Q9D4H8 · CUL2_MOUSE

  • Protein
    Cullin-2
  • Gene
    Cul2
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

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 annotationsall molecular functionvirus receptor activitydna bindingrna bindingcytoskeletal motor activitycatalytic activitygtpase activitystructural molecule activitytransporter activitycytoskeletal protein bindinglipid bindingcyclase activityantioxidant activityoxidoreductase activitytransferase activityhydrolase activitylyase activityisomerase activityligase activityprotein tag activitycargo receptor activityhistone bindingprotein folding chaperonetranslation regulator activitynutrient reservoir activityreceptor ligand activitymolecular transducer activitymolecular adaptor activitytoxin activitycell adhesion mediator activitymolecular function regulator activityvirus coreceptor activitycatalytic activity, acting on a proteincatalytic activity, acting on dnacatalytic activity, acting on rnamolecular carrier activitytranscription regulator activitygeneral transcription initiation factor activitymolecular sensor activitymolecular sequestering activityatp-dependent activityother molecular functionall biological processmitotic cell cyclecytokinesiscytoplasmic translationimmune system processmuscle system processcirculatory system processrenal system processrespiratory system processcarbohydrate metabolic processgeneration of precursor metabolites and energydna replicationdna repairdna recombinationchromatin organizationdna-templated transcriptionregulation of dna-templated transcriptiontrna metabolic processprotein foldingprotein glycosylationamino acid metabolic processmodified amino acid metabolic processlipid metabolic processvitamin metabolic processsulfur compound metabolic processintracellular protein transportnucleocytoplasmic transportautophagyinflammatory responsemitochondrion organizationcytoskeleton organizationmicrotubule-based movementperoxisome organizationlysosome organizationchromosome segregationcell adhesionestablishment or maintenance of cell polarityprogrammed cell deathphotosynthesismrna metabolic processsnrna metabolic processvesicle-mediated transportreproductive processdigestive system processsignalingcell differentiationprotein catabolic processextracellular matrix organizationregulatory ncrna-mediated gene silencingtelomere organizationcell junction organizationwound healingribosome biogenesiscilium organizationanatomical structure developmentcell motilitynervous system processendocrine processprotein maturationtransmembrane transportnucleobase-containing small molecule metabolic processhepaticobiliary system processmembrane organizationprotein-containing complex assemblycell wall organization or biogenesisnitrogen cycle metabolic processprotein localization to plasma membranedefense response to other organismdetoxificationmeiotic nuclear divisionmitotic nuclear divisionmitochondrial gene expressioncarbohydrate derivative metabolic processother biological processall cellular componentnuclear chromosomeextracellular regionextracellular spacecell wallnucleusnuclear envelopenucleoplasmchromosomenucleolusmitochondrionlysosomeendosomevacuoleperoxisomeendoplasmic reticulumgolgi apparatuslipid dropletmicrotubule organizing centercytosolribosomecytoskeletonplasma membraneciliumplastidthylakoidexternal encapsulating structureextracellular matrixcytoplasmic vesicleorganelleother cellular component
Cell color indicative of number of GO terms
AspectTerm
Cellular ComponentCul2-RING ubiquitin ligase complex
Cellular Componentnucleolus
Cellular Componentnucleoplasm
Cellular ComponentVCB complex
Molecular Functionprotein-containing complex binding
Molecular Functionubiquitin ligase complex scaffold activity
Molecular Functionubiquitin protein ligase binding
Biological Processprotein catabolic process
Biological Processprotein ubiquitination
Biological Processubiquitin-dependent protein catabolic process via the C-end degron rule pathway

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Cullin-2
  • Short names
    CUL-2

Gene names

    • Name
      Cul2

Organism names

  • Taxonomic identifier
  • Strains
    • C57BL/6J
    • Czech II
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus

Accessions

  • Primary accession
    Q9D4H8
  • Secondary accessions
    • Q3TUR8

Proteomes

Organism-specific databases

Subcellular Location

PTM/Processing

Features

Showing features for chain, modified residue, cross-link.

TypeIDPosition(s)Description
ChainPRO_00001197911-745Cullin-2
Modified residue393N6-acetyllysine
Modified residue661Phosphothreonine
Cross-link689Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in NEDD8)

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).

Keywords

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).

Protein-protein interaction databases

Miscellaneous

Structure

Family & Domains

Features

Showing features for domain.

TypeIDPosition(s)Description
Domain675-735Cullin neddylation

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

Align isoforms (2)
  • Sequence status
    Complete

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.

  • Length
    745
  • Mass (Da)
    86,877
  • Last updated
    2003-11-07 v2
  • Checksum
    311C05CC262692E0
MSLKPRVVDFDETWNKLLTTIKAVVMLEYVERATWNDRFSDIYALCVAYPEPLGERLYAETKIFLESHVRHLYKRVLESEEQVLVMYHRYWEEYSKGADYMDCLYRYLNTQYIKKNKLTEADIQYGYGGVDMNEPLMEIGELALDMWRKLMVEPLQNILIRMLLREIKNDRGGEDPNQKVIHGVINSFVHVEQYKKKFPLKFYQGIFVSPFLTETGEYYKQEASNLLQESNCSQYMEKVLGRLKDEEIRCRKYLHPSSYTKVIHECQQRMVADHLQFLHSECHSIIQQERKNDMANMYVLLRAVSSGLPHMIEELQKHIHDEGLRATSNLTQEHMPTLFVESVLEVHGKFVQLINTVLNGDQHFMSALDKALTSVVNYREPKSVCKAPELLAKYCDNLLKKSAKGMTENEVEDKLTSFITVFKYIDDKDVFQKFYARMLAKRLIHGLSMSMDSEEAMINKLKQACGYEFTSKLHRMYTDMSVSADLNNKFNNFIRNQDTVIDLGISFQIYVLQAGAWPLTQAPSSTFAIPQELEKSVQMFELFYSQHFSGRKLTWLHYLCTGEVKMNYLGKPYVAMVTTYQMAVLLAFNNSETVSYKELQDSTQMNEKELTKTIKSLLDVKMINHDSEKEDIDAESSFSLNMSFSSKRTKFKITTSMQKDTPQELEQTRSAVDEDRKMYLQAAIVRIMKARKVLRHNALIQEVISQSRARFNPSISMIKKCIEVLIDKQYIERSQASADEYSYVA

Q9D4H8-2

  • Name
    2
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical

Computationally mapped potential isoform sequences

There are 4 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
A0A3Q4EBZ1A0A3Q4EBZ1_MOUSECul2111
H7BX52H7BX52_MOUSECul290
A0A3Q4EI83A0A3Q4EI83_MOUSECul249
E0CYT5E0CYT5_MOUSECul2582

Features

Showing features for sequence conflict, alternative sequence.

TypeIDPosition(s)Description
Sequence conflict612in Ref. 1; BAB30283
Alternative sequenceVSP_008823664-702in isoform 2

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
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

Genome annotation databases

Similar Proteins

Disclaimer

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