Human Gene TRIB3 (ENST00000217233.9_7) from GENCODE V47lift37 |
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 Sequence and Links to Tools and Databases
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Comments and Description Text from UniProtKB
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ID: TRIB3_HUMAN
DESCRIPTION: RecName: Full=Tribbles homolog 3; Short=TRB-3; AltName: Full=Neuronal cell death-inducible putative kinase; AltName: Full=SINK; AltName: Full=p65-interacting inhibitor of NF-kappa-B;
FUNCTION: Disrupts insulin signaling by binding directly to Akt kinases and blocking their activation. May bind directly to and mask the 'Thr-308' phosphorylation site in AKT1. Binds to ATF4 and inhibits its transcriptional activation activity. Interacts with the NF-kappa-B transactivator p65 RELA and inhibits its phosphorylation and thus its transcriptional activation activity. Interacts with MAPK kinases and regulates activation of MAP kinases. May play a role in programmed neuronal cell death but does not appear to affect non-neuronal cells. Does not display kinase activity. Inhibits the transcriptional activity of DDIT3/CHOP and is involved in DDIT3/CHOP-dependent cell death during ER stress.
SUBUNIT: Interacts with AKT1, AKT2, ATF4, MAP2K1 and MAP2K7. Interacts with DDIT3/CHOP and inhibits its interaction with EP300/P300.
INTERACTION: P18848:ATF4; NbExp=2; IntAct=EBI-492476, EBI-492498;
SUBCELLULAR LOCATION: Nucleus (Probable).
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.
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.
SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. Tribbles subfamily.
SIMILARITY: Contains 1 protein kinase domain.
CAUTION: The role of this protein in Akt activation has been demonstrated by Du et al (PubMed:12791994) for the mouse ortholog but Iynedjian (PubMed:15469416) has not been able to reproduce the result in rat hepatocytes.
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Primer design for this transcript
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MalaCards Disease Associations
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Comparative Toxicogenomics Database (CTD)
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 Common Gene Haplotype Alleles
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RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
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Microarray Expression Data
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mRNA Secondary Structure of 3' and 5' UTRs
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The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
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Protein Domain and Structure Information
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InterPro Domains: Graphical view of domain structure
IPR011009 - Kinase-like_dom
IPR000719 - Prot_kinase_cat_dom
IPR024104 - Tribbles/Ser_Thr_kinase_40
IPR024106 - Tribbles_TRB3
Pfam Domains:
PF00069 - Protein kinase domain
PF07714 - Protein tyrosine and serine/threonine kinase
SCOP Domains:
56112 - Protein kinase-like (PK-like)
ModBase Predicted Comparative 3D Structure on Q96RU7
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.
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Orthologous Genes in Other Species
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Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
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Gene Ontology (GO) Annotations with Structured Vocabulary
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Molecular Function:
GO:0003714 transcription corepressor activity
GO:0004860 protein kinase inhibitor activity
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0019901 protein kinase binding
GO:0031434 mitogen-activated protein kinase kinase binding
GO:0031625 ubiquitin protein ligase binding
GO:0055106 ubiquitin-protein transferase regulator activity
GO:0016301 kinase activity
Biological Process:
GO:0000122 negative regulation of transcription from RNA polymerase II promoter
GO:0006351 transcription, DNA-templated
GO:0006355 regulation of transcription, DNA-templated
GO:0006468 protein phosphorylation
GO:0006469 negative regulation of protein kinase activity
GO:0006915 apoptotic process
GO:0010827 regulation of glucose transport
GO:0019216 regulation of lipid metabolic process
GO:0032092 positive regulation of protein binding
GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process
GO:0032869 cellular response to insulin stimulus
GO:0034976 response to endoplasmic reticulum stress
GO:0043405 regulation of MAP kinase activity
GO:0045599 negative regulation of fat cell differentiation
GO:0045717 negative regulation of fatty acid biosynthetic process
GO:0045892 negative regulation of transcription, DNA-templated
GO:0051443 positive regulation of ubiquitin-protein transferase activity
GO:0051898 negative regulation of protein kinase B signaling
GO:0070059 intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress
Cellular Component:
GO:0005634 nucleus
GO:0005829 cytosol
GO:0005886 plasma membrane
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Descriptions from all associated GenBank mRNAs
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KJ894456 - Synthetic construct Homo sapiens clone ccsbBroadEn_03850 TRIB3 gene, encodes complete protein.
KJ905518 - Synthetic construct Homo sapiens clone ccsbBroadEn_15125 TRIB3 gene, encodes complete protein.
KR710261 - Synthetic construct Homo sapiens clone CCSBHm_00010895 TRIB3 (TRIB3) mRNA, encodes complete protein.
AY247738 - Homo sapiens TRB3 protein mRNA, complete cds.
AJ697936 - Homo sapiens mRNA for Neuronal cell death Inducible Putative Kinase (NIPK gene), isoform 1A.
JD487523 - Sequence 468547 from Patent EP1572962.
AK222837 - Homo sapiens mRNA for tribbles 3 variant, clone: HEP10334.
AK026945 - Homo sapiens cDNA: FLJ23292 fis, clone HEP10334.
BC027484 - Homo sapiens tribbles homolog 3 (Drosophila), mRNA (cDNA clone MGC:34909 IMAGE:5104452), complete cds.
JD520744 - Sequence 501768 from Patent EP1572962.
JD520744 - Sequence 501768 from Patent EP1572962.
JD339162 - Sequence 320186 from Patent EP1572962.
JD453379 - Sequence 434403 from Patent EP1572962.
JD108836 - Sequence 89860 from Patent EP1572962.
BC019363 - Homo sapiens tribbles homolog 3 (Drosophila), mRNA (cDNA clone MGC:854 IMAGE:3528490), complete cds.
JD464965 - Sequence 445989 from Patent EP1572962.
AK297546 - Homo sapiens cDNA FLJ59723 complete cds, highly similar to Tribbles homolog 3.
CU676440 - Synthetic construct Homo sapiens gateway clone IMAGE:100023333 5' read TRIB3 mRNA.
CR457366 - Homo sapiens full open reading frame cDNA clone RZPDo834A0114D for gene C20orf97, chromosome 20 open reading frame 97; complete cds, incl. stopcodon.
AB528647 - Synthetic construct DNA, clone: pF1KB6505, Homo sapiens TRIB3 gene for tribbles homolog 3, without stop codon, in Flexi system.
AF250311 - Homo sapiens SKIP3 mRNA, complete cds.
JD529961 - Sequence 510985 from Patent EP1572962.
JD427804 - Sequence 408828 from Patent EP1572962.
JD280236 - Sequence 261260 from Patent EP1572962.
JD288824 - Sequence 269848 from Patent EP1572962.
JD201828 - Sequence 182852 from Patent EP1572962.
JD188781 - Sequence 169805 from Patent EP1572962.
JD437916 - Sequence 418940 from Patent EP1572962.
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Biochemical and Signaling Pathways
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Other Names for This Gene
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Alternate Gene Symbols: C20orf97, ENST00000217233.1, ENST00000217233.2, ENST00000217233.3, ENST00000217233.4, ENST00000217233.5, ENST00000217233.6, ENST00000217233.7, ENST00000217233.8, NIPK, NM_021158, Q53GU4, Q53ZW7, Q6I9Y9, Q8TAI6, Q96RU7, Q9H5M8, Q9NUD2, SKIP3, TRB3, TRIB3_HUMAN, uc317ctf.1, uc317ctf.2
UCSC ID: ENST00000217233.9_7
RefSeq Accession: NM_021158.5
Protein: Q96RU7
(aka TRIB3_HUMAN or TRB3_HUMAN)
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Gene Model Information
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for a detailed description of the fields of the table above.
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Methods, Credits, and Use Restrictions
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for details on how this gene model was made and data restrictions if any.
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US Server
