • TLN1 and TLN2 have distinct functions in the myocardium
  • is essential protein for integrin adhesion
  • would be involved in the integrin-dependent hypertrophic response of the myocardium
  • is not essential in the adult myocardium and its loss from cardiac myocytes (CMs) only leads to a mild stress response
  • appears to be critical in acute costameric force-sensing and mechanical signaling
  • actin-binding proteins TLN1 and VCL cooperate to provide the link between extracellular-matrix-bound integrins and intracellular F-actin, essential for cell spreading and migration
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • part of vinculin-talin-integrin system having a role in the transduction of mechanical force to the extracellular matrix and a key role in the regulation of action potential duration to cardiac myocytes
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding vinculin (activator of vinculin under certain conditions
  • links integrin adhesion receptors with the actin cytoskeleton
  • interacting with VCL
  • TLN1 binding to integrin promotes epiblast adhesion and morphogenesis in part by preventing integrin beta1 degradation
  • alternative linkage for PTK2-talin interactions within nascent adhesions essential for the control of cell migrationv
  • specific inter-domain interactions between talin head and talin rod domain that regulate its subcellular localization
  • talin is a substrate for cathepsin H (CTSH), a lysosomal cysteine protease with a strong aminopeptidase activity
  • actin- and ITGB3 tail-binding protein, playing an important role in cell migration by promoting integrin activation and focal adhesion formation
  • CTSH-mediated processing of TLN1 might promote cancer cell progression by affecting integrin activation and adhesion strength
  • cytoskeletal protein TLN1 is a specific substrate of CTSH that could be associated with regulation of ITGB3 receptors, focal adhesion (FA) strength, and cell migration
  • TLN1 activates integrins, couples them to F-actin, and recruits vinculin to focal adhesions (FAs)
  • WDR1 is essential for TLN1-induced activation of ITGA2B during platelet activation
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • potential value for TLN1 as a marker of tumor progression to metastasis
  • Therapy target
    SystemTypeDisorderPubmed
    cancerreproductiveprostate
    therapeutic significance of disrupting TLN1 signaling/focal adhesion interactions in targeting metastatic prostate cancer
    ANIMAL & CELL MODELS