SYVN1

This gene encodes a protein involved in endoplasmic reticulum (ER)-associated degradation. The encoded protein removes unfolded proteins, accumulated during ER stress, by retrograde transport to the cytosol from the ER. This protein also uses the ubiquitin-proteasome system for additional degradation of unfolded proteins. Sequence analysis identified two transcript variants that encode different isoforms.

Full Name

Synoviolin 1

Function

E3 ubiquitin-protein ligase which accepts ubiquitin specifically from endoplasmic reticulum-associated UBC7 E2 ligase and transfers it to substrates, promoting their degradation (PubMed:12459480, PubMed:12646171, PubMed:12975321, PubMed:14593114, PubMed:16289116, PubMed:16847254, PubMed:17059562, PubMed:17141218, PubMed:17170702, PubMed:22607976, PubMed:26471130, PubMed:28827405).
Component of the endoplasmic reticulum quality control (ERQC) system also called ER-associated degradation (ERAD) involved in ubiquitin-dependent degradation of misfolded endoplasmic reticulum proteins (PubMed:12459480, PubMed:12646171, PubMed:12975321, PubMed:14593114, PubMed:16289116, PubMed:16847254, PubMed:17059562, PubMed:17141218, PubMed:17170702, PubMed:22607976, PubMed:26471130, PubMed:28842558).
Also promotes the degradation of normal but naturally short-lived proteins such as SGK. Protects cells from ER stress-induced apoptosis. Protects neurons from apoptosis induced by polyglutamine-expanded huntingtin (HTT) or unfolded GPR37 by promoting their degradation (PubMed:17141218).
Sequesters p53/TP53 in the cytoplasm and promotes its degradation, thereby negatively regulating its biological function in transcription, cell cycle regulation and apoptosis (PubMed:17170702).
Mediates the ubiquitination and subsequent degradation of cytoplasmic NFE2L1 (By similarity).
During the early stage of B cell development, required for degradation of the pre-B cell receptor (pre-BCR) complex, hence supporting further differentiation into mature B cells (By similarity).

Biological Process

Biological Process endoplasmic reticulum mannose trimmingTAS:Reactome
Biological Process ERAD pathwayIDA:ParkinsonsUK-UCL1 Publication
Biological Process immature B cell differentiationISS:UniProtKB
Biological Process negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathwayIDA:ParkinsonsUK-UCL2 Publications
Biological Process protein K48-linked ubiquitinationIDA:ParkinsonsUK-UCL1 Publication
Biological Process protein stabilizationIMP:ParkinsonsUK-UCL1 Publication
Biological Process protein ubiquitinationIDA:ParkinsonsUK-UCL2 Publications
Biological Process retrograde protein transport, ER to cytosolIMP:ParkinsonsUK-UCL1 Publication
Biological Process ubiquitin-dependent ERAD pathwayIDA:UniProtKB1 Publication
Biological Process ubiquitin-dependent protein catabolic processIDA:ParkinsonsUK-UCL2 Publications

Cellular Location

Endoplasmic reticulum membrane

Involvement in disease

In certain aggressive cases of activated B cell-like diffuse large B-cell lymphoma (ABC-DLBCL), plays a role in the degradation of misfolded N-terminal mutated PRDM1 proteins.

Topology

Cytoplasmic: 1-4
Helical: 5-25
Lumenal: 26-41
Helical: 42-62
Cytoplasmic: 63-98
Helical: 99-119
Lumenal: 120-140
Helical: 141-161
Cytoplasmic: 162-169
Helical: 170-190
Lumenal: 191-224
Helical: 225-245
Cytoplasmic: 246-617

PTM

Not N-glycosylated.
Auto-ubiquitinated.