Reviewed, UniProtKB/Swiss-Prot O00451 (GFRA2_HUMAN)

Names and origin

Protein names

Recommended name:
GDNF family receptor alpha-2
Short name=GFR-alpha-2
Short name=GDNF receptor alpha-2
Short name=GDNFR-alpha-2

Alternative name(s):
Neurturin receptor alpha
Short name=NRTNR-alpha
Short name=NTNR-alpha
TGF-beta-related neurotrophic factor receptor 2
GDNF receptor beta
Short name=GDNFR-beta
RET ligand 2

Gene names

Name:	GFRA2
Synonyms:	GDNFRB, RETL2, TRNR2

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	464 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 neurturin. Mediates the NRTN-induced autophosphorylation and activation of the RET receptor. Also able to mediate GDNF signaling through the RET tyrosine kinase receptor.
Subcellular location	Cell membrane; Lipid-anchor › GPI-anchor By similarity.
Tissue specificity	Isoform 1 is found in both brain and placenta.
Sequence similarities	Belongs to the GDNFR family.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal
Molecular function	Receptor
PTM	GPI-anchor Glycoprotein Lipoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	transmembrane receptor protein tyrosine kinase signaling pathway Traceable author statement. Source: ProtInc
Cellular component	anchored to membrane Inferred from electronic annotation. Source: UniProtKB-KW extrinsic to membrane Traceable author statement. Source: ProtInc plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	glial cell line-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: O00451-1)

Also known as: 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: O00451-2)

Also known as: Short;

The sequence of this isoform differs from the canonical sequence as follows:
     14-146: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 21	21	Potential
	Chain	22 – 444	423	GDNF family receptor alpha-2		PRO_0000010785
	Propeptide	445 – 464	20	Removed in mature form Potential		PRO_0000010786
Amino acid modifications
	Lipidation	444	1	GPI-anchor amidated serine Potential
	Glycosylation	52	1	N-linked (GlcNAc...) Potential
	Glycosylation	357	1	N-linked (GlcNAc...) Potential
	Glycosylation	413	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	14 – 146	133	Missing in isoform 2.		VSP_001661
	Natural variant	462	1	L → Q: dbSNP rs1128397. Ref.1 Ref.2 Ref.4		VAR_059976
Experimental info
	Sequence conflict	6	1	V → A in AAB61922. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Long) [UniParc]. Last modified October 31, 2006. Version 2. Checksum: 8BC61529530FF21F	FASTA	464	51,544
	10 20 30 40 50 60 MILANVFCLF FFLDETLRSL ASPSSLQGPE LHGWRPPVDC VRANELCAAE SNCSSRYRTL 70 80 90 100 110 120 RQCLAGRDRN TMLANKECQA ALEVLQESPL YDCRCKRGMK KELQCLQIYW SIHLGLTEGE 130 140 150 160 170 180 EFYEASPYEP VTSRLSDIFR LASIFSGTGA DPVVSAKSNH CLDAAKACNL NDNCKKLRSS 190 200 210 220 230 240 YISICNREIS PTERCNRRKC HKALRQFFDR VPSEYTYRML FCSCQDQACA ERRRQTILPS 250 260 270 280 290 300 CSYEDKEKPN CLDLRGVCRT DHLCRSRLAD FHANCRASYQ TVTSCPADNY QACLGSYAGM 310 320 330 340 350 360 IGFDMTPNYV DSSPTGIVVS PWCSCRGSGN MEEECEKFLR DFTENPCLRN AIQAFGNGTD 370 380 390 400 410 420 VNVSPKGPSF QATQAPRVEK TPSLPDDLSD STSLGTSVIT TCTSVQEQGL KANNSKELSM 430 440 450 460 CFTELTTNII PGSNKVIKPN SGPSRARPSA ALTVLSVLML KLAL
	Isoform 2 (Short). Checksum: 10ECFBA492E2393C	FASTA	331	36,456
	10 20 30 40 50 60 MILANVFCLF FFLGTGADPV VSAKSNHCLD AAKACNLNDN CKKLRSSYIS ICNREISPTE 70 80 90 100 110 120 RCNRRKCHKA LRQFFDRVPS EYTYRMLFCS CQDQACAERR RQTILPSCSY EDKEKPNCLD 130 140 150 160 170 180 LRGVCRTDHL CRSRLADFHA NCRASYQTVT SCPADNYQAC LGSYAGMIGF DMTPNYVDSS 190 200 210 220 230 240 PTGIVVSPWC SCRGSGNMEE ECEKFLRDFT ENPCLRNAIQ AFGNGTDVNV SPKGPSFQAT 250 260 270 280 290 300 QAPRVEKTPS LPDDLSDSTS LGTSVITTCT SVQEQGLKAN NSKELSMCFT ELTTNIIPGS 310 320 330 NKVIKPNSGP SRARPSAALT VLSVLMLKLA L

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"TrnR2, a novel receptor that mediates neurturin and GDNF signaling through Ret." Baloh R.H., Tansey M.G., Golden J.P., Creedon D.J., Heuckeroth R.O., Keck C.L., Zimonjic D.B., Popescu N.C., Johnson E.M. Jr., Milbrandt J. Neuron 18:793-802(1997) [PubMed: 9182803] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), VARIANT GLN-462.
[2]	"Cloning, mRNA distribution and chromosomal localisation of the gene for glial cell line-derived neurotrophic factor receptor beta, a homologue to GDNFR-alpha." Suvanto P., Wartiovaara K., Lindahl M., Arumae U., Moshnyakov M., Horelli-Kuitunen N., Airaksinen M.S., Palotie A., Sariola H., Saarma M. Hum. Mol. Genet. 6:1267-1273(1997) [PubMed: 9259272] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT GLN-462. Tissue: Fetal brain.
[3]	"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 1). Tissue: Liver.
[4]	Yoong L.F., Too H.P. Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), VARIANT GLN-462.
[5]	"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]. Tissue: Brain.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF002700 mRNA. Translation: AAC52036.1. U93703 mRNA. Translation: AAB61922.1. U97145 mRNA. Translation: AAC51647.1. AY326396 mRNA. Translation: AAP88378.1. BC041688 mRNA. Translation: AAH41688.1.
IPI	IPI00011732. IPI00398301.
RefSeq	NP_001158510.1. NP_001158511.1. NP_001486.4.
UniGene	Hs.441202
3D structure databases
SMR	O00451. Positions 157-355, 247-356.
ModBase	Search...
Protein-protein interaction databases
STRING	O00451.
Proteomic databases
PRIDE	O00451.
Genome annotation databases
Ensembl	ENST00000306793; ENSP00000306654; ENSG00000168546; Homo sapiens. [Genome view]
GeneID	2675.
UCSC	uc003wzu.1. human. uc003wzw.1. human.
Organism-specific databases
CTD	2675.
GeneCards	GC08M021593.
H-InvDB	HIX0025538.
HGNC	HGNC:4244. GFRA2.
HPA	HPA024704.
MIM	601956. gene.
PharmGKB	PA28654.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG11053.
HOGENOM	HBG713385.
HOVERGEN	HBG051725.
InParanoid	O00451.
OMA	YEPVTSR.
OrthoDB	EOG9030C0.
PhylomeDB	O00451.
Enzyme and pathway databases
Reactome	REACT_18266. Axon guidance.
Gene expression databases
ArrayExpress	O00451.
Bgee	O00451.
CleanEx	HS_GFRA2.
Genevestigator	O00451.
GermOnline	ENSG00000168546. Homo sapiens.
Family and domain databases
InterPro	IPR016017. GDNF/GAS1. IPR003438. GDNF_rcpt. IPR003504. GDNF_rcpt_a2. 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	PR01318. GDNFRALPHA2. PR01316. GDNFRECEPTOR.
ProtoNet	Search...
Other Resources
NextBio	10560.
SOURCE	Search...

Entry information

Entry name

GFRA2_HUMAN

Accession

Primary (citable) accession number: O00451
Secondary accession number(s): O15316 , O15328, Q6GTR9, Q7Z5C2

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	October 31, 2006
Last modified:	March 2, 2010
This is version 85 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.