RNF139

The protein encoded by this gene is a multi-membrane spanning protein containing a RING-H2 finger. This protein is located in the endoplasmic reticulum, and has been shown to possess ubiquitin ligase activity. This gene was found to be interrupted by a t(3:8) translocation in a family with hereditary renal and non-medulary thyroid cancer. Studies of the Drosophila counterpart suggested that this protein may interact with tumor suppressor protein VHL, as well as with COPS5/JAB1, a protein responsible for the degradation of tumor suppressor CDKN1B/P27KIP. [provided by RefSeq]

ring finger protein 139

E3-ubiquitin ligase; acts as a negative regulator of cell proliferation through mechanisms involving G2/M arrest and cell death (PubMed:10500182, PubMed:12032852, PubMed:17016439).
Required for MHC class I ubiquitination in cells expressing the cytomegalovirus protein US2 before dislocation from the endoplasmic reticulum (ER) (PubMed:19720873).
Affects SREBP processing by hindering the SREBP-SCAP complex translocation from the ER to the Golgi, thereby reducing SREBF2 target gene expression (PubMed:19706601, PubMed:20068067).
Involved in the sterol-accelerated degradation of HMGCR (PubMed:22143767, PubMed:23223569).
This is achieved through binding of RNF139 to INSIG1 and/or INSIG2 at the ER membrane (PubMed:22143767).
In addition, interaction of RNF139 with AUP1 facilitates interaction of RNF139 with ubiquitin-conjugating enzyme UBE2G2 and ubiquitin ligase AMFR, leading to ubiquitination of HMGCR (PubMed:23223569).
The ubiquitinated HMGCR is then released from the ER into the cytosol for subsequent destruction (PubMed:22143767, PubMed:23223569).
Required for INSIG1 ubiquitination (PubMed:20068067).
May be required for EIF3 complex ubiquitination (PubMed:20068067).

Biological Process endoplasmic reticulum mannose trimmingTAS:Reactome
Biological Process ERAD pathwayManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Biological Process negative regulation of cell population proliferationManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process negative regulation of translationManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process positive regulation of ubiquitin-dependent protein catabolic processManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process protein destabilizationManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process protein ubiquitinationManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process regulation of ER to Golgi vesicle-mediated transportManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process regulation of protein processingManual Assertion Based On ExperimentIDA:UniProtKB

Endoplasmic reticulum membrane

Renal cell carcinoma (RCC):
Renal cell carcinoma is a heterogeneous group of sporadic or hereditary carcinoma derived from cells of the proximal renal tubular epithelium. It is subclassified into clear cell renal carcinoma (non-papillary carcinoma), papillary renal cell carcinoma, chromophobe renal cell carcinoma, collecting duct carcinoma with medullary carcinoma of the kidney, and unclassified renal cell carcinoma. Clear cell renal cell carcinoma is the most common subtype.

Autoubiquitinated. Ubiquitination is induced by sterol and leads to ist degradation via the ubiquitin-proteasome pathway.