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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
General
cytoskeletal protein
phosphoprotein
Properties
SIZE: entity length = 730 aa
MW = 81 kD
COMPARTMENT: cytoplasm
MOTIF: proline-rich region
SITE: 60-106
MOTIF: proline residue (SEVERAL)
SH3-binding site
NAME: SH3-binding site
SITE: 71-74
SH2-binding 1 {94-97}
PH domain {153-249}
Ser phosphorylation site {S282}
Ser phosphorylation site {S336}
Thr phosphorylation site {T337}
Thr phosphorylation site {T341}
Ser phosphorylation site {S342}
Ser phosphorylation site {S343}
PH domain {347-441}
SH2-binding 2 {451-456}
coiled coil {557-648}
MOTIF: F-actin interaction {594-637}
Ser phosphorylation site {S665}
Ser phosphorylation site {S668}
Database Correlations
OMIM 608252
UniProt Q8N556
Pfam PF00169
Kegg hsa:6031
References
- UniProt :accession Q8N556
- Pawson T.
Protein modules and signalling networks.
Nature. 1995 Feb 16;373(6515):573-80. Review.
PMID: 7531822