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O00451 (GFRA2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 121. 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:
GDNF family receptor alpha-2

Short name=GDNF receptor alpha-2
Short name=GDNFR-alpha-2
Short name=GFR-alpha-2
Alternative name(s):
GDNF receptor beta
Short name=GDNFR-beta
Neurturin receptor alpha
Short name=NRTNR-alpha
Short name=NTNR-alpha
RET ligand 2
TGF-beta-related neurotrophic factor receptor 2
Gene names
Name:GFRA2
Synonyms:GDNFRB, RETL2, TRNR2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length464 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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-anchorGPI-anchor By similarity.

Tissue specificity

Isoform 1 is found in both brain and placenta.

Sequence similarities

Belongs to the GDNFR family.

Alternative products

This entry describes 3 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.
Isoform 3 (identifier: O00451-3)

The sequence of this isoform differs from the canonical sequence as follows:
     14-118: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2121 Potential
Chain22 – 444423GDNF family receptor alpha-2
PRO_0000010785
Propeptide445 – 46420Removed in mature form Potential
PRO_0000010786

Amino acid modifications

Lipidation4441GPI-anchor amidated serine Potential
Glycosylation521N-linked (GlcNAc...) Potential
Glycosylation3571N-linked (GlcNAc...) Potential
Glycosylation4131N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence14 – 146133Missing in isoform 2.
VSP_001661
Alternative sequence14 – 118105Missing in isoform 3.
VSP_046112
Natural variant4621L → Q. Ref.1 Ref.2 Ref.4
Corresponds to variant rs1128397 [ dbSNP | Ensembl ].
VAR_059976

Experimental info

Sequence conflict61V → A in AAB61922. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Long) [UniParc].

Last modified October 31, 2006. Version 2.
Checksum: 8BC61529530FF21F

FASTA46451,544
        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 

« Hide

Isoform 2 (Short) [UniParc].

Checksum: 10ECFBA492E2393C
Show »

FASTA33136,456
Isoform 3 [UniParc].

Checksum: 23DD986A230B7AD0
Show »

FASTA35939,649

References

« Hide '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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Liver.
[4]Yoong L.F., Too H.P.
Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3), VARIANT GLN-462.
[5]"DNA sequence and analysis of human chromosome 8."
Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., Asakawa T. expand/collapse author list , Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., Lander E.S.
Nature 439:331-335(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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].
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.
AY941828 mRNA. Translation: AAX46325.1.
AC105186 Genomic DNA. No translation available.
AC129925 Genomic DNA. No translation available.
AP008236 Genomic DNA. No translation available.
BC041688 mRNA. Translation: AAH41688.1.
CCDSCCDS47816.1. [O00451-1]
CCDS55207.1. [O00451-2]
CCDS55208.1. [O00451-3]
RefSeqNP_001158510.1. NM_001165038.1. [O00451-3]
NP_001158511.1. NM_001165039.1. [O00451-2]
NP_001486.4. NM_001495.4. [O00451-1]
XP_005273530.1. XM_005273473.1. [O00451-1]
XP_006716389.1. XM_006716326.1. [O00451-1]
XP_006716390.1. XM_006716327.1. [O00451-1]
UniGeneHs.441202.

3D structure databases

ProteinModelPortalO00451.
SMRO00451. Positions 157-359.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108943. 3 interactions.
STRING9606.ENSP00000306654.

Proteomic databases

PaxDbO00451.
PRIDEO00451.

Protocols and materials databases

DNASU2675.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000400782; ENSP00000383592; ENSG00000168546. [O00451-3]
ENST00000517328; ENSP00000429445; ENSG00000168546. [O00451-1]
ENST00000517892; ENSP00000429979; ENSG00000168546. [O00451-3]
ENST00000518077; ENSP00000429206; ENSG00000168546. [O00451-2]
ENST00000524240; ENSP00000428518; ENSG00000168546. [O00451-1]
GeneID2675.
KEGGhsa:2675.
UCSCuc003wzu.1. human. [O00451-1]
uc003wzv.1. human.
uc003wzw.1. human. [O00451-2]

Organism-specific databases

CTD2675.
GeneCardsGC08M021593.
HGNCHGNC:4244. GFRA2.
HPAHPA024704.
MIM601956. gene.
neXtProtNX_O00451.
PharmGKBPA28654.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG78285.
HOVERGENHBG051725.
InParanoidO00451.
OMANSGPCRA.
OrthoDBEOG7FBRJ3.
PhylomeDBO00451.
TreeFamTF331647.

Enzyme and pathway databases

ReactomeREACT_111045. Developmental Biology.

Gene expression databases

ArrayExpressO00451.
BgeeO00451.
CleanExHS_GFRA2.
GenevestigatorO00451.

Family and domain databases

InterProIPR016017. GDNF/GAS1.
IPR003438. GDNF_rcpt.
IPR003504. GDNF_rcpt_a2.
IPR017372. Glial_neurotroph_fac_rcpt_a1/2.
[Graphical view]
PfamPF02351. GDNF. 3 hits.
[Graphical view]
PIRSFPIRSF038071. GDNF_family_receptor_alpha. 1 hit.
PRINTSPR01318. GDNFRALPHA2.
PR01316. GDNFRECEPTOR.
SMARTSM00907. GDNF. 3 hits.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiGFRA2_(gene).
GenomeRNAi2675.
NextBio10560.
PROO00451.
SOURCESearch...

Entry information

Entry nameGFRA2_HUMAN
AccessionPrimary (citable) accession number: O00451
Secondary accession number(s): E9PD47 expand/collapse secondary AC list , O15316, O15328, Q58J92, Q6GTR9, Q7Z5C2
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: October 31, 2006
Last modified: July 9, 2014
This is version 121 of the entry and version 2 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 8

Human chromosome 8: entries, gene names and cross-references to MIM