Q9D4H8 · CUL2_MOUSE
- ProteinCullin-2
- GeneCul2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids745 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Core component of multiple cullin-RING-based ECS (ElonginB/C-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complexes, which mediate the ubiquitination of target proteins. CUL2 may serve as a rigid scaffold in the complex and may contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The E3 ubiquitin-protein ligase activity of the complex is dependent on the neddylation of the cullin subunit and is inhibited by the association of the deneddylated cullin subunit with TIP120A/CAND1. The functional specificity of the ECS complex depends on the substrate recognition component. ECS(VHL) mediates the ubiquitination of hypoxia-inducible factor (HIF). A number of ECS complexes (containing either KLHDC2, KLHDC3, KLHDC10, APPBP2, FEM1A, FEM1B or FEM1C as substrate-recognition component) are part of the DesCEND (destruction via C-end degrons) pathway, which recognizes a C-degron located at the extreme C terminus of target proteins, leading to their ubiquitination and degradation. ECS complexes and ARIH1 collaborate in tandem to mediate ubiquitination of target proteins. ECS(LRR1) ubiquitinates MCM7 and promotes CMG replisome disassembly by VCP and chromatin extraction during S-phase (PubMed:33590678).
Pathway
Protein modification; protein ubiquitination.
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Aspect | Term | |
---|---|---|
Cellular Component | Cul2-RING ubiquitin ligase complex | |
Cellular Component | nucleolus | |
Cellular Component | nucleoplasm | |
Cellular Component | VCB complex | |
Molecular Function | protein-containing complex binding | |
Molecular Function | ubiquitin ligase complex scaffold activity | |
Molecular Function | ubiquitin protein ligase binding | |
Biological Process | protein catabolic process | |
Biological Process | protein ubiquitination | |
Biological Process | ubiquitin-dependent protein catabolic process via the C-end degron rule pathway |
Keywords
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameCullin-2
- Short namesCUL-2
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ9D4H8
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
PTM/Processing
Features
Showing features for chain, modified residue, cross-link.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000119791 | 1-745 | Cullin-2 | |||
Sequence: MSLKPRVVDFDETWNKLLTTIKAVVMLEYVERATWNDRFSDIYALCVAYPEPLGERLYAETKIFLESHVRHLYKRVLESEEQVLVMYHRYWEEYSKGADYMDCLYRYLNTQYIKKNKLTEADIQYGYGGVDMNEPLMEIGELALDMWRKLMVEPLQNILIRMLLREIKNDRGGEDPNQKVIHGVINSFVHVEQYKKKFPLKFYQGIFVSPFLTETGEYYKQEASNLLQESNCSQYMEKVLGRLKDEEIRCRKYLHPSSYTKVIHECQQRMVADHLQFLHSECHSIIQQERKNDMANMYVLLRAVSSGLPHMIEELQKHIHDEGLRATSNLTQEHMPTLFVESVLEVHGKFVQLINTVLNGDQHFMSALDKALTSVVNYREPKSVCKAPELLAKYCDNLLKKSAKGMTENEVEDKLTSFITVFKYIDDKDVFQKFYARMLAKRLIHGLSMSMDSEEAMINKLKQACGYEFTSKLHRMYTDMSVSADLNNKFNNFIRNQDTVIDLGISFQIYVLQAGAWPLTQAPSSTFAIPQELEKSVQMFELFYSQHFSGRKLTWLHYLCTGEVKMNYLGKPYVAMVTTYQMAVLLAFNNSETVSYKELQDSTQMNEKELTKTIKSLLDVKMINHDSEKEDIDAESSFSLNMSFSSKRTKFKITTSMQKDTPQELEQTRSAVDEDRKMYLQAAIVRIMKARKVLRHNALIQEVISQSRARFNPSISMIKKCIEVLIDKQYIERSQASADEYSYVA | ||||||
Modified residue | 393 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 661 | Phosphothreonine | ||||
Sequence: T | ||||||
Cross-link | 689 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in NEDD8) | ||||
Sequence: K |
Post-translational modification
Neddylated; which enhances the ubiquitination activity of ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complexes (By similarity).
Neddylation leads to structural rearrangment in the complex that allows interaction between the E2 ubiquitin-conjugating enzyme and the acceptor ubiquitin (By similarity).
CBC(VHL) complex formation seems to promote neddylation (By similarity).
Deneddylated via its interaction with the COP9 signalosome (CSN) complex (PubMed:11967155).
Neddylation leads to structural rearrangment in the complex that allows interaction between the E2 ubiquitin-conjugating enzyme and the acceptor ubiquitin (By similarity).
CBC(VHL) complex formation seems to promote neddylation (By similarity).
Deneddylated via its interaction with the COP9 signalosome (CSN) complex (PubMed:11967155).
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Gene expression databases
Interaction
Subunit
Component of multiple Cul2-RING (CRL2) E3 ubiquitin-protein ligase complexes consisting of CUL2, Elongin BC (ELOB and ELOC), RBX1 and a variable substrate-specific adapter; this complex is also known as ECS (Elongin BC-CUL2/5-SOCS-box protein) complex and may consist of CUL2 or CUL5 (By similarity).
Component of the ECS(VHL) or CBC(VHL) complex containing CUL2, RBX1, ELOB, ELOC and VHL (By similarity).
Component of the ECS(MED8) complex with the probable substrate recognition component MED8 (By similarity).
Component of multiple ECS complexes part of the DesCEND (destruction via C-end degrons) pathway, which contain either KLHDC2, KLHDC3, KLHDC10, APPBP2, FEM1A, FEM1B or FEM1C as substrate-recognition component (By similarity).
Component of the ECS(LRR1) complex with the substrate recognition component LRR1 (PubMed:33590678).
Component of a CRL2(FEM1B) complex containing CUL2, RBX1, ELOB, ELOC and FEM1B (By similarity).
Component of a CRL2(FEM1C) complex containing CUL2, RBX1, ELOB, ELOC and FEM1C (By similarity).
Part of an E3 ubiquitin-protein ligase complex including ZYG11B, CUL2 and Elongin BC (By similarity).
Part of an E3 ubiquitin-protein ligase complex including ZER1, CUL2 and Elongin BC (By similarity).
Interacts with RBX1, RNF7, FEM1B and TIP120A/CAND1 (By similarity).
Found in a complex composed of LIMD1, VHL, EGLN1/PHD2, ELOB and CUL2 (By similarity).
Interacts (when neddylated) with ARIH1; leading to activate the E3 ligase activity of ARIH1. Interacts (unneddylated form) with DCUN1D1, DCUN1D2, DCUN1D3, DCUN1D4 and DCUN1D5; these interactions promote the cullin neddylation (By similarity).
Component of VCB (elongins BC/CUL2/VHL) complex that contains at least DCUN1D1, CUL2 and VHL; this complex triggers CUL2 neddylation and consequently cullin ring ligase (CRL) substrates polyubiquitylation (By similarity).
Component of the ECS(VHL) or CBC(VHL) complex containing CUL2, RBX1, ELOB, ELOC and VHL (By similarity).
Component of the ECS(MED8) complex with the probable substrate recognition component MED8 (By similarity).
Component of multiple ECS complexes part of the DesCEND (destruction via C-end degrons) pathway, which contain either KLHDC2, KLHDC3, KLHDC10, APPBP2, FEM1A, FEM1B or FEM1C as substrate-recognition component (By similarity).
Component of the ECS(LRR1) complex with the substrate recognition component LRR1 (PubMed:33590678).
Component of a CRL2(FEM1B) complex containing CUL2, RBX1, ELOB, ELOC and FEM1B (By similarity).
Component of a CRL2(FEM1C) complex containing CUL2, RBX1, ELOB, ELOC and FEM1C (By similarity).
Part of an E3 ubiquitin-protein ligase complex including ZYG11B, CUL2 and Elongin BC (By similarity).
Part of an E3 ubiquitin-protein ligase complex including ZER1, CUL2 and Elongin BC (By similarity).
Interacts with RBX1, RNF7, FEM1B and TIP120A/CAND1 (By similarity).
Found in a complex composed of LIMD1, VHL, EGLN1/PHD2, ELOB and CUL2 (By similarity).
Interacts (when neddylated) with ARIH1; leading to activate the E3 ligase activity of ARIH1. Interacts (unneddylated form) with DCUN1D1, DCUN1D2, DCUN1D3, DCUN1D4 and DCUN1D5; these interactions promote the cullin neddylation (By similarity).
Component of VCB (elongins BC/CUL2/VHL) complex that contains at least DCUN1D1, CUL2 and VHL; this complex triggers CUL2 neddylation and consequently cullin ring ligase (CRL) substrates polyubiquitylation (By similarity).
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 675-735 | Cullin neddylation | ||||
Sequence: DRKMYLQAAIVRIMKARKVLRHNALIQEVISQSRARFNPSISMIKKCIEVLIDKQYIERSQ |
Domain
The Cullin neddylation domain restrains the RING domain of RBX1 in the E3 ubiquitin-protein ligase complex; this restraint is removed upon neddylation of the cullin.
Sequence similarities
Belongs to the cullin family.
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
Q9D4H8-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length745
- Mass (Da)86,877
- Last updated2003-11-07 v2
- Checksum311C05CC262692E0
Q9D4H8-2
- Name2
- Differences from canonical
- 664-702: Missing
Computationally mapped potential isoform sequences
There are 4 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A3Q4EBZ1 | A0A3Q4EBZ1_MOUSE | Cul2 | 111 | ||
H7BX52 | H7BX52_MOUSE | Cul2 | 90 | ||
A0A3Q4EI83 | A0A3Q4EI83_MOUSE | Cul2 | 49 | ||
E0CYT5 | E0CYT5_MOUSE | Cul2 | 582 |
Features
Showing features for sequence conflict, alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 612 | in Ref. 1; BAB30283 | ||||
Sequence: K → R | ||||||
Alternative sequence | VSP_008823 | 664-702 | in isoform 2 | |||
Sequence: Missing |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AK016520 EMBL· GenBank· DDBJ | BAB30283.1 EMBL· GenBank· DDBJ | mRNA | ||
AK160597 EMBL· GenBank· DDBJ | BAE35903.1 EMBL· GenBank· DDBJ | mRNA | ||
BC026779 EMBL· GenBank· DDBJ | AAH26779.1 EMBL· GenBank· DDBJ | mRNA | ||
BC027428 EMBL· GenBank· DDBJ | AAH27428.1 EMBL· GenBank· DDBJ | mRNA | ||
BC025902 EMBL· GenBank· DDBJ | AAH25902.1 EMBL· GenBank· DDBJ | mRNA |