TLR9

Functionⁱ

Key component of innate and adaptive immunity. TLRs (Toll-like receptors) control host immune response against pathogens through recognition of molecular patterns specific to microorganisms. TLR9 is a nucleotide-sensing TLR which is activated by unmethylated cytidine-phosphate-guanosine (CpG) dinucleotides. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response (PubMed:11564765, PubMed:17932028).

Controls lymphocyte response to Helicobacter infection (By similarity).

Upon CpG stimulation, induces B-cell proliferation, activation, survival and antibody production (PubMed:23857366).

By similarity3 Publications

Sites

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Binding siteⁱ	132	DNA; binds CpG-DNABy similarity		1
Binding siteⁱ	208	DNA; binds CpG-DNABy similarity		1

GO - Molecular functionⁱ

Complete GO annotation on QuickGO ...

GO - Biological processⁱ

Complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Receptor
Biological process	Immunity, Inflammatory response, Innate immunity

Enzyme and pathway databases

PathwayCommonsⁱ	Q9NR96
Reactomeⁱ	R-HSA-109704, PI3K Cascade R-HSA-1679131, Trafficking and processing of endosomal TLR R-HSA-168138, Toll Like Receptor 9 (TLR9) Cascade R-HSA-9679191, Potential therapeutics for SARS R-HSA-975110, TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling R-HSA-975138, TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation R-HSA-975155, MyD88 dependent cascade initiated on endosome
SignaLinkⁱ	Q9NR96
SIGNORⁱ	Q9NR96

Names & Taxonomyⁱ

Protein namesⁱ	Recommended name: Toll-like receptor 9 Alternative name(s): CD_antigen: CD289
Gene namesⁱ	Name:TLR9 ORF Names:UNQ5798/PRO19605
Organismⁱ	Homo sapiens (Human)
Taxonomic identifierⁱ	9606 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo
Proteomesⁱ	UP000005640 Componentⁱ: Chromosome 3

Organism-specific databases

Human Gene Nomenclature Database More...HGNCⁱ	HGNC:15633, TLR9
MIMⁱ	605474, gene
neXtProtⁱ	NX_Q9NR96
VEuPathDBⁱ	HostDB:ENSG00000239732

Topology

Feature key	Position(s)	DescriptionActions	Length
Topological domainⁱ	26 – 818	ExtracellularSequence analysisAdd BLAST	793
Transmembraneⁱ	819 – 839	HelicalSequence analysisAdd BLAST	21
Topological domainⁱ	840 – 1032	CytoplasmicSequence analysisAdd BLAST	193

Keywords - Cellular componentⁱ

Cytoplasmic vesicle, Endoplasmic reticulum, Endosome, Lysosome, Membrane

Pathology & Biotechⁱ

Organism-specific databases

DisGeNET More...DisGeNETⁱ	54106
Open Targets More...OpenTargetsⁱ	ENSG00000239732
PharmGKBⁱ	PA38010

Miscellaneous databases

Pharosⁱ	Q9NR96, Tclin

Pharosⁱ

Q9NR96, Tclin

Chemistry databases

ChEMBLⁱ	CHEMBL5804
Drug and drug target database More...DrugBankⁱ	DB00608, Chloroquine DB05530, CPG 10101 DB05475, Golotimod DB01611, Hydroxychloroquine DB05463, ISS-1018
DrugCentral More...DrugCentralⁱ	Q9NR96
IUPHAR/BPS Guide to PHARMACOLOGY More...GuidetoPHARMACOLOGYⁱ	1759

Genetic variation databases

BioMutaⁱ	TLR9
DMDMⁱ	20140872

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Signal peptideⁱ	1 – 25	Sequence analysisAdd BLAST		25
ChainⁱPRO_0000034737	26 – 1032	Toll-like receptor 9Add BLAST		1007

Amino acid modifications

Feature key	Position(s)	DescriptionActions	Length
Disulfide bondⁱ	35 ↔ 45	By similarity
Glycosylationⁱ	64	N-linked (GlcNAc...) asparagineSequence analysis	1
Disulfide bondⁱ	98 ↔ 110	By similarity
Glycosylationⁱ	129	N-linked (GlcNAc...) asparagineSequence analysis	1
Disulfide bondⁱ	178 ↔ 184	By similarity
Glycosylationⁱ	200	N-linked (GlcNAc...) asparagineSequence analysis	1
Glycosylationⁱ	210	N-linked (GlcNAc...) asparagineSequence analysis	1
Glycosylationⁱ	242	N-linked (GlcNAc...) asparagineSequence analysis	1
Disulfide bondⁱ	255 ↔ 268	By similarity
Disulfide bondⁱ	258 ↔ 265	By similarity
Glycosylationⁱ	300	N-linked (GlcNAc...) asparagineSequence analysis	1
Glycosylationⁱ	340	N-linked (GlcNAc...) asparagineSequence analysis	1
Glycosylationⁱ	469	N-linked (GlcNAc...) asparagineSequence analysis	1
Disulfide bondⁱ	470 ↔ 500	By similarity
Glycosylationⁱ	474	N-linked (GlcNAc...) asparagineSequence analysis	1
Glycosylationⁱ	513	N-linked (GlcNAc...) asparagineSequence analysis	1
Glycosylationⁱ	567	N-linked (GlcNAc...) asparagineSequence analysis	1
Glycosylationⁱ	694	N-linked (GlcNAc...) asparagineSequence analysis	1
Glycosylationⁱ	731	N-linked (GlcNAc...) asparagineSequence analysis	1
Disulfide bondⁱ	764 ↔ 790	By similarity
Disulfide bondⁱ	766 ↔ 809	By similarity

Post-translational modificationⁱ

Activated by proteolytic cleavage of the flexible loop between repeats LRR14 and LRR15 within the ectodomain. Cleavage requires UNC93B1. Proteolytically processed by first removing the majority of the ectodomain by either asparagine endopeptidase (AEP) or a cathepsin followed by a trimming event that is solely cathepsin mediated and required for optimal receptor signaling.By similarity

Keywords - PTMⁱ

Disulfide bond, Glycoprotein

Proteomic databases

jPOSTⁱ	Q9NR96
MassIVEⁱ	Q9NR96
MaxQB - The MaxQuant DataBase More...MaxQBⁱ	Q9NR96
PaxDbⁱ	Q9NR96
PeptideAtlas More...PeptideAtlasⁱ	Q9NR96
PRIDEⁱ	Q9NR96

PTM databases

GlyGenⁱ	Q9NR96, 15 sites, 1 O-linked glycan (1 site)
iPTMnetⁱ	Q9NR96
PhosphoSitePlusⁱ	Q9NR96

Expressionⁱ

Tissue specificityⁱ

Highly expressed in spleen, lymph node, tonsil and peripheral blood leukocytes, especially in plasmacytoid pre-dendritic cells. Levels are much lower in monocytes and CD11c+ immature dendritic cells. Also detected in lung and liver.

Gene expression databases

Bgeeⁱ	ENSG00000239732, Expressed in blood and 84 other tissues
Genevisibleⁱ	Q9NR96, HS

Organism-specific databases

Human Protein Atlas More...HPAⁱ	ENSG00000239732, Tissue enhanced (brain, lymphoid tissue)

HPAⁱ

ENSG00000239732, Tissue enhanced (brain, lymphoid tissue)

Interactionⁱ

Subunit structureⁱ

Monomer and homodimer. Exists as a monomer in the absence of unmethylated cytidine-phosphate-guanosine (CpG) ligand. Proteolytic processing of an insertion loop (Z-loop) is required for homodimerization upon binding to the unmethylated CpG ligand leading to its activation (By similarity).

Interacts with MYD88 via their respective TIR domains (By similarity).

Interacts with BTK (PubMed:17932028).

Interacts (via transmembrane domain) with UNC93B1.

Interacts with CD300LH; the interaction may promote full activation of TLR9-triggered innate responses (By similarity).

Interacts with CNPY3 and HSP90B1; this interaction is required for proper folding in the endoplasmic reticulum (PubMed:20865800).

Interacts with SMPDL3B (By similarity).

By similarity2 Publications

GO - Molecular functionⁱ

Complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGRIDⁱ	119902, 66 interactors
Database of interacting proteins More...DIPⁱ	DIP-52371N
IntActⁱ	Q9NR96, 15 interactors
STRINGⁱ	9606.ENSP00000353874

Chemistry databases

BindingDBⁱ

Q9NR96

Miscellaneous databases

RNActⁱ	Q9NR96, protein

RNActⁱ

Q9NR96, protein

Structureⁱ

3D structure databases

SMRⁱ	Q9NR96
ModBaseⁱ	Search...

Family & Domainsⁱ

Domains and Repeats

Feature key	Position(s)	DescriptionActions	Length
Repeatⁱ	62 – 85	LRR 1Add BLAST	24
Repeatⁱ	87 – 110	LRR 2Add BLAST	24
Repeatⁱ	122 – 147	LRR 3Add BLAST	26
Repeatⁱ	150 – 166	LRR 4Add BLAST	17
Repeatⁱ	167 – 190	LRR 5Add BLAST	24
Repeatⁱ	198 – 221	LRR 6Add BLAST	24
Repeatⁱ	223 – 242	LRR 7Add BLAST	20
Repeatⁱ	243 – 268	LRR 8Add BLAST	26
Repeatⁱ	283 – 306	LRR 9Add BLAST	24
Repeatⁱ	308 – 332	LRR 10Add BLAST	25
Repeatⁱ	333 – 356	LRR 11Add BLAST	24
Repeatⁱ	363 – 386	LRR 12Add BLAST	24
Repeatⁱ	390 – 413	LRR 13Add BLAST	24
Repeatⁱ	415 – 440	LRR 14Add BLAST	26
Repeatⁱ	470 – 494	LRR 15Add BLAST	25
Repeatⁱ	496 – 519	LRR 16Add BLAST	24
Repeatⁱ	520 – 543	LRR 17Add BLAST	24
Repeatⁱ	545 – 572	LRR 18Add BLAST	28
Repeatⁱ	574 – 598	LRR 19Add BLAST	25
Repeatⁱ	600 – 622	LRR 20Add BLAST	23
Repeatⁱ	627 – 650	LRR 21Add BLAST	24
Repeatⁱ	652 – 675	LRR 22Add BLAST	24
Repeatⁱ	676 – 699	LRR 23Add BLAST	24
Repeatⁱ	701 – 723	LRR 24Add BLAST	23
Repeatⁱ	724 – 747	LRR 25Add BLAST	24
Repeatⁱ	749 – 772	LRR 26Add BLAST	24
Domainⁱ	868 – 1013	TIRPROSITE-ProRule annotationAdd BLAST	146

Region

Feature key	Position(s)	DescriptionActions	Length
Regionⁱ	47 – 51	DNA binding; binds CpG-DNABy similarity	5
Regionⁱ	72 – 77	DNA binding; binds CpG-DNABy similarity	6
Regionⁱ	95 – 109	DNA binding; binds CpG-DNABy similarityAdd BLAST	15
Regionⁱ	179 – 181	DNA binding; binds CpG-DNABy similarity	3

Sequence similaritiesⁱ

Belongs to the Toll-like receptor family.Curated

Keywords - Domainⁱ

Leucine-rich repeat, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGⁱ	KOG1747, Eukaryota KOG4641, Eukaryota
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00940000162493
HOGENOMⁱ	CLU_006000_2_0_1
InParanoidⁱ	Q9NR96
Database of Orthologous Groups More...OrthoDBⁱ	264244at2759
PhylomeDBⁱ	Q9NR96
TreeFamⁱ	TF325595

Family and domain databases

Gene3Dⁱ	3.40.50.10140, 1 hit 3.80.10.10, 1 hit
InterProⁱ	View protein in InterPro IPR001611, Leu-rich_rpt IPR003591, Leu-rich_rpt_typical-subtyp IPR041283, LRR_12 IPR032675, LRR_dom_sf IPR000157, TIR_dom IPR027181, TLR9 IPR035897, Toll_tir_struct_dom_sf
PANTHERⁱ	PTHR47410:SF3, PTHR47410:SF3, 1 hit
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF18837, LRR_12, 1 hit PF13516, LRR_6, 2 hits PF13855, LRR_8, 7 hits PF01582, TIR, 1 hit
SMARTⁱ	View protein in SMART SM00369, LRR_TYP, 18 hits SM00255, TIR, 1 hit
SUPFAMⁱ	SSF52200, SSF52200, 1 hit
PROSITEⁱ	View protein in PROSITE PS51450, LRR, 17 hits PS50104, TIR, 1 hit

Sequences (5)ⁱ

Sequence statusⁱ: Complete.

Sequence processingⁱ: The displayed sequence is further processed into a mature form.

This entry describes 5 isoformsⁱ produced by alternative splicing. Align Add to basket

Note: Additional isoforms seem to exist.

Isoform 1 (identifier: Q9NR96-1) [UniParc]FASTA Add to basket

Also known as: A

This isoform has been chosen as the canonicalⁱ sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

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        10         20         30         40         50
MGFCRSALHP LSLLVQAIML AMTLALGTLP AFLPCELQPH GLVNCNWLFL 
        60         70         80         90        100
KSVPHFSMAA PRGNVTSLSL SSNRIHHLHD SDFAHLPSLR HLNLKWNCPP 
       110        120        130        140        150
VGLSPMHFPC HMTIEPSTFL AVPTLEELNL SYNNIMTVPA LPKSLISLSL 
       160        170        180        190        200
SHTNILMLDS ASLAGLHALR FLFMDGNCYY KNPCRQALEV APGALLGLGN 
       210        220        230        240        250
LTHLSLKYNN LTVVPRNLPS SLEYLLLSYN RIVKLAPEDL ANLTALRVLD 
       260        270        280        290        300
VGGNCRRCDH APNPCMECPR HFPQLHPDTF SHLSRLEGLV LKDSSLSWLN 
       310        320        330        340        350
ASWFRGLGNL RVLDLSENFL YKCITKTKAF QGLTQLRKLN LSFNYQKRVS 
       360        370        380        390        400
FAHLSLAPSF GSLVALKELD MHGIFFRSLD ETTLRPLARL PMLQTLRLQM 
       410        420        430        440        450
NFINQAQLGI FRAFPGLRYV DLSDNRISGA SELTATMGEA DGGEKVWLQP 
       460        470        480        490        500
GDLAPAPVDT PSSEDFRPNC STLNFTLDLS RNNLVTVQPE MFAQLSHLQC 
       510        520        530        540        550
LRLSHNCISQ AVNGSQFLPL TGLQVLDLSH NKLDLYHEHS FTELPRLEAL 
       560        570        580        590        600
DLSYNSQPFG MQGVGHNFSF VAHLRTLRHL SLAHNNIHSQ VSQQLCSTSL 
       610        620        630        640        650
RALDFSGNAL GHMWAEGDLY LHFFQGLSGL IWLDLSQNRL HTLLPQTLRN 
       660        670        680        690        700
LPKSLQVLRL RDNYLAFFKW WSLHFLPKLE VLDLAGNQLK ALTNGSLPAG 
       710        720        730        740        750
TRLRRLDVSC NSISFVAPGF FSKAKELREL NLSANALKTV DHSWFGPLAS 
       760        770        780        790        800
ALQILDVSAN PLHCACGAAF MDFLLEVQAA VPGLPSRVKC GSPGQLQGLS 
       810        820        830        840        850
IFAQDLRLCL DEALSWDCFA LSLLAVALGL GVPMLHHLCG WDLWYCFHLC 
       860        870        880        890        900
LAWLPWRGRQ SGRDEDALPY DAFVVFDKTQ SAVADWVYNE LRGQLEECRG 
       910        920        930        940        950
RWALRLCLEE RDWLPGKTLF ENLWASVYGS RKTLFVLAHT DRVSGLLRAS 
       960        970        980        990       1000
FLLAQQRLLE DRKDVVVLVI LSPDGRRSRY VRLRQRLCRQ SVLLWPHQPS 
      1010       1020       1030 
GQRSFWAQLG MALTRDNHHF YNRNFCQGPT AE

Length:1,032

Mass (Da):115,860

Last modified:January 31, 2002 - v2

Checksum:ⁱ71280AA9680EDCE2

GO

Isoform 2 (identifier: Q9NR96-2) [UniParc]FASTA Add to basket

Also known as: B

The sequence of this isoform differs from the canonical sequence as follows:
1-57: Missing.

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        10         20         30         40         50
MAAPRGNVTS LSLSSNRIHH LHDSDFAHLP SLRHLNLKWN CPPVGLSPMH 
        60         70         80         90        100
FPCHMTIEPS TFLAVPTLEE LNLSYNNIMT VPALPKSLIS LSLSHTNILM 
       110        120        130        140        150
LDSASLAGLH ALRFLFMDGN CYYKNPCRQA LEVAPGALLG LGNLTHLSLK 
       160        170        180        190        200
YNNLTVVPRN LPSSLEYLLL SYNRIVKLAP EDLANLTALR VLDVGGNCRR 
       210        220        230        240        250
CDHAPNPCME CPRHFPQLHP DTFSHLSRLE GLVLKDSSLS WLNASWFRGL 
       260        270        280        290        300
GNLRVLDLSE NFLYKCITKT KAFQGLTQLR KLNLSFNYQK RVSFAHLSLA 
       310        320        330        340        350
PSFGSLVALK ELDMHGIFFR SLDETTLRPL ARLPMLQTLR LQMNFINQAQ 
       360        370        380        390        400
LGIFRAFPGL RYVDLSDNRI SGASELTATM GEADGGEKVW LQPGDLAPAP 
       410        420        430        440        450
VDTPSSEDFR PNCSTLNFTL DLSRNNLVTV QPEMFAQLSH LQCLRLSHNC 
       460        470        480        490        500
ISQAVNGSQF LPLTGLQVLD LSHNKLDLYH EHSFTELPRL EALDLSYNSQ 
       510        520        530        540        550
PFGMQGVGHN FSFVAHLRTL RHLSLAHNNI HSQVSQQLCS TSLRALDFSG 
       560        570        580        590        600
NALGHMWAEG DLYLHFFQGL SGLIWLDLSQ NRLHTLLPQT LRNLPKSLQV 
       610        620        630        640        650
LRLRDNYLAF FKWWSLHFLP KLEVLDLAGN QLKALTNGSL PAGTRLRRLD 
       660        670        680        690        700
VSCNSISFVA PGFFSKAKEL RELNLSANAL KTVDHSWFGP LASALQILDV 
       710        720        730        740        750
SANPLHCACG AAFMDFLLEV QAAVPGLPSR VKCGSPGQLQ GLSIFAQDLR 
       760        770        780        790        800
LCLDEALSWD CFALSLLAVA LGLGVPMLHH LCGWDLWYCF HLCLAWLPWR 
       810        820        830        840        850
GRQSGRDEDA LPYDAFVVFD KTQSAVADWV YNELRGQLEE CRGRWALRLC 
       860        870        880        890        900
LEERDWLPGK TLFENLWASV YGSRKTLFVL AHTDRVSGLL RASFLLAQQR 
       910        920        930        940        950
LLEDRKDVVV LVILSPDGRR SRYVRLRQRL CRQSVLLWPH QPSGQRSFWA 
       960        970 
QLGMALTRDN HHFYNRNFCQ GPTAE

Show »

Length:975

Mass (Da):109,628

Checksum:ⁱ61D105163587A75F

GO

Isoform 3 (identifier: Q9NR96-3) [UniParc]FASTA Add to basket

The sequence of this isoform differs from the canonical sequence as follows:
1-1: M → MPMKWSGWRWSWGPATHTALPPPQ

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        10         20         30         40         50
MPMKWSGWRW SWGPATHTAL PPPQGFCRSA LHPLSLLVQA IMLAMTLALG 
        60         70         80         90        100
TLPAFLPCEL QPHGLVNCNW LFLKSVPHFS MAAPRGNVTS LSLSSNRIHH 
       110        120        130        140        150
LHDSDFAHLP SLRHLNLKWN CPPVGLSPMH FPCHMTIEPS TFLAVPTLEE 
       160        170        180        190        200
LNLSYNNIMT VPALPKSLIS LSLSHTNILM LDSASLAGLH ALRFLFMDGN 
       210        220        230        240        250
CYYKNPCRQA LEVAPGALLG LGNLTHLSLK YNNLTVVPRN LPSSLEYLLL 
       260        270        280        290        300
SYNRIVKLAP EDLANLTALR VLDVGGNCRR CDHAPNPCME CPRHFPQLHP 
       310        320        330        340        350
DTFSHLSRLE GLVLKDSSLS WLNASWFRGL GNLRVLDLSE NFLYKCITKT 
       360        370        380        390        400
KAFQGLTQLR KLNLSFNYQK RVSFAHLSLA PSFGSLVALK ELDMHGIFFR 
       410        420        430        440        450
SLDETTLRPL ARLPMLQTLR LQMNFINQAQ LGIFRAFPGL RYVDLSDNRI 
       460        470        480        490        500
SGASELTATM GEADGGEKVW LQPGDLAPAP VDTPSSEDFR PNCSTLNFTL 
       510        520        530        540        550
DLSRNNLVTV QPEMFAQLSH LQCLRLSHNC ISQAVNGSQF LPLTGLQVLD 
       560        570        580        590        600
LSHNKLDLYH EHSFTELPRL EALDLSYNSQ PFGMQGVGHN FSFVAHLRTL 
       610        620        630        640        650
RHLSLAHNNI HSQVSQQLCS TSLRALDFSG NALGHMWAEG DLYLHFFQGL 
       660        670        680        690        700
SGLIWLDLSQ NRLHTLLPQT LRNLPKSLQV LRLRDNYLAF FKWWSLHFLP 
       710        720        730        740        750
KLEVLDLAGN QLKALTNGSL PAGTRLRRLD VSCNSISFVA PGFFSKAKEL 
       760        770        780        790        800
RELNLSANAL KTVDHSWFGP LASALQILDV SANPLHCACG AAFMDFLLEV 
       810        820        830        840        850
QAAVPGLPSR VKCGSPGQLQ GLSIFAQDLR LCLDEALSWD CFALSLLAVA 
       860        870        880        890        900
LGLGVPMLHH LCGWDLWYCF HLCLAWLPWR GRQSGRDEDA LPYDAFVVFD 
       910        920        930        940        950
KTQSAVADWV YNELRGQLEE CRGRWALRLC LEERDWLPGK TLFENLWASV 
       960        970        980        990       1000
YGSRKTLFVL AHTDRVSGLL RASFLLAQQR LLEDRKDVVV LVILSPDGRR 
      1010       1020       1030       1040       1050
SRYVRLRQRL CRQSVLLWPH QPSGQRSFWA QLGMALTRDN HHFYNRNFCQ 

GPTAE

Show »

Length:1,055

Mass (Da):118,517

Checksum:ⁱ4072A104D14022F6

GO

Isoform 4 (identifier: Q9NR96-4) [UniParc]FASTA Add to basket

The sequence of this isoform differs from the canonical sequence as follows:
1-1: M → MLYSSCKSRLLDSVEQDFHLEIAKK

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        10         20         30         40         50
MLYSSCKSRL LDSVEQDFHL EIAKKGFCRS ALHPLSLLVQ AIMLAMTLAL 
        60         70         80         90        100
GTLPAFLPCE LQPHGLVNCN WLFLKSVPHF SMAAPRGNVT SLSLSSNRIH 
       110        120        130        140        150
HLHDSDFAHL PSLRHLNLKW NCPPVGLSPM HFPCHMTIEP STFLAVPTLE 
       160        170        180        190        200
ELNLSYNNIM TVPALPKSLI SLSLSHTNIL MLDSASLAGL HALRFLFMDG 
       210        220        230        240        250
NCYYKNPCRQ ALEVAPGALL GLGNLTHLSL KYNNLTVVPR NLPSSLEYLL 
       260        270        280        290        300
LSYNRIVKLA PEDLANLTAL RVLDVGGNCR RCDHAPNPCM ECPRHFPQLH 
       310        320        330        340        350
PDTFSHLSRL EGLVLKDSSL SWLNASWFRG LGNLRVLDLS ENFLYKCITK 
       360        370        380        390        400
TKAFQGLTQL RKLNLSFNYQ KRVSFAHLSL APSFGSLVAL KELDMHGIFF 
       410        420        430        440        450
RSLDETTLRP LARLPMLQTL RLQMNFINQA QLGIFRAFPG LRYVDLSDNR 
       460        470        480        490        500
ISGASELTAT MGEADGGEKV WLQPGDLAPA PVDTPSSEDF RPNCSTLNFT 
       510        520        530        540        550
LDLSRNNLVT VQPEMFAQLS HLQCLRLSHN CISQAVNGSQ FLPLTGLQVL 
       560        570        580        590        600
DLSHNKLDLY HEHSFTELPR LEALDLSYNS QPFGMQGVGH NFSFVAHLRT 
       610        620        630        640        650
LRHLSLAHNN IHSQVSQQLC STSLRALDFS GNALGHMWAE GDLYLHFFQG 
       660        670        680        690        700
LSGLIWLDLS QNRLHTLLPQ TLRNLPKSLQ VLRLRDNYLA FFKWWSLHFL 
       710        720        730        740        750
PKLEVLDLAG NQLKALTNGS LPAGTRLRRL DVSCNSISFV APGFFSKAKE 
       760        770        780        790        800
LRELNLSANA LKTVDHSWFG PLASALQILD VSANPLHCAC GAAFMDFLLE 
       810        820        830        840        850
VQAAVPGLPS RVKCGSPGQL QGLSIFAQDL RLCLDEALSW DCFALSLLAV 
       860        870        880        890        900
ALGLGVPMLH HLCGWDLWYC FHLCLAWLPW RGRQSGRDED ALPYDAFVVF 
       910        920        930        940        950
DKTQSAVADW VYNELRGQLE ECRGRWALRL CLEERDWLPG KTLFENLWAS 
       960        970        980        990       1000
VYGSRKTLFV LAHTDRVSGL LRASFLLAQQ RLLEDRKDVV VLVILSPDGR 
      1010       1020       1030       1040       1050
RSRYVRLRQR LCRQSVLLWP HQPSGQRSFW AQLGMALTRD NHHFYNRNFC 

QGPTAE

Show »

Length:1,056

Mass (Da):118,652

Checksum:ⁱ9159C051473E88FC

GO

Isoform 5 (identifier: Q9NR96-5) [UniParc]FASTA Add to basket

The sequence of this isoform differs from the canonical sequence as follows:
1-16: MGFCRSALHPLSLLVQ → M

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        10         20         30         40         50
MAIMLAMTLA LGTLPAFLPC ELQPHGLVNC NWLFLKSVPH FSMAAPRGNV 
        60         70         80         90        100
TSLSLSSNRI HHLHDSDFAH LPSLRHLNLK WNCPPVGLSP MHFPCHMTIE 
       110        120        130        140        150
PSTFLAVPTL EELNLSYNNI MTVPALPKSL ISLSLSHTNI LMLDSASLAG 
       160        170        180        190        200
LHALRFLFMD GNCYYKNPCR QALEVAPGAL LGLGNLTHLS LKYNNLTVVP 
       210        220        230        240        250
RNLPSSLEYL LLSYNRIVKL APEDLANLTA LRVLDVGGNC RRCDHAPNPC 
       260        270        280        290        300
MECPRHFPQL HPDTFSHLSR LEGLVLKDSS LSWLNASWFR GLGNLRVLDL 
       310        320        330        340        350
SENFLYKCIT KTKAFQGLTQ LRKLNLSFNY QKRVSFAHLS LAPSFGSLVA 
       360        370        380        390        400
LKELDMHGIF FRSLDETTLR PLARLPMLQT LRLQMNFINQ AQLGIFRAFP 
       410        420        430        440        450
GLRYVDLSDN RISGASELTA TMGEADGGEK VWLQPGDLAP APVDTPSSED 
       460        470        480        490        500
FRPNCSTLNF TLDLSRNNLV TVQPEMFAQL SHLQCLRLSH NCISQAVNGS 
       510        520        530        540        550
QFLPLTGLQV LDLSHNKLDL YHEHSFTELP RLEALDLSYN SQPFGMQGVG 
       560        570        580        590        600
HNFSFVAHLR TLRHLSLAHN NIHSQVSQQL CSTSLRALDF SGNALGHMWA 
       610        620        630        640        650
EGDLYLHFFQ GLSGLIWLDL SQNRLHTLLP QTLRNLPKSL QVLRLRDNYL 
       660        670        680        690        700
AFFKWWSLHF LPKLEVLDLA GNQLKALTNG SLPAGTRLRR LDVSCNSISF 
       710        720        730        740        750
VAPGFFSKAK ELRELNLSAN ALKTVDHSWF GPLASALQIL DVSANPLHCA 
       760        770        780        790        800
CGAAFMDFLL EVQAAVPGLP SRVKCGSPGQ LQGLSIFAQD LRLCLDEALS 
       810        820        830        840        850
WDCFALSLLA VALGLGVPML HHLCGWDLWY CFHLCLAWLP WRGRQSGRDE 
       860        870        880        890        900
DALPYDAFVV FDKTQSAVAD WVYNELRGQL EECRGRWALR LCLEERDWLP 
       910        920        930        940        950
GKTLFENLWA SVYGSRKTLF VLAHTDRVSG LLRASFLLAQ QRLLEDRKDV 
       960        970        980        990       1000
VVLVILSPDG RRSRYVRLRQ RLCRQSVLLW PHQPSGQRSF WAQLGMALTR 
      1010 
DNHHFYNRNF CQGPTAE

Show »

Length:1,017

Mass (Da):114,237

Checksum:ⁱ7EF80765E4675C9C

GO

Experimental Info

Feature key	Position(s)	DescriptionActions	Length
Sequence conflictⁱ	200	N → S in AAQ89443 (PubMed:12975309).Curated	1
Sequence conflictⁱ	330	F → L in AAQ89443 (PubMed:12975309).Curated	1
Sequence conflictⁱ	530	H → R in AAF78037 (PubMed:11022120).Curated	1
Sequence conflictⁱ	688	Q → R in AAF78037 (PubMed:11022120).Curated	1

Natural variant

Feature key	Position(s)	DescriptionActions	Length
Natural variantⁱVAR_024668	5	R → C. Corresponds to variant dbSNP:rs5743842EnsemblClinVar.	1
Natural variantⁱVAR_052364	79	H → Q. Corresponds to variant dbSNP:rs5743843Ensembl.	1
Natural variantⁱVAR_034555	863	R → Q. Corresponds to variant dbSNP:rs5743845EnsemblClinVar.	1
Natural variantⁱVAR_052365	882	A → T. Corresponds to variant dbSNP:rs5743846Ensembl.	1
Natural variantⁱVAR_036077	901	R → H in a colorectal cancer sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs755472700Ensembl.	1
Natural variantⁱVAR_036078	933	T → M in a colorectal cancer sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs746622200Ensembl.	1

Alternative sequence

Feature key	Position(s)	DescriptionActions	Length
Alternative sequenceⁱVSP_006520	1 – 57	Missing in isoform 2. 1 PublicationAdd BLAST	57
Alternative sequenceⁱVSP_006523	1 – 16	MGFCR…SLLVQ → M in isoform 5. 1 PublicationAdd BLAST	16
Alternative sequenceⁱVSP_006521	1	M → MPMKWSGWRWSWGPATHTAL PPPQ in isoform 3. 1 Publication	1
Alternative sequenceⁱVSP_006522	1	M → MLYSSCKSRLLDSVEQDFHL EIAKK in isoform 4. 1 Publication	1

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	AF259262 mRNA Translation: AAF72189.1 AF259263 mRNA Translation: AAF72190.1 AF245704 mRNA Translation: AAF78037.1 AF246972 mRNA Translation: AAG01734.1 AF246973 mRNA Translation: AAG01735.1 AF246974 mRNA Translation: AAG01736.1 AB045180 mRNA Translation: BAB19259.1 EU170540 Genomic DNA Translation: ABW37075.1 EU170541 Genomic DNA Translation: ABW37076.1 EU170542 Genomic DNA Translation: ABW37077.1 EU170543 Genomic DNA Translation: ABW37078.1 AB445673 mRNA Translation: BAG55070.1 DQ019992 Genomic DNA Translation: AAZ95513.1 DQ019993 Genomic DNA Translation: AAZ95514.1 DQ019994 Genomic DNA Translation: AAZ95515.1 DQ019995 Genomic DNA Translation: AAZ95516.1 DQ019996 Genomic DNA Translation: AAZ95517.1 DQ019999 Genomic DNA Translation: AAZ95520.1 AY359085 mRNA Translation: AAQ89443.1 CH471055 Genomic DNA Translation: EAW65191.1 BC032713 mRNA Translation: AAH32713.1
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS2848.1 [Q9NR96-1]
NCBI Reference Sequences More...RefSeqⁱ	NP_059138.1, NM_017442.3 [Q9NR96-1]

Genome annotation databases

Ensemblⁱ	ENST00000360658; ENSP00000353874; ENSG00000239732
GeneIDⁱ	54106
KEGGⁱ	hsa:54106
MANE-Selectⁱ	ENST00000360658.3; ENSP00000353874.2; NM_017442.4; NP_059138.1
UCSC genome browser More...UCSCⁱ	uc003dda.2, human [Q9NR96-1]

Keywords - Coding sequence diversityⁱ

Alternative splicing

Similar proteinsⁱ

100% Identity
90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length	Source
Q9NR96-2	Isoform 4 of Toll-like receptor 9		HUMAN		1056	UniRef100_Q9NR96-4
Toll-like receptor 9 (Fragment)		HUMAN		1186
Toll-like receptor 9 (Fragment)		HUMAN		1031

Protein	Similar proteins		Species	Score	Length	Source
Q9NR96	Toll-like receptor 9		HUMAN		1129	UniRef90_Q9NR96
Toll-like receptor 9		MACMU		1056
Toll-like receptor 9		MACFA		1056
Toll-like receptor 9		PANTR		1033
Toll-like receptor 9		COLAP		1033
+75

Protein	Similar proteins		Species	Score	Length	Source
Q9NR96	Toll-like receptor 9	)	HORSE		1031	UniRef50_Q9NR96
Toll-like receptor 9	)	BOVIN		1029
Toll-like receptor 9		SHEEP		1029
Toll-like receptor 9		HUMAN		1129
Toll-like receptor 9		MACFA		1056
+173

Cross-referencesⁱ

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	AF259262 mRNA Translation: AAF72189.1 AF259263 mRNA Translation: AAF72190.1 AF245704 mRNA Translation: AAF78037.1 AF246972 mRNA Translation: AAG01734.1 AF246973 mRNA Translation: AAG01735.1 AF246974 mRNA Translation: AAG01736.1 AB045180 mRNA Translation: BAB19259.1 EU170540 Genomic DNA Translation: ABW37075.1 EU170541 Genomic DNA Translation: ABW37076.1 EU170542 Genomic DNA Translation: ABW37077.1 EU170543 Genomic DNA Translation: ABW37078.1 AB445673 mRNA Translation: BAG55070.1 DQ019992 Genomic DNA Translation: AAZ95513.1 DQ019993 Genomic DNA Translation: AAZ95514.1 DQ019994 Genomic DNA Translation: AAZ95515.1 DQ019995 Genomic DNA Translation: AAZ95516.1 DQ019996 Genomic DNA Translation: AAZ95517.1 DQ019999 Genomic DNA Translation: AAZ95520.1 AY359085 mRNA Translation: AAQ89443.1 CH471055 Genomic DNA Translation: EAW65191.1 BC032713 mRNA Translation: AAH32713.1
CCDSⁱ	CCDS2848.1 [Q9NR96-1]
RefSeqⁱ	NP_059138.1, NM_017442.3 [Q9NR96-1]

3D structure databases

SMRⁱ	Q9NR96
ModBaseⁱ	Search...

Protein-protein interaction databases

BioGRIDⁱ	119902, 66 interactors
DIPⁱ	DIP-52371N
IntActⁱ	Q9NR96, 15 interactors
STRINGⁱ	9606.ENSP00000353874

Chemistry databases

BindingDBⁱ	Q9NR96
ChEMBLⁱ	CHEMBL5804
DrugBankⁱ	DB00608, Chloroquine DB05530, CPG 10101 DB05475, Golotimod DB01611, Hydroxychloroquine DB05463, ISS-1018
DrugCentralⁱ	Q9NR96
GuidetoPHARMACOLOGYⁱ	1759

PTM databases

GlyGenⁱ	Q9NR96, 15 sites, 1 O-linked glycan (1 site)
iPTMnetⁱ	Q9NR96
PhosphoSitePlusⁱ	Q9NR96

Genetic variation databases

BioMutaⁱ	TLR9
DMDMⁱ	20140872

Proteomic databases

jPOSTⁱ	Q9NR96
MassIVEⁱ	Q9NR96
MaxQBⁱ	Q9NR96
PaxDbⁱ	Q9NR96
PeptideAtlasⁱ	Q9NR96
PRIDEⁱ	Q9NR96

Protocols and materials databases

Antibodypediaⁱ	34940, 1077 antibodies from 43 providers
The DNASU plasmid repository More...DNASUⁱ	54106

Genome annotation databases

Ensemblⁱ	ENST00000360658; ENSP00000353874; ENSG00000239732
GeneIDⁱ	54106
KEGGⁱ	hsa:54106
MANE-Selectⁱ	ENST00000360658.3; ENSP00000353874.2; NM_017442.4; NP_059138.1
UCSCⁱ	uc003dda.2, human [Q9NR96-1]

Organism-specific databases

CTDⁱ	54106
DisGeNETⁱ	54106
GeneCardsⁱ	TLR9
HGNCⁱ	HGNC:15633, TLR9
HPAⁱ	ENSG00000239732, Tissue enhanced (brain, lymphoid tissue)
MIMⁱ	605474, gene
neXtProtⁱ	NX_Q9NR96
OpenTargetsⁱ	ENSG00000239732
PharmGKBⁱ	PA38010
VEuPathDBⁱ	HostDB:ENSG00000239732
GenAtlas: human gene database More...GenAtlasⁱ	Search...

Phylogenomic databases

eggNOGⁱ	KOG1747, Eukaryota KOG4641, Eukaryota
GeneTreeⁱ	ENSGT00940000162493
HOGENOMⁱ	CLU_006000_2_0_1
InParanoidⁱ	Q9NR96
OrthoDBⁱ	264244at2759
PhylomeDBⁱ	Q9NR96
TreeFamⁱ	TF325595

Enzyme and pathway databases

PathwayCommonsⁱ	Q9NR96
Reactomeⁱ	R-HSA-109704, PI3K Cascade R-HSA-1679131, Trafficking and processing of endosomal TLR R-HSA-168138, Toll Like Receptor 9 (TLR9) Cascade R-HSA-9679191, Potential therapeutics for SARS R-HSA-975110, TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling R-HSA-975138, TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation R-HSA-975155, MyD88 dependent cascade initiated on endosome
SignaLinkⁱ	Q9NR96
SIGNORⁱ	Q9NR96

Miscellaneous databases

BioGRID-ORCSⁱ	54106, 6 hits in 1031 CRISPR screens
GeneWikiⁱ	TLR9
GenomeRNAiⁱ	54106
Pharosⁱ	Q9NR96, Tclin
Protein Ontology More...PROⁱ	PR:Q9NR96
RNActⁱ	Q9NR96, protein
SOURCEⁱ	Search...

Gene expression databases

Bgeeⁱ	ENSG00000239732, Expressed in blood and 84 other tissues
Genevisibleⁱ	Q9NR96, HS

Family and domain databases

Gene3Dⁱ	3.40.50.10140, 1 hit 3.80.10.10, 1 hit
InterProⁱ	View protein in InterPro IPR001611, Leu-rich_rpt IPR003591, Leu-rich_rpt_typical-subtyp IPR041283, LRR_12 IPR032675, LRR_dom_sf IPR000157, TIR_dom IPR027181, TLR9 IPR035897, Toll_tir_struct_dom_sf
PANTHERⁱ	PTHR47410:SF3, PTHR47410:SF3, 1 hit
Pfamⁱ	View protein in Pfam PF18837, LRR_12, 1 hit PF13516, LRR_6, 2 hits PF13855, LRR_8, 7 hits PF01582, TIR, 1 hit
SMARTⁱ	View protein in SMART SM00369, LRR_TYP, 18 hits SM00255, TIR, 1 hit
SUPFAMⁱ	SSF52200, SSF52200, 1 hit
PROSITEⁱ	View protein in PROSITE PS51450, LRR, 17 hits PS50104, TIR, 1 hit
MobiDBⁱ	Search...

Entry informationⁱ

Entry nameⁱ	TLR9_HUMAN
Accessionⁱ	Q9NR96Primary (citable) accession number: Q9NR96 Secondary accession number(s): B3Y661 Q9NYC3
Entry historyⁱ	Integrated into UniProtKB/Swiss-Prot:	January 31, 2002
	Last sequence update:	January 31, 2002
	Last modified:	February 23, 2022
	This is version 190 of the entry and version 2 of the sequence. See complete history.
Entry statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Chordata Protein Annotation Program
Disclaimer	Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousⁱ

Keywords - Technical termⁱ

Reference proteome

Documents

Human cell differentiation molecules
CD nomenclature of surface proteins of human leucocytes and list of entries
Human chromosome 3
Human chromosome 3: entries, gene names and cross-references to MIM
Human entries with genetic variants
List of human entries with genetic variants
Human variants curated from literature reports
Index of human variants curated from literature reports
MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
SIMILARITY comments
Index of protein domains and families

UniProtKB

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Supporting data

UniProtKB - Q9NR96 (TLR9_HUMAN)

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Toll-like receptor 9

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<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Sites

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<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

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Keywords - Cellular componenti

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<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

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Amino acid modifications

Keywords - PTMi

Proteomic databases

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<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

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<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

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<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

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<p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

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Experimental Info

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Sequence databases

Genome annotation databases

Keywords - Coding sequence diversityi

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Sequence databases

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Proteomic databases

Protocols and materials databases

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Enzyme and pathway databases

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Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

PTM / Processingⁱ

Keywords - PTMⁱ

Expressionⁱ

Interactionⁱ

GO - Molecular functionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Keywords - Domainⁱ

Keywords - Coding sequence diversityⁱ

Cross-referencesⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ