TRIB2_HUMAN
ID TRIB2_HUMAN Reviewed; 343 AA.
AC Q92519; B2R851; D6W510;
DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1997, sequence version 1.
DT 03-AUG-2022, entry version 173.
DE RecName: Full=Tribbles homolog 2;
DE Short=TRB-2;
GN Name=TRIB2 {ECO:0000312|HGNC:HGNC:30809};
GN Synonyms=TRB2 {ECO:0000312|EMBL:AAY15015.1};
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] {ECO:0000312|EMBL:BAA13250.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Cancellous bone;
RA Ohno I., Hashimoto J., Takaoka K., Ochi T., Okubo K., Matsubara K.;
RT "The cloning of a cDNA for putative serine/threonine kinase expressed in
RT human osteoblast.";
RL Submitted (AUG-1996) to the EMBL/GenBank/DDBJ databases.
RN [2] {ECO:0000312|EMBL:BAA13250.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Shan Y.X., Yu L.;
RL Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
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 [4] {ECO:0000305, ECO:0000312|EMBL:AAY15015.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [5] {ECO:0000312|EMBL:BAA13250.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6] {ECO:0000312|EMBL:AAH02637.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Uterus {ECO:0000312|EMBL:AAH02637.1};
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 [7] {ECO:0000305}
RP TISSUE SPECIFICITY.
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 [8]
RP AUTOANTIBODIES.
RX PubMed=15950723; DOI=10.1016/j.molimm.2004.11.020;
RA Zhang Y., Davis J.L., Li W.;
RT "Identification of tribbles homolog 2 as an autoantigen in autoimmune
RT uveitis by phage display.";
RL Mol. Immunol. 42:1275-1281(2005).
RN [9]
RP INTERACTION WITH COP1.
RX PubMed=27041596; DOI=10.1016/j.str.2016.03.002;
RA Uljon S., Xu X., Durzynska I., Stein S., Adelmant G., Marto J.A.,
RA Pear W.S., Blacklow S.C.;
RT "Structural basis for substrate selectivity of the E3 ligase COP1.";
RL Structure 24:687-696(2016).
RN [10]
RP VARIANT [LARGE SCALE ANALYSIS] ARG-4.
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: Interacts with MAPK kinases and regulates activation of MAP
CC kinases. Does not display kinase activity (By similarity).
CC {ECO:0000250|UniProtKB:Q28283, ECO:0000250|UniProtKB:Q96RU8}.
CC -!- SUBUNIT: Interacts with COP1 (PubMed:27041596).
CC {ECO:0000269|PubMed:27041596}.
CC -!- INTERACTION:
CC Q92519; Q9HBI0: PARVG; NbExp=5; IntAct=EBI-947178, EBI-3921217;
CC Q92519; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-947178, EBI-5235340;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cytoplasm, cytoskeleton
CC {ECO:0000250}. Note=May associate with the cytoskeleton. {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Highly expressed in peripheral blood leukocytes.
CC {ECO:0000269|PubMed:15299019}.
CC -!- DOMAIN: The protein kinase domain is predicted to be catalytically
CC inactive.
CC -!- MISCELLANEOUS: Antibodies against TRIB2 are present in sera from
CC patients with autoimmune uveitis.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. Tribbles subfamily. {ECO:0000305}.
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DR EMBL; D87119; BAA13250.1; -; mRNA.
DR EMBL; AY245544; AAO89231.1; -; mRNA.
DR EMBL; AK313237; BAG36048.1; -; mRNA.
DR EMBL; AC009486; AAY15015.1; -; Genomic_DNA.
DR EMBL; CH471053; EAX00907.1; -; Genomic_DNA.
DR EMBL; CH471053; EAX00908.1; -; Genomic_DNA.
DR EMBL; CH471053; EAX00909.1; -; Genomic_DNA.
DR EMBL; BC002637; AAH02637.1; -; mRNA.
DR CCDS; CCDS1683.1; -.
DR RefSeq; NP_067675.1; NM_021643.3.
DR AlphaFoldDB; Q92519; -.
DR SMR; Q92519; -.
DR BioGRID; 118779; 31.
DR IntAct; Q92519; 39.
DR MINT; Q92519; -.
DR STRING; 9606.ENSP00000155926; -.
DR BindingDB; Q92519; -.
DR ChEMBL; CHEMBL4523417; -.
DR GlyGen; Q92519; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q92519; -.
DR PhosphoSitePlus; Q92519; -.
DR BioMuta; TRIB2; -.
DR DMDM; 74762638; -.
DR MassIVE; Q92519; -.
DR PaxDb; Q92519; -.
DR PeptideAtlas; Q92519; -.
DR PRIDE; Q92519; -.
DR ProteomicsDB; 75278; -.
DR Antibodypedia; 674; 280 antibodies from 33 providers.
DR DNASU; 28951; -.
DR Ensembl; ENST00000155926.9; ENSP00000155926.4; ENSG00000071575.12.
DR GeneID; 28951; -.
DR KEGG; hsa:28951; -.
DR MANE-Select; ENST00000155926.9; ENSP00000155926.4; NM_021643.4; NP_067675.1.
DR UCSC; uc002rbv.5; human.
DR CTD; 28951; -.
DR DisGeNET; 28951; -.
DR GeneCards; TRIB2; -.
DR HGNC; HGNC:30809; TRIB2.
DR HPA; ENSG00000071575; Low tissue specificity.
DR MIM; 609462; gene.
DR neXtProt; NX_Q92519; -.
DR OpenTargets; ENSG00000071575; -.
DR PharmGKB; PA128394647; -.
DR VEuPathDB; HostDB:ENSG00000071575; -.
DR eggNOG; KOG0583; Eukaryota.
DR GeneTree; ENSGT00950000182986; -.
DR InParanoid; Q92519; -.
DR OMA; CQDQLVP; -.
DR OrthoDB; 1362510at2759; -.
DR PhylomeDB; Q92519; -.
DR TreeFam; TF329785; -.
DR PathwayCommons; Q92519; -.
DR SignaLink; Q92519; -.
DR SIGNOR; Q92519; -.
DR BioGRID-ORCS; 28951; 20 hits in 1114 CRISPR screens.
DR ChiTaRS; TRIB2; human.
DR GeneWiki; TRIB2; -.
DR GenomeRNAi; 28951; -.
DR Pharos; Q92519; Tbio.
DR PRO; PR:Q92519; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q92519; protein.
DR Bgee; ENSG00000071575; Expressed in left ovary and 197 other tissues.
DR ExpressionAtlas; Q92519; baseline and differential.
DR Genevisible; Q92519; HS.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0031434; F:mitogen-activated protein kinase kinase binding; IBA:GO_Central.
DR GO; GO:0004860; F:protein kinase inhibitor activity; IEA:UniProtKB-KW.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; ISS:BHF-UCL.
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:0045599; P:negative regulation of fat cell differentiation; ISS:BHF-UCL.
DR GO; GO:0032693; P:negative regulation of interleukin-10 production; IMP:BHF-UCL.
DR GO; GO:0006469; P:negative regulation of protein kinase activity; NAS:BHF-UCL.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; ISS:BHF-UCL.
DR GO; GO:0043405; P:regulation of MAP kinase activity; ISS:UniProtKB.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR024104; Tribbles/Ser_Thr_kinase_40.
DR PANTHER; PTHR22961; PTHR22961; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Cytoskeleton; Protein kinase inhibitor; Reference proteome.
FT CHAIN 1..343
FT /note="Tribbles homolog 2"
FT /id="PRO_0000131863"
FT DOMAIN 61..308
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 25..50
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 28..50
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 4
FT /note="H -> R (in dbSNP:rs55813198)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042371"
SQ SEQUENCE 343 AA; 38801 MW; BF8B7366DACB84FA CRC64;
MNIHRSTPIT IARYGRSRNK TQDFEELSSI RSAEPSQSFS PNLGSPSPPE TPNLSHCVSC
IGKYLLLEPL EGDHVFRAVH LHSGEELVCK VFDISCYQES LAPCFCLSAH SNINQITEII
LGETKAYVFF ERSYGDMHSF VRTCKKLREE EAARLFYQIA SAVAHCHDGG LVLRDLKLRK
FIFKDEERTR VKLESLEDAY ILRGDDDSLS DKHGCPAYVS PEILNTSGSY SGKAADVWSL
GVMLYTMLVG RYPFHDIEPS SLFSKIRRGQ FNIPETLSPK AKCLIRSILR REPSERLTSQ
EILDHPWFST DFSVSNSAYG AKEVSDQLVP DVNMEENLDP FFN
