Q8NFM7 (I17RD_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	IL17RD
Synonyms:	IL17RLM, SEF
ORF Names:	UNQ6115/PRO20026

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	739 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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. 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
Sequence similarities	Contains 1 SEFIR domain.

Ontologies

Keywords
Cellular component	Cell membrane Cytoplasm Golgi apparatus Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal Transmembrane Transmembrane helix
Molecular function	Receptor
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Cellular_component	Golgi membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Complete GO annotation...

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 16	16	Potential
	Chain	17 – 739	723	Interleukin-17 receptor D		PRO_0000041871
Regions
	Topological domain	17 – 299	283	Extracellular Potential
	Transmembrane	300 – 320	21	Helical; Potential
	Topological domain	321 – 739	419	Cytoplasmic Potential
	Domain	355 – 509	155	SEFIR
	Compositional bias	695 – 700	6	Poly-Ser
Amino acid modifications
	Glycosylation	19	1	N-linked (GlcNAc...) Potential
	Glycosylation	55	1	N-linked (GlcNAc...) Potential
	Glycosylation	62	1	N-linked (GlcNAc...) Potential
	Glycosylation	80	1	N-linked (GlcNAc...) Potential
	Glycosylation	137	1	N-linked (GlcNAc...) Potential
	Glycosylation	171	1	N-linked (GlcNAc...) Potential
	Glycosylation	206	1	N-linked (GlcNAc...) Potential
	Glycosylation	277	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	1 – 144	144	Missing in isoform 2.		VSP_015582
	Alternative sequence	1 – 42	42	MAPWL…TCGWR → MPRASASGVPALFVSGEQ in isoform 3.		VSP_015583
	Alternative sequence	1 – 42	42	MAPWL…TCGWR → MDYRQSWPWQ in isoform 4.		VSP_015584
	Natural variant	255	1	T → M. Ref.1 Ref.2 Ref.3 Ref.4 Ref.5 Ref.6 Corresponds to variant rs6780995 [ dbSNP | Ensembl ].		VAR_023478
	Natural variant	301	1	V → M. Corresponds to variant rs17057718 [ dbSNP | Ensembl ].		VAR_023479
Experimental info
	Sequence conflict	223	1	H → HGSDMQVSFDHAPH in CAB61408. Ref.4
	Sequence conflict	248	1	K → E in AAM74077. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (hSef-a) (IL17RLM-L) (Long) [UniParc]. Last modified February 20, 2007. Version 3. Checksum: 7A2B45818DBD6E44	FASTA	739	82,411
	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
	Isoform 2 ("IL17RLM-S) (Short) [UniParc]. Checksum: 12307ED8AA4B4041	FASTA	595	66,817
	10 20 30 40 50 60 MESQPFLNMK FETDYFVKVV PFPSIKNESN YHPFFFRTRA CDLLLQPDNL ACKPFWKPRN 70 80 90 100 110 120 LNISQHGSDM QVSFDHAPHN FGFRFFYLHY KLKHEGPFKR KTCKQEQTTE TTSCLLQNVS 130 140 150 160 170 180 PGDYIIELVD DTNTTRKVMH YALKPVHSPW AGPIRAVAIT VPLVVISAFA TLFTVMCRKK 190 200 210 220 230 240 QQENIYSHLD EESSESSTYT AALPRERLRP RPKVFLCYSS KDGQNHMNVV QCFAYFLQDF 250 260 270 280 290 300 CGCEVALDLW EDFSLCREGQ REWVIQKIHE SQFIIVVCSK GMKYFVDKKN YKHKGGGRGS 310 320 330 340 350 360 GKGELFLVAV SAIAEKLRQA KQSSSAALSK FIAVYFDYSC EGDVPGILDL STKYRLMDNL 370 380 390 400 410 420 PQLCSHLHSR DHGLQEPGQH TRQGSRRNYF RSKSGRSLYV AICNMHQFID EEPDWFEKQF 430 440 450 460 470 480 VPFHPPPLRY REPVLEKFDS GLVLNDVMCK PGPESDFCLK VEAAVLGATG PADSQHESQH 490 500 510 520 530 540 GGLDQDGEAR PALDGSAALQ PLLHTVKAGS PSDMPRDSGI YDSSVPSSEL SLPLMEGLST 550 560 570 580 590 DQTETSSLTE SVSSSSGLGE EEPPALPSKL LSSGSCKADL GCRSYTDELH AVAPL
	Isoform 3 [UniParc]. Checksum: 27564B1A6F365EF6	FASTA	715	79,871
	10 20 30 40 50 60 MPRASASGVP ALFVSGEQGV GPASRNSGLY NITFKYDNCT TYLNPVGKHV IADAQNITIS 70 80 90 100 110 120 QYACHDQVAV TILWSPGALG IEFLKGFRVI LEELKSEGRQ CQQLILKDPK QLNSSFKRTG 130 140 150 160 170 180 MESQPFLNMK FETDYFVKVV PFPSIKNESN YHPFFFRTRA CDLLLQPDNL ACKPFWKPRN 190 200 210 220 230 240 LNISQHGSDM QVSFDHAPHN FGFRFFYLHY KLKHEGPFKR KTCKQEQTTE TTSCLLQNVS 250 260 270 280 290 300 PGDYIIELVD DTNTTRKVMH YALKPVHSPW AGPIRAVAIT VPLVVISAFA TLFTVMCRKK 310 320 330 340 350 360 QQENIYSHLD EESSESSTYT AALPRERLRP RPKVFLCYSS KDGQNHMNVV QCFAYFLQDF 370 380 390 400 410 420 CGCEVALDLW EDFSLCREGQ REWVIQKIHE SQFIIVVCSK GMKYFVDKKN YKHKGGGRGS 430 440 450 460 470 480 GKGELFLVAV SAIAEKLRQA KQSSSAALSK FIAVYFDYSC EGDVPGILDL STKYRLMDNL 490 500 510 520 530 540 PQLCSHLHSR DHGLQEPGQH TRQGSRRNYF RSKSGRSLYV AICNMHQFID EEPDWFEKQF 550 560 570 580 590 600 VPFHPPPLRY REPVLEKFDS GLVLNDVMCK PGPESDFCLK VEAAVLGATG PADSQHESQH 610 620 630 640 650 660 GGLDQDGEAR PALDGSAALQ PLLHTVKAGS PSDMPRDSGI YDSSVPSSEL SLPLMEGLST 670 680 690 700 710 DQTETSSLTE SVSSSSGLGE EEPPALPSKL LSSGSCKADL GCRSYTDELH AVAPL
	Isoform 4 (hSef-b) [UniParc]. Checksum: 116027A2BD48902D	FASTA	707	79,463
	10 20 30 40 50 60 MDYRQSWPWQ GVGPASRNSG LYNITFKYDN CTTYLNPVGK HVIADAQNIT ISQYACHDQV 70 80 90 100 110 120 AVTILWSPGA LGIEFLKGFR VILEELKSEG RQCQQLILKD PKQLNSSFKR TGMESQPFLN 130 140 150 160 170 180 MKFETDYFVK VVPFPSIKNE SNYHPFFFRT RACDLLLQPD NLACKPFWKP RNLNISQHGS 190 200 210 220 230 240 DMQVSFDHAP HNFGFRFFYL HYKLKHEGPF KRKTCKQEQT TETTSCLLQN VSPGDYIIEL 250 260 270 280 290 300 VDDTNTTRKV MHYALKPVHS PWAGPIRAVA ITVPLVVISA FATLFTVMCR KKQQENIYSH 310 320 330 340 350 360 LDEESSESST YTAALPRERL RPRPKVFLCY SSKDGQNHMN VVQCFAYFLQ DFCGCEVALD 370 380 390 400 410 420 LWEDFSLCRE GQREWVIQKI HESQFIIVVC SKGMKYFVDK KNYKHKGGGR GSGKGELFLV 430 440 450 460 470 480 AVSAIAEKLR QAKQSSSAAL SKFIAVYFDY SCEGDVPGIL DLSTKYRLMD NLPQLCSHLH 490 500 510 520 530 540 SRDHGLQEPG QHTRQGSRRN YFRSKSGRSL YVAICNMHQF IDEEPDWFEK QFVPFHPPPL 550 560 570 580 590 600 RYREPVLEKF DSGLVLNDVM CKPGPESDFC LKVEAAVLGA TGPADSQHES QHGGLDQDGE 610 620 630 640 650 660 ARPALDGSAA LQPLLHTVKA GSPSDMPRDS GIYDSSVPSS ELSLPLMEGL STDQTETSSL 670 680 690 700 TESVSSSSGL GEEEPPALPS KLLSSGSCKA DLGCRSYTDE LHAVAPL

References

	« Hide 'large scale' referencesShow '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. , 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.
+	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.
IPI	IPI00302984. IPI00395790. IPI00640049. IPI00641705.
PIR	T42695.
RefSeq	NP_060033.3. NM_017563.3.
UniGene	Hs.150725.
3D structure databases
ProteinModelPortal	Q8NFM7.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000296318.
PTM databases
PhosphoSite	Q8NFM7.
Polymorphism databases
DMDM	126302555.
Proteomic databases
PaxDb	Q8NFM7.
PRIDE	Q8NFM7.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000296318; ENSP00000296318; ENSG00000144730. ENST00000320057; ENSP00000322250; ENSG00000144730. ENST00000427856; ENSP00000399209; ENSG00000144730. ENST00000463523; ENSP00000417516; ENSG00000144730.
GeneID	54756.
KEGG	hsa:54756.
UCSC	uc003dik.3. human. uc003dil.3. human.
Organism-specific databases
CTD	54756.
GeneCards	GC03M057124.
H-InvDB	HIX0003391.
HGNC	HGNC:17616. IL17RD.
HPA	HPA039577. HPA043550.
MIM	606807. gene.
neXtProt	NX_Q8NFM7.
PharmGKB	PA134993407.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG45649.
HOVERGEN	HBG081777.
InParanoid	Q8NFM7.
KO	K05167.
OMA	DLWEDFS.
OrthoDB	EOG451DQ6.
PhylomeDB	Q8NFM7.
Enzyme and pathway databases
Pathway_Interaction_DB	fgf_pathway. FGF signaling pathway.
Gene expression databases
ArrayExpress	Q8NFM7.
Bgee	Q8NFM7.
CleanEx	HS_IL17RD.
Genevestigator	Q8NFM7.
GermOnline	ENSG00000144730. Homo sapiens.
Family and domain databases
InterPro	IPR013568. SEFIR. [Graphical view]
Pfam	PF08357. SEFIR. 1 hit. [Graphical view]
PROSITE	PS51534. SEFIR. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	IL17RD. human.
GenomeRNAi	54756.
NextBio	57378.
SOURCE	Search...

Entry information

Entry name

I17RD_HUMAN

Accession

Primary (citable) accession number: Q8NFM7
Secondary accession number(s): Q2NKP7 , Q58EZ7, Q6RVF4, Q6UWI5, Q8N113, Q8NFS0, Q9UFA0

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 13, 2005
Last sequence update:	February 20, 2007
Last modified:	May 1, 2013
This is version 86 of the entry and version 3 of the sequence. [Complete history]

Entry status

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.