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Symbol VCL contributors: mct/npt/shn - updated : 29-06-2016
HGNC name vinculin
HGNC id 12665
Corresponding disease
CMD1W cardiomyopathy, dilated 1W
Location 10q22.2      Physical location : 75.757.871 - 75.879.912
Synonym name
  • metavinculin
  • epididymis luminal protein 114
  • Synonym symbol(s) RP11-178G16.3, CMD1W, CMH15, MVCL, MV, HEL114
    TYPE functioning gene
    STRUCTURE 122.04 kb     22 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Map cen - D10S188 - D10S1737 - VCL - D10S535 - D10S556 - qter
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    21 splicing 5443 116 1066 platelets 2013 23687380
    the major talin-binding protein in platelets
    22 splicing 5443 123.7 1134 muscle-specific isoform, mainly expressed in smooth and cardiac muscle tissue 2013 23687380
  • playing a substantive role in the structural integrity of the heart cytoarchitecture
  • metavinculin, characterized by a 68-AA insert in the tail domain (MVt) and correlates with hereditary idiopathic dilated cardiomyopathy
  • an additional 68 amino-acids based on alternative splicing of exon 19
  • binds actin filaments similarly to the vinculin tail domain
    Type ubiquitous
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivemouthtongue  highly
    Hearing/Equilibriumear   highly
    Respiratoryrespiratory tracttrachea  highly
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    SystemCellPubmedSpeciesStageRna symbol
    skin tegument 
    cell lineage
    cell lines
    at STAGE
  • three Vc repeats of about 130 AAs
  • a lipid-regulated docking site at the C terminus for protein kinase C
  • a globular head domain with 7 helical bundles organized into 3 tandem pairs of bundles (D1-D3) and one unpaired bundle (D4) (Palmer 2009)
  • vinculin tail responsible for the functional link of focal adhesions to the actin cytoskeleton (Humphries 2007)
  • a tail domain (Vt) binding to acidic phospholipids and playing a role in vinculin activation and focal adhesion turnover (Palmer 2009)
    interspecies ortholog to Vcl, Mus musculus
    ortholog to Vcl, Rattus norvegicus
    ortholog to VCL, Pan troglodytes
  • vinculin/alpha-catenin family
  • CATEGORY adhesion
    SUBCELLULAR LOCALIZATION     plasma membrane,junction,adherens
  • located at the cytoplasmic side of adhesion plaques (focal contact)
  • co-localizing with metaVCL to intercalated disc and costameres
  • cytoskeletal protein associated with focal adhesion and adherens junctions
  • localizes to focal adhesions and adherens junctions, connecting cell surface receptors to the actin cytoskeleton
  • basic FUNCTION
  • anchoring F actin to the plasma membrane
  • alphaE-catenin-vinculin interaction plays a role in the assembly of the apical junctional complex in epithelia
  • important in regulating adhesion dynamics and cell migration
  • controls focal adhesion formation by direct interactions with talin and actin (Humphries 2007)
  • involved in tightening of epithelial apical junctions during their maturation
  • plays an important role in cell adhesion and migration through interaction between vinculin and lipid membranes (Diez 2008)
  • involved in linking the actin cytoskeleton to the cell membrane at sites of cellular adhesion (Palmer 2009)
  • plays a role in physiological processes such as cell motility, migration, development, and wound healing (Palmer 2009)
  • facilitates phospholipid membrane insertion
  • protect junctions against overinduced opening by thrombin in remodeling focal adherens junctions
  • needed during active phases of junction remodeling by cytoskeletal force to protect junctions from opening
  • has pleiotropic roles in chondrocytic differentiation
  • tissue-specific function of VCL in cartilage whereby it controls chondrocytic differentiation
  • is a major component of the focal adhesion complex that acts as a mechano-coupler and an actin-binding protein
  • has pleiotropic roles in chondrogenesis and regulates the expression of chondrocyte-specific genes via the integration of various signaling pathways
  • VCL plays a key role in the transmission of extracellular mechanical stimuli leading to the reorganization of cell polarity
  • in cells, APBB1IP is enriched in nascent adhesions at the leading edge whereas VCL is enriched in focal adhesions (FAs)
  • major role for VCL in the control of the cytoskeletal connection affecting mechanical stability and cell motility
  • plays a key structural role in ventricular myocytes that, when disrupted, can lead to contractile dysfunction and dilated cardiomyopathy
  • VCL and TJP1 anchor the actin cytoskeleton to the sarcolemma
  • critical role of vinculin in mechanotransduction at adhesion sites
  • is an essential regulator of both adherens junctions (AJs) and focal adhesion (FA), where it provides links to the actin cytoskeleton
  • a plastic relationship between vinculin-mediated tension and adhesion complex area that controls fundamental cell-matrix adhesion properties
  • essential adhesion protein that links membrane-bound integrin and cadherin receptors through their intracellular binding partners to filamentous actin, facilitating mechanotransduction
  • 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
  • major regulator of cell adhesion and attaches to the cell surface by binding to specific phospholipids
    text an essential regulator of both cell-cell (cadherin-mediated) and cell-matrix (integrin-talin-mediated focal adhesions) junctions
    a component
  • constituent of a complex with alpha-actinin and talin at the adherens type of cell junction
    small molecule other,
  • soluble and membranous phospholipids
  • protein
  • paxillin, PXN
  • F-actin
  • clathrin heavy chain, CHC
  • focal adhesion kinase, FAK
  • E-cadherin
  • alphaE-catenin
  • REF52
  • clipin C, ClipinC
  • vasodilator-stimulated phosphoprotein, VASP
  • polycystin-1, PKD1
  • ribonucleoprotein, PTB-binding 1, RAVER1
  • lipid-dependent protein kinase Calpha
  • talin, TLN1
  • Alpha-actinin
  • actin, talin, alpha-actinin, alpha-catenin, beta-catenin, vinexin, ponsin (Palmer 2009)
  • RAVER1 regulates the assembly of focal adhesions transcriptionally by binding to VCL (metavinculin can bind to RAVER1 in its inactive state)
  • TLN1 activates integrins, couples them to F-actin, and recruits vinculin to focal adhesions (FAs)
  • is a major controller of integrin-mediated adhesion dynamics in B cells
  • direct interaction between VCL and TJP1, illustrating how VCL plays a crucial role in stabilizing gap junctions and myocyte integrity
  • VCL binding TLN1, but not Arp2/3, is critical for osteoclast function, and its selective inhibition retards physiological bone loss
  • interacts with many adhesion proteins, but its interaction with filamentous actin regulates cell morphology, motility, and mechanotransduction
  • INPP5J-binding alters VCL structure to direct higher-order oligomerization and suggests that INPP5J and F-actin binding to VCL are mutually permissive
  • cell & other
  • endothelial VE-cadherin junctions
    Phosphorylated by phosphorylated by SRC kinases
    Other is phosphorylated at Y822 in cell-cell, but not cell-matrix, adhesions
    corresponding disease(s) CMD1W
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    associated with human cardiomyopathy (Palmer 2009)
    Variant & Polymorphism
    Candidate gene
  • potential plasma biomarker for age-related macular degeneration
  • Therapy target
  • vinculin null embryos were small, abnormal, lack of midline fusion of the rostral neural tube, producing a cranial bilobular appearance and attenuation of cranial and spinal nerve development and have heart development defects