protein enabled homolog (ENAH, MENA)

Function: - induces the formation of F-actin rich outgrowths in fibroblasts - acts syngeristically with BAIAP2alpha & downstream of NTN1 to promote filipodia formatio - required for actin-based mobility of Listeria monocytogenes - homotetramer - interacts with APBB1IP, PFN1 & 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 & WW3 domains of NEDD4 & to the WW1 domain of YAP1 - binds the SH3 domain of BAIAP2alpha but only after the autoinhibitory region of BAIAP2alpha has been blocked by interaction with CDC42 - interacts, via the EVH1/WH1 domain, with the Pro-rich domains from VCL, ZYX & Listeria monocytogenes actA - interaction with ZYX is important for targeting ENAH to focal adhesions & enhances production of actin-rich structures at the apical surface of cells - interacts, through the Pro-rich region, with the C-terminal SH3 domain of DNMPB - binds GPHN - NTN1-induced PKA phosphorylation on Ser-265 directly parallels formation of filopodial protrusions - phosphorylated upon DNA damage, probably by ATM or ATR Structure: - belongs to the Ena/VASP family - contains 1 WH1 domain - EVH2 domain is comprised of 3 regions a) 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 & for actin polymerization b) block B is required for F-actin binding & subcellular location c) block C: tetramerization Compartment: - cytoplasm, cytoskeleton - cell projection, lamellipodium, filopodium - cell junction, synapse - targeted to the leading edge of lamellipodia & filopodia by MRL family members - colocalizes at filopodial tips with a number of other proteins including vinculin & zyxlin - colocalizes with N-WASP at the leading edge - colocalizes with GPHN & PFN at synapses Alternative splicing: named isoforms=2 Expression: - expressed in myoepithelia of parotid, breast, bronchial glands & sweat glands - expressed in colon-rectum muscolaris mucosae epithelium, pancreas acinar ductal epithelium, endometrium epithelium, prostate fibromuscolar stroma & placenta vascular media Pathology: - overexpressed in a majority of breast cancer cell lines & primary breast tumor lesions

General

Ena/VASPfamily phosphoprotein

Properties

SIZE: MW = 67 kD entity length = 591 aa COMPARTMENT: cytoplasm MOTIF: WH1 {1-111} Ser phosphorylation site {S125} coiled coil {135-265} MOTIF: consensus repeat {156-160} SEQUENCE-IS: [LMQ]-E-[QR]- E-[QR] consensus repeat {161-165} SEQUENCE-IS: [LMQ]-E-[QR]- E-[QR] consensus repeat {166-170} SEQUENCE-IS: [LMQ]-E-[QR]- E-[QR] consensus repeat {171-175} SEQUENCE-IS: [LMQ]-E-[QR]- E-[QR] consensus repeat {176-180} SEQUENCE-IS: [LMQ]-E-[QR]- E-[QR] consensus repeat {181-185} SEQUENCE-IS: [LMQ]-E-[QR]- E-[QR] consensus repeat {186-190} SEQUENCE-IS: [LMQ]-E-[QR]- E-[QR] consensus repeat {191-195} SEQUENCE-IS: [LMQ]-E-[QR]- E-[QR] consensus repeat {196-200} SEQUENCE-IS: [LMQ]-E-[QR]- E-[QR] Ser phosphorylation site {S265} proline-rich region SITE: 310-373 MOTIF: proline residue (SEVERAL) EVH2 {391-588} MOTIF: EVH2 block A {391-411} KLKR {400-403} EVH2 block B {442-459} Thr phosphorylation site {T489} Ser phosphorylation site {S508} EVH2 block C {554-588} coiled coil {557-587}

Database Correlations

UniProt Q8N8S7 PFAM correlations

References

UniProt :accession Q8N8S7