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FLASH GENE
Symbol CUL3 contributors: mct/pgu - updated : 15-03-2016
HGNC name cullin 3
HGNC id 2553
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularvessel   highly
Digestiveesophagus   highly
 pharynx   highly
Endocrineparathyroid   predominantly
Lymphoid/Immunelymph node   highly
Reproductivemale systemtestis  highly
Urinarykidney   highly
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Connective   moderately
Muscularstriatumcardiac  
Muscularstriatumskeletal  
cell lineage
cell lines
fluid/secretion
at STAGE
cell cycle     cell cycle, checkpoint, G1S
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
conjugated PhosphoP , Other
mono polymer dimer
HOMOLOGY
interspecies homolog to rattus Cul3 (99.6 pc)
homolog to murine Cul3 (99.5 pc)
Homologene
FAMILY
  • cullin family
  • CATEGORY regulatory , tumor suppressor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,Golgi
    intracellular,nucleus,chromatin/chromosome
    text
  • KLHL7 and CUL3 co-localized in punctate structures in the cytoplasm
  • in the absence of Retinoic acid (RA), present in the cytoplasm, and migrates to nuclei in response to RA
  • ZBTB16 transports CUL3 to the nucleus, where the two proteins are associated within a chromatin-modifying complex
  • basic FUNCTION
  • likely involved in cell proliferation control
  • may target other proteins for ubiquitin-dependent proteolysis
  • negative regulator of the cell cycle
  • playing a role in the induction of apoptosis by intracellular signals
  • SPOP/CUL3-ubiquitin ligase plays an essential role in the control of DAXX level and, thus, in the regulation of DAXX-mediated cellular processes, including transcriptional regulation and apoptosis
  • crucial role of CUL3 in regulating late steps in the endolysosomal trafficking pathway
  • potentially required but not limiting for efficient EGF and EGFR trafficking and degradation
  • fundamental role for KLHL3 and CUL3 in blood pressure, K+ and pH homeostasis
  • CUL3-KLHL12 catalyses the monoubiquitylation of the COPII-component SEC31 and drives the assembly of large COPII coats
  • specific role of CUL3 and KLHL3 in electrolyte homeostasis, providing a molecular explanation for the effects of disease-causing mutations in both KLHL3 and WNK4
  • CELLULAR PROCESS cell cycle, checkpoint
    cell life, proliferation/growth
    cell life, cell death/apoptosis
    protein, ubiquitin dependent proteolysis
    PHYSIOLOGICAL PROCESS
    text
  • mitotic G1/S transition
  • third step of ubiquitin conjugation
  • positive regulation of cell proliferation
  • PATHWAY
    metabolism
    signaling
    a component
  • part of a complex consisting of PCGF4, CUL3 and SPOP
  • part of a complex consisting of H2AFY, CUL3 and SPOP
  • neddylated (deneddylated via its interaction with the COP9 signalosome (CSN) complex)
  • dimeric SPOP-CUL3 assembly involving a conserved helical structure C-terminal of BTB domains
  • NFE2L2 serves as a substrate adaptor to link NFE2L2 to CUL3 and RBX1 (NFE2L2 regulates CUL3-RBX1 by controlling regulation of expression and induction of CUL3-RBX1, and the induction of CUL3-RBX1 control NFE2Lf2 by increasing degradation)
  • forms a dimer, assembles with CUL3 through its BTB and BACK domains, and exerts E3 activity
  • KBTBD13 is able to form a complex with CUL3 and RBX1 to reconstitute a functional ubiquitin ligase capable of conjugating ubiquitin onto KBTBD13
  • BCL6-CUL3 complexes also provide essential negative feedback regulation during both thymocyte development and T cell activation to restrain excessive T follicular helper (Tfh) responses
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with RBX1, RNF7, CYCE and TIP120A/CAND1
  • interacting specifically with Keap1
  • KLHL20-CUL3-RBX1 E3 ligase complex promotes DAPK1 polyubiquitination, thereby inducing the proteasomal degradation of DAPK1, and controling interferon response
  • KLHL7 co-localizes with CUL3, and all of the domains are necessary for the punctate subcellular localization
  • CUL3, a component of E3 ubiquitin ligase, is a new binding partner of BRMS1 and the interaction between BRMS1 and CUL3 is mediated by the SPOP adaptor protein
  • responsible for joining the ligase activity-bearing subunit RBX1 with a BTB-containing protein
  • KBTBD13 interacts with Cullin 3 (CUL3) and the BTB domain mediates this interaction
  • CUL3 was also found associated with the BTB-ZF transcription factor BCL6, which directs the germinal-centre B cell and follicular T-helper cell programs
  • WNK4 is a substrate for KLHL3-CUL3 E3 ubiquitin ligase complexes
  • CUL3 has the ability to bind to Kelch-like 3 protein (KLHL3) and therefore mediating the degradation of some members of the WNK kinases
  • CUL3-KLHL20 ubiquitin E3 ligase catalyzes a nondegradable, K33-linked polyubiquitination on CORO7, which facilitates CORO7 targeting to TGN through a ubiquitin-dependent interaction with EPS15
  • KCTD6(BTB) and KCTD11(BTB) bind CUL3 with high affinity forming stable complexes with 4:4 stoichiometries
  • KCTD5 or Cullin3 overexpression increased ZNF711 protein stability
  • ULK1, a serine/threonine kinase critical for autophagy initiation, is a substrate of the CUL3-KLHL20 ubiquitin ligase
  • CUL3 also interacts with both ARRB1, ARRB2 but has no influence on their ubiquitination
  • CUL3 interacts with ACLY through its adaptor protein, KLHL25 (Kelch-like family member 25), to ubiquitinate and degrade ACLY in cells
  • the effects of DCUN1D1 on spermatogenesis likely involve its regulation of cullin-RING-ligase (CRL)-type ubiquitin E3 activity during spermiogenesis through its role in promoting CUL3 neddylation
  • cell & other
    REGULATION
    induced by phorbol 12-myristate 13-acetate (PMA)
    inhibited by salicylate
    ASSOCIATED DISORDERS
    corresponding disease(s) PHA2E
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in colon carcinoma
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS