Table 1 Cellular functions associated with the ATPase VCP. Examples of cofactors that have been linked to specific cellular activities are listed. Components that are part of the UPS and autophagy network were collected from the BioGrid database [12]. Additional references are listed in the table. Most of the complex components interact with VCP directly. However, this has not always been established, and VCP association may be mediated by a protein that is part of a complex. Alternative protein identifiers used in original publications are shown in brackets
VCP-related functions | VCP complex component |
|---|---|
ERAD | UFD1–NPL4, UBXD8, ATXN3, GP78/AMFR, SVIP, VIMP (SELS, SELENOS), SELK, UBX2 (SEL1), HRD1 (SYVN1, DERL3), DERL2, DERL1, NGLY1, UBXN1 (SAKS1), UBXN4 (UBXD2, erasin), RNF103 (KF1), TRIM13 (RFP2), UBXN6 (UBXD1), RHBDL4, RNF19A (Dorfin) [27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44] |
Control of protein translocation into the ER | ZFAND2B (AIRAPL) [45] |
Ubiquitin–proteasome system (UPS) | p47 (NSFL1C), RNF45, UFD1, ATXN3, NPL4, FAF1, VIMP, DERL1, FAF20, SYVN1, UBXN1. UBE4B, UBXN7, SPRTN, VCPIP1, YOD1, PLAA, SIK2, SVIP, UBC, PARK2, RNF31, BAG6, BRCA1, FBXW1, COPS5, Cul1, DERL2, UBQLN1, ZFAND2B, ANKRD13A, UBQLN2, USP13 [12] |
General autophagy, mitophagy | UFD1–NPL4, PARK2, PINK1, MFN (mitofusin), OPTN (optineurin, FIP2), UBQLN2, USP13, UBXN1, WIPI2, WASHC4/SWIP [12, 46,47,48,49] |
Mitochondria-associated degradation (MAD); mitochondrial protein translocation associated degradation (mitoTAD) | UFD1-NPL4, PLAA (UFD3/DOA1), UBXD8 (FAF2), ANKZF1 (VMS1), UBXD1 (UBXN6) [50,51,52] |
Mitochondrial membrane fusion | MFN [50] |
Mitochondria-ER contacts | |
Protein trafficking; mitochondria → peroxisomes | MITOL (March5) [55] |
Ribosome QC, ribophagy, damaged rRNA recognition | ANKZF1 (VMS1), UFD1-NPL4, UFD3, ribosome quality control complex (yeast: Rqc1p-Rkr1p-Tae2p-Cdc48p-Npl4p-Ufd1p) [12, 27, 56,57,58] |
ER to Golgi trafficking; Golgi-ER membrane reassembly, ribosome-ER contacts | SVIP, p47 (NSFL1C), UFD1-NPL4, UBXN2B (p37), STX5A (syntaxin), VCIP135 [59,60,61,62,63] |
Lysosome function and clearance, endolysosomal protein sorting | |
Stress response, stress signaling, transcriptional stress | UFD1-NPL4, BAG1, MEST (mesoderm specific transcript), SMY2 (GIGYF1/2) [27, 67,68,69,70,71,72] |
Stress granule assembly | UFD1L, PLAA [73] |
Granulophagy | UBXD8 (UBX2), UFD1–NPL4 [27] |
Stress granule disassembly | |
Protein inclusions | |
Replication | |
Transcription | RHBDL4, GP78 [43] |
Accumulation of ubiquitinated proteins in nuclear blebs | UBXD1 (UBXN6) [81] |
DNA damage repair | UFD1-NPL4, DOA1, MRE11-RAD50-NBS1, TEX264 [80, 82,83,84,85,86] |
Dendritic spine formation | |
Lipid droplet formation and turnover | |
Regeneration of free monoubiquitin; ubiquitin homeostasis | UFD1-NPL4 [91] |
Ciliogenesis | UBXN10 (UBXD3) [11] |
Apoptosis | |
Anti-viral immune responses | UFD1-NPL4, RIG-1/DDX58 [92] |
Other processes |