TOLIP_MOUSE
ID TOLIP_MOUSE Reviewed; 274 AA.
AC Q9QZ06; Q543N1; Q9D5P5;
DT 27-MAR-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=Toll-interacting protein;
GN Name=Tollip;
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].
RC STRAIN=Swiss Webster;
RX PubMed=10854325; DOI=10.1038/35014038;
RA Burns K., Clatworthy J., Martin L., Martinon F., Plumpton C., Maschera B.,
RA Lewis A., Ray K., Tschopp J., Volpe F.;
RT "Tollip, a new component of the IL-1R1 pathway, links IRAK to the IL-1
RT receptor.";
RL Nat. Cell Biol. 2:346-351(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Corpora quadrigemina, and Testis;
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]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Embryo;
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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Component of the signaling pathway of IL-1 and Toll-like
CC receptors. Inhibits cell activation by microbial products. Recruits
CC IRAK1 to the IL-1 receptor complex. Inhibits IRAK1 phosphorylation and
CC kinase activity. Connects the ubiquitin pathway to autophagy by
CC functioning as a ubiquitin-ATG8 family adapter and thus mediating
CC autophagic clearance of ubiquitin conjugates. The TOLLIP-dependent
CC selective autophagy pathway plays an important role in clearance of
CC cytotoxic polyQ proteins aggregates (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Oligomerizes. Binds to TLR2 and the TLR4-MD2 complex via its
CC C-terminus. Exists as complex with IRAK1 in unstimulated cells. Upon
CC IL-1 signaling, Tollip binds to the activated IL-1 receptor complex
CC containing IL-1RI, IL-1RacP and the adapter protein MyD88, where it
CC interacts with the TIR domain of IL-1RacP. MyD88 then triggers IRAK1
CC autophosphorylation, which in turn leads to the dissociation of IRAK1
CC from Tollip and IL-1RAcP. Interacts with TOM1L2 (By similarity).
CC Interacts with ATG8 family proteins (via the AIM motifs), and ubiquitin
CC (via the CUE domain) (By similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC Q9QZ06; Q61730: Il1rap; NbExp=2; IntAct=EBI-74272, EBI-525035;
CC Q9QZ06; Q62406: Irak1; NbExp=2; IntAct=EBI-74272, EBI-448533;
CC Q9QZ06; O88746: Tom1; NbExp=2; IntAct=EBI-74272, EBI-74264;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Detected in heart, brain, spleen, lung, liver,
CC skeletal muscle, kidney, thymus, pancreas and testis.
CC -!- DOMAIN: Both ATG8-interaction motifs (AIM1 and AIM2) are required for
CC the association with ATG8 family proteins. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the tollip family. {ECO:0000305}.
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DR EMBL; AJ242971; CAB58121.1; -; mRNA.
DR EMBL; AK015062; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AK016482; BAB30262.1; -; mRNA.
DR EMBL; AK045422; BAC32357.1; -; mRNA.
DR EMBL; AK049263; BAC33643.1; -; mRNA.
DR EMBL; AK161312; BAE36316.1; -; mRNA.
DR EMBL; BC062139; AAH62139.1; -; mRNA.
DR CCDS; CCDS22020.1; -.
DR RefSeq; NP_076253.1; NM_023764.3.
DR AlphaFoldDB; Q9QZ06; -.
DR SMR; Q9QZ06; -.
DR BioGRID; 207666; 14.
DR IntAct; Q9QZ06; 7.
DR MINT; Q9QZ06; -.
DR STRING; 10090.ENSMUSP00000001950; -.
DR iPTMnet; Q9QZ06; -.
DR PhosphoSitePlus; Q9QZ06; -.
DR SwissPalm; Q9QZ06; -.
DR REPRODUCTION-2DPAGE; IPI00136618; -.
DR EPD; Q9QZ06; -.
DR jPOST; Q9QZ06; -.
DR MaxQB; Q9QZ06; -.
DR PaxDb; Q9QZ06; -.
DR PeptideAtlas; Q9QZ06; -.
DR PRIDE; Q9QZ06; -.
DR ProteomicsDB; 259491; -.
DR Antibodypedia; 10168; 581 antibodies from 41 providers.
DR DNASU; 54473; -.
DR Ensembl; ENSMUST00000001950; ENSMUSP00000001950; ENSMUSG00000025139.
DR GeneID; 54473; -.
DR KEGG; mmu:54473; -.
DR UCSC; uc009kmd.1; mouse.
DR CTD; 54472; -.
DR MGI; MGI:1891808; Tollip.
DR VEuPathDB; HostDB:ENSMUSG00000025139; -.
DR eggNOG; ENOG502QWQA; Eukaryota.
DR GeneTree; ENSGT00390000013104; -.
DR HOGENOM; CLU_067725_0_0_1; -.
DR InParanoid; Q9QZ06; -.
DR OMA; IYIQIFD; -.
DR OrthoDB; 1219350at2759; -.
DR PhylomeDB; Q9QZ06; -.
DR TreeFam; TF324180; -.
DR Reactome; R-MMU-6798695; Neutrophil degranulation.
DR Reactome; R-MMU-9020702; Interleukin-1 signaling.
DR BioGRID-ORCS; 54473; 0 hits in 74 CRISPR screens.
DR ChiTaRS; Tollip; mouse.
DR PRO; PR:Q9QZ06; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q9QZ06; protein.
DR Bgee; ENSMUSG00000025139; Expressed in spermatocyte and 257 other tissues.
DR ExpressionAtlas; Q9QZ06; baseline and differential.
DR Genevisible; Q9QZ06; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0016604; C:nuclear body; ISO:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0005150; F:interleukin-1, type I receptor binding; ISO:MGI.
DR GO; GO:0019900; F:kinase binding; ISO:MGI.
DR GO; GO:0032183; F:SUMO binding; ISO:MGI.
DR GO; GO:0035325; F:Toll-like receptor binding; ISO:MGI.
DR GO; GO:0043130; F:ubiquitin binding; IBA:GO_Central.
DR GO; GO:0031624; F:ubiquitin conjugating enzyme binding; ISO:MGI.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
DR GO; GO:0030855; P:epithelial cell differentiation; IEA:Ensembl.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0070498; P:interleukin-1-mediated signaling pathway; IDA:UniProtKB.
DR GO; GO:0016310; P:phosphorylation; ISS:UniProtKB.
DR GO; GO:0033235; P:positive regulation of protein sumoylation; ISO:MGI.
DR GO; GO:0036010; P:protein localization to endosome; ISO:MGI.
DR GO; GO:0007165; P:signal transduction; ISO:MGI.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR CDD; cd04016; C2_Tollip; 1.
DR CDD; cd14363; CUE_TOLIP; 1.
DR Gene3D; 2.60.40.150; -; 1.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR003892; CUE.
DR InterPro; IPR041799; TOLIP_CUE.
DR InterPro; IPR037301; Tollip_C2.
DR InterPro; IPR009060; UBA-like_sf.
DR Pfam; PF00168; C2; 1.
DR Pfam; PF02845; CUE; 1.
DR SMART; SM00239; C2; 1.
DR SMART; SM00546; CUE; 1.
DR SUPFAM; SSF46934; SSF46934; 1.
DR SUPFAM; SSF49562; SSF49562; 1.
DR PROSITE; PS50004; C2; 1.
DR PROSITE; PS51140; CUE; 1.
PE 1: Evidence at protein level;
KW Acetylation; Autophagy; Cytoplasm; Immunity; Inflammatory response;
KW Innate immunity; Phosphoprotein; Reference proteome; Repeat.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q9H0E2"
FT CHAIN 2..274
FT /note="Toll-interacting protein"
FT /id="PRO_0000072626"
FT DOMAIN 35..152
FT /note="C2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 229..272
FT /note="CUE"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00468"
FT MOTIF 133..136
FT /note="AIM1"
FT MOTIF 151..154
FT /note="AIM2"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:Q9H0E2"
FT MOD_RES 274
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:A2RUW1"
SQ SEQUENCE 274 AA; 30345 MW; C3624DB407B0C17B CRC64;
MATTVSTQRG PVYIGELPQD FLRITPTQQQ QQIQLDAQAA QQLQYGGTVG TVGRLSITVV
QAKLAKNYGM TRMDPYCRLR LGYAVYETPT AHNGAKNPRW NKVIQCTVPP GVDSFYLEIF
DERAFSMDDR IAWTHITIPE SLKQGQVEDE WYSLSGRQGD DKEGMINLVM SYTSLPAAMM
MPPQPVVLMP TVYQQGVGYV PIAGMPAVCS PGMVPMAMPP PAVAPQPRCN EEDLKAIQDM
FPNMDREVIR SVLEAQRGNK DAAINSLLQM GEES
