Palladin (sarcoma antigen NY-SAR-77, SIH002, PALLD, KIAA0992, CGI-151)

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 Note: has been wrongly assigned as myoneurin

General

cytoskeletal protein phosphoprotein scaffold protein

Properties

SIZE: entity length = 1383 aa MW = 151 kD COMPARTMENT: synaptic membrane CELL: neuron MOTIF: immunoglobulin superfamily domain {271-360} MOTIF: cysteine residue {C292} MODIFICATION: cysteine residue {C344} cysteine residue {C344} MODIFICATION: cysteine residue {C292} Ser phosphorylation site {S401} immunoglobulin superfamily domain {440-539} MOTIF: cysteine residue {C462} MODIFICATION: cysteine residue {C521} cysteine residue {C521} MODIFICATION: cysteine residue {C462} VASP interaction {562-566} proline-rich region SITE: 563-567 MOTIF: proline residue (SEVERAL) membrane region proline-rich region SITE: 634-864 MOTIF: proline residue (SEVERAL) LASP1 interaction {646-676} ARGBP2/SPIN90/SRC interaction {676-696} EPS8 interaction {766-831} ARGBP2/SPIN90/SRC/PFN1 interaction {796-831} VASP interaction {819-823} ACTN interaction {833-890} MOTIF: Thr phosphorylation site {T877} Ser phosphorylation site {S893} Ser phosphorylation site {S979} Ser phosphorylation site {S984} immunoglobulin superfamily domain {1001-1085} Ser phosphorylation site {S1116} Ser phosphorylation site {S1118} Ser phosphorylation site {S1121} immunoglobulin superfamily domain {1135-1226} MOTIF: VIL2 interaction {1137-1226} cysteine residue {C1156} MODIFICATION: cysteine residue {C1208} cysteine residue {C1208} MODIFICATION: cysteine residue {C1156} immunoglobulin superfamily domain {1233-1324} VIL2 interaction {1236-1326} Ser phosphorylation site {S1333}

Database Correlations

OMIM correlations MORBIDMAP 608092 UniProt Q8WX93 Pfam PF07679

References

UniProt :accession Q8WX93