TRIB3_MOUSE
ID TRIB3_MOUSE Reviewed; 354 AA.
AC Q8K4K2; Q3UMQ0; Q921E7;
DT 01-FEB-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-2003, sequence version 2.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Tribbles homolog 3;
DE Short=TRB-3;
DE AltName: Full=Neuronal cell death-inducible putative kinase;
GN Name=Trib3; Synonyms=Nipk, Trb3;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, INDUCTION, AND INTERACTION WITH ATF4.
RX PubMed=12749859; DOI=10.1016/s0014-4827(03)00070-3;
RA Ord D., Ord T.;
RT "Mouse NIPK interacts with ATF4 and affects its transcriptional activity.";
RL Exp. Cell Res. 286:308-320(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INDUCTION, AND INTERACTION WITH AKT1
RP AND AKT2.
RX PubMed=12791994; DOI=10.1126/science.1079817;
RA Du K., Herzig S., Kulkarni R.N., Montminy M.;
RT "TRB3: a tribbles homolog that inhibits Akt/PKB activation by insulin in
RT liver.";
RL Science 300:1574-1577(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Kiss-Toth E., Dempsey C., Jozsa V., Caunt J., Oxley K.M., Bagstaff S.M.,
RA Wyllie D.H., Harte M., O'Neill L.A.J., Qwarnstrom E.E., Dower S.K.;
RT "Mammalian homologs of Drosophila tribbles (htrb) control mitogen activated
RT protein kinase signaling.";
RL Submitted (MAR-2001) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and DBA/2J; TISSUE=Lung, and Placenta;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP FUNCTION, INTERACTION WITH ATF4, AND INDUCTION.
RX PubMed=17369260; DOI=10.1074/jbc.m611723200;
RA Jousse C., Deval C., Maurin A.C., Parry L., Cherasse Y., Chaveroux C.,
RA Lefloch R., Lenormand P., Bruhat A., Fafournoux P.;
RT "TRB3 inhibits the transcriptional activation of stress-regulated genes by
RT a negative feedback on the ATF4 pathway.";
RL J. Biol. Chem. 282:15851-15861(2007).
RN [7]
RP FUNCTION, INTERACTION WITH APOBEC3A, AND SUBCELLULAR LOCATION.
RX PubMed=22977230; DOI=10.1074/jbc.m112.372722;
RA Aynaud M.M., Suspene R., Vidalain P.O., Mussil B., Guetard D., Tangy F.,
RA Wain-Hobson S., Vartanian J.P.;
RT "Human Tribbles 3 protects nuclear DNA from cytidine deamination by
RT APOBEC3A.";
RL J. Biol. Chem. 287:39182-39192(2012).
CC -!- FUNCTION: Inactive protein kinase which acts as a regulator of the
CC integrated stress response (ISR), a process for adaptation to various
CC stress (PubMed:17369260). Inhibits the transcriptional activity of
CC DDIT3/CHOP and is involved in DDIT3/CHOP-dependent cell death during ER
CC stress (By similarity). May play a role in programmed neuronal cell
CC death but does not appear to affect non-neuronal cells (By similarity).
CC Acts as a negative feedback regulator of the ATF4-dependent
CC transcription during the ISR: while TRIB3 expression is promoted by
CC ATF4, TRIB3 protein interacts with ATF4 and inhibits ATF4 transcription
CC activity (PubMed:12749859, PubMed:17369260). Disrupts insulin signaling
CC by binding directly to Akt kinases and blocking their activation
CC (PubMed:12791994). May bind directly to and mask the 'Thr-308'
CC phosphorylation site in AKT1 (PubMed:12791994). Interacts with the NF-
CC kappa-B transactivator p65 RELA and inhibits its phosphorylation and
CC thus its transcriptional activation activity (By similarity). Interacts
CC with MAPK kinases and regulates activation of MAP kinases (By
CC similarity). Can inhibit APOBEC3A editing of nuclear DNA
CC (PubMed:22977230). {ECO:0000250|UniProtKB:Q96RU7,
CC ECO:0000269|PubMed:12749859, ECO:0000269|PubMed:12791994,
CC ECO:0000269|PubMed:17369260, ECO:0000269|PubMed:22977230}.
CC -!- SUBUNIT: Interacts with AKT1, AKT2, MAP2K1 and MAP2K7
CC (PubMed:12791994). Interacts with ATF4 (PubMed:12749859,
CC PubMed:17369260). Interacts with DDIT3/CHOP and inhibits its
CC interaction with EP300/P300 (By similarity). Interacts with APOBEC3C
CC (By similarity). Interacts (via N-terminus) with APOBEC3A
CC (PubMed:22977230). Interacts with RELA (By similarity).
CC {ECO:0000250|UniProtKB:Q96RU7, ECO:0000269|PubMed:12749859,
CC ECO:0000269|PubMed:12791994, ECO:0000269|PubMed:17369260,
CC ECO:0000269|PubMed:22977230}.
CC -!- INTERACTION:
CC Q8K4K2; P31750: Akt1; NbExp=5; IntAct=EBI-448962, EBI-298707;
CC Q8K4K2; Q06507: Atf4; NbExp=3; IntAct=EBI-448962, EBI-77383;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12749859,
CC ECO:0000269|PubMed:22977230}.
CC -!- TISSUE SPECIFICITY: Highly expressed in liver. Not detected in heart,
CC brain, spleen, lung, skeletal muscle, kidney or testis.
CC {ECO:0000269|PubMed:12749859}.
CC -!- INDUCTION: In liver under fasting conditions and by thapsigargin
CC (PubMed:12749859, PubMed:12791994). Expression is activated by ATF4 in
CC response to stress (PubMed:17369260). {ECO:0000269|PubMed:12749859,
CC ECO:0000269|PubMed:12791994, ECO:0000269|PubMed:17369260}.
CC -!- DOMAIN: The protein kinase domain is predicted to be catalytically
CC inactive.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. Tribbles subfamily. {ECO:0000305}.
CC -!- CAUTION: The role of this protein in Akt activation has been
CC demonstrated in PubMed:12749859 but Iynedjian has not been able to
CC reproduce the result in rat hepatocytes. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AJ514260; CAD55728.1; -; mRNA.
DR EMBL; AF358868; AAM45476.1; -; mRNA.
DR EMBL; AK089931; BAC41002.1; -; mRNA.
DR EMBL; AK132257; BAE21062.1; -; mRNA.
DR EMBL; AK144752; BAE26048.1; -; mRNA.
DR EMBL; AK146340; BAE27094.1; -; mRNA.
DR EMBL; AK159760; BAE35351.1; -; mRNA.
DR EMBL; BC012955; AAH12955.1; -; mRNA.
DR CCDS; CCDS16881.1; -.
DR RefSeq; NP_780302.2; NM_175093.2.
DR AlphaFoldDB; Q8K4K2; -.
DR SMR; Q8K4K2; -.
DR BioGRID; 230766; 16.
DR DIP; DIP-31533N; -.
DR IntAct; Q8K4K2; 3.
DR STRING; 10090.ENSMUSP00000041747; -.
DR iPTMnet; Q8K4K2; -.
DR PhosphoSitePlus; Q8K4K2; -.
DR PaxDb; Q8K4K2; -.
DR PRIDE; Q8K4K2; -.
DR Antibodypedia; 6154; 594 antibodies from 34 providers.
DR DNASU; 228775; -.
DR Ensembl; ENSMUST00000040312; ENSMUSP00000041747; ENSMUSG00000032715.
DR GeneID; 228775; -.
DR KEGG; mmu:228775; -.
DR UCSC; uc008nff.1; mouse.
DR CTD; 57761; -.
DR MGI; MGI:1345675; Trib3.
DR VEuPathDB; HostDB:ENSMUSG00000032715; -.
DR eggNOG; KOG0583; Eukaryota.
DR GeneTree; ENSGT00950000182986; -.
DR HOGENOM; CLU_000288_13_1_1; -.
DR InParanoid; Q8K4K2; -.
DR OMA; YFLFERC; -.
DR OrthoDB; 1362510at2759; -.
DR PhylomeDB; Q8K4K2; -.
DR TreeFam; TF329785; -.
DR Reactome; R-MMU-1257604; PIP3 activates AKT signaling.
DR Reactome; R-MMU-165158; Activation of AKT2.
DR Reactome; R-MMU-199418; Negative regulation of the PI3K/AKT network.
DR Reactome; R-MMU-389357; CD28 dependent PI3K/Akt signaling.
DR Reactome; R-MMU-5218920; VEGFR2 mediated vascular permeability.
DR BioGRID-ORCS; 228775; 8 hits in 75 CRISPR screens.
DR ChiTaRS; Trib3; mouse.
DR PRO; PR:Q8K4K2; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q8K4K2; protein.
DR Bgee; ENSMUSG00000032715; Expressed in lumbar dorsal root ganglion and 139 other tissues.
DR Genevisible; Q8K4K2; MM.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:InterPro.
DR GO; GO:0019899; F:enzyme binding; IPI:BHF-UCL.
DR GO; GO:0031434; F:mitogen-activated protein kinase kinase binding; IBA:GO_Central.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR GO; GO:0004860; F:protein kinase inhibitor activity; IEA:UniProtKB-KW.
DR GO; GO:0003714; F:transcription corepressor activity; IDA:MGI.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IDA:BHF-UCL.
DR GO; GO:0055106; F:ubiquitin-protein transferase regulator activity; IDA:BHF-UCL.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IDA:BHF-UCL.
DR GO; GO:0070059; P:intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; ISS:UniProtKB.
DR GO; GO:0045599; P:negative regulation of fat cell differentiation; IMP:BHF-UCL.
DR GO; GO:0045717; P:negative regulation of fatty acid biosynthetic process; IMP:BHF-UCL.
DR GO; GO:0006469; P:negative regulation of protein kinase activity; IDA:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR GO; GO:0032092; P:positive regulation of protein binding; IDA:BHF-UCL.
DR GO; GO:0045732; P:positive regulation of protein catabolic process; IC:BHF-UCL.
DR GO; GO:0051443; P:positive regulation of ubiquitin-protein transferase activity; IDA:BHF-UCL.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR GO; GO:0010506; P:regulation of autophagy; ISS:UniProtKB.
DR GO; GO:0010827; P:regulation of glucose transmembrane transport; IDA:BHF-UCL.
DR GO; GO:0043405; P:regulation of MAP kinase activity; ISS:UniProtKB.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; ISS:UniProtKB.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR024104; Tribbles/Ser_Thr_kinase_40.
DR InterPro; IPR024106; Tribbles_TRB3.
DR PANTHER; PTHR22961; PTHR22961; 1.
DR PANTHER; PTHR22961:SF14; PTHR22961:SF14; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PE 1: Evidence at protein level;
KW Apoptosis; Nucleus; Protein kinase inhibitor; Reference proteome;
KW Transcription; Transcription regulation.
FT CHAIN 1..354
FT /note="Tribbles homolog 3"
FT /id="PRO_0000131867"
FT DOMAIN 68..315
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..127
FT /note="Interaction with DDIT3/CHOP"
FT /evidence="ECO:0000250"
FT REGION 36..61
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 320..354
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 42..59
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 320..337
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CONFLICT 157
FT /note="S -> P (in Ref. 5; AAH12955)"
FT /evidence="ECO:0000305"
FT CONFLICT 219
FT /note="K -> T (in Ref. 3; AAM45476)"
FT /evidence="ECO:0000305"
FT CONFLICT 239..264
FT /note="Missing (in Ref. 5)"
FT /evidence="ECO:0000305"
FT CONFLICT 301..354
FT /note="SERLVALGILLHPWLREDHGRVSPPQSDRREMDQVVPDGPQLEEAEEGEVGL
FT YG -> CRATCGPGNPLASLVERGSRPSLSSTV (in Ref. 4; BAC41002)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 354 AA; 39023 MW; 2CB283FC119F859F CRC64;
MRATPLAASA DVSCRKKPLE FDDNIDAKCP VLKRVRDEPE PGPLPSLLPP SPPPASDLSP
AVAPATRLGP YILLEREQGS CSYRALHCPT GTEYTCKVYP ASEAQAVLAP YARLPTHQHV
ARPTEVLLGS RLLYIFFTKT HGDLHSLVRS RRGIPESEAA GLFRQMASAV AHCHKHGLVL
RDLKLRRFVF SNCERTKLVL ENLEDACVMT GSDDSLWDKH ACPAYVGPEI LSSRPSYSGK
AADVWSLGVA LFTMLAGRYP FHDSEPVLLF GKIRRGTFAL PEGLSAPARC LIRCLLRKEP
SERLVALGIL LHPWLREDHG RVSPPQSDRR EMDQVVPDGP QLEEAEEGEV GLYG
