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CUL3 Gene

protein-coding   GIFtS: 68
GCID: GC02M225298

Cullin 3

  See related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Cullin 31 2
CUL-32 3
PHA2E2 5
cullin-32
KIAA06173

External Ids:    HGNC: 25531   Entrez Gene: 84522   Ensembl: ENSG000000362577   OMIM: 6031365   UniProtKB: Q136183   

Export aliases for CUL3 gene to outside databases

Previous GC identifers: GC02M223357 GC02M224055 GC02M225537 GC02M225160 GC02M225043 GC02M217186


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for CUL3 Gene:
This gene encodes a member of the cullin protein family. The encoded protein plays a critical role in the
polyubiquitination and subsequent degradation of specific protein substrates as the core component and scaffold
protein of an E3 ubiquitin ligase complex. Complexes including the encoded protein may also play a role in late
endosome maturation. Mutations in this gene are a cause of type 2E pseudohypoaldosteronism. Alternatively spliced
transcript variants encoding multiple isoforms have been observed for this gene. (provided by RefSeq, Mar 2012)

GeneCards Summary for CUL3 Gene:
CUL3 (cullin 3) is a protein-coding gene. Diseases associated with CUL3 include pseudohypoaldosteronism type iie, and glomuvenous malformation. GO annotations related to this gene include ubiquitin-protein ligase activity and cyclin binding. An important paralog of this gene is CUL1.

UniProtKB/Swiss-Prot: CUL3_HUMAN, Q13618
Function: Core component of multiple cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complexes
which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. As a scaffold protein
may contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The E3
ubiquitin-protein ligase activity of the complex is dependent on the neddylation of the cullin subunit and is
inhibited by the association of the deneddylated cullin subunit with TIP120A/CAND1 (By similarity). The
functional specificity of the BCR complex depends on the BTB domain-containing protein as the substrate
recognition component. BCR(KLHL42) is involved in ubiquitination of KATNA1. BCR(SPOP) is involved in
ubiquitination of BMI1/PCGF4, BRMS1, H2AFY and DAXX, GLI2 and GLI3. Can also form a cullin-RING-based BCR
(BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex containing homodimeric SPOPL or the heterodimer formed by
SPOP and SPOPL; these complexes have lower ubiquitin ligase activity. BCR(KLHL9-KLHL13) controls the dynamic
behavior of AURKB on mitotic chromosomes and thereby coordinates faithful mitotic progression and completion of
cytokinesis. BCR(KLHL12) is involved in ER-Golgi transport by regulating the size of COPII coats, thereby playing
a key role in collagen export, which is required for embryonic stem (ES) cells division: BCR(KLHL12) acts by
mediating monoubiquitination of SEC31 (SEC31A or SEC31B). BCR(KLHL3) acts as a regulator of ion transport in the
distal nephron; by mediating ubiquitination of WNK4. The BCR(KLHL21) E3 ubiquitin ligase complex regulates
localization of the chromosomal passenger complex (CPC) from chromosomes to the spindle midzone in anaphase and
mediates the ubiquitination of AURKB. The BCR(KLHL22) ubiquitin ligase complex mediates monoubiquitination of
PLK1, leading to PLK1 dissociation from phosphoreceptor proteins and subsequent removal from kinetochores,
allowing silencing of the spindle assembly checkpoint (SAC) and chromosome segregation. The BCR(KLHL25) ubiquitin
ligase complex is involved in translational homeostasis by mediating ubiquitination and subsequent degradation of
hypophosphorylated EIF4EBP1 (4E-BP1). Involved in ubiquitination of cyclin E and of cyclin D1 (in vitro) thus
involved in regulation of G1/S transition. Involved in the ubiquitination of KEAP1, ENC1 and KLHL41. In concert
with ATF2 and RBX1, promotes degradation of KAT5 thereby attenuating its ability to acetylate and activate ATM

Gene Wiki entry for CUL3 Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence:
NC_000002.12  NT_005403.18  NC_018913.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the CUL3 gene promoter:
         E2F-3a   E2F-4   E2F-5   Egr-1   E2F-2   RelA   PPAR-gamma1   E2F   E2F-1   PPAR-gamma2   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 6): CUL3 promoter sequence
   Search Chromatin IP Primers for CUL3

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat CUL3


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 2q36.2   Ensembl cytogenetic band:  2q36.2   HGNC cytogenetic band: 2q36.2

CUL3 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
CUL3 gene location

GeneLoc information about chromosome 2         GeneLoc Exon Structure

GeneLoc location for GC02M225298:  view genomic region     (about GC identifiers)

Start:
225,334,867 bp from pter      End:
225,450,110 bp from pter
Size:
115,244 bases      Orientation:
minus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
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UniProtKB/Swiss-Prot: CUL3_HUMAN, Q13618 (See protein sequence)
Recommended Name: Cullin-3  
Size: 768 amino acids; 88930 Da
Subunit: Forms neddylation-dependent homodimers. Component of multiple BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein
ligase complexes formed of CUL3, RBX1 and a variable BTB domain-containing protein acting as both, adapter to
cullin and substrate recognition subunit. The BCR complex may be active as a heterodimeric complex, in which
NEDD8, covalently attached to one CUL3 molecule, binds to the C-terminus of a second CUL3 molecule. Interacts
with RBX1, RNF7, CYCE and TIP120A/CAND1. Part of the BCR(SPOP) containing SPOP, and of BCR containing homodimeric
SPOPL or the heterodimer formed by SPOP and SPOPL. Part of the probable BCR(KLHL9-KLHL13) complex with BTB domain
proteins KLHL9 and KLHL13. Part of the BCR(KLHL41) complex containing KLHL41. Component of the BCR(KLHL12) E3
ubiquitin ligase complex, at least composed of CUL3 and KLHL12 and RBX1. Component of the BCR(KLHL3) E3 ubiquitin
ligase complex, at least composed of CUL3 and KLHL3 and RBX1 (Probable). Part of the BCR(ENC1) complex containing
ENC1. Part of a complex consisting of BMI1/PCGF4, CUL3 and SPOP. Part of a complex consisting of BRMS1, CUL3 and
SPOP. Component of the BCR(KLHL21) E3 ubiquitin ligase complex, at least composed of CUL3, KLHL21 and RBX1.
Component of the BCR(KLHL22) E3 ubiquitin ligase complex, at least composed of CUL3, KLHL22 and RBX1. Component
of the BCR(KLHL25) E3 ubiquitin ligase complex, at least composed of CUL3, KLHL25 and RBX1. Part of a complex
consisting of H2AFY, CUL3 and SPOP. Component of the BCR(KLHL42) E3 ubiquitin ligase complex, at least composed
of CUL3 and KLHL42. Interacts with KLHL42 (via the BTB domain). Interacts with KATNA1; the interaction is
enhanced by KLHL42. Interacts with KCTD5, KLHL9, KLHL11, KLHL13, GAN, ZBTB16, KLHL3, KLHL15, KLHL20, KLHL36,
GMCL1P1, BTBD1. Part of a complex that contains CUL3, RBX1 and GAN. Interacts (via BTB domain) with KLHL17; the
interaction regulates surface GRIK2 expression. Interacts with KCTD7. Part of the BCR(GAN) complex containing
GAN. Part of the BCR(KEAP1) complex containing KEAP1. Interacts with KLHL10 (By similarity). Interacts with KAT5
and ATF2
Sequence caution: Sequence=AAC28621.1; Type=Frameshift; Positions=452; Sequence=AAC36682.1; Type=Frameshift;
Positions=159, 179; Sequence=BAA31592.2; Type=Erroneous initiation; Note=Translation N-terminally shortened;
4 PDB 3D structures from and Proteopedia for CUL3:
4AP2 (3D)        4APF (3D)        4EOZ (3D)        4HXI (3D)    
Secondary accessions: A8K536 B8ZZC3 O75415 Q569L3 Q9UBI8 Q9UET7
Alternative splicing: 3 isoforms:  Q13618-1   Q13618-2   Q13618-3   

Explore the universe of human proteins at neXtProt for CUL3: NX_Q13618

Explore proteomics data for CUL3 at MOPED

Post-translational modifications: 

  • Neddylated. Attachment of NEDD8 is required for the E3 ubiquitin-protein ligase activity of the BCR complex.
    Deneddylated via its interaction with the COP9 signalosome (CSN) complex1
  • Ubiquitination2 at Lys6, Lys28, Lys262, Lys292, Lys349, Lys638, Lys668, Lys700
  • Modification sites at PhosphoSitePlus

  • See CUL3 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins (3 alternative transcripts): 
    NP_001244126.1  NP_001244127.1  NP_003581.1  

    ENSEMBL proteins: 
     ENSP00000264414   ENSP00000400558   ENSP00000387200   ENSP00000386525   ENSP00000410575  
     ENSP00000400935   ENSP00000343601  
    Reactome Protein details: Q13618

    CUL3 Human Recombinant Protein Products:

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    OriGene Purified Protein for CUL3
    OriGene Protein Over-expression Lysate for CUL3
    OriGene MassSpec for CUL3
    OriGene Custom Protein Services for CUL3
    GenScript Custom Purified and Recombinant Proteins Services for CUL3
    Novus Biologicals CUL3 Proteins
    Novus Biologicals CUL3 Lysate
    Browse Sino Biological Recombinant Proteins
    Browse Sino Biological Cell Lysates
    Browse ProSpec Recombinant Proteins
    Cloud-Clone Corp. Proteins for CUL3

    CUL3 Antibody Products:

    Browse EMD Millipore's Extensive Line of Mono- and Polyclonal Antibodies
    Browse R&D Systems for Antibodies
    Cell Signaling Technology (CST) Antibodies for CUL3 
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    OriGene Custom Antibody Services for CUL3
    Novus Biologicals CUL3 Antibodies
    Abcam antibodies for CUL3 (Q13618, Q569L3)
    Cloud-Clone Corp. Antibodies for CUL3
    ThermoFisher Antibodies for CUL3
    LSBio Antibodies in human, mouse, rat for CUL3

    CUL3 Assay Products:

    Browse Kits and Assays available from EMD Millipore
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    Browse R&D Systems for biochemical assays
    GenScript Custom Assay Services for CUL3
    Browse Enzo Life Sciences for kits & assays
    Cloud-Clone Corp. ELISAs for CUL3
    Cloud-Clone Corp. CLIAs for CUL3


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    Selected InterPro protein domains (see all 6):
     IPR016159 Cullin_repeat-like_dom
     IPR019559 Cullin_neddylation_domain
     IPR016157 Cullin_CS
     IPR001373 Cullin_N
     IPR011991 WHTH_DNA-bd_dom

    Graphical View of Domain Structure for InterPro Entry Q13618

    ProtoNet protein and cluster: Q13618

    1 Blocks protein domain: IPB001373 Cullin

    UniProtKB/Swiss-Prot: CUL3_HUMAN, Q13618
    Similarity: Belongs to the cullin family


    CUL3 for domains           About GeneDecksing


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: CUL3_HUMAN, Q13618
    Function: Core component of multiple cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complexes
    which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. As a scaffold protein
    may contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The E3
    ubiquitin-protein ligase activity of the complex is dependent on the neddylation of the cullin subunit and is
    inhibited by the association of the deneddylated cullin subunit with TIP120A/CAND1 (By similarity). The
    functional specificity of the BCR complex depends on the BTB domain-containing protein as the substrate
    recognition component. BCR(KLHL42) is involved in ubiquitination of KATNA1. BCR(SPOP) is involved in
    ubiquitination of BMI1/PCGF4, BRMS1, H2AFY and DAXX, GLI2 and GLI3. Can also form a cullin-RING-based BCR
    (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex containing homodimeric SPOPL or the heterodimer formed by
    SPOP and SPOPL; these complexes have lower ubiquitin ligase activity. BCR(KLHL9-KLHL13) controls the dynamic
    behavior of AURKB on mitotic chromosomes and thereby coordinates faithful mitotic progression and completion of
    cytokinesis. BCR(KLHL12) is involved in ER-Golgi transport by regulating the size of COPII coats, thereby playing
    a key role in collagen export, which is required for embryonic stem (ES) cells division: BCR(KLHL12) acts by
    mediating monoubiquitination of SEC31 (SEC31A or SEC31B). BCR(KLHL3) acts as a regulator of ion transport in the
    distal nephron; by mediating ubiquitination of WNK4. The BCR(KLHL21) E3 ubiquitin ligase complex regulates
    localization of the chromosomal passenger complex (CPC) from chromosomes to the spindle midzone in anaphase and
    mediates the ubiquitination of AURKB. The BCR(KLHL22) ubiquitin ligase complex mediates monoubiquitination of
    PLK1, leading to PLK1 dissociation from phosphoreceptor proteins and subsequent removal from kinetochores,
    allowing silencing of the spindle assembly checkpoint (SAC) and chromosome segregation. The BCR(KLHL25) ubiquitin
    ligase complex is involved in translational homeostasis by mediating ubiquitination and subsequent degradation of
    hypophosphorylated EIF4EBP1 (4E-BP1). Involved in ubiquitination of cyclin E and of cyclin D1 (in vitro) thus
    involved in regulation of G1/S transition. Involved in the ubiquitination of KEAP1, ENC1 and KLHL41. In concert
    with ATF2 and RBX1, promotes degradation of KAT5 thereby attenuating its ability to acetylate and activate ATM

         Genatlas biochemistry entry for CUL3:
    cullin 3,salicylate suppressible gene,89kDa,C elegans cullin/Cdc53 (CUL) family member,likely involved in cell
    proliferation control

         Gene Ontology (GO): 5 molecular function terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0004842contributes to ubiquitin-protein ligase activity IDA15983046
    GO:0005515protein binding IPI12609982
    GO:0030332cyclin binding IEA--
    GO:0031208POZ domain binding IDA19261606
    GO:0031625ubiquitin protein ligase binding IEA--
         
    CUL3 for ontologies           About GeneDecksing


    Phenotypes:
         4 GenomeRNAi human phenotypes for CUL3:
     Increased G1 DNA content  Increased cell death HMECs cel  Increased cell death in breast  Synthetic lethal with c-Myc af 

         5 MGI mutant phenotypes (inferred from 3 alleles(MGI details for Cul3):
     cellular  embryogenesis  growth/size/body  liver/biliary system  mortality/aging 

    CUL3 for phenotypes           About GeneDecksing

    Animal Models:
         MGI mouse knock-out Cul3tm1Jro for CUL3

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for CUL3
       inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for CUL3

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for CUL3
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for CUL3

    miRNA
    Products:
        
    miRTarBase miRNAs that target CUL3:
    hsa-mir-18a-3p (MIRT040752), hsa-mir-99a-5p (MIRT048703), hsa-let-7b-5p (MIRT032239), hsa-mir-192-5p (MIRT004141), hsa-mir-10a-5p (MIRT047577)

    Block miRNA regulation of human, mouse, rat CUL3 using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate CUL3 (see all 140):
    hsa-miR-140-5p hsa-miR-631 hsa-miR-106a hsa-miR-519a hsa-miR-92b hsa-miR-130b hsa-miR-520b hsa-miR-374b*
    Browse SwitchGear 3'UTR luciferase reporter plasmids
    Inhib. RNA
    Products:
        
    OriGene RNAi products in human, mouse, rat for CUL3
    Predesigned siRNA for gene silencing in human, mouse, rat CUL3

    Gene Editing
    Products:
    DNA2.0 Custom Protein Engineering Service for CUL3

    Clone
    Products:
         
    OriGene clones in human, mouse for CUL3 (see all 8)
    OriGene ORF clones in mouse, rat for CUL3
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector: CUL3 (NM_003590)
    Browse Sino Biological Human cDNA Clones
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for CUL3
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat CUL3

    Cell Line
    Products:
         
    GenScript Custom overexpressing Cell Line Services for CUL3
    Browse ESI BIO Cell Lines and PureStem Progenitors for CUL3 
    In Situ Assay
    Products:
       

     
    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for CUL3


    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    CUL3_HUMAN, Q13618: Nucleus. Golgi apparatus
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    cytoskeleton5
    golgi apparatus5
    nucleus5
    cytosol3

    Gene Ontology (GO): Selected cellular component terms (see all 7):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000139Golgi membrane IMP--
    GO:0005634nucleus IEA--
    GO:0005794Golgi apparatus ----
    GO:0005827polar microtubule IDA19995937
    GO:0031461cullin-RING ubiquitin ligase complex ----

    CUL3 for ontologies           About GeneDecksing


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for CUL3 About    
    See pathways by source

    SuperPathContained pathways About
    1Class I MHC mediated antigen processing and presentation
    Class I MHC mediated antigen processing and presentation0.84
    Adaptive Immune System0.41
    Antigen processing- Ubiquitination and Proteasome degradation0.84
    Ubiquitin mediated proteolysis0.35
    2Protein Stability
    Protein Stability
    3Canonical Wnt signaling pathway
    Canonical Wnt signaling pathway
    4Aurora B signaling
    Aurora B signaling
    5ATF-2 transcription factor network
    ATF-2 transcription factor network

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways


    1 Cell Signaling Technology (CST) Pathway for CUL3
        Protein Stability

    3 BioSystems Pathways for CUL3
        ATF-2 transcription factor network
    Canonical Wnt signaling pathway
    Aurora B signaling

    2 Reactome Pathways for CUL3
        degradation of DVL
    Antigen processing: Ubiquitination & Proteasome degradation


    1 Kegg Pathway  (Kegg details for CUL3):
        Ubiquitin mediated proteolysis

    UniProtKB/Swiss-Prot: CUL3_HUMAN, Q13618
    Pathway: Protein modification; protein ubiquitination


    CUL3 for pathways           About GeneDecksing

        Pathway & Disease-focused RT2 Profiler PCR Arrays including CUL3: 

              Ubiquitination (Ubiquitylation) Pathway in human mouse rat
              Cell Cycle in human mouse rat
              Apoptosis 384HT in human mouse rat
              Ubiquitin Ligases in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for CUL3

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for CUL3 (Q136181, 2, 3 ENSP000002644144) via UniProtKB, MINT, STRING, and/or I2D (see all 298)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    CAND1Q86VP61, 3EBI-456129,EBI-456077 I2D: score=4 
    CALM1P621583, ENSP000003494674I2D: score=1 STRING: ENSP00000349467
    CALM2P621583, ENSP000002722984I2D: score=1 STRING: ENSP00000272298
    CALM3P621583, ENSP000002912954I2D: score=1 STRING: ENSP00000291295
    NEDD8Q158432, 3, ENSP000002504954MINT-6542674 I2D: score=2 STRING: ENSP00000250495
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 27):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000082G1/S transition of mitotic cell cycle TAS8681378
    GO:0000090mitotic anaphase IMP17543862
    GO:0000209protein polyubiquitination IDA19261606
    GO:0000902cell morphogenesis ----
    GO:0000910cytokinesis IMP17543862

    CUL3 for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Browse Tocris compounds for CUL3

    1 Novoseek inferred chemical compound relationship for CUL3 gene    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    lysine 27.5 1 15572695 (1)



    CUL3 for compounds           About GeneDecksing



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    Conferences by KenesGroup, exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, and/or QIAGEN )
    About This Section

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    REFSEQ mRNAs for CUL3 gene (3 alternative transcripts): 
    NM_001257197.1  NM_001257198.1  NM_003590.4  

    Unigene Cluster for CUL3:

    Cullin 3
    Hs.372286  [show with all ESTs]
    Unigene Representative Sequence: NM_003590
    15 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000264414(uc010fwy.1 uc002vny.2) ENST00000497715 ENST00000454323
    ENST00000409096 ENST00000409777 ENST00000451538 ENST00000536702 ENST00000487558
    ENST00000481135 ENST00000484081 ENST00000541548 ENST00000432260 ENST00000436172
    ENST00000546102 ENST00000344951(uc010zls.1)
    miRNA
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    Block miRNA regulation of human, mouse, rat CUL3 using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate CUL3 (see all 140):
    hsa-miR-140-5p hsa-miR-631 hsa-miR-106a hsa-miR-519a hsa-miR-92b hsa-miR-130b hsa-miR-520b hsa-miR-374b*
    Browse SwitchGear 3'UTR luciferase reporter plasmids
    Inhib. RNA
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    Predesigned siRNA for gene silencing in human, mouse, rat CUL3
    Clone
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      QuantiFast Probe-based Assays in human, mouse, rat CUL3

    Additional mRNA sequence: 

    AB014517.2 AF052147.1 AF062537.1 AF064087.1 AK098531.1 AK291151.1 AK299644.1 AK308496.1 
    AY007151.1 AY337761.1 BC031844.1 BC039598.1 BC092409.1 U58089.1 

    18 DOTS entries:

    DT.455114  DT.92409519  DT.100029181  DT.91722547  DT.120999387  DT.91757974  DT.95164412  DT.99928171 
    DT.100728655  DT.120999360  DT.120999410  DT.86851392  DT.91757963  DT.91757978  DT.91830938  DT.97800924 
    DT.102832628  DT.95204178 

    Selected AceView cDNA sequences (see all 367):

    BU619091 AA827138 Z21352 BM693654 BE464384 BF198018 BC031844 BM977573 
    AL542036 AA489370 AI422363 AA282543 BU687479 NM_003590 BQ688156 BM670800 
    Z38731 BM855146 CR603582 CB111647 BG258285 CB306448 BQ004777 AA133493 

    GeneLoc Exon Structure

    Selected Alternative Splicing Database (ASD) splice patterns (SP) for CUL3 (see all 10)    About this scheme

    ExUns: 1 ^ 2 ^ 3 ^ 4a · 4b · 4c ^ 5 ^ 6 ^ 7 ^ 8a · 8b ^ 9a · 9b · 9c ^ 10a · 10b ^ 11a · 11b ^ 12 ^ 13a · 13b ^ 14 ^ 15 ^ 16a · 16b ^ 17 ^
    SP1:                                      -           -                                                                       -                                 
    SP2:        -     -     -     -     -     -           -                                                                       -                                 
    SP3:              -     -     -     -     -           -                                                                                                         
    SP4:                                -     -           -                                                                                                         
    SP5:                                                                                                                                                            

    ExUns: 18a · 18b ^ 19 ^ 20 ^ 21a · 21b · 21c ^ 22a · 22b · 22c
    SP1:        -     -           -                                 
    SP2:        -     -           -                                 
    SP3:                                                            
    SP4:                                                            
    SP5:                                                            


    ECgene alternative splicing isoforms for CUL3

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
    About This Section

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    CUL3 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: TTCTAGACCA
    CUL3 Expression
    About this image


    CUL3 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 4) fully expand
     
     Testis (Reproductive System)
             XY Germ Cells Testis Cord
     
     Gonad
             XY Germ Cells Testis Cord
     
     Eye (Sensory Organs)
             Retina
     
     Esophagus (Gastrointestinal Tract)
    CUL3 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    CUL3 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.372286

    UniProtKB/Swiss-Prot: CUL3_HUMAN, Q13618
    Tissue specificity: Widely expressed

        Pathway & Disease-focused RT2 Profiler PCR Arrays including CUL3: 
              Ubiquitination (Ubiquitylation) Pathway in human mouse rat
              Cell Cycle in human mouse rat
              Apoptosis 384HT in human mouse rat
              Ubiquitin Ligases in human mouse rat

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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
    About This Section

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    This gene was present in the common ancestor of eukaryotes.

    Orthologs for CUL3 gene from Selected species (see all 23)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Cul31 , 5 cullin 31, 5 94.7(n)1
    99.48(a)1
      1 (41.24 cM)5
    265541  NM_016716.41  NP_057925.11 
     802649235 
    chicken
    (Gallus gallus)
    Aves CUL31 cullin 3 90(n)
    99.6(a)
      424804  XM_422620.4  XP_422620.4 
    lizard
    (Anolis carolinensis)
    Reptilia CUL36
    cullin 3
    100(a)
    1 ↔ 1
    3(24757782-24830292)
    African clawed frog
    (Xenopus laevis)
    Amphibia Xl.50892 Xenopus laevis transcribed sequence with strong similarity more 81.66(n)    CD301136.1 
    zebrafish
    (Danio rerio)
    Actinopterygii cul32 cullin 3 79.34(n)   324655  BC060901.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta gft3
    Cul-31
    Cullin-31 69(a)3
    62.2(n)1
    70.17(a)1
      35C53
    348961  NM_165110.21  NP_723907.11 
    worm
    (Caenorhabditis elegans)
    Secernentea cul-31 cul-3 53.04(n)
    49.8(a)
      178547  NM_070750.5  NP_503151.1 
    soybean
    (Glycine max)
    eudicotyledons BM731614.12   -- 76.43(n)    BM731614.1 
    rice
    (Oryza sativa)
    Liliopsida AK072402.12   -- 72.54(n)    AK072402.1 


    ENSEMBL Gene Tree for CUL3 (if available)
    TreeFam Gene Tree for CUL3 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for CUL3 gene
    CUL12  CUL4A2  CUL4B2  CUL22  CUL52  
    4 SIMAP similar genes for CUL3 using alignment to 6 protein entries:     CUL3_HUMAN (see all proteins):
    CUL4B    CUL4A    CUL1    CUL2

    CUL3 for paralogs           About GeneDecksing



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for CUL3 (see all 2272)    About this table    
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 2 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    VAR_0675334
    Pseudohypoaldosteronism 2E (PHA2E)4--see VAR_0675332 K R mis40--------
    VAR_0675324
    Pseudohypoaldosteronism 2E (PHA2E)4--see VAR_0675322 D G mis40--------
    rs729723521,2
    C--217186256(+) ACACAC/TACACA 3 -- ds50010--------
    rs284783001,2
    --217186272(+) ACACAC/TACACA 3 -- ds50010--------
    rs755127151,2
    C--217186279(+) ACACA-/TACACA
            
    CACCC
    3 -- cds10--------
    rs1137274171,2
    C,F--217186287(+) CCCATG/CTGCAA 3 -- ds50011Minor allele frequency- C:0.50CSA 2
    rs739938981,2
    C--217186339(+) GTCAAG/ATATCA 3 -- ds50013Minor allele frequency- A:0.16WA EA 240
    rs1860170231,2
    --217186383(+) GTCATA/CGCCCC 3 -- ds50010--------
    rs413717441,2
    C,F--217186405(+) ACAAAT/CTTTAA 3 -- ds50011Minor allele frequency- C:0.07NA 120
    rs750372801,2
    C,F--217186432(+) TTTAAA/TGATTT 3 -- ds50011Minor allele frequency- T:0.06WA 118

    HapMap Linkage Disequilibrium report for CUL3 (225334867 - 225450110 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 7 variations for CUL3:    About this table    
    Variant IDTypeSubtypePubMed ID
    esv2461086CNV Deletion19546169
    esv2464203CNV Deletion19546169
    nsv875903CNV Loss21882294
    nsv875908CNV Loss21882294
    dgv4440n71CNV Loss21882294
    nsv875909CNV Gain21882294
    nsv875907CNV Gain21882294

    Human Gene Mutation Database (HGMD): CUL3
    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing CUL3
    DNA2.0 Custom Variant and Variant Library Synthesis for CUL3

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
    About This Section

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    OMIM gene information: 603136   
    OMIM disorders: 614496  
    UniProtKB/Swiss-Prot: CUL3_HUMAN, Q13618
  • Pseudohypoaldosteronism 2E (PHA2E) [MIM:614496]: An autosomal dominant disorder characterized by severe
    hypertension, hyperkalemia, hyperchloremia, hyperchloremic metabolic acidosis, and correction of physiologic
    abnormalities by thiazide diuretics. Note=The disease is caused by mutations affecting the gene represented in
    this entry

  • 19 diseases for CUL3:    
    About MalaCards
    pseudohypoaldosteronism type iie    glomuvenous malformation    monkeypox    pseudohypoaldosteronism
    papillary renal cell carcinoma    metabolic acidosis    neuronal ceroid lipofuscinosis    retinitis pigmentosa
    wilms tumor    retinitis    hypertension    prostate cancer
    prostatitis    renal cell carcinoma    myeloma    breast cancer
    multiple myeloma    neuronitis    malaria


    CUL3 for disorders           About GeneDecksing

    Genetic Association Database (GAD): CUL3
    Human Genome Epidemiology (HuGE) Navigator: CUL3 (2 documents)

    Export disorders for CUL3 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for CUL3 gene, integrated from 10 sources (see all 184):
    (articles sorted by number of sources associating them with CUL3)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. The Cullin3 ubiquitin ligase functions as a Nedd8-bound heterodimer. (PubMed id 17192413)1, 2, 3 Wimuttisuk W. and Singer J.D. (Mol. Biol. Cell 2007)
    2. cul-1 is required for cell cycle exit in C. elegans and identifies a novel gene family. (PubMed id 8681378)1, 2, 3 Kipreos E.T.... Hedgecock E.M. (Cell 1996)
    3. Cullin-3 targets cyclin E for ubiquitination and controls S phase in mammalian cells. (PubMed id 10500095)1, 2, 9 Singer J.D.... Roberts J.M. (Genes Dev. 1999)
    4. A Cul3-based E3 ligase removes Aurora B from mitotic chromosomes, regulating mitotic progression and completion of cytokinesis in human cells. (PubMed id 17543862)1, 2, 9 Sumara I....Peter M. (Dev. Cell 2007)
    5. BTB domain-containing speckle-type POZ protein (SPOP) serves as an adaptor of Daxx for ubiquitination by Cul3-based ubiquitin ligase. (PubMed id 16524876)1, 2, 9 Kwon J.E.... Chung C.H. (J. Biol. Chem. 2006)
    6. Ubiquitination of Keap1, a BTB-Kelch substrate adaptor protein for Cul3, targets Keap1 for degradation by a proteasome-independent pathway. (PubMed id 15983046)1, 2, 9 Zhang D.D.... Hannink M. (J. Biol. Chem. 2005)
    7. Kelch-like 3 and Cullin 3 regulate electrolyte homeostasis via ubiquitination and degradation of WNK4. (PubMed id 23576762)1, 2 Shibata S....Lifton R.P. (Proc. Natl. Acad. Sci. U.S.A. 2013)
    8. Crystal structure of KLHL3 in complex with Cullin3. (PubMed id 23573258)1, 2 Ji A.X. and PrivAc G.G. (PLoS ONE 2013)
    9. Structural basis for Cul3 assembly with the BTB-Kelch family of E3 ubiquitin ligases. (PubMed id 23349464)1, 2 Canning P.... Bullock A.N. (J. Biol. Chem. 2013)
    10. The CUL3-KLHL3 E3 ligase complex mutated in Gordon's hypertension syndrome interacts with and ubiquitylates WNK isoforms: disease-causing mutations in KLHL3 and WNK4 disrupt interaction. (PubMed id 23387299)1, 2 Ohta A....Kurz T. (Biochem. J. 2013)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 8452 HGNC: 2553 AceView: CUL3 Ensembl:ENSG00000036257 euGenes: HUgn8452
    ECgene: CUL3 Kegg: 8452 H-InvDB: CUL3

    (According to HUGE)
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    HUGE: KIAA0617

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
    About This Section

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    NameDescription
    PharmGKB entry for CUL3 Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for CUL3 Genetics and Cytogenetics in Oncology and Haematology

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for CUL3 gene:
    Search GeneIP for patents involving CUL3

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



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