ID GPR3_HUMAN Reviewed; 330 AA. AC P46089; A8K570; DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1995, sequence version 1. DT 28-JAN-2026, entry version 187. DE RecName: Full=G-protein coupled receptor 3; DE AltName: Full=ACCA orphan receptor; GN Name=GPR3; Synonyms=ACCA; 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 [GENOMIC DNA]. RX PubMed=8530049; DOI=10.1006/geno.1995.1154; RA Song Z.-H., Modi W., Bonner T.I.; RT "Molecular cloning and chromosomal localization of human genes encoding RT three closely related G protein-coupled receptors."; RL Genomics 28:347-349(1995). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=7698767; DOI=10.1006/geno.1994.1635; RA Iismaa T.P., Kiefer J., Liu M.L., Baker E., Sutherland G.R., Shine J.; RT "Isolation and chromosomal localization of a novel human G-protein-coupled RT receptor (GPR3) expressed predominantly in the central nervous system."; RL Genomics 24:391-394(1994). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=7639700; DOI=10.1042/bj3090837; RA Eggerickx D., Denef J.F., Labbe O., Hayashi Y., Refetoff S., Vassart G., RA Parmentier M., Libert F.; RT "Molecular cloning of an orphan G-protein-coupled receptor that RT constitutively activates adenylate cyclase."; RL Biochem. J. 309:837-843(1995). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [6] 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 [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; 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 [8] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-292. RX PubMed=7851889; DOI=10.1006/geno.1994.1549; RA Marchese A., Docherty J.M., Nguyen T., Heiber M., Cheng R., Heng H.H.Q., RA Tsui L.-C., Shi X., George S.R., O'Dowd B.F.; RT "Cloning of human genes encoding novel G protein-coupled receptors."; RL Genomics 23:609-618(1994). RN [9] RP FUNCTION. RX PubMed=12220620; DOI=10.1016/s0898-6568(02)00041-4; RA Uhlenbrock K., Gassenhuber J., Kostenis E.; RT "Sphingosine 1-phosphate is a ligand of the human gpr3, gpr6 and gpr12 RT family of constitutively active G protein-coupled receptors."; RL Cell. Signal. 14:941-953(2002). RN [10] RP SHOWS THAT IT IS NOT A SPHINGOSINE 1-PHOSPHATE RECEPTOR. RX PubMed=19286662; DOI=10.1074/jbc.m806516200; RA Yin H., Chu A., Li W., Wang B., Shelton F., Otero F., Nguyen D.G., RA Caldwell J.S., Chen Y.A.; RT "Lipid G protein-coupled receptor ligand identification using beta-arrestin RT PathHunter assay."; RL J. Biol. Chem. 284:12328-12338(2009). RN [11] RP FUNCTION. RX PubMed=19213921; DOI=10.1126/science.1160649; RA Thathiah A., Spittaels K., Hoffmann M., Staes M., Cohen A., Horre K., RA Vanbrabant M., Coun F., Baekelandt V., Delacourte A., Fischer D.F., RA Pollet D., De Strooper B., Merchiers P.; RT "The orphan G protein-coupled receptor 3 modulates amyloid-beta peptide RT generation in neurons."; RL Science 323:946-951(2009). RN [12] RP FUNCTION, AND INDUCTION BY COLD. RX PubMed=34048700; DOI=10.1016/j.cell.2021.04.037; RA Sveidahl Johansen O., Ma T., Hansen J.B., Markussen L.K., Schreiber R., RA Reverte-Salisa L., Dong H., Christensen D.P., Sun W., Gnad T., RA Karavaeva I., Nielsen T.S., Kooijman S., Cero C., Dmytriyeva O., Shen Y., RA Razzoli M., O'Brien S.L., Kuipers E.N., Nielsen C.H., Orchard W., RA Willemsen N., Jespersen N.Z., Lundh M., Sustarsic E.G., Hallgren C.M., RA Frost M., McGonigle S., Isidor M.S., Broholm C., Pedersen O., Hansen J.B., RA Grarup N., Hansen T., Kjaer A., Granneman J.G., Babu M.M., Calebiro D., RA Nielsen S., Ryden M., Soccio R., Rensen P.C.N., Treebak J.T., RA Schwartz T.W., Emanuelli B., Bartolomucci A., Pfeifer A., Zechner R., RA Scheele C., Mandrup S., Gerhart-Hines Z.; RT "Lipolysis drives expression of the constitutively active receptor GPR3 to RT induce adipose thermogenesis."; RL Cell 184:3502-3518(2021). RN [13] RP FUNCTION, SUBUNIT, MUTAGENESIS OF TYR-135; GLN-211 AND GLN-215, AND RP ACTIVITY REGULATION. RX PubMed=40866348; DOI=10.1038/s41467-025-63422-1; RA Chen G., Blahova J., Staffen N., Huebner H., Nunhoefer N., Qiu C., RA Gmeiner P., Weikert D., Du Y., Xu J.; RT "Mechanism and function of GPR3 regulated by a negative allosteric RT modulator."; RL Nat. Commun. 16:7988-7988(2025). RN [14] {ECO:0007744|PDB:8U8F} RP STRUCTURE BY ELECTRON MICROSCOPY (3.49 ANGSTROMS) OF 2-330, DISULFIDE RP BONDS, INTERACTION WITH GNAS, AND FUNCTION. RX PubMed=38376112; DOI=10.1021/acs.biochem.3c00647; RA Russell I.C., Zhang X., Bumbak F., McNeill S.M., Josephs T.M., RA Leeming M.G., Christopoulos G., Venugopal H., Flocco M.M., Sexton P.M., RA Wootten D., Belousoff M.J.; RT "Lipid-Dependent Activation of the Orphan G Protein-Coupled Receptor, RT GPR3."; RL Biochemistry 63:625-631(2024). RN [15] {ECO:0007744|PDB:8WW2} RP STRUCTURE BY ELECTRON MICROSCOPY (2.79 ANGSTROMS), DISULFIDE BONDS, RP INTERACTION WITH GNAS, AND FUNCTION. RX PubMed=38287117; DOI=10.1038/s41422-024-00932-5; RA Xiong Y., Xu Z., Li X., Wang Y., Zhao J., Wang N., Duan Y., Xia R., Han Z., RA Qian Y., Liang J., Zhang A., Guo C., Inoue A., Xia Y., Chen Z., He Y.; RT "Identification of oleic acid as an endogenous ligand of GPR3."; RL Cell Res. 34:232-244(2024). RN [16] {ECO:0007744|PDB:8X2K} RP STRUCTURE BY ELECTRON MICROSCOPY (3.03 ANGSTROMS), DISULFIDE BONDS, RP INTERACTION WITH GNAS, AND MUTAGENESIS OF TYR-280. RX PubMed=38287118; DOI=10.1038/s41422-023-00919-8; RA Chen G., Staffen N., Wu Z., Xu X., Pan J., Inoue A., Shi T., Gmeiner P., RA Du Y., Xu J.; RT "Structural and functional characterization of the endogenous agonist for RT orphan receptor GPR3."; RL Cell Res. 34:262-265(2024). CC -!- FUNCTION: Constitutively active G-protein coupled receptor that CC maintains high cAMP levels and contributes to several processes, CC including meiotic arrest in oocytes and neuronal development, through CC activation of intracellular signaling pathways. Essential activator of CC thermogenic adipocytes, where it drives thermogenesis via constitutive CC G(s)-coupling activity in the absence of ligand (PubMed:34048700). May CC be activated by lipid-derived agonists such as oleoylethanolamide CC (OEA), oleic acid or sphingosine 1-phosphate leading to activation of CC the G(s)/cAMP/PKA signaling pathway (PubMed:12220620, PubMed:38376112, CC PubMed:38287117). Plays a potential role in modulating brain functions, CC including behavioral responses to stress and amyloid-beta peptide CC generation in neurons (By similarity). Stimulates neurite outgrowth in CC cerebellar granule neurons via PKA, ERK, and PI3K-mediated signaling CC pathways (By similarity). {ECO:0000250|UniProtKB:P35413, CC ECO:0000269|PubMed:12220620, ECO:0000269|PubMed:19213921, CC ECO:0000269|PubMed:34048700, ECO:0000269|PubMed:38287117, CC ECO:0000269|PubMed:38376112}. CC -!- ACTIVITY REGULATION: GPR3 bound to the lipid agonist is in an CC equilibrium between monomeric and dimeric states. G protein engagement CC leads to dissociation of the dimer, and efficient coupling and CC signaling of the G(s) protein. {ECO:0000269|PubMed:40866348}. CC -!- SUBUNIT: Homodimer (PubMed:40866348). Interacts with GNAS CC (PubMed:38376112, PubMed:38287117, PubMed:38287118). CC {ECO:0000269|PubMed:38287117, ECO:0000269|PubMed:38287118, CC ECO:0000269|PubMed:38376112, ECO:0000269|PubMed:40866348}. CC -!- INTERACTION: CC P46089; P05067-4: APP; NbExp=2; IntAct=EBI-3909653, EBI-302641; CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. CC -!- TISSUE SPECIFICITY: Expressed predominantly in the central nervous CC system, and at low levels in the lung, kidney, testis, ovary and eye. CC Highly expressed in regions of the brain implicated in the Alzheimer CC disease. CC -!- INDUCTION: Upon cold exposure by a lipolytic signal in thermogenic CC adipose tissue. {ECO:0000269|PubMed:34048700}. CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family. CC {ECO:0000255|PROSITE-ProRule:PRU00521}. CC -!- CAUTION: Was originally (PubMed:12220620) thought to be a receptor for CC sphingosine 1-phosphate. PubMed:19286662 demonstrated that it is not CC the case. {ECO:0000305|PubMed:12220620}. 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; U18550; AAB60402.1; -; Genomic_DNA. DR EMBL; L32831; AAA73560.1; -; Genomic_DNA. DR EMBL; X83956; CAA58787.1; -; Genomic_DNA. DR EMBL; AK291185; BAF83874.1; -; mRNA. DR EMBL; AK314868; BAG37383.1; -; mRNA. DR EMBL; AL096774; CAC18517.1; -; Genomic_DNA. DR EMBL; CH471059; EAX07754.1; -; Genomic_DNA. DR EMBL; BC032702; AAH32702.1; -; mRNA. DR EMBL; U13668; AAA64594.1; -; Genomic_DNA. DR CCDS; CCDS303.1; -. DR PIR; A55689; A55689. DR RefSeq; NP_005272.1; NM_005281.4. DR PDB; 8U8F; EM; 3.49 A; R=2-330. DR PDB; 8WW2; EM; 2.79 A; R=1-330. DR PDB; 8X2K; EM; 3.03 A; A=1-330. DR PDB; 9LYB; EM; 3.16 A; R=37-315. DR PDB; 9LYC; EM; 3.06 A; A/D=32-314. DR PDB; 9LYD; EM; 3.66 A; Q/R=1-330. DR PDBsum; 8U8F; -. DR PDBsum; 8WW2; -. DR PDBsum; 8X2K; -. DR PDBsum; 9LYB; -. DR PDBsum; 9LYC; -. DR PDBsum; 9LYD; -. DR AlphaFoldDB; P46089; -. DR EMDB; EMD-37881; -. DR EMDB; EMD-38015; -. DR EMDB; EMD-42023; -. DR SMR; P46089; -. DR BioGRID; 109088; 11. DR FunCoup; P46089; 103. DR IntAct; P46089; 14. DR STRING; 9606.ENSP00000363136; -. DR ChEMBL; CHEMBL4523856; -. DR GuidetoPHARMACOLOGY; 83; -. DR TCDB; 9.A.14.2.7; the g-protein-coupled receptor (gpcr) family. DR GlyCosmos; P46089; 1 site, No reported glycans. DR GlyGen; P46089; 2 sites. DR iPTMnet; P46089; -. DR PhosphoSitePlus; P46089; -. DR BioMuta; GPR3; -. DR DMDM; 1170006; -. DR MassIVE; P46089; -. DR PaxDb; 9606-ENSP00000363136; -. DR PeptideAtlas; P46089; -. DR ProteomicsDB; 55716; -. DR Antibodypedia; 3339; 355 antibodies from 38 providers. DR DNASU; 2827; -. DR Ensembl; ENST00000374024.4; ENSP00000363136.3; ENSG00000181773.8. DR GeneID; 2827; -. DR KEGG; hsa:2827; -. DR MANE-Select; ENST00000374024.4; ENSP00000363136.3; NM_005281.4; NP_005272.1. DR UCSC; uc001bod.5; human. DR AGR; HGNC:4484; -. DR ClinPGx; PA28872; -. DR CTD; 2827; -. DR DisGeNET; 2827; -. DR GeneCards; GPR3; -. DR HGNC; HGNC:4484; GPR3. DR HPA; ENSG00000181773; Tissue enhanced (heart). DR MIM; 600241; gene. DR OpenTargets; ENSG00000181773; -. DR VEuPathDB; HostDB:ENSG00000181773; -. DR eggNOG; KOG3656; Eukaryota. DR GeneTree; ENSGT01140000282530; -. DR HOGENOM; CLU_065071_0_0_1; -. DR InParanoid; P46089; -. DR OMA; FRTPMFL; -. DR OrthoDB; 10042731at2759; -. DR PAN-GO; P46089; 5 GO annotations based on evolutionary models. DR PhylomeDB; P46089; -. DR PathwayCommons; P46089; -. DR SignaLink; P46089; -. DR Agora; ENSG00000181773; -. DR BioGRID-ORCS; 2827; 8 hits in 1153 CRISPR screens. DR GeneWiki; GPR3; -. DR GenomeRNAi; 2827; -. DR Pharos; P46089; Tchem. DR PRO; PR:P46089; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; P46089; protein. DR Bgee; ENSG00000181773; Expressed in secondary oocyte and 98 other cell types or tissues. DR ExpressionAtlas; P46089; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. DR GO; GO:0004930; F:G protein-coupled receptor activity; TAS:ProtInc. DR GO; GO:0038036; F:sphingosine-1-phosphate receptor activity; IBA:GO_Central. DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IBA:GO_Central. DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab. DR GO; GO:0040020; P:regulation of meiotic nuclear division; IEA:Ensembl. DR FunFam; 1.20.1070.10:FF:000067; G-protein coupled receptor 12; 1. DR Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1. DR InterPro; IPR000276; GPCR_Rhodpsn. DR InterPro; IPR017452; GPCR_Rhodpsn_7TM. DR InterPro; IPR000984; GPR3. DR InterPro; IPR000723; GPR_3/6/12_orphan. DR PANTHER; PTHR22750; G-PROTEIN COUPLED RECEPTOR; 1. DR Pfam; PF00001; 7tm_1; 1. DR PRINTS; PR00237; GPCRRHODOPSN. DR PRINTS; PR00648; GPR3ORPHANR. DR PRINTS; PR00644; GPRORPHANR. DR SUPFAM; SSF81321; Family A G protein-coupled receptor-like; 1. DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1. DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Cell membrane; Disulfide bond; G-protein coupled receptor; KW Glycoprotein; Lipoprotein; Membrane; Palmitate; Phosphoprotein; KW Proteomics identification; Receptor; Reference proteome; Transducer; KW Transmembrane; Transmembrane helix. FT CHAIN 1..330 FT /note="G-protein coupled receptor 3" FT /id="PRO_0000069510" FT TOPO_DOM 1..42 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 43..62 FT /note="Helical; Name=1" FT /evidence="ECO:0000255" FT TOPO_DOM 63..74 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 75..98 FT /note="Helical; Name=2" FT /evidence="ECO:0000255" FT TOPO_DOM 99..110 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 111..132 FT /note="Helical; Name=3" FT /evidence="ECO:0000255" FT TOPO_DOM 133..153 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 154..173 FT /note="Helical; Name=4" FT /evidence="ECO:0000255" FT TOPO_DOM 174..198 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 199..217 FT /note="Helical; Name=5" FT /evidence="ECO:0000255" FT TOPO_DOM 218..245 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 246..272 FT /note="Helical; Name=6" FT /evidence="ECO:0000255" FT TOPO_DOM 273..277 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 278..299 FT /note="Helical; Name=7" FT /evidence="ECO:0000255" FT TOPO_DOM 300..330 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT MOD_RES 324 FT /note="Phosphoserine" FT /evidence="ECO:0000255" FT MOD_RES 326 FT /note="Phosphoserine" FT /evidence="ECO:0000255" FT MOD_RES 328 FT /note="Phosphoserine" FT /evidence="ECO:0000255" FT LIPID 313 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000250" FT CARBOHYD 20 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 177..184 FT /evidence="ECO:0000269|PubMed:38287117, FT ECO:0000269|PubMed:38287118, ECO:0000269|PubMed:38376112" FT VARIANT 222 FT /note="R -> H (in dbSNP:rs734852)" FT /id="VAR_011859" FT MUTAGEN 135 FT /note="Y->A: Partial loss of constitutive FT homodimerization." FT /evidence="ECO:0000269|PubMed:40866348" FT MUTAGEN 211 FT /note="Q->A: Partial loss of constitutive FT homodimerization." FT /evidence="ECO:0000269|PubMed:40866348" FT MUTAGEN 215 FT /note="Q->A: Partial loss of constitutive FT homodimerization." FT /evidence="ECO:0000269|PubMed:40866348" FT MUTAGEN 280 FT /note="Y->A: Reduced receptor activity." FT /evidence="ECO:0000269|PubMed:38287118" FT HELIX 42..66 FT /evidence="ECO:0007829|PDB:8WW2" FT STRAND 68..70 FT /evidence="ECO:0007829|PDB:8U8F" FT HELIX 74..91 FT /evidence="ECO:0007829|PDB:8WW2" FT STRAND 93..103 FT /evidence="ECO:0007829|PDB:8WW2" FT HELIX 107..139 FT /evidence="ECO:0007829|PDB:8WW2" FT HELIX 141..143 FT /evidence="ECO:0007829|PDB:8WW2" FT HELIX 147..166 FT /evidence="ECO:0007829|PDB:8WW2" FT TURN 170..174 FT /evidence="ECO:0007829|PDB:8WW2" FT STRAND 177..182 FT /evidence="ECO:0007829|PDB:8WW2" FT HELIX 193..229 FT /evidence="ECO:0007829|PDB:8WW2" FT HELIX 244..269 FT /evidence="ECO:0007829|PDB:8WW2" FT STRAND 272..274 FT /evidence="ECO:0007829|PDB:8WW2" FT HELIX 276..282 FT /evidence="ECO:0007829|PDB:8WW2" FT HELIX 285..297 FT /evidence="ECO:0007829|PDB:8WW2" FT TURN 298..300 FT /evidence="ECO:0007829|PDB:8WW2" FT HELIX 302..312 FT /evidence="ECO:0007829|PDB:8WW2" SQ SEQUENCE 330 AA; 35010 MW; 0F82E89200968D1E CRC64; MMWGAGSPLA WLSAGSGNVN VSSVGPAEGP TGPAAPLPSP KAWDVVLCIS GTLVSCENAL VVAIIVGTPA FRAPMFLLVG SLAVADLLAG LGLVLHFAAV FCIGSAEMSL VLVGVLAMAF TASIGSLLAI TVDRYLSLYN ALTYYSETTV TRTYVMLALV WGGALGLGLL PVLAWNCLDG LTTCGVVYPL SKNHLVVLAI AFFMVFGIML QLYAQICRIV CRHAQQIALQ RHLLPASHYV ATRKGIATLA VVLGAFAACW LPFTVYCLLG DAHSPPLYTY LTLLPATYNS MINPIIYAFR NQDVQKVLWA VCCCCSSSKI PFRSRSPSDV //