CUL5 cullin 5 [Homo sapiens (human)] - Gene

Summary

Official Symbol: CUL5provided by HGNC
Official Full Name: cullin 5provided by HGNC
Primary source: HGNC:HGNC:2556
See related: Ensembl:ENSG00000166266 MIM:601741; AllianceGenome:HGNC:2556
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: CUL-5; VACM1; VACM-1
Summary: Enables ubiquitin ligase complex scaffold activity and ubiquitin protein ligase binding activity. Involved in proteasome-mediated ubiquitin-dependent protein catabolic process and protein K11-linked ubiquitination. Located in site of DNA damage. Part of Cul5-RING ubiquitin ligase complex. Is active in nucleus. [provided by Alliance of Genome Resources, Oct 2024]
Expression: Ubiquitous expression in thyroid (RPKM 9.9), kidney (RPKM 8.6) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 11q22.3

Exon count:: 21

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	11	NC_000011.10 (108008898..108107761)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	11	NC_060935.1 (108015935..108114778)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	11	NC_000011.9 (107879624..107978488)

Chromosome 11 - NC_000011.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Ubiquitylation by Rab40b/Cul5 regulates Rap2 localization and activity during cell migration.
Title: Ubiquitylation by Rab40b/Cul5 regulates Rap2 localization and activity during cell migration.
Cullin-5 (CUL5) as a potential prognostic marker in a pan-cancer analysis of human tumors.
Title: Cullin-5 (CUL5) as a potential prognostic marker in a pan-cancer analysis of human tumors.
Th1 cytokine interferon gamma improves response in HER2 breast cancer by modulating the ubiquitin proteasomal pathway.
Title: Th1 cytokine interferon gamma improves response in HER2 breast cancer by modulating the ubiquitin proteasomal pathway.
Rab40-Cullin5 complex regulates EPLIN and actin cytoskeleton dynamics during cell migration.
Title: Rab40-Cullin5 complex regulates EPLIN and actin cytoskeleton dynamics during cell migration.
Cullin-5 neddylation-mediated NOXA degradation is enhanced by PRDX1 oligomers in colorectal cancer.
Title: Cullin-5 neddylation-mediated NOXA degradation is enhanced by PRDX1 oligomers in colorectal cancer.
miR-19a promotes the metastasis and EMT through CUL5 in prostate cancer cell line PC3.
Title: miR-19a promotes the metastasis and EMT through CUL5 in prostate cancer cell line PC3.
E4orf6 triggers Cullin5 neddylation, which activates the CRL5 E3 ligase for p53 degradation
Title: Adenovirus oncoprotein E4orf6 triggers Cullin5 neddylation to activate the CLR5 E3 ligase for p53 degradation.
BIK ubiquitination by the E3 ligase Cul5-ASB11 determines cell fate during cellular stress.
Title: BIK ubiquitination by the E3 ligase Cul5-ASB11 determines cell fate during cellular stress.
work identifies the essential role of CUL5- and SOCS3-mediated integrin beta1 turnover in controlling small-cell lung cancer metastasis, which might have therapeutic implications.
Title: Cullin5 deficiency promotes small-cell lung cancer metastasis by stabilizing integrin β1.
Accumulation of Noxa caused by depletion of CRL5 components was responsible for re-sensitization to CDK9 inhibitor, but not MCL1 inhibitor. Discovery of a novel role of CRL5 in apoptosis and resistance to multiple types of anticancer agents suggests the potential to improve combination treatments
Title: The CUL5 ubiquitin ligase complex mediates resistance to CDK9 and MCL1 inhibitors in lung cancer cells.

Submit: New GeneRIF Correction See all GeneRIFs (51)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Tat	tat	Cullin 5 is downregulated in HIV-1 Tat and NC cotransfection of HEK 293T cells	PubMed
Vif	vif	HIV-1 Vif interacts with CUL5	PubMed
	vif	Both Cul5-Rbx1 and Cul5-Rbx2 interactions promote APOBEC3G polyubiquitination in vitro and this promotion depends on the presence of the Vif-CBFbeta-EloB-EloC complex	PubMed
	vif	HIV-1 Vif ubiquitination is promoted by Cul5 in vitro and in vivo in a manner that requires an intact SOCS-box motif in Vif, and auto ubiquitination of Vif occurs within an assembled Vif-Cul5 complex	PubMed
	vif	CUL5/RBX2/ELOB/ELOC/Vif/CBF-beta complex catalyzes polyubiquitin chain formation on A3G in the presence of ubiquitin E2 UBE2R1 (CDC34) or UBCH5b (UBE2D2)	PubMed
	vif	HIV-1 Vif, CBF-beta, CUL5, and ELOB/C form a complex that is required for Vif-mediated downregulation of A3G and A3F. CBF-beta regulates HIV-1 infectivity only in the presence of A3G	PubMed
	vif	Two highly conserved Cys residues (C114 and C133) outside the SOCS box (amino acids 144-169) motif in HIV-1 Vif are required for the interaction of Vif with Cul5 but not ElonginC	PubMed
	vif	HIV-1 Vif (amino acids 144-149; SLQXLA motif; BC-box) interacts with cellular proteins Cul5, elongins B and C, and Rbx1 to form an Skp1-Cullin-F-box (SCF)-like complex that allows Vif to interact with APOBEC3G and induce its ubiquitination and degradation	PubMed
	vif	Amino-acid motifs 84GxSIEW89 and 102LADQLI107 in HIV-1 Vif affect its interaction with CUL5, and Vif mutants 84DVAAAA89, 88EW/AA89, G84A, G84D, W89A, S104A, L106S, and I107S have more than 50% reduction in CUL5 binding	PubMed
	vif	UBE2F and RBX2 are required for activation of the polyubiquitin synthesis activity of Vif/CBF-beta/CUL5, leading to HIV-1 Vif-mediated degradation of A3G in cells	PubMed
	vif	The T(Q/D/E)x(5)ADx(2)(I/L) motif, located at residues 96 to 107 in HIV-1 Vif, regulates Vif interaction with Cul5	PubMed
	vif	Simultaneous substitution of the three Vif-interacting residues L52, W53, and D55 and the two ELOC-interacting residues P41 and H48 in CUL5 impairs the ability of CUL5 to interact with the Vif-CBF-beta-ELOB-ELOC protein complex	PubMed
	vif	The absence of Vif-CBF-beta reduces the interaction between the CUL5 and the EloC-EloB complex, indicating that the former two proteins have a critical role in promoting assembly of the pentameric complex	PubMed
	vif	An overall crystal structure indicates that the Vif-CBF-beta-CUL5-ELOB-ELOC complex has a U-shape architecture, including the two straight arms Vif-CBF-beta and CUL5 and the bent arm formation between ELOC and CUL5 and Vif interactions	PubMed
	vif	The interaction between Cul5 and HIV-1, HIV-2, SIVmac, or SIVagm Vif protein require the presence of zinc	PubMed
	vif	The HIV-1 Vif N-terminal motif (residues 18-38) binds CUL5 in mammalian cells and is reguired for A3F and A3G degradation and HIV-1 infectivity	PubMed
	vif	HIV-1 Vif mutants C114S and C133A abolish the interaction with CUL5, which leads to fail to A3G degradation by Vif	PubMed
	vif	HIV-1 Vif YF111/112AA, F115A, I120S and AL123/124SS mutants are unable to recruit Cul5, but retain interactions with Elongin B and C proteins	PubMed
	vif	Deletion of amino acids 120 to 138 in Cul5 significantly reduces its interaction with HIV-1 Vif, but does not affect Cul5 binding to Elongins B/C; the HCCH zinc-binding motif (residues 108-139) in Vif is required for the interaction with Cul5	PubMed
	vif	The interaction between the HIV-1 Vif PPLP motif (residues 161-164) and the 34-amino-acid C-terminal tail (residues 85-118) of EloB plays a role in promoting recruitment of CBF-beta to the Vif-Cul5 E3 complex	PubMed
	vif	The conjugation of NEDD8 to Cullin-5 by UBE2F is required for HIV-1 Vif-mediated A3G degradation	PubMed
	vif	CBF-beta and the N-terminal half of HIV-1 Vif enhance the affinity of Cul5 for Vif	PubMed
	vif	HIV-1 Vif-induced G2 accumulation requires a Cul5-based E3 ligase, but is independent of APOBEC3D/E, F, and G expression. Overexpression of ubiquitin(K48R) abolishes Vif-induced G2 accumulation	PubMed
	vif	Mutations in HIV-1 Vif PPLP motif (amino acids 161-164) reduces Vif binding to A3G without affecting its interaction with ElonginC and Cullin5	PubMed
	vif	Chim3, corresponding to amino acids 126-170 of the natural mutant F12-Vif, interacts poorly with Cul5 but affects HIV-1 Vif/Cul5 interaction	PubMed
	vif	Vif-induced ubiquitination of A3G and A3G20K/R is inhibited by Cul5deltaNedd8	PubMed
	vif	HIV-1 Vif is regulated by Cullin5 E3 ligase and its expression levels increases in the presence of a Cullin5 dominant negative mutant, Cul5deltaNedd8	PubMed
	vif	The amino acids L163 and L169 located downstream of the SOCS-box motif in HIV-1 Vif are required for Vif function and efficient interaction with Cul5-ElonginB-ElonginC	PubMed
	vif	Treatment with the membrane-permeable zinc chelator TPEN prevents Vif function, and causes the blockage of Cul5 recruitment and APOBEC3G (A3G) degradation	PubMed
nucleocapsid	gag	Cullin 5 is downregulated in HIV-1 Tat and NC cotransfection of HEK 293T cells	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

STS-X81882 (e-PCR)
- UniSTS:22543

RH102471 (e-PCR)
- UniSTS:96805

CUL5_2069 (e-PCR)
- UniSTS:280630

RH102489 (e-PCR)
- UniSTS:96823

STS-AA037842 (e-PCR)
- UniSTS:26971

SHGC-81539 (e-PCR)
- UniSTS:104285

RH68294 (e-PCR)
- UniSTS:52578

SHGC-105141 (e-PCR)
- UniSTS:169197

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables calcium channel activity	TAS Traceable Author Statement more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein-macromolecule adaptor activity	IBA Inferred from Biological aspect of Ancestor more info
enables signaling receptor activity	TAS Traceable Author Statement more info	PubMed
enables ubiquitin ligase complex scaffold activity	IDA Inferred from Direct Assay more info	PubMed
enables ubiquitin protein ligase binding	IBA Inferred from Biological aspect of Ancestor more info
enables ubiquitin protein ligase binding	IDA Inferred from Direct Assay more info	PubMed
enables ubiquitin-protein transferase activity	TAS Traceable Author Statement more info

Process	Evidence Code	Pubs
involved_in ERBB2 signaling pathway	TAS Traceable Author Statement more info
involved_in G1/S transition of mitotic cell cycle	TAS Traceable Author Statement more info	PubMed
involved_in SCF-dependent proteasomal ubiquitin-dependent protein catabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in calcium ion transmembrane transport	IEA Inferred from Electronic Annotation more info
involved_in intrinsic apoptotic signaling pathway	TAS Traceable Author Statement more info	PubMed
involved_in proteasome-mediated ubiquitin-dependent protein catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in proteasome-mediated ubiquitin-dependent protein catabolic process	NAS Non-traceable Author Statement more info	PubMed
involved_in protein K11-linked ubiquitination	IDA Inferred from Direct Assay more info	PubMed
involved_in protein ubiquitination	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_negative_effect reelin-mediated signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of neuron migration	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
part_of Cul5-RING ubiquitin ligase complex	IBA Inferred from Biological aspect of Ancestor more info
part_of Cul5-RING ubiquitin ligase complex	IDA Inferred from Direct Assay more info	PubMed
part_of SCF ubiquitin ligase complex	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	TAS Traceable Author Statement more info
is_active_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in site of DNA damage	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: cullin-5

Names: Cullin-5 (vasopressin-activated calcium-mobilizing receptor-1); Vasopressin-activated calcium-mobilizing receptor-1; vasopressin-activated calcium-mobilizing receptor 1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_003478.6 → NP_003469.2 cullin-5

See identical proteins and their annotated locations for NP_003469.2

Status: VALIDATED

Source sequence(s)

AP002433, AP003307

Consensus CDS

CCDS31668.1

UniProtKB/Swiss-Prot

A8K960, O14766, Q93034, Q9BZC6

Related

ENSP00000376808.2, ENST00000393094.7

Conserved Domains (2) summary

pfam00888
Location:19 → 672

Cullin; Cullin family

pfam10557
Location:711 → 771

Cullin_Nedd8; Cullin protein neddylation domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000011.10 Reference GRCh38.p14 Primary Assembly

Range

108008898..108107761

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_017018363.3 → XP_016873852.1 cullin-5 isoform X1
XM_005271682.3 → XP_005271739.1 cullin-5 isoform X2

Conserved Domains (2) summary

pfam00888
Location:20 → 612

Cullin; Cullin family

pfam10557
Location:654 → 713

Cullin_Nedd8; Cullin protein neddylation domain
XM_047427640.1 → XP_047283596.1 cullin-5 isoform X3
XM_011543013.3 → XP_011541315.1 cullin-5 isoform X5

Conserved Domains (1) summary

pfam00888
Location:20 → 371

Cullin; Cullin family
XM_047427641.1 → XP_047283597.1 cullin-5 isoform X4