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Protein

Tribbles homolog 3

Gene

Trib3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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 (By similarity). Can inhibit APOBEC3A editing of nuclear DNA.By similarity3 Publications

Caution

The role of this protein in Akt activation has been demonstrated in PubMed:12749859 but Iynedjian has not been able to reproduce the result in rat hepatocytes.Curated

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionProtein kinase inhibitor
Biological processApoptosis, Transcription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-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 3
Short name:
TRB-3
Alternative name(s):
Neuronal cell death-inducible putative kinase
Gene namesi
Name:Trib3
Synonyms:Nipk, Trb3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:1345675 Trib3

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001318671 – 354Tribbles homolog 3Add BLAST354

Proteomic databases

PaxDbiQ8K4K2
PRIDEiQ8K4K2

PTM databases

iPTMnetiQ8K4K2
PhosphoSitePlusiQ8K4K2

Expressioni

Tissue specificityi

Highly expressed in liver. Not detected in heart, brain, spleen, lung, skeletal muscle, kidney or testis.1 Publication

Inductioni

In liver under fasting conditions and by thapsigargin.2 Publications

Gene expression databases

BgeeiENSMUSG00000032715 Expressed in 178 organ(s), highest expression level in blood
CleanExiMM_TRIB3
GenevisibleiQ8K4K2 MM

Interactioni

Subunit structurei

Interacts with AKT1, AKT2, ATF4, MAP2K1 and MAP2K7. Interacts with DDIT3/CHOP and inhibits its interaction with EP300/P300 (By similarity). Interacts with APOBEC3C (By similarity). Interacts (via N-terminus) with APOBEC3A.By similarity3 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi230766, 2 interactors
DIPiDIP-31533N
IntActiQ8K4K2, 3 interactors
STRINGi10090.ENSMUSP00000041747

Structurei

3D structure databases

ProteinModelPortaliQ8K4K2
SMRiQ8K4K2
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini68 – 315Protein kinasePROSITE-ProRule annotationAdd BLAST248

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 127Interaction with DDIT3/CHOPBy similarityAdd BLAST127

Domaini

The protein kinase domain is predicted to be catalytically inactive.

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0583 Eukaryota
COG0515 LUCA
GeneTreeiENSGT00900000140868
HOGENOMiHOG000231872
HOVERGENiHBG067729
InParanoidiQ8K4K2
KOiK19518
OMAiYTCKVYP
OrthoDBiEOG091G07JM
PhylomeDBiQ8K4K2
TreeFamiTF329785

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR024104 Tribbles/Ser_Thr_kinase_40
IPR024106 Tribbles_TRB3
PANTHERiPTHR22961 PTHR22961, 1 hit
PTHR22961:SF14 PTHR22961:SF14, 1 hit
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS50011 PROTEIN_KINASE_DOM, 1 hit

Sequencei

Sequence statusi: Complete.

Q8K4K2-1 [UniParc]FASTAAdd to basket
« Hide
        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
Length:354
Mass (Da):39,023
Last modified:February 1, 2003 - v2
Checksum:i2CB283FC119F859F
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti157S → P in AAH12955 (PubMed:15489334).Curated1
Sequence conflicti219K → T in AAM45476 (Ref. 3) Curated1
Sequence conflicti239 – 264Missing (PubMed:15489334).CuratedAdd BLAST26
Sequence conflicti301 – 354SERLV…VGLYG → CRATCGPGNPLASLVERGSR PSLSSTV in BAC41002 (PubMed:16141072).CuratedAdd BLAST54

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
CCDSiCCDS16881.1
RefSeqiNP_780302.2, NM_175093.2
UniGeneiMm.276018

Genome annotation databases

EnsembliENSMUST00000040312; ENSMUSP00000041747; ENSMUSG00000032715
GeneIDi228775
KEGGimmu:228775
UCSCiuc008nff.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
CCDSiCCDS16881.1
RefSeqiNP_780302.2, NM_175093.2
UniGeneiMm.276018

3D structure databases

ProteinModelPortaliQ8K4K2
SMRiQ8K4K2
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi230766, 2 interactors
DIPiDIP-31533N
IntActiQ8K4K2, 3 interactors
STRINGi10090.ENSMUSP00000041747

PTM databases

iPTMnetiQ8K4K2
PhosphoSitePlusiQ8K4K2

Proteomic databases

PaxDbiQ8K4K2
PRIDEiQ8K4K2

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000040312; ENSMUSP00000041747; ENSMUSG00000032715
GeneIDi228775
KEGGimmu:228775
UCSCiuc008nff.1 mouse

Organism-specific databases

CTDi57761
MGIiMGI:1345675 Trib3

Phylogenomic databases

eggNOGiKOG0583 Eukaryota
COG0515 LUCA
GeneTreeiENSGT00900000140868
HOGENOMiHOG000231872
HOVERGENiHBG067729
InParanoidiQ8K4K2
KOiK19518
OMAiYTCKVYP
OrthoDBiEOG091G07JM
PhylomeDBiQ8K4K2
TreeFamiTF329785

Enzyme and pathway databases

ReactomeiR-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

ChiTaRSiTrib3 mouse
PROiPR:Q8K4K2
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000032715 Expressed in 178 organ(s), highest expression level in blood
CleanExiMM_TRIB3
GenevisibleiQ8K4K2 MM

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR024104 Tribbles/Ser_Thr_kinase_40
IPR024106 Tribbles_TRB3
PANTHERiPTHR22961 PTHR22961, 1 hit
PTHR22961:SF14 PTHR22961:SF14, 1 hit
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS50011 PROTEIN_KINASE_DOM, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiTRIB3_MOUSE
AccessioniPrimary (citable) accession number: Q8K4K2
Secondary accession number(s): Q3UMQ0, Q921E7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 2003
Last sequence update: February 1, 2003
Last modified: September 12, 2018
This is version 150 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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