TOLIP_HUMAN
ID TOLIP_HUMAN Reviewed; 274 AA.
AC Q9H0E2; B3KXC6; Q9H9E6; Q9UJ69;
DT 27-MAR-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 186.
DE RecName: Full=Toll-interacting protein;
GN Name=TOLLIP;
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] (ISOFORM 1).
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] (ISOFORM 1).
RC TISSUE=Testis;
RX PubMed=11230166; DOI=10.1101/gr.gr1547r;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J.,
RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W.,
RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B.,
RA Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and analysis of
RT 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 34-274 (ISOFORM 1).
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]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Eye, and Placenta;
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 INTERACTION WITH TLR2 AND TLR4, AND FUNCTION.
RX PubMed=11751856; DOI=10.1074/jbc.m109537200;
RA Zhang G., Ghosh S.;
RT "Negative regulation of Toll-like receptor-mediated signaling by Tollip.";
RL J. Biol. Chem. 277:7059-7065(2002).
RN [7]
RP INTERACTION WITH TOM1L2.
RX PubMed=16412388; DOI=10.1016/j.bbrc.2005.12.156;
RA Katoh Y., Imakagura H., Futatsumori M., Nakayama K.;
RT "Recruitment of clathrin onto endosomes by the Tom1-Tollip complex.";
RL Biochem. Biophys. Res. Commun. 341:143-149(2006).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [9]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [10]
RP INTERACTION WITH ATG8 FAMILY PROTEINS AND UBIQUITIN, DOMAIN, AND FUNCTION.
RX PubMed=25042851; DOI=10.1016/j.cell.2014.05.048;
RA Lu K., Psakhye I., Jentsch S.;
RT "Autophagic clearance of PolyQ proteins mediated by ubiquitin-Atg8 adaptors
RT of the conserved CUET protein family.";
RL Cell 158:549-563(2014).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [12]
RP STRUCTURE BY NMR OF 229-274.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of CUE domain in the C-terminal of human Toll-
RT interacting protein (TOLLIP).";
RL Submitted (NOV-2004) to the PDB data bank.
RN [13]
RP VARIANT ASN-161.
RX PubMed=26282398; DOI=10.1186/s13023-015-0316-8;
RA Dahmani M., Ammar-Khodja F., Bonnet C., Lefevre G.M., Hardelin J.P.,
RA Ibrahim H., Mallek Z., Petit C.;
RT "EPS8L2 is a new causal gene for childhood onset autosomal recessive
RT progressive hearing loss.";
RL Orphanet J. Rare Dis. 10:96-96(2015).
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 (PubMed:11751856). Connects the ubiquitin pathway to
CC autophagy by functioning as a ubiquitin-ATG8 family adapter and thus
CC mediating autophagic clearance of ubiquitin conjugates. The TOLLIP-
CC dependent selective autophagy pathway plays an important role in
CC clearance of cytotoxic polyQ proteins aggregates (PubMed:25042851).
CC {ECO:0000269|PubMed:11751856, ECO:0000269|PubMed:25042851}.
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. Interacts with ATG8
CC family proteins (via AIM motifs), and ubiquitin (via CUE domain).
CC {ECO:0000269|PubMed:11751856, ECO:0000269|PubMed:16412388,
CC ECO:0000269|PubMed:25042851}.
CC -!- INTERACTION:
CC Q9H0E2; P35609: ACTN2; NbExp=3; IntAct=EBI-74615, EBI-77797;
CC Q9H0E2; Q96B67: ARRDC3; NbExp=3; IntAct=EBI-74615, EBI-2875665;
CC Q9H0E2; P54253: ATXN1; NbExp=7; IntAct=EBI-74615, EBI-930964;
CC Q9H0E2; Q5BKX5-3: C19orf54; NbExp=3; IntAct=EBI-74615, EBI-11976299;
CC Q9H0E2; Q9H305: CDIP1; NbExp=3; IntAct=EBI-74615, EBI-2876678;
CC Q9H0E2; Q05048: CSTF1; NbExp=2; IntAct=EBI-74615, EBI-1789619;
CC Q9H0E2; O75553: DAB1; NbExp=3; IntAct=EBI-74615, EBI-7875264;
CC Q9H0E2; Q15038: DAZAP2; NbExp=11; IntAct=EBI-74615, EBI-724310;
CC Q9H0E2; Q9UHG0: DCDC2; NbExp=3; IntAct=EBI-74615, EBI-10303987;
CC Q9H0E2; Q14203-5: DCTN1; NbExp=3; IntAct=EBI-74615, EBI-25840379;
CC Q9H0E2; Q96D03: DDIT4L; NbExp=3; IntAct=EBI-74615, EBI-742054;
CC Q9H0E2; Q86Y13: DZIP3; NbExp=2; IntAct=EBI-74615, EBI-948630;
CC Q9H0E2; P19525: EIF2AK2; NbExp=2; IntAct=EBI-74615, EBI-640775;
CC Q9H0E2; A8MTA8-2: FAM166B; NbExp=3; IntAct=EBI-74615, EBI-12160437;
CC Q9H0E2; Q92567-2: FAM168A; NbExp=3; IntAct=EBI-74615, EBI-11978259;
CC Q9H0E2; Q96NT3-2: GUCD1; NbExp=3; IntAct=EBI-74615, EBI-11978177;
CC Q9H0E2; O43187: IRAK2; NbExp=2; IntAct=EBI-74615, EBI-447733;
CC Q9H0E2; Q3SY46: KRTAP13-3; NbExp=5; IntAct=EBI-74615, EBI-10241252;
CC Q9H0E2; Q3LI76: KRTAP15-1; NbExp=3; IntAct=EBI-74615, EBI-11992140;
CC Q9H0E2; Q3SYF9: KRTAP19-7; NbExp=3; IntAct=EBI-74615, EBI-10241353;
CC Q9H0E2; Q3LI64: KRTAP6-1; NbExp=5; IntAct=EBI-74615, EBI-12111050;
CC Q9H0E2; Q3LI66: KRTAP6-2; NbExp=5; IntAct=EBI-74615, EBI-11962084;
CC Q9H0E2; Q8IUC3: KRTAP7-1; NbExp=3; IntAct=EBI-74615, EBI-18394498;
CC Q9H0E2; Q9H492: MAP1LC3A; NbExp=3; IntAct=EBI-74615, EBI-720768;
CC Q9H0E2; Q5VYS4: MEDAG; NbExp=3; IntAct=EBI-74615, EBI-1050881;
CC Q9H0E2; Q4VC12: MSS51; NbExp=3; IntAct=EBI-74615, EBI-11599933;
CC Q9H0E2; P35548: MSX2; NbExp=3; IntAct=EBI-74615, EBI-6447480;
CC Q9H0E2; Q14764: MVP; NbExp=3; IntAct=EBI-74615, EBI-2816254;
CC Q9H0E2; Q16656-4: NRF1; NbExp=3; IntAct=EBI-74615, EBI-11742836;
CC Q9H0E2; Q96HA8: NTAQ1; NbExp=4; IntAct=EBI-74615, EBI-741158;
CC Q9H0E2; Q86TG7: PEG10; NbExp=2; IntAct=EBI-74615, EBI-2858265;
CC Q9H0E2; Q9BSU1: PHAF1; NbExp=5; IntAct=EBI-74615, EBI-946080;
CC Q9H0E2; O60260-5: PRKN; NbExp=3; IntAct=EBI-74615, EBI-21251460;
CC Q9H0E2; Q86UA1: PRPF39; NbExp=3; IntAct=EBI-74615, EBI-2803203;
CC Q9H0E2; P86480: PRR20D; NbExp=3; IntAct=EBI-74615, EBI-12754095;
CC Q9H0E2; P20618: PSMB1; NbExp=3; IntAct=EBI-74615, EBI-372273;
CC Q9H0E2; Q9NWB1-5: RBFOX1; NbExp=3; IntAct=EBI-74615, EBI-12123390;
CC Q9H0E2; Q93062: RBPMS; NbExp=4; IntAct=EBI-74615, EBI-740322;
CC Q9H0E2; Q9BQY4: RHOXF2; NbExp=6; IntAct=EBI-74615, EBI-372094;
CC Q9H0E2; Q9Y3C5: RNF11; NbExp=3; IntAct=EBI-74615, EBI-396669;
CC Q9H0E2; P37840: SNCA; NbExp=3; IntAct=EBI-74615, EBI-985879;
CC Q9H0E2; Q9H668: STN1; NbExp=3; IntAct=EBI-74615, EBI-746930;
CC Q9H0E2; O60784: TOM1; NbExp=5; IntAct=EBI-74615, EBI-74634;
CC Q9H0E2; O60784-2: TOM1; NbExp=5; IntAct=EBI-74615, EBI-12117154;
CC Q9H0E2; O75674: TOM1L1; NbExp=3; IntAct=EBI-74615, EBI-712991;
CC Q9H0E2; O75674-2: TOM1L1; NbExp=5; IntAct=EBI-74615, EBI-12011552;
CC Q9H0E2; Q6ZVM7-2: TOM1L2; NbExp=7; IntAct=EBI-74615, EBI-12147805;
CC Q9H0E2; Q8N5M4: TTC9C; NbExp=3; IntAct=EBI-74615, EBI-2851213;
CC Q9H0E2; Q70EL1-9: USP54; NbExp=3; IntAct=EBI-74615, EBI-11975223;
CC Q9H0E2; Q96S55: WRNIP1; NbExp=2; IntAct=EBI-74615, EBI-2513471;
CC Q9H0E2; Q96E35: ZMYND19; NbExp=3; IntAct=EBI-74615, EBI-746595;
CC Q9H0E2; Q9UGI0: ZRANB1; NbExp=3; IntAct=EBI-74615, EBI-527853;
CC Q9H0E2-1; O60784: TOM1; NbExp=4; IntAct=EBI-16173683, EBI-74634;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9H0E2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9H0E2-2; Sequence=VSP_056301;
CC -!- DOMAIN: Both ATG8-interaction motifs (AIM1 and AIM2) are required for
CC the association with ATG8 family proteins.
CC {ECO:0000269|PubMed:25042851}.
CC -!- PTM: Phosphorylated by IRAK1 upon stimulation by IL-1 or microbial
CC products.
CC -!- SIMILARITY: Belongs to the tollip family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB14283.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AJ242972; CAB58118.1; -; mRNA.
DR EMBL; AL136835; CAB66769.1; -; mRNA.
DR EMBL; AK022871; BAB14283.1; ALT_INIT; mRNA.
DR EMBL; AK127123; BAG54438.1; -; mRNA.
DR EMBL; AC136297; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC004420; AAH04420.1; -; mRNA.
DR EMBL; BC012057; AAH12057.1; -; mRNA.
DR EMBL; BC018272; AAH18272.1; -; mRNA.
DR CCDS; CCDS7723.1; -. [Q9H0E2-1]
DR CCDS; CCDS81532.1; -. [Q9H0E2-2]
DR RefSeq; NP_001305441.1; NM_001318512.1.
DR RefSeq; NP_001305443.1; NM_001318514.1. [Q9H0E2-2]
DR RefSeq; NP_001305444.1; NM_001318515.1.
DR RefSeq; NP_001305445.1; NM_001318516.1.
DR RefSeq; NP_061882.2; NM_019009.3. [Q9H0E2-1]
DR PDB; 1WGL; NMR; -; A=229-274.
DR PDB; 2N31; NMR; -; A=1-53.
DR PDBsum; 1WGL; -.
DR PDBsum; 2N31; -.
DR AlphaFoldDB; Q9H0E2; -.
DR BMRB; Q9H0E2; -.
DR SMR; Q9H0E2; -.
DR BioGRID; 119978; 347.
DR DIP; DIP-30845N; -.
DR IntAct; Q9H0E2; 90.
DR MINT; Q9H0E2; -.
DR STRING; 9606.ENSP00000314733; -.
DR iPTMnet; Q9H0E2; -.
DR MetOSite; Q9H0E2; -.
DR PhosphoSitePlus; Q9H0E2; -.
DR BioMuta; TOLLIP; -.
DR DMDM; 20140803; -.
DR EPD; Q9H0E2; -.
DR jPOST; Q9H0E2; -.
DR MassIVE; Q9H0E2; -.
DR MaxQB; Q9H0E2; -.
DR PaxDb; Q9H0E2; -.
DR PeptideAtlas; Q9H0E2; -.
DR PRIDE; Q9H0E2; -.
DR ProteomicsDB; 3808; -.
DR ProteomicsDB; 80260; -. [Q9H0E2-1]
DR Antibodypedia; 10168; 581 antibodies from 41 providers.
DR DNASU; 54472; -.
DR Ensembl; ENST00000317204.11; ENSP00000314733.5; ENSG00000078902.16. [Q9H0E2-1]
DR Ensembl; ENST00000527886.5; ENSP00000434035.1; ENSG00000078902.16. [Q9H0E2-2]
DR GeneID; 54472; -.
DR KEGG; hsa:54472; -.
DR MANE-Select; ENST00000317204.11; ENSP00000314733.5; NM_019009.4; NP_061882.2.
DR UCSC; uc001ltd.4; human. [Q9H0E2-1]
DR CTD; 54472; -.
DR DisGeNET; 54472; -.
DR GeneCards; TOLLIP; -.
DR HGNC; HGNC:16476; TOLLIP.
DR HPA; ENSG00000078902; Low tissue specificity.
DR MIM; 606277; gene.
DR neXtProt; NX_Q9H0E2; -.
DR OpenTargets; ENSG00000078902; -.
DR PharmGKB; PA134876213; -.
DR VEuPathDB; HostDB:ENSG00000078902; -.
DR eggNOG; ENOG502QWQA; Eukaryota.
DR GeneTree; ENSGT00390000013104; -.
DR HOGENOM; CLU_067725_2_0_1; -.
DR InParanoid; Q9H0E2; -.
DR OMA; IYIQIFD; -.
DR PhylomeDB; Q9H0E2; -.
DR TreeFam; TF324180; -.
DR PathwayCommons; Q9H0E2; -.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR Reactome; R-HSA-9020702; Interleukin-1 signaling.
DR SignaLink; Q9H0E2; -.
DR SIGNOR; Q9H0E2; -.
DR BioGRID-ORCS; 54472; 12 hits in 1083 CRISPR screens.
DR ChiTaRS; TOLLIP; human.
DR EvolutionaryTrace; Q9H0E2; -.
DR GeneWiki; TOLLIP; -.
DR GenomeRNAi; 54472; -.
DR Pharos; Q9H0E2; Tbio.
DR PRO; PR:Q9H0E2; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q9H0E2; protein.
DR Bgee; ENSG00000078902; Expressed in right frontal lobe and 182 other tissues.
DR ExpressionAtlas; Q9H0E2; baseline and differential.
DR Genevisible; Q9H0E2; HS.
DR GO; GO:0035578; C:azurophil granule lumen; TAS:Reactome.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0016604; C:nuclear body; IEA:Ensembl.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0035580; C:specific granule lumen; TAS:Reactome.
DR GO; GO:0005150; F:interleukin-1, type I receptor binding; IEA:Ensembl.
DR GO; GO:0019900; F:kinase binding; IPI:UniProtKB.
DR GO; GO:0032183; F:SUMO binding; IEA:Ensembl.
DR GO; GO:0035325; F:Toll-like receptor binding; IPI:UniProtKB.
DR GO; GO:0043130; F:ubiquitin binding; IBA:GO_Central.
DR GO; GO:0031624; F:ubiquitin conjugating enzyme binding; IBA:GO_Central.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IEA:Ensembl.
DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
DR GO; GO:0030855; P:epithelial cell differentiation; IEP:UniProtKB.
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; IEA:Ensembl.
DR GO; GO:0045321; P:leukocyte activation; NAS:UniProtKB.
DR GO; GO:0016310; P:phosphorylation; IDA:UniProtKB.
DR GO; GO:0033235; P:positive regulation of protein sumoylation; IEA:Ensembl.
DR GO; GO:0036010; P:protein localization to endosome; IDA:UniProtKB.
DR GO; GO:0007165; P:signal transduction; IPI:UniProtKB.
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 3D-structure; Acetylation; Alternative splicing; Autophagy; Cytoplasm;
KW Immunity; Inflammatory response; Innate immunity; Phosphoprotein;
KW Reference proteome; Repeat.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:22814378"
FT CHAIN 2..274
FT /note="Toll-interacting protein"
FT /id="PRO_0000072625"
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:0007744|PubMed:22814378"
FT VAR_SEQ 1..69
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056301"
FT VARIANT 161
FT /note="D -> N (in dbSNP:rs1037270334)"
FT /evidence="ECO:0000269|PubMed:26282398"
FT /id="VAR_079499"
FT VARIANT 222
FT /note="A -> S (in dbSNP:rs5744015)"
FT /id="VAR_034557"
FT CONFLICT 40
FT /note="Missing (in Ref. 1; CAB58118)"
FT /evidence="ECO:0000305"
FT CONFLICT 150
FT /note="K -> E (in Ref. 3; BAB14283)"
FT /evidence="ECO:0000305"
FT STRAND 4..7
FT /evidence="ECO:0007829|PDB:2N31"
FT STRAND 10..13
FT /evidence="ECO:0007829|PDB:2N31"
FT HELIX 231..240
FT /evidence="ECO:0007829|PDB:1WGL"
FT STRAND 242..244
FT /evidence="ECO:0007829|PDB:1WGL"
FT HELIX 246..253
FT /evidence="ECO:0007829|PDB:1WGL"
FT TURN 254..258
FT /evidence="ECO:0007829|PDB:1WGL"
FT HELIX 260..269
FT /evidence="ECO:0007829|PDB:1WGL"
SQ SEQUENCE 274 AA; 30282 MW; 386E0F284D3837DA CRC64;
MATTVSTQRG PVYIGELPQD FLRITPTQQQ RQVQLDAQAA QQLQYGGAVG TVGRLNITVV
QAKLAKNYGM TRMDPYCRLR LGYAVYETPT AHNGAKNPRW NKVIHCTVPP GVDSFYLEIF
DERAFSMDDR IAWTHITIPE SLRQGKVEDK WYSLSGRQGD DKEGMINLVM SYALLPAAMV
MPPQPVVLMP TVYQQGVGYV PITGMPAVCS PGMVPVALPP AAVNAQPRCS EEDLKAIQDM
FPNMDQEVIR SVLEAQRGNK DAAINSLLQM GEEP
