UniProt functional annotation for P70460



	UniProt functional annotation for P70460

UniProt code: P70460.

Organism: Mus musculus (Mouse).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.

Function: Ena/VASP proteins are actin-associated proteins involved in a range of processes dependent on cytoskeleton remodeling and cell polarity such as axon guidance, lamellipodial and filopodial dynamics, platelet activation and cell migration. VASP promotes actin filament elongation. It protects the barbed end of growing actin filaments against capping and increases the rate of actin polymerization in the presence of capping protein. VASP stimulates actin filament elongation by promoting the transfer of profilin-bound actin monomers onto the barbed end of growing actin filaments. Plays a role in actin-based mobility of Listeria monocytogenes in host cells. Regulates actin dynamics in platelets and plays an important role in regulating platelet aggregation (By similarity). {ECO:0000250, ECO:0000269|PubMed:10660044}.

Subunit: Homotetramer (By similarity). Interacts with PFN1, PFN2, LPP, ACTN1 and ACTG1. Interacts, via the EVH1 domain, with the Pro-rich regions of ZYX. This interaction is important for targeting to focal adhesions and the formation of actin-rich structures at the apical surface of cells. Interacts, via the EVH1 domain, with the Pro-rich domain of Listeria monocytogenes actA. Interacts with APBB1IP. Interacts, via the Pro-rich domain, with the C-terminal SH3 domain of DNMBP. Interacts weakly with MEFV (By similarity). {ECO:0000250}.

Subcellular location: Cytoplasm {ECO:0000269|PubMed:10660044}. Cytoplasm, cytoskeleton {ECO:0000269|PubMed:10660044}. Cell junction, focal adhesion {ECO:0000269|PubMed:10660044}. Cell junction, tight junction {ECO:0000250}. Cell projection, lamellipodium membrane {ECO:0000269|PubMed:10660044}. Cell projection, filopodium membrane {ECO:0000269|PubMed:10660044}. Note=Targeted to stress fibers and focal adhesions through interaction with a number of proteins including MRL family members. Localizes to the plasma membrane in protruding lamellipodia and filopodial tips. Stimulation by thrombin or PMA, also translocates VASP to focal adhesions. Localized along the sides of actin filaments throughout the peripheral cytoplasm under basal conditions (By similarity). In pre-apoptotic cells, colocalizes with MEFV in large specks (pyroptosomes) (By similarity). {ECO:0000250}.

Tissue specificity: Highly expressed in thymus and spleen. Lower levels in lung, ovary, placenta and fat. {ECO:0000269|PubMed:10069337}.

Developmental stage: Expressed constantly throughout brain development, with lower levels in adulthood. {ECO:0000269|PubMed:10069337}.

Domain: The EVH2 domain is comprised of 3 regions. Block A is a thymosin-like domain required for G-actin binding. The KLKR motif within this block is essential for the G-actin binding and for actin polymerization. Block B is required for F-actin binding and subcellular location, and Block C for tetramerization.

Domain: The WH1 domain mediates interaction with XIRP1. {ECO:0000250}.

Ptm: Major substrate for cAMP-dependent (PKA) and cGMP-dependent protein kinase (PKG) in platelets. The preferred site for PKA is Ser- 153, the preferred site for PKG, Ser-235. In ADP-activated platelets, phosphorylation by PKA or PKG/PRKG1 on Ser-153 leads to fibrinogen receptor inhibition. Phosphorylation on Thr-274 requires prior phosphorylation on Ser-153 and Ser-235. In response to phorbol ester (PMA) stimulation, phosphorylated by PKC/PRKCA. In response to thrombin, phosphorylated by both PKC and ROCK1. Phosphorylation at Thr- 274 by AMPK does not require prior phosphorylation at Ser-153 or Ser- 235. Phosphorylation at Ser-153 by PKA is required for localization to the tight junctions in epithelial cells. Phosphorylation modulates F- actin binding, actin filament elongation and platelet activation. Phosphorylation at Ser-318 by AMPK also alters actin filament binding. Carbon monoxide (CO) promotes phosphorylation at Ser-153, while nitric oxide (NO) promotes phosphorylation at Ser-153, but also at Ser-235. {ECO:0000269|PubMed:10085070, ECO:0000269|PubMed:10882740, ECO:0000269|PubMed:12372613, ECO:0000269|PubMed:21945940}.

Similarity: Belongs to the Ena/VASP family. {ECO:0000305}.

Sequence caution: Sequence=CAA67108.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Mus musculus (Mouse).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.



Function:		Ena/VASP proteins are actin-associated proteins involved in a range of processes dependent on cytoskeleton remodeling and cell polarity such as axon guidance, lamellipodial and filopodial dynamics, platelet activation and cell migration. VASP promotes actin filament elongation. It protects the barbed end of growing actin filaments against capping and increases the rate of actin polymerization in the presence of capping protein. VASP stimulates actin filament elongation by promoting the transfer of profilin-bound actin monomers onto the barbed end of growing actin filaments. Plays a role in actin-based mobility of Listeria monocytogenes in host cells. Regulates actin dynamics in platelets and plays an important role in regulating platelet aggregation (By similarity). {ECO:0000250, ECO:0000269\|PubMed:10660044}.


Subunit:		Homotetramer (By similarity). Interacts with PFN1, PFN2, LPP, ACTN1 and ACTG1. Interacts, via the EVH1 domain, with the Pro-rich regions of ZYX. This interaction is important for targeting to focal adhesions and the formation of actin-rich structures at the apical surface of cells. Interacts, via the EVH1 domain, with the Pro-rich domain of Listeria monocytogenes actA. Interacts with APBB1IP. Interacts, via the Pro-rich domain, with the C-terminal SH3 domain of DNMBP. Interacts weakly with MEFV (By similarity). {ECO:0000250}.
Subcellular location:		Cytoplasm {ECO:0000269\|PubMed:10660044}. Cytoplasm, cytoskeleton {ECO:0000269\|PubMed:10660044}. Cell junction, focal adhesion {ECO:0000269\|PubMed:10660044}. Cell junction, tight junction {ECO:0000250}. Cell projection, lamellipodium membrane {ECO:0000269\|PubMed:10660044}. Cell projection, filopodium membrane {ECO:0000269\|PubMed:10660044}. Note=Targeted to stress fibers and focal adhesions through interaction with a number of proteins including MRL family members. Localizes to the plasma membrane in protruding lamellipodia and filopodial tips. Stimulation by thrombin or PMA, also translocates VASP to focal adhesions. Localized along the sides of actin filaments throughout the peripheral cytoplasm under basal conditions (By similarity). In pre-apoptotic cells, colocalizes with MEFV in large specks (pyroptosomes) (By similarity). {ECO:0000250}.
Tissue specificity:		Highly expressed in thymus and spleen. Lower levels in lung, ovary, placenta and fat. {ECO:0000269\|PubMed:10069337}.
Developmental stage:		Expressed constantly throughout brain development, with lower levels in adulthood. {ECO:0000269\|PubMed:10069337}.
Domain:		The EVH2 domain is comprised of 3 regions. Block A is a thymosin-like domain required for G-actin binding. The KLKR motif within this block is essential for the G-actin binding and for actin polymerization. Block B is required for F-actin binding and subcellular location, and Block C for tetramerization.
Domain:		The WH1 domain mediates interaction with XIRP1. {ECO:0000250}.
Ptm:		Major substrate for cAMP-dependent (PKA) and cGMP-dependent protein kinase (PKG) in platelets. The preferred site for PKA is Ser- 153, the preferred site for PKG, Ser-235. In ADP-activated platelets, phosphorylation by PKA or PKG/PRKG1 on Ser-153 leads to fibrinogen receptor inhibition. Phosphorylation on Thr-274 requires prior phosphorylation on Ser-153 and Ser-235. In response to phorbol ester (PMA) stimulation, phosphorylated by PKC/PRKCA. In response to thrombin, phosphorylated by both PKC and ROCK1. Phosphorylation at Thr- 274 by AMPK does not require prior phosphorylation at Ser-153 or Ser- 235. Phosphorylation at Ser-153 by PKA is required for localization to the tight junctions in epithelial cells. Phosphorylation modulates F- actin binding, actin filament elongation and platelet activation. Phosphorylation at Ser-318 by AMPK also alters actin filament binding. Carbon monoxide (CO) promotes phosphorylation at Ser-153, while nitric oxide (NO) promotes phosphorylation at Ser-153, but also at Ser-235. {ECO:0000269\|PubMed:10085070, ECO:0000269\|PubMed:10882740, ECO:0000269\|PubMed:12372613, ECO:0000269\|PubMed:21945940}.
Similarity:		Belongs to the Ena/VASP family. {ECO:0000305}.
Sequence caution:		Sequence=CAA67108.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};