ID   TGBR3_MOUSE             Reviewed;         850 AA.
AC   O88393; Q6NS72;
DT   04-JAN-2005, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1998, sequence version 1.
DT   27-MAR-2024, entry version 151.
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;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], GLYCOSYLATION AT SER-533 AND SER-544, AND
RP   MUTAGENESIS OF SER-533 AND SER-544.
RX   PubMed=9659379; DOI=10.1016/s0167-4838(98)00033-8;
RA   Ponce-Castaneda M.V., Esparza-Lopez J., Vilchis-Landeros M.M., Mendoza V.,
RA   Lopez-Casillas F.;
RT   "Murine betaglycan primary structure, expression and glycosaminoglycan
RT   attachment sites.";
RL   Biochim. Biophys. Acta 1384:189-196(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; 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   [3]
RP   DISRUPTION PHENOTYPE, AND FUNCTION.
RX   PubMed=30364975; DOI=10.1210/en.2018-00770;
RA   Li Y., Fortin J., Ongaro L., Zhou X., Boehm U., Schneyer A., Bernard D.J.,
RA   Lin H.Y.;
RT   "Betaglycan (TGFBR3) Functions as an Inhibin A, but Not Inhibin B,
RT   Coreceptor in Pituitary Gonadotrope Cells in Mice.";
RL   Endocrinology 159:4077-4091(2018).
RN   [4]
RP   DISRUPTION PHENOTYPE, AND 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   [5]
RP   X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 591-757, DISULFIDE BONDS, AND
RP   INTERACTION WITH TGF-BETA.
RX   PubMed=23826237; DOI=10.1371/journal.pone.0067214;
RA   Diestel U., Resch M., Meinhardt K., Weiler S., Hellmann T.V., Mueller T.D.,
RA   Nickel J., Eichler J., Muller Y.A.;
RT   "Identification of a novel TGF-beta-binding site in the zona pellucida C-
RT   terminal (ZP-C) domain of TGF-beta-receptor-3 (TGFR-3).";
RL   PLoS ONE 8:E67214-E67214(2013).
CC   -!- FUNCTION: Binds to TGF-beta. Could be involved in capturing and
CC       retaining TGF-beta for presentation to the signaling receptors (By
CC       similarity). In gonadotrope cells, acts as an inhibin A coreceptor and
CC       regulates follicle-stimulating hormone (FSH) levels and female
CC       fertility (PubMed:34910520, PubMed:30364975).
CC       {ECO:0000250|UniProtKB:P26342, ECO:0000269|PubMed:30364975,
CC       ECO:0000269|PubMed:34910520}.
CC   -!- SUBUNIT: Interacts with DYNLT4. {ECO:0000250|UniProtKB:Q03167}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P26342};
CC       Single-pass 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   -!- PTM: Extensively modified by glycosaminoglycan (GAG), either
CC       chondroitin sulfate or heparan sulfate depending upon the tissue of
CC       origin.
CC   -!- DISRUPTION PHENOTYPE: Gonadotrope-specific knockout females are supra-
CC       fertile with enhanced folliculogenesis, numbers of ovulated eggs per
CC       cycle and litter sizes relative to control mice (PubMed:30364975).
CC       Double knockout females for TGFBR3L and gonadotrope-specific TGFBR3 are
CC       infertile. They have increased serum follicle-stimulating hormone
CC       (FSH), pituitary protein content relative to controls. They have larger
CC       ovaries with increased numbers of antral follicles and corpora lutea
CC       (PubMed:34910520). {ECO:0000269|PubMed:30364975,
CC       ECO:0000269|PubMed:34910520}.
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DR   EMBL; AF039601; AAC28564.1; -; mRNA.
DR   EMBL; BC070428; AAH70428.1; -; mRNA.
DR   CCDS; CCDS19499.1; -.
DR   RefSeq; NP_035708.2; NM_011578.4.
DR   PDB; 4AJV; X-ray; 2.70 A; A=591-757.
DR   PDBsum; 4AJV; -.
DR   AlphaFoldDB; O88393; -.
DR   SMR; O88393; -.
DR   BioGRID; 204165; 2.
DR   STRING; 10090.ENSMUSP00000031224; -.
DR   GlyCosmos; O88393; 7 sites, No reported glycans.
DR   GlyGen; O88393; 7 sites.
DR   iPTMnet; O88393; -.
DR   PhosphoSitePlus; O88393; -.
DR   MaxQB; O88393; -.
DR   PaxDb; 10090-ENSMUSP00000031224; -.
DR   PeptideAtlas; O88393; -.
DR   ProteomicsDB; 263036; -.
DR   Pumba; O88393; -.
DR   DNASU; 21814; -.
DR   GeneID; 21814; -.
DR   KEGG; mmu:21814; -.
DR   UCSC; uc008ylz.2; mouse.
DR   AGR; MGI:104637; -.
DR   CTD; 7049; -.
DR   MGI; MGI:104637; Tgfbr3.
DR   eggNOG; ENOG502QWNZ; Eukaryota.
DR   InParanoid; O88393; -.
DR   OrthoDB; 2949260at2759; -.
DR   PhylomeDB; O88393; -.
DR   TreeFam; TF337375; -.
DR   Reactome; R-MMU-1502540; Signaling by Activin.
DR   Reactome; R-MMU-190370; FGFR1b ligand binding and activation.
DR   Reactome; R-MMU-190373; FGFR1c ligand binding and activation.
DR   Reactome; R-MMU-201451; Signaling by BMP.
DR   Reactome; R-MMU-2173789; TGF-beta receptor signaling activates SMADs.
DR   BioGRID-ORCS; 21814; 5 hits in 79 CRISPR screens.
DR   ChiTaRS; Tgfbr3; mouse.
DR   PRO; PR:O88393; -.
DR   Proteomes; UP000000589; Unplaced.
DR   RNAct; O88393; Protein.
DR   GO; GO:0009986; C:cell surface; IDA:BHF-UCL.
DR   GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR   GO; GO:0005783; C:endoplasmic reticulum; IDA:MGI.
DR   GO; GO:0009897; C:external side of plasma membrane; ISO:MGI.
DR   GO; GO:0005615; C:extracellular space; ISO:MGI.
DR   GO; GO:0034673; C:inhibin-betaglycan-ActRII complex; ISO:MGI.
DR   GO; GO:0016020; C:membrane; ISO:MGI.
DR   GO; GO:0005886; C:plasma membrane; TAS:DFLAT.
DR   GO; GO:0043235; C:receptor complex; ISO:MGI.
DR   GO; GO:0048185; F:activin binding; ISO:MGI.
DR   GO; GO:0036122; F:BMP binding; ISO:MGI.
DR   GO; GO:0015026; F:coreceptor activity; ISO:MGI.
DR   GO; GO:0017134; F:fibroblast growth factor binding; ISO:MGI.
DR   GO; GO:0005539; F:glycosaminoglycan binding; IDA:BHF-UCL.
DR   GO; GO:0008201; F:heparin binding; ISO:MGI.
DR   GO; GO:0030165; F:PDZ domain binding; IPI: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; ISO:MGI.
DR   GO; GO:0005160; F:transforming growth factor beta receptor binding; ISO:MGI.
DR   GO; GO:0004888; F:transmembrane signaling receptor activity; ISO:MGI.
DR   GO; GO:0005114; F:type II transforming growth factor beta receptor binding; ISO:MGI.
DR   GO; GO:0060561; P:apoptotic process involved in morphogenesis; IMP:MGI.
DR   GO; GO:0001824; P:blastocyst development; IDA:MGI.
DR   GO; GO:0001568; P:blood vessel development; IMP:MGI.
DR   GO; GO:0097746; P:blood vessel diameter maintenance; TAS:DFLAT.
DR   GO; GO:0001974; P:blood vessel remodeling; IMP:MGI.
DR   GO; GO:0030509; P:BMP signaling pathway; IMP:MGI.
DR   GO; GO:0060317; P:cardiac epithelial to mesenchymal transition; ISO:MGI.
DR   GO; GO:0060038; P:cardiac muscle cell proliferation; IMP:BHF-UCL.
DR   GO; GO:0016477; P:cell migration; IBA:GO_Central.
DR   GO; GO:0008283; P:cell population proliferation; IMP:MGI.
DR   GO; GO:0032963; P:collagen metabolic process; IGI:BHF-UCL.
DR   GO; GO:0060976; P:coronary vasculature development; TAS:DFLAT.
DR   GO; GO:0060977; P:coronary vasculature morphogenesis; TAS:DFLAT.
DR   GO; GO:0060318; P:definitive erythrocyte differentiation; IMP:BHF-UCL.
DR   GO; GO:0060216; P:definitive hemopoiesis; IMP:BHF-UCL.
DR   GO; GO:0003347; P:epicardial cell to mesenchymal cell transition; TAS:DFLAT.
DR   GO; GO:0060939; P:epicardium-derived cardiac fibroblast cell development; IMP:BHF-UCL.
DR   GO; GO:0001837; P:epithelial to mesenchymal transition; ISO:MGI.
DR   GO; GO:0060347; P:heart trabecula formation; IMP:BHF-UCL.
DR   GO; GO:0061384; P:heart trabecula morphogenesis; IMP:BHF-UCL.
DR   GO; GO:0006955; P:immune response; ISO:MGI.
DR   GO; GO:0001701; P:in utero embryonic development; IMP:MGI.
DR   GO; GO:0035556; P:intracellular signal transduction; ISO:MGI.
DR   GO; GO:0001889; P:liver development; IMP:BHF-UCL.
DR   GO; GO:0003150; P:muscular septum morphogenesis; IMP:BHF-UCL.
DR   GO; GO:1902338; P:negative regulation of apoptotic process involved in morphogenesis; IMP:MGI.
DR   GO; GO:0043124; P:negative regulation of canonical NF-kappaB signal transduction; ISO:MGI.
DR   GO; GO:0030336; P:negative regulation of cell migration; ISO:MGI.
DR   GO; GO:0010633; P:negative regulation of epithelial cell migration; IMP:MGI.
DR   GO; GO:0050680; P:negative regulation of epithelial cell proliferation; IMP:BHF-UCL.
DR   GO; GO:0010719; P:negative regulation of epithelial to mesenchymal transition; IMP:MGI.
DR   GO; GO:1901202; P:negative regulation of extracellular matrix assembly; ISO:MGI.
DR   GO; GO:0010629; P:negative regulation of gene expression; IDA:BHF-UCL.
DR   GO; GO:0060392; P:negative regulation of SMAD protein signal transduction; ISO:MGI.
DR   GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; ISO:MGI.
DR   GO; GO:0001649; P:osteoblast differentiation; IMP:MGI.
DR   GO; GO:0003151; P:outflow tract morphogenesis; IMP:BHF-UCL.
DR   GO; GO:0030513; P:positive regulation of BMP signaling pathway; IMP:MGI.
DR   GO; GO:0060045; P:positive regulation of cardiac muscle cell proliferation; IMP:BHF-UCL.
DR   GO; GO:0090050; P:positive regulation of cell migration involved in sprouting angiogenesis; ISO:MGI.
DR   GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:MGI.
DR   GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI.
DR   GO; GO:0060391; P:positive regulation of SMAD protein signal transduction; IMP:BHF-UCL.
DR   GO; GO:0030511; P:positive regulation of transforming growth factor beta receptor signaling pathway; IMP:MGI.
DR   GO; GO:0065003; P:protein-containing complex assembly; ISO:MGI.
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; ISO:MGI.
DR   GO; GO:0034699; P:response to luteinizing hormone; ISO:MGI.
DR   GO; GO:0034695; P:response to prostaglandin E; ISO:MGI.
DR   GO; GO:0060021; P:roof of mouth development; IMP:MGI.
DR   GO; GO:0062009; P:secondary palate development; IMP:BHF-UCL.
DR   GO; GO:0007181; P:transforming growth factor beta receptor complex assembly; ISO:MGI.
DR   GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IDA:BHF-UCL.
DR   GO; GO:0001570; P:vasculogenesis; IMP:MGI.
DR   GO; GO:0060979; P:vasculogenesis involved in coronary vascular morphogenesis; IMP:BHF-UCL.
DR   GO; GO:0055010; P:ventricular cardiac muscle tissue morphogenesis; IMP:BHF-UCL.
DR   GO; GO:0003223; P:ventricular compact myocardium morphogenesis; IMP:BHF-UCL.
DR   GO; GO:0060412; P:ventricular septum morphogenesis; IMP:BHF-UCL.
DR   GO; GO:0061032; P:visceral serous pericardium development; TAS:DFLAT.
DR   DisProt; DP02636; -.
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; IPR042235; ZP-C.
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; PF00100; Zona_pellucida; 1.
DR   PRINTS; PR00023; ZPELLUCIDA.
DR   SMART; SM00241; ZP; 1.
DR   PROSITE; PS00682; ZP_1; 1.
DR   PROSITE; PS51034; ZP_2; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Cell membrane; Disulfide bond; Extracellular matrix;
KW   Glycoprotein; Membrane; Proteoglycan; Receptor; Reference proteome;
KW   Secreted; Signal; Transmembrane; Transmembrane helix.
FT   SIGNAL          1..22
FT                   /evidence="ECO:0000255"
FT   CHAIN           23..850
FT                   /note="Transforming growth factor beta receptor type 3"
FT                   /id="PRO_0000041664"
FT   TOPO_DOM        23..785
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        786..808
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        809..850
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          454..728
FT                   /note="ZP"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00375"
FT   REGION          528..557
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          735..749
FT                   /note="Interaction with TGF-beta ligand"
FT   REGION          817..850
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   CARBOHYD        143
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        491
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        533
FT                   /note="O-linked (Xyl...) (glycosaminoglycan) serine"
FT                   /evidence="ECO:0000269|PubMed:9659379"
FT   CARBOHYD        544
FT                   /note="O-linked (Xyl...) (glycosaminoglycan) serine"
FT                   /evidence="ECO:0000269|PubMed:9659379"
FT   CARBOHYD        570
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        589
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        696
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        638..704
FT                   /evidence="ECO:0000269|PubMed:23826237"
FT   DISULFID        659..728
FT                   /evidence="ECO:0000269|PubMed:23826237"
FT   DISULFID        709..721
FT                   /evidence="ECO:0000269|PubMed:23826237"
FT   MUTAGEN         533
FT                   /note="S->A: Loss of glycosaminoglycan chains; when
FT                   associated with A-544."
FT                   /evidence="ECO:0000269|PubMed:9659379"
FT   MUTAGEN         544
FT                   /note="S->A: Loss of glycosaminoglycan chains; when
FT                   associated with A-533."
FT                   /evidence="ECO:0000269|PubMed:9659379"
FT   CONFLICT        322
FT                   /note="Y -> I (in Ref. 2; AAH70428)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        391
FT                   /note="P -> S (in Ref. 2; AAH70428)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        712
FT                   /note="N -> K (in Ref. 2; AAH70428)"
FT                   /evidence="ECO:0000305"
FT   STRAND          592..599
FT                   /evidence="ECO:0007829|PDB:4AJV"
FT   STRAND          607..612
FT                   /evidence="ECO:0007829|PDB:4AJV"
FT   STRAND          617..627
FT                   /evidence="ECO:0007829|PDB:4AJV"
FT   STRAND          629..644
FT                   /evidence="ECO:0007829|PDB:4AJV"
FT   STRAND          646..648
FT                   /evidence="ECO:0007829|PDB:4AJV"
FT   STRAND          653..656
FT                   /evidence="ECO:0007829|PDB:4AJV"
FT   STRAND          666..675
FT                   /evidence="ECO:0007829|PDB:4AJV"
FT   TURN            676..679
FT                   /evidence="ECO:0007829|PDB:4AJV"
FT   STRAND          680..690
FT                   /evidence="ECO:0007829|PDB:4AJV"
FT   STRAND          695..714
FT                   /evidence="ECO:0007829|PDB:4AJV"
FT   TURN            724..728
FT                   /evidence="ECO:0007829|PDB:4AJV"
FT   STRAND          747..756
FT                   /evidence="ECO:0007829|PDB:4AJV"
SQ   SEQUENCE   850 AA;  93829 MW;  4154D034C7307C86 CRC64;
     MAVTSHHMVP VFVLMSACLA TAGPEPSTRC ELSPISASHP VQALMESFTV LSGCASRGTT
     GLPREVHILN LRSTDQGLGQ PQREVTLHLN PIASVHTHHK PVVFLLNSPQ PLVWHVKTER
     LAAGVPRLFL VSEGSVVQFS SGNFSLTAET EERSFPQENE HLLHWAQKEY GAVTSFTELK
     IARNIYIKVG EDQVFPPTCN IGKNFLSLNY LAEYLQPKAA EGCVLASQPH EKEVHIIELI
     SPNSNPYSTF QVDIIIDIRP AREDPEVVKN LVLILKCKKS VNWVIKSFDV KGNLKVIAPD
     SIGFGKESER SMTVTKLVRN DYPSTQENLM KWALDNGYSP VTSYTIAPVA NRFHLRLENN
     EEMRDEEVHT IPPELRILLG PDHLPALDSP PFQGEIPNGG FPFPFPDIPR RGWKEGEDRI
     PRPKEPIIPR VQLLPDHREP EEVQGGVNIA LSVKCDNEKM VVAVDKDSFQ TNGYSGMELT
     LLDPSCKAKM NGTHFVLESP LNGCGTRHRR SAPDGVVYYN SIVVQAPSPG DSSGWPDGYE
     DLESGDNGFP GDTDEGETAP LSRAGVVVFN CSLRQLRSPS GFQDQLDGNA TFNMELYNTD
     LFLVPSPGVF SVAENEHVYV EVSVTKADQD LGFAIQTCFI SPYSNPDRMS DYTIIENICP
     KDDSVKFYSS KRVHFPIPHA EVDKKRFSFV FKSVFNTSLL FLHCELTLCS RNKGSQKLPK
     CVTPDDACTS LDATMIWTMM QNKKTFTKPL AVVLQVDYKE NVPNMKESSP VPPPPQIFHG
     LDTLTVMGIA FAAFVIGALL TGALWYIYSH TGETARRQQV PTSPPASENS SAAHSIGSTQ
     STPCSSSSTA
//