InterPro domain: IPR033294

This entry includes Erlin1/2 (also known as SPFH1/2) from animals and their homologues from plants. Mammalian Erlin1 and Erlin2 form a complex that mediates the endoplasmic reticulum-associated degradation (ERAD) of inositol 1,4,5-trisphosphate receptors (IP3Rs) such as ITPR1 [ 1 , 2 , 3 ]. The Erlin1/2 complex may recruit RNF170 (an E3 ubiquitin-protein ligase) to activated IP(3) receptors where it mediates IP(3) receptor ubiquitination [ 4 ].

Interestingly, C. elegans erlin homologue, ERL-1, does not play an essential role in the endoplasmic reticulum-associated degradation (ERAD) of inositol 1,4,5-triphosphate receptors (IP3Rs) [ 5 ].

1. An endoplasmic reticulum (ER) membrane complex composed of SPFH1 and SPFH2 mediates the ER-associated degradation of inositol 1,4,5-trisphosphate receptors. J. Biol. Chem. 284, 10433-45
2. SPFH2 mediates the endoplasmic reticulum-associated degradation of inositol 1,4,5-trisphosphate receptors and other substrates in mammalian cells. J. Biol. Chem. 282, 20104-15
3. SPFH1 and SPFH2 mediate the ubiquitination and degradation of inositol 1,4,5-trisphosphate receptors in muscarinic receptor-expressing HeLa cells. Biochim. Biophys. Acta 1793, 1710-8
4. RNF170 protein, an endoplasmic reticulum membrane ubiquitin ligase, mediates inositol 1,4,5-trisphosphate receptor ubiquitination and degradation. J. Biol. Chem. 286, 24426-33
5. Characterization of the C. elegans erlin homologue. BMC Cell Biol. 13, 2