TRIB3_HUMAN
ID TRIB3_HUMAN Reviewed; 358 AA.
AC Q96RU7; Q53GU4; Q53ZW7; Q6I9Y9; Q8TAI6; Q9H5M8; Q9NUD2;
DT 01-FEB-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-2003, sequence version 2.
DT 03-AUG-2022, entry version 189.
DE RecName: Full=Tribbles homolog 3;
DE Short=TRB-3;
DE AltName: Full=Neuronal cell death-inducible putative kinase;
DE AltName: Full=SINK;
DE AltName: Full=p65-interacting inhibitor of NF-kappa-B;
GN Name=TRIB3; Synonyms=C20orf97, NIPK, SKIP3, TRB3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, INDUCTION, AND INTERACTION
RP WITH ATF4.
RX PubMed=12743605; DOI=10.1038/sj.onc.1206367;
RA Bowers A.J., Scully S., Boylan J.F.;
RT "SKIP3, a novel Drosophila tribbles ortholog, is overexpressed in human
RT tumors and is regulated by hypoxia.";
RL Oncogene 22:2823-2835(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, INDUCTION, AND
RP INTERACTION WITH RELA.
RX PubMed=12736262; DOI=10.1074/jbc.m209814200;
RA Wu M., Xu L.G., Zhai Z., Shu H.B.;
RT "SINK is a p65-interacting negative regulator of NF-kappaB-dependent
RT transcription.";
RL J. Biol. Chem. 278:27072-27079(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, AND INTERACTION
RP WITH MAP2K1 AND MAP2K7.
RX PubMed=15299019; DOI=10.1074/jbc.m407732200;
RA Kiss-Toth E., Bagstaff S.M., Sung H.Y., Jozsa V., Dempsey C., Caunt J.C.,
RA Oxley K.M., Wyllie D.H., Polgar T., Harte M., O'Neill L.A.J.,
RA Qwarnstrom E.E., Dower S.K.;
RT "Human tribbles, a protein family controlling mitogen-activated protein
RT kinase cascades.";
RL J. Biol. Chem. 279:42703-42708(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RX PubMed=15781252; DOI=10.1016/j.bbrc.2005.02.149;
RA Ord D., Ord T.;
RT "Characterization of human NIPK (TRB3, SKIP3) gene activation in stressful
RT conditions.";
RL Biochem. Biophys. Res. Commun. 330:210-218(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Shan Y.X., Yu L.;
RL Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Liver;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ARG-84.
RC TISSUE=Cervix, and Muscle;
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 [11]
RP FUNCTION, INDUCTION, AND INTERACTION WITH DDIT3.
RX PubMed=15775988; DOI=10.1038/sj.emboj.7600596;
RA Ohoka N., Yoshii S., Hattori T., Onozaki K., Hayashi H.;
RT "TRB3, a novel ER stress-inducible gene, is induced via ATF4-CHOP pathway
RT and is involved in cell death.";
RL EMBO J. 24:1243-1255(2005).
RN [12]
RP INDUCTION.
RX PubMed=16129579; DOI=10.1016/j.cellsig.2005.08.002;
RA Schwarzer R., Dames S., Tondera D., Klippel A., Kaufmann J.;
RT "TRB3 is a PI 3-kinase dependent indicator for nutrient starvation.";
RL Cell. Signal. 18:899-909(2006).
RN [13]
RP INTERACTION WITH DDIT3.
RX PubMed=17872950; DOI=10.1074/jbc.m703735200;
RA Ohoka N., Hattori T., Kitagawa M., Onozaki K., Hayashi H.;
RT "Critical and functional regulation of CHOP (C/EBP homologous protein)
RT through the N-terminal portion.";
RL J. Biol. Chem. 282:35687-35694(2007).
RN [14]
RP FUNCTION, INTERACTION WITH APOBEC3A AND APOBEC3C, 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).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-12, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [16]
RP VARIANTS [LARGE SCALE ANALYSIS] ILE-60; ARG-84; HIS-153; HIS-274 AND
RP LYS-347.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
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:15781252, PubMed:15775988). Inhibits the transcriptional
CC activity of DDIT3/CHOP and is involved in DDIT3/CHOP-dependent cell
CC death during ER stress (PubMed:15781252, PubMed:15775988). May play a
CC role in programmed neuronal cell death but does not appear to affect
CC non-neuronal cells (PubMed:15781252, PubMed:15775988). Acts as a
CC negative feedback regulator of the ATF4-dependent transcription during
CC the ISR: while TRIB3 expression is promoted by ATF4, TRIB3 protein
CC interacts with ATF4 and inhibits ATF4 transcription activity (By
CC similarity). Disrupts insulin signaling by binding directly to Akt
CC kinases and blocking their activation (By similarity). May bind
CC directly to and mask the 'Thr-308' phosphorylation site in AKT1 (By
CC similarity). Interacts with the NF-kappa-B transactivator p65 RELA and
CC inhibits its phosphorylation and thus its transcriptional activation
CC activity (PubMed:12736262). Interacts with MAPK kinases and regulates
CC activation of MAP kinases (PubMed:15299019). Can inhibit APOBEC3A
CC editing of nuclear DNA (PubMed:22977230).
CC {ECO:0000250|UniProtKB:Q8K4K2, ECO:0000269|PubMed:12736262,
CC ECO:0000269|PubMed:15299019, ECO:0000269|PubMed:15775988,
CC ECO:0000269|PubMed:15781252, ECO:0000269|PubMed:22977230}.
CC -!- SUBUNIT: Interacts with AKT1, AKT2, MAP2K1 and MAP2K7
CC (PubMed:15299019). Interacts with ATF4 (PubMed:12743605). Interacts
CC with DDIT3/CHOP and inhibits its interaction with EP300/P300
CC (PubMed:15775988, PubMed:17872950). Interacts with APOBEC3C
CC (PubMed:22977230). Interacts (via N-terminus) with APOBEC3A
CC (PubMed:22977230). Interacts with RELA (PubMed:12736262).
CC {ECO:0000269|PubMed:12736262, ECO:0000269|PubMed:12743605,
CC ECO:0000269|PubMed:15299019, ECO:0000269|PubMed:15775988,
CC ECO:0000269|PubMed:17872950, ECO:0000269|PubMed:22977230}.
CC -!- INTERACTION:
CC Q96RU7; Q9ULX6: AKAP8L; NbExp=3; IntAct=EBI-492476, EBI-357530;
CC Q96RU7; Q9NRW3: APOBEC3C; NbExp=5; IntAct=EBI-492476, EBI-1044593;
CC Q96RU7; Q9H6L4: ARMC7; NbExp=3; IntAct=EBI-492476, EBI-742909;
CC Q96RU7; P18848: ATF4; NbExp=16; IntAct=EBI-492476, EBI-492498;
CC Q96RU7; O95817: BAG3; NbExp=3; IntAct=EBI-492476, EBI-747185;
CC Q96RU7; P41182: BCL6; NbExp=4; IntAct=EBI-492476, EBI-765407;
CC Q96RU7; Q13515: BFSP2; NbExp=3; IntAct=EBI-492476, EBI-10229433;
CC Q96RU7; Q0VAL7: C21orf58; NbExp=3; IntAct=EBI-492476, EBI-10226774;
CC Q96RU7; Q6P5X5: C22orf39; NbExp=3; IntAct=EBI-492476, EBI-7317823;
CC Q96RU7; Q9HC52: CBX8; NbExp=3; IntAct=EBI-492476, EBI-712912;
CC Q96RU7; Q13111: CHAF1A; NbExp=5; IntAct=EBI-492476, EBI-1020839;
CC Q96RU7; P51800-3: CLCNKA; NbExp=3; IntAct=EBI-492476, EBI-11980535;
CC Q96RU7; P78358: CTAG1B; NbExp=3; IntAct=EBI-492476, EBI-1188472;
CC Q96RU7; G5E9A7: DMWD; NbExp=3; IntAct=EBI-492476, EBI-10976677;
CC Q96RU7; Q6W0C5: DPPA3; NbExp=3; IntAct=EBI-492476, EBI-12082590;
CC Q96RU7; Q86UW9: DTX2; NbExp=3; IntAct=EBI-492476, EBI-740376;
CC Q96RU7; O95967: EFEMP2; NbExp=3; IntAct=EBI-492476, EBI-743414;
CC Q96RU7; O15197-2: EPHB6; NbExp=3; IntAct=EBI-492476, EBI-10182490;
CC Q96RU7; Q9NQT4: EXOSC5; NbExp=3; IntAct=EBI-492476, EBI-371876;
CC Q96RU7; Q6NZ36-4: FAAP20; NbExp=3; IntAct=EBI-492476, EBI-12013806;
CC Q96RU7; Q3B820: FAM161A; NbExp=3; IntAct=EBI-492476, EBI-719941;
CC Q96RU7; Q86YD7: FAM90A1; NbExp=3; IntAct=EBI-492476, EBI-6658203;
CC Q96RU7; Q8NEA6-2: GLIS3; NbExp=3; IntAct=EBI-492476, EBI-12232117;
CC Q96RU7; Q9NWQ4-1: GPATCH2L; NbExp=3; IntAct=EBI-492476, EBI-11959863;
CC Q96RU7; P62993: GRB2; NbExp=3; IntAct=EBI-492476, EBI-401755;
CC Q96RU7; O14929: HAT1; NbExp=3; IntAct=EBI-492476, EBI-2339359;
CC Q96RU7; P56524-2: HDAC4; NbExp=3; IntAct=EBI-492476, EBI-11953488;
CC Q96RU7; P52597: HNRNPF; NbExp=3; IntAct=EBI-492476, EBI-352986;
CC Q96RU7; P09067: HOXB5; NbExp=3; IntAct=EBI-492476, EBI-3893317;
CC Q96RU7; P31273: HOXC8; NbExp=3; IntAct=EBI-492476, EBI-1752118;
CC Q96RU7; Q14005-2: IL16; NbExp=3; IntAct=EBI-492476, EBI-17178971;
CC Q96RU7; Q0VD86: INCA1; NbExp=3; IntAct=EBI-492476, EBI-6509505;
CC Q96RU7; Q9C086: INO80B; NbExp=3; IntAct=EBI-492476, EBI-715611;
CC Q96RU7; P78412: IRX6; NbExp=3; IntAct=EBI-492476, EBI-12100506;
CC Q96RU7; Q63ZY3: KANK2; NbExp=5; IntAct=EBI-492476, EBI-2556193;
CC Q96RU7; Q2WGJ6: KLHL38; NbExp=3; IntAct=EBI-492476, EBI-6426443;
CC Q96RU7; Q7Z3Y9: KRT26; NbExp=3; IntAct=EBI-492476, EBI-12084444;
CC Q96RU7; Q96BZ8: LENG1; NbExp=3; IntAct=EBI-492476, EBI-726510;
CC Q96RU7; P25791-3: LMO2; NbExp=3; IntAct=EBI-492476, EBI-11959475;
CC Q96RU7; Q8TAP4-4: LMO3; NbExp=3; IntAct=EBI-492476, EBI-11742507;
CC Q96RU7; Q99750: MDFI; NbExp=3; IntAct=EBI-492476, EBI-724076;
CC Q96RU7; Q8IVT2: MISP; NbExp=3; IntAct=EBI-492476, EBI-2555085;
CC Q96RU7; O43482: OIP5; NbExp=3; IntAct=EBI-492476, EBI-536879;
CC Q96RU7; Q9UM07: PADI4; NbExp=3; IntAct=EBI-492476, EBI-1042511;
CC Q96RU7; Q9BYG5: PARD6B; NbExp=3; IntAct=EBI-492476, EBI-295391;
CC Q96RU7; Q92824-2: PCSK5; NbExp=3; IntAct=EBI-492476, EBI-11956269;
CC Q96RU7; Q99697-2: PITX2; NbExp=3; IntAct=EBI-492476, EBI-12138495;
CC Q96RU7; Q96KN3: PKNOX2; NbExp=3; IntAct=EBI-492476, EBI-2692890;
CC Q96RU7; Q5T8A7: PPP1R26; NbExp=3; IntAct=EBI-492476, EBI-308500;
CC Q96RU7; Q7Z5V6-2: PPP1R32; NbExp=3; IntAct=EBI-492476, EBI-12000762;
CC Q96RU7; O43741: PRKAB2; NbExp=3; IntAct=EBI-492476, EBI-1053424;
CC Q96RU7; O14744: PRMT5; NbExp=2; IntAct=EBI-492476, EBI-351098;
CC Q96RU7; A6NJB7-2: PRR19; NbExp=3; IntAct=EBI-492476, EBI-11998870;
CC Q96RU7; Q96KN7: RPGRIP1; NbExp=3; IntAct=EBI-492476, EBI-1050213;
CC Q96RU7; Q96KN7-4: RPGRIP1; NbExp=3; IntAct=EBI-492476, EBI-11525164;
CC Q96RU7; Q96NU1: SAMD11; NbExp=3; IntAct=EBI-492476, EBI-14067109;
CC Q96RU7; Q8IYX7: SAXO1; NbExp=3; IntAct=EBI-492476, EBI-3957636;
CC Q96RU7; Q9BWG6: SCNM1; NbExp=3; IntAct=EBI-492476, EBI-748391;
CC Q96RU7; Q9NUL5-4: SHFL; NbExp=3; IntAct=EBI-492476, EBI-11955083;
CC Q96RU7; P09234: SNRPC; NbExp=3; IntAct=EBI-492476, EBI-766589;
CC Q96RU7; Q99932-2: SPAG8; NbExp=3; IntAct=EBI-492476, EBI-11959123;
CC Q96RU7; Q9NZD8: SPG21; NbExp=3; IntAct=EBI-492476, EBI-742688;
CC Q96RU7; Q7Z699: SPRED1; NbExp=4; IntAct=EBI-492476, EBI-5235340;
CC Q96RU7; P51687: SUOX; NbExp=3; IntAct=EBI-492476, EBI-3921347;
CC Q96RU7; Q9Y242: TCF19; NbExp=3; IntAct=EBI-492476, EBI-7413767;
CC Q96RU7; Q9BXF9: TEKT3; NbExp=3; IntAct=EBI-492476, EBI-8644516;
CC Q96RU7; Q8WW24: TEKT4; NbExp=5; IntAct=EBI-492476, EBI-750487;
CC Q96RU7; Q08117-2: TLE5; NbExp=3; IntAct=EBI-492476, EBI-11741437;
CC Q96RU7; Q5W5X9-3: TTC23; NbExp=3; IntAct=EBI-492476, EBI-9090990;
CC Q96RU7; Q8WUN7: UBTD2; NbExp=3; IntAct=EBI-492476, EBI-12867288;
CC Q96RU7; A0A024R8A9: USP20; NbExp=3; IntAct=EBI-492476, EBI-14096082;
CC Q96RU7; Q9BRU9: UTP23; NbExp=3; IntAct=EBI-492476, EBI-5457544;
CC Q96RU7; Q8TAU3: ZNF417; NbExp=3; IntAct=EBI-492476, EBI-740727;
CC Q96RU7; Q96SQ5: ZNF587; NbExp=3; IntAct=EBI-492476, EBI-6427977;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:22977230}.
CC -!- TISSUE SPECIFICITY: Highest expression in liver, pancreas, peripheral
CC blood leukocytes and bone marrow. Also highly expressed in a number of
CC primary lung, colon and breast tumors. Expressed in spleen, thymus, and
CC prostate and is undetectable in other examined tissues, including
CC testis, ovary, small intestine, colon, leukocyte, heart, brain,
CC placenta, lung, skeletal muscle, and kidney.
CC {ECO:0000269|PubMed:12736262, ECO:0000269|PubMed:12743605,
CC ECO:0000269|PubMed:15299019}.
CC -!- INDUCTION: By hypoxia, TNF, and by nutrient starvation. Expression is
CC PI 3-kinase and/or NF-kappa-B-dependent. Induced by ER stress via ATF4-
CC DDIT3/CHOP pathway and can down-regulate its own induction by
CC repression of ATF4-DDIT3/CHOP functions. {ECO:0000269|PubMed:12736262,
CC ECO:0000269|PubMed:12743605, ECO:0000269|PubMed:15775988,
CC ECO:0000269|PubMed:16129579}.
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 by Du et al (PubMed:12791994) for the mouse ortholog but
CC Iynedjian (PubMed:15469416) has not been able to reproduce the result
CC in rat hepatocytes. {ECO:0000305}.
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DR EMBL; AF250311; AAK58175.1; -; mRNA.
DR EMBL; AJ697936; CAG27047.1; -; mRNA.
DR EMBL; AY247738; AAP04407.1; -; mRNA.
DR EMBL; AK026945; BAB15597.1; -; mRNA.
DR EMBL; CR457366; CAG33647.1; -; mRNA.
DR EMBL; AK222837; BAD96557.1; -; mRNA.
DR EMBL; AL034548; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC019363; AAH19363.1; -; mRNA.
DR EMBL; BC027484; AAH27484.1; -; mRNA.
DR CCDS; CCDS12997.1; -.
DR RefSeq; NP_001288117.1; NM_001301188.1.
DR RefSeq; NP_001288119.1; NM_001301190.1.
DR RefSeq; NP_001288122.1; NM_001301193.1.
DR RefSeq; NP_001288125.1; NM_001301196.1.
DR RefSeq; NP_001288130.1; NM_001301201.1.
DR RefSeq; NP_066981.2; NM_021158.4.
DR AlphaFoldDB; Q96RU7; -.
DR SMR; Q96RU7; -.
DR BioGRID; 121756; 126.
DR CORUM; Q96RU7; -.
DR IntAct; Q96RU7; 102.
DR MINT; Q96RU7; -.
DR STRING; 9606.ENSP00000217233; -.
DR GlyGen; Q96RU7; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q96RU7; -.
DR PhosphoSitePlus; Q96RU7; -.
DR BioMuta; TRIB3; -.
DR DMDM; 28201830; -.
DR EPD; Q96RU7; -.
DR jPOST; Q96RU7; -.
DR MassIVE; Q96RU7; -.
DR MaxQB; Q96RU7; -.
DR PaxDb; Q96RU7; -.
DR PeptideAtlas; Q96RU7; -.
DR PRIDE; Q96RU7; -.
DR ProteomicsDB; 78040; -.
DR Antibodypedia; 6154; 594 antibodies from 34 providers.
DR DNASU; 57761; -.
DR Ensembl; ENST00000217233.9; ENSP00000217233.3; ENSG00000101255.12.
DR GeneID; 57761; -.
DR KEGG; hsa:57761; -.
DR MANE-Select; ENST00000217233.9; ENSP00000217233.3; NM_021158.5; NP_066981.2.
DR UCSC; uc002wdm.4; human.
DR CTD; 57761; -.
DR DisGeNET; 57761; -.
DR GeneCards; TRIB3; -.
DR HGNC; HGNC:16228; TRIB3.
DR HPA; ENSG00000101255; Tissue enhanced (liver).
DR MIM; 607898; gene.
DR neXtProt; NX_Q96RU7; -.
DR OpenTargets; ENSG00000101255; -.
DR PharmGKB; PA25804; -.
DR VEuPathDB; HostDB:ENSG00000101255; -.
DR eggNOG; KOG0583; Eukaryota.
DR GeneTree; ENSGT00950000182986; -.
DR InParanoid; Q96RU7; -.
DR PhylomeDB; Q96RU7; -.
DR TreeFam; TF329785; -.
DR PathwayCommons; Q96RU7; -.
DR Reactome; R-HSA-1257604; PIP3 activates AKT signaling.
DR Reactome; R-HSA-165158; Activation of AKT2.
DR Reactome; R-HSA-1989781; PPARA activates gene expression.
DR Reactome; R-HSA-199418; Negative regulation of the PI3K/AKT network.
DR Reactome; R-HSA-389357; CD28 dependent PI3K/Akt signaling.
DR Reactome; R-HSA-5218920; VEGFR2 mediated vascular permeability.
DR Reactome; R-HSA-9633012; Response of EIF2AK4 (GCN2) to amino acid deficiency.
DR Reactome; R-HSA-9648895; Response of EIF2AK1 (HRI) to heme deficiency.
DR SignaLink; Q96RU7; -.
DR SIGNOR; Q96RU7; -.
DR BioGRID-ORCS; 57761; 10 hits in 1112 CRISPR screens.
DR ChiTaRS; TRIB3; human.
DR GeneWiki; TRIB3; -.
DR GenomeRNAi; 57761; -.
DR Pharos; Q96RU7; Tbio.
DR PRO; PR:Q96RU7; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; Q96RU7; protein.
DR Bgee; ENSG00000101255; Expressed in right lobe of liver and 127 other tissues.
DR ExpressionAtlas; Q96RU7; baseline and differential.
DR Genevisible; Q96RU7; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0005524; F:ATP binding; IEA:InterPro.
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; ISS:UniProtKB.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISS:BHF-UCL.
DR GO; GO:0055106; F:ubiquitin-protein transferase regulator activity; ISS:BHF-UCL.
DR GO; GO:0032869; P:cellular response to insulin stimulus; ISS:BHF-UCL.
DR GO; GO:0070059; P:intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; IDA:UniProtKB.
DR GO; GO:0045599; P:negative regulation of fat cell differentiation; ISS:BHF-UCL.
DR GO; GO:0045717; P:negative regulation of fatty acid biosynthetic process; ISS:BHF-UCL.
DR GO; GO:0006469; P:negative regulation of protein kinase activity; IDA:BHF-UCL.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:ParkinsonsUK-UCL.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IMP: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; ISS:BHF-UCL.
DR GO; GO:0051443; P:positive regulation of ubiquitin-protein transferase activity; ISS: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; ISS:BHF-UCL.
DR GO; GO:0043405; P:regulation of MAP kinase activity; IDA:UniProtKB.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; IDA: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; Phosphoprotein; Protein kinase inhibitor;
KW Reference proteome; Stress response; Transcription;
KW Transcription regulation.
FT CHAIN 1..358
FT /note="Tribbles homolog 3"
FT /id="PRO_0000131866"
FT DOMAIN 68..316
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..127
FT /note="Interaction with DDIT3/CHOP"
FT REGION 1..54
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 15..35
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 12
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VARIANT 60
FT /note="T -> I (in a glioblastoma multiforme sample; somatic
FT mutation; dbSNP:rs757496714)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042372"
FT VARIANT 84
FT /note="Q -> R (in dbSNP:rs2295490)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:17344846"
FT /id="VAR_023965"
FT VARIANT 153
FT /note="R -> H (in dbSNP:rs35051116)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042373"
FT VARIANT 274
FT /note="R -> H (in dbSNP:rs56291463)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042374"
FT VARIANT 347
FT /note="E -> K (in dbSNP:rs56342286)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042375"
FT CONFLICT 24
FT /note="N -> D (in Ref. 7; CAG33647)"
FT /evidence="ECO:0000305"
FT CONFLICT 105
FT /note="L -> P (in Ref. 6; BAB15597 and 8; BAD96557)"
FT /evidence="ECO:0000305"
FT CONFLICT 114
FT /note="L -> V (in Ref. 3; AAK58175)"
FT /evidence="ECO:0000305"
FT CONFLICT 194..195
FT /note="ER -> DREK (in Ref. 3; AAK58175)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 358 AA; 39578 MW; CE15FD89A81E8D63 CRC64;
MRATPLAAPA GSLSRKKRLE LDDNLDTERP VQKRARSGPQ PRLPPCLLPL SPPTAPDRAT
AVATASRLGP YVLLEPEEGG RAYQALHCPT GTEYTCKVYP VQEALAVLEP YARLPPHKHV
ARPTEVLAGT QLLYAFFTRT HGDMHSLVRS RHRIPEPEAA VLFRQMATAL AHCHQHGLVL
RDLKLCRFVF ADRERKKLVL ENLEDSCVLT GPDDSLWDKH ACPAYVGPEI LSSRASYSGK
AADVWSLGVA LFTMLAGHYP FQDSEPVLLF GKIRRGAYAL PAGLSAPARC LVRCLLRREP
AERLTATGIL LHPWLRQDPM PLAPTRSHLW EAAQVVPDGL GLDEAREEEG DREVVLYG
