UniProt functional annotation for P18206



	UniProt functional annotation for P18206

UniProt code: P18206.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Actin filament (F-actin)-binding protein involved in cell- matrix adhesion and cell-cell adhesion. Regulates cell-surface E- cadherin expression and potentiates mechanosensing by the E-cadherin complex. May also play important roles in cell morphology and locomotion. {ECO:0000269|PubMed:20484056}.

Subunit: Exhibits self-association properties. Part of a complex composed of THSD1, PTK2/FAK1, TLN1 and VCL (PubMed:29069646). Interacts with APBB1IP and NRAP (By similarity). Interacts with TLN1. Interacts with CTNNB1 and this interaction is necessary for its localization to the cell-cell junctions and for its function in regulating cell surface expression of E-cadherin (By similarity). Interacts with SYNM. Interacts with SORBS1 (By similarity). Interacts with CTNNA1 (PubMed:26691986). Binds to ACTN4; this interaction triggers conformational changes (PubMed:15988023). {ECO:0000250|UniProtKB:P12003, ECO:0000250|UniProtKB:Q64727, ECO:0000269|PubMed:14702644, ECO:0000269|PubMed:15070891, ECO:0000269|PubMed:15988023, ECO:0000269|PubMed:18028034, ECO:0000269|PubMed:26691986, ECO:0000269|PubMed:29069646}.

Subcellular location: Cell membrane {ECO:0000250|UniProtKB:P12003}; Peripheral membrane protein {ECO:0000250|UniProtKB:P12003}; Cytoplasmic side {ECO:0000250|UniProtKB:P12003}. Cell junction, adherens junction {ECO:0000250|UniProtKB:P12003}. Cell junction, focal adhesion {ECO:0000250|UniProtKB:P12003}. Cytoplasm, cytoskeleton {ECO:0000250|UniProtKB:P85972}. Cell membrane, sarcolemma {ECO:0000250|UniProtKB:Q64727}; Peripheral membrane protein {ECO:0000250|UniProtKB:Q64727}; Cytoplasmic side {ECO:0000250|UniProtKB:Q64727}. Note=Recruitment to cell-cell junctions occurs in a myosin II-dependent manner. Interaction with CTNNB1 is necessary for its localization to the cell-cell junctions. {ECO:0000250|UniProtKB:P12003}.

Tissue specificity: Metavinculin is muscle-specific.

Domain: Exists in at least two conformations. When in the closed, 'inactive' conformation, extensive interactions between the head and tail domains prevent detectable binding to most of its ligands. It takes on an 'active' conformation after cooperative and simultaneous binding of two different ligands. This activation involves displacement of the head-tail interactions and leads to a significant accumulation of ternary complexes. The active form then binds a number of proteins that have both signaling and structural roles that are essential for cell adhesion. {ECO:0000269|PubMed:20484056}.

Domain: The N-terminal globular head (Vh) comprises of subdomains D1- D4. The C-terminal tail (Vt) binds F-actin and cross-links actin filaments into bundles. In isoform 2 (metavinculin) a 68 residue insertion in the tail domain promotes actin severing instead of bundling. An intramolecular interaction between Vh and Vt masks the F- actin-binding domain located in Vt. The binding of talin and alpha- actinin to the D1 subdomain of vinculin induces a helical bundle conversion of this subdomain, leading to the disruption of the intramolecular interaction and the exposure of the cryptic F-actin- binding domain of Vt. Vt inhibits actin filament barbed end elongation without affecting the critical concentration of actin assembly. {ECO:0000269|PubMed:20484056}.

Ptm: Phosphorylated; on serines, threonines and tyrosines. Phosphorylation on Tyr-1133 in activated platelets affects head-tail interactions and cell spreading but has no effect on actin binding nor on localization to focal adhesion plaques (By similarity). {ECO:0000250|UniProtKB:P12003}.

Ptm: Acetylated; mainly by myristic acid but also by a small amount of palmitic acid. {ECO:0000250|UniProtKB:P12003}.

Disease: Cardiomyopathy, dilated 1W (CMD1W) [MIM:611407]: A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. {ECO:0000269|PubMed:11815424, ECO:0000269|PubMed:16236538}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Cardiomyopathy, familial hypertrophic 15 (CMH15) [MIM:613255]: A hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death. {ECO:0000269|PubMed:16712796}. Note=The disease is caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the vinculin/alpha-catenin family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Actin filament (F-actin)-binding protein involved in cell- matrix adhesion and cell-cell adhesion. Regulates cell-surface E- cadherin expression and potentiates mechanosensing by the E-cadherin complex. May also play important roles in cell morphology and locomotion. {ECO:0000269\|PubMed:20484056}.


Subunit:		Exhibits self-association properties. Part of a complex composed of THSD1, PTK2/FAK1, TLN1 and VCL (PubMed:29069646). Interacts with APBB1IP and NRAP (By similarity). Interacts with TLN1. Interacts with CTNNB1 and this interaction is necessary for its localization to the cell-cell junctions and for its function in regulating cell surface expression of E-cadherin (By similarity). Interacts with SYNM. Interacts with SORBS1 (By similarity). Interacts with CTNNA1 (PubMed:26691986). Binds to ACTN4; this interaction triggers conformational changes (PubMed:15988023). {ECO:0000250\|UniProtKB:P12003, ECO:0000250\|UniProtKB:Q64727, ECO:0000269\|PubMed:14702644, ECO:0000269\|PubMed:15070891, ECO:0000269\|PubMed:15988023, ECO:0000269\|PubMed:18028034, ECO:0000269\|PubMed:26691986, ECO:0000269\|PubMed:29069646}.
Subcellular location:		Cell membrane {ECO:0000250\|UniProtKB:P12003}; Peripheral membrane protein {ECO:0000250\|UniProtKB:P12003}; Cytoplasmic side {ECO:0000250\|UniProtKB:P12003}. Cell junction, adherens junction {ECO:0000250\|UniProtKB:P12003}. Cell junction, focal adhesion {ECO:0000250\|UniProtKB:P12003}. Cytoplasm, cytoskeleton {ECO:0000250\|UniProtKB:P85972}. Cell membrane, sarcolemma {ECO:0000250\|UniProtKB:Q64727}; Peripheral membrane protein {ECO:0000250\|UniProtKB:Q64727}; Cytoplasmic side {ECO:0000250\|UniProtKB:Q64727}. Note=Recruitment to cell-cell junctions occurs in a myosin II-dependent manner. Interaction with CTNNB1 is necessary for its localization to the cell-cell junctions. {ECO:0000250\|UniProtKB:P12003}.
Tissue specificity:		Metavinculin is muscle-specific.
Domain:		Exists in at least two conformations. When in the closed, 'inactive' conformation, extensive interactions between the head and tail domains prevent detectable binding to most of its ligands. It takes on an 'active' conformation after cooperative and simultaneous binding of two different ligands. This activation involves displacement of the head-tail interactions and leads to a significant accumulation of ternary complexes. The active form then binds a number of proteins that have both signaling and structural roles that are essential for cell adhesion. {ECO:0000269\|PubMed:20484056}.
Domain:		The N-terminal globular head (Vh) comprises of subdomains D1- D4. The C-terminal tail (Vt) binds F-actin and cross-links actin filaments into bundles. In isoform 2 (metavinculin) a 68 residue insertion in the tail domain promotes actin severing instead of bundling. An intramolecular interaction between Vh and Vt masks the F- actin-binding domain located in Vt. The binding of talin and alpha- actinin to the D1 subdomain of vinculin induces a helical bundle conversion of this subdomain, leading to the disruption of the intramolecular interaction and the exposure of the cryptic F-actin- binding domain of Vt. Vt inhibits actin filament barbed end elongation without affecting the critical concentration of actin assembly. {ECO:0000269\|PubMed:20484056}.
Ptm:		Phosphorylated; on serines, threonines and tyrosines. Phosphorylation on Tyr-1133 in activated platelets affects head-tail interactions and cell spreading but has no effect on actin binding nor on localization to focal adhesion plaques (By similarity). {ECO:0000250\|UniProtKB:P12003}.
Ptm:		Acetylated; mainly by myristic acid but also by a small amount of palmitic acid. {ECO:0000250\|UniProtKB:P12003}.
Disease:		Cardiomyopathy, dilated 1W (CMD1W) [MIM:611407]: A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. {ECO:0000269\|PubMed:11815424, ECO:0000269\|PubMed:16236538}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Cardiomyopathy, familial hypertrophic 15 (CMH15) [MIM:613255]: A hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death. {ECO:0000269\|PubMed:16712796}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the vinculin/alpha-catenin family. {ECO:0000305}.