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Aliases for CUL2 Gene

Aliases for CUL2 Gene

  • Cullin 2 2 3 5
  • CUL-2 3 4
  • Testis Secretory Sperm-Binding Protein Li 238E 3
  • Cullin-2 3

External Ids for CUL2 Gene

Previous GeneCards Identifiers for CUL2 Gene

  • GC10M035449
  • GC10M035302
  • GC10M035338

Summaries for CUL2 Gene

GeneCards Summary for CUL2 Gene

CUL2 (Cullin 2) is a Protein Coding gene. Diseases associated with CUL2 include Renal Cell Carcinoma and Kidney Cancer. Among its related pathways are Hypoxic and oxygen homeostasis regulation of HIF-1-alpha and Immune System. GO annotations related to this gene include ubiquitin protein ligase binding and protein complex binding. An important paralog of this gene is CUL1.

UniProtKB/Swiss-Prot for CUL2 Gene

  • Core component of multiple cullin-RING-based ECS (ElonginB/C-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complexes, which mediate the ubiquitination of target proteins. ECS complexes and ARIH1 collaborate in tandem to mediate ubiquitination of target proteins (PubMed:27565346). May serve as a rigid scaffold in the complex and 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. The functional specificity of the ECS complex depends on the substrate recognition component. ECS(VHL) mediates the ubiquitination of hypoxia-inducible factor (HIF).

Gene Wiki entry for CUL2 Gene

No data available for Entrez Gene Summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for CUL2 Gene

Genomics for CUL2 Gene

Regulatory Elements for CUL2 Gene

Enhancers for CUL2 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH10F035057 1.1 Ensembl ENCODE 17.2 +68.4 68373 1.8 JUN SIN3A FEZF1 JUND ZNF600 FOS MAFK NFE2L2 CREM CUL2 RNU7-77P MIR3611 GC10M034983
GH10F035040 1 Ensembl ENCODE 16.6 +85.8 85766 1.5 SCRT1 ZNF362 CEBPB TSHZ1 POLR2H ZNF121 POLR2A SCRT2 ZNF600 ZNF391 CUL2 PARD3 PARD3-AS1 CREM MIR3611 GC10M034983
GH10F035004 0.8 Ensembl ENCODE 16.1 +120.5 120542 3.1 PKNOX1 FEZF1 GATA2 ELK1 SCRT2 RCOR1 FOS CREM ELK4 CEBPB CUL2 CREM ENSG00000230534 GC10M034983 MIR3611
GH10F035212 1.2 Ensembl ENCODE 15.8 -86.4 -86441 1.5 CTCF PBX2 RAD21 CREM CUL2 RNU7-77P ENSG00000230534 ENSG00000269952 RNU6-794P
GH10F035191 1.1 Ensembl ENCODE 15.6 -67.5 -67460 6.1 HDGF PKNOX1 CREB3L1 ZFP64 SIN3A FEZF1 ZNF2 YY1 ZNF302 CBX5 CREM ENSG00000271335 CUL2 RNU7-77P ENSG00000230534 GC10M035186 ENSG00000269952
- Elite enhancer/Elite enhancer-gene association Download Table
Download GeneHancer data dump

Enhancers around CUL2 on UCSC Golden Path with GeneCards custom track

Promoters for CUL2 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00000353491 -601 2601 HDGF PKNOX1 CREB3L1 ARID4B SIN3A DMAP1 ZNF2 YY1 ZNF143 FOS

Genomic Location for CUL2 Gene

Chromosome:
10
Start:
35,008,551 bp from pter
End:
35,126,899 bp from pter
Size:
118,349 bases
Orientation:
Minus strand

Genomic View for CUL2 Gene

Genes around CUL2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CUL2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for CUL2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for CUL2 Gene

Proteins for CUL2 Gene

  • Protein details for CUL2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q13617-CUL2_HUMAN
    Recommended name:
    Cullin-2
    Protein Accession:
    Q13617
    Secondary Accessions:
    • B3KT95
    • B7Z6K8
    • D3DRY6
    • G3V1S2
    • O00200
    • Q5T2B6
    • Q9UNF9

    Protein attributes for CUL2 Gene

    Size:
    745 amino acids
    Molecular mass:
    86983 Da
    Quaternary structure:
    • Component of multiple ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complexes formed of CUL2, Elongin BC (TCEB1 and TCEB2), RBX1 and a variable substrate-specific adapter. Component of the ECS(VHL) or CBC(VHL) complex containing VHL. Component of the ECS(MED8) complex with the probable substrate recognition component MED8. Component of the ECS(LRR1) complex with the probable substrate recognition component LRR1. Component of a probable ECS E3 ubiquitin-protein ligase complex containing CUL2, RBX1, TCEB1, TCEB2 and FEM1B. Part of an E3 ubiquitin-protein ligase complex including ZYG11B, CUL2 and Elongin BC. Part of an E3 ubiquitin-protein ligase complex including ZYG11BL, CUL2 and Elongin BC. Interacts with RBX1, RNF7, FEM1B and TIP120A/CAND1. Interacts with COPS2, and MED8. Found in a complex composed of LIMD1, VHL, EGLN1/PHD2, TCEB2 and CUL2. Interacts with KLHDC10; which may be an E3 ubiquitin ligase complex substrate recognition component. Interacts (when neddylated) with ARIH1; leading to activate the E3 ligase activity of ARIH1 (PubMed:24076655, PubMed:27565346).
    • (Microbial infection) Interacts with human respiratory syncytial virus (HRSV) protein NS1.

    Three dimensional structures from OCA and Proteopedia for CUL2 Gene

    Alternative splice isoforms for CUL2 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for CUL2 Gene

Post-translational modifications for CUL2 Gene

  • Neddylated; which enhances the ubiquitination activity of ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complexes. CBC(VHL) complex formation seems to promote neddylation. Deneddylated via its interaction with the COP9 signalosome (CSN) complex (By similarity).
  • Ubiquitination at Lys 16
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for CUL2 Gene

Domains & Families for CUL2 Gene

Gene Families for CUL2 Gene

Suggested Antigen Peptide Sequences for CUL2 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

Q13617

UniProtKB/Swiss-Prot:

CUL2_HUMAN :
  • Belongs to the cullin family.
Family:
  • Belongs to the cullin family.
genes like me logo Genes that share domains with CUL2: view

Function for CUL2 Gene

Molecular function for CUL2 Gene

GENATLAS Biochemistry:
cullin 2,complexing with VHL/elongin B and C to form an ubiquitin-ligase complex referred to VCB-CUL2(see VHL),putatively targetting certain proteins for degradation,not a major renal cell carcinoma,tumor suppressor gene,but maybe involved in other carcinomas,see TSG10
UniProtKB/Swiss-Prot Function:
Core component of multiple cullin-RING-based ECS (ElonginB/C-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complexes, which mediate the ubiquitination of target proteins. ECS complexes and ARIH1 collaborate in tandem to mediate ubiquitination of target proteins (PubMed:27565346). May serve as a rigid scaffold in the complex and 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. The functional specificity of the ECS complex depends on the substrate recognition component. ECS(VHL) mediates the ubiquitination of hypoxia-inducible factor (HIF).

Gene Ontology (GO) - Molecular Function for CUL2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 12504026
GO:0031625 ubiquitin protein ligase binding IEA,IDA 17636018
GO:0032403 protein complex binding IEA --
GO:0061630 contributes_to ubiquitin protein ligase activity IBA --
genes like me logo Genes that share ontologies with CUL2: view
genes like me logo Genes that share phenotypes with CUL2: view

Animal Model Products

Flow Cytometry Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for CUL2 Gene

Localization for CUL2 Gene

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for CUL2 Gene COMPARTMENTS Subcellular localization image for CUL2 gene
Compartment Confidence
cytosol 5
nucleus 5
endoplasmic reticulum 1
mitochondrion 1
peroxisome 1

Gene Ontology (GO) - Cellular Components for CUL2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005654 nucleoplasm IDA,TAS --
GO:0005730 nucleolus IEA --
GO:0005829 cytosol TAS --
GO:0030891 VCB complex IEA --
GO:0031461 cullin-RING ubiquitin ligase complex IEA --
genes like me logo Genes that share ontologies with CUL2: view

No data available for Subcellular locations from UniProtKB/Swiss-Prot for CUL2 Gene

Pathways & Interactions for CUL2 Gene

genes like me logo Genes that share pathways with CUL2: view

UniProtKB/Swiss-Prot Q13617-CUL2_HUMAN

  • Pathway: Protein modification; protein ubiquitination.

Gene Ontology (GO) - Biological Process for CUL2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000082 G1/S transition of mitotic cell cycle TAS 8681378
GO:0006511 ubiquitin-dependent protein catabolic process IEA --
GO:0007050 cell cycle arrest TAS 8681378
GO:0008285 negative regulation of cell proliferation TAS 8681378
GO:0016032 viral process IEA --
genes like me logo Genes that share ontologies with CUL2: view

No data available for SIGNOR curated interactions for CUL2 Gene

Drugs & Compounds for CUL2 Gene

(1) Drugs for CUL2 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
genes like me logo Genes that share compounds with CUL2: view

Transcripts for CUL2 Gene

Unigene Clusters for CUL2 Gene

Cullin 2:
Representative Sequences:

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for CUL2 Gene

No ASD Table

Relevant External Links for CUL2 Gene

GeneLoc Exon Structure for
CUL2
ECgene alternative splicing isoforms for
CUL2

Expression for CUL2 Gene

mRNA expression in normal human tissues for CUL2 Gene

Protein differential expression in normal tissues from HIPED for CUL2 Gene

This gene is overexpressed in Lymph node (12.6) and Peripheral blood mononuclear cells (7.4).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for CUL2 Gene



Protein tissue co-expression partners for CUL2 Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of CUL2 Gene:

CUL2

SOURCE GeneReport for Unigene cluster for CUL2 Gene:

Hs.82919
genes like me logo Genes that share expression patterns with CUL2: view

Primer Products

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues and mRNA Expression by UniProt/SwissProt for CUL2 Gene

Orthologs for CUL2 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for CUL2 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia CUL2 34 35
  • 99.69 (n)
oppossum
(Monodelphis domestica)
Mammalia CUL2 35
  • 97 (a)
OneToOne
dog
(Canis familiaris)
Mammalia CUL2 34 35
  • 94.99 (n)
cow
(Bos Taurus)
Mammalia CUL2 34 35
  • 94.14 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia CUL2 35
  • 92 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Cul2 34 16 35
  • 91.36 (n)
rat
(Rattus norvegicus)
Mammalia Cul2 34
  • 90.62 (n)
chicken
(Gallus gallus)
Aves CUL2 34 35
  • 87.81 (n)
lizard
(Anolis carolinensis)
Reptilia CUL2 35
  • 93 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia cul2 34
  • 83.8 (n)
African clawed frog
(Xenopus laevis)
Amphibia MGC69167 34
zebrafish
(Danio rerio)
Actinopterygii cul2 34 35
  • 76.87 (n)
wufj48a06 34
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.763 34
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP003605 34
  • 55.01 (n)
fruit fly
(Drosophila melanogaster)
Insecta Cul-2 34 35
  • 54.2 (n)
cul-2 36
  • 50 (a)
worm
(Caenorhabditis elegans)
Secernentea cul-2 34 35
  • 50.65 (n)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes CDC53 35
  • 27 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea CSA.2270 35
  • 42 (a)
OneToOne
Species where no ortholog for CUL2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for CUL2 Gene

ENSEMBL:
Gene Tree for CUL2 (if available)
TreeFam:
Gene Tree for CUL2 (if available)

Paralogs for CUL2 Gene

Paralogs for CUL2 Gene

(5) SIMAP similar genes for CUL2 Gene using alignment to 5 proteins:

Pseudogenes.org Pseudogenes for CUL2 Gene

genes like me logo Genes that share paralogs with CUL2: view

Variants for CUL2 Gene

Sequence variations from dbSNP and Humsavar for CUL2 Gene

SNP ID Clin Chr 10 pos Sequence Context AA Info Type
rs10047349 -- 35,115,127(+) gaatc(A/G)cttga intron-variant
rs10160202 -- 35,032,824(+) AAACA(C/T)ATCTA intron-variant
rs10437420 -- 35,046,116(+) GAGAA(A/C)TATTT intron-variant
rs10466072 -- 35,113,828(+) caggc(C/T)cctga intron-variant
rs10508815 -- 35,043,693(+) TATGA(A/C)CACTT intron-variant

Structural Variations from Database of Genomic Variants (DGV) for CUL2 Gene

Variant ID Type Subtype PubMed ID
dgv202e212 CNV gain 25503493
dgv703n100 CNV gain 25217958
dgv705n100 CNV gain 25217958
dgv706n100 CNV gain 25217958
esv2677225 CNV deletion 23128226
esv3576372 CNV gain 25503493
esv3622891 CNV loss 21293372
nsv1039051 CNV gain 25217958
nsv1133987 CNV deletion 24896259
nsv1161937 CNV duplication 26073780
nsv466860 CNV gain 19166990
nsv466862 CNV gain 19166990
nsv466869 CNV gain 19166990
nsv466870 CNV loss 19166990
nsv470931 CNV gain 18288195
nsv507549 OTHER sequence alteration 20534489
nsv525060 CNV gain 19592680
nsv550391 CNV gain 21841781
nsv550398 CNV gain 21841781
nsv550401 CNV gain 21841781
nsv550402 CNV gain 21841781
nsv975796 CNV duplication 23825009

Variation tolerance for CUL2 Gene

Residual Variation Intolerance Score: 8.6% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.97; 19.95% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for CUL2 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
CUL2

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for CUL2 Gene

Disorders for CUL2 Gene

MalaCards: The human disease database

(4) MalaCards diseases for CUL2 Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
renal cell carcinoma
  • renal cell carcinoma, clear cell, somatic
kidney cancer
  • malignant neoplasm of kidney except pelvis
renal clear cell carcinoma
  • clear cell carcinoma of kidney
familial renal papillary carcinoma
  • hereditary papillary renal carcinoma
- elite association - COSMIC cancer census association via MalaCards
Search CUL2 in MalaCards View complete list of genes associated with diseases

Relevant External Links for CUL2

Genetic Association Database (GAD)
CUL2
Human Genome Epidemiology (HuGE) Navigator
CUL2
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
CUL2
genes like me logo Genes that share disorders with CUL2: view

No data available for UniProtKB/Swiss-Prot and Genatlas for CUL2 Gene

Publications for CUL2 Gene

  1. Mutational analysis of hypoxia-related genes HIF1alpha and CUL2 in common human cancers. (PMID: 20078552) Park S.W. … Lee S.H. (APMIS 2009) 3 22 46 64
  2. Identification of NEDD8-conjugation site in human cullin-2. (PMID: 10092517) Wada H. … Kamitani T. (Biochem. Biophys. Res. Commun. 1999) 3 4 22 64
  3. cul-1 is required for cell cycle exit in C. elegans and identifies a novel gene family. (PMID: 8681378) Kipreos E.T. … Hedgecock E.M. (Cell 1996) 2 3 4 64
  4. TRIAD1 and HHARI bind to and are activated by distinct neddylated Cullin-RING ligase complexes. (PMID: 24076655) Kelsall I.R. … Alpi A.F. (EMBO J. 2013) 3 4 64
  5. The LIMD1 protein bridges an association between the prolyl hydroxylases and VHL to repress HIF-1 activity. (PMID: 22286099) Foxler D.E. … Sharp T.V. (Nat. Cell Biol. 2012) 3 4 64

Products for CUL2 Gene

Sources for CUL2 Gene

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