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Details on Person UniProt:Q93034 CUL5

Class:Id	ReferenceGeneProduct:67084
_chainChangeLog	initiator methionine:1 added on Sat February 7 2015;chain:2-780 added on Sat February 7 2015
_displayName	UniProt:Q93034 CUL5
_timestamp	2026-02-20 22:31:18
chain	chain:1-780
checksum	57463CB4ED76E303
comment	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). 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). May form a cell surface vasopressin receptor (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).FUNCTION (Microbial infection) Seems to be involved in proteasomal degradation of p53/TP53 stimulated by adenovirus E1B-55 kDa protein.PATHWAY Protein modification; protein ubiquitination.SUBUNIT Component of multiple cullin-5-RING E3 ubiquitin-protein ligase complexes (ECS complexes, also named CRL5 complexes) formed of CUL5, Elongin BC (ELOB and ELOC), RNF7/RBX2 and a variable SOCS box domain-containing protein as substrate-specific recognition component (PubMed:11384984, PubMed:15601820, PubMed:16325183, PubMed:21119685, PubMed:27910872, PubMed:32513959, PubMed:33268465, PubMed:35512830, PubMed:26598620, PubMed:33999101, PubMed:35293963, PubMed:40440427). CUL5-containing ECS complexes specifically contain RNF7/RBX2, and not RBX1, as catalytic subunit (PubMed:11384984, PubMed:15601820, PubMed:32513959, PubMed:33268465). Component of the ECS(ASB2) complex with the substrate recognition component ASB2 (PubMed:16325183, PubMed:21119685). Component of the ECS(ASB6) complex with the substrate recognition component ASB6 (PubMed:16325183). Component of the ECS(ASB7) complex with the substrate recognition component ASB7 (PubMed:16325183, PubMed:40440427). Component of the ECS(ASB9) complex with the substrate recognition component ASB9 (PubMed:33268465). Component of the ECS(ASB11) complex with the substrate recognition component ASB11 (PubMed:24337577, PubMed:31387940, PubMed:38574733). Component of the ECS(ASB12) complex with the substrate recognition component ASB12 (PubMed:16325183). Component of the ECS(LRRC41) complex with the substrate recognition component LRRC41 (PubMed:11384984). Component of the ECS(SOCS1) complex with the substrate recognition component SOCS1 (PubMed:11384984). Component of the ECS(SOCS2) complex with the substrate recognition component SOCS2 (PubMed:21980433, PubMed:23897481, PubMed:25505247). Component of the ECS(WSB1) complex with the substrate recognition subunit WSB1 (PubMed:15601820). Component of the ECS(SOCS3) complex with the substrate recognition component SOCS3 (PubMed:15601820). Component of the ECS(SOCS7) complex with the substrate recognition component SOCS7 (By similarity). Component of the ECS(SPSB1) complex with the substrate recognition component SPSB1 (PubMed:15601820). Component of the ECS(SPSB3) complex with the substrate recognition component SPSB3 (PubMed:38418882). Component of the ECS(SPSB2) complex with the substrate recognition component SPSB2 (PubMed:15601820). Component of the ECS(SPSB4) complex with the substrate recognition component SPSB4 (PubMed:15601820). Component of the ECS(RAB40) complex with the substrate recognition subunit RAB40A, RAB40B or RAB40C (PubMed:15601820, PubMed:35512830, PubMed:26598620, PubMed:33999101, PubMed:35293963). Component of the ECS(KLHDC1) complex with the substrate recognition component KLHDC1 (PubMed:32200094). Component of the ECS(PCMTD1) complex with the substrate recognition subunit PCMTD1 (PubMed:35486881). May also form complexes containing RBX1 and ELOA or VHL; additional evidence is however required to confirm this result in vivo (PubMed:10230407, PubMed:11384984, PubMed:18805092, PubMed:19920177). Interacts (when neddylated) with ARIH2; leading to activate the E3 ligase activity of ARIH2 (PubMed:24076655, PubMed:33268465, PubMed:34518685). Interacts with ERCC6; the interaction is induced by DNA damaging agents or inhibitors of RNA polymerase II elongation (PubMed:28292928). Interacts with ELOA (via the BC-box) (PubMed:28292928). Interacts (unneddylated form) with DCUN1D1, DCUN1D2, DCUN1D3, DCUN1D4 and DCUN1D5; these interactions promote the cullin neddylation (PubMed:23201271, PubMed:26906416).SUBUNIT (Microbial infection) Interacts (via the substrate recognition component) with HIV-1 Vif; forming an active cullin-5-RING E3 ubiquitin-protein ligase complex (ECS complex).SUBUNIT (Microbial infection) Interacts (via the substrate recognition component) with human adenovirus 5 proteins E1B-55K and E4-orf6.SUBUNIT (Microbial infection) Interacts with herpes virus 8 protein LANA1; this interaction promotes the degradation of NF-kappa-B component RELA.SUBUNIT (Microbial infection) Interacts with molluscum contagiosum virus protein MC132; this interaction promotes the degradation of NF-kappa-B component RELA.INTERACTION Localizes to sites of DNA damage in a UBAP2 and UBAP2L-dependent manner.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).SIMILARITY Belongs to the cullin family.
description	recommendedName: fullName evidence="48"Cullin-5 shortName evidence="48"CUL-5 alternativeName: fullName evidence="47"Vasopressin-activated calcium-mobilizing receptor 1 shortName evidence="47"VACM-1
geneName	CUL5 VACM1
identifier	Q93034
isSequenceChanged	FALSE
keyword	3D-structure Host-virus interaction Isopeptide bond Nucleus Phosphoprotein Proteomics identification Receptor Reference proteome Ubl conjugation Ubl conjugation pathway
modified	[InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9841277] Weiser, Joel [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 [InstanceEdit:9963647] Weiser, Joel, 2025-08-15 [InstanceEdit:9983091] Weiser, Joel, 2026-02-20
name	CUL5
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:8997661] ENSEMBL:ENSG00000166266 CUL5 [Homo sapiens]
secondaryIdentifier	CUL5_HUMAN A8K960 O14766 Q9BZC6
sequenceLength	780
species	[Species:48887] Homo sapiens
(referenceEntity)	[EntityWithAccessionedSequence:180528] CUL5 [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:8952014] G76-NEDD8-K724-CUL5 [cytosol] [Homo sapiens]
(referenceSequence)	[GroupModifiedResidue:8952013] neddylated lysine (monoNEDD8 [cytosol]) at 724
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No pathways have been reviewed or authored by UniProt:Q93034 CUL5 (67084)