UniProt functional annotation for P02640



	UniProt functional annotation for P02640

UniProt code: P02640.

Organism: Gallus gallus (Chicken).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda; Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae; Phasianinae; Gallus.

Function: Epithelial cell-specific Ca(2+)-regulated actin-modifying protein that modulates the reorganization of microvillar actin filaments. Plays a role in the actin nucleation, actin filament bundle assembly, actin filament capping and severing. Binds phosphatidylinositol 4,5-bisphosphate (PIP2) and lysophosphatidic acid (LPA); binds LPA with higher affinity than PIP2. Binding to LPA increases its phosphorylation by SRC and inhibits all actin-modifying activities. Binding to PIP2 inhibits actin-capping and -severing activities but enhances actin-bundling activity. Regulates the intestinal epithelial cell morphology, cell invasion, cell migration and apoptosis. Protects against apoptosis induced by dextran sodium sulfate (DSS) in the gastrointestinal epithelium. Appears to regulate cell death by maintaining mitochondrial integrity. Enhances hepatocyte growth factor (HGF)-induced epithelial cell motility, chemotaxis and wound repair (By similarity). Its actin-bundling activity is inhibited by tropomyosin. {ECO:0000250, ECO:0000269|PubMed:1618806, ECO:0000269|PubMed:3793760}.

Subunit: Monomer. Homodimer (By similarity). Associates with F-actin; the association with F-actin is inhibited by tropomyosin. {ECO:0000250}.

Subcellular location: Cytoplasm, cytoskeleton {ECO:0000269|PubMed:3793760}. Cell projection, microvillus {ECO:0000269|PubMed:3793760}. Cell projection, lamellipodium {ECO:0000250}. Cell projection, ruffle {ECO:0000250}. Cell projection, filopodium tip {ECO:0000250}. Cell projection, filopodium {ECO:0000250}.

Tissue specificity: Specifically expressed in epithelial cells. Component of brush border microvilli. {ECO:0000269|PubMed:3793760}.

Domain: Consists of a large core fragment in the N-terminal portion and a small headpiece (HP) in the C-terminal portion. The core fragment is necessary for both actin-nucleating and -severing activities, whereas the HP binds F-actin strongly in both the presence and absence of calcium and is necessary in actin-bundling activity. The Gelsolin-like 1 repeat is necessary for the actin-capping activity. The entire core fragment is necessary for the actin-severing activity (By similarity). {ECO:0000250}.

Ptm: Phosphorylated on tyrosine residues. The unphosphorylated form increases the initial rate of actin-nucleating activity, whereas the tyrosine-phosphorylated form inhibits actin-nucleating activity, enhances actin-bundling activity and enhances actin-severing activity by reducing high Ca(2+) requirements. The tyrosine-phosphorylated form does not regulate actin-capping activity. Tyrosine phosphorylation is essential for cell migration: tyrosine phosphorylation sites in the N- terminus half regulate actin reorganization and cell morphology, whereas tyrosine phosphorylation sites in the C-terminus half regulate cell migration. Tyrosine phosphorylation is induced by epidermal growth factor (EGF) and stimulates cell migration (By similarity). {ECO:0000250}.

Similarity: Belongs to the villin/gelsolin family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Gallus gallus (Chicken).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda; Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae; Phasianinae; Gallus.



Function:		Epithelial cell-specific Ca(2+)-regulated actin-modifying protein that modulates the reorganization of microvillar actin filaments. Plays a role in the actin nucleation, actin filament bundle assembly, actin filament capping and severing. Binds phosphatidylinositol 4,5-bisphosphate (PIP2) and lysophosphatidic acid (LPA); binds LPA with higher affinity than PIP2. Binding to LPA increases its phosphorylation by SRC and inhibits all actin-modifying activities. Binding to PIP2 inhibits actin-capping and -severing activities but enhances actin-bundling activity. Regulates the intestinal epithelial cell morphology, cell invasion, cell migration and apoptosis. Protects against apoptosis induced by dextran sodium sulfate (DSS) in the gastrointestinal epithelium. Appears to regulate cell death by maintaining mitochondrial integrity. Enhances hepatocyte growth factor (HGF)-induced epithelial cell motility, chemotaxis and wound repair (By similarity). Its actin-bundling activity is inhibited by tropomyosin. {ECO:0000250, ECO:0000269\|PubMed:1618806, ECO:0000269\|PubMed:3793760}.


Subunit:		Monomer. Homodimer (By similarity). Associates with F-actin; the association with F-actin is inhibited by tropomyosin. {ECO:0000250}.
Subcellular location:		Cytoplasm, cytoskeleton {ECO:0000269\|PubMed:3793760}. Cell projection, microvillus {ECO:0000269\|PubMed:3793760}. Cell projection, lamellipodium {ECO:0000250}. Cell projection, ruffle {ECO:0000250}. Cell projection, filopodium tip {ECO:0000250}. Cell projection, filopodium {ECO:0000250}.
Tissue specificity:		Specifically expressed in epithelial cells. Component of brush border microvilli. {ECO:0000269\|PubMed:3793760}.
Domain:		Consists of a large core fragment in the N-terminal portion and a small headpiece (HP) in the C-terminal portion. The core fragment is necessary for both actin-nucleating and -severing activities, whereas the HP binds F-actin strongly in both the presence and absence of calcium and is necessary in actin-bundling activity. The Gelsolin-like 1 repeat is necessary for the actin-capping activity. The entire core fragment is necessary for the actin-severing activity (By similarity). {ECO:0000250}.
Ptm:		Phosphorylated on tyrosine residues. The unphosphorylated form increases the initial rate of actin-nucleating activity, whereas the tyrosine-phosphorylated form inhibits actin-nucleating activity, enhances actin-bundling activity and enhances actin-severing activity by reducing high Ca(2+) requirements. The tyrosine-phosphorylated form does not regulate actin-capping activity. Tyrosine phosphorylation is essential for cell migration: tyrosine phosphorylation sites in the N- terminus half regulate actin reorganization and cell morphology, whereas tyrosine phosphorylation sites in the C-terminus half regulate cell migration. Tyrosine phosphorylation is induced by epidermal growth factor (EGF) and stimulates cell migration (By similarity). {ECO:0000250}.
Similarity:		Belongs to the villin/gelsolin family. {ECO:0000305}.