DWORF of 34 aas and 1 TMS (Nelson et al. 2016). Counteracts the inhibitory effects of single transmembrane peptides, phospholamban (TC# 1.A.50.1), sarcolipin (1.A.50.2) and myoregulin (1.A.50.3), on SERCA (TC# 3.A.3.2). DWORF also activates SERCA in the absence of PLM (Li et al. 2021). Homology with the inhibitory peptides has been established for these peptides, all of which have about the same size with a single C-terminal TMS (D. Tyler & M. Saier, unpublished results). These single-pass membrane proteins are called regulins. Unlike other regulins, dwarf open reading frame (DWORF) expressed in cardiac muscle has a unique activating effect. Reddy et al. 2021 determined the structure and topology of DWORF in lipid bilayers using a combination of oriented sample solid-state NMR spectroscopy and replica-averaged orientationally restrained molecular dynamics. They found that DWORF's structural topology consists of a dynamic N-terminal domain, an amphipathic juxtamembrane helix that crosses the lipid groups at an angle of 64 degrees , and a transmembrane C-terminal helix with an angle of 32 degrees. A kink induced by Pro15, unique to DWORF, separates the two helical domains. A single Pro15Ala mutant significantly decreases the kink and eliminates DWORF's activating effect on SERCA.
|Protein Name:||Sarcoplasmic/endoplasmic reticulum calcium ATPase regulator DWORF|
|Species:||Homo sapiens (Human)  |
|Number of TMSs:||1|
|Location1 / Topology2 / Orientation3:
Sarcoplasmic reticulum membrane1 / Single-pass membrane protein2
1: MAEKAGSTFS HLLVPILLLI GWIVGCIIMI YVVFS