Ubiquitin-conjugating enzyme E2 K (UBE2K)
The protein contains 200 amino acids for an estimated molecular weight of 22407 Da.
Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro, in the presence or in the absence of BRCA1-BARD1 E3 ubiquitin-protein ligase complex, catalyzes the synthesis of 'Lys-48'-linked polyubiquitin chains. Does not transfer ubiquitin directly to but elongates monoubiquitinated substrate protein. Mediates the selective degradation of short-lived and abnormal proteins, such as the endoplasmic reticulum-associated degradation (ERAD) of misfolded lumenal proteins. Ubiquitinates huntingtin. May mediate foam cell formation by the suppression of apoptosis of lipid-bearing macrophages through ubiquitination and subsequence degradation of p53/TP53. Proposed to be involved in ubiquitination and proteolytic processing of NF-kappa-B; in vitro supports ubiquitination of NFKB1. In case of infection by cytomegaloviruses may be involved in the US11-dependent degradation of MHC class I heavy chains following their export from the ER to the cytosol. In case of viral infections may be involved in the HPV E7 protein-dependent degradation of RB1. (updated: April 1, 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.
- 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.
- 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.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- 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.
| 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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Biological Process
Cellular response to interferon-beta
Free ubiquitin chain polymerization
Intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress
Positive regulation of peptidyl-threonine phosphorylation
Positive regulation of tumor necrosis factor-mediated signaling pathway
Positive regulation of type I interferon-mediated signaling pathway
Proteasome-mediated ubiquitin-dependent protein catabolic process
Protein K48-linked ubiquitination
Protein polyubiquitination
Protein ubiquitination
Regulation of proteasomal ubiquitin-dependent protein catabolic process
Ubiquitin-dependent protein catabolic process
The reference OMIM entry for this protein is 602846
Ubiquitin-conjugating enzyme e2k; ube2k
Huntingtin-interacting protein 2; hip2
Ubiquitin-conjugating enzyme e2-25k
DESCRIPTION
The HIP2 gene encodes a ubiquitin-conjugating enzyme that interacts with huntingtin (HTT; 613004) (Kalchman et al., 1996).CLONING
By use of the yeast 2-hybrid system, Kalchman et al. (1996) identified the HIP2 protein. The 200-amino acid HIP2 protein sequence was identical to that of bovine ubiquitin-conjugating enzyme E2-25K. Assays of the interaction of HIP2 with huntingtin revealed that HIP2 binds selectively to a large region at the N terminus of huntingtin. This interaction is not influenced by the length of the huntingtin polyglutamine tract. Northern blot analysis revealed that HIP2 was transcribed as 1.2- and 1.4-kb mRNAs in all human tissues studied. Western blot analysis detected protein bands of 25 kD, 28 kD, and 45 kD; the 28-kD band appeared to be selective for tissues of the central nervous system. Kalchman et al. (1996) showed that huntingtin is ubiquitinated in peripheral cells, suggesting a role for HIP2 in the degradation of huntingtin.MAPPING
By fluorescence in situ hybridization, Kalchman et al. (1996) mapped the HIP2 gene to human chromosome 4p14. ... More on the omim web site
May 13, 2019: Protein entry updated
Automatic update: model status changed
Nov. 17, 2018: Protein entry updated
Automatic update: model status changed
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 16, 2016: Protein entry updated
Automatic update: OMIM entry 602846 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed