Palladin (sarcoma antigen NY-SAR-77, SIH002, PALLD, KIAA0992, CGI-151)
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Function
- cytoskeletal protein required for organization of normal actin cytoskeleton
- roles in establishing cell morphology, motility, cell adhesion & cell-extracellular matrix interactions in a variety of cell types
- may function as a scaffolding molecule with the potential to influence both actin polymerization & the assembly of existing actin filaments into higher-order arrays
- binds to proteins that bind to either monomeric or filamentous actin
- localizes at sites where active actin remodeling takes place, such as lamellipodia & membrane ruffles
- different isoforms may have functional differences
- involved in the control of morphological & cytoskeletal changes associated with dendritic cell maturation
- involved in targeting ACTN to specific subcellular foci
- interacts with EPS8, LASP1 & VASP (putative)
- interacts with ACTN, ARGBP2, LPP, PFN1, SPIN90, SRC & VIL2
- phosphorylated predominantly on Ser &, to a lesser extent, on Tyr (putative)
- hosphorylated upon DNA damage, probably by ATM or ATR
Structure
- belongs to the myotilin/palladin family
- contains 5 Ig-like C2-type domain (immunoglobulin-like)
Compartment
- cytoplasm, cytoskeleton
- localizes to stress fibers & Z-disks
- cell junction, focal adhesion
- cell projection, ruffle, lamellipodium
Alternative splicing
named isoforms=7
Expression
- detected in both muscle & non-muscle tissues
- high expression in prostate, ovary, colon, & kidney
- not detected in spleen, skeletal muscle, lung & peripheral blood lymphocytes (at protein level)
- isoform 3 is expressed de novo
- isoform 4 is up- regulated by TGFB1 during myofibroblast differentiation
Pathology
- genetic variations in PALLD are associated with susceptibility to pancreatic cancer type 1 expression is increased early in the development of pancreatic cancer, in normal-appearing whole tissue immediately adjacent to cancer, in the pre-cancer, & in both the familial & sporadic forms of the cancer overexpressed in FA6, HPAF, IMIMPC2, SUIT2 & PATU2 sporadic pancreatic cancer cell lines
- genetic variations in PALLD may be associated with myocardial infarction
Notes
has been wrongly assigned as myoneurin