VCL

Protein identityUniProt · HPA

UniProt accession

P18206

Gene

VCL

Ensembl

ENSG00000035403

Chromosome

10

Canonical length

1134 aa

Protein class

Disease related genes, Human disease related genes, Plasma proteins, Predicted intracellular proteins

Subcellular location

Focal adhesion sites

OverviewNCBI Gene

Vinculin is a cytoskeletal protein associated with cell-cell and cell-matrix junctions, where it is thought to function as one of several interacting proteins involved in anchoring F-actin to the membrane. Defects in VCL are the cause of cardiomyopathy dilated type 1W. Dilated cardiomyopathy is a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Multiple alternatively spliced transcript variants have been found for this gene, but the biological validity of some variants has not been determined. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

1134 residues, UniProt reviewed canonical sequence.

>P18206|VCL
     1  MPVFHTRTIE SILEPVAQQI SHLVIMHEEG EVDGKAIPDL TAPVAAVQAA VSNLVRVGKE
    61  TVQTTEDQIL KRDMPPAFIK VENACTKLVQ AAQMLQSDPY SVPARDYLID GSRGILSGTS
   121  DLLLTFDEAE VRKIIRVCKG ILEYLTVAEV VETMEDLVTY TKNLGPGMTK MAKMIDERQQ
   181  ELTHQEHRVM LVNSMNTVKE LLPVLISAMK IFVTTKNSKN QGIEEALKNR NFTVEKMSAE
   241  INEIIRVLQL TSWDEDAWAS KDTEAMKRAL ASIDSKLNQA KGWLRDPSAS PGDAGEQAIR
   301  QILDEAGKVG ELCAGKERRE ILGTCKMLGQ MTDQVADLRA RGQGSSPVAM QKAQQVSQGL
   361  DVLTAKVENA ARKLEAMTNS KQSIAKKIDA AQNWLADPNG GPEGEEQIRG ALAEARKIAE
   421  LCDDPKERDD ILRSLGEISA LTSKLADLRR QGKGDSPEAR ALAKQVATAL QNLQTKTNRA
   481  VANSRPAKAA VHLEGKIEQA QRWIDNPTVD DRGVGQAAIR GLVAEGHRLA NVMMGPYRQD
   541  LLAKCDRVDQ LTAQLADLAA RGEGESPQAR ALASQLQDSL KDLKARMQEA MTQEVSDVFS
   601  DTTTPIKLLA VAATAPPDAP NREEVFDERA ANFENHSGKL GATAEKAAAV GTANKSTVEG
   661  IQASVKTARE LTPQVVSAAR ILLRNPGNQA AYEHFETMKN QWIDNVEKMT GLVDEAIDTK
   721  SLLDASEEAI KKDLDKCKVA MANIQPQMLV AGATSIARRA NRILLVAKRE VENSEDPKFR
   781  EAVKAASDEL SKTISPMVMD AKAVAGNISD PGLQKSFLDS GYRILGAVAK VREAFQPQEP
   841  DFPPPPPDLE QLRLTDELAP PKPPLPEGEV PPPRPPPPEE KDEEFPEQKA GEVINQPMMM
   901  AARQLHDEAR KWSSKPGIPA AEVGIGVVAE ADAADAAGFP VPPDMEDDYE PELLLMPSNQ
   961  PVNQPILAAA QSLHREATKW SSKGNDIIAA AKRMALLMAE MSRLVRGGSG TKRALIQCAK
  1021  DIAKASDEVT RLAKEVAKQC TDKRIRTNLL QVCERIPTIS TQLKILSTVK ATMLGRTNIS
  1081  DEESEQATEM LVHNAQNLMQ SVKETVREAE AASIKIRTDA GFTLRWVRKT PWYQ

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against VCL can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.28

Highest tissue expression

220 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about VCL.

Disease | AllUniProt

Conditions VCL is implicated in, by any mechanism.

• Cardiomyopathy, dilated, 1W (CMD1W) MIM:611407
• Cardiomyopathy, familial hypertrophic, 15 (CMH15) MIM:613255

Disease | GeneticClinVar

4 pathogenic / likely-pathogenic of 1,756 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Primary dilated cardiomyopathy
• Hypertrophic cardiomyopathy 15

Disease | ImmuneIEDB

Conditions an epitope on VCL was assayed in.

• rheumatoid arthritis B cell

Disease | AutoantibodyPubMed

Conditions in which antibodies against VCL are reported. Each links to that disease's full target list.

• Scleroderma, Systemic 3

Showing 1 of 2 — disease pages carrying at least 10 antigens.

ReferencesPubMed · IEDB

Publications for VCL from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.4

gnomAD pLI

0.05

gnomAD missense Z

2.71

DepMap mean gene effect

-0.4

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• adherens junction assembly
• apical junction assembly
• axon extension
• cell adhesion
• cell-matrix adhesion
• epithelial cell-cell adhesion
• lamellipodium assembly
• maintenance of blood-brain barrier
• morphogenesis of an epithelium
• negative regulation of cell migration
• platelet aggregation
• protein localization to cell surface
• regulation of establishment of endothelial barrier
• regulation of focal adhesion assembly
• regulation of protein localization to adherens junction

Molecular functions

• actin binding
• alpha-catenin binding
• beta-catenin binding
• cadherin binding
• dystroglycan binding
• molecular adaptor activity
• structural molecule activity
• ubiquitin protein ligase binding

Cellular components

• adherens junction
• brush border
• cell-cell contact zone
• cell-cell junction
• cell-substrate junction
• costamere
• cytoplasm
• cytoskeleton
• cytosol
• extracellular exosome
• extracellular region
• extracellular vesicle
• fascia adherens
• ficolin-1-rich granule lumen
• focal adhesion
• membrane raft
• perinuclear region of cytoplasm
• plasma membrane
• protein-containing complex
• sarcolemma
• secretory granule lumen
• specific granule lumen
• terminal web
• zonula adherens
• inner dense plaque of desmosome
• outer dense plaque of desmosome
• podosome ring

Protein domainsUniProt · Pfam · InterPro

• Vinculin, conserved site
• Vinculin/alpha-catenin
• Alpha-catenin/vinculin-like superfamily
• Vinculin family
• Vinculin

KeywordsUniProt

• Acetylation
• Actin-binding
• Cardiomyopathy
• Cell adhesion
• Cell junction
• Cell membrane
• Cell projection
• Cytoplasm
• Cytoskeleton
• Lipoprotein
• Membrane
• Palmitate
• Phosphoprotein
• Repeat

InteractionsUniProt · HPA

Protein binding partners of VCL in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• APBB1IP
• CTNNA1
• CTNNB1
• FER1L6
• FLII
• NRAP
• SORBS1
• SYNM
• TLN1
• FOCAD
• TGFB1I1
• RAVER1
• ABI2
• BRCA1
• CLTA
• TRIP6