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Q8NFM7 (I17RD_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 97. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:IL17RD
Synonyms:IL17RLM, SEF
ORF Names:UNQ6115/PRO20026
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length739 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.1 Ref.7 Ref.8

Subunit structure

Interacts with MAP3K7 By similarity. Self-associates. Interacts with FGFR1, FGFR2 and phosphorylated MAP2K1 or MAP2K2. Associates with a MAP2K1/2-MAPK1/3 complex. Ref.1 Ref.7 Ref.8

Subcellular location

Golgi apparatus membrane; Single-pass type I membrane protein. Cell membrane; Single-pass type I membrane protein. Note: Predominantly associated with the Golgi apparatus and is partially translocated to the plasma membrane upon stimulation. Ref.2

Isoform 4: Cytoplasm Ref.2.

Tissue specificity

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. Ref.7

Involvement in disease

Hypogonadotropic hypogonadism 18 with or without anosmia (HH18) [MIM:615267]: A 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).
Note: 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 (Ref.9). Ref.9

Sequence similarities

Contains 1 SEFIR domain.

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q8NFM7-1)

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.
Isoform 2 (identifier: Q8NFM7-2)

Also known as: "IL17RLM-S; Short;

The sequence of this isoform differs from the canonical sequence as follows:
     1-144: Missing.
Isoform 3 (identifier: Q8NFM7-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-42: MAPWLQLCSVFFTVNACLNGSQLAVAAGGSGRARGADTCGWR → MPRASASGVPALFVSGEQ
Isoform 4 (identifier: Q8NFM7-4)

Also known as: hSef-b;

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1616 Potential
Chain17 – 739723Interleukin-17 receptor D
PRO_0000041871

Regions

Topological domain17 – 299283Extracellular Potential
Transmembrane300 – 32021Helical; Potential
Topological domain321 – 739419Cytoplasmic Potential
Domain355 – 509155SEFIR
Compositional bias695 – 7006Poly-Ser

Amino acid modifications

Glycosylation191N-linked (GlcNAc...) Potential
Glycosylation551N-linked (GlcNAc...) Potential
Glycosylation621N-linked (GlcNAc...) Potential
Glycosylation801N-linked (GlcNAc...) Potential
Glycosylation1371N-linked (GlcNAc...) Potential
Glycosylation1711N-linked (GlcNAc...) Potential
Glycosylation2061N-linked (GlcNAc...) Potential
Glycosylation2771N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence1 – 144144Missing in isoform 2.
VSP_015582
Alternative sequence1 – 4242MAPWL…TCGWR → MPRASASGVPALFVSGEQ in isoform 3.
VSP_015583
Alternative sequence1 – 4242MAPWL…TCGWR → MDYRQSWPWQ in isoform 4.
VSP_015584
Natural variant1311K → T in HH18; results in decreased expression at the cell surface and reduced activity. Ref.9
Corresponds to variant rs184758350 [ dbSNP | Ensembl ].
VAR_069936
Natural variant1621K → R in HH18; results in decreased expression at the cell surface. Ref.9
VAR_069937
Natural variant2551T → M. Ref.1 Ref.2 Ref.3 Ref.4 Ref.5 Ref.6
Corresponds to variant rs6780995 [ dbSNP | Ensembl ].
VAR_023478
Natural variant3011V → M.
Corresponds to variant rs17057718 [ dbSNP | Ensembl ].
VAR_023479
Natural variant3061P → S in HH18; reduced activity. Ref.9
VAR_069938
Natural variant3791Y → C in HH18; rare variant associated with susceptibility to disease; some patients have a second mutation in the HH-associated gene FGFR1; reduced activity. Ref.9
Corresponds to variant rs369641068 [ dbSNP | Ensembl ].
VAR_069939
Natural variant4681S → L in HH18; reduced activity. Ref.9
VAR_069940
Natural variant5771P → Q in HH18; reduced activity. Ref.9
VAR_069941
Natural variant7351A → 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. Ref.9
VAR_069942

Experimental info

Sequence conflict2231H → HGSDMQVSFDHAPH in CAB61408. Ref.4
Sequence conflict2481K → E in AAM74077. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (hSef-a) (IL17RLM-L) (Long) [UniParc].

Last modified February 20, 2007. Version 3.
Checksum: 7A2B45818DBD6E44

FASTA73982,411
        10         20         30         40         50         60 
MAPWLQLCSV FFTVNACLNG SQLAVAAGGS GRARGADTCG WRGVGPASRN SGLYNITFKY 

        70         80         90        100        110        120 
DNCTTYLNPV GKHVIADAQN ITISQYACHD QVAVTILWSP GALGIEFLKG FRVILEELKS 

       130        140        150        160        170        180 
EGRQCQQLIL KDPKQLNSSF KRTGMESQPF LNMKFETDYF VKVVPFPSIK NESNYHPFFF 

       190        200        210        220        230        240 
RTRACDLLLQ PDNLACKPFW KPRNLNISQH GSDMQVSFDH APHNFGFRFF YLHYKLKHEG 

       250        260        270        280        290        300 
PFKRKTCKQE QTTETTSCLL QNVSPGDYII ELVDDTNTTR KVMHYALKPV HSPWAGPIRA 

       310        320        330        340        350        360 
VAITVPLVVI SAFATLFTVM CRKKQQENIY SHLDEESSES STYTAALPRE RLRPRPKVFL 

       370        380        390        400        410        420 
CYSSKDGQNH MNVVQCFAYF LQDFCGCEVA LDLWEDFSLC REGQREWVIQ KIHESQFIIV 

       430        440        450        460        470        480 
VCSKGMKYFV DKKNYKHKGG GRGSGKGELF LVAVSAIAEK LRQAKQSSSA ALSKFIAVYF 

       490        500        510        520        530        540 
DYSCEGDVPG ILDLSTKYRL MDNLPQLCSH LHSRDHGLQE PGQHTRQGSR RNYFRSKSGR 

       550        560        570        580        590        600 
SLYVAICNMH QFIDEEPDWF EKQFVPFHPP PLRYREPVLE KFDSGLVLND VMCKPGPESD 

       610        620        630        640        650        660 
FCLKVEAAVL GATGPADSQH ESQHGGLDQD GEARPALDGS AALQPLLHTV KAGSPSDMPR 

       670        680        690        700        710        720 
DSGIYDSSVP SSELSLPLME GLSTDQTETS SLTESVSSSS GLGEEEPPAL PSKLLSSGSC 

       730 
KADLGCRSYT DELHAVAPL 

« Hide

Isoform 2 ("IL17RLM-S) (Short) [UniParc].

Checksum: 12307ED8AA4B4041
Show »

FASTA59566,817
Isoform 3 [UniParc].

Checksum: 27564B1A6F365EF6
Show »

FASTA71579,871
Isoform 4 (hSef-b) [UniParc].

Checksum: 116027A2BD48902D
Show »

FASTA70779,463

References

« Hide 'large scale' references
[1]"hSef inhibits PC-12 cell differentiation by interfering with Ras-mitogen-activated protein kinase MAPK signaling."
Xiong S.Q., Zhao Q.H., Rong Z., Huang G.R., Huang Y., Chen P.L., Zhang S., Liu L., Chang Z.J.
J. Biol. Chem. 278:50273-50282(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), VARIANT MET-255, FUNCTION, INTERACTION WITH FGFR1 AND FGFR2.
[2]"Alternative splicing generates an isoform of the human Sef gene with altered subcellular localization and specificity."
Preger E., Ziv I., Shabtay A., Sher I., Tsang M., Dawid I.B., Altuvia Y., Ron D.
Proc. Natl. Acad. Sci. U.S.A. 101:1229-1234(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), VARIANT MET-255, SUBCELLULAR LOCATION.
Tissue: Testis.
[3]"Identification of novel IL-17 related receptors."
Gilbert J.M., Gorman D.M.
Submitted (DEC-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT MET-255.
[4]"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment."
Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. expand/collapse author list , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.
Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), VARIANT MET-255.
[5]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT MET-255.
Tissue: Testis.
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4), VARIANT MET-255.
[7]"A novel interleukin-17 receptor-like protein identified in human umbilical vein endothelial cells antagonizes basic fibroblast growth factor-induced signaling."
Yang R.-B., Domingos Ng C.K., Wasserman S.M., Koemueves L.G., Gerritsen M.E., Topper J.N.
J. Biol. Chem. 278:33232-33238(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY, HOMOOLIGOMERIZATION, INTERACTION WITH FGFR1.
[8]"Sef is a spatial regulator for Ras/MAP kinase signaling."
Torii S., Kusakabe M., Yamamoto T., Maekawa M., Nishida E.
Dev. Cell 7:33-44(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH MAP2K1/2, IDENTIFICATION IN A COMPLEX WITH MAP2K1/2 AND MAPK1/3.
[9]"Mutations in FGF17, IL17RD, DUSP6, SPRY4, and FLRT3 are identified in individuals with congenital hypogonadotropic hypogonadism."
Miraoui H., Dwyer A.A., Sykiotis G.P., Plummer L., Chung W., Feng B., Beenken A., Clarke J., Pers T.H., Dworzynski P., Keefe K., Niedziela M., Raivio T., Crowley W.F. Jr., Seminara S.B., Quinton R., Hughes V.A., Kumanov P. expand/collapse author list , Young J., Yialamas M.A., Hall J.E., Van Vliet G., Chanoine J.P., Rubenstein J., Mohammadi M., Tsai P.S., Sidis Y., Lage K., Pitteloud N.
Am. J. Hum. Genet. 92:725-743(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HH18 THR-131; ARG-162; SER-306; CYS-379; LEU-468; GLN-577 AND VAL-735, CHARACTERIZATION OF VARIANTS HH18 THR-131; ARG-162; SER-306; CYS-379; LEU-468; GLN-577 AND VAL-735.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS2880.2. [Q8NFM7-1]
PIRT42695.
RefSeqNP_060033.3. NM_017563.3. [Q8NFM7-1]
XP_006713272.1. XM_006713209.1. [Q8NFM7-2]
UniGeneHs.150725.

3D structure databases

ProteinModelPortalQ8NFM7.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid120132. 1 interaction.
STRING9606.ENSP00000296318.

PTM databases

PhosphoSiteQ8NFM7.

Polymorphism databases

DMDM126302555.

Proteomic databases

PaxDbQ8NFM7.
PRIDEQ8NFM7.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000296318; ENSP00000296318; ENSG00000144730. [Q8NFM7-1]
ENST00000320057; ENSP00000322250; ENSG00000144730. [Q8NFM7-2]
ENST00000427856; ENSP00000399209; ENSG00000144730. [Q8NFM7-3]
ENST00000463523; ENSP00000417516; ENSG00000144730. [Q8NFM7-2]
GeneID54756.
KEGGhsa:54756.
UCSCuc003dik.3. human. [Q8NFM7-3]
uc003dil.3. human. [Q8NFM7-1]

Organism-specific databases

CTD54756.
GeneCardsGC03M057124.
H-InvDBHIX0003391.
HGNCHGNC:17616. IL17RD.
HPAHPA039577.
HPA043550.
MIM606807. gene.
615267. phenotype.
neXtProtNX_Q8NFM7.
Orphanet478. Kallmann syndrome.
PharmGKBPA134993407.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG45649.
HOVERGENHBG081777.
InParanoidQ8NFM7.
KOK05167.
OMASTKYKLM.
OrthoDBEOG7P8P7V.
PhylomeDBQ8NFM7.
TreeFamTF329644.

Gene expression databases

ArrayExpressQ8NFM7.
BgeeQ8NFM7.
CleanExHS_IL17RD.
GenevestigatorQ8NFM7.

Family and domain databases

InterProIPR013568. SEFIR.
IPR000157. TIR_dom.
[Graphical view]
PfamPF08357. SEFIR. 1 hit.
[Graphical view]
SUPFAMSSF52200. SSF52200. 1 hit.
PROSITEPS51534. SEFIR. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSIL17RD. human.
GenomeRNAi54756.
NextBio57378.
PROQ8NFM7.
SOURCESearch...

Entry information

Entry nameI17RD_HUMAN
AccessionPrimary (citable) accession number: Q8NFM7
Secondary accession number(s): Q2NKP7 expand/collapse secondary AC list , Q58EZ7, Q6RVF4, Q6UWI5, Q8N113, Q8NFS0, Q9UFA0
Entry history
Integrated into UniProtKB/Swiss-Prot: September 13, 2005
Last sequence update: February 20, 2007
Last modified: July 9, 2014
This is version 97 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM