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CUL5 cullin 5 [ Homo sapiens (human) ]

Gene ID: 8065, updated on 6-Jan-2019

Summary

Official Symbol
CUL5provided by HGNC
Official Full Name
cullin 5provided by HGNC
Primary source
HGNC:HGNC:2556
See related
Ensembl:ENSG00000166266 MIM:601741
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
Expression
Ubiquitous expression in thyroid (RPKM 9.9), kidney (RPKM 8.6) and 25 other tissues See more
Orthologs

Genomic context

See CUL5 in Genome Data Viewer
Location:
11q22.3
Exon count:
22
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 11 NC_000011.10 (108008733..108107776)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 11 NC_000011.9 (107879408..107978495)

Chromosome 11 - NC_000011.10Genomic Context describing neighboring genes Neighboring gene ribosomal protein lateral stalk subunit P2 pseudogene 3 Neighboring gene RAB39A, member RAS oncogene family Neighboring gene acetyl-CoA acetyltransferase 1 Neighboring gene nuclear protein, coactivator of histone transcription Neighboring gene ATM serine/threonine kinase

Genomic regions, transcripts, and products

Expression

  • Project title: 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

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

HIV-1 interactions

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

Go to the HIV-1, Human Interaction Database

Pathways from BioSystems

  • Adaptive Immune System, organism-specific biosystem (from REACTOME)
    Adaptive Immune System, organism-specific biosystemAdaptive immunity refers to antigen-specific immune response efficiently involved in clearing the pathogens. The adaptive immune system is comprised of B and T lymphocytes that express receptors with...
  • Antigen processing: Ubiquitination & Proteasome degradation, organism-specific biosystem (from REACTOME)
    Antigen processing: Ubiquitination & Proteasome degradation, organism-specific biosystemIntracellular foreign or aberrant host proteins are cleaved into peptide fragments of a precise size, such that they can be loaded on to class I MHC molecules and presented externally to cytotoxic T ...
  • Apoptosis-related network due to altered Notch3 in ovarian cancer, organism-specific biosystem (from WikiPathways)
    Apoptosis-related network due to altered Notch3 in ovarian cancer, organism-specific biosystemResults of pathway analysis of apoptosis-related genes in OVCAR3 cells treated with Notch3 siRNA or control siRNA.
  • Class I MHC mediated antigen processing & presentation, organism-specific biosystem (from REACTOME)
    Class I MHC mediated antigen processing & presentation, organism-specific biosystemMajor histocompatibility complex (MHC) class I molecules play an important role in cell mediated immunity by reporting on intracellular events such as viral infection, the presence of intracellular b...
  • Disease, organism-specific biosystem (from REACTOME)
    Disease, organism-specific biosystemBiological processes are captured in Reactome by identifying the molecules (DNA, RNA, protein, small molecules) involved in them and describing the details of their interactions. From this molecular ...
  • Downregulation of ERBB2 signaling, organism-specific biosystem (from REACTOME)
    Downregulation of ERBB2 signaling, organism-specific biosystemSignaling by ERBB2 can be downregulated by ubiquitination and subsequent proteasome-dependent degradation of ERBB2 or activated ERBB2 heterodimers. In addition, protein tyrosine phosphatases that dep...
  • Dual hijack model of Vif in HIV infection, organism-specific biosystem (from WikiPathways)
    Dual hijack model of Vif in HIV infection, organism-specific biosystemBy hijacking CBF-b, Vif is manipulating the ubquitination machinery and adversely effecting host transcriptional regulation. Vif: Viral infectivity factor, HIV protein.
  • ECS complex, organism-specific biosystem (from KEGG)
    ECS complex, organism-specific biosystemStructural complex; Genetic information processing; Ubiquitin system
  • ECS complex, conserved biosystem (from KEGG)
    ECS complex, conserved biosystemStructural complex; Genetic information processing; Ubiquitin system
  • HIV Infection, organism-specific biosystem (from REACTOME)
    HIV Infection, organism-specific biosystemThe global pandemic of Human Immunodeficiency Virus (HIV) infection has resulted in tens of millions of people infected by the virus and millions more affected. UNAIDS estimates around 40 million ...
  • Host Interactions of HIV factors, organism-specific biosystem (from REACTOME)
    Host Interactions of HIV factors, organism-specific biosystemLike all viruses, HIV-1 must co-opt the host cell macromolecular transport and processing machinery. HIV-1 Vpr and Rev proteins play key roles in this co-optation. Efficient HIV-1 replication likewis...
  • Immune System, organism-specific biosystem (from REACTOME)
    Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
  • Infectious disease, organism-specific biosystem (from REACTOME)
    Infectious disease, organism-specific biosystem
    Infectious disease
  • Signal Transduction, organism-specific biosystem (from REACTOME)
    Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
  • Signaling by ERBB2, organism-specific biosystem (from REACTOME)
    Signaling by ERBB2, organism-specific biosystemERBB2, also known as HER2 or NEU, is a receptor tyrosine kinase (RTK) belonging to the EGFR family. ERBB2 possesses an extracellular domain that does not bind any known ligand, contrary to other EGFR...
  • Ubiquitin mediated proteolysis, organism-specific biosystem (from KEGG)
    Ubiquitin mediated proteolysis, organism-specific biosystemProtein ubiquitination plays an important role in eukaryotic cellular processes. It mainly functions as a signal for 26S proteasome dependent protein degradation. The addition of ubiquitin to protein...
  • Ubiquitin mediated proteolysis, conserved biosystem (from KEGG)
    Ubiquitin mediated proteolysis, conserved biosystemProtein ubiquitination plays an important role in eukaryotic cellular processes. It mainly functions as a signal for 26S proteasome dependent protein degradation. The addition of ubiquitin to protein...
  • Vif-mediated degradation of APOBEC3G, organism-specific biosystem (from REACTOME)
    Vif-mediated degradation of APOBEC3G, organism-specific biosystemThe HIV-1 accessory protein Vif (Viral infectivity factor) is required for the efficient infection of primary cell populations (e.g., lymphocytes and macrophages) and 'non-permissive' cell lines. Vif...

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
calcium channel activity TAS
Traceable Author Statement
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
signaling receptor activity TAS
Traceable Author Statement
more info
PubMed 
contributes_to ubiquitin protein ligase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
ubiquitin protein ligase binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
ubiquitin protein ligase binding IDA
Inferred from Direct Assay
more info
PubMed 
ubiquitin-protein transferase activity TAS
Traceable Author Statement
more info
 
Process Evidence Code Pubs
ERBB2 signaling pathway TAS
Traceable Author Statement
more info
 
G1/S transition of mitotic cell cycle TAS
Traceable Author Statement
more info
PubMed 
SCF-dependent proteasomal ubiquitin-dependent protein catabolic process IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
calcium ion transmembrane transport IEA
Inferred from Electronic Annotation
more info
 
cell cycle arrest TAS
Traceable Author Statement
more info
PubMed 
cell proliferation TAS
Traceable Author Statement
more info
PubMed 
intrinsic apoptotic signaling pathway TAS
Traceable Author Statement
more info
PubMed 
negative regulation of cell proliferation TAS
Traceable Author Statement
more info
PubMed 
post-translational protein modification TAS
Traceable Author Statement
more info
 
proteasome-mediated ubiquitin-dependent protein catabolic process IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
protein ubiquitination IEA
Inferred from Electronic Annotation
more info
 
ubiquitin-dependent protein catabolic process IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
viral process IEA
Inferred from Electronic Annotation
more info
 
Component Evidence Code Pubs
Cul5-RING ubiquitin ligase complex IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
Cul5-RING ubiquitin ligase complex IDA
Inferred from Direct Assay
more info
PubMed 
SCF ubiquitin ligase complex IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
cullin-RING ubiquitin ligase complex IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
cytosol TAS
Traceable Author Statement
more info
 

General protein information

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)

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)

  1. NM_003478.5NP_003469.2  cullin-5

    See identical proteins and their annotated locations for NP_003469.2

    Status: VALIDATED

    Source sequence(s)
    AI688961, AK125294, AP002433, AP003307, BC037203, BC063306
    Consensus CDS
    CCDS31668.1
    UniProtKB/Swiss-Prot
    Q93034
    Related
    ENSP00000376808.2, ENST00000393094.6
    Conserved Domains (2) summary
    pfam00888
    Location:20671
    Cullin; Cullin family
    pfam10557
    Location:713772
    Cullin_Nedd8; Cullin protein neddylation domain

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109

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

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000011.10 Reference GRCh38.p12 Primary Assembly

    Range
    108008733..108107776
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017018363.2XP_016873852.1  cullin-5 isoform X1

  2. XM_011543013.2XP_011541315.1  cullin-5 isoform X4

    Conserved Domains (1) summary
    pfam00888
    Location:20371
    Cullin; Cullin family
  3. XM_005271682.2XP_005271739.1  cullin-5 isoform X2

    Conserved Domains (2) summary
    pfam00888
    Location:20612
    Cullin; Cullin family
    pfam10557
    Location:654713
    Cullin_Nedd8; Cullin protein neddylation domain
  4. XM_017018364.1XP_016873853.1  cullin-5 isoform X3

    Conserved Domains (3) summary
    smart00182
    Location:182325
    CULLIN; Cullin
    pfam00888
    Location:1410
    Cullin; Cullin family
    pfam10557
    Location:452511
    Cullin_Nedd8; Cullin protein neddylation domain
  5. XM_017018365.1XP_016873854.1  cullin-5 isoform X3

    Conserved Domains (3) summary
    smart00182
    Location:182325
    CULLIN; Cullin
    pfam00888
    Location:1410
    Cullin; Cullin family
    pfam10557
    Location:452511
    Cullin_Nedd8; Cullin protein neddylation domain
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