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Protein

GDNF family receptor alpha-2

Gene

Gfra2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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.1 Publication
Isoform 2: Participates to NRTN-induced 'Ser-727' phosphorylation of STAT3.1 Publication

GO - Molecular functioni

  1. glial cell-derived neurotrophic factor receptor activity Source: Ensembl

GO - Biological processi

  1. negative regulation of protein autophosphorylation Source: Ensembl
  2. nervous system development Source: MGI
  3. transmembrane receptor protein tyrosine kinase signaling pathway Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Receptor

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
TGF-beta-related neurotrophic factor receptor 2
Gene namesi
Name:Gfra2Imported
Synonyms:Gdnfrb, Trnr21 Publication
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 14

Organism-specific databases

MGIiMGI:1195462. Gfra2.

Subcellular locationi

  1. Cell membrane 1 Publication; Lipid-anchorGPI-anchor 1 Publication

GO - Cellular componenti

  1. anchored component of membrane Source: UniProtKB-KW
  2. plasma membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2121Sequence AnalysisAdd
BLAST
Chaini22 – 443422GDNF family receptor alpha-2PRO_0000010787Add
BLAST
Propeptidei444 – 46421Removed in mature formSequence AnalysisPRO_0000010788Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi52 – 521N-linked (GlcNAc...)Sequence Analysis
Glycosylationi357 – 3571N-linked (GlcNAc...)Sequence Analysis
Glycosylationi413 – 4131N-linked (GlcNAc...)Sequence Analysis
Lipidationi443 – 4431GPI-anchor amidated serineSequence Analysis

Keywords - PTMi

Glycoprotein, GPI-anchor, Lipoprotein

Proteomic databases

PaxDbiO08842.
PRIDEiO08842.

Expressioni

Tissue specificityi

Neurons of the superior cervical and dorsal root ganglia, and adult brain and testis. Low level in the substantia nigra, spleen and adrenal gland (PubMed:9182803). Isoform 1, isoform 2 and isoform 3 are all expressed in brain, liver, ileum, spleen, heart and kidney (PubMed:9875703). In brain, isoform 1 is most abundant, isoform 2 slightly less and isoform 3 is lowest. No significant levels of isoform 1, isoform 2 or isoform 3 expression in testis (PubMed:12829325).3 Publications

Developmental stagei

Expressed at low level in the ventral mesencephalon at E14. Highly expressed in the developing dorsal root ganglia (PubMed:9182803). Isoform 1, isoform 2 and isoform 3 are all highly expressed in the late embryonic development (E15 and E17) (PubMed:12829325).2 Publications

Gene expression databases

BgeeiO08842.
ExpressionAtlasiO08842. baseline and differential.
GenevestigatoriO08842.

Structurei

3D structure databases

ProteinModelPortaliO08842.
SMRiO08842. Positions 157-359.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the GDNFR family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG78285.
GeneTreeiENSGT00550000074579.
HOGENOMiHOG000008695.
HOVERGENiHBG051725.
InParanoidiO08842.
OMAiSLCRTDH.
OrthoDBiEOG7FBRJ3.
TreeFamiTF331647.

Family and domain databases

InterProiIPR016017. GDNF/GAS1.
IPR003438. GDNF_rcpt.
IPR003504. GDNF_rcpt_a2.
IPR017372. Glial_neurotroph_fac_rcpt_a1/2.
[Graphical view]
PfamiPF02351. GDNF. 3 hits.
[Graphical view]
PIRSFiPIRSF038071. GDNF_family_receptor_alpha. 1 hit.
PRINTSiPR01318. GDNFRALPHA2.
PR01316. GDNFRECEPTOR.
SMARTiSM00907. GDNF. 3 hits.
[Graphical view]

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

Note: Additional isoforms seem to exist.1 Publication

Isoform 1 (identifier: O08842-1) [UniParc]FASTAAdd to basket

Also known as: Long, 2a2 Publications

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
MILANAFCLF FFLDETLRSL ASPSSPQGSE LHGWRPQVDC 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
CLDLRSLCRT DHLCRSRLAD FHANCRASYR TITSCPADNY QACLGSYAGM
310 320 330 340 350
IGFDMTPNYV DSNPTGIVVS PWCNCRGSGN MEEECEKFLK DFTENPCLRN
360 370 380 390 400
AIQAFGNGTD VNMSPKGPTF SATQAPRVEK TPSLPDDLSD STSLGTSVIT
410 420 430 440 450
TCTSIQEQGL KANNSKELSM CFTELTTNIS PGSKKVIKLY SGSCRARLST
460
ALTALPLLMV TLAQ
Length:464
Mass (Da):51,727
Last modified:September 18, 2013 - v2
Checksum:i3A7FB495FA58C61F
GO
Isoform 2 (identifier: O08842-2) [UniParc]FASTAAdd to basket

Also known as: Short, 2c2 Publications

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

Show »
Length:331
Mass (Da):36,634
Checksum:i63FDA76F5CE275F9
GO
Isoform 3 (identifier: O08842-3) [UniParc]FASTAAdd to basket

Also known as: 2b2 Publications

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

Show »
Length:359
Mass (Da):39,827
Checksum:i971446EA933F601E
GO

Sequence cautioni

The sequence AAC53548.1 differs from that shown. Reason: Erroneous termination at position 464. Translated as Gln.Curated
The sequence AAC82464.1 differs from that shown. Reason: Erroneous termination at position 464. Translated as Gln.Curated
The sequence AAC82465.1 differs from that shown. Reason: Erroneous termination at position 464. Translated as Gln.Curated
The sequence AAK97483.1 differs from that shown. Reason: Erroneous termination at position 464. Translated as Gln.Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti157 – 1571K → E in AAC82464 (PubMed:9875703).Curated
Sequence conflicti157 – 1571K → E in AAC82465 (PubMed:9875703).Curated
Sequence conflicti387 – 3871D → E in AAK97483 (PubMed:12829325).Curated
Sequence conflicti388 – 3881L → I in AAK97483 (PubMed:12829325).Curated
Sequence conflicti391 – 3911S → G in AAK97483 (PubMed:12829325).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei14 – 146133Missing in isoform 2. 2 PublicationsVSP_001662Add
BLAST
Alternative sequencei14 – 118105Missing in isoform 3. 1 PublicationVSP_057520Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF002701 mRNA. Translation: AAC53548.1. Sequence problems.
AF079107 mRNA. Translation: AAC82464.1. Sequence problems.
AF079108 mRNA. Translation: AAC82465.1. Sequence problems.
AF398416
, AF398411, AF398412, AF398413, AF398414, AF398415 Genomic DNA. Translation: AAK97483.1. Sequence problems.
AK138512 mRNA. Translation: BAE23689.1.
AC124202 Genomic DNA. No translation available.
CH466535 Genomic DNA. Translation: EDL35876.1.
BC138561 mRNA. Translation: AAI38562.1.
CCDSiCCDS27263.1. [O08842-1]
RefSeqiNP_001289023.1. NM_001302094.1.
NP_001289024.1. NM_001302095.1. [O08842-2]
NP_032141.2. NM_008115.3. [O08842-1]
UniGeneiMm.32619.

Genome annotation databases

EnsembliENSMUST00000022699; ENSMUSP00000022699; ENSMUSG00000022103. [O08842-1]
GeneIDi14586.
KEGGimmu:14586.
UCSCiuc007uoz.1. mouse.
uc007upb.1. mouse. [O08842-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF002701 mRNA. Translation: AAC53548.1. Sequence problems.
AF079107 mRNA. Translation: AAC82464.1. Sequence problems.
AF079108 mRNA. Translation: AAC82465.1. Sequence problems.
AF398416
, AF398411, AF398412, AF398413, AF398414, AF398415 Genomic DNA. Translation: AAK97483.1. Sequence problems.
AK138512 mRNA. Translation: BAE23689.1.
AC124202 Genomic DNA. No translation available.
CH466535 Genomic DNA. Translation: EDL35876.1.
BC138561 mRNA. Translation: AAI38562.1.
CCDSiCCDS27263.1. [O08842-1]
RefSeqiNP_001289023.1. NM_001302094.1.
NP_001289024.1. NM_001302095.1. [O08842-2]
NP_032141.2. NM_008115.3. [O08842-1]
UniGeneiMm.32619.

3D structure databases

ProteinModelPortaliO08842.
SMRiO08842. Positions 157-359.
ModBaseiSearch...
MobiDBiSearch...

Proteomic databases

PaxDbiO08842.
PRIDEiO08842.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000022699; ENSMUSP00000022699; ENSMUSG00000022103. [O08842-1]
GeneIDi14586.
KEGGimmu:14586.
UCSCiuc007uoz.1. mouse.
uc007upb.1. mouse. [O08842-2]

Organism-specific databases

CTDi2675.
MGIiMGI:1195462. Gfra2.

Phylogenomic databases

eggNOGiNOG78285.
GeneTreeiENSGT00550000074579.
HOGENOMiHOG000008695.
HOVERGENiHBG051725.
InParanoidiO08842.
OMAiSLCRTDH.
OrthoDBiEOG7FBRJ3.
TreeFamiTF331647.

Miscellaneous databases

ChiTaRSiGfra2. mouse.
NextBioi286330.
PROiO08842.
SOURCEiSearch...

Gene expression databases

BgeeiO08842.
ExpressionAtlasiO08842. baseline and differential.
GenevestigatoriO08842.

Family and domain databases

InterProiIPR016017. GDNF/GAS1.
IPR003438. GDNF_rcpt.
IPR003504. GDNF_rcpt_a2.
IPR017372. Glial_neurotroph_fac_rcpt_a1/2.
[Graphical view]
PfamiPF02351. GDNF. 3 hits.
[Graphical view]
PIRSFiPIRSF038071. GDNF_family_receptor_alpha. 1 hit.
PRINTSiPR01318. GDNFRALPHA2.
PR01316. GDNFRECEPTOR.
SMARTiSM00907. GDNF. 3 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
  2. "Identification of mammalian GFRalpha-2 splice isoforms."
    Wong Y.W., Too H.P.
    NeuroReport 9:3767-3773(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3), TISSUE SPECIFICITY.
    Tissue: Brain1 Publication.
  3. "Real time PCR quantification of GFRalpha-2 alternatively spliced isoforms in murine brain and peripheral tissues."
    Too H.P.
    Brain Res. Mol. Brain Res. 114:146-153(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
    Strain: C57BL/6JImported.
  4. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Strain: C57BL/6J.
    Tissue: Spinal cord.
  5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  6. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
    Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  7. "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] (ISOFORM 1).
    Tissue: Brain.
  8. "GDNF family ligand dependent STAT3 activation is mediated by specific alternatively spliced isoforms of GFRalpha2 and RET."
    Zhou L., Too H.P.
    Biochim. Biophys. Acta 1833:2789-2802(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION (ISOFORM 2).

Entry informationi

Entry nameiGFRA2_MOUSE
AccessioniPrimary (citable) accession number: O08842
Secondary accession number(s): Q3UUD8
, Q920Y3, Q9Z2A2, Q9Z2A3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: September 18, 2013
Last modified: April 1, 2015
This is version 117 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.