P56159 (GFRA1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
GDNF family receptor alpha-1
Short name=GDNF receptor alpha-1
Short name=GDNFR-alpha-1
Short name=GFR-alpha-1

Alternative name(s):
RET ligand 1
TGF-beta-related neurotrophic factor receptor 1

Gene names

Name:	GFRA1
Synonyms:	GDNFRA, RETL1, TRNR1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	465 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Receptor for GDNF. Mediates the GDNF-induced autophosphorylation and activation of the RET receptor By similarity.
Subunit structure	2 molecules of GDNFR-alpha are thought to form a complex with the disulfide-linked GDNF dimer and with 2 molecules of RET By similarity.
Subcellular location	Cell membrane; Lipid-anchor › GPI-anchor By similarity.
Sequence similarities	Belongs to the GDNFR family.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat Signal
Molecular function	Receptor
PTM	Disulfide bond GPI-anchor Glycoprotein Lipoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	axon guidance Traceable author statement. Source: Reactome
Cellular component	anchored to membrane Inferred from electronic annotation. Source: UniProtKB-KW extrinsic to membrane Non-traceable author statement. Source: UniProtKB plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	glial cell-derived neurotrophic factor receptor activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P56159-1)

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: P56159-2)

The sequence of this isoform differs from the canonical sequence as follows:
     140-144: Missing.

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 24	24	Potential
	Chain	25 – 429	405	GDNF family receptor alpha-1		PRO_0000010777
	Propeptide	430 – 465	36	Removed in mature form Potential		PRO_0000010778
Regions
	Repeat	25 – 113	89	1
	Repeat	150 – 238	89	2
	Repeat	239 – 342	104	3
	Compositional bias	362 – 369	8	Poly-Thr
Amino acid modifications
	Lipidation	429	1	GPI-anchor amidated serine Potential
	Glycosylation	59	1	N-linked (GlcNAc...) Potential
	Glycosylation	347	1	N-linked (GlcNAc...) Potential
	Glycosylation	406	1	N-linked (GlcNAc...) Potential
	Disulfide bond	29 ↔ 87		By similarity
	Disulfide bond	36 ↔ 42		By similarity
	Disulfide bond	52 ↔ 72		By similarity
	Disulfide bond	89 ↔ 99		By similarity
	Disulfide bond	154 ↔ 214		By similarity
	Disulfide bond	161 ↔ 167		By similarity
	Disulfide bond	178 ↔ 192		By similarity
	Disulfide bond	187 ↔ 233		By similarity
	Disulfide bond	216 ↔ 221		By similarity
	Disulfide bond	243 ↔ 313		By similarity
	Disulfide bond	250 ↔ 256		By similarity
	Disulfide bond	267 ↔ 285		By similarity
	Disulfide bond	277 ↔ 337		By similarity
	Disulfide bond	315 ↔ 325		By similarity
Natural variations
	Alternative sequence	140 – 144	5	Missing in isoform 2.		VSP_001660
	Natural variant	85	1	Y → N. Ref.3 Corresponds to variant rs8192662 [ dbSNP | Ensembl ].		VAR_012488
	Natural variant	366	1	T → A. Ref.3 Ref.10 Corresponds to variant rs2072276 [ dbSNP | Ensembl ].		VAR_012489
	Natural variant	371	1	L → R May be involved in congenital central hypoventilation syndrome. Ref.10		VAR_018261
Experimental info
	Sequence conflict	245	1	Missing no nucleotide entry Ref.1
	Sequence conflict	358	1	F → P no nucleotide entry Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 23, 2002. Version 2. Checksum: 91A550D06A6777BD	FASTA	465	51,456
	10 20 30 40 50 60 MFLATLYFAL PLLDLLLSAE VSGGDRLDCV KASDQCLKEQ SCSTKYRTLR QCVAGKETNF 70 80 90 100 110 120 SLASGLEAKD ECRSAMEALK QKSLYNCRCK RGMKKEKNCL RIYWSMYQSL QGNDLLEDSP 130 140 150 160 170 180 YEPVNSRLSD IFRVVPFISD VFQQVEHIPK GNNCLDAAKA CNLDDICKKY RSAYITPCTT 190 200 210 220 230 240 SVSNDVCNRR KCHKALRQFF DKVPAKHSYG MLFCSCRDIA CTERRRQTIV PVCSYEEREK 250 260 270 280 290 300 PNCLNLQDSC KTNYICRSRL ADFFTNCQPE SRSVSSCLKE NYADCLLAYS GLIGTVMTPN 310 320 330 340 350 360 YIDSSSLSVA PWCDCSNSGN DLEECLKFLN FFKDNTCLKN AIQAFGNGSD VTVWQPAFPV 370 380 390 400 410 420 QTTTATTTTA LRVKNKPLGP AGSENEIPTH VLPPCANLQA QKLKSNVSGN THLCISNGNY 430 440 450 460 EKEGLGASSH ITTKSMAAPP SCGLSPLLVL VVTALSTLLS LTETS
	Isoform 2 [UniParc]. Checksum: F5620DE4F2E122AA	FASTA	460	50,838
	10 20 30 40 50 60 MFLATLYFAL PLLDLLLSAE VSGGDRLDCV KASDQCLKEQ SCSTKYRTLR QCVAGKETNF 70 80 90 100 110 120 SLASGLEAKD ECRSAMEALK QKSLYNCRCK RGMKKEKNCL RIYWSMYQSL QGNDLLEDSP 130 140 150 160 170 180 YEPVNSRLSD IFRVVPFISV EHIPKGNNCL DAAKACNLDD ICKKYRSAYI TPCTTSVSND 190 200 210 220 230 240 VCNRRKCHKA LRQFFDKVPA KHSYGMLFCS CRDIACTERR RQTIVPVCSY EEREKPNCLN 250 260 270 280 290 300 LQDSCKTNYI CRSRLADFFT NCQPESRSVS SCLKENYADC LLAYSGLIGT VMTPNYIDSS 310 320 330 340 350 360 SLSVAPWCDC SNSGNDLEEC LKFLNFFKDN TCLKNAIQAF GNGSDVTVWQ PAFPVQTTTA 370 380 390 400 410 420 TTTTALRVKN KPLGPAGSEN EIPTHVLPPC ANLQAQKLKS NVSGNTHLCI SNGNYEKEGL 430 440 450 460 GASSHITTKS MAAPPSCGLS PLLVLVVTAL STLLSLTETS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"GDNF-induced activation of the ret protein tyrosine kinase is mediated by GDNFR-alpha, a novel receptor for GDNF." Jing S., Wen D., Yu Y., Holst P.L., Luo Y., Fang M., Tamir R., Antonio L., Hu Z., Cupples R., Louis J.-C., Hu S., Altrock B.W., Fox G.M. Cell 85:1113-1124(1996) [PubMed: 8674117] [Abstract] Cited for: NUCLEOTIDE SEQUENCE (ISOFORM 1). Tissue: Substantia nigra.
[2]	"Glial cell line-derived neurotrophic factor-dependent RET activation can be mediated by two different cell-surface accessory proteins." Sanicola M., Hession C.A., Worley D.S., Carmillo P., Ehrenfels C., Walus L., Robinson S., Jaworski G., Wei H., Tizard R., Whitty A., Pepinsky R.B., Cate R.L. Proc. Natl. Acad. Sci. U.S.A. 94:6238-6243(1997) [PubMed: 9177201] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Kidney.
[3]	"Human GFRA1: cloning, mapping, genomic structure, and evaluation as a candidate gene for Hirschsprung disease susceptibility." Angrist M., Jing S., Bolk S., Bentley K., Nallasamy S., Halushka M., Fox G.M., Chakravarti A. Genomics 48:354-362(1998) [PubMed: 9545641] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), VARIANTS ASN-85 AND ALA-366.
[4]	"Mutational analysis of the GDNF/RET-GDNFR-alpha signaling complex in a kindred with vesicoureteral reflux." Shefelbine S.E., Khorana S., Schultz P.N., Huang E., Thobe N., Hu Z.J., Fox G.M., Jing S., Cote G.J., Gagel R.F. Hum. Genet. 102:474-478(1998) [PubMed: 9600247] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Thyroid carcinoma.
[5]	"GDNF-induced differentiation and its enhancement by retinoic acid in primary human neuroblastomas expressing c-Ret and GDNFR-alpha." Hishiki T., Kondoh K., Ichimiya S., Nimura Y., Seki N., Ozaki T., Sakiyama S., Takahashi H., Ohnuma N., Tanabe M., Fujimura S., Nakagawara A. Submitted (OCT-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Substantia nigra.
[6]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Trachea.
[7]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Eye.
[9]	"An unappreciated role for RNA surveillance." Hillman R.T., Green R.E., Brenner S.E. Genome Biol. 5:R8.1-R8.16(2004) [PubMed: 14759258] [Abstract] Cited for: SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
[10]	"Molecular analysis of congenital central hypoventilation syndrome." Sasaki A., Kanai M., Kijima K., Akaba K., Hashimoto M., Hasegawa H., Otaki S., Koizumi T., Kusuda S., Ogawa Y., Tuchiya K., Yamamoto W., Nakamura T., Hayasaka K. Hum. Genet. 114:22-26(2003) [PubMed: 14566559] [Abstract] Cited for: VARIANTS ALA-366 AND ARG-371.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U97144 mRNA. Translation: AAC51646.1. AF038420 , AF038411, AF038412, AF038413, AF038414, AF038415, AF038416, AF038417, AF038418, AF038419 Genomic DNA. Translation: AAC39693.1. AF038421 mRNA. Translation: AAC39692.1. AF042080 mRNA. Translation: AAB97371.1. AF058999 , AF058990, AF058991, AF058992, AF058993, AF058994, AF058995, AF058996, AF058997, AF058998 Genomic DNA. Translation: AAC14431.1. U95847 mRNA. Translation: AAB71811.1. AK292886 mRNA. Translation: BAF85575.1. CH471066 Genomic DNA. Translation: EAW49458.1. BC014962 mRNA. Translation: AAH14962.1.
IPI	IPI00008148. IPI00220291.
RefSeq	NP_001138925.1. NM_001145453.1. NP_005255.1. NM_005264.4. NP_665736.1. NM_145793.3.
UniGene	Hs.388347.
3D structure databases
ProteinModelPortal	P56159.
SMR	P56159. Positions 150-349.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-59052N.
IntAct	P56159. 1 interaction.
STRING	P56159.
Polymorphism databases
DMDM	20141405.
Proteomic databases
PRIDE	P56159.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000439649; ENSP00000393725; ENSG00000151892.
GeneID	2674.
KEGG	hsa:2674.
UCSC	uc001lci.1. human. uc001lcj.1. human.
Organism-specific databases
CTD	2674.
GeneCards	GC10M117813.
H-InvDB	HIX0009233.
HGNC	HGNC:4243. GFRA1.
MIM	601496. gene.
neXtProt	NX_P56159.
PharmGKB	PA28653.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG10169.
GeneTree	ENSGT00550000074579.
HOGENOM	HBG713385.
HOVERGEN	HBG051725.
InParanoid	P56159.
OMA	SCRDIAC.
PhylomeDB	P56159.
Enzyme and pathway databases
Pathway_Interaction_DB	ret_pathway. Signaling events regulated by Ret tyrosine kinase.
Reactome	REACT_111045. Developmental Biology.
Gene expression databases
ArrayExpress	P56159.
Bgee	P56159.
CleanEx	HS_GFRA1.
Genevestigator	P56159.
GermOnline	ENSG00000151892. Homo sapiens.
Family and domain databases
InterPro	IPR016017. GDNF/GAS1. IPR003438. GDNF_rcpt. IPR003503. GDNF_rcpt_A1. IPR017372. Glial_neurotroph_fac_rcpt_a1/2. [Graphical view]
Pfam	PF02351. GDNF. 3 hits. [Graphical view]
PIRSF	PIRSF038071. GDNF_family_receptor_alpha. 1 hit.
PRINTS	PR01317. GDNFRALPHA1. PR01316. GDNFRECEPTOR.
SMART	SM00907. GDNF. 3 hits. [Graphical view]
ProtoNet	Search...
Other
NextBio	10554.
SOURCE	Search...

Entry information

Entry name

GFRA1_HUMAN

Accession

Primary (citable) accession number: P56159
Secondary accession number(s): A8KA21, O15507, O43912

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	January 23, 2002
Last modified:	January 25, 2012
This is version 104 of the entry and version 2 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.