Online Mendelian Inheritance in Man (OMIM)

* 602995

UBIQUITIN-CONJUGATING ENZYME E2 V1; UBE2V1

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Description

UBE2V1 forms a heterodimeric complex with UBC13 (603679) to mediate activation of IKK (see 600664) by TRAF6 (602355) (Deng et al., 2000).

Cloning and Expression

Rothofsky and Lin (1997) isolated human brain cDNAs encoding UBE2V1, which they called CROC1. They identified 2 alternative 5-prime CROC1 cDNA sequences that result in predicted 221- and 170-amino acid proteins, designated CROC1B and CROC1A, respectively, with different N-terminal ends. The CROC1 isoforms have an acidic domain and a C-terminal basic domain. They show sequence similarity to ubiquitin-conjugating enzymes (UBCs, or E2s, e.g., UBE2D1; 602961), but they lack the conserved cysteine critical for E2 catalytic activity. The CROC1 C-terminal domain has 42% sequence identity with the potential DNA-binding domain of TAFII250 (TAF2A; 313650). Immunofluorescence microscopy localized recombinant CROC1 to the nucleus, excluding the nucleolar organizer regions. Northern blot analysis detected 2.1- and 2.5-kb CROC1 transcripts in all human tissues examined, with highest levels in brain, skeletal muscle, and kidney.

Sancho et al. (1998) isolated partial human intestinal epithelial cell cDNAs containing the 3-prime coding sequence and 3-prime UTR of UBE2V1, which they called UEV1. RT-PCR identified 4 alternatively spliced UEV1 transcripts encoding proteins with identical 90-amino acid C-terminal sequences, including the region homologous to the conserved Ubc domain of E2 enzymes, but unique N-terminal sequences. The 140-amino acid C terminus of the deduced 221- and 170-amino acid UEV1 isoforms identified by Rothofsky and Lin (1997), which Sancho et al. (1998) called UEV1B and UEV1A, respectively, is 90% identical to UEV2 (UBE2V2; 603001) and 18%, 24%, and 22% identical to the Ubc domain of human UBE2I (601661), S. cerevisiae UBC4 and UBC7, and A. thaliana UBC1, respectively.

Thomson et al. (2000) determined that the 5-prime UEV1 splice variant identified as CROC1B by Rothofsky and Lin (1997) and UEV1B by Sancho et al. (1998) is a fusion transcripts resulting from splicing of the first 5 exons of the KUA gene (610994) with the last 3 exons of the UEV1 gene. The last exon of KUA and the first exon of UEV1 are skipped. The deduced protein contains an N-terminal KUA domain and a C-terminal UEV1 domain. See 610994 for further information on the KUA/UEV1 fusion transcript.

Gene Function

Rothofsky and Lin (1997) demonstrated that CROC1 can cause transcriptional activation of the human FOS (164810) promoter.

Sancho et al. (1998) showed that UEV1 does not have ubiquitin-conjugating activity in vitro. UEV1 transcripts were downregulated upon differentiation of a colon carcinoma cell line. Constitutive expression of exogenous UEV1 protein in these colon carcinoma cells inhibited their capacity to differentiate upon confluence and induced changes in their cell cycle behavior, which was associated with an inhibition of the mitotic kinase CDK1 (see CDC2; 116940).

Deng et al. (2000) purified a heterodimeric protein complex that links TRAF6 (602355) to IKK (see 600664) activation. Peptide mass fingerprinting analysis revealed that this complex is composed of the ubiquitin conjugating enzyme UBC13 (603679) and the UBC-like protein UBE2V1, which the authors called UEV1A. They found that TRAF6, a RING domain protein, functions together with UBC13/UEV1A to catalyze the synthesis of unique polyubiquitin chains linked through lysine-63 (K63) of ubiquitin. Blockade of this polyubiquitin chain synthesis, but not inhibition of the proteasome, prevents the activation of IKK by TRAF6. These results unveil a new regulatory function for ubiquitin, in which IKK is activated through the assembly of K63-linked polyubiquitin chains.

Pertel et al. (2011) demonstrated that TRIM5 (608487) promotes innate immune signaling and that this activity is amplified by retroviral infection and interaction with the capsid lattice. Acting with the heterodimeric, ubiquitin-conjugating enzyme UBC13-UEV1A, TRIM5 catalyzes the synthesis of unattached K63-linked ubiquitin chains that activate the TAK1 (602614) kinase complex and stimulate AP1 (see 165160) and NF-kappa-B (see 164011) signaling. Interaction with the HIV-1 capsid lattice greatly enhanced the UBC13-UEV1A-dependent E3 activity of TRIM5, and challenge with retroviruses induced the transcription of AP1- and NF-kappa-B-dependent factors with a magnitude that tracked with TRIM5 avidity for the invading capsid. Finally, TAK1 and UBC13-UEV1A contribute to capsid-specific restriction by TRIM5. Pertel et al. (2011) concluded that the retroviral restriction factor TRIM5 has 2 additional activities that are linked to restriction: it constitutively promotes innate immune signaling, and it acts as a pattern recognition receptor specific for the retrovirus capsid lattice.

Gene Structure

Sancho et al. (1998) determined that the UEV1 gene contains at least 6 exons and has at least 3 alternative polyadenylation sites in the 3-prime UTR. However, Thomson et al. (2000) determined that UBE2V1 gene contains 4 exons. The most 5-prime UBE2V1 exon described by Sancho et al. (1998) originates from exons 4 and 5 of the upstream KUA gene.

Mapping

By fluorescence in situ hybridization, Sancho et al. (1998) mapped the human UEV1 gene to chromosome 20q13.2.

REFERENCES

Contributors:

Ada Hamosh - updated : 7/8/2011
Patricia A. Hartz - updated : 3/14/2007
Stylianos E. Antonarakis - updated : 10/24/2000
Stylianos E. Antonarakis - updated : 3/25/1999

Creation Date:

Patti M. Sherman : 8/21/1998

Edit History:

alopez : 01/05/2023
mgross : 04/18/2022
alopez : 07/12/2011
terry : 7/8/2011
mgross : 5/7/2007
terry : 3/14/2007
carol : 10/24/2000
carol : 10/24/2000
mgross : 3/31/1999
mgross : 3/29/1999
terry : 3/25/1999
alopez : 9/22/1998