dematin; dematin actin-binding protein; erythrocyte membrane protein band 4.9 (DMTN, EPB49. DMT)
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Function
- actin-bundling protein
- may function in mitogen-activated protein kinase pathway
- actin-bundling activity is abolished by phosphorylation by cAMP-dependent protein kinase
- exists in solution as a trimer of two short isoforms & one long isoform linked by disulfide bonds (probable)
- interacts with RASGRF2
- binds to the erythrocyte membrane glucose transporter-1 SLC2A1/GLUT1, & hence stabilizes & attaches the spectrin-actin network to the erythrocytic plasma membrane.
- role in maintaining the functional integrity of PKA-activated erythrocyte shape & the membrane mechanical properties
- role as a modulator of actin dynamics in fibroblasts
- negative regulator of the RhoA activation pathway
- in platelets, functions as a regulator of internal Ca+2 mobilization across the dense tubular system that affects platelet granule secretion pathways & aggregation
- also required for formation of cell protrusions, such as filopodia & lamellipodia, necessary for platelet cell spreading, motility & migration
- acts as a tumor suppressor & inhibits malignant cell transformation
- phosphorylation at Ser-403 by PKA causes the C-terminal headpiece domain to associate with the N-terminal core domain, & leads to the inhibition of its actin bundling activity
- exists under oxidizing condition as a trimer of two isoforms 2 & isoform 1 linked by disulfide bonds (probable)
- found in a complex with DMTN, F-actin & spectrin
- found in a complex with ADD2, DMTN & SLC2A1
- interacts with F-actin, ITPKB, RASGRF2 & spectrin
- isoform 2 interacts with SLC2A1 (via C-terminus cytoplasmic region)
- isoform 1 & isoform 2 interact (phosphorylated form) with Plasmodium berghei 14-3-3 protein
- interaction occurs in a PKA-dependent manner
Structure
- N-terminus is blocked
- contains at least two actin-binding sites, one in the headpiece domain & one in the amino-terminal portion
- consists of a large core fragment, the amino-terminal portion, & a small headpiece, the C-terminal portion
- the headpiece can bind but cannot bundle actin filaments
- belongs to the villin/gelsolin family
- contains 1 HP domain (headpiece)
Compartment
- cytoplasm, cytoskeleton, perinuclear region
- endomembrane system
- cell projection
- localized at the spectrin-actin junction of erythrocyte plasma membrane
- localized to intracellular membranes & 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 & at the parasitophorous vacuol in malaria- infected erythrocytes at late stages of Plasmodium berghei or Plasmodium falciparum development
Alternative splicing
named isoforms=3; long, short
Expression
- expressed in platelets (at protein level)
- expressed in heart, brain, lung, skeletal muscle, & kidney