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 24-JAN-2024, entry version 179. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 EMDB; EMD-20579; -. DR SMR; O60609; -. DR BioGRID; 108944; 19. DR CORUM; O60609; -. DR DIP; DIP-29114N; -. DR IntAct; O60609; 1. DR STRING; 9606.ENSP00000274721; -. DR GlyCosmos; O60609; 4 sites, 1 glycan. 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; 9606-ENSP00000274721; -. DR PeptideAtlas; O60609; -. DR ProteomicsDB; 49482; -. [O60609-1] DR ProteomicsDB; 49483; -. [O60609-2] DR Antibodypedia; 14907; 367 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 AGR; HGNC:4245; -. DR CTD; 2676; -. DR DisGeNET; 2676; -. DR GeneCards; GFRA3; -. DR HGNC; HGNC:4245; GFRA3. DR HPA; ENSG00000146013; Tissue enhanced (intestine). 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; NSISWMG; -. DR OrthoDB; 3899332at2759; -. 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; 14 hits in 1144 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 111 other cell types or tissues. DR ExpressionAtlas; O60609; baseline and differential. 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: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 Gene3D; 1.10.220.110; GDNF binding domain; 1. DR InterPro; IPR016017; GDNF/GAS1. DR InterPro; IPR037193; GDNF_alpha. DR InterPro; IPR003438; GDNF_rcpt. DR InterPro; IPR003505; GDNF_rcpt_A3. DR PANTHER; PTHR10269:SF15; GDNF FAMILY RECEPTOR ALPHA-3; 1. DR PANTHER; PTHR10269; GDNF RECEPTOR ALPHA; 1. DR Pfam; PF02351; GDNF; 3. DR PRINTS; PR01319; GDNFRALPHA3. DR PRINTS; PR01316; GDNFRECEPTOR. DR SMART; SM00907; GDNF; 3. DR SUPFAM; SSF110035; GDNF receptor-like; 1. DR Genevisible; O60609; HS. 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 //