CUL2 Gene (Protein Coding)

Cullin 2

GC10M035046
GIFtS:
43
See more...

Aliases for CUL2 Gene

Aliases for CUL2 Gene

  • Cullin 2 2 3 5
  • Cullin-2 3 4
  • CUL-2 3 4
  • Testis Secretory Sperm-Binding Protein Li 238E 3
  • CUL2 5

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 Von Hippel-Lindau Syndrome and Hypoxia. Among its related pathways are HIF1Alpha Pathway and Class I MHC mediated antigen processing and presentation. Gene Ontology (GO) annotations related to this gene include ubiquitin protein ligase binding. An important paralog of this gene is CUL1.

UniProtKB/Swiss-Prot Summary 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

Additional gene information for CUL2 Gene

No data available for Entrez Gene Summary , CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for CUL2 Gene

Genomics for CUL2 Gene

GeneHancer (GH) Regulatory Elements Pubs

Download GeneHancer 2017 data
Promoters and enhancers for CUL2 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around CUL2 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for CUL2

Top Transcription factor binding sites by QIAGEN in the CUL2 gene promoter:
  • ATF-2
  • c-Jun

Genomic Locations for CUL2 Gene

Latest Assembly
chr10:35,008,551-35,126,899
(GRCh38/hg38)
Size:
118,349 bases
Orientation:
Minus strand

Previous Assembly
chr10:35,297,479-35,379,542
(GRCh37/hg19 by Entrez Gene)
Size:
82,064 bases
Orientation:
Minus strand

chr10:35,297,479-35,379,570
(GRCh37/hg19 by Ensembl)
Size:
82,092 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 Structure • Gene Density

RefSeq DNA sequence for CUL2 Gene

Proteins for CUL2 Gene

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  • 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 (ELOB and ELOC), 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, ELOB, ELOC 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 ZER1, 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, ELOB 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). Interacts (unneddylated form) with DCUN1D1, DCUN1D2, DCUN1D3, DCUN1D4 and DCUN1D5; these interactions promote the cullin neddylation (PubMed:24192928, PubMed:26906416, PubMed:23201271, PubMed:23401859). Component of VCB (elongins BC/CUL2/VHL) complex that contains at least DCUN1D1, CUL2 and VHL; this complex triggers CUL2 neddylation and consequently cullin ring ligase (CRL) substrates polyubiquitylation (PubMed:23401859).
    • (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

Protein Expression for CUL2 Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

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 Lys16 and Lys608
  • Modification sites at PhosphoSitePlus

Other Protein References for CUL2 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for CUL2 Gene

Domains & Families for CUL2 Gene

Gene Families for CUL2 Gene

HGNC:
Human Protein Atlas (HPA):
  • Cancer-related genes
  • Predicted intracellular proteins

Protein Domains for CUL2 Gene

InterPro:
Blocks:
  • Cullin

Suggested Antigen Peptide Sequences for CUL2 Gene

GenScript: Design optimal peptide antigens:
  • Cullin-2 (CUL2_HUMAN)

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

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  6. Cell Lines for research

Molecular function for CUL2 Gene

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).
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

Phenotypes From GWAS Catalog for CUL2 Gene

Gene Ontology (GO) - Molecular Function for CUL2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004842 ubiquitin-protein transferase activity IBA 21873635
GO:0005515 protein binding IPI 12504026
GO:0031625 ubiquitin protein ligase binding IEA,IDA 17636018
GO:0044877 protein-containing complex binding IEA --
genes like me logo Genes that share ontologies with CUL2: view
genes like me logo Genes that share phenotypes with CUL2: view

Animal Models for research

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for CUL2

Clone products for research

  • Addgene plasmids for CUL2

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
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for CUL2 gene
Compartment Confidence
nucleus 5
cytosol 5
plasma membrane 2
extracellular 2
cytoskeleton 2
mitochondrion 2
endoplasmic reticulum 2
peroxisome 1
endosome 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nucleoplasm (4)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for CUL2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005654 nucleoplasm IDA,TAS --
GO:0005829 cytosol TAS --
GO:0019005 SCF ubiquitin ligase complex IBA 21873635
GO:0030891 VCB complex IEA --
GO:0031461 cullin-RING ubiquitin ligase complex IEA,IBA 21873635
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

Pathways by source for CUL2 Gene

3 Qiagen pathways for CUL2 Gene
  • HIF1Alpha Pathway
  • JAK-STAT Pathway
  • SOCS Pathway
2 GeneTex pathways for CUL2 Gene

UniProtKB/Swiss-Prot Q13617-CUL2_HUMAN

  • Pathway: Protein modification; protein ubiquitination.

SIGNOR curated interactions for CUL2 Gene

Inactivates:

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:0016032 viral process IEA --
GO:0016567 protein ubiquitination IEA,TAS --
GO:0031146 SCF-dependent proteasomal ubiquitin-dependent protein catabolic process IBA 21873635
genes like me logo Genes that share ontologies with CUL2: view

Drugs & Compounds for CUL2 Gene

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(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

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mRNA/cDNA for CUL2 Gene

6 REFSEQ mRNAs :
15 NCBI additional mRNA sequence :
11 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for CUL2

Clone products for research

  • Addgene plasmids for CUL2

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

No ASD Table

Relevant External Links for CUL2 Gene

GeneLoc Exon Structure for
CUL2

Expression for CUL2 Gene

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  1. Primer products for research
  2. Gene Expression Assays for research

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for CUL2 Gene

mRNA expression in normal human tissues for CUL2 Gene
mRNA expression by GTEx for CUL2 GenemRNA expression by BioGPS 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, MaxQB, and MOPED for CUL2 Gene



Protein tissue co-expression partners for CUL2 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for CUL2

SOURCE GeneReport for Unigene cluster for CUL2 Gene:

Hs.82919

Evidence on tissue expression from TISSUES for CUL2 Gene

  • Nervous system(4.8)
  • Kidney(4.5)
  • Skin(4.4)
  • Heart(2.7)
  • Blood(2.5)
  • Intestine(2.5)
  • Liver(2.4)
  • Muscle(2.4)
  • Spleen(2.2)
  • Adrenal gland(2.2)
  • Eye(2.2)
  • Lung(2)
genes like me logo Genes that share expression patterns with CUL2: view

Primer products for research

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer 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 29 30
  • 99.69 (n)
 OneToOne
Oppossum
(Monodelphis domestica)
 Mammalia CUL2 30
  • 97 (a)
 OneToOne
Dog
(Canis familiaris)
 Mammalia CUL2 29 30
  • 94.99 (n)
 OneToOne
Cow
(Bos Taurus)
 Mammalia CUL2 29 30
  • 94.14 (n)
 OneToOne
Platypus
(Ornithorhynchus anatinus)
 Mammalia CUL2 30
  • 92 (a)
 OneToOne
Mouse
(Mus musculus)
 Mammalia Cul2 29 16 30
  • 91.36 (n)
 OneToOne
Rat
(Rattus norvegicus)
 Mammalia Cul2 29
  • 90.62 (n)
Chicken
(Gallus gallus)
 Aves CUL2 29 30
  • 87.81 (n)
 OneToOne
Lizard
(Anolis carolinensis)
 Reptilia CUL2 30
  • 93 (a)
 OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
 Amphibia cul2 29
  • 83.8 (n)
African clawed frog
(Xenopus laevis)
 Amphibia MGC69167 29
Zebrafish
(Danio rerio)
 Actinopterygii cul2 29 30
  • 76.87 (n)
 OneToOne
wufj48a06 29
Rainbow Trout
(Oncorhynchus mykiss)
 Actinopterygii Omy.763 29
African malaria mosquito
(Anopheles gambiae)
 Insecta AgaP_AGAP003605 29
  • 55.01 (n)
Fruit Fly
(Drosophila melanogaster)
 Insecta Cul-2 29 30
  • 54.2 (n)
 OneToOne
cul-2 31
  • 50 (a)
Worm
(Caenorhabditis elegans)
 Secernentea cul-2 29 30
  • 50.65 (n)
 OneToOne
Baker's yeast
(Saccharomyces cerevisiae)
 Saccharomycetes CDC53 30
  • 27 (a)
 OneToMany
Sea Squirt
(Ciona savignyi)
 Ascidiacea CSA.2270 30
  • 42 (a)
 OneToOne
Species where no ortholog for CUL2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium 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 Vase (Ciona intestinalis)
  • 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)
Aminode:
Evolutionary constrained regions (ECRs) for CUL2: view image
Alliance of Genome Resources:
Additional Orthologs for CUL2

Paralogs for CUL2 Gene

Paralogs for CUL2 Gene

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

  • CUL2_HUMAN
  • Q5T2B4_HUMAN
  • Q5T2B5_HUMAN
  • Q5T2B7_HUMAN
  • R4GNH8_HUMAN

Pseudogenes.org Pseudogenes for CUL2 Gene

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

Variants for CUL2 Gene

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Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for CUL2 Gene

SNP ID Clinical significance and condition Chr 10 pos Variation AA Info Type
982195 Likely Pathogenic: Moyamoya angiopathy 35,010,357(-) A/G
NM_003591.4(CUL2):c.2192T>C (p.Ile731Thr) 		MISSENSE
rs115271125 Benign: not provided 35,062,956(-) T/C
NM_003591.4(CUL2):c.222+4A>G 		INTRON
rs141211442 Benign: not provided 35,028,849(-) C/T
NM_003591.4(CUL2):c.1578G>A (p.Thr526=) 		SYNONYMOUS
rs145366778 Benign: not provided 35,049,676(-) C/G
NM_003591.4(CUL2):c.506+7G>C 		INTRON
rs7897024 Benign: not provided 35,049,745(-) C/T
NM_003591.4(CUL2):c.444G>A (p.Arg148=) 		SYNONYMOUS_VARIANT,INTRON

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for CUL2 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

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)

Additional Variant Information for CUL2 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
CUL2
Leiden Open Variation Database (LOVD)
CUL2

SNP Genotyping and Copy Number Assays for research

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

Disorders for CUL2 Gene

MalaCards: The human disease database

(13) MalaCards diseases for CUL2 Gene - From: COP and GCD

Disorder Aliases PubMed IDs
von hippel-lindau syndrome
  • vhls
hypoxia
retinal hemangioblastoma
leiomyoma cutis
  • cutaneous leiomyoma
dermis tumor
  • dermis tumour
- elite association - COSMIC cancer census association via MalaCards
Search CUL2 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for CUL2

Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
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 SW … Lee SH (APMIS : acta pathologica, microbiologica, et immunologica Scandinavica 2009) 3 22 40
  2. Identification of NEDD8-conjugation site in human cullin-2. (PMID: 10092517) Wada H … Kamitani T (Biochemical and biophysical research communications 1999) 3 4 22
  3. cul-1 is required for cell cycle exit in C. elegans and identifies a novel gene family. (PMID: 8681378) Kipreos ET … Hedgecock EM (Cell 1996) 2 3 4
  4. Two Distinct Types of E3 Ligases Work in Unison to Regulate Substrate Ubiquitylation. (PMID: 27565346) Scott DC … Schulman BA (Cell 2016) 3 4
  5. Characterization of the mammalian family of DCN-type NEDD8 E3 ligases. (PMID: 26906416) Keuss MJ … Kurz T (Journal of cell science 2016) 3 4

ExternalLinks

View latest publications for CUL2 gene in Mastermind

Products for CUL2 Gene

  • Addgene plasmids for CUL2

Sources for CUL2 Gene