DCN1-like protein 1 (DCUN1D1)
The protein contains 259 amino acids for an estimated molecular weight of 30124 Da.
Part of an E3 ubiquitin ligase complex for neddylation (PubMed:18826954). Promotes neddylation of cullin components of E3 cullin-RING ubiquitin ligase complexes (PubMed:26906416, PubMed:23201271, PubMed:19617556, PubMed:23401859). Acts by binding to cullin-RBX1 complexes in the cytoplasm and promoting their nuclear translocation, enhancing recruitment of E2-NEDD8 (UBE2M-NEDD8) thioester to the complex, and optimizing the orientation of proteins in the complex to allow efficient transfer of NEDD8 from the E2 to the cullin substrates. Involved in the release of inhibitory effets of CAND1 on cullin-RING ligase E3 complex assembly and activity (PubMed:25349211, PubMed:28581483). Acts also as an oncogene facilitating malignant transformation and carcinogenic progression (By similarity). (updated: Feb. 10, 2021)
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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The reference OMIM entry for this protein is 605905
Dcn1 domain-containing protein 1; dcun1d1
Rp42 homolog; rp42
Squamous cell carcinoma-related oncogene 1; sccro1
DESCRIPTION
Covalent attachment of NEDD8 (603171) to cullins (see CUL1, 603134), a process called neddylation, results in nuclear cullin accumulation, which promotes cell growth, migration, and transformation. DCUN1D1 functions as an E3 ligase in cullin neddylation (summary by Huang et al., 2014).CLONING
In a systematic search for genes expressed in proliferating neuroblasts whose human orthologs map to susceptibility loci for autism (209850), Mas et al. (2000) isolated a novel mouse gene, which they designated RP42. They obtained the human homolog by combining contigs of human ESTs and RT-PCR of human embryonic mRNAs. The deduced human and mouse RP42 proteins contain 259 amino acids and differ by only 2 residues. They show 30 to 36% overall sequence identity to an S. pombe and a C. elegans protein, suggesting that the RP42 protein has an important cellular function. Northern blot analysis in the mouse embryo demonstrated expression of 2 transcripts, with the larger transcript reaching peak expression from E11 to E15, and the smaller transcript showing high expression from E7 to E15, indicating developmentally regulated expression, which was found particularly in proliferating neuroblasts. In mouse adult tissues, 3 transcripts were expressed in testis, kidney, liver, skeletal muscle, and heart, with weaker expression in brain. Northern blot analysis of adult human tissues detected 2 RP42 transcripts of approximately 3.7 and 2.7 kb at lower levels of expression than in mouse. RT-PCR showed that RP42 is expressed in the human embryo telencephalon. By searching databases for sequences similar to S. cerevisiae and C. elegans Dcn1, Kurz et al. (2005) identified mouse and human DCUN1D1. Like Dcn1, DCUN1D1 contains a DUF298 domain and a UBA-like ubiquitin (see 191339)-binding domain.GENE FUNCTION
Kurz et al. (2005) found that Dcn1 was required for cullin neddylation in C. elegans and S. cerevisiae. Dcn1 from both species bound cullin directly, and overexpression of Dcn1 in yeast resulted in accumulation of Nedd8 (603171)-modified Cdc53, a Cul1 ortholog. Scott et al. (2011) found that N-terminal acetylation of the E2 enzyme UBC12 (603173) dictates distinctive E3-dependent ligation of the ubiquitin-like protein NEDD8 (603171) to CUL1 (603134). Structural, biochemical, biophysical, and genetic analyses revealed how complete burial of UBC12's N-acetyl-methionine in a hydrophobic pocket in the E3 DCN1 promotes cullin neddylation. The results suggested that the N-terminal acetyl both directs UBC12's interactions with DCN1 and prevents repulsion of a charged N terminus. Scott et al. (2011) concluded that their data provided a link between acetylation and ubiquitin-like protein conjugation and defined a mechanism for N-terminal acetylation-dependent recognition. Huang et al. (2014) found that expression of DCUN1D1, which they called SCCRO1, was inversely proportional to that of SCCRO3 (DCUN1D3; 616167). Knockdown and overexpression studies revealed that SCCRO1 promoted cullin neddylation and nuclear accumulation, concomitant with induction of cell growth, migration, and transformation, as well as colony formation and rearrangement of the actin cytoskeleton. SCCRO3 had the opposite effects and functioned by interacting with and sequestering cullins at the cell membrane. When both SCCRO1 and SCCRO3 were coexpressed at relatively equal levels, CUL1 predominantly localized to the plasma membrane with SCCRO3. Huang et al. ... More on the omim web site
Feb. 16, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.
May 26, 2018: 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
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 605905 was added.