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FLASH GENE
Symbol CUL3 contributors: mct/pgu - updated : 15-03-2016
HGNC name cullin 3
HGNC id 2553
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