The protein encoded by this gene is a putative protein kinase that is induced by the transcription factor NF-kappaB. The encoded protein is a negative regulator of NF-kappaB and can also sensitize cells to TNF- and TRAIL-induced apoptosis. In addition, this protein can negatively regulate the cell survival serine-threonine kinase AKT1. Differential promoter usage and alternate ... See more...

Aliases for TRIB3 Gene

Aliases for TRIB3 Gene

  • Tribbles Pseudokinase 3 2 3 5
  • TRB3 2 3 4
  • P65-Interacting Inhibitor Of NF-Kappa-B 3 4
  • Tribbles Homolog 3 3 4
  • C20orf97 3 4
  • SKIP3 3 4
  • TRB-3 3 4
  • NIPK 3 4
  • SINK 3 4
  • Neuronal Cell Death Inducible Putative Kinase 3
  • Neuronal Cell Death-Inducible Putative Kinase 4
  • P65-Interacting Inhibitor Of NF-KappaB 3
  • Chromosome 20 Open Reading Frame 97 2
  • Tribbles Homolog 3 (Drosophila) 2
  • DJ1103G7.3 2
  • TRIB3 5

External Ids for TRIB3 Gene

Previous HGNC Symbols for TRIB3 Gene

  • C20orf97

Previous GeneCards Identifiers for TRIB3 Gene

  • GC20P000357
  • GC20P000309

Summaries for TRIB3 Gene

Entrez Gene Summary for TRIB3 Gene

  • The protein encoded by this gene is a putative protein kinase that is induced by the transcription factor NF-kappaB. The encoded protein is a negative regulator of NF-kappaB and can also sensitize cells to TNF- and TRAIL-induced apoptosis. In addition, this protein can negatively regulate the cell survival serine-threonine kinase AKT1. Differential promoter usage and alternate splicing result in multiple transcript variants. [provided by RefSeq, Jul 2014]

GeneCards Summary for TRIB3 Gene

TRIB3 (Tribbles Pseudokinase 3) is a Protein Coding gene. Diseases associated with TRIB3 include Diabetes Mellitus, Noninsulin-Dependent. Among its related pathways are RET signaling and CD28 co-stimulation. Gene Ontology (GO) annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein kinase binding. An important paralog of this gene is TRIB1.

UniProtKB/Swiss-Prot Summary for TRIB3 Gene

  • Inactive protein kinase which acts as a regulator of the integrated stress response (ISR), a process for adaptation to various stress (PubMed:15781252, PubMed:15775988). Inhibits the transcriptional activity of DDIT3/CHOP and is involved in DDIT3/CHOP-dependent cell death during ER stress (PubMed:15781252, PubMed:15775988). May play a role in programmed neuronal cell death but does not appear to affect non-neuronal cells (PubMed:15781252, PubMed:15775988). Acts as a negative feedback regulator of the ATF4-dependent transcription during the ISR: while TRIB3 expression is promoted by ATF4, TRIB3 protein interacts with ATF4 and inhibits ATF4 transcription activity (By similarity). Disrupts insulin signaling by binding directly to Akt kinases and blocking their activation (By similarity). May bind directly to and mask the 'Thr-308' phosphorylation site in AKT1 (By similarity). Interacts with the NF-kappa-B transactivator p65 RELA and inhibits its phosphorylation and thus its transcriptional activation activity (PubMed:12736262). Interacts with MAPK kinases and regulates activation of MAP kinases (PubMed:15299019). Can inhibit APOBEC3A editing of nuclear DNA (PubMed:22977230).

Gene Wiki entry for TRIB3 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for TRIB3 Gene

Genomics for TRIB3 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for TRIB3 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 TRIB3 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for TRIB3

Top Transcription factor binding sites by QIAGEN in the TRIB3 gene promoter:
  • AP-1
  • ATF-2
  • c-Fos
  • c-Jun

Genomic Locations for TRIB3 Gene

Genomic Locations for TRIB3 Gene
chr20:362,835-397,559
(GRCh38/hg38)
Size:
34,725 bases
Orientation:
Plus strand
chr20:361,261-378,203
(GRCh37/hg19)
Size:
16,943 bases
Orientation:
Plus strand

Genomic View for TRIB3 Gene

Genes around TRIB3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
TRIB3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for TRIB3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for TRIB3 Gene

Proteins for TRIB3 Gene

  • Protein details for TRIB3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q96RU7-TRIB3_HUMAN
    Recommended name:
    Tribbles homolog 3
    Protein Accession:
    Q96RU7
    Secondary Accessions:
    • Q53GU4
    • Q53ZW7
    • Q6I9Y9
    • Q8TAI6
    • Q9H5M8
    • Q9NUD2

    Protein attributes for TRIB3 Gene

    Size:
    358 amino acids
    Molecular mass:
    39578 Da
    Quaternary structure:
    • Interacts with AKT1, AKT2, MAP2K1 and MAP2K7 (PubMed:15299019). Interacts with ATF4 (PubMed:12743605). Interacts with DDIT3/CHOP and inhibits its interaction with EP300/P300 (PubMed:15775988, PubMed:17872950). Interacts with APOBEC3C (PubMed:22977230). Interacts (via N-terminus) with APOBEC3A (PubMed:22977230). Interacts with RELA (PubMed:12736262).

neXtProt entry for TRIB3 Gene

Post-translational modifications for TRIB3 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Protein Products

  • Abcam proteins for TRIB3

No data available for DME Specific Peptides for TRIB3 Gene

Domains & Families for TRIB3 Gene

Gene Families for TRIB3 Gene

IUPHAR :
Human Protein Atlas (HPA):
  • Enzymes
  • Predicted intracellular proteins

Protein Domains for TRIB3 Gene

Suggested Antigen Peptide Sequences for TRIB3 Gene

GenScript: Design optimal peptide antigens:
  • p65-interacting inhibitor of NF-kappa-B (TRIB3_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q96RU7

UniProtKB/Swiss-Prot:

TRIB3_HUMAN :
  • The protein kinase domain is predicted to be catalytically inactive.
  • Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. Tribbles subfamily.
Domain:
  • The protein kinase domain is predicted to be catalytically inactive.
Family:
  • Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. Tribbles subfamily.
genes like me logo Genes that share domains with TRIB3: view

Function for TRIB3 Gene

Molecular function for TRIB3 Gene

UniProtKB/Swiss-Prot Function:
Inactive protein kinase which acts as a regulator of the integrated stress response (ISR), a process for adaptation to various stress (PubMed:15781252, PubMed:15775988). Inhibits the transcriptional activity of DDIT3/CHOP and is involved in DDIT3/CHOP-dependent cell death during ER stress (PubMed:15781252, PubMed:15775988). May play a role in programmed neuronal cell death but does not appear to affect non-neuronal cells (PubMed:15781252, PubMed:15775988). Acts as a negative feedback regulator of the ATF4-dependent transcription during the ISR: while TRIB3 expression is promoted by ATF4, TRIB3 protein interacts with ATF4 and inhibits ATF4 transcription activity (By similarity). Disrupts insulin signaling by binding directly to Akt kinases and blocking their activation (By similarity). May bind directly to and mask the 'Thr-308' phosphorylation site in AKT1 (By similarity). Interacts with the NF-kappa-B transactivator p65 RELA and inhibits its phosphorylation and thus its transcriptional activation activity (PubMed:12736262). Interacts with MAPK kinases and regulates activation of MAP kinases (PubMed:15299019). Can inhibit APOBEC3A editing of nuclear DNA (PubMed:22977230).
UniProtKB/Swiss-Prot Induction:
By hypoxia, TNF, and by nutrient starvation. Expression is PI 3-kinase and/or NF-kappa-B-dependent. Induced by ER stress via ATF4-DDIT3/CHOP pathway and can downregulate its own induction by repression of ATF4-DDIT3/CHOP functions.

Phenotypes From GWAS Catalog for TRIB3 Gene

Gene Ontology (GO) - Molecular Function for TRIB3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003714 transcription corepressor activity IEA,ISS --
GO:0004672 protein kinase activity IEA --
GO:0004860 protein kinase inhibitor activity IEA --
GO:0005515 protein binding IPI 12743605
GO:0005524 ATP binding IEA --
genes like me logo Genes that share ontologies with TRIB3: view
genes like me logo Genes that share phenotypes with TRIB3: view

Animal Models for TRIB3 Gene

MGI Knock Outs for TRIB3:

Animal Model Products

  • Taconic Biosciences Mouse Models for TRIB3

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for TRIB3

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for TRIB3 Gene

Localization for TRIB3 Gene

Subcellular locations from UniProtKB/Swiss-Prot for TRIB3 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 TRIB3 gene
Compartment Confidence
nucleus 5
plasma membrane 4
cytosol 4
mitochondrion 3
extracellular 2
cytoskeleton 2
peroxisome 2
endoplasmic reticulum 2
endosome 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for TRIB3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IEA,ISS --
GO:0005654 nucleoplasm IDA --
GO:0005829 cytosol TAS --
GO:0005886 plasma membrane TAS --
genes like me logo Genes that share ontologies with TRIB3: view

Pathways & Interactions for TRIB3 Gene

genes like me logo Genes that share pathways with TRIB3: view

SIGNOR curated interactions for TRIB3 Gene

Inactivates:
Is activated by:

Gene Ontology (GO) - Biological Process for TRIB3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription by RNA polymerase II IDA 15775988
GO:0006468 protein phosphorylation IEA --
GO:0006469 negative regulation of protein kinase activity IEA,IDA 12791994
GO:0006915 apoptotic process IEA --
GO:0010506 regulation of autophagy IEA,ISS --
genes like me logo Genes that share ontologies with TRIB3: view

Drugs & Compounds for TRIB3 Gene

(1) Drugs for TRIB3 Gene - From: PharmGKB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Methylphenidate Approved, Investigational Pharma 431

(1) Additional Compounds for TRIB3 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with TRIB3: view

Transcripts for TRIB3 Gene

mRNA/cDNA for TRIB3 Gene

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

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for TRIB3

Alternative Splicing Database (ASD) splice patterns (SP) for TRIB3 Gene

ExUns: 1a · 1b ^ 2a · 2b · 2c · 2d ^ 3 ^ 4 ^ 5a · 5b ^ 6 ^ 7a · 7b · 7c ^ 8a · 8b · 8c
SP1: - - - - - - -
SP2: - - - - - -
SP3: - - -
SP4: -
SP5: - -
SP6:

Relevant External Links for TRIB3 Gene

GeneLoc Exon Structure for
TRIB3

Expression for TRIB3 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for TRIB3 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for TRIB3 Gene

This gene is overexpressed in Liver (x9.4).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for TRIB3 Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for TRIB3

SOURCE GeneReport for Unigene cluster for TRIB3 Gene:

Hs.516826

mRNA Expression by UniProt/SwissProt for TRIB3 Gene:

Q96RU7-TRIB3_HUMAN
Tissue specificity: Highest expression in liver, pancreas, peripheral blood leukocytes and bone marrow. Also highly expressed in a number of primary lung, colon and breast tumors. Expressed in spleen, thymus, and prostate and is undetectable in other examined tissues, including testis, ovary, small intestine, colon, leukocyte, heart, brain, placenta, lung, skeletal muscle, and kidney.

Evidence on tissue expression from TISSUES for TRIB3 Gene

  • Muscle(4.6)
  • Liver(4.5)
  • Lung(3)
  • Skin(2.8)
  • Intestine(2.7)
  • Pancreas(2.6)
  • Kidney(2.5)
  • Thyroid gland(2.3)
  • Blood(2.2)
  • Nervous system(2.2)
genes like me logo Genes that share expression patterns with TRIB3: view

No data available for Protein differential expression in normal tissues , Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for TRIB3 Gene

Orthologs for TRIB3 Gene

This gene was present in the common ancestor of animals.

Orthologs for TRIB3 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia TRIB3 30 31
  • 96.37 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia TRIB3 30 31
  • 84.97 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia TRIB3 30 31
  • 81.7 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Trib3 30 17 31
  • 76.84 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Trib3 30
  • 75.17 (n)
Oppossum
(Monodelphis domestica)
Mammalia TRIB3 31
  • 64 (a)
OneToOne
Chicken
(Gallus gallus)
Aves -- 31
  • 21 (a)
ManyToMany
Lizard
(Anolis carolinensis)
Reptilia TRIB3 31
  • 60 (a)
OneToOne
Zebrafish
(Danio rerio)
Actinopterygii trib3 30 31
  • 57.91 (n)
OneToOne
Fruit Fly
(Drosophila melanogaster)
Insecta trbl 31
  • 23 (a)
OneToMany
Worm
(Caenorhabditis elegans)
Secernentea nipi-3 31
  • 11 (a)
OneToMany
Sea Squirt
(Ciona savignyi)
Ascidiacea CSA.8356 31
  • 32 (a)
OneToMany
Species where no ortholog for TRIB3 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)
  • 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)
  • Platypus (Ornithorhynchus anatinus)
  • Rainbow Trout (Oncorhynchus mykiss)
  • 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)
  • Tropical Clawed Frog (Silurana tropicalis)
  • Wheat (Triticum aestivum)

Evolution for TRIB3 Gene

ENSEMBL:
Gene Tree for TRIB3 (if available)
TreeFam:
Gene Tree for TRIB3 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for TRIB3: view image

Paralogs for TRIB3 Gene

Paralogs for TRIB3 Gene

(5) SIMAP similar genes for TRIB3 Gene using alignment to 3 proteins:

  • TRIB3_HUMAN
  • B0QYQ2_HUMAN
  • J3KR25_HUMAN
genes like me logo Genes that share paralogs with TRIB3: view

Variants for TRIB3 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for TRIB3 Gene

SNP ID Clinical significance and condition Chr 20 pos Variation AA Info Type
710947 Benign: not provided 388,091(+) C/T SYNONYMOUS_VARIANT
733898 Benign: not provided 396,363(+) G/A SYNONYMOUS_VARIANT
rs757496714 A glioblastoma multiforme sample p.Thr60Ile
rs2295490 - p.Gln84Arg
rs35051116 - p.Arg153His

Additional dbSNP identifiers (rs#s) for TRIB3 Gene

Structural Variations from Database of Genomic Variants (DGV) for TRIB3 Gene

Variant ID Type Subtype PubMed ID
dgv4219n100 CNV gain 25217958
dgv773e199 CNV deletion 23128226
esv2057444 CNV deletion 18987734
esv2657243 CNV deletion 23128226
esv3644950 CNV loss 21293372
esv3644951 CNV loss 21293372
esv3644952 CNV gain 21293372
esv3644953 CNV gain 21293372
esv3893263 CNV loss 25118596
nsv1065287 CNV loss 25217958
nsv1109346 CNV deletion 24896259
nsv458839 CNV loss 19166990
nsv458841 CNV loss 19166990
nsv458842 CNV loss 19166990
nsv470534 CNV loss 18288195
nsv510777 CNV deletion 20534489
nsv519415 CNV loss 19592680
nsv585169 CNV loss 21841781
nsv585170 CNV loss 21841781
nsv585171 CNV loss 21841781

Variation tolerance for TRIB3 Gene

Residual Variation Intolerance Score: 92.5% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 7.14; 80.69% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for TRIB3 Gene

Human Gene Mutation Database (HGMD)
TRIB3
SNPedia medical, phenotypic, and genealogical associations of SNPs for
TRIB3

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for TRIB3 Gene

Disorders for TRIB3 Gene

MalaCards: The human disease database

(1) MalaCards diseases for TRIB3 Gene - From: DISEASES and Novoseek

Disorder Aliases PubMed IDs
diabetes mellitus, noninsulin-dependent
  • niddm
- elite association - COSMIC cancer census association via MalaCards
Search TRIB3 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for TRIB3

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with TRIB3: view

No data available for UniProtKB/Swiss-Prot and Genatlas for TRIB3 Gene

Publications for TRIB3 Gene

  1. Association of TRB3 gene Q84R polymorphism with type 2 diabetes mellitus in Chinese population. (PMID: 19291425) Shi Z … Zhang J (Endocrine 2009) 3 23 41
  2. TRB3 is a PI 3-kinase dependent indicator for nutrient starvation. (PMID: 16129579) Schwarzer R … Kaufmann J (Cellular signalling 2006) 3 4 23
  3. The functional Q84R polymorphism of mammalian Tribbles homolog TRB3 is associated with insulin resistance and related cardiovascular risk in Caucasians from Italy. (PMID: 16123373) Prudente S … Trischitta V (Diabetes 2005) 3 23 41
  4. Characterization of human NIPK (TRB3, SKIP3) gene activation in stressful conditions. (PMID: 15781252) Ord D … Ord T (Biochemical and biophysical research communications 2005) 3 4 23
  5. TRB3, a novel ER stress-inducible gene, is induced via ATF4-CHOP pathway and is involved in cell death. (PMID: 15775988) Ohoka N … Hayashi H (The EMBO journal 2005) 3 4 23

Products for TRIB3 Gene

Sources for TRIB3 Gene