FB2020_01, released Feb 12, 2020

Gene: Dmel\Cul1

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General Information
Symbol
Dmel\Cul1
Species
D. melanogaster
Name
Cullin 1
Annotation Symbol
CG1877
Feature Type
protein_coding_gene
FlyBase ID
FBgn0015509
Gene Model Status
Current
Stock Availability
16 publicly available
Gene Snapshot
In progress.Contributions welcome.
Other Summaries
Also Known As

lin19, Cul-1, dCul1, l(2)k01207, lin19-like

Key Links
Genomic Location
Cytogenetic map
43F1-43F2
Sequence location
2R:7,916,856..7,921,579 [+]
Recombination map

2-57

RefSeq locus
NT_033778 REGION:7916856..7921579
Sequence
Get Decorated FASTA
Genomic Maps
Other Genome Views
The following external sites may use different assemblies or annotations than FlyBase.
NCBI
UCSC
Ensembl
PopFly
Function
GO Summary Ribbons
Gene Group (FlyBase)
Pathway (FlyBase)
Protein Family (UniProt)
Belongs to the cullin family. (Q24311)
Protein Signatures (InterPro)
Molecular Function (GO)
[Detailed GO annotations]
Experimental Evidence
protein binding; ubiquitin protein ligase binding
Predictions / Assertions
ubiquitin protein ligase binding
Summaries
Gene Group (FlyBase)
CULLINS -
Cullins are an evolutionarily conserved, structurally-related gene family, with an N-terminal bearing cullin repeats followed by a cullin homology domain and a neddylation site. Cullins act as scaffolds to assemble multi-subunit Cullin-RING E3 ubiquitin ligase (CRL) complexes. A CRL complex is characterised by a cullin-RING-type E3 ubiquitin ligase interaction, which acts as the catalytic core and recruits the E2 ubiquitin-conjugating enzyme, and a cullin-adaptor protein-substrate recognition protein interaction which links the E3 ligase to its target for ubiquitination. (Adapted from FBrf0224296).
SCF-SLMB UBIQUITIN LIGASE COMPLEX -
SCF-slmb ubiquitin ligase complex ubiquitinates proteins, targeting them for degradation by the proteasome. (FBrf0217546).
Pathway (FlyBase)
Negative Regulators of Wnt-TCF Signaling Pathway -
Negative regulators of canonical Wnt signaling down-regulate the pathway, resulting in the attenuation of transcriptional regulation mediated by β-catenin (arm).
Negative Regulators of Insulin-like Receptor Signaling Pathway -
Negative regulators of the Insulin-like Receptor signaling pathway suppress Insulin-like receptor (InR) activation or the activity of intracellular effectors. (Adapted from FBrf0232297, FBrf0230017 and FBrf0229989).
Negative Regulators of Hedgehog Signaling Pathway -
Negative regulators of hedgehog signaling down-regulation the pathway, resulting in the repression of transcription of hh-responsive genes.
Protein Function (UniProtKB)
Core component of multiple SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complexes which mediate the ubiquitination of proteins involved in cell cycle progression, signal transduction and transcription. In the SCF complex, serves as a rigid scaffold that organizes the SKP1-F-box protein and RBX1 subunits. May contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. During early metamorphosis, part of the SCF-slmb complex that negatively regulates the InR/PI3K/TOR pathway to activate the pruning of unnecessary larval ddaC dendrites and mushroom body axons (PubMed:24068890). The SCF-slmb complex also regulates asymmetrical division of neuroblasts and inhibits ectopic neuroblast formation partly through SAK and Akt1 (PubMed:24413555). Also part of an SCF complex required for caspase activation during sperm differentiation (PubMed:20392747). Necessary for auditory transduction: plays a role in Johnston's organ organization by acting in the regulation of zip and ck function in scolopidial apical attachment (PubMed:27331610). May function by acting in a Ubr3-mediated pathway that negatively regulates the ubiquitination of zip, consequently affecting its interaction with ck (PubMed:27331610).
(UniProt, Q24311)
Summary (Interactive Fly)

a major component of a series of multimeric ubiquitin ligases that control the degradation of a broad range of proteins

Gene Model and Products
Number of Transcripts
4
Number of Unique Polypeptides
1

Please see the GBrowse view of Dmel\Cul1 or the JBrowse view of Dmel\Cul1 for information on other features

To submit a correction to a gene model please use the Contact FlyBase form

Protein Domains (via Pfam)
Isoform displayed:
Pfam protein domains
InterPro name
classification
start
end
Protein Domains (via SMART)
Isoform displayed:
SMART protein domains
InterPro name
classification
start
end
Comments on Gene Model

Low-frequency RNA-Seq exon junction(s) not annotated.

Gene model reviewed during 5.49

Sequence Ontology: Class of Gene
nuclear_gene
protein_coding_gene
Transcript Data
Annotated Transcripts
Name
FlyBase ID
RefSeq ID
Length (nt)
Assoc. CDS (aa)
Cul1-RA
FBtr0088847
NM_165569
3207
774
Cul1-RB
FBtr0088846
NM_165570
3886
774
Cul1-RC
FBtr0088845
NM_165571
3225
774
Cul1-RD
FBtr0088848
NM_078931
3184
774
Additional Transcript Data and Comments
Reported size (kB)
Comments
External Data
Crossreferences
Polypeptide Data
Annotated Polypeptides
Name
FlyBase ID
Predicted MW (kDa)
Length (aa)
Theoretical pI
RefSeq ID
GenBank
Cul1-PA
FBpp0087923
89.5
774
8.01
NP_724621
AAF59174
Cul1-PB
FBpp0087922
89.5
774
8.01
NP_724622
AAF59175
Cul1-PC
FBpp0087921
89.5
774
8.01
NP_724623
AAM68871
Cul1-PD
FBpp0087924
89.5
774
8.01
NP_523655
AAM68872
Polypeptides with Identical Sequences

The group(s) of polypeptides indicated below share identical sequence to each other.

774 aa isoforms: Cul1-PA, Cul1-PB, Cul1-PC, Cul1-PD
Additional Polypeptide Data and Comments
Reported size (kDa)
Comments
External Data
Subunit Structure (UniProtKB)

Component of SCF E3 ubiquitin-protein ligase complexes consisting of Skpa, Cul1, Roc1a and an F-box protein. In larval neuroblast self renewal and asymmetric division, as well as ddaC dendrite and mushroom body axon pruning, the complex contains the F-box protein slmb (SCF-slmb) (PubMed:24068890, PubMed:24413555). In caspase activation during sperm differentiation, the complex contains the F-box protein ntc (PubMed:20392747). Interacts directly with Roc1a (PubMed:11500045). Interacts with Fsn (PubMed:20123973). Interacts with Dlish (PubMed:27692068). Interacts with Cad99C (via the cytoplasmic domain) (PubMed:27331610). Interacts with Sans (PubMed:27331610).

(UniProt, Q24311)
Post Translational Modification

Neddylated (PubMed:12183637, PubMed:18493598). Deneddylated via its interaction with the COP9 signalosome (CSN) complex (PubMed:12183637).

(UniProt, Q24311)
Crossreferences
InterPro - A database of protein families, domains and functional sites
Linkouts
Sequences Consistent with the Gene Model
Nucleotide / Polypeptide Records
 
UniProt
Mapped Features

Click to get a list of regulatory features (enhancers, TFBS, etc.) and gene disruptions (point mutations, indels, etc.) within or overlapping Dmel\Cul1 using the Feature Mapper tool.

External Data
Crossreferences
Eukaryotic Promoter Database - A collection of databases of experimentally validated promoters for selected model organisms.
Linkouts
Gene Ontology (20 terms)
Molecular Function (2 terms)
Terms Based on Experimental Evidence (2 terms)
CV Term
Evidence
References
protein binding
inferred from physical interaction with FLYBASE:mi; FB:FBgn0261786
(Szuplewski et al., 2009)
ubiquitin protein ligase binding
inferred from physical interaction with FLYBASE:Roc1a; FB:FBgn0025638
(Reynolds et al., 2008, Bocca et al., 2001)
Terms Based on Predictions or Assertions (1 term)
CV Term
Evidence
References
ubiquitin protein ligase binding
inferred from biological aspect of ancestor with PANTHER:PTN000231993
(assigned by GO_Central )
(Gaudet et al., 2011)
Biological Process (15 terms)
Terms Based on Experimental Evidence (12 terms)
CV Term
Evidence
References
negative regulation of apoptotic process
inferred from mutant phenotype
(Fereres et al., 2013)
negative regulation of canonical Wnt signaling pathway
inferred from mutant phenotype
(Roberts et al., 2012, Swarup and Verheyen, 2011)
negative regulation of insulin receptor signaling pathway
inferred from genetic interaction with FLYBASE:InR; FB:FBgn0283499
(Wong et al., 2013)
negative regulation of phosphatidylinositol 3-kinase signaling
inferred from genetic interaction with FLYBASE:Pi3K92E; FB:FBgn0015279, FLYBASE:Pten; FB:FBgn0026379
(Wong et al., 2013)
negative regulation of smoothened signaling pathway
inferred from mutant phenotype
(Zhou et al., 2015)
negative regulation of TOR signaling
inferred from genetic interaction with FLYBASE:gig; FB:FBgn0005198
(Wong et al., 2013)
inferred from genetic interaction with FLYBASE:Akt1; FB:FBgn0010379
(Wong et al., 2013)
inferred from genetic interaction with FLYBASE:Pi3K92E; FB:FBgn0015279
(Wong et al., 2013)
inferred from genetic interaction with FLYBASE:Tor; FB:FBgn0021796
(Wong et al., 2013)
inferred from genetic interaction with FLYBASE:Tsc1; FB:FBgn0026317
(Wong et al., 2013)
inferred from genetic interaction with FLYBASE:Pten; FB:FBgn0026379
(Wong et al., 2013)
inferred from genetic interaction with FLYBASE:Thor; FB:FBgn0261560
(Wong et al., 2013)
inferred from genetic interaction with FLYBASE:S6k; FB:FBgn0283472
(Wong et al., 2013)
positive regulation of neuron remodeling
inferred from mutant phenotype
(Wong et al., 2013)
positive regulation of proteasomal ubiquitin-dependent protein catabolic process
inferred from mutant phenotype
(Roberts et al., 2012)
positive regulation of protein ubiquitination
inferred from mutant phenotype
(Chen et al., 2019)
protein catabolic process
inferred from mutant phenotype
(Wong et al., 2013)
protein K11-linked ubiquitination
inferred from direct assay
(Zhang et al., 2013)
protein ubiquitination
inferred from direct assay
(Zhou et al., 2015)
Terms Based on Predictions or Assertions (4 terms)
CV Term
Evidence
References
proteasome-mediated ubiquitin-dependent protein catabolic process
inferred from biological aspect of ancestor with PANTHER:PTN000231993
(assigned by GO_Central )
(Gaudet et al., 2011)
protein ubiquitination
inferred by curator from GO:0019005,GO:0030163
(Wong et al., 2013)
inferred by curator from GO:0019005,GO:0031625
(Reynolds et al., 2008)
SCF-dependent proteasomal ubiquitin-dependent protein catabolic process
inferred from biological aspect of ancestor with PANTHER:PTN000231993
(assigned by GO_Central )
(Gaudet et al., 2011)
ubiquitin-dependent protein catabolic process
inferred from biological aspect of ancestor with PANTHER:PTN000231993
(assigned by GO_Central )
(Gaudet et al., 2011)
Cellular Component (3 terms)
Terms Based on Experimental Evidence (2 terms)
CV Term
Evidence
References
nucleus
inferred from direct assay
(Doronkin et al., 2003)
SCF ubiquitin ligase complex
inferred from direct assay
(Wong et al., 2013, Kugler et al., 2010, Reynolds et al., 2008, Bocca et al., 2001)
inferred from mutant phenotype
(Roberts et al., 2012)
Terms Based on Predictions or Assertions (2 terms)
CV Term
Evidence
References
cullin-RING ubiquitin ligase complex
inferred from biological aspect of ancestor with PANTHER:PTN000231993
(assigned by GO_Central )
(Gaudet et al., 2011)
SCF ubiquitin ligase complex
inferred from biological aspect of ancestor with PANTHER:PTN000231993
(assigned by GO_Central )
(Gaudet et al., 2011)
Expression Data
Expression Summary Ribbons
Colored tiles in ribbon indicate that expression data has been curated by FlyBase for that anatomical location. Colorless tiles indicate that there is no curated data for that location.
For complete stage-specific expression data, view the modENCODE Development RNA-Seq section under High-Throughput Expression below.
Transcript Expression
in situ
Stage
Tissue/Position (including subcellular localization)
Reference
third instar larval stage
eye disc | ubiquitous
(Ou et al., 2002)
adult stage | femaleoogenesis stage S1 -- S10
nurse cell
(Filippov et al., 2000)
adult stage | femaleoogenesis stage S10 -- S11
oocyte
(Filippov et al., 2000)
embryonic stage 3
organism | intense | ubiquitous
(Filippov et al., 2000)
embryonic stage 4 -- 5
organism | intense | ubiquitous | uniform
(Filippov et al., 2000)
embryonic stage 6 -- 7
organism | ubiquitous

Comment: higher in proliferative tissue

(Filippov et al., 2000)
embryonic stage 8 -- 17
organism | faint | ubiquitous

Comment: higher in proliferative tissue

(Filippov et al., 2000)
embryonic stage 1 -- 3
organism | ubiquitous

Comment: maternally deposited

(Fisher et al., 2012)
embryonic stage 4 -- 6
organism | ubiquitous
(Fisher et al., 2012)
pole cell
(Fisher et al., 2012)
embryonic stage 7 -- 8
organism | ubiquitous
(Fisher et al., 2012)
head mesoderm
(Fisher et al., 2012)
organism | faint | ubiquitous
(Fisher et al., 2012)
pole cell
(Fisher et al., 2012)
trunk mesoderm
(Fisher et al., 2012)
embryonic stage 9 -- 10
organism | ubiquitous
(Fisher et al., 2012)
anterior endoderm
(Fisher et al., 2012)
organism | faint | ubiquitous
(Fisher et al., 2012)
embryonic stage 11 -- 12
organism | ubiquitous
(Fisher et al., 2012)
anterior midgut primordium
(Fisher et al., 2012)
organism | faint | ubiquitous
(Fisher et al., 2012)
posterior midgut primordium
(Fisher et al., 2012)
embryonic stage 13 -- 16
organism | ubiquitous
(Fisher et al., 2012)
embryonic/larval midgut
(Fisher et al., 2012)
organism | faint | ubiquitous
(Fisher et al., 2012)
northern blot
Stage
Tissue/Position (including subcellular localization)
Reference
embryonic stage 1 -- 9
organism | intense

Comment: high expression level; 0-4 hr AEL

(Filippov et al., 2000)
embryonic stage 10 -- 16
organism

Comment: moderate expression level; 4-16 hr AEL

(Filippov et al., 2000)
larval stage
organism | faint

Comment: low expession level

(Filippov et al., 2000)
pupal stage P6
organism

Comment: moderate expression level; 1 day APF

(Filippov et al., 2000)
adult stage | male
organism

Comment: moderate expression level

(Filippov et al., 2000)
adult stage | female
organism | intense

Comment: high expression level

(Filippov et al., 2000)
Additional Descriptive Data
Marker for
 
Subcellular Localization
CV Term
Polypeptide Expression
immunolocalization
Stage
Tissue/Position (including subcellular localization)
Reference
adult stage | femaleoogenesis stage S1 -- S10
nurse cell
(Filippov et al., 2000)
adult stage | femaleoogenesis stage S10 -- S14
oocyte
(Filippov et al., 2000)
unfertilized egg stage
unfertilized egg
(Filippov et al., 2000)
embryonic stage 3 -- 17
organism | uniform
(Filippov et al., 2000)
third instar larval stage
gonad
(Filippov et al., 2000)
imaginal disc
(Filippov et al., 2000)
mass spectroscopy
Stage
Tissue/Position (including subcellular localization)
Reference
adult stage
adult head
(Aradska et al., 2015)
western blot
Stage
Tissue/Position (including subcellular localization)
Reference
embryonic stage -- larval stage
organism
(Filippov et al., 2000)
Additional Descriptive Data

Cul1 protein is present in the nuclei of all cells, but is preferentially expressed in proliferating tissue.

(Filippov et al., 2000)
Marker for
 
Subcellular Localization
CV Term
Evidence
References
nucleus
inferred from direct assay
(Doronkin et al., 2003)
SCF ubiquitin ligase complex
inferred from direct assay
(Wong et al., 2013, Kugler et al., 2010, Reynolds et al., 2008, Bocca et al., 2001)
inferred from mutant phenotype
(Roberts et al., 2012)
Expression Deduced from Reporters
High-Throughput Expression Data
Associated Tools

GBrowse - Visual display of RNA-Seq signals

View Dmel\Cul1 in GBrowse 2
RNA-Seq by Region - Search RNA-Seq expression levels by exon or genomic region
Bulk Downloads
RNA-Seq RPKM values for all genes
Reference
See Gelbart and Emmert, 2013 for analysis details and data files for all genes.
Developmental Proteome: Life Cycle
Developmental Proteome: Embryogenesis
External Data and Images
Linkouts
BDGP expression data - Patterns of gene expression in Drosophila embryogenesis
FLIGHT - Cell culture data for RNAi and other high-throughput technologies
FlyAtlas - Adult expression by tissue, using Affymetrix Dros2 array
Fly-FISH - A database of Drosophila embryo and larvae mRNA localization patterns
Flygut - An atlas of the Drosophila adult midgut
Images
FlyBase Wiki
Image Based Resources
Alleles, Insertions, and Transgenic Constructs
Classical and Insertion Alleles ( 11 )
For All Classical and Insertion Alleles Show
 
Other relevant insertions
Transgenic Constructs ( 11 )
For All Alleles Carried on Transgenic Constructs Show
Transgenic constructs containing/affecting coding region of Cul1
Transgenic constructs containing regulatory region of Cul1
Deletions and Duplications ( 7 )
Phenotypes
For more details about a specific phenotype click on the relevant allele symbol.
Lethality
Allele
lethal | recessive
lethal - all die before end of larval stage (with Df(2R)CA53)
lethal - all die before end of larval stage | recessive
lethal - all die before end of pupal stage
lethal - all die before end of pupal stage, with Scer\GAL4pnr-MD237
partially lethal, with Dcr-2UAS.cDa, Scer\GAL4elav.PLu
viable, with Scer\GAL4GMR.PU
viable, with Scer\GAL4tin.CΔ4
Sterility
Allele
female sterile | germline clone
Other Phenotypes
Allele
decreased cell death | pupal stage | somatic clone
exocytosis defective | third instar larval stage, with Scer\GAL4SPARC-MI00329-GAL4
increased cell death
increased cell death, with Scer\GAL4sd.PU
neuroanatomy defective
neuroanatomy defective | pupal stage, with Scer\GAL4ppk.PG
neuroanatomy defective | pupal stage | somatic clone
neuroanatomy defective | somatic clone
neuroanatomy defective | somatic clone | third instar larval stage
short lived | heat sensitive, with Scer\GAL4tin.CΔ4
some die during larval stage (with Df(2R)CA53)
some die during larval stage | recessive
some die during pupal stage
some die during pupal stage, with Scer\GAL4pnr-MD237
visible, with Scer\GAL4GMR.PU
visible | adult stage | somatic clone
Phenotype manifest in
Allele
alpha/beta Kenyon cell | somatic clone
embryonic/larval fat body | third instar larval stage, with Scer\GAL4SPARC-MI00329-GAL4
extracellular matrix | third instar larval stage, with Scer\GAL4SPARC-MI00329-GAL4
eye, with Scer\GAL4GMR.PU
eye disc | somatic clone
gamma Kenyon cell | pupal stage | somatic clone
gamma Kenyon cell | somatic clone | third instar larval stage
Johnston organ | P-stage | somatic clone, with Scer\GAL4Act.PU
larval dorsal multidendritic neuron ddaC | pupal stage, with Scer\GAL4ppk.PG
larval dorsal multidendritic neuron ddaC | pupal stage | somatic clone
larval dorsal multidendritic neuron ddaD | pupal stage | somatic clone
larval dorsal multidendritic neuron ddaE | pupal stage | somatic clone
larval dorsal multidendritic neuron ddaF | pupal stage | somatic clone
neuroblast | somatic clone
ovary | germline clone
scolopidium | P-stage | somatic clone, with Scer\GAL4Act.PU
wing, with Scer\GAL4sd.PU
wing disc, with Scer\GAL4sd.PU
wing vein | somatic clone
Orthologs
Downloads
Download All DIOPT Orthologs
Download All OrthoDB Orthologs
Human Orthologs (via DIOPT v7.1)
Homo sapiens (Human) (7)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Source
Compara
eggNOG
Hieranoid
Homologene
Inparanoid
Isobase
OMA
OrthoDB
OrthoFinder
OrthoInspector
orthoMCL
Panther
Phylome
RoundUp
TreeFam
ZFIN
Alignment
Complementation?
Transgene?
Hsap\CUL1
14 of 15
Yes
Yes
 
Hsap\CACUL1
1 of 15
No
Yes
Hsap\CUL2
1 of 15
No
No
Hsap\CUL3
1 of 15
No
No
Hsap\CUL4A
1 of 15
No
No
Hsap\CUL4B
1 of 15
No
No
 
Hsap\CUL5
1 of 15
No
No
Model Organism Orthologs (via DIOPT v7.1)
Mus musculus (laboratory mouse) (6)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Source
Compara
eggNOG
Hieranoid
Homologene
Inparanoid
Isobase
OMA
OrthoDB
OrthoFinder
OrthoInspector
orthoMCL
Panther
Phylome
RoundUp
TreeFam
ZFIN
Alignment
Complementation?
Transgene?
Mmus\Cul1
14 of 15
Yes
Yes
Mmus\Cacul1
1 of 15
No
Yes
Mmus\Cul2
1 of 15
No
No
Mmus\Cul4a
1 of 15
No
No
Mmus\Cul4b
1 of 15
No
No
Mmus\Cul5
1 of 15
No
No
Rattus norvegicus (Norway rat) (7)
Rnor\Cul1
13 of 13
Yes
Yes
Rnor\Cacul1
1 of 13
No
Yes
Rnor\Cul2
1 of 13
No
No
Rnor\Cul3
1 of 13
No
No
Rnor\Cul4a
1 of 13
No
No
Rnor\Cul4b
1 of 13
No
No
Rnor\Cul5
1 of 13
No
No
Xenopus tropicalis (Western clawed frog) (3)
Xtro\cul1
12 of 12
Yes
Yes
Xtro\cul3
1 of 12
No
No
Xtro\cul5
1 of 12
No
No
Danio rerio (Zebrafish) (10)
Drer\cul1a
13 of 15
Yes
Yes
Drer\cul1b
8 of 15
No
Yes
Drer\cacul1
1 of 15
No
Yes
Drer\cul2
1 of 15
No
No
Drer\cul3a
1 of 15
No
No
Drer\cul3b
1 of 15
No
No
Drer\cul5a
1 of 15
No
No
Drer\cul5b
1 of 15
No
No
Drer\ddhd2
1 of 15
No
No
Drer\lim2.4
1 of 15
No
Yes
Caenorhabditis elegans (Nematode, roundworm) (6)
Cele\cul-1
14 of 15
Yes
Yes
Cele\cul-6
10 of 15
No
Yes
Cele\cul-2
1 of 15
No
No
Cele\cul-3
1 of 15
No
No
Cele\cul-4
1 of 15
No
No
Cele\cul-5
1 of 15
No
No
Arabidopsis thaliana (thale-cress) (8)
Atha\AT1G43140
3 of 9
Yes
Yes
Atha\CUL1
3 of 9
Yes
Yes
Atha\CUL2
3 of 9
Yes
Yes
Atha\AT1G59790
2 of 9
No
Yes
Atha\AT1G59800
2 of 9
No
Yes
Atha\CUL3
1 of 9
No
No
Atha\CUL3B
1 of 9
No
No
Atha\CUL4
1 of 9
No
No
Saccharomyces cerevisiae (Brewer's yeast) (3)
Scer\CDC53
13 of 15
Yes
Yes
Scer\RTT101
2 of 15
No
Yes
Scer\CUL3
1 of 15
No
No
Schizosaccharomyces pombe (Fission yeast) (3)
Spom\cul1
12 of 12
Yes
Yes
Spom\cul3
1 of 12
No
No
Spom\pcu4
1 of 12
No
No
Orthologs in Drosophila Species (via OrthoDB v9.1) ( EOG091902SD )
Organism
Common Name
Gene
AAA Syntenic Ortholog
Multiple Dmel Genes in this Orthologous Group
Drosophila melanogaster
fruit fly
Dmel\Cul1
Drosophila suzukii
Spotted wing Drosophila
Dsuz\DS10_00002873
Drosophila simulans
Dsim\GD10516
Drosophila sechellia
Dsec\GM20989
Drosophila erecta
Dere\GG23311
Drosophila yakuba
Dyak\GE19156
Drosophila ananassae
Dana\GF13641
Drosophila pseudoobscura pseudoobscura
Dpse\GA15074
Drosophila persimilis
Dper\GL11695
Drosophila willistoni
Dwil\GK21971
Drosophila virilis
Dvir\GJ17750
Drosophila mojavensis
Dmoj\GI19786
Drosophila grimshawi
Dgri\GH21298
Orthologs in non-Drosophila Dipterans (via OrthoDB v9.1) ( EOG091501I7 )
Organism
Common Name
Gene
Multiple Dmel Genes in this Orthologous Group
Musca domestica
House fly
Mdoa\17021486
Glossina morsitans
Tsetse fly
Gmor\GMOY002197
Lucilia cuprina
Australian sheep blowfly
Lcup\FF38_11546
Mayetiola destructor
Hessian fly
Mdes\Mdes008738
Aedes aegypti
Yellow fever mosquito
Aaeg\AAEL013530
Anopheles darlingi
American malaria mosquito
Adar\ADAC009479
Anopheles gambiae
Malaria mosquito
Agam\AGAP008007
Culex quinquefasciatus
Southern house mosquito
Cqui\CPIJ003090
Orthologs in non-Dipteran Insects (via OrthoDB v9.1) ( EOG090W02LO )
Organism
Common Name
Gene
Multiple Dmel Genes in this Orthologous Group
Bombyx mori
Silkmoth
Bmor\BGIBMGA002161
Bombyx mori
Silkmoth
Bmor\BGIBMGA009674
Danaus plexippus
Monarch butterfly
Dple\DPOGS203191-PA
Danaus plexippus
Monarch butterfly
Dple\DPOGS205581-PA
Heliconius melpomene
Postman butterfly
Hmel\HMEL008503
Heliconius melpomene
Postman butterfly
Hmel\HMEL015033
Apis florea
Little honeybee
Aflo\2277713636
Apis florea
Little honeybee
Aflo\2710638836
Apis mellifera
Western honey bee
Amel\GB52704
Apis mellifera
Western honey bee
Amel\LOC410565
Bombus impatiens
Common eastern bumble bee
Bimp\BIMP24386
Bombus impatiens
Common eastern bumble bee
Bimp\BIMP19767
Bombus terrestris
Buff-tailed bumblebee
Bter\15207559
Bombus terrestris
Buff-tailed bumblebee
Bter\15206159
Linepithema humile
Argentine ant
Lhum\LH24642
Linepithema humile
Argentine ant
Lhum\LH17060
Linepithema humile
Argentine ant
Lhum\LH24641
Megachile rotundata
Alfalfa leafcutting bee
Mrot\MROTU:001163
Megachile rotundata
Alfalfa leafcutting bee
Mrot\MROTU:002eaa
Nasonia vitripennis
Parasitic wasp
Nvit\Nasvi2EG020674
Nasonia vitripennis
Parasitic wasp
Nvit\Nasvi2EG003852
Dendroctonus ponderosae
Mountain pine beetle
Dpod\YQE_10614
Dendroctonus ponderosae
Mountain pine beetle
Dpod\YQE_10842
Tribolium castaneum
Red flour beetle
Tcas\GLEAN_15524
Tribolium castaneum
Red flour beetle
Tcas\TC009545
Pediculus humanus
Human body louse
Phum\PHUM422860
Pediculus humanus
Human body louse
Phum\PHUM546660
Pediculus humanus
Human body louse
Phum\PHUM207700
Rhodnius prolixus
Kissing bug
Rpro\RPRC007192
Rhodnius prolixus
Kissing bug
Rpro\RPRC015438
Rhodnius prolixus
Kissing bug
Rpro\RPRC009664
Cimex lectularius
Bed bug
Clec\CLEC002250
Cimex lectularius
Bed bug
Clec\CLEC003999
Acyrthosiphon pisum
Pea aphid
Apim\ACYPI002168
Acyrthosiphon pisum
Pea aphid
Apim\ACYPI005859
Acyrthosiphon pisum
Pea aphid
Apim\ACYPI002700
Zootermopsis nevadensis
Nevada dampwood termite
Znev\Znev_01520
Zootermopsis nevadensis
Nevada dampwood termite
Znev\Znev_09845
Orthologs in non-Insect Arthropods (via OrthoDB v9.1) ( EOG090X0299 )
Organism
Common Name
Gene
Multiple Dmel Genes in this Orthologous Group
Strigamia maritima
European centipede
Smar\SMAR014270
Strigamia maritima
European centipede
Smar\SMAR004154
Ixodes scapularis
Black-legged tick
Isca\ISCW021256
Ixodes scapularis
Black-legged tick
Isca\ISCW013256
Stegodyphus mimosarum
African social velvet spider
Smim\KFM75968.1
Stegodyphus mimosarum
African social velvet spider
Smim\KFM67294.1
Stegodyphus mimosarum
African social velvet spider
Smim\KFM57787.1
Tetranychus urticae
Two-spotted spider mite
Turt\tetur17g00940
Tetranychus urticae
Two-spotted spider mite
Turt\tetur13g04290
Daphnia pulex
Water flea
Dpux\DAPPUDRAFT_58155
Daphnia pulex
Water flea
Dpux\DAPPUDRAFT_333213
Daphnia pulex
Water flea
Dpux\DAPPUDRAFT_255909
Daphnia pulex
Water flea
Dpux\DAPPUDRAFT_303500
Orthologs in non-Arthropod Metazoa (via OrthoDB v9.1) ( EOG091G02WR )
Organism
Common Name
Gene
Multiple Dmel Genes in this Orthologous Group
Strongylocentrotus purpuratus
Purple sea urchin
Spur\Sp-Cul1
Ciona intestinalis
Vase tunicate
Cint\LOC100177902
Gallus gallus
Domestic chicken
Ggal\CUL1
Paralogs
Downloads
Download All DIOPT Paralogs
Paralogs (via DIOPT v7.1)
Drosophila melanogaster (Fruit fly) (5)
Gene Symbol
Score
Source
Compara
eggNOG
Homologene
Inparanoid
Isobase
OrthoDB
OrthoFinder
orthoMCL
Panther
RoundUp
Alignment
Cul6
4 of 10
Cul2
3 of 10
Cul3
3 of 10
Cul4
3 of 10
Cul5
2 of 10
Human Disease Associations
FlyBase Human Disease Model Reports
    Disease Model Summary Ribbon
    Disease Ontology (DO) Annotations
    Models Based on Experimental Evidence ( 0 )
    Allele
    Disease
    Evidence
    References
    Potential Models Based on Orthology ( 0 )
    Human Ortholog
    Disease
    Evidence
    References
    Modifiers Based on Experimental Evidence ( 0 )
    Allele
    Disease
    Interaction
    References
    Disease Associations of Human Orthologs (via DIOPT v7.1 and OMIM)
    Note that ortholog calls supported by only 1 or 2 algorithms (DIOPT score < 3) are not shown.
    Homo sapiens (Human)
    Gene name
    Score
    OMIM
    OMIM Phenotype
    DO term
    Complementation?
    Transgene?
    CUL1; cullin 1
    14 of 15
    603134
         
        Functional Complementation Data
        Functional complementation data is computed by FlyBase using a combination of the orthology data obtained from DIOPT and OrthoDB and the allele-level genetic interaction data curated from the literature.
        Interactions
        Summary of Physical Interactions
        esyN Network Diagram
        Show neighbor-neighbor interactions:
        Select Layout:
        Legend:
        Protein
        RNA
        Selected Interactor(s)
        Interactions Browser
        View in Interactions Browser
        Please see the Physical Interaction reports below for full details
        protein-protein
        Physical Interaction
        Assay
        References
        Cul1 - CG7148
        experimental knowledge based
        (Guruharsha et al., 2011)
        Cul1 - Cad99C
        anti tag coimmunoprecipitation, anti tag western blot
        (Li et al., 2016)
        Cul1 - Cand1
        pull down, autoradiography
        (Kim et al., 2010)
        Cul1 - Dlish
        anti tag coimmunoprecipitation, western blot
        (Zhang et al., 2016)
        Cul1 - Fbxl7
        anti tag coimmunoprecipitation, anti tag western blot
        (Bosch et al., 2014)
        Cul1 - Fsn
        anti tag coimmunoprecipitation, western blot
        (Kugler et al., 2010)
        Cul1 - Nedd8
        anti bait coimmunoprecipitation, anti tag western blot, western blot
        (Chan et al., 2008, Ou et al., 2002)
        Cul1 - Pi3K21B
        anti tag coimmunoprecipitation, peptide massfingerprinting
        (Glatter et al., 2011)
        Cul1 - RYBP
        anti bait coimmunoprecipitation, western blot
        (Fereres et al., 2013)
        Cul1 - Roc1a
        anti tag coimmunoprecipitation, anti tag western blot, western blot
        (Zhang et al., 2013, Reynolds et al., 2008)
        Cul1 - Sans
        anti tag coimmunoprecipitation, anti tag western blot
        (Li et al., 2016)
        Cul1 - SkpA
        anti tag coimmunoprecipitation, anti tag western blot, experimental knowledge based
        (Zhang et al., 2013, Guruharsha et al., 2011)
        Cul1 - SkpB
        experimental knowledge based
        (Guruharsha et al., 2011)
        Cul1 - Smn
        anti tag coimmunoprecipitation, western blot, Identification by mass spectrometry
        (Gray et al., 2018)
        Cul1 - TER94
        anti tag coimmunoprecipitation, anti tag western blot
        (Zhang et al., 2013)
        Cul1 - ci
        pull down, anti tag western blot, enzymatic study, peptide massfingerprinting
        (Zhang et al., 2013, Smelkinson et al., 2007)
        Cul1 - ex
        anti tag coimmunoprecipitation, peptide massfingerprinting
        (Ribeiro et al., 2014)
        Cul1 - mi
        pull down, western blot
        (Szuplewski et al., 2009)
        Cul1 - ntc
        anti tag coimmunoprecipitation, western blot
        (Bader et al., 2010)
        Cul1 - slmb
        anti tag coimmunoprecipitation, western blot, anti tag western blot
        (Wong et al., 2013, Zhang et al., 2013, Smelkinson et al., 2007)
        Summary of Genetic Interactions
        esyN Network Diagram
        esyN Network Key:
        Suppression
        Enhancement
        View in Interactions Browser
        Please look at the allele data for full details of the genetic interactions
        Starting gene(s)
        Interaction type
        Interacting gene(s)
        Reference
        Cul1
        suppressible
        Akt1
        (Wong et al., 2013)
        Cul1
        suppressible
        InR
        (Wong et al., 2013)
        Cul1
        suppressible
        Pi3K92E
        (Wong et al., 2013)
        Cul1
        suppressible
        Pten
        (Wong et al., 2013)
        Cul1
        suppressible
        S6k
        (Wong et al., 2013)
        Cul1
        suppressible
        Thor
        (Wong et al., 2013)
        Cul1
        suppressible
        Tor
        (Wong et al., 2013)
        Cul1
        suppressible
        Tsc1|gig
        (Wong et al., 2013)
        Starting gene(s)
        Interaction type
        Interacting gene(s)
        Reference
        COX5A
        suppressible
        Cul1
        (Mandal et al., 2010)
        enc
        enhanceable
        Cul1
        (Ohlmeyer and Schupbach, 2003)
        prd1
        enhanceable
        Cul1
        (Zong et al., 2018)
        slmb
        enhanceable
        Cul1
        (Muzzopappa and Wappner, 2005)
        External Data
        Subunit Structure (UniProtKB)
        Component of SCF E3 ubiquitin-protein ligase complexes consisting of Skpa, Cul1, Roc1a and an F-box protein. In larval neuroblast self renewal and asymmetric division, as well as ddaC dendrite and mushroom body axon pruning, the complex contains the F-box protein slmb (SCF-slmb) (PubMed:24068890, PubMed:24413555). In caspase activation during sperm differentiation, the complex contains the F-box protein ntc (PubMed:20392747). Interacts directly with Roc1a (PubMed:11500045). Interacts with Fsn (PubMed:20123973). Interacts with Dlish (PubMed:27692068). Interacts with Cad99C (via the cytoplasmic domain) (PubMed:27331610). Interacts with Sans (PubMed:27331610).
        (UniProt, Q24311 )
        Linkouts
        BioGRID - A database of protein and genetic interactions.
        DroID - A comprehensive database of gene and protein interactions.
        InterologFinder - Protein-protein interactions (PPI) from both known and predicted PPI data sets.
        MIST (genetic) - An integrated Molecular Interaction Database
        MIST (protein-protein) - An integrated Molecular Interaction Database
        Pathways
        Signaling Pathways (FlyBase)
        Negative Regulators of Wnt-TCF Signaling Pathway -
        Negative regulators of canonical Wnt signaling down-regulate the pathway, resulting in the attenuation of transcriptional regulation mediated by β-catenin (arm).
        Negative Regulators of Insulin-like Receptor Signaling Pathway -
        Negative regulators of the Insulin-like Receptor signaling pathway suppress Insulin-like receptor (InR) activation or the activity of intracellular effectors. (Adapted from FBrf0232297, FBrf0230017 and FBrf0229989).
        Negative Regulators of Hedgehog Signaling Pathway -
        Negative regulators of hedgehog signaling down-regulation the pathway, resulting in the repression of transcription of hh-responsive genes.
        Metabolic Pathways
        External Data
        Genomic Location and Detailed Mapping Data
        Chromosome (arm)
        2R
        Recombination map

        2-57

        Cytogenetic map
        43F1-43F2
        Sequence location
        2R:7,916,856..7,921,579 [+]
        FlyBase Computed Cytological Location
        Cytogenetic map
        Evidence for location
        43F1-43F2
        Limits computationally determined from genome sequence between P{EP}CanB2EP774 and P{lacW}lin19k01207&P{lacW}rnh1k07624
        Experimentally Determined Cytological Location
        Cytogenetic map
        Notes
        References
        43F-44A
        (Heriche, 1999.3.19)
        43F1-43F2
        (determined by in situ hybridisation)
        (Spradling et al., 1999)
        43F1-43F6
        (determined by in situ hybridisation)
        (Filippova et al., 1997)
        43F1-43F2
        (BDGP Project Members, 1994-1999)
        Experimentally Determined Recombination Data
        Location

        2-57

        (FlyBase, 2016)

        2-57.2

        (Comeron et al., 2012)

        2-

        (Filippova et al., 1997)
        Left of (cM)
        Right of (cM)
        Notes
        Stocks and Reagents
        Stocks (16)
        Genomic Clones (12)
         

        Please Note FlyBase no longer curates genomic clone accessions so this list may not be complete

        cDNA Clones (215)
         

        Please Note This section lists cDNAs and ESTs that fall within the genomic extent of the gene model, which may include cDNAs and ESTs of genes within introns, or of overlapping genes. Please see GBrowse for alignment of the cDNAs and ESTs to the gene model.

        cDNA clones, fully sequences
        BDGP DGC clones
        Other clones
          Drosophila Genomics Resource Center cDNA clones

          For each fully sequenced cDNA the DGRC maintains various forms of the cDNA (e.g tagged or untagged) in several different host vectors for subsequent cloning and expression in Drosophila and Drosophila cell lines.

          cDNA Clones, End Sequenced (ESTs)
          BDGP DGC clones
          Other clones
          RNAi and Array Information
          Linkouts
          DRSC - Results frm RNAi screens
          GenomeRNAi - A database for cell-based and in vivo RNAi phenotypes and reagents
          Antibody Information
          Laboratory Generated Antibodies
           

          polyclonal

          (Higa et al., 2006)
          Commercially Available Antibodies
           
          Other Information
          Relationship to Other Genes
          Source for database identify of

          Source for identity of: lin19 CG1877

          (Heiman, 1999.11)

          Source for identity of: Cul1 lin19

          (FlyBase, 2009-)
          Source for database merge of

          Source for merge of: lin19 l(2)k01207

          (Spradling et al., 1999)
          Additional comments

          Renamed from 'lin19' to 'Cul1' to reflect usage in the literature and make the nomenclature of Cullin genes consistent.

          (FlyBase, 2009-)
          Other Comments

          S2 cells are treated with dsRNA made from templates generated with primers directed against this gene to assess effect on degradation of dup and geminin genes.

          (Higa et al., 2003)

          Northern analysis reveals lin19 is expressed in all developmental stages with maximal expression on 0-4 hour embryos. In situ hybridisation demonstrates elevated transcription during oogenesis and early embryogenesis. Maternally derived protein is also detected in eggs of virgin females.

          (Filippova et al., 1997)
          Origin and Etymology
          Discoverer
          Etymology
          Identification
          External Crossreferences and Linkouts ( 83 )
          Sequence Crossreferences
          NCBI Gene - Gene integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes, and links to genome-, phenotype-, and locus-specific resources worldwide.
          GenBank Nucleotide - A collection of sequences from several sources, including GenBank, RefSeq, TPA, and PDB.
          GenBank Protein - A collection of sequences from several sources, including translations from annotated coding regions in GenBank, RefSeq and TPA, as well as records from SwissProt, PIR, PRF, and PDB.
          RefSeq - A comprehensive, integrated, non-redundant, well-annotated set of reference sequences including genomic, transcript, and protein.
          UniProt/Swiss-Prot - Manually annotated and reviewed records of protein sequence and functional information
          Other crossreferences
          BDGP expression data - Patterns of gene expression in Drosophila embryogenesis
          Drosophila Genomics Resource Center - Drosophila Genomics Resource Center (DGRC) cDNA clones
          Eukaryotic Promoter Database - A collection of databases of experimentally validated promoters for selected model organisms.
          Fly-FISH - A database of Drosophila embryo and larvae mRNA localization patterns
          Flygut - An atlas of the Drosophila adult midgut
          Reactome - An open-source, open access, manually curated and peer-reviewed pathway database.
          GenomeRNAi - A database for cell-based and in vivo RNAi phenotypes and reagents
          iBeetle-Base - RNAi phenotypes in the red flour beetle (Tribolium castaneum)
          InterPro - A database of protein families, domains and functional sites
          KEGG Genes - Molecular building blocks of life in the genomic space.
          modMine - A data warehouse for the modENCODE project
          SignaLink - A signaling pathway resource with multi-layered regulatory networks.
          Linkouts
          ApoDroso - Functional genomic database for photoreceptor development, survival and function
          BioGRID - A database of protein and genetic interactions.
          DroID - A comprehensive database of gene and protein interactions.
          DRSC - Results frm RNAi screens
          FLIGHT - Cell culture data for RNAi and other high-throughput technologies
          FlyAtlas - Adult expression by tissue, using Affymetrix Dros2 array
          FlyCyc Genes - Genes from a BioCyc PGDB for Dmel
          FlyMine - An integrated database for Drosophila genomics
          Interactive Fly - A cyberspace guide to Drosophila development and metazoan evolution
          InterologFinder - Protein-protein interactions (PPI) from both known and predicted PPI data sets.
          KEGG Pathways - Wiring diagrams of molecular interactions, reactions and relations.
          MIST (genetic) - An integrated Molecular Interaction Database
          MIST (protein-protein) - An integrated Molecular Interaction Database
          Reactome - An open-source, open access, manually curated and peer-reviewed pathway database.
          Synonyms and Secondary IDs (28)
          Reported As
          Symbol Synonym
          CG1877
          (Çiçek et al., 2016, Hosono et al., 2015, Ribeiro et al., 2014, Schertel et al., 2013, Chen et al., 2012, Christis and Munro, 2012, Glatter et al., 2011, Ni et al., 2011.7.19, Zhang et al., 2010, Keleman et al., 2009.8.5, Perkins et al., 2009, Grieder et al., 2007, Donaldson et al., 2004)
          CUL1
          (Brownlee and Rogers, 2013, Kondo and Perrimon, 2011, Higa et al., 2006, Higa et al., 2003)
          Cul-1
          (Kohzaki et al., 2018, Bonke et al., 2013, Strutt et al., 2013, Du et al., 2011, Kugler et al., 2010, Cunha-Ferreira et al., 2009, Franc et al., 2007, Bjorklund et al., 2006, Kuo et al., 2006, Gemmill et al., 2005, Muzzopappa and Wappner, 2004)
          Cul1
          (Chen et al., 2019, Sato et al., 2019, Collu et al., 2018, Gray et al., 2018, Rosa-Ferreira et al., 2018, Zong et al., 2018, Ketosugbo et al., 2017, Pan et al., 2017, Suisse et al., 2017, Fu et al., 2016, Zhang et al., 2016, Zhou et al., 2015, Bosch et al., 2014, Huang et al., 2014, Wong et al., 2013, Zhang et al., 2013, Zhang et al., 2013, Fabian and Brill, 2012, Du et al., 2011, Sarikas et al., 2011, Stavropoulos and Young, 2011, Kim et al., 2010, Szuplewski et al., 2009, Chan et al., 2008, Chan et al., 2008, Hall et al., 2008, Oren-Giladi et al., 2008, Rencus-Lazar et al., 2008, Reynolds et al., 2008, Shibutani et al., 2008, Kim et al., 2007, Ou et al., 2007, Smelkinson et al., 2007, Zielke et al., 2006, Wu et al., 2005, Zhu et al., 2005, Wu and Chien, 2004, Heriche et al., 2003, Ou et al., 2003, Ou et al., 2003, Cope et al., 2002, Jiang, 2002, Jin and Harper, 2002, Ou et al., 2002)
          Cullin-1
          (Strutt et al., 2013)
          Cullin1
          (Cronin et al., 2009)
          Lin-19
          (Tokusumi et al., 2012)
          Lin19
          (Glatter et al., 2011)
          Q9V312
          (Rojas et al., 2012)
          cul-1
          (Rumpf et al., 2014, Buster et al., 2013, Christiansen et al., 2013, Kugler et al., 2010, Rogers et al., 2009, Kuo et al., 2006, Das et al., 2002, Filippov et al., 2000, Heriche, 1999.3.19)
          cul1
          (Neukomm et al., 2017, Li et al., 2016, Qian et al., 2015, Wong et al., 2013, Ayyub, 2011, Mandal et al., 2010, Djagaeva and Doronkin, 2009, Corrigall et al., 2007, Ohlmeyer and Schupbach, 2004, Ohlmeyer and Schupbach, 2003)
          dCUL1
          (Bhutani et al., 2012)
          dCul-1
          (Heriche and O'Farrell, 2001)
          dCul1
          (Fereres et al., 2013, Heriche et al., 2003, Bocca et al., 2001, Muzzopappa et al., 2001)
          dmCUL1
          (Higa et al., 2006)
          l(2)02074
          (Han et al., 2003, Khush et al., 2002)
          l(2)k01207
          (BDGP Project Members, 1994-1999)
          lin 19
          (Du et al., 2011)
          lin-19/cul-1
          (Sandmann et al., 2007)
          lin19
          (Ugrankar et al., 2018, Aradska et al., 2015, Ugrankar et al., 2015, Van Bortle et al., 2015, Ribeiro et al., 2014, de Celis et al., 2013.9.11, Kroeger et al., 2013, Schertel et al., 2013, Strutt et al., 2013, Wong et al., 2013, Japanese National Institute of Genetics, 2012.5.21, Joyce et al., 2012, Rohn et al., 2011, Sarikas et al., 2011, Toku et al., 2011, Christensen and Cook, 2007.3.22, Grieder et al., 2007, Zhou et al., 2007, Heriche et al., 2003)
          lin19-like
          (Elmore and Smith, 2001)
          Name Synonyms
          Cullin
          (Alexandre et al., 2008)
          Cullin 1
          (Rosa-Ferreira et al., 2018, Mandal et al., 2010, Zielke et al., 2006)
          Cullin-1
          (Wong et al., 2013, Bader et al., 2010, Kugler et al., 2010)
          Cullin1
          (Kim et al., 2010, Djagaeva and Doronkin, 2009, Djagaeva and Doronkin, 2009, Szuplewski et al., 2009, Khush et al., 2002, Lin et al., 2002)
          cullin-1
          (Wong et al., 2013)
          cullin1
          (Segal et al., 2007, Wu et al., 2005, Doronkin et al., 2003)
          dCullin
          (Hoopfer et al., 2008)
          dCullin1
          (Khush, 2003.2.25)
          lin-19-like
          lin19-like
          (Zhou et al., 2007)
          Secondary FlyBase IDs
          • FBgn0020308
          • FBgn0022252
          Datasets (0)
          Study focus (0)
          Experimental Role
          Project
          Project Type
          Title
          References (165)