protein enabled homolog (ENAH, MENA)

^[1]

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

belongs to the Ena/VASP family
contains 1 WH1 domain
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 & for actin polymerization
- block B is required for F-actin binding & subcellular location
- block C: tetramerization

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

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

overexpressed in a majority of breast cancer cell lines & primary breast tumor lesions