TRIB1_MOUSE
ID TRIB1_MOUSE Reviewed; 372 AA.
AC Q8K4K4; Q8BFS7; Q8BJR9; Q8BZX3; Q91W04;
DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 06-DEC-2005, sequence version 2.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=Tribbles homolog 1;
DE Short=TRB-1;
GN Name=Trib1 {ECO:0000312|MGI:MGI:2443397};
GN Synonyms=Trb1 {ECO:0000312|MGI:MGI:2443397};
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] (ISOFORM 1).
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 [2] {ECO:0000305, ECO:0000312|EMBL:BAC28245.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:BAC37854.1};
RC TISSUE=Aorta {ECO:0000312|EMBL:BAC37854.1},
RC Hypothalamus {ECO:0000312|EMBL:BAE37097.1},
RC Lung {ECO:0000312|EMBL:BAC28245.1}, Skin {ECO:0000312|EMBL:BAC26038.1}, and
RC Vein {ECO:0000312|EMBL:BAC37854.1};
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 [3] {ECO:0000305, ECO:0000312|EMBL:AAH06800.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=FVB/N-3 {ECO:0000312|EMBL:AAH06800.1};
RC TISSUE=Mammary gland {ECO:0000312|EMBL:AAH06800.1};
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 [4]
RP FUNCTION.
RX PubMed=20410507; DOI=10.1182/blood-2009-07-229450;
RA Dedhia P.H., Keeshan K., Uljon S., Xu L., Vega M.E., Shestova O.,
RA Zaks-Zilberman M., Romany C., Blacklow S.C., Pear W.S.;
RT "Differential ability of Tribbles family members to promote degradation of
RT C/EBPalpha and induce acute myelogenous leukemia.";
RL Blood 116:1321-1328(2010).
RN [5]
RP FUNCTION, AND DOMAIN.
RX PubMed=24003916; DOI=10.1111/dom.12151;
RA Akira S., Misawa T., Satoh T., Saitoh T.;
RT "Macrophages control innate inflammation.";
RL Diabetes Obes. Metab. Suppl. 3:10-18(2013).
RN [6]
RP FUNCTION.
RX PubMed=23515163; DOI=10.1038/nature11930;
RA Satoh T., Kidoya H., Naito H., Yamamoto M., Takemura N., Nakagawa K.,
RA Yoshioka Y., Morii E., Takakura N., Takeuchi O., Akira S.;
RT "Critical role of Trib1 in differentiation of tissue-resident M2-like
RT macrophages.";
RL Nature 495:524-528(2013).
CC -!- FUNCTION: Adapter protein involved in protein degradation by
CC interacting with COP1 ubiquitin ligase (PubMed:23515163,
CC PubMed:20410507). Promotes CEBPA degradation and inhibits its function
CC (PubMed:20410507). Controls macrophage, eosinophil and neutrophil
CC differentiation via the COP1-binding domain (PubMed:24003916,
CC PubMed:23515163). Regulates myeloid cell differentiation by altering
CC the expression of CEBPA in a COP1-dependent manner (PubMed:23515163).
CC Interacts with MAPK kinases and regulates activation of MAP kinases,
CC but has no kinase activity (By similarity).
CC {ECO:0000250|UniProtKB:Q96RU8, ECO:0000269|PubMed:20410507,
CC ECO:0000269|PubMed:23515163, ECO:0000269|PubMed:24003916}.
CC -!- SUBUNIT: Monomer. Interacts (via protein kinase domain) with CEBPA.
CC Interacts with COP1. {ECO:0000250|UniProtKB:Q96RU8}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1 {ECO:0000269|PubMed:15299019};
CC IsoId=Q8K4K4-1; Sequence=Displayed;
CC Name=2 {ECO:0000305};
CC IsoId=Q8K4K4-2; Sequence=VSP_051888;
CC -!- DOMAIN: The COP1-binding motif (355-360) is required for regulation
CC activity (PubMed:24003916). {ECO:0000269|PubMed:24003916}.
CC -!- DOMAIN: The C-terminus (351-372) is required for interaction with COP1
CC (By similarity). {ECO:0000250|UniProtKB:Q96RU8}.
CC -!- DOMAIN: The protein kinase active site is incompatible with ATP binding
CC and is inactive (By similarity). {ECO:0000250|UniProtKB:Q96RU8}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. Tribbles subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC28245.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAC37854.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF358866; AAM45478.1; -; mRNA.
DR EMBL; AK028626; BAC26038.1; -; mRNA.
DR EMBL; AK033358; BAC28245.1; ALT_INIT; mRNA.
DR EMBL; AK040738; BAC30688.1; -; mRNA.
DR EMBL; AK041212; BAC30865.1; -; mRNA.
DR EMBL; AK080228; BAC37854.1; ALT_INIT; mRNA.
DR EMBL; AK162876; BAE37097.1; -; mRNA.
DR EMBL; BC006800; AAH06800.1; -; mRNA.
DR CCDS; CCDS27499.1; -. [Q8K4K4-1]
DR RefSeq; NP_653132.1; NM_144549.4. [Q8K4K4-1]
DR AlphaFoldDB; Q8K4K4; -.
DR SMR; Q8K4K4; -.
DR BioGRID; 229263; 3.
DR IntAct; Q8K4K4; 1.
DR STRING; 10090.ENSMUSP00000068834; -.
DR iPTMnet; Q8K4K4; -.
DR PhosphoSitePlus; Q8K4K4; -.
DR PaxDb; Q8K4K4; -.
DR PRIDE; Q8K4K4; -.
DR ProteomicsDB; 259096; -. [Q8K4K4-1]
DR ProteomicsDB; 259097; -. [Q8K4K4-2]
DR Antibodypedia; 27210; 389 antibodies from 32 providers.
DR DNASU; 211770; -.
DR Ensembl; ENSMUST00000067543; ENSMUSP00000068834; ENSMUSG00000032501. [Q8K4K4-1]
DR Ensembl; ENSMUST00000118228; ENSMUSP00000112828; ENSMUSG00000032501. [Q8K4K4-2]
DR GeneID; 211770; -.
DR KEGG; mmu:211770; -.
DR UCSC; uc007vxw.1; mouse. [Q8K4K4-1]
DR CTD; 10221; -.
DR MGI; MGI:2443397; Trib1.
DR VEuPathDB; HostDB:ENSMUSG00000032501; -.
DR eggNOG; KOG0583; Eukaryota.
DR GeneTree; ENSGT00950000182986; -.
DR HOGENOM; CLU_000288_13_1_1; -.
DR InParanoid; Q8K4K4; -.
DR OMA; KEPWERL; -.
DR OrthoDB; 1362510at2759; -.
DR PhylomeDB; Q8K4K4; -.
DR TreeFam; TF329785; -.
DR BioGRID-ORCS; 211770; 4 hits in 77 CRISPR screens.
DR ChiTaRS; Trib1; mouse.
DR PRO; PR:Q8K4K4; -.
DR Proteomes; UP000000589; Chromosome 15.
DR RNAct; Q8K4K4; protein.
DR Bgee; ENSMUSG00000032501; Expressed in granulocyte and 178 other tissues.
DR Genevisible; Q8K4K4; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0031434; F:mitogen-activated protein kinase kinase binding; ISO:MGI.
DR GO; GO:0004860; F:protein kinase inhibitor activity; ISO:MGI.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:BHF-UCL.
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:0007254; P:JNK cascade; ISO:MGI.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; IDA:BHF-UCL.
DR GO; GO:0031665; P:negative regulation of lipopolysaccharide-mediated signaling pathway; ISO:MGI.
DR GO; GO:0045659; P:negative regulation of neutrophil differentiation; IMP:CACAO.
DR GO; GO:0006469; P:negative regulation of protein kinase activity; ISO:MGI.
DR GO; GO:0014912; P:negative regulation of smooth muscle cell migration; ISO:MGI.
DR GO; GO:0048662; P:negative regulation of smooth muscle cell proliferation; ISO:MGI.
DR GO; GO:0045645; P:positive regulation of eosinophil differentiation; IMP:CACAO.
DR GO; GO:0045651; P:positive regulation of macrophage differentiation; IMP:CACAO.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IDA:BHF-UCL.
DR GO; GO:0051443; P:positive regulation of ubiquitin-protein transferase activity; IC:BHF-UCL.
DR GO; GO:0043405; P:regulation of MAP kinase activity; ISS:UniProtKB.
DR GO; GO:0032496; P:response to lipopolysaccharide; IMP:BHF-UCL.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR024105; TRB1.
DR InterPro; IPR024104; Tribbles/Ser_Thr_kinase_40.
DR PANTHER; PTHR22961; PTHR22961; 1.
DR PANTHER; PTHR22961:SF17; PTHR22961:SF17; 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 2: Evidence at transcript level;
KW Alternative splicing; Protein kinase inhibitor; Reference proteome.
FT CHAIN 1..372
FT /note="Tribbles homolog 1"
FT /id="PRO_0000131860"
FT DOMAIN 1..338
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..26
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 49..85
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 355..360
FT /note="COP1-binding"
FT /evidence="ECO:0000269|PubMed:24003916"
FT COMPBIAS 59..73
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 219..372
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_051888"
FT CONFLICT 224
FT /note="E -> G (in Ref. 1; AAM45478)"
FT /evidence="ECO:0000305"
FT CONFLICT 278
FT /note="L -> W (in Ref. 1; AAM45478)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 372 AA; 41281 MW; AD29BB4E640B4B62 CRC64;
MRVGPVRFAL SGASQPRGPG LLFPAARGTP AKRLLDTDDA GAVAAKCPRL SECSSPPDYL
SPPGSPCSPQ PPPSTQGTGG SCVSSPGPSR IADYLLLPLA EREHVSRALC IHTGRELRCK
EFPIKHYQDK IRPYIQLPSH SNITGIVEVL LGESKAYVFF EKDFGDMHSY VRSRKRLREE
EAARLFKQIV SAVAHCHQSA IVLGDLKLRK FVFSTEERTQ LRLESLEDTH IIKGEDDALS
DKHGCPAYVS PEILNTTGTY SGKAADVWSL GVMLYTLLVG RYPFHDSDPS ALFSKIRRGQ
FCIPEHVSPK ARCLIRSLLR REPSERLTAP QILLHPWFEY VLEPGYVDSE IGTSDQIVPE
YQEDSDISSF FC
