UniProt functional annotation for Q03173



	UniProt functional annotation for Q03173

UniProt code: Q03173.

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 and lamellipodial and filopodial dynamics in migrating cells. ENAH induces the formation of F-actin rich outgrowths in fibroblasts. Acts synergistically with BAIAP2-alpha and downstream of NTN1 to promote filipodia formation. {ECO:0000269|PubMed:10069337, ECO:0000269|PubMed:12134088, ECO:0000269|PubMed:15066263, ECO:0000269|PubMed:8861907}.

Subunit: Homotetramer (By similarity). Interacts with APBB1IP, APBB1, PFN1 and ROBO4. Isoforms, containing the polyproline-rich regions with PPLP motifs, bind the WW domain of APBB1IP. Isoforms, containing the PPSY motif, bind, in vitro, to the WW2 and WW3 domains of NEDD4 and to the WW1 domain of YAP1. Binds the SH3 domain of BAIAP2-alpha but only after the autoinhibitory region of BAIAP2-alpha has been blocked by interaction with CDC42. Interacts, via the EVH1/WH1 domain, with the Pro-rich domains from VCL, ZYX and Listeria monocytogenes actA and with TES (via LIM domain). The TES LIM domain and the Pro-rich domains from VCL or ZYX compete for the same binding site. Interaction with ZYX is important for targeting ENAH to focal adhesions and enhances production of actin-rich structures at the apical surface of cells. Binds GPHN. Heterotrimer with TES and ACTL7A (By similarity). Interacts with FAT1 (via EVH1 domains) (PubMed:15148305). Interacts, through the Pro-rich region, with the C-terminal SH3 domain of DNMPB (PubMed:14506234) (Probable). Interacts with PRPF40A (PubMed:9171351). {ECO:0000250, ECO:0000269|PubMed:10338211, ECO:0000269|PubMed:12672821, ECO:0000269|PubMed:12941633, ECO:0000269|PubMed:14506234, ECO:0000269|PubMed:15148305, ECO:0000269|PubMed:15642358, ECO:0000269|PubMed:8861907, ECO:0000269|PubMed:9171351, ECO:0000269|PubMed:9407065, ECO:0000305|PubMed:24332715}.

Subcellular location: Cytoplasm {ECO:0000269|PubMed:10069337, ECO:0000269|PubMed:12134088, ECO:0000269|PubMed:8861907}. Cytoplasm, cytoskeleton {ECO:0000250}. Cell projection, lamellipodium {ECO:0000250}. Cell projection, filopodium {ECO:0000250}. Cell junction, synapse {ECO:0000250}. Cell junction, focal adhesion {ECO:0000250}. Note=Targeted to the leading edge of lamellipodia and filopodia by MRL family members. Colocalizes at filopodial tips with a number of other proteins including vinculin and zyxlin. Colocalizes with N-WASP at the leading edge. Colocalizes with GPHN and PFN at synapses (By similarity). {ECO:0000250}.

Tissue specificity: Expressed in heart and testis, lower levels in lung, skeletal muscle, kidney, pancreas and brain. Isoform 5 is expressed exclusively in the brain. Isoform 2 is expressed predominantly in brain, testis, ovary and fat. In the brain, isoforms 2 and 5 are expressed at highest levels in the hippocampus, cortex and midbrain, and at lowest levels in the striatum and cerebellum. Isoform 6 is expressed in brain and spleen. {ECO:0000269|PubMed:10069337, ECO:0000269|PubMed:1420303, ECO:0000269|PubMed:8861907}.

Developmental stage: At 8.5 dpc, particularly enriched in the neuroepithelium, the forebrain and the somites. Highly expressed in the edges of the neural folds. By 10.5 dpc, detected in the brain, dorsal root ganglia (DRG), somites and limb buds. Highly expressed in the branchial and pharyngeal arches, neural crest-derived structures that give rise to portions of the face and neck. At 11 dpc, isoform 2, isoform 3 and isoform 5 are expressed in embryonic brain (at protein level). Expression of isoform 3 decreases steadily and becomes almost undetectable by 16 dpc, while expression of isoform 5 begins to increase from 13 dpc and peaks between 16 and 18 dpc (at protein level). {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.

Ptm: NTN1-induced PKA phosphorylation on Ser-255 directly parallels the formation of filopodial protrusions. {ECO:0000269|PubMed:12672821, ECO:0000269|PubMed:15066263}.

Disruption phenotype: Mutant animals are viable and recovered in the appropriate Mendelian ratios. they are smaller than their littermates until adulthood and exhibit abnormal cage behavior, including reduced activity. {ECO:0000269|PubMed:10069337}.

Miscellaneous: Required to transform actin polymerization into active movement for the propulsive force of Listeria monocytogenes.

Miscellaneous: [Isoform 3]: Phosphorylated during neural development. {ECO:0000305}.

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

Sequence caution: Sequence=BAA01570.1; Type=Frameshift; Evidence={ECO:0000305};

Sequence caution: [Isoform 1]: Sequence=BAA01570.1; Type=Frameshift; 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 and lamellipodial and filopodial dynamics in migrating cells. ENAH induces the formation of F-actin rich outgrowths in fibroblasts. Acts synergistically with BAIAP2-alpha and downstream of NTN1 to promote filipodia formation. {ECO:0000269\|PubMed:10069337, ECO:0000269\|PubMed:12134088, ECO:0000269\|PubMed:15066263, ECO:0000269\|PubMed:8861907}.


Subunit:		Homotetramer (By similarity). Interacts with APBB1IP, APBB1, PFN1 and ROBO4. Isoforms, containing the polyproline-rich regions with PPLP motifs, bind the WW domain of APBB1IP. Isoforms, containing the PPSY motif, bind, in vitro, to the WW2 and WW3 domains of NEDD4 and to the WW1 domain of YAP1. Binds the SH3 domain of BAIAP2-alpha but only after the autoinhibitory region of BAIAP2-alpha has been blocked by interaction with CDC42. Interacts, via the EVH1/WH1 domain, with the Pro-rich domains from VCL, ZYX and Listeria monocytogenes actA and with TES (via LIM domain). The TES LIM domain and the Pro-rich domains from VCL or ZYX compete for the same binding site. Interaction with ZYX is important for targeting ENAH to focal adhesions and enhances production of actin-rich structures at the apical surface of cells. Binds GPHN. Heterotrimer with TES and ACTL7A (By similarity). Interacts with FAT1 (via EVH1 domains) (PubMed:15148305). Interacts, through the Pro-rich region, with the C-terminal SH3 domain of DNMPB (PubMed:14506234) (Probable). Interacts with PRPF40A (PubMed:9171351). {ECO:0000250, ECO:0000269\|PubMed:10338211, ECO:0000269\|PubMed:12672821, ECO:0000269\|PubMed:12941633, ECO:0000269\|PubMed:14506234, ECO:0000269\|PubMed:15148305, ECO:0000269\|PubMed:15642358, ECO:0000269\|PubMed:8861907, ECO:0000269\|PubMed:9171351, ECO:0000269\|PubMed:9407065, ECO:0000305\|PubMed:24332715}.
Subcellular location:		Cytoplasm {ECO:0000269\|PubMed:10069337, ECO:0000269\|PubMed:12134088, ECO:0000269\|PubMed:8861907}. Cytoplasm, cytoskeleton {ECO:0000250}. Cell projection, lamellipodium {ECO:0000250}. Cell projection, filopodium {ECO:0000250}. Cell junction, synapse {ECO:0000250}. Cell junction, focal adhesion {ECO:0000250}. Note=Targeted to the leading edge of lamellipodia and filopodia by MRL family members. Colocalizes at filopodial tips with a number of other proteins including vinculin and zyxlin. Colocalizes with N-WASP at the leading edge. Colocalizes with GPHN and PFN at synapses (By similarity). {ECO:0000250}.
Tissue specificity:		Expressed in heart and testis, lower levels in lung, skeletal muscle, kidney, pancreas and brain. Isoform 5 is expressed exclusively in the brain. Isoform 2 is expressed predominantly in brain, testis, ovary and fat. In the brain, isoforms 2 and 5 are expressed at highest levels in the hippocampus, cortex and midbrain, and at lowest levels in the striatum and cerebellum. Isoform 6 is expressed in brain and spleen. {ECO:0000269\|PubMed:10069337, ECO:0000269\|PubMed:1420303, ECO:0000269\|PubMed:8861907}.
Developmental stage:		At 8.5 dpc, particularly enriched in the neuroepithelium, the forebrain and the somites. Highly expressed in the edges of the neural folds. By 10.5 dpc, detected in the brain, dorsal root ganglia (DRG), somites and limb buds. Highly expressed in the branchial and pharyngeal arches, neural crest-derived structures that give rise to portions of the face and neck. At 11 dpc, isoform 2, isoform 3 and isoform 5 are expressed in embryonic brain (at protein level). Expression of isoform 3 decreases steadily and becomes almost undetectable by 16 dpc, while expression of isoform 5 begins to increase from 13 dpc and peaks between 16 and 18 dpc (at protein level). {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.
Ptm:		NTN1-induced PKA phosphorylation on Ser-255 directly parallels the formation of filopodial protrusions. {ECO:0000269\|PubMed:12672821, ECO:0000269\|PubMed:15066263}.
Disruption phenotype:		Mutant animals are viable and recovered in the appropriate Mendelian ratios. they are smaller than their littermates until adulthood and exhibit abnormal cage behavior, including reduced activity. {ECO:0000269\|PubMed:10069337}.
Miscellaneous:		Required to transform actin polymerization into active movement for the propulsive force of Listeria monocytogenes.
Miscellaneous:		[Isoform 3]: Phosphorylated during neural development. {ECO:0000305}.
Similarity:		Belongs to the Ena/VASP family. {ECO:0000305}.
Sequence caution:		Sequence=BAA01570.1; Type=Frameshift; Evidence={ECO:0000305};
Sequence caution:		[Isoform 1]: Sequence=BAA01570.1; Type=Frameshift; Evidence={ECO:0000305};