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Protein

GDNF family receptor alpha-2

Gene

GFRA2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.
Isoform 2: participates in NRTN-induced 'Ser-727' phosphorylation of STAT3.By similarity

Caution

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionReceptor

Enzyme and pathway databases

ReactomeiR-HSA-419037 NCAM1 interactions
R-HSA-5673001 RAF/MAP kinase cascade
R-HSA-8853659 RET signaling
SIGNORiO00451

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:GFRA2
Synonyms:GDNFRB, RETL2, TRNR2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

EuPathDBiHostDB:ENSG00000168546.10
HGNCiHGNC:4244 GFRA2
MIMi601956 gene
neXtProtiNX_O00451

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi2675
OpenTargetsiENSG00000168546
PharmGKBiPA28654

Polymorphism and mutation databases

BioMutaiGFRA2

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 21Sequence analysisAdd BLAST21
ChainiPRO_000001078522 – 444GDNF family receptor alpha-2Add BLAST423
PropeptideiPRO_0000010786445 – 464Removed in mature formSequence analysisAdd BLAST20

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi52N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi357N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi413N-linked (GlcNAc...) asparagineSequence analysis1
Lipidationi444GPI-anchor amidated serineSequence analysis1

Keywords - PTMi

Glycoprotein, GPI-anchor, Lipoprotein

Proteomic databases

PaxDbiO00451
PeptideAtlasiO00451
PRIDEiO00451

PTM databases

iPTMnetiO00451
PhosphoSitePlusiO00451

Expressioni

Tissue specificityi

Isoform 1 is found in both brain and placenta.

Gene expression databases

BgeeiENSG00000168546
CleanExiHS_GFRA2
ExpressionAtlasiO00451 baseline and differential
GenevisibleiO00451 HS

Organism-specific databases

HPAiCAB032791
HPA024704

Interactioni

GO - Molecular functioni

Protein-protein interaction databases

BioGridi1089433 interactors.
STRINGi9606.ENSP00000428518

Structurei

Secondary structure

1464
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi40 – 48Combined sources9
Helixi51 – 64Combined sources14
Helixi76 – 86Combined sources11
Turni89 – 92Combined sources4
Helixi102 – 111Combined sources10
Helixi160 – 169Combined sources10
Helixi172 – 186Combined sources15
Beta strandi193 – 195Combined sources3
Helixi197 – 210Combined sources14
Helixi213 – 220Combined sources8
Helixi227 – 235Combined sources9
Helixi239 – 242Combined sources4
Helixi251 – 260Combined sources10
Helixi262 – 275Combined sources14
Beta strandi279 – 281Combined sources3
Helixi286 – 288Combined sources3
Helixi290 – 298Combined sources9
Turni299 – 302Combined sources4
Beta strandi307 – 309Combined sources3
Beta strandi314 – 316Combined sources3
Beta strandi319 – 322Combined sources4
Helixi329 – 331Combined sources3
Helixi332 – 343Combined sources12
Helixi346 – 355Combined sources10

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5MR4X-ray2.40C/D1-458[»]
5MR5X-ray2.00C/D147-362[»]
ProteinModelPortaliO00451
SMRiO00451
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the GDNFR family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IU4F Eukaryota
ENOG410XPTA LUCA
GeneTreeiENSGT00550000074579
HOGENOMiHOG000008695
HOVERGENiHBG051725
InParanoidiO00451
OMAiSLCRTDH
OrthoDBiEOG091G087B
PhylomeDBiO00451
TreeFamiTF331647

Family and domain databases

InterProiView protein in InterPro
IPR016017 GDNF/GAS1
IPR037193 GDNF_alpha
IPR003438 GDNF_rcpt
IPR003504 GDNF_rcpt_a2
IPR017372 Glial_neurotroph_fac_rcpt_a1/2
PANTHERiPTHR10269 PTHR10269, 1 hit
PfamiView protein in Pfam
PF02351 GDNF, 3 hits
PIRSFiPIRSF038071 GDNF_family_receptor_alpha, 1 hit
PRINTSiPR01318 GDNFRALPHA2
PR01316 GDNFRECEPTOR
SMARTiView protein in SMART
SM00907 GDNF, 3 hits
SUPFAMiSSF110035 SSF110035, 1 hit

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O00451-1) [UniParc]FASTAAdd to basket
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.

« Hide

        10         20         30         40         50
MILANVFCLF FFLDETLRSL ASPSSLQGPE LHGWRPPVDC VRANELCAAE
60 70 80 90 100
SNCSSRYRTL RQCLAGRDRN TMLANKECQA ALEVLQESPL YDCRCKRGMK
110 120 130 140 150
KELQCLQIYW SIHLGLTEGE EFYEASPYEP VTSRLSDIFR LASIFSGTGA
160 170 180 190 200
DPVVSAKSNH CLDAAKACNL NDNCKKLRSS YISICNREIS PTERCNRRKC
210 220 230 240 250
HKALRQFFDR VPSEYTYRML FCSCQDQACA ERRRQTILPS CSYEDKEKPN
260 270 280 290 300
CLDLRGVCRT DHLCRSRLAD FHANCRASYQ TVTSCPADNY QACLGSYAGM
310 320 330 340 350
IGFDMTPNYV DSSPTGIVVS PWCSCRGSGN MEEECEKFLR DFTENPCLRN
360 370 380 390 400
AIQAFGNGTD VNVSPKGPSF QATQAPRVEK TPSLPDDLSD STSLGTSVIT
410 420 430 440 450
TCTSVQEQGL KANNSKELSM CFTELTTNII PGSNKVIKPN SGPSRARPSA
460
ALTVLSVLML KLAL
Length:464
Mass (Da):51,544
Last modified:October 31, 2006 - v2
Checksum:i8BC61529530FF21F
GO
Isoform 2 (identifier: O00451-2) [UniParc]FASTAAdd to basket
Also known as: Short

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

Show »
Length:331
Mass (Da):36,456
Checksum:i10ECFBA492E2393C
GO
Isoform 3 (identifier: O00451-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     14-118: Missing.

Note: No experimental confirmation available.
Show »
Length:359
Mass (Da):39,649
Checksum:i23DD986A230B7AD0
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti6V → A in AAB61922 (PubMed:9259272).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_059976462L → Q3 PublicationsCorresponds to variant dbSNP:rs1128397Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_00166114 – 146Missing in isoform 2. 2 PublicationsAdd BLAST133
Alternative sequenceiVSP_04611214 – 118Missing in isoform 3. 1 PublicationAdd BLAST105

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS47816.1 [O00451-1]
CCDS55207.1 [O00451-2]
CCDS55208.1 [O00451-3]
RefSeqiNP_001158510.1, NM_001165038.1 [O00451-3]
NP_001158511.1, NM_001165039.1 [O00451-2]
NP_001486.4, NM_001495.4 [O00451-1]
XP_006716390.1, XM_006716327.3 [O00451-1]
XP_011542786.1, XM_011544484.2 [O00451-1]
UniGeneiHs.441202

Genome annotation databases

EnsembliENST00000517328; ENSP00000429445; ENSG00000168546 [O00451-1]
ENST00000517892; ENSP00000429979; ENSG00000168546 [O00451-3]
ENST00000518077; ENSP00000429206; ENSG00000168546 [O00451-2]
ENST00000524240; ENSP00000428518; ENSG00000168546 [O00451-1]
GeneIDi2675
KEGGihsa:2675
UCSCiuc003wzu.2 human [O00451-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiGFRA2_HUMAN
AccessioniPrimary (citable) accession number: O00451
Secondary accession number(s): E9PD47
, O15316, O15328, Q58J92, Q6GTR9, Q7Z5C2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: October 31, 2006
Last modified: March 28, 2018
This is version 151 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome