Aliases for DENND3 Gene

Aliases for DENND3 Gene

  • DENN Domain Containing 3 2 3 5
  • DENN Domain-Containing Protein 3 3 4
  • DENN/MADD Domain Containing 3 2 3
  • KIAA0870 2 4
  • DENND3 5

External Ids for DENND3 Gene

Previous GeneCards Identifiers for DENND3 Gene

  • GC08P142156
  • GC08P137450
  • GC08P142127

Summaries for DENND3 Gene

GeneCards Summary for DENND3 Gene

DENND3 (DENN Domain Containing 3) is a Protein Coding gene. Diseases associated with DENND3 include Hirschsprung Disease 1 and Janus Kinase-3 Deficiency. Among its related pathways are Vesicle-mediated transport and RAB GEFs exchange GTP for GDP on RABs. Gene Ontology (GO) annotations related to this gene include Rab guanyl-nucleotide exchange factor activity. An important paralog of this gene is DENND4A.

UniProtKB/Swiss-Prot Summary for DENND3 Gene

  • Guanine nucleotide exchange factor (GEF) activating RAB12. Promotes the exchange of GDP to GTP, converting inactive GDP-bound RAB12 into its active GTP-bound form (PubMed:20937701). Regulates autophagy in response to starvation through RAB12 activation. Starvation leads to ULK1/2-dependent phosphorylation of Ser-472 and Ser-490, which in turn allows recruitment of 14-3-3 adapter proteins and leads to up-regulation of GEF activity towards RAB12 (By similarity). Also plays a role in protein transport from recycling endosomes to lysosomes, regulating, for instance, the degradation of the transferrin receptor and of the amino acid transporter PAT4 (PubMed:20937701). Starvation also induces phosphorylation at Tyr-858, which leads to up-regulated GEF activity and initiates autophagy (By similarity).

No data available for Entrez Gene Summary , CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for DENND3 Gene

Genomics for DENND3 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for DENND3 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 DENND3 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for DENND3

Top Transcription factor binding sites by QIAGEN in the DENND3 gene promoter:
  • AML1a
  • AP-4
  • AREB6
  • ATF
  • GATA-1
  • POU2F1
  • POU2F1a
  • RP58
  • STAT3

Genomic Locations for DENND3 Gene

Latest Assembly
chr8:141,117,278-141,195,808
(GRCh38/hg38)
Size:
78,531 bases
Orientation:
Plus strand

Previous Assembly
chr8:142,138,688-142,205,903
(GRCh37/hg19 by Entrez Gene)
Size:
67,216 bases
Orientation:
Plus strand

chr8:142,127,377-142,205,907
(GRCh37/hg19 by Ensembl)
Size:
78,531 bases
Orientation:
Plus strand

Genomic View for DENND3 Gene

Genes around DENND3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
DENND3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for DENND3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for DENND3 Gene

Proteins for DENND3 Gene

  • Protein details for DENND3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    A2RUS2-DEND3_HUMAN
    Recommended name:
    DENN domain-containing protein 3
    Protein Accession:
    A2RUS2
    Secondary Accessions:
    • B7ZM28
    • O94947
    • Q2TAM7
    • Q6ZMS6
    • Q96DK3

    Protein attributes for DENND3 Gene

    Size:
    1198 amino acids
    Molecular mass:
    135890 Da
    Quaternary structure:
    • Forms oligomers. Interacts with 6 of the 7 known isoforms of 14-3-3 proteins.

    Alternative splice isoforms for DENND3 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for DENND3 Gene

Post-translational modifications for DENND3 Gene

  • Ubiquitination at Lys391, Lys511, and Lys517
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for DENND3 Gene

Domains & Families for DENND3 Gene

Gene Families for DENND3 Gene

HGNC:
Human Protein Atlas (HPA):
  • Predicted intracellular proteins
  • Predicted membrane proteins

Suggested Antigen Peptide Sequences for DENND3 Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ34237 fis, clone FCBBF3027328 (B3KRG7_HUMAN)
  • DENN domain-containing protein 3 (DEND3_HUMAN)

Graphical View of Domain Structure for InterPro Entry

A2RUS2

UniProtKB/Swiss-Prot:

DEND3_HUMAN :
  • Inactive DENND3 is found in a closed conformation, in which the linker region interacts with the DENN domain. Phosphorylation of Tyr-858 in the linker region intereferes with this interaction leading to an open conformation and enhances the GEF activity of the protein towards RAB12.
Domain:
  • Inactive DENND3 is found in a closed conformation, in which the linker region interacts with the DENN domain. Phosphorylation of Tyr-858 in the linker region intereferes with this interaction leading to an open conformation and enhances the GEF activity of the protein towards RAB12.
genes like me logo Genes that share domains with DENND3: view

Function for DENND3 Gene

Molecular function for DENND3 Gene

UniProtKB/Swiss-Prot Function:
Guanine nucleotide exchange factor (GEF) activating RAB12. Promotes the exchange of GDP to GTP, converting inactive GDP-bound RAB12 into its active GTP-bound form (PubMed:20937701). Regulates autophagy in response to starvation through RAB12 activation. Starvation leads to ULK1/2-dependent phosphorylation of Ser-472 and Ser-490, which in turn allows recruitment of 14-3-3 adapter proteins and leads to up-regulation of GEF activity towards RAB12 (By similarity). Also plays a role in protein transport from recycling endosomes to lysosomes, regulating, for instance, the degradation of the transferrin receptor and of the amino acid transporter PAT4 (PubMed:20937701). Starvation also induces phosphorylation at Tyr-858, which leads to up-regulated GEF activity and initiates autophagy (By similarity).

Phenotypes From GWAS Catalog for DENND3 Gene

Gene Ontology (GO) - Molecular Function for DENND3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005085 guanyl-nucleotide exchange factor activity IBA,IDA 20937701
GO:0005515 protein binding IEA --
genes like me logo Genes that share ontologies with DENND3: view
genes like me logo Genes that share phenotypes with DENND3: view

miRNA for DENND3 Gene

miRTarBase miRNAs that target DENND3

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for DENND3

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for DENND3 Gene

Localization for DENND3 Gene

Subcellular locations from UniProtKB/Swiss-Prot for DENND3 Gene

Cytoplasm. Note=Transiently recruited to membranes to activate RAB12. {ECO:0000250 UniProtKB:A2RT67}.

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 DENND3 gene
Compartment Confidence
cytosol 4
nucleus 2
plasma membrane 1
mitochondrion 1
endosome 1
lysosome 1
golgi apparatus 1
peroxisome 0

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (2)
  • Vesicles (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for DENND3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IEA --
GO:0005829 cytosol TAS --
GO:0031410 cytoplasmic vesicle IBA 21873635
genes like me logo Genes that share ontologies with DENND3: view

Pathways & Interactions for DENND3 Gene

genes like me logo Genes that share pathways with DENND3: view

Pathways by source for DENND3 Gene

Interacting Proteins for DENND3 Gene

Gene Ontology (GO) - Biological Process for DENND3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0008333 endosome to lysosome transport ISS --
GO:0032483 regulation of Rab protein signal transduction IBA 21873635
GO:0044257 cellular protein catabolic process ISS --
GO:0050790 regulation of catalytic activity IEA --
genes like me logo Genes that share ontologies with DENND3: view

No data available for SIGNOR curated interactions for DENND3 Gene

Drugs & Compounds for DENND3 Gene

No Compound Related Data Available

Transcripts for DENND3 Gene

mRNA/cDNA for DENND3 Gene

4 REFSEQ mRNAs :
18 NCBI additional mRNA sequence :
22 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 DENND3

Alternative Splicing Database (ASD) splice patterns (SP) for DENND3 Gene

ExUns: 1a · 1b · 1c · 1d ^ 2a · 2b · 2c ^ 3 ^ 4a · 4b · 4c ^ 5a · 5b ^ 6a · 6b · 6c ^ 7a · 7b ^ 8a · 8b ^ 9a · 9b ^ 10 ^ 11 ^ 12a · 12b ·
SP1:
SP2: - -
SP3: -
SP4:
SP5: - - - - -
SP6:
SP7:
SP8: -
SP9:
SP10: -
SP11: -
SP12:
SP13:
SP14:
SP15:
SP16:
SP17:
SP18:

ExUns: 12c ^ 13a · 13b ^ 14 ^ 15 ^ 16a · 16b ^ 17a · 17b · 17c ^ 18 ^ 19a · 19b · 19c ^ 20a · 20b · 20c ^ 21a · 21b ^ 22a · 22b · 22c ^ 23a · 23b ^ 24
SP1: - - - - - - - -
SP2:
SP3:
SP4:
SP5:
SP6: - - - - -
SP7: - - -
SP8:
SP9:
SP10:
SP11:
SP12:
SP13: - -
SP14:
SP15: -
SP16:
SP17:
SP18:

Relevant External Links for DENND3 Gene

GeneLoc Exon Structure for
DENND3

Expression for DENND3 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for DENND3 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for DENND3 Gene

This gene is overexpressed in Whole Blood (x12.4).

Protein differential expression in normal tissues from HIPED for DENND3 Gene

This gene is overexpressed in Peripheral blood mononuclear cells (52.9).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for DENND3 Gene



Protein tissue co-expression partners for DENND3 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for DENND3

SOURCE GeneReport for Unigene cluster for DENND3 Gene:

Hs.18166

Evidence on tissue expression from TISSUES for DENND3 Gene

  • Nervous system(4.5)
  • Stomach(4.2)
genes like me logo Genes that share expression patterns with DENND3: view

Primer products for research

No data available for mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for DENND3 Gene

Orthologs for DENND3 Gene

This gene was present in the common ancestor of chordates.

Orthologs for DENND3 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia DENND3 30 31
  • 98.33 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia DENND3 30 31
  • 81.7 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia DENND3 30 31
  • 81.62 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Dennd3 30 17 31
  • 79.26 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Dennd3 30
  • 78.8 (n)
Platypus
(Ornithorhynchus anatinus)
Mammalia DENND3 31
  • 70 (a)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia -- 31
  • 69 (a)
OneToMany
-- 31
  • 61 (a)
OneToMany
Chicken
(Gallus gallus)
Aves DENND3 30 31
  • 66.69 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia DENND3 31
  • 63 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia dennd3 30
  • 64.95 (n)
Zebrafish
(Danio rerio)
Actinopterygii dennd3a 30 31
  • 60.69 (n)
OneToMany
dennd3b 31
  • 48 (a)
OneToMany
Rainbow Trout
(Oncorhynchus mykiss)
Actinopterygii Omy.5903 30
Species where no ortholog for DENND3 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • 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)
  • Fruit Fly (Drosophila melanogaster)
  • 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 Squirt (Ciona savignyi)
  • 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)
  • Worm (Caenorhabditis elegans)

Evolution for DENND3 Gene

ENSEMBL:
Gene Tree for DENND3 (if available)
TreeFam:
Gene Tree for DENND3 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for DENND3: view image

Paralogs for DENND3 Gene

Paralogs for DENND3 Gene

(1) SIMAP similar genes for DENND3 Gene using alignment to 13 proteins:

  • DEND3_HUMAN
  • B3KRG7_HUMAN
  • E5RH95_HUMAN
  • E5RHH2_HUMAN
  • E5RI43_HUMAN
  • E5RIR7_HUMAN
  • E5RJ42_HUMAN
  • E9PF32_HUMAN
  • H0YAW2_HUMAN
  • H0YAY3_HUMAN
  • H0YBH5_HUMAN
  • H0YBK9_HUMAN
  • L8E848_HUMAN

Pseudogenes.org Pseudogenes for DENND3 Gene

genes like me logo Genes that share paralogs with DENND3: view

Variants for DENND3 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for DENND3 Gene

SNP ID Clinical significance and condition Chr 08 pos Variation AA Info Type
rs1045303 Uncertain Significance: Hirschsprung disease 141,190,368(+) G/A
NM_001352890.3(DENND3):c.3330G>A (p.Pro1110=)
NON_CODING_TRANSCRIPT_VARIANT,SYNONYMOUS
rs1057519052 Likely Pathogenic: Hirschsprung disease 1 141,168,409(+) AG/A
NM_014957.5(DENND3):c.1959del (p.Lys653fs)
FRAMESHIFT_VARIANT,NON_CODING_TRANSCRIPT
rs116789554 Benign: not provided 141,144,160(+) T/A
NM_001352890.3(DENND3):c.636T>A (p.Leu212=)
NON_CODING_TRANSCRIPT_VARIANT,SYNONYMOUS
rs11997191 Benign: not provided. - 141,160,766(+) A/Gp.Gln364Arg
NM_001352890.3(DENND3):c.1331A>G (p.Gln444Arg)
MISSENSE_VARIANT,NON_CODING_TRANSCRIPT
rs144082723 Benign: not provided 141,136,755(+) G/A
NM_001352890.3(DENND3):c.349G>A (p.Val117Met)
MISSENSE_VARIANT,NON_CODING_TRANSCRIPT

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for DENND3 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 DENND3 Gene

Variant ID Type Subtype PubMed ID
dgv1426e214 CNV loss 21293372
esv2737756 CNV deletion 23290073
esv3415271 CNV duplication 20981092
esv3619054 CNV loss 21293372
esv3619055 CNV loss 21293372
nsv1126125 CNV deletion 24896259
nsv470239 CNV loss 18288195
nsv473858 CNV novel sequence insertion 20440878
nsv509284 CNV insertion 20534489
nsv612568 CNV gain 21841781
nsv824750 CNV loss 20364138
nsv831483 CNV gain 17160897

Variation tolerance for DENND3 Gene

Residual Variation Intolerance Score: 8.54% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 7.86; 83.63% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for DENND3 Gene

Human Gene Mutation Database (HGMD)
DENND3
SNPedia medical, phenotypic, and genealogical associations of SNPs for
DENND3

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for DENND3 Gene

Disorders for DENND3 Gene

MalaCards: The human disease database

(3) MalaCards diseases for DENND3 Gene - From: CVR, COP, and GCD

Disorder Aliases PubMed IDs
hirschsprung disease 1
  • hirschsprung disease, susceptibility to, 1
janus kinase-3 deficiency
megacystis-microcolon-intestinal hypoperistalsis syndrome
  • mmihs
- elite association - COSMIC cancer census association via MalaCards

Additional Disease Information for DENND3

Genetic Association Database
(GAD)
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 DENND3: view

No data available for UniProtKB/Swiss-Prot and Genatlas for DENND3 Gene

Publications for DENND3 Gene

  1. Regulation of DENND3, the exchange factor for the small GTPase Rab12 through an intramolecular interaction. (PMID: 28249939) Xu J … McPherson PS (The Journal of biological chemistry 2017) 2 3
  2. Family-wide characterization of the DENN domain Rab GDP-GTP exchange factors. (PMID: 20937701) Yoshimura S … Barr FA (The Journal of cell biology 2010) 3 4
  3. Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. (PMID: 20379614) Rose JE … Uhl GR (Molecular medicine (Cambridge, Mass.) 2010) 3 41
  4. Complete sequencing and characterization of 21,243 full-length human cDNAs. (PMID: 14702039) Ota T … Sugano S (Nature genetics 2004) 3 4
  5. Prediction of the coding sequences of unidentified human genes. XII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. (PMID: 10048485) Nagase T … Ohara O (DNA research : an international journal for rapid publication of reports on genes and genomes 1998) 3 4

Products for DENND3 Gene

Sources for DENND3 Gene