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Protein

Tribbles homolog 3

Gene

Trib3

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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 similarity).By similarity1 Publication

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Protein kinase inhibitor

Keywords - Biological processi

Apoptosis, Transcription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-RNO-1257604. PIP3 activates AKT signaling.
R-RNO-165158. Activation of AKT2.
R-RNO-199418. Negative regulation of the PI3K/AKT network.
R-RNO-389357. CD28 dependent PI3K/Akt signaling.
R-RNO-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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 3

Organism-specific databases

RGDi708432. Trib3.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001318681 – 349Tribbles homolog 3Add BLAST349

Proteomic databases

PaxDbiQ9WTQ6.

Expressioni

Tissue specificityi

Detected only in the lung. Not detected in the heart, brain, spleen, liver, skeletal muscle, kidney and testis.

Inductioni

Expression induced during programmed cell death evoked in neuronal cells by NGF-depletion.

Gene expression databases

BgeeiENSRNOG00000007319.
GenevisibleiQ9WTQ6. RN.

Interactioni

Subunit structurei

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

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000009840.

Structurei

3D structure databases

ProteinModelPortaliQ9WTQ6.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini63 – 310Protein kinasePROSITE-ProRule annotationAdd BLAST248

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 122Interaction with DDIT3/CHOPBy similarityAdd BLAST122

Domaini

The protein kinase domain is predicted to be catalytically inactive.

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0583. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00840000129780.
HOGENOMiHOG000231872.
HOVERGENiHBG067729.
InParanoidiQ9WTQ6.
KOiK19518.
OMAiYTCKVYP.
OrthoDBiEOG091G07JM.
PhylomeDBiQ9WTQ6.
TreeFamiTF329785.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR024104. Tribbles/Ser_Thr_kinase_40.
IPR024106. Tribbles_TRB3.
[Graphical view]
PANTHERiPTHR22961. PTHR22961. 1 hit.
PTHR22961:SF14. PTHR22961:SF14. 1 hit.
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9WTQ6-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRATSLAASA DVPCRKKPLE FDDNIDVECP VLKRVRDEPE PGPTPSLPPA
60 70 80 90 100
SDLSPAVAPA TRLGPYILLE REQGNCTYRA LHCPTGTEYT CKVYPASEAQ
110 120 130 140 150
AVLAPYARLP THQHVARPTE VLLGSQLLYT FFTKTHGDLH SLVRSRRGIP
160 170 180 190 200
EPEAAALFRQ MASAVAHCHK HGLILRDLKL RRFVFSNCER TKLVLENLED
210 220 230 240 250
ACVMTGPDDS LWDKHACPAY VGPEILSSRP SYSGRAADVW SLGVALFTML
260 270 280 290 300
AGRYPFQDSE PALLFGKIRR GTFALPEGLS ASARCLIRCL LRREPSERLV
310 320 330 340
ALGILLHPWL REDCSQVSPP RSDRREMDQV VPDGPQLEEA EEGEVGLYG
Length:349
Mass (Da):38,602
Last modified:November 1, 1999 - v1
Checksum:i3050F9BFE946D815
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB020967 mRNA. Translation: BAA77582.1.
BC091120 mRNA. Translation: AAH91120.1.
RefSeqiNP_653356.1. NM_144755.2.
UniGeneiRn.22325.

Genome annotation databases

EnsembliENSRNOT00000009840; ENSRNOP00000009840; ENSRNOG00000007319.
GeneIDi246273.
KEGGirno:246273.
UCSCiRGD:708432. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB020967 mRNA. Translation: BAA77582.1.
BC091120 mRNA. Translation: AAH91120.1.
RefSeqiNP_653356.1. NM_144755.2.
UniGeneiRn.22325.

3D structure databases

ProteinModelPortaliQ9WTQ6.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000009840.

Proteomic databases

PaxDbiQ9WTQ6.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000009840; ENSRNOP00000009840; ENSRNOG00000007319.
GeneIDi246273.
KEGGirno:246273.
UCSCiRGD:708432. rat.

Organism-specific databases

CTDi57761.
RGDi708432. Trib3.

Phylogenomic databases

eggNOGiKOG0583. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00840000129780.
HOGENOMiHOG000231872.
HOVERGENiHBG067729.
InParanoidiQ9WTQ6.
KOiK19518.
OMAiYTCKVYP.
OrthoDBiEOG091G07JM.
PhylomeDBiQ9WTQ6.
TreeFamiTF329785.

Enzyme and pathway databases

ReactomeiR-RNO-1257604. PIP3 activates AKT signaling.
R-RNO-165158. Activation of AKT2.
R-RNO-199418. Negative regulation of the PI3K/AKT network.
R-RNO-389357. CD28 dependent PI3K/Akt signaling.
R-RNO-5218920. VEGFR2 mediated vascular permeability.

Miscellaneous databases

PROiQ9WTQ6.

Gene expression databases

BgeeiENSRNOG00000007319.
GenevisibleiQ9WTQ6. RN.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR024104. Tribbles/Ser_Thr_kinase_40.
IPR024106. Tribbles_TRB3.
[Graphical view]
PANTHERiPTHR22961. PTHR22961. 1 hit.
PTHR22961:SF14. PTHR22961:SF14. 1 hit.
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTRIB3_RAT
AccessioniPrimary (citable) accession number: Q9WTQ6
Secondary accession number(s): Q5BKD1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 2003
Last sequence update: November 1, 1999
Last modified: November 2, 2016
This is version 124 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Caution

The role of this protein in Akt activation has been demonstrated by Du et al for the mouse ortholog but PubMed:15469416 has not been able to reproduce the result in rat hepatocytes.Curated

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.