CUL2
entrez
8453
canonical
uniprot
Q13617
canonical
ensembl
ENSG00000108094
resolver
ensp
ENSP00000363880
resolver
ensp
ENSP00000363881
resolver
ensp
ENSP00000363883
resolver
ensp
ENSP00000414095
resolver
ensp
ENSP00000444856
resolver
ensp
ENSP00000508924
resolver
enst
ENST00000537177
resolver
enst
ENST00000690123
resolver
genesymbol
CUL2
resolver
hgnc
HGNC:2552
resolver
uniprot
A0A0A0MTN0
resolver
uniprot
A0A140VKB1
resolver
uniprot
A0A8I5KVR3
resolver
uniprot
B3KT95
resolver
uniprot
B7Z1Y1
resolver
uniprot
B7Z6K8
resolver
uniprot
D3DRY6
resolver
uniprot
G3V1S2
resolver
uniprot
O00200
resolver
uniprot
Q5T2B6
resolver
uniprot
Q9UNF9
resolver
uniprot_entry
A0A0A0MTN0_HUMAN
resolver
uniprot_entry
A0A140VKB1_HUMAN
resolver
uniprot_entry
A0A8I5KVR3_HUMAN
resolver
uniprot_entry
B7Z1Y1_HUMAN
resolver
uniprot_entry
CUL2_HUMAN
resolver
uniprot_sec
B3KT95
resolver
uniprot_sec
B7Z6K8
resolver
uniprot_sec
D3DRY6
resolver
uniprot_sec
G3V1S2
resolver
uniprot_sec
O00200
resolver
uniprot_sec
Q5T2B6
resolver
uniprot_sec
Q9UNF9
resolver
amino_acid_sequence
MSLKPRVVDFDETWNKLLTTIKAVVMLEYVERATWNDRFSDIYALCVAYPEPLGERLYTETKIFLENHVRHLHKRVLESEEQVLVMYHRYWEEYSKGADYMDCLYRYLNTQFIKKNKLTEADLQYGYGGVDMNEPLMEIGELALDMWRKLMVEPLQAILIRMLLREIKNDRGGEDPNQKVIHGVINSFVHVEQYKKKFPLKFYQEIFESPFLTETGEYYKQEASNLLQESNCSQYMEKVLGRLKDEEIRCRKYLHPSSYTKVIHECQQRMVADHLQFLHAECHNIIRQEKKNDMANMYVLLRAVSTGLPHMIQELQNHIHDEGLRATSNLTQENMPTLFVESVLEVHGKFVQLINTVLNGDQHFMSALDKALTSVVNYREPKSVCKAPELLAKYCDNLLKKSAKGMTENEVEDRLTSFITVFKYIDDKDVFQKFYARMLAKRLIHGLSMSMDSEEAMINKLKQACGYEFTSKLHRMYTDMSVSADLNNKFNNFIKNQDTVIDLGISFQIYVLQAGAWPLTQAPSSTFAIPQELEKSVQMFELFYSQHFSGRKLTWLHYLCTGEVKMNYLGKPYVAMVTTYQMAVLLAFNNSETVSYKELQDSTQMNEKELTKTIKSLLDVKMINHDSEKEDIDAESSFSLNMNFSSKRTKFKITTSMQKDTPQEMEQTRSAVDEDRKMYLQAAIVRIMKARKVLRHNALIQEVISQSRARFNPSISMIKKCIEVLIDKQYIERSQASADEYSYVA
uniprot
proteins
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 (PubMed:11384984, PubMed:26138980, PubMed:29775578, PubMed:29779948, PubMed:37844242, PubMed:38326650). CUL2 serves as a rigid scaffold in the complex and may contribute to catalysis through positioning of the substrate and the E2 ubiquitin-conjugating enzyme (PubMed:10973499, PubMed:11384984, PubMed:12609982, PubMed:24076655, PubMed:9122164, PubMed:37844242, PubMed:38326650). 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 (PubMed:12609982, PubMed:24076655, PubMed:27565346, PubMed:38326650). The functional specificity of the ECS complex depends on the substrate recognition component (PubMed:10973499, PubMed:26138980, PubMed:29775578, PubMed:29779948, PubMed:9122164, PubMed:38326650). ECS(VHL) mediates the ubiquitination of hypoxia-inducible factor (HIF) (PubMed:10973499, PubMed:9122164). 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 (PubMed:26138980, PubMed:29775578, PubMed:29779948, PubMed:37844242). ECS complexes and ARIH1 collaborate in tandem to mediate ubiquitination of target proteins (PubMed:27565346). ECS(LRR1) ubiquitinates MCM7 and promotes CMG replisome disassembly by VCP and chromatin extraction during S-phase (By similarity). {ECO:0000250|UniProtKB:Q9D4H8, ECO:0000269|PubMed:10973499, ECO:0000269|PubMed:11384984, ECO:0000269|PubMed:12609982, ECO:0000269|PubMed:24076655, ECO:0000269|PubMed:26138980, ECO:0000269|PubMed:27565346, ECO:0000269|PubMed:29775578, ECO:0000269|PubMed:29779948, ECO:0000269|PubMed:37844242, ECO:0000269|PubMed:38326650, ECO:0000269|PubMed:9122164}.
uniprot
proteins
mass_dalton
86983
uniprot
proteins
mutagenesis
MUTAGEN 621; /note="K->R: No effect on conjugation with NEDD8."; /evidence="ECO:0000269|PubMed:10092517"; MUTAGEN 660; /note="D->K: Activates UBE2R2-mediated ubiquitin chain extension in the absence of neddylation; when associated with K-664 and K-675."; /evidence="ECO:0000269|PubMed:38326650"; MUTAGEN 664; /note="E->K: Activates UBE2R2-mediated ubiquitin chain extension in the absence of neddylation; when associated with K-660 and K-675."; /evidence="ECO:0000269|PubMed:38326650"; MUTAGEN 675; /note="D->K: Activates UBE2R2-mediated ubiquitin chain extension in the absence of neddylation; when associated with K-660 and K-664."; /evidence="ECO:0000269|PubMed:38326650"; MUTAGEN 689; /note="K->R: Loss of conjugation with NEDD8."; /evidence="ECO:0000269|PubMed:10092517"; MUTAGEN 719; /note="K->R: No effect on conjugation with NEDD8."; /evidence="ECO:0000269|PubMed:10092517
uniprot
proteins
pathway_participation
PATHWAY: Protein modification; protein ubiquitination. {ECO:0000269|PubMed:26138980, ECO:0000269|PubMed:29775578, ECO:0000269|PubMed:29779948, ECO:0000269|PubMed:37844242, ECO:0000269|PubMed:38326650}.
uniprot
proteins
post_translational_modification
PTM: Neddylated; which enhances the ubiquitination activity of ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complexes (PubMed:24076655, PubMed:27565346, PubMed:38326650). Neddylation leads to structural rearrangment in the complex that allows interaction between the E2 ubiquitin-conjugating enzyme and the acceptor ubiquitin (PubMed:38326650). CBC(VHL) complex formation seems to promote neddylation. Deneddylated via its interaction with the COP9 signalosome (CSN) complex (By similarity). {ECO:0000250|UniProtKB:Q9D4H8, ECO:0000269|PubMed:24076655, ECO:0000269|PubMed:27565346, ECO:0000269|PubMed:38326650}.
uniprot
proteins
protein_family
Cullin family
uniprot
proteins
pubmed
10092517
uniprot
proteins
pubmed
10230407
uniprot
proteins
pubmed
10597293
uniprot
proteins
pubmed
10973499
uniprot
proteins
pubmed
11384984
uniprot
proteins
pubmed
12149480
uniprot
proteins
pubmed
12609982
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15164054
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15601820
uniprot
proteins
pubmed
17251292
uniprot
proteins
pubmed
17304241
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
19608861
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
22286099
uniprot
proteins
pubmed
23102700
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23201271
uniprot
proteins
pubmed
23401859
uniprot
proteins
pubmed
24076655
uniprot
proteins
pubmed
24192928
uniprot
proteins
pubmed
26138980
uniprot
proteins
pubmed
26906416
uniprot
proteins
pubmed
27565346
uniprot
proteins
pubmed
29775578
uniprot
proteins
pubmed
29779948
uniprot
proteins
pubmed
34700328
uniprot
proteins
pubmed
37844242
uniprot
proteins
pubmed
38326650
uniprot
proteins
pubmed
8681378
uniprot
proteins
pubmed
9122164
uniprot
proteins
sequence_length
745
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q9D4H8}.
uniprot
proteins