Ubiquitin-protein ligase E3C (UBE3C)
The protein contains 1083 amino acids for an estimated molecular weight of 123923 Da.
E3 ubiquitin-protein ligase that accepts ubiquitin from the E2 ubiquitin-conjugating enzyme UBE2D1 in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Can assemble unanchored poly-ubiquitin chains in either 'Lys-29'- or 'Lys-48'-linked polyubiquitin chains. Has preference for 'Lys-48' linkages. It can target itself for ubiquitination in vitro and may promote its own degradation in vivo. (updated: March 4, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- 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.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
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.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
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.
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The reference OMIM entry for this protein is 614454
Ubiquitin protein ligase e3c; ube3c
Hecth2
Kiaa0010
Kiaa10
DESCRIPTION
Ubiquitin (UBB; 191339) modification of lysine residues targets proteins for degradation via the proteasome (see 606223). Ubiquitination requires a ubiquitin-activating enzyme (E1; see 314370), a ubiquitin-carrier protein (E2; see 602961), and a ubiquitin-protein ligase (E3), such as UBE3C. E3 enzymes transiently accept ubiquitin from the E2 in a thiol ester linkage prior to transferring ubiquitin to the target lysine (summary by You and Pickart, 2001).CLONING
By sequencing clones obtained from a size-fractionated human immature myeloid cell line KG-1, Nomura et al. (1994) obtained a partial UBE3C clone, which they designated KIAA0010. The deduced protein shares significant similarity with E6AP (UBE3A; 601623), and it contains a lipid attachment site and a tyrosine kinase phosphorylation site. Northern blot analysis detected KIAA0010 expression in all tissues and cell lines examined, with highest expression in lung, liver, skeletal muscle, kidney, spleen, testis, and ovary, and weakest expression in thymus. You and Pickart (2001) cloned full-length UBE3C, which they called KIAA10. The deduced 1,083-amino acid protein has a calculated molecular mass of about 120 kD. KIAA10 has a unique N-terminal domain predicted to mediate substrate binding and a C-terminal HECT domain, suggesting that it functions as a HECT domain family E3 ligase.GENE FUNCTION
Schwarz et al. (1998) showed that in vitro-translated human UBE3C, which they called HECTH2, formed a thioester complex with ubiquitin in the presence of an E1 enzyme and the E2 enzyme UBCH5 (UBE2D1; 602961), with reduced efficiency with the E2 UBCH7 (UBE2L3; 603721). You and Pickart (2001) showed that full-length KIAA10 and its isolated 428-amino acid C terminus, including the HECT domain, assembled polyubiquitin chains linked through lys29 or lys48. KIAA10 also displayed autoubiquitination. The N-terminal KIAA10 domain was devoid of activity. Mutation analysis revealed that the N terminus of KIAA10 interacted directly with the S2 subunit of the proteasome 26S complex (PSMD2; 606223).MAPPING
By PCR of a human-rodent hybrid cell line panel, Nomura et al. (1994) mapped the UBE3C gene to chromosome 7. Hartz (2012) mapped the UBE3C gene to chromosome 7q36.3 based on an alignment of the UBE3C sequence (GenBank GENBANK D13635) with the genomic sequence (GRCh37). ... More on the omim web site
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 614454 was added.