ID TGFR2_RAT Reviewed; 567 AA. AC P38438; DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-1994, sequence version 1. DT 27-MAR-2024, entry version 190. DE RecName: Full=TGF-beta receptor type-2; DE Short=TGFR-2; DE EC=2.7.11.30; DE AltName: Full=TGF-beta type II receptor; DE AltName: Full=Transforming growth factor-beta receptor type II; DE Short=TGF-beta receptor type II; DE Short=TbetaR-II; DE Flags: Precursor; GN Name=Tgfbr2; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=Sprague-Dawley; TISSUE=Pituitary; RX PubMed=8385453; DOI=10.1006/bbrc.1993.1286; RA Tsuchida K., Lewis K.A., Mathews L.S., Vale W.W.; RT "Molecular characterization of rat transforming growth factor-beta type II RT receptor."; RL Biochem. Biophys. Res. Commun. 191:790-795(1993). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=8264154; DOI=10.1038/ki.1993.336; RA Choi M.E., Kim E.G., Huang Q., Ballermann B.J.; RT "Rat mesangial cell hypertrophy in response to transforming growth factor- RT beta 1."; RL Kidney Int. 44:948-958(1993). RN [3] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-548, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22673903; DOI=10.1038/ncomms1871; RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., RA Olsen J.V.; RT "Quantitative maps of protein phosphorylation sites across 14 different rat RT organs and tissues."; RL Nat. Commun. 3:876-876(2012). CC -!- FUNCTION: Transmembrane serine/threonine kinase forming with the TGF- CC beta type I serine/threonine kinase receptor, TGFBR1, the non- CC promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3. CC Transduces the TGFB1, TGFB2 and TGFB3 signal from the cell surface to CC the cytoplasm and is thus regulating a plethora of physiological and CC pathological processes including cell cycle arrest in epithelial and CC hematopoietic cells, control of mesenchymal cell proliferation and CC differentiation, wound healing, extracellular matrix production, CC immunosuppression and carcinogenesis. The formation of the receptor CC complex composed of 2 TGFBR1 and 2 TGFBR2 molecules symmetrically bound CC to the cytokine dimer results in the phosphorylation and the activation CC of TGFRB1 by the constitutively active TGFBR2. Activated TGFBR1 CC phosphorylates SMAD2 which dissociates from the receptor and interacts CC with SMAD4. The SMAD2-SMAD4 complex is subsequently translocated to the CC nucleus where it modulates the transcription of the TGF-beta-regulated CC genes. This constitutes the canonical SMAD-dependent TGF-beta signaling CC cascade. Also involved in non-canonical, SMAD-independent TGF-beta CC signaling pathways (By similarity). {ECO:0000250|UniProtKB:P37173}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-threonyl-[receptor-protein] = ADP + H(+) + O-phospho- CC L-threonyl-[receptor-protein]; Xref=Rhea:RHEA:44880, Rhea:RHEA- CC COMP:11024, Rhea:RHEA-COMP:11025, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, CC ChEBI:CHEBI:456216; EC=2.7.11.30; CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-seryl-[receptor-protein] = ADP + H(+) + O-phospho-L- CC seryl-[receptor-protein]; Xref=Rhea:RHEA:18673, Rhea:RHEA-COMP:11022, CC Rhea:RHEA-COMP:11023, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, CC ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; CC EC=2.7.11.30; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250}; CC -!- SUBUNIT: Homodimer. Heterohexamer; TGFB1, TGFB2 and TGFB3 homodimeric CC ligands assemble a functional receptor composed of two TGFBR1 and CC TGFBR2 heterodimers to form a ligand-receptor heterohexamer. The CC respective affinity of TGFRB1 and TGFRB2 for the ligands may modulate CC the kinetics of assembly of the receptor and may explain the different CC biological activities of TGFB1, TGFB2 and TGFB3. Component of a complex CC composed of TSC22D1 (via N-terminus), TGFBR1 and TGFBR2; the CC interaction between TSC22D1 and TGFBR1 is inhibited by SMAD7 and CC promoted by TGFB1 (By similarity). Interacts with DAXX. Interacts with CC DYNLT4. Interacts with ZFYVE9; ZFYVE9 recruits SMAD2 and SMAD3 to the CC TGF-beta receptor (By similarity). Interacts with and is activated by CC SCUBE3; this interaction does not affect TGFB1-binding to TGFBR2 (By CC similarity). Interacts with VPS39; this interaction is independent of CC the receptor kinase activity and of the presence of TGF-beta (By CC similarity). Interacts with CLU (By similarity). CC {ECO:0000250|UniProtKB:P37173}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P37173}; CC Single-pass type I membrane protein {ECO:0000250|UniProtKB:P37173}. CC Membrane raft {ECO:0000250|UniProtKB:P37173}. CC -!- PTM: Phosphorylated on a Ser/Thr residue in the cytoplasmic domain. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. TKL Ser/Thr CC protein kinase family. TGFB receptor subfamily. {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; L09653; AAA42237.1; -; mRNA. DR EMBL; S67770; AAB29352.2; -; mRNA. DR PIR; JN0459; JN0459. DR RefSeq; NP_112394.3; NM_031132.3. DR AlphaFoldDB; P38438; -. DR SMR; P38438; -. DR BioGRID; 249668; 3. DR CORUM; P38438; -. DR IntAct; P38438; 1. DR STRING; 10116.ENSRNOP00000035501; -. DR GlyCosmos; P38438; 2 sites, No reported glycans. DR GlyGen; P38438; 2 sites. DR iPTMnet; P38438; -. DR PhosphoSitePlus; P38438; -. DR SwissPalm; P38438; -. DR PaxDb; 10116-ENSRNOP00000035501; -. DR Ensembl; ENSRNOT00000116107.1; ENSRNOP00000093892.1; ENSRNOG00000013265.7. DR Ensembl; ENSRNOT00055010808; ENSRNOP00055008392; ENSRNOG00055006638. DR Ensembl; ENSRNOT00060053114; ENSRNOP00060044162; ENSRNOG00060030566. DR Ensembl; ENSRNOT00065005407; ENSRNOP00065003934; ENSRNOG00065003711. DR GeneID; 81810; -. DR KEGG; rno:81810; -. DR UCSC; RGD:69651; rat. DR AGR; RGD:69651; -. DR CTD; 7048; -. DR RGD; 69651; Tgfbr2. DR eggNOG; KOG3653; Eukaryota. DR GeneTree; ENSGT00940000157527; -. DR HOGENOM; CLU_000288_8_3_1; -. DR InParanoid; P38438; -. DR OrthoDB; 3900892at2759; -. DR PhylomeDB; P38438; -. DR BRENDA; 2.7.10.2; 5301. DR Reactome; R-RNO-2173788; Downregulation of TGF-beta receptor signaling. DR Reactome; R-RNO-2173789; TGF-beta receptor signaling activates SMADs. DR Reactome; R-RNO-2173791; TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition). DR PRO; PR:P38438; -. DR Proteomes; UP000002494; Chromosome 8. DR Bgee; ENSRNOG00000013265; Expressed in lung and 18 other cell types or tissues. DR ExpressionAtlas; P38438; baseline and differential. DR GO; GO:0005901; C:caveola; IDA:MGI. DR GO; GO:0009986; C:cell surface; IDA:RGD. DR GO; GO:0009897; C:external side of plasma membrane; ISO:RGD. DR GO; GO:0016020; C:membrane; ISO:RGD. DR GO; GO:0045121; C:membrane raft; IDA:MGI. DR GO; GO:0005886; C:plasma membrane; ISO:RGD. DR GO; GO:0043235; C:receptor complex; ISO:RGD. DR GO; GO:0070021; C:transforming growth factor beta ligand-receptor complex; ISO:RGD. DR GO; GO:0048185; F:activin binding; IBA:GO_Central. DR GO; GO:0017002; F:activin receptor activity; IBA:GO_Central. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0005539; F:glycosaminoglycan binding; ISO:RGD. DR GO; GO:0019209; F:kinase activator activity; ISO:RGD. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0031435; F:mitogen-activated protein kinase kinase kinase binding; IPI:RGD. DR GO; GO:0060090; F:molecular adaptor activity; ISO:RGD. DR GO; GO:0042803; F:protein homodimerization activity; TAS:RGD. DR GO; GO:0044877; F:protein-containing complex binding; TAS:RGD. DR GO; GO:0046332; F:SMAD binding; ISO:RGD. DR GO; GO:0050431; F:transforming growth factor beta binding; ISO:RGD. DR GO; GO:0005024; F:transforming growth factor beta receptor activity; ISO:RGD. DR GO; GO:0005026; F:transforming growth factor beta receptor activity, type II; IMP:RGD. DR GO; GO:0004675; F:transmembrane receptor protein serine/threonine kinase activity; ISO:RGD. DR GO; GO:0034713; F:type I transforming growth factor beta receptor binding; ISO:RGD. DR GO; GO:0009887; P:animal organ morphogenesis; IMP:RGD. DR GO; GO:0031100; P:animal organ regeneration; IEP:RGD. DR GO; GO:0035909; P:aorta morphogenesis; ISO:RGD. DR GO; GO:0003180; P:aortic valve morphogenesis; ISO:RGD. DR GO; GO:0006915; P:apoptotic process; ISO:RGD. DR GO; GO:0048844; P:artery morphogenesis; ISO:RGD. DR GO; GO:0003181; P:atrioventricular valve morphogenesis; ISO:RGD. DR GO; GO:0007420; P:brain development; ISO:RGD. DR GO; GO:0001569; P:branching involved in blood vessel morphogenesis; ISO:RGD. DR GO; GO:0060433; P:bronchus development; ISO:RGD. DR GO; GO:0060434; P:bronchus morphogenesis; ISO:RGD. DR GO; GO:0003214; P:cardiac left ventricle morphogenesis; ISO:RGD. DR GO; GO:0051216; P:cartilage development; ISO:RGD. DR GO; GO:0071363; P:cellular response to growth factor stimulus; IBA:GO_Central. DR GO; GO:0048565; P:digestive tract development; IEP:RGD. DR GO; GO:0007566; P:embryo implantation; IEP:RGD. DR GO; GO:0048701; P:embryonic cranial skeleton morphogenesis; ISO:RGD. DR GO; GO:0035162; P:embryonic hemopoiesis; ISO:RGD. DR GO; GO:0003274; P:endocardial cushion fusion; ISO:RGD. DR GO; GO:0001837; P:epithelial to mesenchymal transition; ISO:RGD. DR GO; GO:0007369; P:gastrulation; ISO:RGD. DR GO; GO:0003430; P:growth plate cartilage chondrocyte growth; ISO:RGD. DR GO; GO:0003417; P:growth plate cartilage development; ISO:RGD. DR GO; GO:0007507; P:heart development; ISO:RGD. DR GO; GO:0001947; P:heart looping; ISO:RGD. DR GO; GO:0001701; P:in utero embryonic development; ISO:RGD. DR GO; GO:1905317; P:inferior endocardial cushion morphogenesis; ISO:RGD. DR GO; GO:0061520; P:Langerhans cell differentiation; ISO:RGD. DR GO; GO:0002088; P:lens development in camera-type eye; ISO:RGD. DR GO; GO:1990086; P:lens fiber cell apoptotic process; ISO:RGD. DR GO; GO:0030324; P:lung development; IEP:RGD. DR GO; GO:0060463; P:lung lobe morphogenesis; ISO:RGD. DR GO; GO:0060425; P:lung morphogenesis; ISO:RGD. DR GO; GO:0060443; P:mammary gland morphogenesis; ISO:RGD. DR GO; GO:0003149; P:membranous septum morphogenesis; ISO:RGD. DR GO; GO:1990428; P:miRNA transport; ISO:RGD. DR GO; GO:0060044; P:negative regulation of cardiac muscle cell proliferation; IMP:RGD. DR GO; GO:0008285; P:negative regulation of cell population proliferation; IMP:RGD. DR GO; GO:0007219; P:Notch signaling pathway; ISO:RGD. DR GO; GO:0003151; P:outflow tract morphogenesis; ISO:RGD. DR GO; GO:0003148; P:outflow tract septum morphogenesis; ISO:RGD. DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW. DR GO; GO:0045766; P:positive regulation of angiogenesis; ISO:RGD. DR GO; GO:0002663; P:positive regulation of B cell tolerance induction; ISO:RGD. DR GO; GO:2000563; P:positive regulation of CD4-positive, alpha-beta T cell proliferation; ISO:RGD. DR GO; GO:0010634; P:positive regulation of epithelial cell migration; ISO:RGD. DR GO; GO:0010718; P:positive regulation of epithelial to mesenchymal transition; ISO:RGD. DR GO; GO:1905007; P:positive regulation of epithelial to mesenchymal transition involved in endocardial cushion formation; ISO:RGD. DR GO; GO:0002053; P:positive regulation of mesenchymal cell proliferation; ISO:RGD. DR GO; GO:0051138; P:positive regulation of NK T cell differentiation; ISO:RGD. DR GO; GO:2000379; P:positive regulation of reactive oxygen species metabolic process; ISO:RGD. DR GO; GO:0043415; P:positive regulation of skeletal muscle tissue regeneration; IEP:RGD. DR GO; GO:0060391; P:positive regulation of SMAD protein signal transduction; ISO:RGD. DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; IMP:RGD. DR GO; GO:0002666; P:positive regulation of T cell tolerance induction; ISO:RGD. DR GO; GO:0002651; P:positive regulation of tolerance induction to self antigen; ISO:RGD. DR GO; GO:0006898; P:receptor-mediated endocytosis; IDA:RGD. DR GO; GO:0042127; P:regulation of cell population proliferation; ISO:RGD. DR GO; GO:0010468; P:regulation of gene expression; ISO:RGD. DR GO; GO:2000736; P:regulation of stem cell differentiation; ISO:RGD. DR GO; GO:0072091; P:regulation of stem cell proliferation; ISO:RGD. DR GO; GO:0070723; P:response to cholesterol; ISO:RGD. DR GO; GO:0043627; P:response to estrogen; IEP:RGD. DR GO; GO:0009749; P:response to glucose; IEP:RGD. DR GO; GO:0001666; P:response to hypoxia; IEP:RGD. DR GO; GO:0009612; P:response to mechanical stimulus; IEP:RGD. DR GO; GO:0007584; P:response to nutrient; IEP:RGD. DR GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD. DR GO; GO:0010033; P:response to organic substance; IEP:RGD. DR GO; GO:0048545; P:response to steroid hormone; IEP:RGD. DR GO; GO:0009410; P:response to xenobiotic stimulus; ISO:RGD. DR GO; GO:0060021; P:roof of mouth development; ISO:RGD. DR GO; GO:0062009; P:secondary palate development; ISO:RGD. DR GO; GO:0060395; P:SMAD protein signal transduction; ISO:RGD. DR GO; GO:0007224; P:smoothened signaling pathway; ISO:RGD. DR GO; GO:0060440; P:trachea formation; ISO:RGD. DR GO; GO:0060439; P:trachea morphogenesis; ISO:RGD. DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IMP:RGD. DR GO; GO:0003186; P:tricuspid valve morphogenesis; ISO:RGD. DR GO; GO:0001570; P:vasculogenesis; IEP:RGD. DR GO; GO:0060412; P:ventricular septum morphogenesis; ISO:RGD. DR CDD; cd14055; STKc_TGFbR2_like; 1. DR Gene3D; 2.10.60.10; CD59; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom. DR InterPro; IPR008271; Ser/Thr_kinase_AS. DR InterPro; IPR045860; Snake_toxin-like_sf. DR InterPro; IPR000333; TGFB_receptor. DR InterPro; IPR017194; Transform_growth_fac-b_typ-2. DR InterPro; IPR015013; Transforming_GF_b_rcpt_2_ecto. DR PANTHER; PTHR23255:SF55; TGF-BETA RECEPTOR TYPE-2; 1. DR PANTHER; PTHR23255; TRANSFORMING GROWTH FACTOR-BETA RECEPTOR TYPE I AND II; 1. DR Pfam; PF08917; ecTbetaR2; 1. DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1. DR PIRSF; PIRSF037393; TGFRII; 1. DR PRINTS; PR00653; ACTIVIN2R. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR SUPFAM; SSF57302; Snake toxin-like; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. DR Genevisible; P38438; RN. PE 1: Evidence at protein level; KW Apoptosis; ATP-binding; Cell membrane; Differentiation; Disulfide bond; KW Glycoprotein; Growth regulation; Kinase; Magnesium; Manganese; Membrane; KW Metal-binding; Nucleotide-binding; Phosphoprotein; Receptor; KW Reference proteome; Serine/threonine-protein kinase; Signal; Transferase; KW Transmembrane; Transmembrane helix. FT SIGNAL 1..23 FT /evidence="ECO:0000255" FT CHAIN 24..567 FT /note="TGF-beta receptor type-2" FT /id="PRO_0000024429" FT TOPO_DOM 24..166 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 167..187 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 188..567 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 244..546 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT REGION 546..567 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 379 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10027" FT BINDING 250..258 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 277 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT MOD_RES 409 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q62312" FT MOD_RES 548 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:22673903" FT MOD_RES 553 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q62312" FT CARBOHYD 70 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 94 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 51..84 FT /evidence="ECO:0000250|UniProtKB:P37173" FT DISULFID 54..71 FT /evidence="ECO:0000250|UniProtKB:P37173" FT DISULFID 61..67 FT /evidence="ECO:0000250|UniProtKB:P37173" FT DISULFID 77..101 FT /evidence="ECO:0000250|UniProtKB:P37173" FT DISULFID 121..136 FT /evidence="ECO:0000250|UniProtKB:P37173" FT DISULFID 138..143 FT /evidence="ECO:0000250|UniProtKB:P37173" FT CONFLICT 388..389 FT /note="KN -> RS (in Ref. 2; AAB29352)" FT /evidence="ECO:0000305" FT CONFLICT 403 FT /note="R -> G (in Ref. 2; AAB29352)" FT /evidence="ECO:0000305" FT CONFLICT 405 FT /note="D -> S (in Ref. 2; AAB29352)" FT /evidence="ECO:0000305" FT CONFLICT 477 FT /note="K -> R (in Ref. 2; AAB29352)" FT /evidence="ECO:0000305" SQ SEQUENCE 567 AA; 64241 MW; EC1D7642A51A3B75 CRC64; MGRGLLRGLW PLHIVLWTRI ASTIPPHVPK SVNSDLMAGD NSGAVKLPQL CKFCDVTLST CDNQKSCMSN CSVTSICEKP QEVCVAVWRK NDKNITLETV CHDPKFTYHG FTLEDATSPT CVMKEKKRAG ETFFMCSCNT EECNDYIIFN EEYTTSSPDL LLVIIQVTGV SLLPPLGIAI AVIAIFYCYR VHRQQKLSPS WESSKPRKLM DFSDNCAIIL EDDRSDISST CANNINHNTE LLPIELDTLV GKGRFAEVYK AKLKQNTSEQ FETVAVKIFP YEEYSSWKTE KDIFSDINLK HENILQFLTA EERKTEMGKQ YWLITAFHAK GNLQEYLTRH VISWEDLRKL GSSLARGIAH LHSDHTPCGR PKMPIVHRDL KSSNILVKND LTCCLCDFGL SLRLDPTLSV DDLANSGQVG TARYMAPEVL ESRMNLENME SFKQTDVYSM ALVLWEMTSR CNAVGEVKDY EPPFGSKVRE HPCVESMKDN VLRDRGRPEI PSFWLNHQGI QIVCETLTEC WDHDPEARLT AQCVAERFSE LEHPDRLSGR SCSQEKIPED GSLNTTK //