Cullin-associated NEDD8-dissociated protein 1 (CAND1)
The protein contains 1230 amino acids for an estimated molecular weight of 136376 Da.
Key assembly factor of SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complexes that promotes the exchange of the substrate-recognition F-box subunit in SCF complexes, thereby playing a key role in the cellular repertoire of SCF complexes. Acts as a F-box protein exchange factor. The exchange activity of CAND1 is coupled with cycles of neddylation conjugation: in the deneddylated state, cullin-binding CAND1 binds CUL1-RBX1, increasing dissociation of the SCF complex and promoting exchange of the F-box protein. Probably plays a similar role in other cullin-RING E3 ubiquitin ligase complexes. (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.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- 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.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
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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| Variant | Description |
|---|---|
| dbSNP:rs12580996 | |
| dbSNP:rs17854618 |
Biological Process
Cell differentiation
Cellular iron ion homeostasis
Negative regulation of catalytic activity
Neutrophil degranulation
Positive regulation of RNA polymerase II transcription preinitiation complex assembly
Post-translational protein modification
Protein ubiquitination
SCF complex assembly
The reference OMIM entry for this protein is 607727
Cullin-associated neddylation-dissociated protein 1; cand1
Tbp-interacting protein, 120-kd, a
Tip120a
Tip120
P120(cand1)
Kiaa0829
CLONING
Using histidine-tagged TATA-binding protein (TBP; 600075) as a ligand for affinity-purification of TBP-interacting proteins, Yogosawa et al. (1996) purified a 120-kD protein, which they termed Tip120, from rat liver nuclear extracts. They obtained a full-length cDNA encoding Tip120 by screening a rat liver cDNA library. The rat Tip120 protein contains 1,230 amino acids and has a calculated molecular mass of 135 kD. Northern blot analysis detected a 4.5-kb transcript.GENE FUNCTION
Yogosawa et al. (1996) showed that recombinant rat Tip120 interacted directly with TBP under a physiologic condition in vitro. Immunoprecipitation analysis indicated that Tip120 associated with TBP in nuclear extracts. Zheng et al. (2002) isolated TIP120A as a cullin-1 (CUL1; 603134)-binding protein that they designated CAND1. They determined that the majority of CUL1 is in a complex with CAND1 and ROC1 (603814) independent of SKP1 (601434) and the F box protein SKP2 (601436). Both in vivo and in vitro, CAND1 prevented binding of SKP1 and SKP2 to CUL1, while dissociation of CAND1 from CUL1 promoted the reverse reaction. Neddylation of CUL1 or the presence of SKP1 and ATP caused CAND1 dissociation. These data suggested that CAND1 regulates the formation of the SCF (SKP1, CUL1/Cdc53, F box protein) complex and that its dissociation from CUL1 is coupled with the incorporation of F box proteins into the SCF complex, causing their destabilization. Liu et al. (2002) showed that p120(CAND1) selectively binds to unneddylated CUL1 and is dissociated by CUL1 neddylation. CAND1 formed a ternary complex with CUL1 and ROC1. It dissociated SKP1 from CUL1 and inhibited SCF ligase activity in vitro. Suppression of CAND1 in vivo increased the level of the CUL1-SKP1 complex. The authors concluded that, by restricting SKP1-CUL1 interaction, CAND1 regulates the assembly of productive SCF ubiquitin ligases, allowing a common CUL1-ROC core to be utilized by a large number of SKP1-F box-substrate subcomplexes. Min et al. (2005) stated that the COP9 signalosome (CSN; see 601934) inactivates SCF by catalyzing deconjugation of NEDD8 from CUL1. They found that CSN interacted with CUL1 irrespective of its neddylation state. Addition of CAND1, which bound only unneddylated CUL1, inhibited binding of CUL1 to CSN and enhanced the deneddylase activity of CSN in vitro.MAPPING
By FISH, Yogosawa et al. (1999) mapped the CAND1 gene to chromosome 12q14. ... 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
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 607727 was added.