ID   TGFR2_PIG               Reviewed;         297 AA.
AC   P38551;
DT   01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1994, sequence version 1.
DT   08-NOV-2023, entry version 138.
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; Fragment;
GN   Name=TGFBR2;
OS   Sus scrofa (Pig).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX   NCBI_TaxID=9823;
RN   [1]
RP   NUCLEOTIDE SEQUENCE.
RX   PubMed=1310899; DOI=10.1016/0092-8674(92)90152-3;
RA   Lin H.Y., Wang X.-F., Ng-Eaton E., Weinberg R.A., Lodish H.F.;
RT   "Expression cloning of the TGF-beta type II receptor, a functional
RT   transmembrane serine/threonine kinase.";
RL   Cell 68:775-785(1992).
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}.
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DR   AlphaFoldDB; P38551; -.
DR   SMR; P38551; -.
DR   STRING; 9823.ENSSSCP00000028622; -.
DR   GlyCosmos; P38551; 2 sites, No reported glycans.
DR   PaxDb; 9823-ENSSSCP00000028622; -.
DR   eggNOG; KOG3653; Eukaryota.
DR   InParanoid; P38551; -.
DR   Proteomes; UP000008227; Unplaced.
DR   Proteomes; UP000314985; Unplaced.
DR   Proteomes; UP000694570; Unplaced.
DR   Proteomes; UP000694571; Unplaced.
DR   Proteomes; UP000694720; Unplaced.
DR   Proteomes; UP000694722; Unplaced.
DR   Proteomes; UP000694723; Unplaced.
DR   Proteomes; UP000694724; Unplaced.
DR   Proteomes; UP000694725; Unplaced.
DR   Proteomes; UP000694726; Unplaced.
DR   Proteomes; UP000694727; Unplaced.
DR   Proteomes; UP000694728; Unplaced.
DR   GO; GO:0045121; C:membrane raft; ISS:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR   GO; GO:0043235; C:receptor complex; IBA:GO_Central.
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:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0046332; F:SMAD binding; IBA:GO_Central.
DR   GO; GO:0050431; F:transforming growth factor beta binding; IBA:GO_Central.
DR   GO; GO:0005024; F:transforming growth factor beta receptor activity; IBA:GO_Central.
DR   GO; GO:0005026; F:transforming growth factor beta receptor activity, type II; IEA:InterPro.
DR   GO; GO:0034713; F:type I transforming growth factor beta receptor binding; IBA:GO_Central.
DR   GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR   GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR   GO; GO:0071363; P:cellular response to growth factor stimulus; IBA:GO_Central.
DR   GO; GO:0007507; P:heart development; IBA:GO_Central.
DR   GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR   GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IBA:GO_Central.
DR   Gene3D; 2.10.60.10; CD59; 1.
DR   InterPro; IPR011009; Kinase-like_dom_sf.
DR   InterPro; IPR000719; Prot_kinase_dom.
DR   InterPro; IPR017441; Protein_kinase_ATP_BS.
DR   InterPro; IPR045860; Snake_toxin-like_sf.
DR   InterPro; IPR000333; TGFB_receptor.
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   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.
PE   3: Inferred from homology;
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..>297
FT                   /note="TGF-beta receptor type-2"
FT                   /id="PRO_0000024428"
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..>297
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          244..>297
FT                   /note="Protein kinase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
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   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   NON_TER         297
SQ   SEQUENCE   297 AA;  33302 MW;  F9869D3079B66A15 CRC64;
     MGRGLLGGLW PLHVVLWTRI ASTIPPHVPK SVNSDMMVTD SNGAVKLPQL CKFCDVRSST
     CDNQKSCLSN CSITAICEKP QEVCVAVWRK NDENITIETV CDDPKIAYHG FVLDDAASSK
     CIMKERKGSG ETFFMCSCSS DECNDHIIFS EEYATNNPDL LLVIFQVTGV SLLPPLGIAI
     AVIITFYCYR VHRQQKLSPS WDSGKPRKLM EFSEHLAIIL EDDRSDISST CANNINHNTE
     LLPIELDTLV GKGRFAEVYK AKLRQNTSEQ FETVAVKIFP YEEYASWKTE KDIFSDL
//