EPB49 (DMTN) Antibody – Mouse Polyclonal

Dematin, or EPB49, is an actin-bundling protein originally identified in the erythroid membrane skeleton. Its actin-bundling activity is abolished upon phosphorylation by cAMP-dependent protein kinase and is restored after dephosphorylation (Rana et al., 1993 [PubMed 8341682]).[supplied by OMIM, Apr 2009]

Function: Membrane-cytoskeleton-associated protein with F-actin-binding activity that induces F-actin bundles formation and stabilization. Its F-actin-bundling activity is reversibly regulated upon its phosphorylation by the cAMP-dependent protein kinase A (PKA). Binds to the erythrocyte membrane glucose transporter-1 SLC2A1/GLUT1, and hence stabilizes and attaches the spectrin-actin network to the erythrocytic plasma membrane. Plays a role in maintaining the functional integrity of PKA-activated erythrocyte shape and the membrane mechanical properties. Plays also a role as a modulator of actin dynamics in fibroblasts; acts as a negative regulator of the RhoA activation pathway. In platelets, functions as a regulator of internal calcium mobilization across the dense tubular system that affects platelet granule secretion pathways and aggregation. Also required for the formation of a diverse set of cell protrusions, such as filopodia and lamellipodia, necessary for platelet cell spreading, motility and migration. Acts as a tumor suppressor and inhibits malignant cell transformation. Ref.7 Ref.8 Ref.9 Ref.13 Ref.17 Ref.19

Subunit structure: Monomeric (isoform 2); under reducing conditions. Self-associates. Exists under oxidizing condition as a trimer of two isoforms 2 and isoform 1 linked by disulfide bonds

Probable. Found in a complex with DMTN, F-actin and spectrin. Found in a complex with ADD2, DMTN and SLC2A1. Interacts with F-actin, ITPKB, RASGRF2 and spectrin. Isoform 2 interacts with SLC2A1 (via C-terminus cytoplasmic region). Isoform 1 and isoform 2 interact (phosphorylated form) with plasmodium berghei 14-3-3 protein; the interaction occurs in a PKA-dependent manner. Ref.2 Ref.8 Ref.9 Ref.13 Ref.16 Ref.17 Ref.18 Ref.19

Subcellular location: Cytoplasm. Cytoplasm › cytosol. Cytoplasm › perinuclear region

By similarity. Cytoplasm › cytoskeleton. Cell membrane. Membrane

By similarity. Endomembrane system. Cell projection

By similarity. Note: Localized at the spectrin-actin junction of erythrocyte plasma membrane. Localized to intracellular membranes and the cytoskeletal network. Localized at intracellular membrane-bounded organelle compartment in platelets that likely represent the dense tubular network membrane. Detected at the cell membrane and at the parasitophorous vacuol in malaria-infected erythrocytes at late stages of plasmodium berghei or falciparum development. Ref.8 Ref.16 Ref.18

Tissue specificity: Expressed in platelets (at protein level). Expressed in heart, brain, lung, skeletal muscle, and kidney. Ref.18

Domain: Both the N-terminal core domain and the C-terminal headpiece domain are sufficient for binding to F-actin and necessary for actin bundling activity.

Post-translational modification: Phosphorylated. Phosphorylation at Ser-403 by PKA causes the C-terminal headpiece domain to associate with the N-terminal core domain, and leads to the inhibition of its actin bundling activity. Ref.2 Ref.17 Ref.19 Ref.21The N-terminus is blocked.

Sequence similarities: Belongs to the villin/gelsolin family.Contains 1 HP (headpiece) domain.