UniProtKB - Q8K4K2 (TRIB3_MOUSE)
Tribbles homolog 3
Trib3
Functioni
Inactive protein kinase which acts as a regulator of the integrated stress response (ISR), a process for adaptation to various stress (PubMed:17369260).
Inhibits the transcriptional activity of DDIT3/CHOP and is involved in DDIT3/CHOP-dependent cell death during ER stress (By similarity).
May play a role in programmed neuronal cell death but does not appear to affect non-neuronal cells (By similarity).
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 (PubMed:12749859, PubMed:17369260).
Disrupts insulin signaling by binding directly to Akt kinases and blocking their activation (PubMed:12791994).
May bind directly to and mask the 'Thr-308' phosphorylation site in AKT1 (PubMed:12791994).
Interacts with the NF-kappa-B transactivator p65 RELA and inhibits its phosphorylation and thus its transcriptional activation activity (By similarity).
Interacts with MAPK kinases and regulates activation of MAP kinases (By similarity).
Can inhibit APOBEC3A editing of nuclear DNA (PubMed:22977230).
By similarity4 PublicationsCaution
GO - Molecular functioni
- ATP binding Source: InterPro
- enzyme binding Source: BHF-UCL
- mitogen-activated protein kinase kinase binding Source: GO_Central
- protein kinase binding Source: UniProtKB
- protein kinase inhibitor activity Source: UniProtKB-KW
- transcription corepressor activity Source: MGI
- ubiquitin protein ligase binding Source: BHF-UCL
- ubiquitin-protein transferase regulator activity Source: BHF-UCL
GO - Biological processi
- cellular response to insulin stimulus Source: BHF-UCL
- intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress Source: UniProtKB
- negative regulation of fat cell differentiation Source: BHF-UCL
- negative regulation of fatty acid biosynthetic process Source: BHF-UCL
- negative regulation of protein kinase activity Source: UniProtKB
- negative regulation of transcription, DNA-templated Source: UniProtKB
- negative regulation of transcription by RNA polymerase II Source: MGI
- positive regulation of proteasomal ubiquitin-dependent protein catabolic process Source: GO_Central
- positive regulation of protein binding Source: BHF-UCL
- positive regulation of protein catabolic process Source: BHF-UCL
- positive regulation of ubiquitin-protein transferase activity Source: BHF-UCL
- protein phosphorylation Source: InterPro
- regulation of autophagy Source: UniProtKB
- regulation of glucose transmembrane transport Source: BHF-UCL
- regulation of MAP kinase activity Source: UniProtKB
- response to endoplasmic reticulum stress Source: UniProtKB
Keywordsi
Molecular function | Protein kinase inhibitor |
Biological process | Apoptosis, Transcription, Transcription regulation |
Enzyme and pathway databases
Reactomei | R-MMU-1257604, PIP3 activates AKT signaling R-MMU-165158, Activation of AKT2 R-MMU-199418, Negative regulation of the PI3K/AKT network R-MMU-389357, CD28 dependent PI3K/Akt signaling R-MMU-5218920, VEGFR2 mediated vascular permeability |
Names & Taxonomyi
Protein namesi | Recommended name: Tribbles homolog 3Short name: TRB-3 Alternative name(s): Neuronal cell death-inducible putative kinase |
Gene namesi | Name:Trib3 Synonyms:Nipk, Trb3 |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:1345675, Trib3 |
VEuPathDBi | HostDB:ENSMUSG00000032715 |
Subcellular locationi
Nucleus
- Nucleus 2 Publications
Nucleus
- nucleoplasm Source: MGI
- nucleus Source: MGI
Keywords - Cellular componenti
NucleusPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000131867 | 1 – 354 | Tribbles homolog 3Add BLAST | 354 |
Proteomic databases
PaxDbi | Q8K4K2 |
PRIDEi | Q8K4K2 |
PTM databases
iPTMneti | Q8K4K2 |
PhosphoSitePlusi | Q8K4K2 |
Expressioni
Tissue specificityi
Inductioni
Gene expression databases
Bgeei | ENSMUSG00000032715, Expressed in blood and 206 other tissues |
Genevisiblei | Q8K4K2, MM |
Interactioni
Subunit structurei
Interacts with AKT1, AKT2, MAP2K1 and MAP2K7 (PubMed:12791994).
Interacts with ATF4 (PubMed:12749859, PubMed:17369260).
Interacts with DDIT3/CHOP and inhibits its interaction with EP300/P300 (By similarity).
Interacts with APOBEC3C (By similarity).
Interacts (via N-terminus) with APOBEC3A (PubMed:22977230).
Interacts with RELA (By similarity).
By similarity4 PublicationsBinary interactionsi
GO - Molecular functioni
- enzyme binding Source: BHF-UCL
- mitogen-activated protein kinase kinase binding Source: GO_Central
- protein kinase binding Source: UniProtKB
- ubiquitin protein ligase binding Source: BHF-UCL
Protein-protein interaction databases
BioGRIDi | 230766, 16 interactors |
DIPi | DIP-31533N |
IntActi | Q8K4K2, 3 interactors |
STRINGi | 10090.ENSMUSP00000041747 |
Miscellaneous databases
RNActi | Q8K4K2, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 68 – 315 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 248 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 127 | Interaction with DDIT3/CHOPBy similarityAdd BLAST | 127 | |
Regioni | 36 – 61 | DisorderedSequence analysisAdd BLAST | 26 | |
Regioni | 320 – 354 | DisorderedSequence analysisAdd BLAST | 35 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 42 – 59 | Pro residuesSequence analysisAdd BLAST | 18 | |
Compositional biasi | 320 – 337 | Basic and acidic residuesSequence analysisAdd BLAST | 18 |
Domaini
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG0583, Eukaryota |
GeneTreei | ENSGT00950000182986 |
HOGENOMi | CLU_000288_13_1_1 |
InParanoidi | Q8K4K2 |
OMAi | YFLFERC |
OrthoDBi | 1362510at2759 |
PhylomeDBi | Q8K4K2 |
TreeFami | TF329785 |
Family and domain databases
InterProi | View protein in InterPro IPR011009, Kinase-like_dom_sf IPR000719, Prot_kinase_dom IPR024104, Tribbles/Ser_Thr_kinase_40 IPR024106, Tribbles_TRB3 |
PANTHERi | PTHR22961, PTHR22961, 1 hit PTHR22961:SF14, PTHR22961:SF14, 1 hit |
Pfami | View protein in Pfam PF00069, Pkinase, 1 hit |
SMARTi | View protein in SMART SM00220, S_TKc, 1 hit |
SUPFAMi | SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS50011, PROTEIN_KINASE_DOM, 1 hit |
i Sequence
Sequence statusi: Complete.
10 20 30 40 50
MRATPLAASA DVSCRKKPLE FDDNIDAKCP VLKRVRDEPE PGPLPSLLPP
60 70 80 90 100
SPPPASDLSP AVAPATRLGP YILLEREQGS CSYRALHCPT GTEYTCKVYP
110 120 130 140 150
ASEAQAVLAP YARLPTHQHV ARPTEVLLGS RLLYIFFTKT HGDLHSLVRS
160 170 180 190 200
RRGIPESEAA GLFRQMASAV AHCHKHGLVL RDLKLRRFVF SNCERTKLVL
210 220 230 240 250
ENLEDACVMT GSDDSLWDKH ACPAYVGPEI LSSRPSYSGK AADVWSLGVA
260 270 280 290 300
LFTMLAGRYP FHDSEPVLLF GKIRRGTFAL PEGLSAPARC LIRCLLRKEP
310 320 330 340 350
SERLVALGIL LHPWLREDHG RVSPPQSDRR EMDQVVPDGP QLEEAEEGEV
GLYG
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 157 | S → P in AAH12955 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 219 | K → T in AAM45476 (Ref. 3) Curated | 1 | |
Sequence conflicti | 239 – 264 | Missing (PubMed:15489334).CuratedAdd BLAST | 26 | |
Sequence conflicti | 301 – 354 | SERLV…VGLYG → CRATCGPGNPLASLVERGSR PSLSSTV in BAC41002 (PubMed:16141072).CuratedAdd BLAST | 54 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AJ514260 mRNA Translation: CAD55728.1 AF358868 mRNA Translation: AAM45476.1 AK089931 mRNA Translation: BAC41002.1 AK132257 mRNA Translation: BAE21062.1 AK144752 mRNA Translation: BAE26048.1 AK146340 mRNA Translation: BAE27094.1 AK159760 mRNA Translation: BAE35351.1 BC012955 mRNA Translation: AAH12955.1 |
CCDSi | CCDS16881.1 |
RefSeqi | NP_780302.2, NM_175093.2 |
Genome annotation databases
Ensembli | ENSMUST00000040312; ENSMUSP00000041747; ENSMUSG00000032715 |
GeneIDi | 228775 |
KEGGi | mmu:228775 |
UCSCi | uc008nff.1, mouse |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AJ514260 mRNA Translation: CAD55728.1 AF358868 mRNA Translation: AAM45476.1 AK089931 mRNA Translation: BAC41002.1 AK132257 mRNA Translation: BAE21062.1 AK144752 mRNA Translation: BAE26048.1 AK146340 mRNA Translation: BAE27094.1 AK159760 mRNA Translation: BAE35351.1 BC012955 mRNA Translation: AAH12955.1 |
CCDSi | CCDS16881.1 |
RefSeqi | NP_780302.2, NM_175093.2 |
3D structure databases
AlphaFoldDBi | Q8K4K2 |
SMRi | Q8K4K2 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 230766, 16 interactors |
DIPi | DIP-31533N |
IntActi | Q8K4K2, 3 interactors |
STRINGi | 10090.ENSMUSP00000041747 |
PTM databases
iPTMneti | Q8K4K2 |
PhosphoSitePlusi | Q8K4K2 |
Proteomic databases
PaxDbi | Q8K4K2 |
PRIDEi | Q8K4K2 |
Protocols and materials databases
Antibodypediai | 6154, 579 antibodies from 34 providers |
DNASUi | 228775 |
Genome annotation databases
Ensembli | ENSMUST00000040312; ENSMUSP00000041747; ENSMUSG00000032715 |
GeneIDi | 228775 |
KEGGi | mmu:228775 |
UCSCi | uc008nff.1, mouse |
Organism-specific databases
CTDi | 57761 |
MGIi | MGI:1345675, Trib3 |
VEuPathDBi | HostDB:ENSMUSG00000032715 |
Phylogenomic databases
eggNOGi | KOG0583, Eukaryota |
GeneTreei | ENSGT00950000182986 |
HOGENOMi | CLU_000288_13_1_1 |
InParanoidi | Q8K4K2 |
OMAi | YFLFERC |
OrthoDBi | 1362510at2759 |
PhylomeDBi | Q8K4K2 |
TreeFami | TF329785 |
Enzyme and pathway databases
Reactomei | R-MMU-1257604, PIP3 activates AKT signaling R-MMU-165158, Activation of AKT2 R-MMU-199418, Negative regulation of the PI3K/AKT network R-MMU-389357, CD28 dependent PI3K/Akt signaling R-MMU-5218920, VEGFR2 mediated vascular permeability |
Miscellaneous databases
BioGRID-ORCSi | 228775, 8 hits in 75 CRISPR screens |
ChiTaRSi | Trib3, mouse |
PROi | PR:Q8K4K2 |
RNActi | Q8K4K2, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000032715, Expressed in blood and 206 other tissues |
Genevisiblei | Q8K4K2, MM |
Family and domain databases
InterProi | View protein in InterPro IPR011009, Kinase-like_dom_sf IPR000719, Prot_kinase_dom IPR024104, Tribbles/Ser_Thr_kinase_40 IPR024106, Tribbles_TRB3 |
PANTHERi | PTHR22961, PTHR22961, 1 hit PTHR22961:SF14, PTHR22961:SF14, 1 hit |
Pfami | View protein in Pfam PF00069, Pkinase, 1 hit |
SMARTi | View protein in SMART SM00220, S_TKc, 1 hit |
SUPFAMi | SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS50011, PROTEIN_KINASE_DOM, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | TRIB3_MOUSE | |
Accessioni | Q8K4K2Primary (citable) accession number: Q8K4K2 Secondary accession number(s): Q3UMQ0, Q921E7 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | February 1, 2003 |
Last sequence update: | February 1, 2003 | |
Last modified: | May 25, 2022 | |
This is version 170 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human and mouse protein kinases
Human and mouse protein kinases: classification and index - MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families