RNF139 (translocation in renal carcinoma, chromosome 8 gene)

2004-06-01   Anita Bonné , Eric Schoenmakers , Ad Geurts van Kessel 

Department of Human Genetics (417), P.O. Box 9101, 6500 HB Nijmegen, The Netherlands

Identity

HGNC
LOCATION
8q24.13
LOCUSID
ALIAS
HRCA1,RCA1,TRC8
FUSION GENES

DNA/RNA

Description

The TRC8 gene covers 13.96 kb. The gene contains 2 confirmed introns, 2 of which are alternative. The gene showed similarity to the hereditary basal cell carcinoma/segment polarity gene, patched (PTCH) This similarity involved 2 regions of patched, the putative sterol-sensing domain and the second extracellular loop that participates in the binding of sonic hedgehog (SHH). In the t(3;8) translocation, TRC8 was found to be fused to FHIT and disrupted within the sterol-sensing domain. In contrast, the FHIT coding region was maintained and expressed. In a series of sporadic renal carcinomas, an acquired TRC8 mutation was identified. By analogy to patched, TRC8 might function as a signaling receptor, and other pathway members, to be defined, are mutation candidates in malignant diseases involving the kidney and thyroid.

Proteins

Localisation

Plasma membrane

Function

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

Implicated in

Entity name
t(3;8)(p14.2;q24.1) and hereditary renal cell cancer.
Disease
familial renal cell cancer
Cytogenetics
Disruption of the gene because of the t(3;8) translocation.
Hybrid gene
FHIT/TRC8. Although studies demonstrated that the 3p14.2 breakpoint interrupted the fragile histidine triad gene (FHIT) in its 5-prime noncoding region, several reasons made it unlikely that FHIT is causally related to renal or other malignancies.

Bibliography

Pubmed IDLast YearTitleAuthors
117557782002Sonic Hedgehog signalling in the developing and adult brain.Charytoniuk D et al
4709811979Hereditary renal-cell carcinoma associated with a chromosomal translocation.Cohen AJ et al
96891221998The hereditary renal cell carcinoma 3;8 translocation fuses FHIT to a patched-related gene, TRC8.Gemmill RM et al
105001821999RING fingers mediate ubiquitin-conjugating enzyme (E2)-dependent ubiquitination.Lorick KL et al

Other Information

Locus ID:

NCBI: 11236
MIM: 603046
HGNC: 17023
Ensembl: ENSG00000170881

Variants:

dbSNP: 11236
ClinVar: 11236
TCGA: ENSG00000170881
COSMIC: RNF139

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000170881ENST00000303545Q8WU17
ENSG00000170881ENST00000517684E5RH85

Expression (GTEx)

0
50
100
150

Pathways

PathwaySourceExternal ID
Metabolism of proteinsREACTOMER-HSA-392499
Post-translational protein modificationREACTOMER-HSA-597592
Asparagine N-linked glycosylationREACTOMER-HSA-446203
N-glycan trimming in the ER and Calnexin/Calreticulin cycleREACTOMER-HSA-532668
Calnexin/calreticulin cycleREACTOMER-HSA-901042
ER Quality Control Compartment (ERQC)REACTOMER-HSA-901032

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
197208732009The TRC8 E3 ligase ubiquitinates MHC class I molecules before dislocation from the ER.61
200680672010The TRC8 ubiquitin ligase is sterol regulated and interacts with lipid and protein biosynthetic pathways.30
197066012009The sterol-sensing endoplasmic reticulum (ER) membrane protein TRC8 hampers ER to Golgi transport of sterol regulatory element-binding protein-2 (SREBP-2)/SREBP cleavage-activated protein and reduces SREBP-2 cleavage.20
170164392007RING-dependent tumor suppression and G2/M arrest induced by the TRC8 hereditary kidney cancer gene.18
226890532013TRC8 suppresses tumorigenesis through targeting heme oxygenase-1 for ubiquitination and degradation.17
262101832015Identifying the ERAD ubiquitin E3 ligases for viral and cellular targeting of MHC class I.17
175390222007A constitutional balanced t(3;8)(p14;q24.1) translocation results in disruption of the TRC8 gene and predisposition to clear cell renal cell carcinoma.15
295198972018MARCH6 and TRC8 facilitate the quality control of cytosolic and tail-anchored proteins.15
279989832017Bag1 Co-chaperone Promotes TRC8 E3 Ligase-dependent Degradation of Misfolded Human Ether a Go-Go-related Gene (hERG) Potassium Channels.6
286626432017E3 ubiquitin ligase, RNF139, inhibits the progression of tongue cancer.1

Citation

Anita Bonné ; Eric Schoenmakers ; Ad Geurts van Kessel

RNF139 (translocation in renal carcinoma, chromosome 8 gene)

Atlas Genet Cytogenet Oncol Haematol. 2004-06-01

Online version: http://atlasgeneticsoncology.org/gene/500/rnf139