ID   TLR2_PANTR              Reviewed;         784 AA.
AC   B3Y613;
DT   10-FEB-2009, integrated into UniProtKB/Swiss-Prot.
DT   23-SEP-2008, sequence version 1.
DT   24-JAN-2024, entry version 80.
DE   RecName: Full=Toll-like receptor 2;
DE   AltName: CD_antigen=CD282;
DE   Flags: Precursor;
GN   Name=TLR2;
OS   Pan troglodytes (Chimpanzee).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Pan.
OX   NCBI_TaxID=9598;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RA   Nakajima T., Ohtani H., Satta Y., Uno Y., Akari H., Ishida T., Kimura A.;
RT   "Molecular evolution of the Toll-like receptor-related genes in primates.";
RL   Submitted (JUL-2008) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: Cooperates with LY96 to mediate the innate immune response to
CC       bacterial lipoproteins and other microbial cell wall components.
CC       Cooperates with TLR1 or TLR6 to mediate the innate immune response to
CC       bacterial lipoproteins or lipopeptides. Acts via MYD88 and TRAF6,
CC       leading to NF-kappa-B activation, cytokine secretion and the
CC       inflammatory response (By similarity). May also promote apoptosis in
CC       response to lipoproteins. Forms activation clusters composed of several
CC       receptors depending on the ligand, these clusters trigger signaling
CC       from the cell surface and subsequently are targeted to the Golgi in a
CC       lipid-raft dependent pathway. Forms the cluster TLR2:TLR6:CD14:CD36 in
CC       response to diacylated lipopeptides and TLR2:TLR1:CD14 in response to
CC       triacylated lipopeptides (By similarity).
CC       {ECO:0000250|UniProtKB:O60603, ECO:0000250|UniProtKB:Q9QUN7}.
CC   -!- SUBUNIT: Interacts with LY96, TLR1 and TLR6 (via extracellular domain).
CC       TLR2 seems to exist in heterodimers with either TLR1 or TLR6 before
CC       stimulation by the ligand. The heterodimers form bigger oligomers in
CC       response to their corresponding ligands as well as further heterotypic
CC       associations with other receptors such as CD14 and/or CD36. Binds MYD88
CC       (via TIR domain). Interacts with TICAM1. Interacts with CNPY3.
CC       Interacts with ATG16L1. Interacts with PPP1R11. Interacts with TICAM2.
CC       Interacts with TIRAP (By similarity). {ECO:0000250|UniProtKB:O60603,
CC       ECO:0000250|UniProtKB:Q9QUN7}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250|UniProtKB:Q9QUN7}; Single-
CC       pass type I membrane protein {ECO:0000255}. Cytoplasmic vesicle,
CC       phagosome membrane {ECO:0000250|UniProtKB:Q9QUN7}; Single-pass type I
CC       membrane protein {ECO:0000255}. Membrane raft
CC       {ECO:0000250|UniProtKB:O60603}. Note=Does not reside in lipid rafts
CC       before stimulation but accumulates increasingly in the raft upon the
CC       presence of the microbial ligand. In response to diacylated
CC       lipoproteins, TLR2:TLR6 heterodimers are recruited in lipid rafts, this
CC       recruitment determine the intracellular targeting to the Golgi
CC       apparatus. Triacylated lipoproteins induce the same mechanism for
CC       TLR2:TLR1 heterodimers. {ECO:0000250|UniProtKB:O60603}.
CC   -!- DOMAIN: Ester-bound lipid substrates are bound through a crevice formed
CC       between the LRR 11 and LRR 12. {ECO:0000250}.
CC   -!- DOMAIN: The ATG16L1-binding motif mediates interaction with ATG16L1.
CC       {ECO:0000250}.
CC   -!- PTM: Ubiquitinated at Lys-754 by PPP1R11, leading to its degradation.
CC       Deubiquitinated by USP2. {ECO:0000250|UniProtKB:Q9QUN7}.
CC   -!- PTM: Glycosylation of Asn-442 is critical for secretion of the N-
CC       terminal ectodomain of TLR2. {ECO:0000250|UniProtKB:O60603}.
CC   -!- SIMILARITY: Belongs to the Toll-like receptor family. {ECO:0000305}.
CC   -!- CAUTION: In some plant proteins and in human SARM1, the TIR domain has
CC       NAD(+) hydrolase (NADase) activity (By similarity). However, despite
CC       the presence of the catalytic Asp residue, the isolated TIR domain of
CC       human TLR4 lacks NADase activity (By similarity). Based on this, it is
CC       unlikely that Toll-like receptors have NADase activity.
CC       {ECO:0000250|UniProtKB:O00206, ECO:0000305}.
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DR   EMBL; AB445625; BAG55022.1; -; mRNA.
DR   RefSeq; NP_001123941.1; NM_001130469.1.
DR   AlphaFoldDB; B3Y613; -.
DR   SMR; B3Y613; -.
DR   STRING; 9598.ENSPTRP00000028379; -.
DR   GlyCosmos; B3Y613; 4 sites, No reported glycans.
DR   PaxDb; 9598-ENSPTRP00000028379; -.
DR   GeneID; 471325; -.
DR   KEGG; ptr:471325; -.
DR   CTD; 7097; -.
DR   eggNOG; KOG4641; Eukaryota.
DR   InParanoid; B3Y613; -.
DR   OrthoDB; 21383at2759; -.
DR   Proteomes; UP000002277; Unplaced.
DR   GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR   GO; GO:0045121; C:membrane raft; ISS:UniProtKB.
DR   GO; GO:0030670; C:phagocytic vesicle membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0050135; F:NAD(P)+ nucleosidase activity; IEA:UniProtKB-EC.
DR   GO; GO:0061809; F:NAD+ nucleotidase, cyclic ADP-ribose generating; IEA:UniProtKB-EC.
DR   GO; GO:0038023; F:signaling receptor activity; IBA:GO_Central.
DR   GO; GO:0004888; F:transmembrane signaling receptor activity; IEA:InterPro.
DR   GO; GO:0042497; F:triacyl lipopeptide binding; IBA:GO_Central.
DR   GO; GO:0071726; P:cellular response to diacyl bacterial lipopeptide; ISS:UniProtKB.
DR   GO; GO:0071727; P:cellular response to triacyl bacterial lipopeptide; ISS:UniProtKB.
DR   GO; GO:0006954; P:inflammatory response; IBA:GO_Central.
DR   GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR   GO; GO:0002224; P:toll-like receptor signaling pathway; IBA:GO_Central.
DR   Gene3D; 3.80.10.10; Ribonuclease Inhibitor; 1.
DR   Gene3D; 3.40.50.10140; Toll/interleukin-1 receptor homology (TIR) domain; 1.
DR   InterPro; IPR000483; Cys-rich_flank_reg_C.
DR   InterPro; IPR001611; Leu-rich_rpt.
DR   InterPro; IPR003591; Leu-rich_rpt_typical-subtyp.
DR   InterPro; IPR032675; LRR_dom_sf.
DR   InterPro; IPR000157; TIR_dom.
DR   InterPro; IPR017241; Toll-like_receptor.
DR   InterPro; IPR035897; Toll_tir_struct_dom_sf.
DR   PANTHER; PTHR24365; TOLL-LIKE RECEPTOR; 1.
DR   PANTHER; PTHR24365:SF17; TOLL-LIKE RECEPTOR 2; 1.
DR   Pfam; PF00560; LRR_1; 1.
DR   Pfam; PF13855; LRR_8; 2.
DR   Pfam; PF01463; LRRCT; 1.
DR   Pfam; PF01582; TIR; 1.
DR   PIRSF; PIRSF037595; Toll-like_receptor; 1.
DR   PRINTS; PR01537; INTRLKN1R1F.
DR   PRINTS; PR00019; LEURICHRPT.
DR   SMART; SM00364; LRR_BAC; 3.
DR   SMART; SM00365; LRR_SD22; 5.
DR   SMART; SM00369; LRR_TYP; 7.
DR   SMART; SM00082; LRRCT; 1.
DR   SMART; SM00255; TIR; 1.
DR   SUPFAM; SSF52058; L domain-like; 2.
DR   SUPFAM; SSF52047; RNI-like; 1.
DR   SUPFAM; SSF52200; Toll/Interleukin receptor TIR domain; 1.
DR   PROSITE; PS51450; LRR; 11.
DR   PROSITE; PS50104; TIR; 1.
PE   2: Evidence at transcript level;
KW   Cytoplasmic vesicle; Disulfide bond; Glycoprotein; Immunity;
KW   Inflammatory response; Innate immunity; Isopeptide bond;
KW   Leucine-rich repeat; Membrane; NAD; Receptor; Reference proteome; Repeat;
KW   Signal; Transmembrane; Transmembrane helix; Ubl conjugation.
FT   SIGNAL          1..20
FT                   /evidence="ECO:0000255"
FT   CHAIN           21..784
FT                   /note="Toll-like receptor 2"
FT                   /id="PRO_0000363777"
FT   TOPO_DOM        21..587
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        588..608
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        609..784
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   REPEAT          54..77
FT                   /note="LRR 1"
FT   REPEAT          78..101
FT                   /note="LRR 2"
FT   REPEAT          102..125
FT                   /note="LRR 3"
FT   REPEAT          126..150
FT                   /note="LRR 4"
FT   REPEAT          151..175
FT                   /note="LRR 5"
FT   REPEAT          176..199
FT                   /note="LRR 6"
FT   REPEAT          200..223
FT                   /note="LRR 7"
FT   REPEAT          224..250
FT                   /note="LRR 8"
FT   REPEAT          251..278
FT                   /note="LRR 9"
FT   REPEAT          279..308
FT                   /note="LRR 10"
FT   REPEAT          309..337
FT                   /note="LRR 11"
FT   REPEAT          338..361
FT                   /note="LRR 12"
FT   REPEAT          362..388
FT                   /note="LRR 13"
FT   REPEAT          389..414
FT                   /note="LRR 14"
FT   REPEAT          415..437
FT                   /note="LRR 15"
FT   REPEAT          438..457
FT                   /note="LRR 16"
FT   REPEAT          458..478
FT                   /note="LRR 17"
FT   REPEAT          479..500
FT                   /note="LRR 18"
FT   REPEAT          501..524
FT                   /note="LRR 19"
FT   DOMAIN          525..579
FT                   /note="LRRCT"
FT   DOMAIN          639..782
FT                   /note="TIR"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00204"
FT   MOTIF           761..778
FT                   /note="ATG16L1-binding motif"
FT   SITE            349
FT                   /note="Interaction with bacterial lipopeptide"
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        114
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        199
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        414
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        442
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        30..36
FT                   /evidence="ECO:0000250"
FT   DISULFID        353..382
FT                   /evidence="ECO:0000250"
FT   DISULFID        432..454
FT                   /evidence="ECO:0000250"
FT   CROSSLNK        754
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in ubiquitin)"
FT                   /evidence="ECO:0000250|UniProtKB:O60603"
SQ   SEQUENCE   784 AA;  89825 MW;  9F46005D894F7CB5 CRC64;
     MPHTLWMVWV LGVIISLSKE ESSNQASLSC DRNGICKGSS GSLNSIPSGL TEAVKSLDLS
     NNRITYISNS DLQRCVNLQA LVLTSNGINT IEEDSFSSLG SLEHLDLSYN YLSNLSSSWF
     KPLSSLTFLN LLGNPYKTLG ETSLFSHLTK LQILRVGNMD TFTKIQRKDF AGLTFLEELE
     IDASDLQSYE PKSLKSIQNV SHLILHMKQH ILLLEIFVDV TSSVECLELR DTDLDTFRFS
     ELSTGETNSL IKKFTFRNVK ITDESLFQVM KLLNQISGLL ELEFDDCTLN GVGNFRASDN
     DRVIDPGKVE TLTIRRLHIP RFYLFYDLST LYSLTERVKR ITVENSKVFL VPCLLSQHLK
     SLEYLDLSEN LIVEEYLKNS ACEDAWPSLQ TLILRQNHLA SLEKTGETLL TLKNLTNVDI
     SKNSFHSMPE TCQWPEKMKY LNLSSTRIHS VTGCIPKTLE ILDVSNNNLN LFSLNLPQLK
     ELYISRNKLM TLPDASLLPM LLVLKISRNA ITTFSKEQLD SFHTLKTLEA GGNNFICSCE
     FLSFTQEQQA LAKVLIDWPA NYLCDSPSHV RGQQVQDVRL SVSECHRTAL VSGMCCALFL
     LILLTGVLCH RFHGLWYMKM MWAWLQAKRK PRKAPSRNIC YDAFVSYSER DAYWVENLMV
     QELENFNPPF KLCLHKRDFI PGKWIIDNII DSIEKSHKTV FVLSENFVKS EWCKYELDFS
     HFRLFDENND AAILILLEPI EKKAIPQRFC KLRKIMNTKT YLEWPMDEAQ REGFWVNLRA
     AIKS
//