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CUL3 cullin 3 [ Homo sapiens (human) ]

Gene ID: 8452, updated on 7-Apr-2024

Summary

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Official Symbol
CUL3provided by HGNC
Official Full Name
cullin 3provided by HGNC
Primary source
HGNC:HGNC:2553
See related
Ensembl:ENSG00000036257 MIM:603136; AllianceGenome:HGNC:2553
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
CUL-3; PHA2E; NEDAUS
Summary
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]
Expression
Broad expression in testis (RPKM 53.6), esophagus (RPKM 12.6) and 24 other tissues See more
Orthologs
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Genomic context

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Location:
2q36.2
Exon count:
20
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (224470150..224585363, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (224952401..225067578, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (225334867..225450080, complement)

Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC124907992 Neighboring gene Sharpr-MPRA regulatory region 15583 Neighboring gene family with sequence similarity 124 member B Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:225297524-225298143 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:225298144-225298762 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12380 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr2:225349417-225350616 Neighboring gene ANKRD49 pseudogene 1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12381 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12382 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12383 Neighboring gene uncharacterized LOC105373909 Neighboring gene uncharacterized LOC105373910 Neighboring gene coiled-coil domain containing 195

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • 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

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Related articles in PubMed

  1. Renal effects of cullin 3 mutations causing familial hyperkalemic hypertension. Cornelius RJ, et al. Curr Opin Nephrol Hypertens, 2023 Jul 1. PMID 37070483,
  2. The differentially expressed gene signatures of the Cullin 3-RING ubiquitin ligases in neuroendocrine cancer. Park JU, et al. Biochem Biophys Res Commun, 2022 Dec 25. PMID 36368157, Free PMC Article
  3. Cullin3 (CUL3) suppresses proliferation, migration and phenotypic transformation of PDGF-BB-stimulated vascular smooth muscle cells and mitigates inflammatory response by repressing Hedgehog signaling pathway. Xiang Y, et al. Bioengineered, 2021 Dec. PMID 34699319, Free PMC Article
  4. Loss-of-function Mutations of CUL3, a High Confidence Gene for Psychiatric Disorders, Lead to Aberrant Neurodevelopment In Human Induced Pluripotent Stem Cells. Fischer S, et al. Neuroscience, 2020 Nov 10. PMID 32890664
  5. The E3 Ubiquitin-Protein Ligase Cullin 3 Regulates HIV-1 Transcription. Langer S, et al. Cells, 2020 Sep 1. PMID 32882949, Free PMC Article

See all (403) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. CUL3 induces mitochondrial dysfunction via MRPL12 ubiquitination in renal tubular epithelial cells.
    Title: CUL3 induces mitochondrial dysfunction via MRPL12 ubiquitination in renal tubular epithelial cells.
  2. Investigation of cullin-3 gene expression changes in people with colorectal cancer and polyps in China.
    Title: Investigation of cullin-3 gene expression changes in people with colorectal cancer and polyps in China.
  3. BCLAF1-induced HIF-1alpha accumulation under normoxia enhances PD-L1 treatment resistances via BCLAF1-CUL3 complex.
    Title: BCLAF1-induced HIF-1α accumulation under normoxia enhances PD-L1 treatment resistances via BCLAF1-CUL3 complex.
  4. Structure and Function of RhoBTB1 Required for Substrate Specificity and Cullin-3 Ubiquitination.
    Title: Structure and Function of RhoBTB1 Required for Substrate Specificity and Cullin-3 Ubiquitination.
  5. Renal effects of cullin 3 mutations causing familial hyperkalemic hypertension.
    Title: Renal effects of cullin 3 mutations causing familial hyperkalemic hypertension.
  6. Structural and biochemical characterization establishes a detailed understanding of KEAP1-CUL3 complex assembly.
    Title: Structural and biochemical characterization establishes a detailed understanding of KEAP1-CUL3 complex assembly.
  7. Prenatal phthalate exposure and cord blood DNA methylation.
    Title: Prenatal phthalate exposure and cord blood DNA methylation.
  8. The differentially expressed gene signatures of the Cullin 3-RING ubiquitin ligases in neuroendocrine cancer.
    Title: The differentially expressed gene signatures of the Cullin 3-RING ubiquitin ligases in neuroendocrine cancer.
  9. CUL3/SPOP complex prevents immune escape and enhances chemotherapy sensitivity of ovarian cancer cells through degradation of PD-L1 protein.
    Title: CUL3/SPOP complex prevents immune escape and enhances chemotherapy sensitivity of ovarian cancer cells through degradation of PD-L1 protein.
  10. The expression of microRNA-197-3p regulates the proliferation of ovarian granulosa cells through CUL3 in polycystic ovarian syndrome.
    Title: The expression of microRNA-197-3p regulates the proliferation of ovarian granulosa cells through CUL3 in polycystic ovarian syndrome.
Submit: New GeneRIF Correction See all GeneRIFs (114)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Biological insights from 108 schizophrenia-associated genetic loci.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • FLJ25665

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables Notch binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables POZ domain binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables cyclin binding IEA
Inferred from Electronic Annotation
more info
  
enables identical protein binding IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables ubiquitin ligase complex scaffold activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables ubiquitin protein ligase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables ubiquitin protein ligase binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables ubiquitin protein ligase binding IPI
Inferred from Physical Interaction
more info
 PubMed 
contributes_to ubiquitin-protein transferase activity IDA
Inferred from Direct Assay
more info
 PubMed 
Process Evidence Code Pubs
involved_in COPII vesicle coating IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in G1/S transition of mitotic cell cycle TAS
Traceable Author Statement
more info
 PubMed 
involved_in Wnt signaling pathway IEA
Inferred from Electronic Annotation
more info
  
acts_upstream_of_or_within anaphase-promoting complex-dependent catabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in cell migration IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in cell projection organization IEA
Inferred from Electronic Annotation
more info
  
involved_in cellular response to amino acid stimulus IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in embryonic cleavage ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in endoplasmic reticulum to Golgi vesicle-mediated transport IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in fibroblast apoptotic process IEA
Inferred from Electronic Annotation
more info
  
involved_in gastrulation IEA
Inferred from Electronic Annotation
more info
  
involved_in gene expression IEA
Inferred from Electronic Annotation
more info
  
involved_in inflammatory response IEA
Inferred from Electronic Annotation
more info
  
involved_in integrin-mediated signaling pathway ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in intrinsic apoptotic signaling pathway TAS
Traceable Author Statement
more info
 PubMed 
involved_in liver morphogenesis IEA
Inferred from Electronic Annotation
more info
  
involved_in mitotic metaphase chromosome alignment IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in negative regulation of Rho protein signal transduction IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in negative regulation of transcription by RNA polymerase II IEA
Inferred from Electronic Annotation
more info
  
involved_in negative regulation of type I interferon production IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in nuclear protein quality control by the ubiquitin-proteasome system IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of TORC1 signaling IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of cell population proliferation TAS
Traceable Author Statement
more info
 PubMed 
involved_in positive regulation of cytokinesis IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of mitotic cell cycle phase transition IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of mitotic metaphase/anaphase transition IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of protein ubiquitination IGI
Inferred from Genetic Interaction
more info
 PubMed 
involved_in proteasome-mediated ubiquitin-dependent protein catabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in proteasome-mediated ubiquitin-dependent protein catabolic process IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in protein K48-linked ubiquitination IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in protein autoubiquitination IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in protein destabilization IGI
Inferred from Genetic Interaction
more info
 PubMed 
involved_in protein monoubiquitination IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in protein polyubiquitination IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in protein ubiquitination IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in protein ubiquitination IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in regulation protein catabolic process at postsynapse IEA
Inferred from Electronic Annotation
more info
  
involved_in stem cell division ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in stress fiber assembly IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in trophectodermal cellular morphogenesis IEA
Inferred from Electronic Annotation
more info
  
acts_upstream_of_or_within ubiquitin-dependent protein catabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in ubiquitin-dependent protein catabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
Component Evidence Code Pubs
part_of Cul3-RING ubiquitin ligase complex IBA
Inferred from Biological aspect of Ancestor
more info
  
part_of Cul3-RING ubiquitin ligase complex IDA
Inferred from Direct Assay
more info
 PubMed 
located_in Golgi apparatus IEA
Inferred from Electronic Annotation
more info
  
located_in centrosome IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytosol TAS
Traceable Author Statement
more info
  
located_in extracellular exosome HDA PubMed 
located_in glutamatergic synapse IEA
Inferred from Electronic Annotation
more info
  
located_in membrane HDA PubMed 
located_in mitotic spindle IDA
Inferred from Direct Assay
more info
 PubMed 
located_in nucleoplasm TAS
Traceable Author Statement
more info
  
located_in nucleus IDA
Inferred from Direct Assay
more info
 PubMed 
located_in plasma membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in polar microtubule IDA
Inferred from Direct Assay
more info
 PubMed 
located_in postsynapse IEA
Inferred from Electronic Annotation
more info
  
located_in sperm flagellum IDA
Inferred from Direct Assay
more info
 PubMed 
located_in spindle pole IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
cullin-3

NCBI Reference Sequences (RefSeq)

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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.

Genomic

  1. NG_032169.1 RefSeqGene

    Range
    5035..120248
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001257197.2 → NP_001244126.1  cullin-3 isoform 2

    See identical proteins and their annotated locations for NP_001244126.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an exon in the 5' coding region, but maintains the reading frame, comapred to variant 1. The encoded isoform (2) is shorter than isoform 1.
    Source sequence(s)
    AB014517, AC073052, AK299644, BQ688156
    Consensus CDS
    CCDS58751.1
    UniProtKB/Swiss-Prot
    Q13618
    UniProtKB/TrEMBL
    B7Z600
    Related
    ENSP00000343601.4, ENST00000344951.8
    Conserved Domains (2) summary
    pfam00888
    Location:32 → 599
    Cullin; Cullin family
    pfam10557
    Location:632 → 693
    Cullin_Nedd8; Cullin protein neddylation domain

  2. NM_001257198.2 → NP_001244127.1  cullin-3 isoform 3

    See identical proteins and their annotated locations for NP_001244127.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) differs in the 5' UTR, lacks a portion of the 5' coding region and initiates translation at an alternate start codon, compared to variant 1. The encoded isoform (3) is longer and has a distinct N-terminus, compared to isoform 1.
    Source sequence(s)
    AB014517, AC073052, AK308496
    UniProtKB/Swiss-Prot
    Q13618
    Related
    ENSP00000387200.1, ENST00000409096.5
    Conserved Domains (3) summary
    smart00182
    Location:427 → 569
    CULLIN; Cullin
    pfam00888
    Location:41 → 670
    Cullin; Cullin family
    pfam10557
    Location:706 → 766
    Cullin_Nedd8; Cullin protein neddylation domain

  3. NM_003590.5 → NP_003581.1  cullin-3 isoform 1

    See identical proteins and their annotated locations for NP_003581.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes isoform 1.
    Source sequence(s)
    AB014517, AC073052, BQ688156
    Consensus CDS
    CCDS2462.1
    UniProtKB/Swiss-Prot
    A8K536, B8ZZC3, O75415, Q13618, Q569L3, Q9UBI8, Q9UET7
    Related
    ENSP00000264414.4, ENST00000264414.9
    Conserved Domains (2) summary
    pfam00888
    Location:34 → 665
    Cullin; Cullin family
    pfam10557
    Location:698 → 759
    Cullin_Nedd8; Cullin protein neddylation domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000002.12 Reference GRCh38.p14 Primary Assembly

    Range
    224470150..224585363 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_006712800.3 → XP_006712863.2  cullin-3 isoform X1

    See identical proteins and their annotated locations for XP_006712863.2

    Related
    ENSP00000386525.1, ENST00000409777.5
    Conserved Domains (2) summary
    smart00884
    Location:684 → 751
    Cullin_Nedd8; Cullin protein neddylation domain
    pfam00888
    Location:23 → 654
    Cullin; Cullin family

  2. XM_011511995.2 → XP_011510297.1  cullin-3 isoform X2

    Conserved Domains (3) summary
    smart00182
    Location:407 → 549
    CULLIN; Cullin
    pfam00888
    Location:21 → 650
    Cullin; Cullin family
    pfam10557
    Location:686 → 746
    Cullin_Nedd8; Cullin protein neddylation domain

  3. XM_011511996.3 → XP_011510298.1  cullin-3 isoform X3

    See identical proteins and their annotated locations for XP_011510298.1

    Conserved Domains (2) summary
    pfam00888
    Location:34 → 601
    Cullin; Cullin family
    pfam10557
    Location:634 → 695
    Cullin_Nedd8; Cullin protein neddylation domain

  4. XM_047446024.1 → XP_047301980.1  cullin-3 isoform X3

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060926.1 Alternate T2T-CHM13v2.0

    Range
    224952401..225067578 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054344200.1 → XP_054200175.1  cullin-3 isoform X1

  2. XM_054344201.1 → XP_054200176.1  cullin-3 isoform X2

  3. XM_054344202.1 → XP_054200177.1  cullin-3 isoform X3

  4. XM_054344203.1 → XP_054200178.1  cullin-3 isoform X3

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q13618.2 GenPept UniProtKB/Swiss-Prot:Q13618

Gene LinkOut

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