Ubiquitin-conjugating enzyme E2 variant 1 (UBE2V1)

The protein contains 147 amino acids for an estimated molecular weight of 16495 Da.

 

Has no ubiquitin ligase activity on its own. The UBE2V1-UBE2N heterodimer catalyzes the synthesis of non-canonical poly-ubiquitin chains that are linked through Lys-63. This type of poly-ubiquitination activates IKK and does not seem to involve protein degradation by the proteasome. Plays a role in the activation of NF-kappa-B mediated by IL1B, TNF, TRAF6 and TRAF2. Mediates transcriptional activation of target genes. Plays a role in the control of progress through the cell cycle and differentiation. Plays a role in the error-free DNA repair pathway and contributes to the survival of cells after DNA damage. Promotes TRIM5 capsid-specific restriction activity and the UBE2V1-UBE2N heterodimer acts in concert with TRIM5 to generate 'Lys-63'-linked polyubiquitin chains which activate the MAP3K7/TAK1 complex which in turn results in the induction and expression of NF-kappa-B and MAPK-responsive inflammatory genes. Together with RNF135 and UBE2N, catalyzes the viral RNA-dependent 'Lys-63'-linked polyubiquitination of RIG-I/DDX58 to activate the downstream signaling pathway that leads to interferon beta production (PubMed:31006531). UBE2V1-UBE2N together with TRAF3IP2 E3 ubiquitin ligase mediate 'Lys-63'-linked polyubiquitination of TRAF6, a component of IL17A-mediated signaling pathway. (updated: Oct. 7, 2020)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
  3. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  4. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  5. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.

Interpro domains
Total structural coverage: 100%
Model score: 25

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The reference OMIM entry for this protein is 602995

Ubiquitin-conjugating enzyme e2 variant 1; ube2v1
Uev1; uev1a
Croc1

CLONING

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 u ... More on the omim web site

Subscribe to this protein entry history

Oct. 20, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.

Jan. 22, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

June 20, 2017: Protein entry updated
Automatic update: comparative model was added.

March 25, 2017: Additional information
No protein expression data in P. Mayeux work for UBE2V1

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 602995 was added.

Jan. 28, 2016: Protein entry updated
Automatic update: model status changed

Jan. 25, 2016: Protein entry updated
Automatic update: model status changed