UniProtKB - Q96F46 (I17RA_HUMAN)
Interleukin-17 receptor A
IL17RA
Functioni
Receptor for IL17A and IL17F, major effector cytokines of innate and adaptive immune system involved in antimicrobial host defense and maintenance of tissue integrity. Receptor for IL17A (PubMed:17911633, PubMed:9367539).
Receptor for IL17F (PubMed:19838198, PubMed:17911633).
Binds to IL17A with higher affinity than to IL17F (PubMed:17911633).
Binds IL17A and IL17F homodimers as part of a heterodimeric complex with IL17RC (PubMed:16785495).
Also binds heterodimers formed by IL17A and IL17F as part of a heterodimeric complex with IL17RC (PubMed:18684971).
Cytokine binding triggers homotypic interaction of IL17RA and IL17RC chains with TRAF3IP2 adapter, leading to TRAF6-mediated activation of NF-kappa-B and MAPkinase pathways, ultimately resulting in transcriptional activation of cytokines, chemokines, antimicrobial peptides and matrix metalloproteinases, with potential strong immune inflammation (PubMed:16785495, PubMed:24120361, PubMed:17911633, PubMed:18684971, PubMed:21350122).
Involved in antimicrobial host defense primarily promoting neutrophil activation and recruitment at infection sites to destroy extracellular bacteria and fungi (By similarity).
In secondary lymphoid organs, contributes to germinal center formation by regulating the chemotactic response of B cells to CXCL12 and CXCL13, enhancing retention of B cells within the germinal centers, B cell somatic hypermutation rate and selection toward plasma cells (By similarity).
Plays a role in the maintenance of the integrity of epithelial barriers during homeostasis and pathogen infection. Stimulates the production of antimicrobial beta-defensins DEFB1, DEFB103A, and DEFB104A by mucosal epithelial cells, limiting the entry of microbes through the epithelial barriers (By similarity).
Involved in antiviral host defense through various mechanisms. Enhances immunity against West Nile virus by promoting T cell cytotoxicity. Contributes to Influenza virus clearance by driving the differentiation of B-1a B cells, providing for production of virus-specific IgM antibodies at first line of host defense (By similarity).
Receptor for IL17C as part of a heterodimeric complex with IL17RE (PubMed:21993848).
By similarity8 Publications(Microbial infection) Receptor for SARS coronavirus-2/SARS-CoV-2 virus protein ORF8, leading to IL17 pathway activation and an increased secretion of pro-inflammatory factors through activating NF-kappa-B signaling pathway.
1 PublicationGO - Molecular functioni
- interleukin-17 receptor activity Source: UniProtKB
- signaling receptor binding Source: Ensembl
GO - Biological processi
- cell surface receptor signaling pathway Source: UniProtKB
- defense response to fungus Source: Ensembl
- fibroblast activation Source: BHF-UCL
- granulocyte chemotaxis Source: Ensembl
- inflammatory response Source: UniProtKB-KW
- innate immune response Source: UniProtKB-KW
- interleukin-17-mediated signaling pathway Source: UniProtKB
- positive regulation of chemokine (C-X-C motif) ligand 1 production Source: UniProtKB
- positive regulation of cytokine production involved in inflammatory response Source: UniProtKB
- positive regulation of inflammatory response Source: UniProtKB
- positive regulation of interleukin-13 production Source: Ensembl
- positive regulation of interleukin-23 production Source: BHF-UCL
- positive regulation of interleukin-5 production Source: Ensembl
- positive regulation of interleukin-6 production Source: UniProtKB
- protein catabolic process Source: Ensembl
- response to virus Source: UniProtKB
- T-helper 17 type immune response Source: Ensembl
Keywordsi
Molecular function | Receptor |
Biological process | Adaptive immunity, Host-virus interaction, Immunity, Inflammatory response, Innate immunity |
Enzyme and pathway databases
PathwayCommonsi | Q96F46 |
Reactomei | R-HSA-448424, Interleukin-17 signaling |
SignaLinki | Q96F46 |
SIGNORi | Q96F46 |
Names & Taxonomyi
Protein namesi | Recommended name: Interleukin-17 receptor ACuratedShort name: IL-17 receptor A Short name: IL-17RA Alternative name(s): CDw217 CD_antigen: CD217 |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:5985, IL17RA |
MIMi | 605461, gene |
neXtProti | NX_Q96F46 |
VEuPathDBi | HostDB:ENSG00000177663 |
Subcellular locationi
Plasma membrane
- Cell membrane 1 Publication; Single-pass type I membrane protein Sequence analysis
Extracellular region or secreted
- Secreted 1 Publication
Extracellular region or secreted
- extracellular region Source: UniProtKB-SubCell
Plasma Membrane
- integral component of plasma membrane Source: UniProtKB
- plasma membrane Source: Reactome
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 33 – 320 | ExtracellularSequence analysisAdd BLAST | 288 | |
Transmembranei | 321 – 341 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 342 – 866 | CytoplasmicSequence analysisAdd BLAST | 525 |
Keywords - Cellular componenti
Cell membrane, Membrane, SecretedPathology & Biotechi
Involvement in diseasei
Immunodeficiency 51 (IMD51)1 Publication
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_083722 | 284 – 866 | Missing in IMD51; results in complete loss of expression and loss-of-function. 1 PublicationAdd BLAST | 583 |
Organism-specific databases
DisGeNETi | 23765 |
MalaCardsi | IL17RA |
MIMi | 613953, phenotype |
OpenTargetsi | ENSG00000177663 |
Orphaneti | 1334, Chronic mucocutaneous candidiasis |
PharmGKBi | PA29801 |
Miscellaneous databases
Pharosi | Q96F46, Tclin |
Chemistry databases
ChEMBLi | CHEMBL3580485 |
DrugCentrali | Q96F46 |
GuidetoPHARMACOLOGYi | 1738 |
Genetic variation databases
BioMutai | IL17RA |
DMDMi | 116242517 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 32 | 1 PublicationAdd BLAST | 32 | |
ChainiPRO_0000011030 | 33 – 866 | Interleukin-17 receptor AAdd BLAST | 834 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 43 ↔ 50 | 2 Publications | ||
Glycosylationi | 49 | N-linked (GlcNAc...) asparagine2 Publications | 1 | |
Glycosylationi | 54 | N-linked (GlcNAc...) asparagine2 Publications | 1 | |
Disulfide bondi | 57 ↔ 126 | 2 Publications | ||
Glycosylationi | 67 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Disulfide bondi | 185 ↔ 196 | 2 Publications | ||
Glycosylationi | 206 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 225 | N-linked (GlcNAc...) asparagine2 Publications | 1 | |
Glycosylationi | 242 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 245 ↔ 276 | 2 Publications | ||
Glycosylationi | 265 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Disulfide bondi | 277 ↔ 303 | 1 Publication | ||
Disulfide bondi | 290 ↔ 294 | 2 Publications | ||
Modified residuei | 708 | PhosphoserineCombined sources | 1 | |
Modified residuei | 736 | PhosphoserineBy similarity | 1 |
Post-translational modificationi
Keywords - PTMi
Disulfide bond, Glycoprotein, PhosphoproteinProteomic databases
EPDi | Q96F46 |
jPOSTi | Q96F46 |
MassIVEi | Q96F46 |
MaxQBi | Q96F46 |
PaxDbi | Q96F46 |
PeptideAtlasi | Q96F46 |
PRIDEi | Q96F46 |
ProteomicsDBi | 76496 [Q96F46-1] |
PTM databases
GlyGeni | Q96F46, 7 sites |
iPTMneti | Q96F46 |
PhosphoSitePlusi | Q96F46 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000177663, Expressed in blood and 225 other tissues |
Genevisiblei | Q96F46, HS |
Organism-specific databases
HPAi | ENSG00000177663, Tissue enhanced (bone) |
Interactioni
Subunit structurei
Forms heterodimers with IL17RC; the heterodimer binds IL17A and IL17F homodimers as well as the heterodimer formed by IL17A and IL17F (PubMed:16785495, PubMed:18684971, PubMed:32187518). Forms complexes with 2:1 binding stoichiometry: two receptor chains for one interleukin molecule (PubMed:32187518). IL17A homodimer preferentially drives the formation of IL17RA-IL17RC heterodimeric receptor complex, whereas IL17F homodimer forms predominantly complexes with IL17RC homodimer (PubMed:32187518). IL17A homodimer adopts an asymmetrical ternary structure with one IL17RA molecule, allowing for high affinity interactions of one IL17A monomer with one IL17RA molecule (via D1 and D2 domains), while disfavoring binding of a second IL17RA molecule on the other IL17A monomer (PubMed:23695682). IL17A-IL17F forms complexes with IL17RA-IL17RC, but with lower affinity when compared to IL17A homodimer (PubMed:32187518). IL17RA chain cannot distinguish between IL17A and IL17F molecules, potentially enabling the formation of topologically distinct complexes (PubMed:28827714).
Interacts with TRAF3IP2 (PubMed:24120361). Forms heterodimers with IL17RE; the heterodimer binds IL17C (PubMed:21993848, PubMed:16785495, PubMed:18684971).
7 Publications(Microbial infection) Interacts with SARS coronavirus-2/SARS-CoV-2 virus protein ORF8.
2 PublicationsBinary interactionsi
Q96F46
With | #Exp. | IntAct |
---|---|---|
IL17RE [Q8NFR9] | 2 | EBI-5591258,EBI-5591275 |
8 [P0DTC8] from Severe acute respiratory syndrome coronavirus 2. | 3 | EBI-5591258,EBI-25475900 |
GO - Molecular functioni
- signaling receptor binding Source: Ensembl
Protein-protein interaction databases
BioGRIDi | 117265, 151 interactors |
IntActi | Q96F46, 67 interactors |
STRINGi | 9606.ENSP00000320936 |
Miscellaneous databases
RNActi | Q96F46, protein |
Structurei
Secondary structure
3D structure databases
SMRi | Q96F46 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q96F46 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 377 – 534 | SEFIRPROSITE-ProRule annotationAdd BLAST | 158 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 717 – 736 | DisorderedSequence analysisAdd BLAST | 20 | |
Regioni | 773 – 840 | DisorderedSequence analysisAdd BLAST | 68 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 787 – 805 | Polar residuesSequence analysisAdd BLAST | 19 |
Keywords - Domaini
Signal, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | ENOG502QV5J, Eukaryota |
GeneTreei | ENSGT00940000159018 |
HOGENOMi | CLU_018087_0_0_1 |
InParanoidi | Q96F46 |
OMAi | KRWHFTF |
OrthoDBi | 577180at2759 |
PhylomeDBi | Q96F46 |
TreeFami | TF329644 |
Family and domain databases
Gene3Di | 2.60.40.2150, 1 hit 2.60.40.2160, 1 hit |
InterProi | View protein in InterPro IPR039465, IL-17_rcpt-like IPR032356, IL17R_fnIII_D1 IPR038683, IL17RA/B_FnIII-like_1_sf IPR043046, IL17RA/B_FnIII-like_2_sf IPR013568, SEFIR_dom |
PANTHERi | PTHR15583, PTHR15583, 1 hit |
Pfami | View protein in Pfam PF16556, IL17R_fnIII_D1, 1 hit PF08357, SEFIR, 1 hit |
PROSITEi | View protein in PROSITE PS51534, SEFIR, 1 hit |
s (2)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MGAARSPPSA VPGPLLGLLL LLLGVLAPGG ASLRLLDHRA LVCSQPGLNC
60 70 80 90 100
TVKNSTCLDD SWIHPRNLTP SSPKDLQIQL HFAHTQQGDL FPVAHIEWTL
110 120 130 140 150
QTDASILYLE GAELSVLQLN TNERLCVRFE FLSKLRHHHR RWRFTFSHFV
160 170 180 190 200
VDPDQEYEVT VHHLPKPIPD GDPNHQSKNF LVPDCEHARM KVTTPCMSSG
210 220 230 240 250
SLWDPNITVE TLEAHQLRVS FTLWNESTHY QILLTSFPHM ENHSCFEHMH
260 270 280 290 300
HIPAPRPEEF HQRSNVTLTL RNLKGCCRHQ VQIQPFFSSC LNDCLRHSAT
310 320 330 340 350
VSCPEMPDTP EPIPDYMPLW VYWFITGISI LLVGSVILLI VCMTWRLAGP
360 370 380 390 400
GSEKYSDDTK YTDGLPAADL IPPPLKPRKV WIIYSADHPL YVDVVLKFAQ
410 420 430 440 450
FLLTACGTEV ALDLLEEQAI SEAGVMTWVG RQKQEMVESN SKIIVLCSRG
460 470 480 490 500
TRAKWQALLG RGAPVRLRCD HGKPVGDLFT AAMNMILPDF KRPACFGTYV
510 520 530 540 550
VCYFSEVSCD GDVPDLFGAA PRYPLMDRFE EVYFRIQDLE MFQPGRMHRV
560 570 580 590 600
GELSGDNYLR SPGGRQLRAA LDRFRDWQVR CPDWFECENL YSADDQDAPS
610 620 630 640 650
LDEEVFEEPL LPPGTGIVKR APLVREPGSQ ACLAIDPLVG EEGGAAVAKL
660 670 680 690 700
EPHLQPRGQP APQPLHTLVL AAEEGALVAA VEPGPLADGA AVRLALAGEG
710 720 730 740 750
EACPLLGSPG AGRNSVLFLP VDPEDSPLGS STPMASPDLL PEDVREHLEG
760 770 780 790 800
LMLSLFEQSL SCQAQGGCSR PAMVLTDPHT PYEEEQRQSV QSDQGYISRS
810 820 830 840 850
SPQPPEGLTE MEEEEEEEQD PGKPALPLSP EDLESLRSLQ RQLLFRQLQK
860
NSGWDTMGSE SEGPSA
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_083722 | 284 – 866 | Missing in IMD51; results in complete loss of expression and loss-of-function. 1 PublicationAdd BLAST | 583 | |
Natural variantiVAR_027966 | 367 | A → V1 PublicationCorresponds to variant dbSNP:rs879577EnsemblClinVar. | 1 | |
Natural variantiVAR_049176 | 562 | P → Q. Corresponds to variant dbSNP:rs12484684EnsemblClinVar. | 1 | |
Natural variantiVAR_027967 | 580 | R → H1 PublicationCorresponds to variant dbSNP:rs17850765Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_053496 | 315 – 348 | Missing in isoform 2. 1 PublicationAdd BLAST | 34 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U58917 mRNA Translation: AAB99730.1 CT841520 mRNA Translation: CAJ86450.1 CH471193 Genomic DNA Translation: EAW57739.1 BC011624 mRNA Translation: AAH11624.1 BX368715 mRNA No translation available. |
CCDSi | CCDS13739.1 [Q96F46-1] CCDS77645.1 [Q96F46-2] |
RefSeqi | NP_001276834.1, NM_001289905.1 [Q96F46-2] NP_055154.3, NM_014339.6 [Q96F46-1] |
Genome annotation databases
Ensembli | ENST00000319363; ENSP00000320936; ENSG00000177663 ENST00000612619; ENSP00000479970; ENSG00000177663 [Q96F46-2] |
GeneIDi | 23765 |
KEGGi | hsa:23765 |
MANE-Selecti | ENST00000319363.11; ENSP00000320936.6; NM_014339.7; NP_055154.3 |
UCSCi | uc002zly.5, human [Q96F46-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U58917 mRNA Translation: AAB99730.1 CT841520 mRNA Translation: CAJ86450.1 CH471193 Genomic DNA Translation: EAW57739.1 BC011624 mRNA Translation: AAH11624.1 BX368715 mRNA No translation available. |
CCDSi | CCDS13739.1 [Q96F46-1] CCDS77645.1 [Q96F46-2] |
RefSeqi | NP_001276834.1, NM_001289905.1 [Q96F46-2] NP_055154.3, NM_014339.6 [Q96F46-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
3JVF | X-ray | 3.30 | C | 32-317 | [»] | |
4HSA | X-ray | 3.15 | C/F | 32-317 | [»] | |
4NUX | X-ray | 2.30 | A | 376-591 | [»] | |
5N9B | X-ray | 1.90 | A | 33-318 | [»] | |
5NAN | X-ray | 3.30 | B/C | 33-320 | [»] | |
SMRi | Q96F46 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 117265, 151 interactors |
IntActi | Q96F46, 67 interactors |
STRINGi | 9606.ENSP00000320936 |
Chemistry databases
ChEMBLi | CHEMBL3580485 |
DrugCentrali | Q96F46 |
GuidetoPHARMACOLOGYi | 1738 |
PTM databases
GlyGeni | Q96F46, 7 sites |
iPTMneti | Q96F46 |
PhosphoSitePlusi | Q96F46 |
Genetic variation databases
BioMutai | IL17RA |
DMDMi | 116242517 |
Proteomic databases
EPDi | Q96F46 |
jPOSTi | Q96F46 |
MassIVEi | Q96F46 |
MaxQBi | Q96F46 |
PaxDbi | Q96F46 |
PeptideAtlasi | Q96F46 |
PRIDEi | Q96F46 |
ProteomicsDBi | 76496 [Q96F46-1] |
Protocols and materials databases
ABCDi | Q96F46, 25 sequenced antibodies |
Antibodypediai | 22632, 779 antibodies from 42 providers |
DNASUi | 23765 |
Genome annotation databases
Ensembli | ENST00000319363; ENSP00000320936; ENSG00000177663 ENST00000612619; ENSP00000479970; ENSG00000177663 [Q96F46-2] |
GeneIDi | 23765 |
KEGGi | hsa:23765 |
MANE-Selecti | ENST00000319363.11; ENSP00000320936.6; NM_014339.7; NP_055154.3 |
UCSCi | uc002zly.5, human [Q96F46-1] |
Organism-specific databases
CTDi | 23765 |
DisGeNETi | 23765 |
GeneCardsi | IL17RA |
HGNCi | HGNC:5985, IL17RA |
HPAi | ENSG00000177663, Tissue enhanced (bone) |
MalaCardsi | IL17RA |
MIMi | 605461, gene 613953, phenotype |
neXtProti | NX_Q96F46 |
OpenTargetsi | ENSG00000177663 |
Orphaneti | 1334, Chronic mucocutaneous candidiasis |
PharmGKBi | PA29801 |
VEuPathDBi | HostDB:ENSG00000177663 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502QV5J, Eukaryota |
GeneTreei | ENSGT00940000159018 |
HOGENOMi | CLU_018087_0_0_1 |
InParanoidi | Q96F46 |
OMAi | KRWHFTF |
OrthoDBi | 577180at2759 |
PhylomeDBi | Q96F46 |
TreeFami | TF329644 |
Enzyme and pathway databases
PathwayCommonsi | Q96F46 |
Reactomei | R-HSA-448424, Interleukin-17 signaling |
SignaLinki | Q96F46 |
SIGNORi | Q96F46 |
Miscellaneous databases
BioGRID-ORCSi | 23765, 8 hits in 1055 CRISPR screens |
ChiTaRSi | IL17RA, human |
EvolutionaryTracei | Q96F46 |
GeneWikii | IL17RA |
GenomeRNAii | 23765 |
Pharosi | Q96F46, Tclin |
PROi | PR:Q96F46 |
RNActi | Q96F46, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000177663, Expressed in blood and 225 other tissues |
Genevisiblei | Q96F46, HS |
Family and domain databases
Gene3Di | 2.60.40.2150, 1 hit 2.60.40.2160, 1 hit |
InterProi | View protein in InterPro IPR039465, IL-17_rcpt-like IPR032356, IL17R_fnIII_D1 IPR038683, IL17RA/B_FnIII-like_1_sf IPR043046, IL17RA/B_FnIII-like_2_sf IPR013568, SEFIR_dom |
PANTHERi | PTHR15583, PTHR15583, 1 hit |
Pfami | View protein in Pfam PF16556, IL17R_fnIII_D1, 1 hit PF08357, SEFIR, 1 hit |
PROSITEi | View protein in PROSITE PS51534, SEFIR, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | I17RA_HUMAN | |
Accessioni | Q96F46Primary (citable) accession number: Q96F46 Secondary accession number(s): O43844, Q20WK1 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | May 2, 2002 |
Last sequence update: | October 17, 2006 | |
Last modified: | February 23, 2022 | |
This is version 177 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
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- Human cell differentiation molecules
CD nomenclature of surface proteins of human leucocytes and list of entries - Human chromosome 22
Human chromosome 22: 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 - PDB cross-references
Index of Protein Data Bank (PDB) cross-references