CUL5
entrez
8065
canonical
uniprot
Q93034
canonical
ensembl
ENSG00000166266
resolver
ensp
ENSP00000376808
resolver
ensp
ENSP00000435376
resolver
ensp
ENSP00000786683
resolver
enst
ENST00000393094
resolver
enst
ENST00000531427
resolver
genesymbol
CUL5
resolver
genesymbol_syn
VACM1
resolver
hgnc
HGNC:2556
resolver
uniprot
A8K960
resolver
uniprot
O14766
resolver
uniprot
Q9BZC6
resolver
uniprot_entry
CUL5_HUMAN
resolver
uniprot_sec
A8K960
resolver
uniprot_sec
O14766
resolver
uniprot_sec
Q9BZC6
resolver
amino_acid_sequence
MATSNLLKNKGSLQFEDKWDFMRPIVLKLLRQESVTKQQWFDLFSDVHAVCLWDDKGPAKIHQALKEDILEFIKQAQARVLSHQDDTALLKAYIVEWRKFFTQCDILPKPFCQLEITLMGKQGSNKKSNVEDSIVRKLMLDTWNESIFSNIKNRLQDSAMKLVHAERLGEAFDSQLVIGVRESYVNLCSNPEDKLQIYRDNFEKAYLDSTERFYRTQAPSYLQQNGVQNYMKYADAKLKEEEKRALRYLETRRECNSVEALMECCVNALVTSFKETILAECQGMIKRNETEKLHLMFSLMDKVPNGIEPMLKDLEEHIISAGLADMVAAAETITTDSEKYVEQLLTLFNRFSKLVKEAFQDDPRFLTARDKAYKAVVNDATIFKLELPLKQKGVGLKTQPESKCPELLANYCDMLLRKTPLSKKLTSEEIEAKLKEVLLVLKYVQNKDVFMRYHKAHLTRRLILDISADSEIEENMVEWLREVGMPADYVNKLARMFQDIKVSEDLNQAFKEMHKNNKLALPADSVNIKILNAGAWSRSSEKVFVSLPTELEDLIPEVEEFYKKNHSGRKLHWHHLMSNGIITFKNEVGQYDLEVTTFQLAVLFAWNQRPREKISFENLKLATELPDAELRRTLWSLVAFPKLKRQVLLYEPQVNSPKDFTEGTLFSVNQEFSLIKNAKVQKRGKINLIGRLQLTTERMREEENEGIVQLRILRTQEAIIQIMKMRKKISNAQLQTELVEILKNMFLPQKKMIKEQIEWLIEHKYIRRDESDINTFIYMA
uniprot
proteins
function
FUNCTION: Core component of multiple cullin-5-RING E3 ubiquitin-protein ligase complexes (ECS complexes, also named CRL5 complexes), which mediate the ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:11384984, PubMed:15601820, PubMed:21199876, PubMed:21980433, PubMed:23897481, PubMed:25505247, PubMed:27910872, PubMed:32200094, PubMed:33268465, PubMed:35512830, PubMed:38418882, PubMed:40963025). Acts a scaffold protein that contributes to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme (PubMed:11384984, PubMed:15601820, PubMed:33268465). The functional specificity of the E3 ubiquitin-protein ligase complex depends on the variable SOCS box-containing substrate recognition component (PubMed:11384984, PubMed:15601820, PubMed:33268465). Acts as a key regulator of neuron positioning during cortex development: component of various SOCS-containing ECS complexes, such as the ECS(SOCS7) complex, that regulate reelin signaling by mediating ubiquitination and degradation of DAB1 (By similarity). ECS(SOCS1) seems to direct ubiquitination of JAK2 (PubMed:11384984). The ECS(SOCS2) complex mediates the ubiquitination and subsequent proteasomal degradation of phosphorylated EPOR and GHR (PubMed:21980433, PubMed:25505247). The ECS(SPSB3) complex catalyzes ubiquitination of nuclear CGAS (PubMed:38418882). ECS(KLHDC1) complex is part of the DesCEND (destruction via C-end degrons) pathway and mediates ubiquitination and degradation of truncated SELENOS selenoprotein produced by failed UGA/Sec decoding, which ends with a glycine (PubMed:32200094). The ECS(ASB9) complex mediates ubiquitination and degradation of CKB (PubMed:33268465). As part of some ECS complex, promotes 'Lys-11'-linked ubiquitination and degradation of BTRC (PubMed:27910872). As part of a multisubunit ECS complex, polyubiquitinates monoubiquitinated POLR2A (PubMed:19920177). As part of the ECS(RAB40C) complex, mediates ANKRD28 ubiquitination and degradation, thereby inhibiting protein phosphatase 6 (PP6) complex activity and focal adhesion assembly during cell migration (PubMed:35512830). As part of the ECS(RAB40A) complex, mediates RHOU 'Lys-48'-linked ubiquitination and degradation, thus inhibiting focal adhesion disassembly during cell migration (PubMed:26598620). As part of the ECS(RAB40B) complex, mediates LIMA1/EPLIN and RAP2 ubiquitination, thereby regulating actin cytoskeleton dynamics and stress fiber formation during cell migration (PubMed:33999101, PubMed:35293963). The ECS(ASB7) complex acts a negative regulator of H3K9me3 histone mark by mediating ubiquitination and degradation of SUV39H1 (PubMed:40440427). As part of the ECS(LRRC58) complex, mediates CDO1 ubiquitination and degradation, regulating cysteine catabolism (PubMed:40963025). May form a cell surface vasopressin receptor (PubMed:9037604). {ECO:0000250|UniProtKB:Q9D5V5, ECO:0000269|PubMed:11384984, ECO:0000269|PubMed:15601820, ECO:0000269|PubMed:19920177, ECO:0000269|PubMed:21199876, ECO:0000269|PubMed:21980433, ECO:0000269|PubMed:23897481, ECO:0000269|PubMed:25505247, ECO:0000269|PubMed:26598620, ECO:0000269|PubMed:27910872, ECO:0000269|PubMed:32200094, ECO:0000269|PubMed:33268465, ECO:0000269|PubMed:33999101, ECO:0000269|PubMed:35293963, ECO:0000269|PubMed:35512830, ECO:0000269|PubMed:38418882, ECO:0000269|PubMed:40440427, ECO:0000269|PubMed:40963025, ECO:0000269|PubMed:9037604}.; FUNCTION: (Microbial infection) Following infection by HIV-1 virus, CUL5 associates with HIV-1 Vif proteins and forms a cullin-5-RING E3 ubiquitin-protein ligase complex (ECS complex) that catalyzes ubiquitination and degradation of APOBEC3F and APOBEC3G (PubMed:16636053, PubMed:22190037). The complex can also ubiquitinate APOBEC3H to some extent (PubMed:37640699). {ECO:0000269|PubMed:16636053, ECO:0000269|PubMed:22190037, ECO:0000269|PubMed:37640699}.; FUNCTION: (Microbial infection) Seems to be involved in proteasomal degradation of p53/TP53 stimulated by adenovirus E1B-55 kDa protein. {ECO:0000269|PubMed:12186903}.
uniprot
proteins
mass_dalton
90955
uniprot
proteins
mutagenesis
MUTAGEN 52; /note="L->V: Strongly impaired interaction with HIV-1 Vif protein."; /evidence="ECO:0000269|PubMed:24402281"; MUTAGEN 53; /note="W->A: Strongly impaired interaction with HIV-1 Vif protein. Decreased interaction ith SOCS2."; /evidence="ECO:0000269|PubMed:23897481, ECO:0000269|PubMed:24402281"; MUTAGEN 55; /note="D->A: Strongly impaired interaction with HIV-1 Vif protein."; /evidence="ECO:0000269|PubMed:24402281"; MUTAGEN 460; /note="R->A: Impaired interaction with ARIH2."; /evidence="ECO:0000269|PubMed:34518685"; MUTAGEN 617..624; /note="ENLKLATE->ANLKAATA: Impaired interaction with ARIH2."; /evidence="ECO:0000269|PubMed:34518685"; MUTAGEN 691; /note="R->A: Impaired interaction with ARIH2."; /evidence="ECO:0000269|PubMed:34518685"; MUTAGEN 710; /note="L->D: Impaired interaction with ARIH2."; /evidence="ECO:0000269|PubMed:34518685"; MUTAGEN 717; /note="E->A: Impaired interaction with ARIH2."; /evidence="ECO:0000269|PubMed:34518685"; MUTAGEN 724; /note="K->R: Abolished neddylation and interaction with ARIH2."; /evidence="ECO:0000269|PubMed:33268465
uniprot
proteins
pathway_participation
PATHWAY: Protein modification; protein ubiquitination. {ECO:0000269|PubMed:11384984, ECO:0000269|PubMed:15601820, ECO:0000269|PubMed:21980433, ECO:0000269|PubMed:25505247, ECO:0000269|PubMed:27910872, ECO:0000269|PubMed:32200094, ECO:0000269|PubMed:33268465, ECO:0000269|PubMed:38418882, ECO:0000269|PubMed:40440427, ECO:0000269|PubMed:40963025}.
uniprot
proteins
post_translational_modification
PTM: Neddylated; which enhances the ubiquitination activity of ECS complexes and prevents binding of the inhibitor CAND1. Deneddylated via its interaction with the COP9 signalosome (CSN). {ECO:0000269|PubMed:10597293, ECO:0000269|PubMed:12186903, ECO:0000269|PubMed:18805092, ECO:0000269|PubMed:24076655}.
uniprot
proteins
protein_family
Cullin family
uniprot
proteins
pubmed
10230407
uniprot
proteins
pubmed
10597293
uniprot
proteins
pubmed
11384984
uniprot
proteins
pubmed
12186903
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15574592
uniprot
proteins
pubmed
15601820
uniprot
proteins
pubmed
16325183
uniprot
proteins
pubmed
16636053
uniprot
proteins
pubmed
18562529
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18805092
uniprot
proteins
pubmed
19920177
uniprot
proteins
pubmed
20532212
uniprot
proteins
pubmed
21119685
uniprot
proteins
pubmed
21199876
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21697472
uniprot
proteins
pubmed
21980433
uniprot
proteins
pubmed
22190037
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23201271
uniprot
proteins
pubmed
23897481
uniprot
proteins
pubmed
24076655
uniprot
proteins
pubmed
24337577
uniprot
proteins
pubmed
24402281
uniprot
proteins
pubmed
25505247
uniprot
proteins
pubmed
26041281
uniprot
proteins
pubmed
26598620
uniprot
proteins
pubmed
26906416
uniprot
proteins
pubmed
27910872
uniprot
proteins
pubmed
28292928
uniprot
proteins
pubmed
31387940
uniprot
proteins
pubmed
32200094
uniprot
proteins
pubmed
32513959
uniprot
proteins
pubmed
33268465
uniprot
proteins
pubmed
33999101
uniprot
proteins
pubmed
34518685
uniprot
proteins
pubmed
35293963
uniprot
proteins
pubmed
35486881
uniprot
proteins
pubmed
35512830
uniprot
proteins
pubmed
35633597
uniprot
proteins
pubmed
37640699
uniprot
proteins
pubmed
38418882
uniprot
proteins
pubmed
38574733
uniprot
proteins
pubmed
40440427
uniprot
proteins
pubmed
40963025
uniprot
proteins
pubmed
9037604
uniprot
proteins
sequence_length
780
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:35633597, ECO:0000269|PubMed:38418882}. Note=Localizes to sites of DNA damage in a UBAP2 and UBAP2L-dependent manner. {ECO:0000269|PubMed:35633597}.
uniprot
proteins