E3 ubiquitin-protein ligase ARIH1 (ARIH1)
The protein contains 557 amino acids for an estimated molecular weight of 64118 Da.
E3 ubiquitin-protein ligase, which catalyzes ubiquitination of target proteins together with ubiquitin-conjugating enzyme E2 UBE2L3 (PubMed:15236971, PubMed:21532592, PubMed:24076655, PubMed:27565346, PubMed:23707686). Acts as an atypical E3 ubiquitin-protein ligase by working together with cullin-RING ubiquitin ligase (CRL) complexes and initiating ubiquitination of CRL substrates: associates with CRL complexes and specifically mediates addition of the first ubiquitin on CRLs targets (PubMed:27565346). The initial ubiquitin is then elongated by CDC34/UBE2R1 and UBE2R2 (PubMed:27565346). E3 ubiquitin-protein ligase activity is activated upon binding to neddylated cullin-RING ubiquitin ligase complexes (PubMed:24076655, PubMed:27565346). Plays a role in protein translation in response to DNA damage by mediating ubiquitination of EIF4E2, the consequences of EIF4E2 ubiquitination are however unclear (PubMed:25624349). According to a report, EIF4E2 ubiquitination leads to promote EIF4E2 cap-binding and protein translation arrest (PubMed:25624349). According to another report EIF4E2 ubiquitination leads to its subsequent degradation (PubMed:14623119). Acts as the ligase involved in ISGylation of EIF4E2 (PubMed:17289916). In vitro, controls the degradation of the LINC (LInker of Nucleoskeleton and Cytoskeleton) complex member SUN2 and may therefore have a role in the formation and localization of the LINC complex, and as a consequence, nuclear subcellular localization and nuclear (updated: Dec. 11, 2019)
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.
- 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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Biological Process
Cytokine-mediated signaling pathway
Positive regulation of proteasomal ubiquitin-dependent protein catabolic process
Protein polyubiquitination
Protein ubiquitination
Protein ubiquitination involved in ubiquitin-dependent protein catabolic process
Ubiquitin-dependent protein catabolic process
Cellular Component
Cajal body
Cytoplasm
Cytosol
Lewy body
Nuclear body
Nucleus
Ubiquitin ligase complex
The reference OMIM entry for this protein is 605624
Ariadne, drosophila, homolog of, 1; arih1
Hhari
Ubch7-binding protein; ubch7bp
CLONING
Using the yeast 2-hybrid system to isolate proteins interacting with the ubiquitin-conjugating enzyme UBCH7 (UBE2L3; 603721), followed by screening a fetal brain cDNA library, Moynihan et al. (1999) obtained a cDNA encoding ARIH1, which they termed HHARI (human homolog of Drosophila ariadne). Sequence analysis predicted that the 557-amino acid protein, which is 72% identical to the Drosophila ariadne protein, contains a highly acidic domain and a poly(gly) tract in its N terminus, followed by 3 cys/his-rich motifs (2 RING fingers and an IBR, or 'in between RING fingers' domain) in its central region. Northern blot analysis detected ubiquitous expression of 2.2-, 2.7-, and 6.5-kb transcripts. The smallest transcript was weakly expressed except in testis, where it was predominant.GENE FUNCTION
Using binding analysis, Moynihan et al. (1999) showed that ARIH1, through a RING finger and its IBR motif, associates with at least the C-terminal 54 residues of UBCH7, as well as with UBCH8 (UBE2L6; 603890). ARIH1 did not associate with UBCH1 or UBCH5 (UBE2D1; 602961). Wenzel et al. (2011) showed that, unlike many ubiquitin-conjugating enzymes (E2) that transfer ubiquitin with RINGs, UBCH7 (603721) lacks intrinsic ubiquitin ligase (E3)-independent reactivity with lysine, explaining its preference for HECTs. Despite lacking lysine reactivity, UBCH7 exhibits activity with the RING-in-between-RING (RBR) family of E3s that includes parkin (602544) and HHARI. Found in all eukaryotes, RBRs regulate processes such as translation and immune signaling. RBRs contain a canonical C3HC4-type RING, followed by 2 conserved cys/his-rich zinc-binding domains, in-between-RING (IBR) and RING2 domains, which together define this E3 family. Wenzel et al. (2011) showed that RBRs function like RING/HECT hybrids: they bind E2s via a RING domain, but transfer ubiquitin through an obligate thioester-linked ubiquitin, requiring a conserved cysteine residue in RING2. Wenzel et al. (2011) concluded that their results defined the functional cadre of E3s for UBCH7, an E2 involved in cell proliferation and immune function, and indicated a novel mechanism for an entire class of E3s.MAPPING
By radiation hybrid analysis, Moynihan et al. (1999) mapped the ARIH1 gene to chromosome 15q. By FISH, Tan et al. (2000) mapped the ARIH1 gene to 15q24.GENE STRUCTURE
By genomic sequence analysis, Tan et al. (2000) determined that ARIH1, as well as its 98% identical mouse homolog, contains 14 exons. ... More on the omim web site
Jan. 22, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 10, 2018: 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
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 605624 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed