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Protein

Interleukin-17 receptor D

Gene

IL17RD

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Feedback inhibitor of fibroblast growth factor mediated Ras-MAPK signaling and ERK activation. May inhibit FGF-induced FGFR1 tyrosine phosphorylation. Regulates the nuclear ERK signaling pathway by spatially blocking nuclear translocation of activated ERK without inhibiting cytoplasmic phosphorylation of ERK. Mediates JNK activation and may be involved in apoptosis. Might have a role in the early stages of fate specification of GnRH-secreting neurons (By similarity).By similarity3 Publications

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Receptor

Enzyme and pathway databases

BioCyciZFISH:ENSG00000144730-MONOMER.
ReactomeiR-HSA-5674135. MAP2K and MAPK activation.

Names & Taxonomyi

Protein namesi
Recommended name:
Interleukin-17 receptor D
Short name:
IL-17 receptor D
Short name:
IL-17RD
Alternative name(s):
IL17Rhom
Interleukin-17 receptor-like protein
Sef homolog
Short name:
hSef
Gene namesi
Name:IL17RD
Synonyms:IL17RLM, SEF
ORF Names:UNQ6115/PRO20026
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:17616. IL17RD.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini17 – 299ExtracellularSequence analysisAdd BLAST283
Transmembranei300 – 320HelicalSequence analysisAdd BLAST21
Topological domaini321 – 739CytoplasmicSequence analysisAdd BLAST419

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Golgi apparatus, Membrane

Pathology & Biotechi

Involvement in diseasei

Hypogonadotropic hypogonadism 18 with or without anosmia (HH18)1 Publication
The disease is caused by mutations affecting distinct genetic loci, including the gene represented in this entry. Some patients carrying mutations in IL17RD also have a heterozygous mutation in another HH-associated gene including FGFR1 and KISS1R (PubMed:23643382).1 Publication
Disease descriptionA disorder characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic-pituitary axis. In some cases, it is associated with non-reproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss. Anosmia or hyposmia is related to the absence or hypoplasia of the olfactory bulbs and tracts. Hypogonadism is due to deficiency in gonadotropin-releasing hormone and probably results from a failure of embryonic migration of gonadotropin-releasing hormone-synthesizing neurons. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism is referred to as Kallmann syndrome, whereas in the presence of a normal sense of smell, it has been termed normosmic idiopathic hypogonadotropic hypogonadism (nIHH).
See also OMIM:615267
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_069936131K → T in HH18; results in decreased expression at the cell surface and reduced activity. 1 PublicationCorresponds to variant rs184758350dbSNPEnsembl.1
Natural variantiVAR_069937162K → R in HH18; results in decreased expression at the cell surface. 1 Publication1
Natural variantiVAR_069938306P → S in HH18; reduced activity. 1 Publication1
Natural variantiVAR_069939379Y → C in HH18; rare variant associated with susceptibility to disease; some patients have a second mutation in the HH-associated gene FGFR1; reduced activity. 1 PublicationCorresponds to variant rs369641068dbSNPEnsembl.1
Natural variantiVAR_069940468S → L in HH18; reduced activity. 1 PublicationCorresponds to variant rs145221454dbSNPEnsembl.1
Natural variantiVAR_069941577P → Q in HH18; reduced activity. 1 PublicationCorresponds to variant rs587776980dbSNPEnsembl.1
Natural variantiVAR_069942735A → V in HH18; rare variant associated with susceptibility to disease; the patient carries a second mutation in the HH-associated gene KISS1R; results in decreased expression at the cell surface. 1 PublicationCorresponds to variant rs587776979dbSNPEnsembl.1

Keywords - Diseasei

Disease mutation, Hypogonadotropic hypogonadism, Kallmann syndrome

Organism-specific databases

DisGeNETi54756.
MalaCardsiIL17RD.
MIMi615267. phenotype.
OpenTargetsiENSG00000144730.
Orphaneti478. Kallmann syndrome.
PharmGKBiPA134993407.

Polymorphism and mutation databases

BioMutaiIL17RD.
DMDMi126302555.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 16Sequence analysisAdd BLAST16
ChainiPRO_000004187117 – 739Interleukin-17 receptor DAdd BLAST723

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi19N-linked (GlcNAc...)Sequence analysis1
Glycosylationi55N-linked (GlcNAc...)Sequence analysis1
Glycosylationi62N-linked (GlcNAc...)Sequence analysis1
Glycosylationi80N-linked (GlcNAc...)Sequence analysis1
Glycosylationi137N-linked (GlcNAc...)Sequence analysis1
Glycosylationi171N-linked (GlcNAc...)Sequence analysis1
Glycosylationi206N-linked (GlcNAc...)Sequence analysis1
Glycosylationi277N-linked (GlcNAc...)Sequence analysis1

Keywords - PTMi

Glycoprotein

Proteomic databases

EPDiQ8NFM7.
PaxDbiQ8NFM7.
PeptideAtlasiQ8NFM7.
PRIDEiQ8NFM7.

PTM databases

iPTMnetiQ8NFM7.
PhosphoSitePlusiQ8NFM7.

Expressioni

Tissue specificityi

Expressed in umbilical vein endothelial cells and in several highly vascularized tissues such as kidney, colon, skeletal muscle, heart and small intestine. Highly expressed in ductal epithelial cells of salivary glands, seminal vesicles and the collecting tubules of the kidney. Isoform 1 is also highly expressed in both fetal and adult brain, pituitary, tonsils, spleen, adenoids, fetal kidney, liver, testes and ovary. Isoform 1 is also expressed at moderate levels in primary aortic endothelial cells and adrenal medulla, and at low levels in adrenal cortex. Isoform 4 is specifically and highly expressed in pituitary, fetal brain and umbilical vein endothelial cells.1 Publication

Gene expression databases

BgeeiENSG00000144730.
CleanExiHS_IL17RD.
ExpressionAtlasiQ8NFM7. baseline and differential.
GenevisibleiQ8NFM7. HS.

Organism-specific databases

HPAiHPA039577.
HPA043550.

Interactioni

Subunit structurei

Interacts with MAP3K7 (By similarity). Self-associates. Interacts with FGFR1, FGFR2 and phosphorylated MAP2K1 or MAP2K2. Associates with a MAP2K1/2-MAPK1/3 complex.By similarity3 Publications

Protein-protein interaction databases

BioGridi120132. 5 interactors.
STRINGi9606.ENSP00000296318.

Structurei

3D structure databases

ProteinModelPortaliQ8NFM7.
SMRiQ8NFM7.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini355 – 509SEFIRPROSITE-ProRule annotationAdd BLAST155

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi695 – 700Poly-Ser6

Sequence similaritiesi

Contains 1 SEFIR domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IEYK. Eukaryota.
ENOG4110CUP. LUCA.
GeneTreeiENSGT00860000133857.
HOVERGENiHBG081777.
InParanoidiQ8NFM7.
KOiK05167.
OMAiSTKYKLM.
OrthoDBiEOG091G01XZ.
PhylomeDBiQ8NFM7.
TreeFamiTF329644.

Family and domain databases

InterProiIPR031951. IL17R_D_N.
IPR013568. SEFIR_dom.
IPR000157. TIR_dom.
[Graphical view]
PfamiPF16742. IL17R_D_N. 1 hit.
PF08357. SEFIR. 1 hit.
[Graphical view]
SUPFAMiSSF52200. SSF52200. 1 hit.
PROSITEiPS51534. SEFIR. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

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

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8NFM7-1) [UniParc]FASTAAdd to basket
Also known as: hSef-a, IL17RLM-L, Long

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

« Hide

        10         20         30         40         50
MAPWLQLCSV FFTVNACLNG SQLAVAAGGS GRARGADTCG WRGVGPASRN
60 70 80 90 100
SGLYNITFKY DNCTTYLNPV GKHVIADAQN ITISQYACHD QVAVTILWSP
110 120 130 140 150
GALGIEFLKG FRVILEELKS EGRQCQQLIL KDPKQLNSSF KRTGMESQPF
160 170 180 190 200
LNMKFETDYF VKVVPFPSIK NESNYHPFFF RTRACDLLLQ PDNLACKPFW
210 220 230 240 250
KPRNLNISQH GSDMQVSFDH APHNFGFRFF YLHYKLKHEG PFKRKTCKQE
260 270 280 290 300
QTTETTSCLL QNVSPGDYII ELVDDTNTTR KVMHYALKPV HSPWAGPIRA
310 320 330 340 350
VAITVPLVVI SAFATLFTVM CRKKQQENIY SHLDEESSES STYTAALPRE
360 370 380 390 400
RLRPRPKVFL CYSSKDGQNH MNVVQCFAYF LQDFCGCEVA LDLWEDFSLC
410 420 430 440 450
REGQREWVIQ KIHESQFIIV VCSKGMKYFV DKKNYKHKGG GRGSGKGELF
460 470 480 490 500
LVAVSAIAEK LRQAKQSSSA ALSKFIAVYF DYSCEGDVPG ILDLSTKYRL
510 520 530 540 550
MDNLPQLCSH LHSRDHGLQE PGQHTRQGSR RNYFRSKSGR SLYVAICNMH
560 570 580 590 600
QFIDEEPDWF EKQFVPFHPP PLRYREPVLE KFDSGLVLND VMCKPGPESD
610 620 630 640 650
FCLKVEAAVL GATGPADSQH ESQHGGLDQD GEARPALDGS AALQPLLHTV
660 670 680 690 700
KAGSPSDMPR DSGIYDSSVP SSELSLPLME GLSTDQTETS SLTESVSSSS
710 720 730
GLGEEEPPAL PSKLLSSGSC KADLGCRSYT DELHAVAPL
Length:739
Mass (Da):82,411
Last modified:February 20, 2007 - v3
Checksum:i7A2B45818DBD6E44
GO
Isoform 2 (identifier: Q8NFM7-2) [UniParc]FASTAAdd to basket
Also known as: "IL17RLM-S, Short

The sequence of this isoform differs from the canonical sequence as follows:
     1-144: Missing.

Show »
Length:595
Mass (Da):66,817
Checksum:i12307ED8AA4B4041
GO
Isoform 3 (identifier: Q8NFM7-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-42: MAPWLQLCSVFFTVNACLNGSQLAVAAGGSGRARGADTCGWR → MPRASASGVPALFVSGEQ

Show »
Length:715
Mass (Da):79,871
Checksum:i27564B1A6F365EF6
GO
Isoform 4 (identifier: Q8NFM7-4) [UniParc]FASTAAdd to basket
Also known as: hSef-b

The sequence of this isoform differs from the canonical sequence as follows:
     1-42: MAPWLQLCSVFFTVNACLNGSQLAVAAGGSGRARGADTCGWR → MDYRQSWPWQ

Show »
Length:707
Mass (Da):79,463
Checksum:i116027A2BD48902D
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti223H → HGSDMQVSFDHAPH in CAB61408 (PubMed:12975309).Curated1
Sequence conflicti248K → E in AAM74077 (PubMed:12958313).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_069936131K → T in HH18; results in decreased expression at the cell surface and reduced activity. 1 PublicationCorresponds to variant rs184758350dbSNPEnsembl.1
Natural variantiVAR_069937162K → R in HH18; results in decreased expression at the cell surface. 1 Publication1
Natural variantiVAR_023478255T → M.6 PublicationsCorresponds to variant rs6780995dbSNPEnsembl.1
Natural variantiVAR_023479301V → M.Corresponds to variant rs17057718dbSNPEnsembl.1
Natural variantiVAR_069938306P → S in HH18; reduced activity. 1 Publication1
Natural variantiVAR_069939379Y → C in HH18; rare variant associated with susceptibility to disease; some patients have a second mutation in the HH-associated gene FGFR1; reduced activity. 1 PublicationCorresponds to variant rs369641068dbSNPEnsembl.1
Natural variantiVAR_069940468S → L in HH18; reduced activity. 1 PublicationCorresponds to variant rs145221454dbSNPEnsembl.1
Natural variantiVAR_069941577P → Q in HH18; reduced activity. 1 PublicationCorresponds to variant rs587776980dbSNPEnsembl.1
Natural variantiVAR_069942735A → V in HH18; rare variant associated with susceptibility to disease; the patient carries a second mutation in the HH-associated gene KISS1R; results in decreased expression at the cell surface. 1 PublicationCorresponds to variant rs587776979dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0155821 – 144Missing in isoform 2. 2 PublicationsAdd BLAST144
Alternative sequenceiVSP_0155831 – 42MAPWL…TCGWR → MPRASASGVPALFVSGEQ in isoform 3. 1 PublicationAdd BLAST42
Alternative sequenceiVSP_0155841 – 42MAPWL…TCGWR → MDYRQSWPWQ in isoform 4. 2 PublicationsAdd BLAST42

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF494208 mRNA. Translation: AAM74077.1.
AF494211 mRNA. Translation: AAM74080.1.
AY489047 mRNA. Translation: AAS15051.2.
AF458067 mRNA. Translation: AAM77571.1.
AY358774 mRNA. Translation: AAQ89134.1.
AL133097 mRNA. Translation: CAB61408.1.
AL833913 mRNA. Translation: CAD38769.1.
BC111702 mRNA. Translation: AAI11703.2.
CCDSiCCDS2880.2. [Q8NFM7-1]
CCDS82790.1. [Q8NFM7-2]
PIRiT42695.
RefSeqiNP_001305793.1. NM_001318864.1. [Q8NFM7-2]
NP_060033.3. NM_017563.4. [Q8NFM7-1]
XP_006713272.1. XM_006713209.3. [Q8NFM7-2]
XP_011532151.2. XM_011533849.2. [Q8NFM7-2]
UniGeneiHs.150725.

Genome annotation databases

EnsembliENST00000296318; ENSP00000296318; ENSG00000144730. [Q8NFM7-1]
ENST00000320057; ENSP00000322250; ENSG00000144730. [Q8NFM7-2]
ENST00000463523; ENSP00000417516; ENSG00000144730. [Q8NFM7-2]
GeneIDi54756.
KEGGihsa:54756.
UCSCiuc003dil.3. human. [Q8NFM7-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF494208 mRNA. Translation: AAM74077.1.
AF494211 mRNA. Translation: AAM74080.1.
AY489047 mRNA. Translation: AAS15051.2.
AF458067 mRNA. Translation: AAM77571.1.
AY358774 mRNA. Translation: AAQ89134.1.
AL133097 mRNA. Translation: CAB61408.1.
AL833913 mRNA. Translation: CAD38769.1.
BC111702 mRNA. Translation: AAI11703.2.
CCDSiCCDS2880.2. [Q8NFM7-1]
CCDS82790.1. [Q8NFM7-2]
PIRiT42695.
RefSeqiNP_001305793.1. NM_001318864.1. [Q8NFM7-2]
NP_060033.3. NM_017563.4. [Q8NFM7-1]
XP_006713272.1. XM_006713209.3. [Q8NFM7-2]
XP_011532151.2. XM_011533849.2. [Q8NFM7-2]
UniGeneiHs.150725.

3D structure databases

ProteinModelPortaliQ8NFM7.
SMRiQ8NFM7.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi120132. 5 interactors.
STRINGi9606.ENSP00000296318.

PTM databases

iPTMnetiQ8NFM7.
PhosphoSitePlusiQ8NFM7.

Polymorphism and mutation databases

BioMutaiIL17RD.
DMDMi126302555.

Proteomic databases

EPDiQ8NFM7.
PaxDbiQ8NFM7.
PeptideAtlasiQ8NFM7.
PRIDEiQ8NFM7.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000296318; ENSP00000296318; ENSG00000144730. [Q8NFM7-1]
ENST00000320057; ENSP00000322250; ENSG00000144730. [Q8NFM7-2]
ENST00000463523; ENSP00000417516; ENSG00000144730. [Q8NFM7-2]
GeneIDi54756.
KEGGihsa:54756.
UCSCiuc003dil.3. human. [Q8NFM7-1]

Organism-specific databases

CTDi54756.
DisGeNETi54756.
GeneCardsiIL17RD.
H-InvDBHIX0003391.
HGNCiHGNC:17616. IL17RD.
HPAiHPA039577.
HPA043550.
MalaCardsiIL17RD.
MIMi606807. gene.
615267. phenotype.
neXtProtiNX_Q8NFM7.
OpenTargetsiENSG00000144730.
Orphaneti478. Kallmann syndrome.
PharmGKBiPA134993407.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IEYK. Eukaryota.
ENOG4110CUP. LUCA.
GeneTreeiENSGT00860000133857.
HOVERGENiHBG081777.
InParanoidiQ8NFM7.
KOiK05167.
OMAiSTKYKLM.
OrthoDBiEOG091G01XZ.
PhylomeDBiQ8NFM7.
TreeFamiTF329644.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000144730-MONOMER.
ReactomeiR-HSA-5674135. MAP2K and MAPK activation.

Miscellaneous databases

ChiTaRSiIL17RD. human.
GenomeRNAii54756.
PROiQ8NFM7.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000144730.
CleanExiHS_IL17RD.
ExpressionAtlasiQ8NFM7. baseline and differential.
GenevisibleiQ8NFM7. HS.

Family and domain databases

InterProiIPR031951. IL17R_D_N.
IPR013568. SEFIR_dom.
IPR000157. TIR_dom.
[Graphical view]
PfamiPF16742. IL17R_D_N. 1 hit.
PF08357. SEFIR. 1 hit.
[Graphical view]
SUPFAMiSSF52200. SSF52200. 1 hit.
PROSITEiPS51534. SEFIR. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiI17RD_HUMAN
AccessioniPrimary (citable) accession number: Q8NFM7
Secondary accession number(s): Q2NKP7
, Q58EZ7, Q6RVF4, Q6UWI5, Q8N113, Q8NFS0, Q9UFA0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 13, 2005
Last sequence update: February 20, 2007
Last modified: November 30, 2016
This is version 119 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.