ID A0A2K5D936_AOTNA Unreviewed; 593 AA.
AC A0A2K5D936;
DT 28-MAR-2018, integrated into UniProtKB/TrEMBL.
DT 28-MAR-2018, sequence version 1.
DT 27-MAR-2024, entry version 29.
DE RecName: Full=TGF-beta receptor type-2 {ECO:0000256|PIRNR:PIRNR037393};
DE Short=TGFR-2 {ECO:0000256|PIRNR:PIRNR037393};
DE EC=2.7.11.30 {ECO:0000256|PIRNR:PIRNR037393};
DE AltName: Full=TGF-beta type II receptor {ECO:0000256|PIRNR:PIRNR037393};
DE AltName: Full=Transforming growth factor-beta receptor type II {ECO:0000256|PIRNR:PIRNR037393};
GN Name=TGFBR2 {ECO:0000313|Ensembl:ENSANAP00000017484.1};
OS Aotus nancymaae (Ma's night monkey).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Platyrrhini; Aotidae;
OC Aotus.
OX NCBI_TaxID=37293 {ECO:0000313|Ensembl:ENSANAP00000017484.1, ECO:0000313|Proteomes:UP000233020};
RN [1] {ECO:0000313|Ensembl:ENSANAP00000017484.1}
RP IDENTIFICATION.
RG Ensembl;
RL Submitted (SEP-2023) to UniProtKB.
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. {ECO:0000256|PIRNR:PIRNR037393}.
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 Evidence={ECO:0000256|PIRNR:PIRNR037393,
CC ECO:0000256|RuleBase:RU361271};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000256|PIRNR:PIRNR037393,
CC ECO:0000256|RuleBase:RU361271};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000256|PIRNR:PIRNR037393,
CC ECO:0000256|RuleBase:RU361271};
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000256|ARBA:ARBA00004251};
CC Single-pass type I membrane protein {ECO:0000256|ARBA:ARBA00004251}.
CC Membrane raft {ECO:0000256|ARBA:ARBA00004285}. Membrane
CC {ECO:0000256|ARBA:ARBA00004479, ECO:0000256|RuleBase:RU361271}; Single-
CC pass type I membrane protein {ECO:0000256|ARBA:ARBA00004479,
CC ECO:0000256|RuleBase:RU361271}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. TKL Ser/Thr
CC protein kinase family. TGFB receptor subfamily.
CC {ECO:0000256|ARBA:ARBA00009605, ECO:0000256|PIRNR:PIRNR037393,
CC ECO:0000256|RuleBase:RU361271}.
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DR RefSeq; XP_012290977.1; XM_012435554.1.
DR STRING; 37293.ENSANAP00000017484; -.
DR Ensembl; ENSANAT00000035342.1; ENSANAP00000017484.1; ENSANAG00000026606.1.
DR Ensembl; ENSANAT00000035346.1; ENSANAP00000017488.1; ENSANAG00000026606.1.
DR GeneID; 105705624; -.
DR CTD; 7048; -.
DR GeneTree; ENSGT00940000157527; -.
DR OrthoDB; 3900892at2759; -.
DR Proteomes; UP000233020; Unplaced.
DR GO; GO:0005901; C:caveola; IEA:Ensembl.
DR GO; GO:0009897; C:external side of plasma membrane; IEA:Ensembl.
DR GO; GO:0070021; C:transforming growth factor beta ligand-receptor complex; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-UniRule.
DR GO; GO:0005539; F:glycosaminoglycan binding; IEA:Ensembl.
DR GO; GO:0019209; F:kinase activator activity; IEA:Ensembl.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0046332; F:SMAD binding; IEA:Ensembl.
DR GO; GO:0050431; F:transforming growth factor beta binding; IEA:Ensembl.
DR GO; GO:0005026; F:transforming growth factor beta receptor activity, type II; IEA:UniProtKB-UniRule.
DR GO; GO:0034713; F:type I transforming growth factor beta receptor binding; IEA:Ensembl.
DR GO; GO:0035909; P:aorta morphogenesis; IEA:Ensembl.
DR GO; GO:0003180; P:aortic valve morphogenesis; IEA:Ensembl.
DR GO; GO:0007420; P:brain development; IEA:Ensembl.
DR GO; GO:0001569; P:branching involved in blood vessel morphogenesis; IEA:Ensembl.
DR GO; GO:0060434; P:bronchus morphogenesis; IEA:Ensembl.
DR GO; GO:0003214; P:cardiac left ventricle morphogenesis; IEA:Ensembl.
DR GO; GO:0048701; P:embryonic cranial skeleton morphogenesis; IEA:Ensembl.
DR GO; GO:0035162; P:embryonic hemopoiesis; IEA:Ensembl.
DR GO; GO:0003274; P:endocardial cushion fusion; IEA:Ensembl.
DR GO; GO:0001837; P:epithelial to mesenchymal transition; IEA:Ensembl.
DR GO; GO:0007369; P:gastrulation; IEA:Ensembl.
DR GO; GO:0003430; P:growth plate cartilage chondrocyte growth; IEA:Ensembl.
DR GO; GO:0001947; P:heart looping; IEA:Ensembl.
DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
DR GO; GO:1905317; P:inferior endocardial cushion morphogenesis; IEA:Ensembl.
DR GO; GO:0061520; P:Langerhans cell differentiation; IEA:Ensembl.
DR GO; GO:0002088; P:lens development in camera-type eye; IEA:Ensembl.
DR GO; GO:1990086; P:lens fiber cell apoptotic process; IEA:Ensembl.
DR GO; GO:0060463; P:lung lobe morphogenesis; IEA:Ensembl.
DR GO; GO:0060443; P:mammary gland morphogenesis; IEA:Ensembl.
DR GO; GO:0003149; P:membranous septum morphogenesis; IEA:Ensembl.
DR GO; GO:1990428; P:miRNA transport; IEA:Ensembl.
DR GO; GO:0007219; P:Notch signaling pathway; IEA:Ensembl.
DR GO; GO:0003148; P:outflow tract septum morphogenesis; IEA:Ensembl.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0045766; P:positive regulation of angiogenesis; IEA:Ensembl.
DR GO; GO:0002663; P:positive regulation of B cell tolerance induction; IEA:Ensembl.
DR GO; GO:2000563; P:positive regulation of CD4-positive, alpha-beta T cell proliferation; IEA:Ensembl.
DR GO; GO:0010634; P:positive regulation of epithelial cell migration; IEA:Ensembl.
DR GO; GO:1905007; P:positive regulation of epithelial to mesenchymal transition involved in endocardial cushion formation; IEA:Ensembl.
DR GO; GO:0002053; P:positive regulation of mesenchymal cell proliferation; IEA:Ensembl.
DR GO; GO:0051138; P:positive regulation of NK T cell differentiation; IEA:Ensembl.
DR GO; GO:2000379; P:positive regulation of reactive oxygen species metabolic process; IEA:Ensembl.
DR GO; GO:0060391; P:positive regulation of SMAD protein signal transduction; IEA:Ensembl.
DR GO; GO:0002666; P:positive regulation of T cell tolerance induction; IEA:Ensembl.
DR GO; GO:0002651; P:positive regulation of tolerance induction to self antigen; IEA:Ensembl.
DR GO; GO:0010468; P:regulation of gene expression; IEA:Ensembl.
DR GO; GO:2000736; P:regulation of stem cell differentiation; IEA:Ensembl.
DR GO; GO:0072091; P:regulation of stem cell proliferation; IEA:Ensembl.
DR GO; GO:0070723; P:response to cholesterol; IEA:Ensembl.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0062009; P:secondary palate development; IEA:Ensembl.
DR GO; GO:0060395; P:SMAD protein signal transduction; IEA:Ensembl.
DR GO; GO:0007224; P:smoothened signaling pathway; IEA:Ensembl.
DR GO; GO:0060440; P:trachea formation; IEA:Ensembl.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0003186; P:tricuspid valve morphogenesis; IEA:Ensembl.
DR GO; GO:0001570; P:vasculogenesis; IEA:Ensembl.
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.
PE 3: Inferred from homology;
KW Apoptosis {ECO:0000256|ARBA:ARBA00022703, ECO:0000256|PIRNR:PIRNR037393};
KW ATP-binding {ECO:0000256|ARBA:ARBA00022840, ECO:0000256|PIRNR:PIRNR037393};
KW Cell membrane {ECO:0000256|ARBA:ARBA00022475,
KW ECO:0000256|PIRNR:PIRNR037393};
KW Differentiation {ECO:0000256|PIRNR:PIRNR037393};
KW Disulfide bond {ECO:0000256|PIRSR:PIRSR037393-3};
KW Growth regulation {ECO:0000256|ARBA:ARBA00022604,
KW ECO:0000256|PIRNR:PIRNR037393};
KW Kinase {ECO:0000256|PIRNR:PIRNR037393, ECO:0000256|RuleBase:RU361271};
KW Magnesium {ECO:0000256|ARBA:ARBA00022842, ECO:0000256|PIRNR:PIRNR037393};
KW Manganese {ECO:0000256|ARBA:ARBA00023211, ECO:0000256|PIRNR:PIRNR037393};
KW Membrane {ECO:0000256|ARBA:ARBA00023136, ECO:0000256|PIRNR:PIRNR037393};
KW Metal-binding {ECO:0000256|PIRNR:PIRNR037393,
KW ECO:0000256|RuleBase:RU361271};
KW Nucleotide-binding {ECO:0000256|ARBA:ARBA00022741,
KW ECO:0000256|PIRNR:PIRNR037393};
KW Phosphoprotein {ECO:0000256|ARBA:ARBA00022553};
KW Receptor {ECO:0000256|ARBA:ARBA00023170, ECO:0000256|PIRNR:PIRNR037393};
KW Reference proteome {ECO:0000313|Proteomes:UP000233020};
KW Serine/threonine-protein kinase {ECO:0000256|ARBA:ARBA00022527,
KW ECO:0000256|PIRNR:PIRNR037393};
KW Signal {ECO:0000256|ARBA:ARBA00022729, ECO:0000256|SAM:SignalP};
KW Transferase {ECO:0000256|PIRNR:PIRNR037393, ECO:0000256|RuleBase:RU361271};
KW Transmembrane {ECO:0000256|ARBA:ARBA00022692,
KW ECO:0000256|RuleBase:RU361271};
KW Transmembrane helix {ECO:0000256|ARBA:ARBA00022989,
KW ECO:0000256|RuleBase:RU361271}.
FT SIGNAL 1..23
FT /evidence="ECO:0000256|SAM:SignalP"
FT CHAIN 24..593
FT /note="TGF-beta receptor type-2"
FT /evidence="ECO:0000256|SAM:SignalP"
FT /id="PRO_5014561315"
FT TRANSMEM 185..214
FT /note="Helical"
FT /evidence="ECO:0000256|RuleBase:RU361271"
FT DOMAIN 270..570
FT /note="Protein kinase"
FT /evidence="ECO:0000259|PROSITE:PS50011"
FT ACT_SITE 405
FT /note="Proton acceptor"
FT /evidence="ECO:0000256|PIRSR:PIRSR037393-1"
FT BINDING 276..284
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000256|PIRSR:PIRSR037393-2"
FT BINDING 303
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000256|PIRSR:PIRSR037393-2,
FT ECO:0000256|PROSITE-ProRule:PRU10141"
FT DISULFID 76..109
FT /evidence="ECO:0000256|PIRSR:PIRSR037393-3"
FT DISULFID 79..96
FT /evidence="ECO:0000256|PIRSR:PIRSR037393-3"
FT DISULFID 86..92
FT /evidence="ECO:0000256|PIRSR:PIRSR037393-3"
FT DISULFID 102..126
FT /evidence="ECO:0000256|PIRSR:PIRSR037393-3"
FT DISULFID 146..161
FT /evidence="ECO:0000256|PIRSR:PIRSR037393-3"
FT DISULFID 163..168
FT /evidence="ECO:0000256|PIRSR:PIRSR037393-3"
SQ SEQUENCE 593 AA; 67375 MW; D3DB7D47C5467C94 CRC64;
MGRGLLRGLW PLHIVLWTRI ASTIPPQVPK SDVKMEPQKD EIIRPGCNRT AHPLTHINND
MMVTDSNGAV KLPQLCKFCD VRFSTCDNQK SCMSNCSITA ICEKPQEVCV AVWRKNDENI
TLETVCHDPR LPYHDFILED AASPKCIMKE KKKPGETFFM CSCSSEECND NIIFSEDYNT
SNPDLLLVIF QVTGVSLLPP LAIAISVIII FYCYRVNRQQ KLSSSWETTK PRKLMEFSSE
HCAIILEDDR SDISSTCANN INHNTELLPI ELDTLVGKGR FAEVYKAKLK QNTSEQFETV
AVKIFPYEEY ASWKTEKDIF SDVNLKHENI LQFLTAEERK TELGKQYWLI TAFHAKGNLQ
EYLTRHIISW EDLSKLGSSL ARGIAHLHSD HTPCGRPKVP IVHRDLKSSN ILVKNDLTCC
LCDFGLSLRL DPALSVDDLA NSGQVGTARY MAPEVLESRM NLENVESFKQ TDVYSMALVL
WEMTSRCNAV GEVKDYEPPF GSKVREHPCV ESMKDNVLRD RGRPEIPSFW LNHQGIQMVC
ETLTECWDHD PEARLTAQCV AERFSELEHL DRLSGRSCSE EKIPEDGSLN TTK
//
