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Protein

GDNF family receptor alpha-1

Gene

GFRA1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

Receptor for GDNF. Mediates the GDNF-induced autophosphorylation and activation of the RET receptor (By similarity).By similarity

GO - Molecular functioni

  • glial cell-derived neurotrophic factor receptor activity Source: ProtInc
  • Ras guanyl-nucleotide exchange factor activity Source: Reactome
  • receptor binding Source: ProtInc

GO - Biological processi

  • cell surface receptor signaling pathway Source: UniProtKB
  • MAPK cascade Source: Reactome
  • nervous system development Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Receptor

Enzyme and pathway databases

BioCyciZFISH:ENSG00000151892-MONOMER.
ReactomeiR-HSA-419037. NCAM1 interactions.
R-HSA-5673001. RAF/MAP kinase cascade.
R-HSA-8853659. RET signaling.
SignaLinkiP56159.
SIGNORiP56159.

Names & Taxonomyi

Protein namesi
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 namesi
Name:GFRA1
Synonyms:GDNFRA, RETL1, TRNR1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

HGNCiHGNC:4243. GFRA1.

Subcellular locationi

GO - Cellular componenti

  • anchored component of membrane Source: UniProtKB-KW
  • extracellular exosome Source: UniProtKB
  • extrinsic component of membrane Source: ProtInc
  • intracellular Source: GOC
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi2674.
OpenTargetsiENSG00000151892.
PharmGKBiPA28653.

Chemistry databases

GuidetoPHARMACOLOGYi1743.

Polymorphism and mutation databases

BioMutaiGFRA1.
DMDMi20141405.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 24Sequence analysisAdd BLAST24
ChainiPRO_000001077725 – 429GDNF family receptor alpha-1Add BLAST405
PropeptideiPRO_0000010778430 – 465Removed in mature formSequence analysisAdd BLAST36

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi29 ↔ 87By similarity
Disulfide bondi36 ↔ 42By similarity
Disulfide bondi52 ↔ 72By similarity
Glycosylationi59N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi89 ↔ 99By similarity
Disulfide bondi154 ↔ 214By similarity
Disulfide bondi161 ↔ 167By similarity
Disulfide bondi178 ↔ 192By similarity
Disulfide bondi187 ↔ 233By similarity
Disulfide bondi216 ↔ 221By similarity
Disulfide bondi243 ↔ 313By similarity
Disulfide bondi250 ↔ 256By similarity
Disulfide bondi267 ↔ 285By similarity
Disulfide bondi277 ↔ 337By similarity
Disulfide bondi315 ↔ 325By similarity
Glycosylationi347N-linked (GlcNAc...)Sequence analysis1
Glycosylationi406N-linked (GlcNAc...)Sequence analysis1
Lipidationi429GPI-anchor amidated serineSequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein, GPI-anchor, Lipoprotein

Proteomic databases

MaxQBiP56159.
PaxDbiP56159.
PeptideAtlasiP56159.
PRIDEiP56159.

PTM databases

iPTMnetiP56159.
PhosphoSitePlusiP56159.

Expressioni

Gene expression databases

BgeeiENSG00000151892.
CleanExiHS_GFRA1.
GenevisibleiP56159. HS.

Organism-specific databases

HPAiHPA043829.

Interactioni

Subunit structurei

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

GO - Molecular functioni

  • receptor binding Source: ProtInc

Protein-protein interaction databases

BioGridi108942. 5 interactors.
DIPiDIP-59052N.
IntActiP56159. 1 interactor.
STRINGi9606.ENSP00000393725.

Structurei

3D structure databases

ProteinModelPortaliP56159.
SMRiP56159.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati25 – 1131Add BLAST89
Repeati150 – 2382Add BLAST89
Repeati239 – 3423Add BLAST104

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi362 – 369Poly-Thr8

Sequence similaritiesi

Belongs to the GDNFR family.Curated

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

eggNOGiENOG410IU4F. Eukaryota.
ENOG410XPTA. LUCA.
GeneTreeiENSGT00550000074579.
HOGENOMiHOG000008695.
HOVERGENiHBG051725.
InParanoidiP56159.
KOiK19895.
OMAiVFQQVEH.
OrthoDBiEOG091G087B.
PhylomeDBiP56159.
TreeFamiTF331647.

Family and domain databases

InterProiIPR016017. GDNF/GAS1.
IPR003438. GDNF_rcpt.
IPR003503. GDNF_rcpt_A1.
IPR017372. Glial_neurotroph_fac_rcpt_a1/2.
[Graphical view]
PfamiPF02351. GDNF. 3 hits.
[Graphical view]
PIRSFiPIRSF038071. GDNF_family_receptor_alpha. 1 hit.
PRINTSiPR01317. GDNFRALPHA1.
PR01316. GDNFRECEPTOR.
SMARTiSM00907. GDNF. 3 hits.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P56159-1) [UniParc]FASTAAdd to basket

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
MFLATLYFAL PLLDLLLSAE VSGGDRLDCV KASDQCLKEQ SCSTKYRTLR
60 70 80 90 100
QCVAGKETNF SLASGLEAKD ECRSAMEALK QKSLYNCRCK RGMKKEKNCL
110 120 130 140 150
RIYWSMYQSL QGNDLLEDSP YEPVNSRLSD IFRVVPFISD VFQQVEHIPK
160 170 180 190 200
GNNCLDAAKA CNLDDICKKY RSAYITPCTT SVSNDVCNRR KCHKALRQFF
210 220 230 240 250
DKVPAKHSYG MLFCSCRDIA CTERRRQTIV PVCSYEEREK PNCLNLQDSC
260 270 280 290 300
KTNYICRSRL ADFFTNCQPE SRSVSSCLKE NYADCLLAYS GLIGTVMTPN
310 320 330 340 350
YIDSSSLSVA PWCDCSNSGN DLEECLKFLN FFKDNTCLKN AIQAFGNGSD
360 370 380 390 400
VTVWQPAFPV QTTTATTTTA LRVKNKPLGP AGSENEIPTH VLPPCANLQA
410 420 430 440 450
QKLKSNVSGN THLCISNGNY EKEGLGASSH ITTKSMAAPP SCGLSPLLVL
460
VVTALSTLLS LTETS
Length:465
Mass (Da):51,456
Last modified:January 23, 2002 - v2
Checksum:i91A550D06A6777BD
GO
Isoform 2 (identifier: P56159-2) [UniParc]FASTAAdd to basket

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.
Show »
Length:460
Mass (Da):50,838
Checksum:iF5620DE4F2E122AA
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti245Missing no nucleotide entry (PubMed:8674117).Curated1
Sequence conflicti358F → P no nucleotide entry (PubMed:8674117).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01248885Y → N.1 PublicationCorresponds to variant rs8192662dbSNPEnsembl.1
Natural variantiVAR_012489366T → A.2 PublicationsCorresponds to variant rs2072276dbSNPEnsembl.1
Natural variantiVAR_018261371L → R May be involved in congenital central hypoventilation syndrome. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_001660140 – 144Missing in isoform 2. 4 Publications5

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS44481.1. [P56159-1]
CCDS7593.1. [P56159-2]
RefSeqiNP_001138925.1. NM_001145453.2. [P56159-2]
NP_005255.1. NM_005264.5. [P56159-1]
NP_665736.1. NM_145793.3. [P56159-2]
XP_005269753.1. XM_005269696.1. [P56159-1]
XP_011537936.1. XM_011539634.1. [P56159-1]
UniGeneiHs.388347.

Genome annotation databases

EnsembliENST00000355422; ENSP00000347591; ENSG00000151892. [P56159-1]
ENST00000369234; ENSP00000358237; ENSG00000151892. [P56159-1]
ENST00000369236; ENSP00000358239; ENSG00000151892. [P56159-2]
ENST00000439649; ENSP00000393725; ENSG00000151892. [P56159-2]
GeneIDi2674.
KEGGihsa:2674.
UCSCiuc001lci.4. human. [P56159-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS44481.1. [P56159-1]
CCDS7593.1. [P56159-2]
RefSeqiNP_001138925.1. NM_001145453.2. [P56159-2]
NP_005255.1. NM_005264.5. [P56159-1]
NP_665736.1. NM_145793.3. [P56159-2]
XP_005269753.1. XM_005269696.1. [P56159-1]
XP_011537936.1. XM_011539634.1. [P56159-1]
UniGeneiHs.388347.

3D structure databases

ProteinModelPortaliP56159.
SMRiP56159.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108942. 5 interactors.
DIPiDIP-59052N.
IntActiP56159. 1 interactor.
STRINGi9606.ENSP00000393725.

Chemistry databases

GuidetoPHARMACOLOGYi1743.

PTM databases

iPTMnetiP56159.
PhosphoSitePlusiP56159.

Polymorphism and mutation databases

BioMutaiGFRA1.
DMDMi20141405.

Proteomic databases

MaxQBiP56159.
PaxDbiP56159.
PeptideAtlasiP56159.
PRIDEiP56159.

Protocols and materials databases

DNASUi2674.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000355422; ENSP00000347591; ENSG00000151892. [P56159-1]
ENST00000369234; ENSP00000358237; ENSG00000151892. [P56159-1]
ENST00000369236; ENSP00000358239; ENSG00000151892. [P56159-2]
ENST00000439649; ENSP00000393725; ENSG00000151892. [P56159-2]
GeneIDi2674.
KEGGihsa:2674.
UCSCiuc001lci.4. human. [P56159-1]

Organism-specific databases

CTDi2674.
DisGeNETi2674.
GeneCardsiGFRA1.
HGNCiHGNC:4243. GFRA1.
HPAiHPA043829.
MIMi601496. gene.
neXtProtiNX_P56159.
OpenTargetsiENSG00000151892.
PharmGKBiPA28653.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IU4F. Eukaryota.
ENOG410XPTA. LUCA.
GeneTreeiENSGT00550000074579.
HOGENOMiHOG000008695.
HOVERGENiHBG051725.
InParanoidiP56159.
KOiK19895.
OMAiVFQQVEH.
OrthoDBiEOG091G087B.
PhylomeDBiP56159.
TreeFamiTF331647.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000151892-MONOMER.
ReactomeiR-HSA-419037. NCAM1 interactions.
R-HSA-5673001. RAF/MAP kinase cascade.
R-HSA-8853659. RET signaling.
SignaLinkiP56159.
SIGNORiP56159.

Miscellaneous databases

ChiTaRSiGFRA1. human.
GeneWikiiGDNF_family_receptor_alpha_1.
GenomeRNAii2674.
PROiP56159.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000151892.
CleanExiHS_GFRA1.
GenevisibleiP56159. HS.

Family and domain databases

InterProiIPR016017. GDNF/GAS1.
IPR003438. GDNF_rcpt.
IPR003503. GDNF_rcpt_A1.
IPR017372. Glial_neurotroph_fac_rcpt_a1/2.
[Graphical view]
PfamiPF02351. GDNF. 3 hits.
[Graphical view]
PIRSFiPIRSF038071. GDNF_family_receptor_alpha. 1 hit.
PRINTSiPR01317. GDNFRALPHA1.
PR01316. GDNFRECEPTOR.
SMARTiSM00907. GDNF. 3 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiGFRA1_HUMAN
AccessioniPrimary (citable) accession number: P56159
Secondary accession number(s): A8KA21, O15507, O43912
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: January 23, 2002
Last modified: November 2, 2016
This is version 148 of the entry and version 2 of the sequence. [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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.