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Protein

Tribbles homolog 3

Gene

Trib3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

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 from RNA polymerase II promoter Source: MGI
  • positive regulation of proteasomal ubiquitin-dependent protein catabolic process Source: BHF-UCL
  • 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 glucose transport Source: BHF-UCL
  • regulation of MAP kinase activity Source: UniProtKB
  • response to endoplasmic reticulum stress Source: UniProtKB
  • transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Protein kinase inhibitor

Keywords - Biological processi

Apoptosis, 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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:1345675. Trib3.

Subcellular locationi

GO - Cellular componenti

  • nuclear membrane Source: Ensembl
  • nucleolus Source: Ensembl
  • nucleoplasm Source: MGI
  • nucleus Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 354354Tribbles homolog 3PRO_0000131867Add
BLAST

Proteomic databases

PaxDbiQ8K4K2.
PRIDEiQ8K4K2.

PTM databases

iPTMnetiQ8K4K2.
PhosphoSiteiQ8K4K2.

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

BgeeiQ8K4K2.
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

WithEntry#Exp.IntActNotes
Akt1P317505EBI-448962,EBI-298707
Atf4Q065073EBI-448962,EBI-77383

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

BioGridi230766. 2 interactions.
DIPiDIP-31533N.
IntActiQ8K4K2. 2 interactions.
STRINGi10090.ENSMUSP00000041747.

Structurei

3D structure databases

ProteinModelPortaliQ8K4K2.
SMRiQ8K4K2. Positions 68-351.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini68 – 315248Protein kinasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 127127Interaction with DDIT3/CHOPBy similarityAdd
BLAST

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.
InParanoidiQ8K4K2.
KOiK19518.
OMAiYTCKVYP.
OrthoDBiEOG7RJPR4.
PhylomeDBiQ8K4K2.
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.

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti157 – 1571S → P in AAH12955 (PubMed:15489334).Curated
Sequence conflicti219 – 2191K → T in AAM45476 (Ref. 3) Curated
Sequence conflicti239 – 26426Missing (PubMed:15489334).CuratedAdd
BLAST
Sequence conflicti301 – 35454SERLV…VGLYG → CRATCGPGNPLASLVERGSR PSLSSTV in BAC41002 (PubMed:16141072).CuratedAdd
BLAST

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.

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. Positions 68-351.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi230766. 2 interactions.
DIPiDIP-31533N.
IntActiQ8K4K2. 2 interactions.
STRINGi10090.ENSMUSP00000041747.

PTM databases

iPTMnetiQ8K4K2.
PhosphoSiteiQ8K4K2.

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.
GeneTreeiENSGT00840000129780.
HOGENOMiHOG000231872.
HOVERGENiHBG067729.
InParanoidiQ8K4K2.
KOiK19518.
OMAiYTCKVYP.
OrthoDBiEOG7RJPR4.
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.
PROiQ8K4K2.
SOURCEiSearch...

Gene expression databases

BgeeiQ8K4K2.
CleanExiMM_TRIB3.
GenevisibleiQ8K4K2. MM.

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...

Publicationsi

« Hide 'large scale' publications
  1. "Mouse NIPK interacts with ATF4 and affects its transcriptional activity."
    Ord D., Ord T.
    Exp. Cell Res. 286:308-320(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INDUCTION, INTERACTION WITH ATF4.
  2. "TRB3: a tribbles homolog that inhibits Akt/PKB activation by insulin in liver."
    Du K., Herzig S., Kulkarni R.N., Montminy M.
    Science 300:1574-1577(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INDUCTION, INTERACTION WITH AKT1 AND AKT2.
  3. "Mammalian homologs of Drosophila tribbles (htrb) control mitogen activated protein kinase signaling."
    Kiss-Toth E., Dempsey C., Jozsa V., Caunt J., Oxley K.M., Bagstaff S.M., Wyllie D.H., Harte M., O'Neill L.A.J., Qwarnstrom E.E., Dower S.K.
    Submitted (MAR-2001) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  4. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J and DBA/2.
    Tissue: Lung and Placenta.
  5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  6. "Human Tribbles 3 protects nuclear DNA from cytidine deamination by APOBEC3A."
    Aynaud M.M., Suspene R., Vidalain P.O., Mussil B., Guetard D., Tangy F., Wain-Hobson S., Vartanian J.P.
    J. Biol. Chem. 287:39182-39192(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH APOBEC3A, SUBCELLULAR LOCATION.

Entry informationi

Entry nameiTRIB3_MOUSE
AccessioniPrimary (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: July 6, 2016
This is version 137 of the entry and version 2 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 in PubMed:12749859 but Iynedjian has not been able to reproduce the result in rat hepatocytes.Curated

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. 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.