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Gene Review

UBE2V1  -  ubiquitin-conjugating enzyme E2 variant 1

Homo sapiens

Synonyms: CIR1, CROC-1, CROC1, P/OKcl.19, TRAF6-regulated IKK activator 1 beta Uev1A, ...
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Disease relevance of UBE2V1

  • FN, BBC1, and UEV-1 localize to regions of chromosomal aberration (2q3.4, 16q24.3, and 20q13.2, respectively) associated with advanced prostate cancer and thus may be highly relevant to disease progression [1].
  • In this report, we show that constitutive high-level expression of UEV1A alone in cultured human cells was sufficient to cause a significant increase in NF-kappaB activity as well as the expression of its target anti-apoptotic protein, Bcl-2 (B-cell leukemia/lymphoma 2) [2].

High impact information on UBE2V1

  • Here we report the crystal structure of a complex between hMms2 (Uev1) and hUbc13 at 1.85 A resolution and a structure of free hMms2 at 1.9 A resolution [3].
  • Role of UEV-1, an inactive variant of the E2 ubiquitin-conjugating enzymes, in in vitro differentiation and cell cycle behavior of HT-29-M6 intestinal mucosecretory cells [4].
  • Upstream of the ESX promoter region in this genomic fragment lies the terminal exon of a newly identified gene that encodes a ubiquitin-conjugating enzyme variant, UEV-1 [5].
  • The TSG101B isoform lacks the leucine zipper near the C-terminus, a transcriptional repressor domain, and retains most of the N-terminal region which has homology to E2 ubiquitin regulatory enzymes and the CROC-1 transcriptional regulator [6].
  • A 5-6-fold elevation in CIR1/CROC1 expression and a 2-3-fold elevation in CIR2 expression were observed in SV40-transformed human embryonic kidney cells immediately following proliferative crisis, suggesting a potential role for these genes in immortalization [7].

Biological context of UBE2V1

  • These results are compatible with induction of CIR1/CROC1 being an early event in the acquisition of immortality and with a role for this gene in the immortal phenotype of tumor cells [7].
  • Up-regulation of CIR1/CROC1 expression upon cell immortalization and in tumor-derived human cell lines [7].
  • The CROC-1 gene was isolated by its ability to transactivate c- fos expression in cell culture through a tandem repeat enhancer sequence [8].
  • The hMMS2 and CROC-1 genes are able to functionally complement the yeast mms2 defects with regard to sensitivity to DNA damaging agents and spontaneous mutagenesis [8].
  • DNA sequencing revealed the first plasmid, denoted CROC-1, to contain a 1.8-kb cDNA encoding a 16.5-kDa nuclear protein possessing a bipartite structure comprised an amino-terminal acidic domain and a carboxy-terminal basic domain, and displaying partial homology to the HMG domain of the TAF(II)250 transcription cofactor [9].

Anatomical context of UBE2V1

  • Expression of CIR1/CROC1 was found to be elevated also in a variety of immortal human tumor-derived cell lines, as compared to their normal tissue counterparts [7].
  • Unlike CROC-1 , whose transcript appears to be elevated in all tumor cell lines examined, the hMMS2 transcript is only elevated in some tumor cell lines [8].
  • We also show that the mutant phenotype is fully complemented by expression of the human UEV-1A cDNA and we propose that UEV-1 proteins could also have a role in protecting higher eukaryotic cells from DNA damaging agents [10].
  • 5. It is suggested that A23187 causes the release of Ca2+ from the S.R. by a mechanism that differs from both excitation and the CROC; the resultant rise in [Ca2+]i again causes myofibril degradation [11].
  • Cir1 also controls the known major virulence factors of the pathogen including the capsule, the formation of the anti-oxidant melanin in the cell wall, and the ability to grow at host body temperature [12].

Associations of UBE2V1 with chemical compounds

  • 3. It is argued that caffeine causes a Ca2+-induced release of Ca2+ (the CROC) from the S.R. and that the consequent rise in [Ca2+]i promotes the ultrastructural damage observed [11].

Other interactions of UBE2V1


Analytical, diagnostic and therapeutic context of UBE2V1

  • The sequence analysis of two cDNA indicates open reading frames which show significant similarities to known proteins involved in mechanisms of regulation: 1) nifR3, an element of the nitrogen regulatory system in bacteria and 2) CROC-1, a newly identified human transcription factor [13].


  1. Differentially expressed genes in hormone refractory prostate cancer: association with chromosomal regions involved with genetic aberrations. Stubbs, A.P., Abel, P.D., Golding, M., Bhangal, G., Wang, Q., Waxman, J., Stamp, G.W., Lalani, E.N. Am. J. Pathol. (1999) [Pubmed]
  2. Uev1A, a ubiquitin conjugating enzyme variant, inhibits stress-induced apoptosis through NF-kappaB activation. Syed, N.A., Andersen, P.L., Warrington, R.C., Xiao, W. Apoptosis (2006) [Pubmed]
  3. Crystal structure of the human ubiquitin conjugating enzyme complex, hMms2-hUbc13. Moraes, T.F., Edwards, R.A., McKenna, S., Pastushok, L., Xiao, W., Glover, J.N., Ellison, M.J. Nat. Struct. Biol. (2001) [Pubmed]
  4. Role of UEV-1, an inactive variant of the E2 ubiquitin-conjugating enzymes, in in vitro differentiation and cell cycle behavior of HT-29-M6 intestinal mucosecretory cells. Sancho, E., Vilá, M.R., Sánchez-Pulido, L., Lozano, J.J., Paciucci, R., Nadal, M., Fox, M., Harvey, C., Bercovich, B., Loukili, N., Ciechanover, A., Lin, S.L., Sanz, F., Estivill, X., Valencia, A., Thomson, T.M. Mol. Cell. Biol. (1998) [Pubmed]
  5. Exon 4-encoded acidic domain in the epithelium-restricted Ets factor, ESX, confers potent transactivating capacity and binds to TATA-binding protein (TBP). Chang, C.H., Scott, G.K., Baldwin, M.A., Benz, C.C. Oncogene (1999) [Pubmed]
  6. Expression of a new isoform of the tumor susceptibility TSG101 protein lacking a leucine zipper domain in Burkitt lymphoma cell lines. Ferrer, M., López-Borges, S., Lazo, P.A. Oncogene (1999) [Pubmed]
  7. Up-regulation of CIR1/CROC1 expression upon cell immortalization and in tumor-derived human cell lines. Ma, L., Broomfield, S., Lavery, C., Lin, S.L., Xiao, W., Bacchetti, S. Oncogene (1998) [Pubmed]
  8. The products of the yeast MMS2 and two human homologs (hMMS2 and CROC-1) define a structurally and functionally conserved Ubc-like protein family. Xiao, W., Lin, S.L., Broomfield, S., Chow, B.L., Wei, Y.F. Nucleic Acids Res. (1998) [Pubmed]
  9. CROC-1 encodes a protein which mediates transcriptional activation of the human FOS promoter. Rothofsky, M.L., Lin, S.L. Gene (1997) [Pubmed]
  10. Role of UEV-1A, a homologue of the tumor suppressor protein TSG101, in protection from DNA damage. Thomson, T.M., Khalid, H., Lozano, J.J., Sancho, E., Ariño, J. FEBS Lett. (1998) [Pubmed]
  11. The action of caffeine in promoting ultrastructural damage in frog skeletal muscle fibres. Evidence for the involvement of the calcium-induced release of calcium from the sarcoplasmic reticulum. Duncan, C.J., Smith, J.L. Naunyn Schmiedebergs Arch. Pharmacol. (1978) [Pubmed]
  12. Iron regulation of the major virulence factors in the AIDS-associated pathogen Cryptococcus neoformans. Jung, W.H., Sham, A., White, R., Kronstad, J.W. PLoS Biol. (2006) [Pubmed]
  13. Messenger RNA in dormant cells of Sterkiella histriomuscorum (Oxytrichiade): indentification of putative regulatory gene transcripts. Tourancheau, A.B., Morin, L., Yang, T., Perasso, R. Protist (1999) [Pubmed]
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