ID TGBR3_HUMAN Reviewed; 851 AA. AC Q03167; A0AUW8; A8K5N0; B9EG88; Q5T2T4; Q5U731; Q9UGI2; DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot. DT 02-NOV-2010, sequence version 3. DT 02-SEP-2026, entry version 204. DE RecName: Full=Transforming growth factor beta receptor type 3; DE Short=TGF-beta receptor type 3; DE Short=TGFR-3; DE AltName: Full=Betaglycan; DE AltName: Full=Transforming growth factor beta receptor III; DE Short=TGF-beta receptor type III; DE Flags: Precursor; GN Name=TGFBR3 {ECO:0000312|HGNC:HGNC:11774}; 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 2), AND VARIANT PHE-15. RC TISSUE=Placenta; RX PubMed=1333192; DOI=10.1016/0006-291x(92)91566-9; RA Moren A., Ichijo H., Miyazono K.; RT "Molecular cloning and characterization of the human and porcine RT transforming growth factor-beta type III receptors."; RL Biochem. Biophys. Res. Commun. 189:356-362(1992). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT PHE-15. RC TISSUE=Blood; RX PubMed=10944857; DOI=10.1007/s100380070035; RA Zippert R., Baessler A., Holmer S.R., Hengstenberg C., Schunkert H.; RT "Eleven single nucleotide polymorphisms and one triple nucleotide insertion RT of the human TGF-beta III receptor gene."; RL J. Hum. Genet. 45:250-253(2000). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ASN-14; PHE-15; LEU-163; RP THR-635 AND ARG-765. RG NIEHS SNPs program; RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Tongue; 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 MRNA] (ISOFORM 1). 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 [7] RP FUNCTION, PHOSPHORYLATION, AND SUBUNIT. RX PubMed=11323414; DOI=10.1074/jbc.m100188200; RA Blobe G.C., Schiemann W.P., Pepin M.C., Beauchemin M., Moustakas A., RA Lodish H.F., O'Connor-McCourt M.D.; RT "Functional roles for the cytoplasmic domain of the type III transforming RT growth factor beta receptor in regulating transforming growth factor beta RT signaling."; RL J. Biol. Chem. 276:24627-24637(2001). RN [8] RP FUNCTION, INTERACTION WITH ARRB2, AND PHOSPHORYLATION AT THR-840. RX PubMed=12958365; DOI=10.1126/science.1083195; RA Chen W., Kirkbride K.C., How T., Nelson C.D., Mo J., Frederick J.P., RA Wang X.-F., Lefkowitz R.J., Blobe G.C.; RT "Beta-arrestin 2 mediates endocytosis of type III TGF-beta receptor and RT down-regulation of its signaling."; RL Science 301:1394-1397(2003). RN [9] RP INTERACTION WITH DYNLT4. RX PubMed=16982625; DOI=10.1074/jbc.m608614200; RA Meng Q.-J., Lux A., Holloschi A., Li J., Hughes J.M.X., Foerg T., RA McCarthy J.E.G., Heagerty A.M., Kioschis P., Hafner M., Garland J.M.; RT "Identification of Tctex2beta, a novel dynein light chain family member RT that interacts with different transforming growth factor-beta receptors."; RL J. Biol. Chem. 281:37069-37080(2006). RN [10] RP FUNCTION, AND INTERACTION WITH TGFB1; BMP2; BMP4; BMP7 AND GDF5. RX PubMed=18184661; DOI=10.1074/jbc.m704883200; RA Kirkbride K.C., Townsend T.A., Bruinsma M.W., Barnett J.V., Blobe G.C.; RT "Bone morphogenetic proteins signal through the transforming growth factor- RT beta type III receptor."; RL J. Biol. Chem. 283:7628-7637(2008). RN [11] RP INTERACTION WITH BMPR1A; BMPR1B AND ARRB2, FUNCTION, AND SUBCELLULAR RP LOCATION. RX PubMed=19726563; DOI=10.1091/mbc.e09-07-0539; RA Lee N.Y., Kirkbride K.C., Sheu R.D., Blobe G.C.; RT "The transforming growth factor-beta type III receptor mediates distinct RT subcellular trafficking and downstream signaling of activin-like kinase RT (ALK)3 and ALK6 receptors."; RL Mol. Biol. Cell 20:4362-4370(2009). RN [12] RP FUNCTION, MUTAGENESIS OF THR-840, INTERACTION WITH ARRB2, AND SUBCELLULAR RP LOCATION. RX PubMed=19416857; DOI=10.1073/pnas.0812879106; RA Mythreye K., Blobe G.C.; RT "The type III TGF-beta receptor regulates epithelial and cancer cell RT migration through beta-arrestin2-mediated activation of Cdc42."; RL Proc. Natl. Acad. Sci. U.S.A. 106:8221-8226(2009). RN [13] RP FUNCTION, AND INTERACTION WITH ARRB2. RX PubMed=19325136; DOI=10.1093/carcin/bgp071; RA You H.J., How T., Blobe G.C.; RT "The type III transforming growth factor-beta receptor negatively regulates RT nuclear factor kappa B signaling through its interaction with beta- RT arrestin2."; RL Carcinogenesis 30:1281-1287(2009). RN [14] RP FUNCTION, AND INTERACTION WITH GIPC. RX PubMed=21871877; DOI=10.1016/j.ydbio.2011.08.008; RA Sanchez N.S., Hill C.R., Love J.D., Soslow J.H., Craig E., Austin A.F., RA Brown C.B., Czirok A., Camenisch T.D., Barnett J.V.; RT "The cytoplasmic domain of TGFbetaR3 through its interaction with the RT scaffolding protein, GIPC, directs epicardial cell behavior."; RL Dev. Biol. 358:331-343(2011). RN [15] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH INTEGRIN ALPHA5/BETA1. RX PubMed=22562249; DOI=10.1038/onc.2012.157; RA Mythreye K., Knelson E.H., Gatza C.E., Gatza M.L., Blobe G.C.; RT "TbetaRIII/beta-arrestin2 regulates integrin alpha5beta1 trafficking, RT function, and localization in epithelial cells."; RL Oncogene 32:1416-1427(2013). RN [16] RP FUNCTION. RX PubMed=34910520; DOI=10.1126/sciadv.abl4391; RA Brule E., Wang Y., Li Y., Lin Y.F., Zhou X., Ongaro L., Alonso C.A.I., RA Buddle E.R.S., Schneyer A.L., Byeon C.H., Hinck C.S., Mendelev N., RA Russell J.P., Cowan M., Boehm U., Ruf-Zamojski F., Zamojski M., RA Andoniadou C.L., Sealfon S.C., Harrison C.A., Walton K.L., Hinck A.P., RA Bernard D.J.; RT "TGFBR3L is an inhibin B co-receptor that regulates female fertility."; RL Sci. Adv. 7:eabl4391-eabl4391(2021). RN [17] {ECO:0007744|PDB:7LBG} RP STRUCTURE BY ELECTRON MICROSCOPY (2.60 ANGSTROMS) OF 1-781, DISULFIDE RP BONDS, INTERACTION WITH HCMV GH-GL-GO TRIMER (MICROBIAL INFECTION), AND RP FUNCTION (MICROBIAL INFECTION). RX PubMed=33626330; DOI=10.1016/j.cell.2021.01.036; RA Kschonsak M., Rouge L., Arthur C.P., Hoangdung H., Patel N., Kim I., RA Johnson M.C., Kraft E., Rohou A.L., Gill A., Martinez-Martin N., RA Payandeh J., Ciferri C.; RT "Structures of HCMV Trimer reveal the basis for receptor recognition and RT cell entry."; RL Cell 184:1232-1244(2021). CC -!- FUNCTION: Cell surface receptor that regulates diverse cellular CC processes including cell proliferation, differentiation, migration, and CC apoptosis (PubMed:12958365, PubMed:19416857). Initiates BMP, inhibin, CC and TGF-beta signaling pathways by interacting with different ligands CC including TGFB1, BMP2, BMP5, BMP7 or GDF5 (PubMed:18184661). CC Alternatively, acts as a cell surface coreceptor for BMP ligands, CC serving to enhance ligand binding by differentially regulating CC BMPR1A/ALK3 and BMPR1B/ALK6 receptor trafficking (PubMed:19726563). CC Promotes epithelial cell adhesion, focal adhesion formation and CC integrin signaling during epithelial cell spreading on fibronectin CC (PubMed:22562249). By interacting with the scaffolding protein beta- CC arrestin2/ARRB2, regulates migration or actin cytoskeleton and promotes CC the activation of CDC42 as well as the inhibition of NF-kappa-B CC (PubMed:19416857, PubMed:19325136). In gonadotrope cells, acts as an CC inhibin A coreceptor and regulates follicle-stimulating hormone (FSH) CC levels and female fertility (By similarity). Plays a role in the CC inhibition of directed and random cell migration in epithelial cells by CC altering the actin cytoskeletal organization (PubMed:19416857). CC Participates in epithelial-mesenchymal transformation (EMT) upon CC binding to BMP2 or TGFB2, by activating the PAR6/SMURF1/RHOA pathway CC (By similarity). {ECO:0000250|UniProtKB:P26342, CC ECO:0000269|PubMed:18184661, ECO:0000269|PubMed:19325136, CC ECO:0000269|PubMed:19416857, ECO:0000269|PubMed:19726563, CC ECO:0000269|PubMed:22562249, ECO:0000269|PubMed:34910520}. CC -!- FUNCTION: (Microbial infection) May act as a receptor for human CC cytomegalovirus in different cell types by interacting with HCMV trimer CC composed of GO, GH and GL. {ECO:0000269|PubMed:33626330}. CC -!- SUBUNIT: Forms homodimers and homooligomers (PubMed:11323414). CC Interacts with DYNLT4 (PubMed:16982625). Interacts with integrin CC ITGA5:ITGB1; this interaction promotes the internalization and CC trafficking of ITGA5:ITGB1 into endocytic vesicles (PubMed:22562249). CC Interacts with TGFB1, BMP2, BMP5, BMP7 or GDF5 and inhibin A via the CC ligand binding domains (PubMed:18184661). Interacts with ALK3/BMPR1A; CC this interaction results in the cell surface retention of BMPR1A CC (PubMed:19726563). Interacts with ALK6/BMPR1B; this interaction CC enhances BMPR1B-mediated stimulation of the BMP signaling pathway CC (PubMed:19726563). Interacts with the scaffolding protein beta- CC arrestin2/ARRB2; this interaction mediates internalization of TGFBR3 CC and thus regulates migration, actin cytoskeleton and activation of CC CDC42 (PubMed:12958365, PubMed:18184661, PubMed:19416857, CC PubMed:19325136). {ECO:0000269|PubMed:11323414, CC ECO:0000269|PubMed:12958365, ECO:0000269|PubMed:16982625, CC ECO:0000269|PubMed:18184661, ECO:0000269|PubMed:19325136, CC ECO:0000269|PubMed:19416857, ECO:0000269|PubMed:19726563, CC ECO:0000269|PubMed:22562249}. CC -!- SUBUNIT: (Microbial infection) Interacts with human cytomegalovirus CC trimer complex composed of gH, gL, and gO; these interactions may CC promote HCMV cell entry in specific cell types. CC {ECO:0000269|PubMed:33626330}. CC -!- INTERACTION: CC Q03167; P22455: FGFR4; NbExp=2; IntAct=EBI-2852679, EBI-6256193; CC Q03167; O14908: GIPC1; NbExp=3; IntAct=EBI-2852679, EBI-373132; CC Q03167; P01137: TGFB1; NbExp=2; IntAct=EBI-2852679, EBI-779636; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:19416857, CC ECO:0000269|PubMed:19726563, ECO:0000269|PubMed:22562249}; Single-pass CC type I membrane protein {ECO:0000255}. Secreted CC {ECO:0000250|UniProtKB:P26342}. Secreted, extracellular space, CC extracellular matrix {ECO:0000250|UniProtKB:P26342}. Note=Exists both CC as a membrane-bound form and as soluble form in serum and in the CC extracellular matrix. {ECO:0000250|UniProtKB:P26342}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q03167-1; Sequence=Displayed; CC Name=2; CC IsoId=Q03167-2; Sequence=VSP_040018; CC -!- PTM: Extensively modified by glycosaminoglycan groups (GAG). CC -!- PTM: Phosphorylated in the cytoplasmic domain by the type II receptor CC TGFBR2 at THR-840 to mediate recruitment of ARRB2 and subsequent CC internalization of TGFBR2 and TGFBR3. {ECO:0000269|PubMed:11323414, CC ECO:0000269|PubMed:12958365}. CC -!- SEQUENCE CAUTION: CC Sequence=AAA67061.1; Type=Frameshift; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/42541/TGFBR3"; 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; L07594; AAA67061.1; ALT_FRAME; mRNA. DR EMBL; AJ251961; CAB64374.1; -; mRNA. DR EMBL; AY796304; AAV50003.1; -; Genomic_DNA. DR EMBL; AK291345; BAF84034.1; -; mRNA. DR EMBL; AC099334; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL162263; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL390780; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL445992; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC126116; AAI26117.1; -; mRNA. DR EMBL; BC136295; AAI36296.1; -; mRNA. DR CCDS; CCDS30770.1; -. [Q03167-1] DR CCDS; CCDS55614.1; -. [Q03167-2] DR PIR; JC1350; JC1350. DR RefSeq; NP_001182612.1; NM_001195683.2. [Q03167-2] DR RefSeq; NP_001182613.1; NM_001195684.1. [Q03167-2] DR RefSeq; NP_003234.2; NM_003243.5. [Q03167-1] DR RefSeq; XP_006710930.1; XM_006710867.3. [Q03167-1] DR RefSeq; XP_047285203.1; XM_047429247.1. [Q03167-1] DR RefSeq; XP_047285210.1; XM_047429254.1. [Q03167-1] DR RefSeq; XP_047285211.1; XM_047429255.1. [Q03167-1] DR RefSeq; XP_047285212.1; XM_047429256.1. [Q03167-2] DR RefSeq; XP_047285217.1; XM_047429261.1. [Q03167-2] DR RefSeq; XP_047285227.1; XM_047429271.1. [Q03167-2] DR PDB; 7LBG; EM; 2.60 A; D=1-781. DR AlphaFoldDB; Q03167; -. DR EMDB; EMD-23254; -. DR SMR; Q03167; -. DR BioGRID; 112907; 44. DR DIP; DIP-5940N; -. DR FunCoup; Q03167; 331. DR IntAct; Q03167; 37. DR MINT; Q03167; -. DR NDEx; IQUERY-CP-TGFBR3; 10 NDEx IQuery Curated Pathways. DR STRING; 9606.ENSP00000212355; -. DR GlyCosmos; Q03167; 8 sites, 1 glycan. DR GlyGen; Q03167; 10 sites, 4 N-linked glycans (2 sites), 2 O-linked glycans (2 sites). DR iPTMnet; Q03167; -. DR PhosphoSitePlus; Q03167; -. DR BioMuta; TGFBR3; -. DR DMDM; 311033535; -. DR jPOST; Q03167; -. DR MassIVE; Q03167; -. DR PaxDb; 9606-ENSP00000212355; -. DR PeptideAtlas; Q03167; -. DR ProteomicsDB; 58197; -. [Q03167-1] DR ProteomicsDB; 58198; -. [Q03167-2] DR Pumba; Q03167; -. DR Antibodypedia; 1634; 516 antibodies from 45 providers. DR DNASU; 7049; -. DR Ensembl; ENST00000212355.9; ENSP00000212355.4; ENSG00000069702.12. [Q03167-1] DR Ensembl; ENST00000370399.6; ENSP00000359426.2; ENSG00000069702.12. [Q03167-2] DR Ensembl; ENST00000465892.6; ENSP00000432638.1; ENSG00000069702.12. [Q03167-2] DR Ensembl; ENST00000525962.5; ENSP00000436127.1; ENSG00000069702.12. [Q03167-1] DR Ensembl; ENST00000868418.1; ENSP00000538477.1; ENSG00000069702.12. [Q03167-2] DR Ensembl; ENST00000868428.1; ENSP00000538487.1; ENSG00000069702.12. [Q03167-1] DR Ensembl; ENST00000868431.1; ENSP00000538490.1; ENSG00000069702.12. [Q03167-2] DR GeneID; 7049; -. DR KEGG; hsa:7049; -. DR MANE-Select; ENST00000212355.9; ENSP00000212355.4; NM_003243.5; NP_003234.2. DR UCSC; uc001doh.4; human. [Q03167-1] DR AGR; HGNC:11774; -. DR CIViC; 7049; 1 evidence item across 1 molecular profile. DR ClinPGx; PA36487; -. DR CTD; 7049; -. DR DisGeNET; 7049; -. DR GeneCards; TGFBR3; -. DR HGNC; HGNC:11774; TGFBR3. DR HPA; ENSG00000069702; Low tissue specificity. DR MalaCards; TGFBR3; -. DR MIM; 600742; gene. DR OpenTargets; ENSG00000069702; -. DR Orphanet; 231160; Familial cerebral saccular aneurysm. DR VEuPathDB; HostDB:ENSG00000069702; -. DR eggNOG; ENOG502QWNZ; Eukaryota. DR GeneTree; ENSGT00530000063861; -. DR HOGENOM; CLU_018613_0_0_1; -. DR InParanoid; Q03167; -. DR OMA; VPQRECV; -. DR OrthoDB; 6420824at2759; -. DR PAN-GO; Q03167; 8 GO annotations based on evolutionary models. DR PhylomeDB; Q03167; -. DR PathwayCommons; Q03167; -. DR Reactome; R-HSA-1502540; Signaling by Activin. DR Reactome; R-HSA-190370; FGFR1b ligand binding and activation. DR Reactome; R-HSA-190373; FGFR1c ligand binding and activation. DR Reactome; R-HSA-201451; Signaling by BMP. DR Reactome; R-HSA-2173789; TGF-beta receptor signaling activates SMADs. DR Reactome; R-HSA-9839383; TGFBR3 PTM regulation. DR Reactome; R-HSA-9839389; TGFBR3 regulates TGF-beta signaling. DR Reactome; R-HSA-9839394; TGFBR3 expression. DR Reactome; R-HSA-9839397; TGFBR3 regulates FGF2 signaling. DR Reactome; R-HSA-9839406; TGFBR3 regulates activin signaling. DR SignaLink; Q03167; -. DR SIGNOR; Q03167; -. DR Agora; ENSG00000069702; -. DR BioGRID-ORCS; 7049; 12 hits in 1156 CRISPR screens. DR ChiTaRS; TGFBR3; human. DR GeneWiki; TGFBR3; -. DR GenomeRNAi; 7049; -. DR Pharos; Q03167; Tbio. DR PRO; PR:Q03167; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; Q03167; protein. DR Bgee; ENSG00000069702; Expressed in renal glomerulus and 205 other cell types or tissues. DR ExpressionAtlas; Q03167; baseline and differential. DR GO; GO:0016323; C:basolateral plasma membrane; TAS:Reactome. DR GO; GO:0009986; C:cell surface; ISS:BHF-UCL. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0009897; C:external side of plasma membrane; IDA:BHF-UCL. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; HDA:UniProtKB. DR GO; GO:0034673; C:inhibin-betaglycan-ActRII complex; IDA:BHF-UCL. DR GO; GO:0005886; C:plasma membrane; EXP:UniProtKB. DR GO; GO:0043235; C:signaling receptor complex; IDA:BHF-UCL. DR GO; GO:0048185; F:activin binding; IEA:Ensembl. DR GO; GO:0036122; F:BMP binding; IPI:BHF-UCL. DR GO; GO:0015026; F:coreceptor activity; IDA:BHF-UCL. DR GO; GO:0017134; F:fibroblast growth factor binding; IEA:Ensembl. DR GO; GO:0005539; F:glycosaminoglycan binding; ISS:BHF-UCL. DR GO; GO:0008201; F:heparin binding; ISS:BHF-UCL. DR GO; GO:0030165; F:PDZ domain binding; ISS:BHF-UCL. DR GO; GO:0046332; F:SMAD binding; IMP:BHF-UCL. DR GO; GO:0050431; F:transforming growth factor beta binding; IDA:BHF-UCL. DR GO; GO:0005024; F:transforming growth factor beta receptor activity; IDA:BHF-UCL. DR GO; GO:0070123; F:transforming growth factor beta receptor activity, type III; IDA:BHF-UCL. DR GO; GO:0005160; F:transforming growth factor beta receptor binding; ISS:BHF-UCL. DR GO; GO:0004888; F:transmembrane signaling receptor activity; IDA:BHF-UCL. DR GO; GO:0005114; F:type II transforming growth factor beta receptor binding; IDA:BHF-UCL. DR GO; GO:0031100; P:animal organ regeneration; IEA:Ensembl. DR GO; GO:0030509; P:BMP signaling pathway; IDA:BHF-UCL. DR GO; GO:0060317; P:cardiac epithelial to mesenchymal transition; IDA:BHF-UCL. DR GO; GO:0060038; P:cardiac muscle cell proliferation; ISS:BHF-UCL. DR GO; GO:0016477; P:cell migration; ISS:BHF-UCL. DR GO; GO:0060318; P:definitive erythrocyte differentiation; ISS:BHF-UCL. DR GO; GO:0060216; P:definitive hemopoiesis; ISS:BHF-UCL. DR GO; GO:0060939; P:epicardium-derived cardiac fibroblast cell development; ISS:BHF-UCL. DR GO; GO:0001837; P:epithelial to mesenchymal transition; IDA:BHF-UCL. DR GO; GO:0003007; P:heart morphogenesis; ISS:BHF-UCL. DR GO; GO:0060347; P:heart trabecula formation; ISS:BHF-UCL. DR GO; GO:0061384; P:heart trabecula morphogenesis; ISS:BHF-UCL. DR GO; GO:0006955; P:immune response; IMP:BHF-UCL. DR GO; GO:0035556; P:intracellular signal transduction; IMP:BHF-UCL. DR GO; GO:0001889; P:liver development; ISS:BHF-UCL. DR GO; GO:0003150; P:muscular septum morphogenesis; ISS:BHF-UCL. DR GO; GO:0043124; P:negative regulation of canonical NF-kappaB signal transduction; IDA:BHF-UCL. DR GO; GO:0030336; P:negative regulation of cell migration; IDA:BHF-UCL. DR GO; GO:0050680; P:negative regulation of epithelial cell proliferation; ISS:BHF-UCL. DR GO; GO:1901202; P:negative regulation of extracellular matrix assembly; IMP:BHF-UCL. DR GO; GO:0060392; P:negative regulation of SMAD protein signal transduction; IMP:BHF-UCL. DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; IEA:Ensembl. DR GO; GO:0003151; P:outflow tract morphogenesis; ISS:BHF-UCL. DR GO; GO:0060045; P:positive regulation of cardiac muscle cell proliferation; ISS:BHF-UCL. DR GO; GO:0090050; P:positive regulation of cell migration involved in sprouting angiogenesis; IMP:BHF-UCL. DR GO; GO:0010628; P:positive regulation of gene expression; IMP:BHF-UCL. DR GO; GO:0060391; P:positive regulation of SMAD protein signal transduction; IDA:BHF-UCL. DR GO; GO:0030511; P:positive regulation of transforming growth factor beta receptor signaling pathway; IEA:Ensembl. DR GO; GO:0017015; P:regulation of transforming growth factor beta receptor signaling pathway; IBA:GO_Central. DR GO; GO:0032354; P:response to follicle-stimulating hormone; IDA:BHF-UCL. DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl. DR GO; GO:0034699; P:response to luteinizing hormone; IDA:BHF-UCL. DR GO; GO:0034695; P:response to prostaglandin E; IDA:BHF-UCL. DR GO; GO:0062009; P:secondary palate development; ISS:BHF-UCL. DR GO; GO:0007181; P:transforming growth factor beta receptor complex assembly; IEA:Ensembl. DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IDA:BHF-UCL. DR GO; GO:0060979; P:vasculogenesis involved in coronary vascular morphogenesis; ISS:BHF-UCL. DR GO; GO:0055010; P:ventricular cardiac muscle tissue morphogenesis; ISS:BHF-UCL. DR GO; GO:0003223; P:ventricular compact myocardium morphogenesis; ISS:BHF-UCL. DR GO; GO:0060412; P:ventricular septum morphogenesis; ISS:BHF-UCL. DR FunFam; 2.60.40.3210:FF:000008; Transforming growth factor beta receptor 3; 1. DR FunFam; 2.60.40.4100:FF:000003; Transforming growth factor beta receptor type 3; 1. DR Gene3D; 2.60.40.4100; Zona pellucida, ZP-C domain; 1. DR Gene3D; 2.60.40.3210; Zona pellucida, ZP-N domain; 1. DR InterPro; IPR058899; TGFBR3/Endoglin-like_N. DR InterPro; IPR055355; ZP-C. DR InterPro; IPR042235; ZP-C_dom. DR InterPro; IPR055356; ZP-N. DR InterPro; IPR048290; ZP_chr. DR InterPro; IPR001507; ZP_dom. DR InterPro; IPR017977; ZP_dom_CS. DR PANTHER; PTHR14002; ENDOGLIN/TGF-BETA RECEPTOR TYPE III; 1. DR PANTHER; PTHR14002:SF7; TRANSFORMING GROWTH FACTOR BETA RECEPTOR TYPE 3; 1. DR Pfam; PF26060; TGFBR3_N; 2. DR Pfam; PF00100; Zona_pellucida; 1. DR Pfam; PF23344; ZP-N; 1. DR PRINTS; PR00023; ZPELLUCIDA. DR SMART; SM00241; ZP; 1. DR PROSITE; PS00682; ZP_1; 1. DR PROSITE; PS51034; ZP_2; 1. DR PDBsum; 7LBG; -. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell membrane; Disulfide bond; KW Extracellular matrix; Glycoprotein; Membrane; Phosphoprotein; Proteoglycan; KW Proteomics identification; Receptor; Reference proteome; Secreted; Signal; KW Transmembrane; Transmembrane helix. FT SIGNAL 1..20 FT /evidence="ECO:0000255" FT CHAIN 21..851 FT /note="Transforming growth factor beta receptor type 3" FT /id="PRO_0000041663" FT TOPO_DOM 21..787 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 788..809 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 810..851 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 455..730 FT /note="ZP" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00375" FT REGION 737..751 FT /note="Interaction with TGF-beta ligand" FT /evidence="ECO:0000250" FT REGION 816..851 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 817..834 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 836..851 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 840 FT /note="Phosphothreonine" FT /evidence="ECO:0000269|PubMed:12958365" FT CARBOHYD 141 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 492 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 534 FT /note="O-linked (Xyl...) (glycosaminoglycan) serine" FT /evidence="ECO:0000250" FT CARBOHYD 545 FT /note="O-linked (Xyl...) (glycosaminoglycan) serine" FT /evidence="ECO:0000250" FT CARBOHYD 571 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 590 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 697 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 52..197 FT /evidence="ECO:0000269|PubMed:33626330, FT ECO:0007744|PDB:7LBG" FT DISULFID 639..705 FT /evidence="ECO:0000250|UniProtKB:P26342" FT DISULFID 660..730 FT /evidence="ECO:0000250|UniProtKB:P26342" FT DISULFID 710..723 FT /evidence="ECO:0000250|UniProtKB:O88393" FT VAR_SEQ 359 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:1333192" FT /id="VSP_040018" FT VARIANT 14 FT /note="S -> N (in dbSNP:rs17884205)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_020891" FT VARIANT 15 FT /note="S -> F (in dbSNP:rs1805110)" FT /evidence="ECO:0000269|PubMed:10944857, FT ECO:0000269|PubMed:1333192, ECO:0000269|Ref.3" FT /id="VAR_014920" FT VARIANT 163 FT /note="W -> L (in dbSNP:rs17885124)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_020892" FT VARIANT 351 FT /note="F -> I (in dbSNP:rs11466592)" FT /id="VAR_057499" FT VARIANT 635 FT /note="A -> T (in dbSNP:rs17882578)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_020893" FT VARIANT 765 FT /note="G -> R (in dbSNP:rs17882828)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_020894" FT VARIANT 777 FT /note="P -> S (in dbSNP:rs2228363)" FT /id="VAR_066625" FT MUTAGEN 840 FT /note="T->A: Partial loss of phosphorylation by TGFBR2." FT /evidence="ECO:0000269|PubMed:12958365, FT ECO:0000269|PubMed:19416857" FT CONFLICT 89 FT /note="P -> S (in Ref. 4; BAF84034)" FT /evidence="ECO:0000305" FT CONFLICT 238 FT /note="I -> V (in Ref. 4; BAF84034)" FT /evidence="ECO:0000305" FT STRAND 49..51 FT /evidence="ECO:0007829|PDB:7LBG" FT HELIX 56..59 FT /evidence="ECO:0007829|PDB:7LBG" FT STRAND 60..70 FT /evidence="ECO:0007829|PDB:7LBG" FT STRAND 82..89 FT /evidence="ECO:0007829|PDB:7LBG" FT STRAND 94..96 FT /evidence="ECO:0007829|PDB:7LBG" FT STRAND 100..105 FT /evidence="ECO:0007829|PDB:7LBG" FT STRAND 111..116 FT /evidence="ECO:0007829|PDB:7LBG" FT STRAND 125..129 FT /evidence="ECO:0007829|PDB:7LBG" FT STRAND 134..138 FT /evidence="ECO:0007829|PDB:7LBG" FT HELIX 140..143 FT /evidence="ECO:0007829|PDB:7LBG" FT STRAND 146..150 FT /evidence="ECO:0007829|PDB:7LBG" FT HELIX 157..168 FT /evidence="ECO:0007829|PDB:7LBG" FT STRAND 172..178 FT /evidence="ECO:0007829|PDB:7LBG" FT STRAND 181..187 FT /evidence="ECO:0007829|PDB:7LBG" SQ SEQUENCE 851 AA; 93499 MW; AEC56C4477C003B2 CRC64; MTSHYVIAIF ALMSSCLATA GPEPGALCEL SPVSASHPVQ ALMESFTVLS GCASRGTTGL PQEVHVLNLR TAGQGPGQLQ REVTLHLNPI SSVHIHHKSV VFLLNSPHPL VWHLKTERLA TGVSRLFLVS EGSVVQFSSA NFSLTAETEE RNFPHGNEHL LNWARKEYGA VTSFTELKIA RNIYIKVGED QVFPPKCNIG KNFLSLNYLA EYLQPKAAEG CVMSSQPQNE EVHIIELITP NSNPYSAFQV DITIDIRPSQ EDLEVVKNLI LILKCKKSVN WVIKSFDVKG SLKIIAPNSI GFGKESERSM TMTKSIRDDI PSTQGNLVKW ALDNGYSPIT SYTMAPVANR FHLRLENNAE EMGDEEVHTI PPELRILLDP GALPALQNPP IRGGEGQNGG LPFPFPDISR RVWNEEGEDG LPRPKDPVIP SIQLFPGLRE PEEVQGSVDI ALSVKCDNEK MIVAVEKDSF QASGYSGMDV TLLDPTCKAK MNGTHFVLES PLNGCGTRPR WSALDGVVYY NSIVIQVPAL GDSSGWPDGY EDLESGDNGF PGDMDEGDAS LFTRPEIVVF NCSLQQVRNP SSFQEQPHGN ITFNMELYNT DLFLVPSQGV FSVPENGHVY VEVSVTKAEQ ELGFAIQTCF ISPYSNPDRM SHYTIIENIC PKDESVKFYS PKRVHFPIPQ ADMDKKRFSF VFKPVFNTSL LFLQCELTLC TKMEKHPQKL PKCVPPDEAC TSLDASIIWA MMQNKKTFTK PLAVIHHEAE SKEKGPSMKE PNPISPPIFH GLDTLTVMGI AFAAFVIGAL LTGALWYIYS HTGETAGRQQ VPTSPPASEN SSAAHSIGST QSTPCSSSST A //