actin filament-associated protein 1; 110 kD actin filament-associated protein (AFAP-110, AFAP1, AFAP)

Function

• can cross-link actin filaments into both network & bundle structures (putative)
• may modulate changes in actin filament integrity & induce lamellipodia formation
• may function as an adapter molecule that links other proteins, such as SRC & PKC to the actin cytoskeleton
• phosphorylated on Tyr by SRC
• interacts with SRC via pTyr-SH2 & Pro rich-SH3
• may target SRC to actin stress fibers
• knockdown in MDA-MB-231 cells results in loss of actin stress fibers, decreased adhesion & spreading on fibronectin

Structure

• monomer & homomultimer
• interacts via its C-terminus with F-actin, probably involving AFAP1 multimers (putative)
• interacts with activated SRC SH3-SH2 domains
• interacts via first PH domain with PRKCA, PRKCB & PRKCI (putative)
• contains 2 PH domains

Compartment

• cytoplasm, cytoskeleton
• localizes with stress fibers in quiescent cells
• concentrated in cell motility structures such as lamellipodia, filopodia & membrane ruffles upon their induction

Expression

• low expression in normal breast epithelial cell line MCF-10A & in tumorigenic breast cancer cell lines MCF- 7, T-47D, & ZR75-1

Pathology

• highly expressed in the invasive breast cancer cell lines MDA-MB-231 & MDA-MB-435
• overexpressed in prostate carcinoma, expression levels positively correlate with aggressiveness of the disease
• seems to play a role in the development & progression of prostate adenocarcinoma by regulating cell-matrix adhesions & migration in the cancer cells

More general terms

• phosphoprotein
• cytoskeletal protein

Database

• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:6031
• OMIM: https://mirror.omim.org/entry/608252
• UniProt: http://www.uniprot.org/uniprot/Q8N556.html