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FLASH GENE
Symbol CUL5 contributors: mct/npt - updated : 28-05-2020
HGNC name cullin 5
HGNC id 2556
Location 11q22.3      Physical location : 107.879.407 - 107.978.484
Synonym name vasopressin activated calcium mobilizing receptor 1
Synonym symbol(s) VACM1, VACM-1, CUL-5
DNA
TYPE functioning gene
STRUCTURE 99.03 kb     19 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status confirmed
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
19 - 6171 90.8 780 - 2019 31294695
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularvessel     Homo sapiens
Digestivemouthtongue  highly
Endocrineneuroendocrinepituitary  highly
Urinarykidneytubule    Homo sapiens
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Connectiveadipose  highly
cells
SystemCellPubmedSpeciesStageRna symbol
Cardiovascularendothelial cell Homo sapiens
Urinarytubular cell Homo sapiens
cell lineage
cell lines
fluid/secretion
at STAGE
cell cycle     cell cycle, checkpoint, G1S
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a nuclear localization signal (NLS) playing a role in the cellular localization of CUL5, its effect on cellular growth and critical for the control of cell proliferation
  • HOMOLOGY
    interspecies homolog to C.elegans
    homolog to rabbit vasopressin-activated calcium mobilizing repressor
    Homologene
    FAMILY
  • cullin (CUL) family
  • CATEGORY regulatory , tumor suppressor , transport channel
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    text
  • disappears during the cell cycle S phase; it localizes to the cytosol during cell division and to the cell membrane at the completion of cytokinesis, suggesting that it plays a role in cell division
  • basic FUNCTION
  • negative regulator of cell cycle
  • inhibits cellular growth by a mechanism that involves cAMP, MAPK phosphorylation, and TP53 expression (Van Dort 2003)
  • involved in the regulation of cellular growth (Burnatowska-Hledin 2004)
  • component of E3 ubiquitin ligase complexes, which mediate the ubiquitination and subsequent proteasomal
  • degradation of target proteins
  • may be involved in proteosomal degradation of TP53
  • stimulated by adenovirus E1B-55 kDa protein
  • CUL5-containing E3 ubiquitin ligase complex may play an important role in granulocytic differentiation (Baxter 2008)
  • plays an essential role in regulating neuron migrations during cortical development, possibly by opposing a promigratory effect of DAB1 (Feng 2007)
  • importance of CUL5 in multiple aspects of the cellular response to HSP90AA1 inhibition
  • involved in the formation of E3-specific ligase complexes that are responsible for delivering the ubiquitin protein to their target substrate proteins selected for ubiquitin-dependent degradation
  • CUL5 expression is affected by water deprivation in some tissues and there is a potential relationship between neddylated CUL5 and aquaporins
  • CUL5-containing ubiquitin ligases regulate a variety of signaling pathways by targeting particular substrates for proteasomal degradation or competing for protein–protein interactions
  • CUL5 functions as a novel tumor suppressor with prognostic relevance in Clear cell renal cell carcinoma (ccRCC) and is critically involved in the maintenance of genome stability
  • CELLULAR PROCESS cell cycle, checkpoint
    cell life, proliferation/growth
    PHYSIOLOGICAL PROCESS
    text
  • negative regulaotr of cell proliferation
  • transport : calcium channel
  • G1/S transition
  • PATHWAY
    metabolism
    signaling signal transduction
    a component
  • forms complexes with SOCS (suppressors of cytokine signaling) proteins, which bind to phosphorylated DAB1 (Feng 2007)
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • is involved in the regulation of AQP2 protein concentration and may play a role in regulating water balance
  • CUL5 interacts extensively with ELOB/ELOC via residues that are highly conserved in CUL2 but not in other cullins, and also interacts with SOCS2, but via only two residues, Pro184 and Arg186, which are located in the C-terminal part of the SOCS box called the CUL5 box
  • binding to ELOB/ELOC induces conformational changes in HIV1 Vif, facilitating its interaction with CBFB and consequent interaction with CUL5
  • CUL5 is a scaffold protein that recruits RNF7, the ELOB/ELOC complex, and SOCS box proteins
  • ANKRD9 associates with CUL5 (not CUL2), ELOB, ELOC, and presumably RNF7 subunits, which together assemble into a cullin-RING superfamily E3 ligase complex
  • CUL5-ASB11 is the E3 ligase targeting BIK for ubiquitination and degradation
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in small cell carcinoma of the lung
    tumoral     --other  
    deregulation playing a role in the pathogenesis of B-cell chronic lymphocytic leukaemia (Kalla 2007)
    tumoral     --over  
    with granulocytic differentiation in promyelocytic leukemia (Baxter 2009)
    tumoral       loss of function
    deficiency in the E3 ligase subunit cullin 5 (CUL5) promotes chromosomal instability and is an independent negative prognostic factor in Clear cell renal cell carcinoma (ccRCC)
    tumoral     --over  
    high mRNA expression of CUL2, CUL4B, and CUL5 were correlated with better survival for breast cancers
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS