Recombinant Human E3 ubiquitin-protein ligase synoviolin (SYVN1) Protein

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:27827840, 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)

Subcellular Location

Endoplasmic reticulum membrane (Multi-pass membrane protein)

Disease Association

[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]

Tissue Specificity

Ubiquitously expressed, with highest levels in liver and kidney (at protein level). Up-regulated in synovial tissues from patients with rheumatoid arthritis (at protein level)

Subunit

Homodimer (PubMed:16289116). Interacts with p53/TP53 (PubMed:17170702). Interacts with HTT (PubMed:17141218). Component of the HRD1 complex, which comprises at least SYNV1/HRD1, DERL1/2, FAM8A1, HERPUD1/HERP, OS9, SEL1L and UBE2J1 (PubMed:16186509, PubMed:16289116, PubMed:18264092, PubMed:26471130, PubMed:28827405, PubMed:37943610). FAM8A1 is stabilized by interaction with SYNV1, which prevents its proteasomal degradation. OS9 and UBE2J1 recruitment to the complex may be mediated by SEL1L (PubMed:28827405). SYNV1 assembles with SEL1L and FAM8A1 through its transmembrane domains, but interaction with its cytoplasmic domain is required to confer stability to FAM8A1 and enhance recruitment of HERPUD1 (PubMed:28827405). The HRD1 complex also associates with VIMP and may transfer misfolded proteins from the endoplasmic reticulum to VCP (PubMed:16289116). May form a complex with ERLEC1, HSPA5, OS9 and SEL1L (PubMed:18264092, PubMed:18502753). Interacts with VCP (PubMed:16186510, PubMed:16289116). Interacts with UBXN6 (PubMed:18656546). Interacts with BAG6 (PubMed:21636303). Interacts with NFE2L1 (By similarity). Interacts (via N-terminus) with components of the pre-B cell receptor, including IGLL1 and VPREB1 (By similarity). Interacts with CREB3L3; this interaction leads to CREB3L3 ubiquitination and proteasomal degradation (By similarity)

Pathway

Protein modification; protein ubiquitination

• Kaneko M. et al. Human HRD1 protects against ER stress-induced apoptosis through ER-associated degradation. — FEBS Lett. (2002)
• Nadav E. et al. A novel mammalian endoplasmic reticulum ubiquitin ligase homologous to the yeast Hrd1. — Biochem. Biophys. Res. Commun. (2003)
• Amano T. et al. Synoviolin/Hrd1, an E3 ubiquitin ligase, as a novel pathogenic factor for arthropathy. — Genes Dev. (2003)
• Kikkert M. et al. Human HRD1 is an E3 ubiquitin ligase involved in degradation of proteins from the endoplasmic reticulum. — J. Biol. Chem. (2004)
• Nagase T. et al. Prediction of the coding sequences of unidentified human genes. XX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. — DNA Res. (2001)
• Bechtel S. et al. The full-ORF clone resource of the German cDNA consortium. — BMC Genomics (2007)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Schulze A. et al. The ubiquitin-domain protein HERP forms a complex with components of the endoplasmic reticulum associated degradation pathway. — J. Mol. Biol. (2005)