The reference OMIM entry for this protein is 193065

Vinculin; vcl metavinculin, included

DESCRIPTION

Vinculin is a cytoskeletal protein associated with the cytoplasmic face of both cell-cell and cell-extracellular matrix adherens-type junctions, where it is thought to function as one of several interacting proteins involved in anchoring F-actin to the membrane (Weller et al., 1990).

CLONING

Weller et al. (1990) determined the complete sequence of the human vinculin gene. They found that both human and chicken embryo sequences of vinculin contain 1,066 amino acids and, furthermore, that the 2 proteins exhibit a high level of sequence identity (greater than 95%). Southern blots of human genomic DNA hybridized with short vinculin cDNA fragments indicated that there is a single vinculin gene. Koteliansky et al. (1992) determined that metavinculin is the result of alternative splicing of the VCL gene and contains an additional exon. Across species, the deduced protein differs from vinculin in having an additional insert of 68 to 79 amino acids in the C-terminal half of the molecule. By comparison of metavinculin sequences from pig, man, chicken, and frog, Strasser et al. (1993) found a division of the insert into 2 parts: the first variable and the second highly conserved. The longest insert, 79 amino acids, was found in Xenopus laevis. Three different C-terminal constructs of vinculin and metavinculin overexpressed in E. coli could be purified by column chromatography. Using amino acid sequencing methods on the intact molecules and their proteolytic subfragments, together with a polyclonal antibody specific only for metavinculin from porcine stomach, Gimona et al. (1988) identified and sequenced the insert in the porcine metavinculin molecule. By alignment with the complete sequence of chick fibroblast vinculin, they determined the exact location of the insert. In porcine metavinculin, this insert lies between the 90-kD protease-resistant N-terminal core and the C terminus of the molecule. It contains 68 amino acids and is flanked by KWSSK sequences, one of which is present in vinculin. The identity of the mapped vinculin and metavinculin sequences outside this different peptide is consistent with 2 proteins arising via alternative splicing at the mRNA level.

GENE STRUCTURE

Moiseyeva et al. (1993) determined that the VCL gene contains 22 exons spanning greater than 75 kb. Alternative splicing of exon 19 results in the cardiac- and smooth muscle-specific metavinculin isoform, containing an additional 68 amino acids.

MAPPING

By use of a panel of human-rodent somatic cell hybrids, Weller et al. (1990) mapped the VCL gene to chromosome 10q11.2-qter. By linkage studies in a 3-generation family, Mulligan et al. (1992) mapped the VCL gene to chromosome 10q22.1-q23, distal to D10S22. They confirmed the assignment by hybridization of the vinculin cDNA to flow-sorted translocation derivative chromosomes containing that portion of chromosome 10.

BIOCHEMICAL FEATURES

- Crystal Structure Bakolitsa et al. (2004) described the crystal structure of the full-length vinculin molecule (1,066 amino acids), which shows a 5-domain autoinhibited conformation in which the carboxy-terminal tail domain is held pincer-like by the vinculin head, and ligand binding is regulated both sterically and allosterically. Bakolitsa et al. (2004) showed that the conformational changes in the head, tail, and proline-rich domains are linked structurally and thermodynamically, and proposed a combinatorial pathway t ... More on the omim web site

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Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 193065 was added.

Jan. 28, 2016: Protein entry updated
Automatic update: model status changed

Jan. 25, 2016: Protein entry updated
Automatic update: model status changed