pfam12595: iRhom1-2_N (This model is not part of the current CDD release)
Inactive rhomboid proteins 1/2, N-terminal
This entry includes inactive rhomboid proteins (iRhom1/2), which are catalytically inactive rhomboid protease homologues that play crucial roles within the secretory pathway, including protein degradation, trafficking regulation, and inflammatory signaling. These are metazoan specific pseudoproteases which regulate ADAM17 protease, a sheddase of the epidermal growth factor (EGF) receptor ligands and TNF, acting as trafficking factors that escort ADAM17 from the ER to the later secretory pathway. They are required for the cleavage and release of a variety of membrane-associated proteins. iRhoms share a common structure comprising 7-helix transmembrane-spanning domains (TMDs) which is a conserved rhomboid fold (pfam01694), an extended N-terminal cytosolic domain and a luminal loop. These proteins have been linked to the development and progression of several autoimmune diseases including rheumatoid arthritis, lupus nephritis, as well as as hemophilic arthropathy and also in neurological disorders such a Alzheimer's and Parkinson's diseases, inflammation, cancer and skin diseases. This entry represents an N-terminal helical segment of iRhom 1/2.
Jiyao W et al.(2023). "The conserved domain database in 2023.",