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 13-FEB-2019, entry version 153. 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; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; 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 RT receptor 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., RA Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., RA Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., RA Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., RA Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., RA Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., RA Wood W.I., Godowski P.J., Gray A.M.; RT "The secreted protein discovery initiative (SPDI), a large-scale RT effort to identify novel human secreted and transmembrane proteins: a RT bioinformatics 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., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA 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., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., 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., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA 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 RT project: 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 RT verified 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., RA Milbrandt J.; RT "Artemin, a novel member of the GDNF ligand family, supports RT peripheral and central neurons and signals through the GFRalpha3-RET RT receptor complex."; RL Neuron 21:1291-1302(1998). RN [8] RP X-RAY CRYSTALLOGRAPHY (1.92 ANGSTROMS) OF 151-363 IN COMPLEX WITH RP ARTN, AND 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: RT convergent recognition of glial cell line-derived neurotrophic RT factors."; RL Structure 14:1083-1092(2006). CC -!- FUNCTION: Receptor for the glial cell line-derived neurotrophic CC factor, ARTN (artemin). Mediates the artemin-induced CC autophosphorylation and activation of the RET receptor tyrosine CC kinase. {ECO:0000269|PubMed:9883723}. CC -!- INTERACTION: CC 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 CC exhibit a similar pattern. Essentially not expressed in the CC central nervous system, but highly expressed in several sensory CC and sympathetic ganglia of the peripheral nervous system. Moderate CC expression in many non-neuronal tissues, particularly those of the CC digestive and urogenital systems, but high expression in stomach CC and appendix. Several types of glandular tissues show low CC expression. Very low or no expression detected in the CC 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 UniGene; Hs.58042; -. DR PDB; 2GH0; X-ray; 1.92 A; A/B=151-363. DR PDBsum; 2GH0; -. DR ProteinModelPortal; O60609; -. DR SMR; O60609; -. DR BioGrid; 108944; 1. DR CORUM; O60609; -. DR DIP; DIP-29114N; -. DR IntAct; O60609; 1. DR STRING; 9606.ENSP00000274721; -. DR iPTMnet; O60609; -. DR PhosphoSitePlus; O60609; -. DR BioMuta; GFRA3; -. DR PaxDb; O60609; -. DR PeptideAtlas; O60609; -. DR PRIDE; O60609; -. DR ProteomicsDB; 49482; -. DR ProteomicsDB; 49483; -. [O60609-2] DR DNASU; 2676; -. DR Ensembl; ENST00000274721; ENSP00000274721; ENSG00000146013. [O60609-1] DR Ensembl; ENST00000378362; ENSP00000367613; ENSG00000146013. [O60609-2] DR GeneID; 2676; -. DR KEGG; hsa:2676; -. DR UCSC; uc003lcn.4; human. [O60609-1] DR CTD; 2676; -. DR DisGeNET; 2676; -. DR EuPathDB; HostDB:ENSG00000146013.10; -. DR GeneCards; GFRA3; -. DR HGNC; HGNC:4245; GFRA3. DR HPA; HPA020731; -. DR MIM; 605710; gene. DR neXtProt; NX_O60609; -. DR OpenTargets; ENSG00000146013; -. DR PharmGKB; PA28655; -. DR eggNOG; ENOG410IIBW; Eukaryota. DR eggNOG; ENOG4111VG4; LUCA. DR GeneTree; ENSGT00940000161256; -. DR HOGENOM; HOG000059598; -. DR HOVERGEN; HBG051726; -. DR InParanoid; O60609; -. DR OMA; LFSQDWA; -. DR OrthoDB; 921584at2759; -. DR PhylomeDB; O60609; -. DR TreeFam; TF331647; -. DR Reactome; R-HSA-5673001; RAF/MAP kinase cascade. DR Reactome; R-HSA-8853659; RET signaling. DR SIGNOR; O60609; -. DR ChiTaRS; GFRA3; human. DR EvolutionaryTrace; O60609; -. DR GeneWiki; GFRA3; -. DR GenomeRNAi; 2676; -. DR PRO; PR:O60609; -. DR Proteomes; UP000005640; Chromosome 5. DR Bgee; ENSG00000146013; Expressed in 108 organ(s), highest expression level in dorsal root ganglion. 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; IBA:GO_Central. DR GO; GO:0005088; F:Ras guanyl-nucleotide exchange factor activity; TAS:Reactome. DR GO; GO:0005102; F:signaling receptor binding; TAS:ProtInc. DR GO; GO:0007411; P:axon guidance; TAS:Reactome. DR GO; GO:0000165; P:MAPK cascade; TAS:Reactome. 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; Complete proteome; KW Direct protein sequencing; Glycoprotein; GPI-anchor; Lipoprotein; KW Membrane; Receptor; Reference proteome; Signal. FT SIGNAL 1 31 {ECO:0000269|PubMed:15340161}. FT CHAIN 32 374 GDNF family receptor alpha-3. FT /FTId=PRO_0000010789. FT PROPEP 375 400 Removed in mature form. {ECO:0000255}. FT /FTId=PRO_0000010790. FT LIPID 374 374 GPI-anchor amidated asparagine. FT {ECO:0000255}. FT CARBOHYD 95 95 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 148 148 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 309 309 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:16765900}. FT VAR_SEQ 127 157 Missing (in isoform 2). FT {ECO:0000303|PubMed:12975309, FT ECO:0000303|PubMed:14702039}. FT /FTId=VSP_010942. FT CONFLICT 108 108 K -> R (in Ref. 1; AAC24355). FT {ECO:0000305}. FT HELIX 161 170 {ECO:0000244|PDB:2GH0}. FT HELIX 173 185 {ECO:0000244|PDB:2GH0}. FT TURN 188 190 {ECO:0000244|PDB:2GH0}. FT HELIX 193 206 {ECO:0000244|PDB:2GH0}. FT HELIX 209 216 {ECO:0000244|PDB:2GH0}. FT HELIX 225 233 {ECO:0000244|PDB:2GH0}. FT HELIX 237 240 {ECO:0000244|PDB:2GH0}. FT HELIX 248 256 {ECO:0000244|PDB:2GH0}. FT HELIX 259 271 {ECO:0000244|PDB:2GH0}. FT STRAND 274 276 {ECO:0000244|PDB:2GH0}. FT STRAND 281 283 {ECO:0000244|PDB:2GH0}. FT HELIX 285 293 {ECO:0000244|PDB:2GH0}. FT TURN 294 297 {ECO:0000244|PDB:2GH0}. FT STRAND 302 304 {ECO:0000244|PDB:2GH0}. FT STRAND 307 309 {ECO:0000244|PDB:2GH0}. FT STRAND 312 315 {ECO:0000244|PDB:2GH0}. FT HELIX 322 324 {ECO:0000244|PDB:2GH0}. FT HELIX 325 336 {ECO:0000244|PDB:2GH0}. FT HELIX 339 355 {ECO:0000244|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 //