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FLASH GENE
Symbol TLN1 contributors: mct - updated : 27-03-2015
HGNC name talin 1
HGNC id 11845
Location 9p13.3      Physical location : 35.697.333 - 35.732.392
Synonym symbol(s) CPLI, TLN, KIAA1027, ILWEQ
DNA
TYPE functioning gene
STRUCTURE 35.06 kb     57 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status confirmed
Map pter - D9S129 - D9S54 - D9S178 - D9S132 - D9S1792 - D9S288 - D9S199 - RLN1 /RLN2 /INSL4 - D9S281 - D9S749 - D9S144 - D9S775 - D9S168 - D9S269 - D9S1217 - TYRP1 - D9S267 - D9S268 - D9S274 - D9S1211 - TLN1 - D9S156 - D9S157 - MLLT3 - CDKN2A - D9S171 - D9S265 - D9S270 - D9S104 - D9S319 - D9S43 - D9S304 - cen
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
57 - 8187 270 2541 - 2008 18156175
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascular    moderately Homo sapiensAdult
     highly Homo sapiensFetal
cells
SystemCellPubmedSpeciesStageRna symbol
Cardiovascularendothelial cell Homo sapiens
Muscularmyocyte Homo sapiens
cell lineage
cell lines
fluid/secretion
at STAGE
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