GFRA3_HUMAN
ID GFRA3_HUMAN Reviewed; 400 AA.
AC O60609; B2RA36; B4DMY9; Q6UW20; Q8IUZ2;
DT 11-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2004, sequence version 2.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=GDNF family receptor alpha-3;
DE Short=GDNF receptor alpha-3;
DE Short=GDNFR-alpha-3;
DE Short=GFR-alpha-3;
DE Flags: Precursor;
GN Name=GFRA3; ORFNames=UNQ339/PRO538/PRO3664;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RX PubMed=9576965; DOI=10.1073/pnas.95.10.5801;
RA Baloh R.H., Gorodinsky A., Golden J.P., Tansey M.G., Keck C.L.,
RA Popescu N.C., Johnson E.M. Jr., Milbrandt J.;
RT "GFRalpha3 is an orphan member of the GDNF/neurturin/persephin receptor
RT family.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:5801-5806(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Lung, and Substantia nigra;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Pancreas;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP PROTEIN SEQUENCE OF 32-46.
RX PubMed=15340161; DOI=10.1110/ps.04682504;
RA Zhang Z., Henzel W.J.;
RT "Signal peptide prediction based on analysis of experimentally verified
RT cleavage sites.";
RL Protein Sci. 13:2819-2824(2004).
RN [7]
RP FUNCTION.
RX PubMed=9883723; DOI=10.1016/s0896-6273(00)80649-2;
RA Baloh R.H., Tansey M.G., Lampe P.A., Fahrner T.J., Enomoto H.,
RA Simburger K.S., Leitner M.L., Araki T., Johnson E.M. Jr., Milbrandt J.;
RT "Artemin, a novel member of the GDNF ligand family, supports peripheral and
RT central neurons and signals through the GFRalpha3-RET receptor complex.";
RL Neuron 21:1291-1302(1998).
RN [8]
RP INTERACTION WITH SORL1.
RX PubMed=23333276; DOI=10.1016/j.celrep.2012.12.011;
RA Glerup S., Lume M., Olsen D., Nyengaard J.R., Vaegter C.B., Gustafsen C.,
RA Christensen E.I., Kjolby M., Hay-Schmidt A., Bender D., Madsen P.,
RA Saarma M., Nykjaer A., Petersen C.M.;
RT "SorLA controls neurotrophic activity by sorting of GDNF and its receptors
RT GFRalpha1 and RET.";
RL Cell Rep. 3:186-199(2013).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.92 ANGSTROMS) OF 151-363 IN COMPLEX WITH ARTN, AND
RP GLYCOSYLATION AT ASN-309.
RX PubMed=16765900; DOI=10.1016/j.str.2006.05.010;
RA Wang X., Baloh R.H., Milbrandt J., Garcia K.C.;
RT "Structure of artemin complexed with its receptor GFRalpha3: convergent
RT recognition of glial cell line-derived neurotrophic factors.";
RL Structure 14:1083-1092(2006).
CC -!- FUNCTION: Receptor for the glial cell line-derived neurotrophic factor,
CC ARTN (artemin). Mediates the artemin-induced autophosphorylation and
CC activation of the RET receptor tyrosine kinase.
CC {ECO:0000269|PubMed:9883723}.
CC -!- SUBUNIT: Interacts with SORL1. {ECO:0000269|PubMed:23333276}.
CC -!- INTERACTION:
CC O60609; Q5T4W7: ARTN; NbExp=4; IntAct=EBI-15586309, EBI-15586241;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Lipid-anchor, GPI-anchor.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O60609-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O60609-2; Sequence=VSP_010942;
CC -!- TISSUE SPECIFICITY: Widely expressed in adult and fetus which exhibit a
CC similar pattern. Essentially not expressed in the central nervous
CC system, but highly expressed in several sensory and sympathetic ganglia
CC of the peripheral nervous system. Moderate expression in many non-
CC neuronal tissues, particularly those of the digestive and urogenital
CC systems, but high expression in stomach and appendix. Several types of
CC glandular tissues show low expression. Very low or no expression
CC detected in the hematopoietic system. {ECO:0000269|PubMed:9576965}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:16765900}.
CC -!- SIMILARITY: Belongs to the GDNFR family. {ECO:0000305}.
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DR EMBL; AF051767; AAC24355.1; -; mRNA.
DR EMBL; AY358997; AAQ89356.1; -; mRNA.
DR EMBL; AY359037; AAQ89396.1; -; mRNA.
DR EMBL; AK297693; BAG60051.1; -; mRNA.
DR EMBL; AK314022; BAG36733.1; -; mRNA.
DR EMBL; CH471062; EAW62152.1; -; Genomic_DNA.
DR EMBL; CH471062; EAW62153.1; -; Genomic_DNA.
DR EMBL; BC037951; AAH37951.1; -; mRNA.
DR CCDS; CCDS4201.1; -. [O60609-1]
DR RefSeq; NP_001487.2; NM_001496.3. [O60609-1]
DR PDB; 2GH0; X-ray; 1.92 A; A/B=151-363.
DR PDB; 6Q2S; EM; 3.80 A; C/D=32-363.
DR PDBsum; 2GH0; -.
DR PDBsum; 6Q2S; -.
DR AlphaFoldDB; O60609; -.
DR SMR; O60609; -.
DR BioGRID; 108944; 19.
DR CORUM; O60609; -.
DR DIP; DIP-29114N; -.
DR IntAct; O60609; 1.
DR STRING; 9606.ENSP00000274721; -.
DR GlyGen; O60609; 4 sites, 1 O-linked glycan (1 site).
DR iPTMnet; O60609; -.
DR PhosphoSitePlus; O60609; -.
DR BioMuta; GFRA3; -.
DR MassIVE; O60609; -.
DR PaxDb; O60609; -.
DR PeptideAtlas; O60609; -.
DR PRIDE; O60609; -.
DR ProteomicsDB; 49482; -. [O60609-1]
DR ProteomicsDB; 49483; -. [O60609-2]
DR Antibodypedia; 14907; 323 antibodies from 36 providers.
DR DNASU; 2676; -.
DR Ensembl; ENST00000274721.8; ENSP00000274721.3; ENSG00000146013.11. [O60609-1]
DR Ensembl; ENST00000378362.3; ENSP00000367613.3; ENSG00000146013.11. [O60609-2]
DR GeneID; 2676; -.
DR KEGG; hsa:2676; -.
DR MANE-Select; ENST00000274721.8; ENSP00000274721.3; NM_001496.4; NP_001487.2.
DR UCSC; uc003lcn.4; human. [O60609-1]
DR CTD; 2676; -.
DR DisGeNET; 2676; -.
DR GeneCards; GFRA3; -.
DR HGNC; HGNC:4245; GFRA3.
DR HPA; ENSG00000146013; Low tissue specificity.
DR MIM; 605710; gene.
DR neXtProt; NX_O60609; -.
DR OpenTargets; ENSG00000146013; -.
DR PharmGKB; PA28655; -.
DR VEuPathDB; HostDB:ENSG00000146013; -.
DR eggNOG; ENOG502QWSW; Eukaryota.
DR GeneTree; ENSGT00940000161256; -.
DR HOGENOM; CLU_040179_3_0_1; -.
DR InParanoid; O60609; -.
DR OMA; NLQDECE; -.
DR OrthoDB; 921584at2759; -.
DR PhylomeDB; O60609; -.
DR TreeFam; TF331647; -.
DR PathwayCommons; O60609; -.
DR Reactome; R-HSA-5673001; RAF/MAP kinase cascade.
DR Reactome; R-HSA-8853659; RET signaling.
DR SignaLink; O60609; -.
DR SIGNOR; O60609; -.
DR BioGRID-ORCS; 2676; 13 hits in 1068 CRISPR screens.
DR ChiTaRS; GFRA3; human.
DR EvolutionaryTrace; O60609; -.
DR GeneWiki; GFRA3; -.
DR GenomeRNAi; 2676; -.
DR Pharos; O60609; Tbio.
DR PRO; PR:O60609; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; O60609; protein.
DR Bgee; ENSG00000146013; Expressed in dorsal root ganglion and 109 other tissues.
DR ExpressionAtlas; O60609; baseline and differential.
DR Genevisible; O60609; HS.
DR GO; GO:0031225; C:anchored component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
DR GO; GO:0019898; C:extrinsic component of membrane; TAS:ProtInc.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR GO; GO:0008046; F:axon guidance receptor activity; IEA:Ensembl.
DR GO; GO:0016167; F:glial cell-derived neurotrophic factor receptor activity; IBA:GO_Central.
DR GO; GO:0038023; F:signaling receptor activity; IBA:GO_Central.
DR GO; GO:0005102; F:signaling receptor binding; TAS:ProtInc.
DR GO; GO:0007399; P:nervous system development; IBA:GO_Central.
DR GO; GO:0001764; P:neuron migration; IEA:Ensembl.
DR GO; GO:0007422; P:peripheral nervous system development; TAS:ProtInc.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR GO; GO:0048485; P:sympathetic nervous system development; IEA:Ensembl.
DR InterPro; IPR016017; GDNF/GAS1.
DR InterPro; IPR037193; GDNF_alpha.
DR InterPro; IPR003438; GDNF_rcpt.
DR InterPro; IPR003505; GDNF_rcpt_A3.
DR PANTHER; PTHR10269; PTHR10269; 1.
DR Pfam; PF02351; GDNF; 3.
DR PRINTS; PR01319; GDNFRALPHA3.
DR PRINTS; PR01316; GDNFRECEPTOR.
DR SMART; SM00907; GDNF; 3.
DR SUPFAM; SSF110035; SSF110035; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane;
KW Direct protein sequencing; Glycoprotein; GPI-anchor; Lipoprotein; Membrane;
KW Receptor; Reference proteome; Signal.
FT SIGNAL 1..31
FT /evidence="ECO:0000269|PubMed:15340161"
FT CHAIN 32..374
FT /note="GDNF family receptor alpha-3"
FT /id="PRO_0000010789"
FT PROPEP 375..400
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000010790"
FT LIPID 374
FT /note="GPI-anchor amidated asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 95
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 148
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 309
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16765900"
FT VAR_SEQ 127..157
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12975309,
FT ECO:0000303|PubMed:14702039"
FT /id="VSP_010942"
FT CONFLICT 108
FT /note="K -> R (in Ref. 1; AAC24355)"
FT /evidence="ECO:0000305"
FT HELIX 161..170
FT /evidence="ECO:0007829|PDB:2GH0"
FT HELIX 173..185
FT /evidence="ECO:0007829|PDB:2GH0"
FT TURN 188..190
FT /evidence="ECO:0007829|PDB:2GH0"
FT HELIX 193..206
FT /evidence="ECO:0007829|PDB:2GH0"
FT HELIX 209..216
FT /evidence="ECO:0007829|PDB:2GH0"
FT HELIX 225..233
FT /evidence="ECO:0007829|PDB:2GH0"
FT HELIX 237..240
FT /evidence="ECO:0007829|PDB:2GH0"
FT HELIX 248..256
FT /evidence="ECO:0007829|PDB:2GH0"
FT HELIX 259..271
FT /evidence="ECO:0007829|PDB:2GH0"
FT STRAND 274..276
FT /evidence="ECO:0007829|PDB:2GH0"
FT STRAND 281..283
FT /evidence="ECO:0007829|PDB:2GH0"
FT HELIX 285..293
FT /evidence="ECO:0007829|PDB:2GH0"
FT TURN 294..297
FT /evidence="ECO:0007829|PDB:2GH0"
FT STRAND 302..304
FT /evidence="ECO:0007829|PDB:2GH0"
FT STRAND 307..309
FT /evidence="ECO:0007829|PDB:2GH0"
FT STRAND 312..315
FT /evidence="ECO:0007829|PDB:2GH0"
FT HELIX 322..324
FT /evidence="ECO:0007829|PDB:2GH0"
FT HELIX 325..336
FT /evidence="ECO:0007829|PDB:2GH0"
FT HELIX 339..355
FT /evidence="ECO:0007829|PDB:2GH0"
SQ SEQUENCE 400 AA; 44511 MW; B0BC252FE1F072C7 CRC64;
MVRPLNPRPL PPVVLMLLLL LPPSPLPLAA GDPLPTESRL MNSCLQARRK CQADPTCSAA
YHHLDSCTSS ISTPLPSEEP SVPADCLEAA QQLRNSSLIG CMCHRRMKNQ VACLDIYWTV
HRARSLGNYE LDVSPYEDTV TSKPWKMNLS KLNMLKPDSD LCLKFAMLCT LNDKCDRLRK
AYGEACSGPH CQRHVCLRQL LTFFEKAAEP HAQGLLLCPC APNDRGCGER RRNTIAPNCA
LPPVAPNCLE LRRLCFSDPL CRSRLVDFQT HCHPMDILGT CATEQSRCLR AYLGLIGTAM
TPNFVSNVNT SVALSCTCRG SGNLQEECEM LEGFFSHNPC LTEAIAAKMR FHSQLFSQDW
PHPTFAVMAH QNENPAVRPQ PWVPSLFSCT LPLILLLSLW
