UniProt functional annotation for Q86VP6



	UniProt functional annotation for Q86VP6

UniProt code: Q86VP6.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: 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. {ECO:0000269|PubMed:12504025, ECO:0000269|PubMed:12504026, ECO:0000269|PubMed:12609982, ECO:0000269|PubMed:16449638, ECO:0000269|PubMed:21249194, ECO:0000269|PubMed:23453757}.

Subunit: Interacts with TBP (By similarity). Part of a complex that contains CUL1 and RBX1. Interacts with unneddylated cullins: interacts with CUL1, CUL2, CUL3, CUL4A, CUL4B and CUL5. Does not bind neddylated CUL1. Interaction with cullins is abolished in presence of COMMD1, which antagonizes with CAND1 for interacting with cullins. Interacts with ERCC6 (PubMed:26030138). Interacts with DCUN1D1, DCUN1D2, DCUN1D3, DCUN1D4 AND DCUN1D5; these interactions are bridged by cullins and strongly inhibits the neddylation of cullins (PubMed:24192928, PubMed:26906416, PubMed:25349211). {ECO:0000250|UniProtKB:P97536, ECO:0000269|PubMed:12504025, ECO:0000269|PubMed:12504026, ECO:0000269|PubMed:12609982, ECO:0000269|PubMed:15537541, ECO:0000269|PubMed:16449638, ECO:0000269|PubMed:21249194, ECO:0000269|PubMed:21778237, ECO:0000269|PubMed:22118460, ECO:0000269|PubMed:24192928, ECO:0000269|PubMed:25349211, ECO:0000269|PubMed:26030138, ECO:0000269|PubMed:26906416}.

Subcellular location: Cytoplasm {ECO:0000269|PubMed:21249194}. Nucleus {ECO:0000269|PubMed:21249194}. Note=Predominantly cytoplasmic.

Induction: Repressed by miR-148a. {ECO:0000269|PubMed:20820187}.

Miscellaneous: A model has been proposed to explain the mechanisms of cullin-RING E3 ubiquitin ligase complexes assembly. According to this hypothesis, cullin-RING E3 ubiquitin ligase complexes exist in a 'stable' active state when saturated with substrate, occluding access to deneddylation by the COP9 signalosome (CSN) complex. The neddylation-conjugated cullin-RING E3 ubiquitin ligase complexes mediate ubiquitination of substrates and can recruit downstream factors involved in substrate degradation. Depletion of the substrate promotes the ability of CSN to bind the cullin-RING E3 ubiquitin ligase complex and mediate deneddylation. In this 'intermediate' deneddylated state, the complex can bind CAND1 and enter the 'exchange' state, resulting in high increase in dissociation rate of the substrate-recognition subunit. The resulting CAND1-cullin-RING complex rapidly assembles with another available substrate-recognition subunit to form an unstable ternary intermediate and yield a new cullin-RING E3 ubiquitin ligase complex. Subsequent neddylation of the cullin, which is stabilized by substrate, completes the cycle (PubMed:23453757). {ECO:0000305|PubMed:23453757}.

Similarity: Belongs to the CAND family. {ECO:0000305}.

Sequence caution: Sequence=BAA74852.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=BAB55090.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		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. {ECO:0000269\|PubMed:12504025, ECO:0000269\|PubMed:12504026, ECO:0000269\|PubMed:12609982, ECO:0000269\|PubMed:16449638, ECO:0000269\|PubMed:21249194, ECO:0000269\|PubMed:23453757}.


Subunit:		Interacts with TBP (By similarity). Part of a complex that contains CUL1 and RBX1. Interacts with unneddylated cullins: interacts with CUL1, CUL2, CUL3, CUL4A, CUL4B and CUL5. Does not bind neddylated CUL1. Interaction with cullins is abolished in presence of COMMD1, which antagonizes with CAND1 for interacting with cullins. Interacts with ERCC6 (PubMed:26030138). Interacts with DCUN1D1, DCUN1D2, DCUN1D3, DCUN1D4 AND DCUN1D5; these interactions are bridged by cullins and strongly inhibits the neddylation of cullins (PubMed:24192928, PubMed:26906416, PubMed:25349211). {ECO:0000250\|UniProtKB:P97536, ECO:0000269\|PubMed:12504025, ECO:0000269\|PubMed:12504026, ECO:0000269\|PubMed:12609982, ECO:0000269\|PubMed:15537541, ECO:0000269\|PubMed:16449638, ECO:0000269\|PubMed:21249194, ECO:0000269\|PubMed:21778237, ECO:0000269\|PubMed:22118460, ECO:0000269\|PubMed:24192928, ECO:0000269\|PubMed:25349211, ECO:0000269\|PubMed:26030138, ECO:0000269\|PubMed:26906416}.
Subcellular location:		Cytoplasm {ECO:0000269\|PubMed:21249194}. Nucleus {ECO:0000269\|PubMed:21249194}. Note=Predominantly cytoplasmic.
Induction:		Repressed by miR-148a. {ECO:0000269\|PubMed:20820187}.
Miscellaneous:		A model has been proposed to explain the mechanisms of cullin-RING E3 ubiquitin ligase complexes assembly. According to this hypothesis, cullin-RING E3 ubiquitin ligase complexes exist in a 'stable' active state when saturated with substrate, occluding access to deneddylation by the COP9 signalosome (CSN) complex. The neddylation-conjugated cullin-RING E3 ubiquitin ligase complexes mediate ubiquitination of substrates and can recruit downstream factors involved in substrate degradation. Depletion of the substrate promotes the ability of CSN to bind the cullin-RING E3 ubiquitin ligase complex and mediate deneddylation. In this 'intermediate' deneddylated state, the complex can bind CAND1 and enter the 'exchange' state, resulting in high increase in dissociation rate of the substrate-recognition subunit. The resulting CAND1-cullin-RING complex rapidly assembles with another available substrate-recognition subunit to form an unstable ternary intermediate and yield a new cullin-RING E3 ubiquitin ligase complex. Subsequent neddylation of the cullin, which is stabilized by substrate, completes the cycle (PubMed:23453757). {ECO:0000305\|PubMed:23453757}.
Similarity:		Belongs to the CAND family. {ECO:0000305}.
Sequence caution:		Sequence=BAA74852.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=BAB55090.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};