Q96RU7 · TRIB3_HUMAN
- ProteinTribbles homolog 3
- GeneTRIB3
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids358 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Inactive protein kinase which acts as a regulator of the integrated stress response (ISR), a process for adaptation to various stress (PubMed:15775988, PubMed:15781252).
Inhibits the transcriptional activity of DDIT3/CHOP and is involved in DDIT3/CHOP-dependent cell death during ER stress (PubMed:15775988, PubMed:15781252).
May play a role in programmed neuronal cell death but does not appear to affect non-neuronal cells (PubMed:15775988, PubMed:15781252).
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).
Inhibits the transcriptional activity of DDIT3/CHOP and is involved in DDIT3/CHOP-dependent cell death during ER stress (PubMed:15775988, PubMed:15781252).
May play a role in programmed neuronal cell death but does not appear to affect non-neuronal cells (PubMed:15775988, PubMed:15781252).
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).
GO annotations
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameTribbles homolog 3
- Short namesTRB-3
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ96RU7
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Disease & Variants
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_042372 | 60 | in a glioblastoma multiforme sample; somatic mutation; dbSNP:rs757496714 | |||
Sequence: T → I | ||||||
Natural variant | VAR_023965 | 84 | in dbSNP:rs2295490 | |||
Sequence: Q → R | ||||||
Natural variant | VAR_042373 | 153 | in dbSNP:rs35051116 | |||
Sequence: R → H | ||||||
Natural variant | VAR_042374 | 274 | in dbSNP:rs56291463 | |||
Sequence: R → H | ||||||
Natural variant | VAR_042375 | 347 | in dbSNP:rs56342286 | |||
Sequence: E → K |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 531 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000131866 | 1-358 | UniProt | Tribbles homolog 3 | |||
Sequence: MRATPLAAPAGSLSRKKRLELDDNLDTERPVQKRARSGPQPRLPPCLLPLSPPTAPDRATAVATASRLGPYVLLEPEEGGRAYQALHCPTGTEYTCKVYPVQEALAVLEPYARLPPHKHVARPTEVLAGTQLLYAFFTRTHGDMHSLVRSRHRIPEPEAAVLFRQMATALAHCHQHGLVLRDLKLCRFVFADRERKKLVLENLEDSCVLTGPDDSLWDKHACPAYVGPEILSSRASYSGKAADVWSLGVALFTMLAGHYPFQDSEPVLLFGKIRRGAYALPAGLSAPARCLVRCLLRREPAERLTATGILLHPWLRQDPMPLAPTRSHLWEAAQVVPDGLGLDEAREEEGDREVVLYG | |||||||
Modified residue | 12 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 51 | PRIDE | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
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 down-regulate its own induction by repression of ATF4-DDIT3/CHOP functions.
Gene expression databases
Organism-specific databases
Interaction
Subunit
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).
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).
Binary interactions
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, compositional bias, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-54 | Disordered | ||||
Sequence: MRATPLAAPAGSLSRKKRLELDDNLDTERPVQKRARSGPQPRLPPCLLPLSPPT | ||||||
Region | 1-127 | Interaction with DDIT3/CHOP | ||||
Sequence: MRATPLAAPAGSLSRKKRLELDDNLDTERPVQKRARSGPQPRLPPCLLPLSPPTAPDRATAVATASRLGPYVLLEPEEGGRAYQALHCPTGTEYTCKVYPVQEALAVLEPYARLPPHKHVARPTEVL | ||||||
Compositional bias | 15-35 | Basic and acidic residues | ||||
Sequence: RKKRLELDDNLDTERPVQKRA | ||||||
Domain | 68-316 | Protein kinase | ||||
Sequence: LGPYVLLEPEEGGRAYQALHCPTGTEYTCKVYPVQEALAVLEPYARLPPHKHVARPTEVLAGTQLLYAFFTRTHGDMHSLVRSRHRIPEPEAAVLFRQMATALAHCHQHGLVLRDLKLCRFVFADRERKKLVLENLEDSCVLTGPDDSLWDKHACPAYVGPEILSSRASYSGKAADVWSLGVALFTMLAGHYPFQDSEPVLLFGKIRRGAYALPAGLSAPARCLVRCLLRREPAERLTATGILLHPWLR |
Domain
The protein kinase domain is predicted to be catalytically inactive.
Sequence similarities
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length358
- Mass (Da)39,578
- Last updated2003-02-01 v2
- ChecksumCE15FD89A81E8D63
Computationally mapped potential isoform sequences
There are 4 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
B0QYQ2 | B0QYQ2_HUMAN | TRIB3 | 271 | ||
J3KR25 | J3KR25_HUMAN | TRIB3 | 385 | ||
A0AAQ5BHY5 | A0AAQ5BHY5_HUMAN | TRIB3 | 115 | ||
A0A087WTX3 | A0A087WTX3_HUMAN | TRIB3 | 130 |
Features
Showing features for compositional bias, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 15-35 | Basic and acidic residues | ||||
Sequence: RKKRLELDDNLDTERPVQKRA | ||||||
Sequence conflict | 24 | in Ref. 7; CAG33647 | ||||
Sequence: N → D | ||||||
Sequence conflict | 105 | in Ref. 6; BAB15597 and 8; BAD96557 | ||||
Sequence: L → P | ||||||
Sequence conflict | 114 | in Ref. 3; AAK58175 | ||||
Sequence: L → V | ||||||
Sequence conflict | 194-195 | in Ref. 3; AAK58175 | ||||
Sequence: ER → DREK |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF250311 EMBL· GenBank· DDBJ | AAK58175.1 EMBL· GenBank· DDBJ | mRNA | ||
AJ697936 EMBL· GenBank· DDBJ | CAG27047.1 EMBL· GenBank· DDBJ | mRNA | ||
AY247738 EMBL· GenBank· DDBJ | AAP04407.1 EMBL· GenBank· DDBJ | mRNA | ||
AK026945 EMBL· GenBank· DDBJ | BAB15597.1 EMBL· GenBank· DDBJ | mRNA | ||
CR457366 EMBL· GenBank· DDBJ | CAG33647.1 EMBL· GenBank· DDBJ | mRNA | ||
AK222837 EMBL· GenBank· DDBJ | BAD96557.1 EMBL· GenBank· DDBJ | mRNA | ||
AL034548 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC019363 EMBL· GenBank· DDBJ | AAH19363.1 EMBL· GenBank· DDBJ | mRNA | ||
BC027484 EMBL· GenBank· DDBJ | AAH27484.1 EMBL· GenBank· DDBJ | mRNA |