TGFR2_PIG
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 03-AUG-2022, entry version 131.
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. Interacts with DAXX.
CC Interacts with DYNLT4. Interacts with ZFYVE9; ZFYVE9 recruits SMAD2 and
CC SMAD3 to the TGF-beta receptor (By similarity). Interacts with and is
CC activated by SCUBE3; this interaction does not affect TGFB1-binding to
CC TGFBR2 (By similarity). Interacts with VPS39; this interaction is
CC independent of the receptor kinase activity and of the presence of TGF-
CC beta (By 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 PaxDb; P38551; -.
DR eggNOG; KOG3653; Eukaryota.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Unplaced.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central.
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:0006468; P:protein phosphorylation; IBA:GO_Central.
DR GO; GO:0040008; P:regulation of growth; IEA:UniProtKB-KW.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IBA:GO_Central.
DR Gene3D; 2.10.60.10; -; 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; PTHR23255; 1.
DR Pfam; PF08917; ecTbetaR2; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR SUPFAM; SSF57302; SSF57302; 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
