TOLIP_BOVIN
ID TOLIP_BOVIN Reviewed; 273 AA.
AC Q2LGB5; Q58D12;
DT 22-SEP-2009, integrated into UniProtKB/Swiss-Prot.
DT 21-FEB-2006, sequence version 1.
DT 03-AUG-2022, entry version 93.
DE RecName: Full=Toll-interacting protein;
GN Name=TOLLIP;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Mammary gland;
RX PubMed=16621030; DOI=10.1016/j.vetimm.2006.03.003;
RA Connor E.E., Cates E.A., Williams J.L., Bannerman D.D.;
RT "Cloning and radiation hybrid mapping of bovine toll-like receptor-4 (TLR-
RT 4) signaling molecules.";
RL Vet. Immunol. Immunopathol. 112:302-308(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Werling D., Willcocks S.;
RT "Identification of signalling molecules involved in bovine TLR
RT signalling.";
RL Submitted (FEB-2006) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=16305752; DOI=10.1186/1471-2164-6-166;
RA Harhay G.P., Sonstegard T.S., Keele J.W., Heaton M.P., Clawson M.L.,
RA Snelling W.M., Wiedmann R.T., Van Tassell C.P., Smith T.P.L.;
RT "Characterization of 954 bovine full-CDS cDNA sequences.";
RL BMC Genomics 6:166-166(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Hippocampus;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (SEP-2006) to the EMBL/GenBank/DDBJ databases.
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 AIM motifs), and ubiquitin
CC (via 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; DQ319073; ABC47876.1; -; mRNA.
DR EMBL; DQ407275; ABD72515.1; -; mRNA.
DR EMBL; BT021785; AAX46632.1; -; mRNA.
DR EMBL; BC123457; AAI23458.1; -; mRNA.
DR RefSeq; NP_001035050.1; NM_001039961.1.
DR AlphaFoldDB; Q2LGB5; -.
DR SMR; Q2LGB5; -.
DR STRING; 9913.ENSBTAP00000010835; -.
DR PaxDb; Q2LGB5; -.
DR PeptideAtlas; Q2LGB5; -.
DR PRIDE; Q2LGB5; -.
DR Ensembl; ENSBTAT00000010835; ENSBTAP00000010835; ENSBTAG00000008237.
DR GeneID; 539480; -.
DR KEGG; bta:539480; -.
DR CTD; 54472; -.
DR VEuPathDB; HostDB:ENSBTAG00000008237; -.
DR VGNC; VGNC:36216; TOLLIP.
DR eggNOG; ENOG502QWQA; Eukaryota.
DR GeneTree; ENSGT00390000013104; -.
DR HOGENOM; CLU_067725_0_0_1; -.
DR InParanoid; Q2LGB5; -.
DR OMA; IYIQIFD; -.
DR OrthoDB; 1219350at2759; -.
DR TreeFam; TF324180; -.
DR Reactome; R-BTA-6798695; Neutrophil degranulation.
DR Proteomes; UP000009136; Chromosome 29.
DR Bgee; ENSBTAG00000008237; Expressed in temporal cortex and 105 other tissues.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0032991; C:protein-containing complex; IEA:Ensembl.
DR GO; GO:0019900; F:kinase binding; IEA:Ensembl.
DR GO; GO:0035325; F:Toll-like receptor binding; IEA:Ensembl.
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: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; IEA:Ensembl.
DR GO; GO:0016310; P:phosphorylation; ISS:UniProtKB.
DR GO; GO:0036010; P:protein localization to endosome; IEA:Ensembl.
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 2: Evidence at transcript 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..273
FT /note="Toll-interacting protein"
FT /id="PRO_0000384931"
FT DOMAIN 35..152
FT /note="C2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 228..271
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 273
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:A2RUW1"
FT CONFLICT 56
FT /note="S -> I (in Ref. 2; ABD72515 and 3; AAX46632)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 273 AA; 30082 MW; E74C60B1CADE8B9D CRC64;
MATTVSTQRG PVYIGELPQD FLRITPTQQQ QQIQLDAQAA QQLQYGGALG TVGRLSVTVV
QAKLAKNYGM TRMDPYCRLR LGYAVYETPT AHNGAKNPRW NKVIQCTVPP GVDSFYLEIF
DERAFSMDDR IAWTHVTIPE ALKQGKVVDE WYSLSGRQGD DKEGMINLVL SYTSLPAAMM
MPPQPVVLMP TVYQQGVGYV PITGMPTVCS PGVVPVALPP AVSAQPRCSE EDLKAIQDMF
PNMDREVIRS VLEAQRGSRD AAINSLLQMG EES
