RNF170

RNF170 is a multi-pass endoplasmic reticulum membrane RING-type E3 ubiquitin-protein ligase (EC 2.3.2.27, 258 aa) with three transmembrane helices and a large cytoplasmic loop carrying a C3HC4 RING domain (catalytic Cys-102/His-104). Its defining function is in ER-associated degradation (ERAD) of the inositol 1,4,5-trisphosphate receptor (ITPR1/IP3R): RNF170 is essential for stimulus-induced ubiquitination and degradation of activated ITPR1 and also contributes to ITPR1 turnover in resting cells, thereby controlling IP3R abundance and ER calcium-release signaling. To do this it is constitutively associated with the ERLIN1/ERLIN2 (SPFH-domain) complex, which recognizes activated IP3R and recruits RNF170 to ubiquitinate it. RNF170 also has a secondary, ligase-dependent immune-regulatory role: it binds Toll-like receptor 3 (TLR3) and builds K48-linked polyubiquitin chains on Lys-766 in the TLR3 TIR domain to drive its proteasomal degradation, selectively dampening TLR3-triggered innate immune responses. RNF170 is broadly expressed (including spinal cord); loss-of-function and RING-region missense variants cause autosomal dominant sensory ataxia (SNAX1) and autosomal recessive hereditary spastic paraplegia (SPG85), linking its ER ubiquitin-ligase activity to neuronal homeostasis. Its core localization and site of action is the ER membrane.

Disorders

Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.