TOLIP_RAT
ID TOLIP_RAT Reviewed; 274 AA.
AC A2RUW1;
DT 23-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 06-MAR-2007, sequence version 1.
DT 03-AUG-2022, entry version 96.
DE RecName: Full=Toll-interacting protein;
GN Name=Tollip {ECO:0000312|EMBL:AAI33068.1};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1] {ECO:0000312|EMBL:AAI33068.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Heart {ECO:0000312|EMBL:AAI33068.1};
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 [2]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-274, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
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 -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}.
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; BC133067; AAI33068.1; -; mRNA.
DR RefSeq; NP_001103138.1; NM_001109668.1.
DR AlphaFoldDB; A2RUW1; -.
DR SMR; A2RUW1; -.
DR BioGRID; 262870; 17.
DR IntAct; A2RUW1; 2.
DR MINT; A2RUW1; -.
DR STRING; 10116.ENSRNOP00000049498; -.
DR iPTMnet; A2RUW1; -.
DR PhosphoSitePlus; A2RUW1; -.
DR jPOST; A2RUW1; -.
DR PaxDb; A2RUW1; -.
DR PeptideAtlas; A2RUW1; -.
DR PRIDE; A2RUW1; -.
DR Ensembl; ENSRNOT00000046344; ENSRNOP00000049498; ENSRNOG00000019861.
DR GeneID; 361677; -.
DR KEGG; rno:361677; -.
DR UCSC; RGD:1304676; rat.
DR CTD; 54472; -.
DR RGD; 1304676; Tollip.
DR eggNOG; ENOG502QWQA; Eukaryota.
DR GeneTree; ENSGT00390000013104; -.
DR HOGENOM; CLU_067725_0_0_1; -.
DR InParanoid; A2RUW1; -.
DR OMA; IYIQIFD; -.
DR OrthoDB; 1219350at2759; -.
DR PhylomeDB; A2RUW1; -.
DR TreeFam; TF324180; -.
DR Reactome; R-RNO-6798695; Neutrophil degranulation.
DR Reactome; R-RNO-9020702; Interleukin-1 signaling.
DR PRO; PR:A2RUW1; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000019861; Expressed in Ammon's horn and 19 other tissues.
DR Genevisible; A2RUW1; RN.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0016604; C:nuclear body; IDA:RGD.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:RGD.
DR GO; GO:0032991; C:protein-containing complex; ISO:RGD.
DR GO; GO:0005150; F:interleukin-1, type I receptor binding; IPI:RGD.
DR GO; GO:0019900; F:kinase binding; ISO:RGD.
DR GO; GO:0032183; F:SUMO binding; IPI:RGD.
DR GO; GO:0035325; F:Toll-like receptor binding; ISO:RGD.
DR GO; GO:0043130; F:ubiquitin binding; IBA:GO_Central.
DR GO; GO:0031624; F:ubiquitin conjugating enzyme binding; IPI:RGD.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:RGD.
DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
DR GO; GO:0030855; P:epithelial cell differentiation; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0016310; P:phosphorylation; ISS:UniProtKB.
DR GO; GO:0033235; P:positive regulation of protein sumoylation; IDA:RGD.
DR GO; GO:0036010; P:protein localization to endosome; ISO:RGD.
DR GO; GO:0007165; P:signal transduction; ISO:RGD.
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_0000308183"
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:0007744|PubMed:22673903"
SQ SEQUENCE 274 AA; 30315 MW; 89C8E01F77AD66B1 CRC64;
MATTVSTQRG PVYIGELPQD FLRITPTQQQ QQIQLDAQAA QQLQYGGAVG TVGRLSITVV
QAKLAKNYGM TRMDPYCRLR LGYAVYETPT AHNGAKNPRW NKVIQCTVPP GVDSFYLEIF
DERAFSMDDR IAWTHITIPE SLKQGQVEDE WYSLSGRQGD DKEGMINLVM SYTSLPAAMM
MPPQPVVLMP TVYQQGVGYV PIAGMPAVCS PGMVPMAMPP PAVAPQPRCN EEDLKAIQDM
FPNMDREVIR SVLEAQRGNK DAAINSLLQM GEES
