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TGF-beta receptor type-2 (TGFR-2) (EC 2 7 11 30) (TGF-beta type II receptor) (Transforming growth factor-beta receptor type II)

 A0A2K6A8U0_MANLE        Unreviewed;       560 AA.
A0A2K6A8U0;
28-MAR-2018, integrated into UniProtKB/TrEMBL.
28-MAR-2018, sequence version 1.
11-DEC-2019, entry version 12.
RecName: Full=TGF-beta receptor type-2 {ECO:0000256|PIRNR:PIRNR037393};
Short=TGFR-2 {ECO:0000256|PIRNR:PIRNR037393};
EC=2.7.11.30 {ECO:0000256|PIRNR:PIRNR037393};
AltName: Full=TGF-beta type II receptor {ECO:0000256|PIRNR:PIRNR037393};
AltName: Full=Transforming growth factor-beta receptor type II {ECO:0000256|PIRNR:PIRNR037393};
Name=TGFBR2 {ECO:0000313|Ensembl:ENSMLEP00000036460};
Mandrillus leucophaeus (Drill) (Papio leucophaeus).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
Cercopithecidae; Cercopithecinae; Mandrillus.
NCBI_TaxID=9568 {ECO:0000313|Ensembl:ENSMLEP00000036460, ECO:0000313|Proteomes:UP000233140};
[1] {ECO:0000313|Ensembl:ENSMLEP00000036460, ECO:0000313|Proteomes:UP000233140}
NUCLEOTIDE SEQUENCE.
Murali S., Hughes D.S., Raveendran M., Korchina V., Bandaranaike D.,
Bellair M., Blankenburg K., Chao H., Dahdouli M., Dinh H., Doddapaneni H.,
Gnanaolivu R., Gross S., Jayaseelan J., Khan Z., Kovar C., Kurapati P.,
Le B., Lee S., Mathew T., Narasimhan A., Okwuonu G., Ongeri F., Osuji N.,
Qu C., Quiroz J., Rajbhandari K., Reid J.G., Santibanez J., Skinner E.,
Wang Y., Xin Y., Han Y., Muzny D.M., Richards S., Worley K.C., Rogers J.,
Gibbs R.A.;
"Drill reference genome project.";
Submitted (FEB-2015) to the EMBL/GenBank/DDBJ databases.
[2] {ECO:0000313|Ensembl:ENSMLEP00000036460}
IDENTIFICATION.
Ensembl;
Submitted (FEB-2018) to UniProtKB.
-!- FUNCTION: Transmembrane serine/threonine kinase forming with the TGF-
beta type I serine/threonine kinase receptor, TGFBR1, the non-
promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3.
Transduces the TGFB1, TGFB2 and TGFB3 signal from the cell surface to
the cytoplasm and is thus regulating a plethora of physiological and
pathological processes including cell cycle arrest in epithelial and
hematopoietic cells, control of mesenchymal cell proliferation and
differentiation, wound healing, extracellular matrix production,
immunosuppression and carcinogenesis. The formation of the receptor
complex composed of 2 TGFBR1 and 2 TGFBR2 molecules symmetrically bound
to the cytokine dimer results in the phosphorylation and the activation
of TGFRB1 by the constitutively active TGFBR2. Activated TGFBR1
phosphorylates SMAD2 which dissociates from the receptor and interacts
with SMAD4. The SMAD2-SMAD4 complex is subsequently translocated to the
nucleus where it modulates the transcription of the TGF-beta-regulated
genes. This constitutes the canonical SMAD-dependent TGF-beta signaling
cascade. Also involved in non-canonical, SMAD-independent TGF-beta
signaling pathways. {ECO:0000256|PIRNR:PIRNR037393}.
-!- CATALYTIC ACTIVITY:
Reaction=[receptor-protein]-L-serine + ATP = [receptor-protein]-O-
phospho-L-serine + ADP + H(+); Xref=Rhea:RHEA:18673, Rhea:RHEA-
COMP:11022, Rhea:RHEA-COMP:11023, ChEBI:CHEBI:15378,
ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421,
ChEBI:CHEBI:456216; EC=2.7.11.30;
Evidence={ECO:0000256|SAAS:SAAS01128400};
-!- CATALYTIC ACTIVITY:
Reaction=[receptor-protein]-L-threonine + ATP = [receptor-protein]-O-
phospho-L-threonine + ADP + H(+); Xref=Rhea:RHEA:44880, Rhea:RHEA-
COMP:11024, Rhea:RHEA-COMP:11025, ChEBI:CHEBI:15378,
ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977,
ChEBI:CHEBI:456216; EC=2.7.11.30;
Evidence={ECO:0000256|PIRNR:PIRNR037393,
ECO:0000256|RuleBase:RU361271, ECO:0000256|SAAS:SAAS01128404};
-!- COFACTOR:
Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
Evidence={ECO:0000256|PIRNR:PIRNR037393,
ECO:0000256|RuleBase:RU361271};
Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
Evidence={ECO:0000256|PIRNR:PIRNR037393,
ECO:0000256|RuleBase:RU361271};
-!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000256|PIRNR:PIRNR037393}.
Membrane {ECO:0000256|RuleBase:RU361271}; Single-pass type I membrane
protein {ECO:0000256|RuleBase:RU361271}.
-!- SIMILARITY: Belongs to the protein kinase superfamily. TKL Ser/Thr
protein kinase family. TGFB receptor subfamily.
{ECO:0000256|PIRNR:PIRNR037393, ECO:0000256|RuleBase:RU361271,
ECO:0000256|SAAS:SAAS00595019}.
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Ensembl; ENSMLET00000060062; ENSMLEP00000036460; ENSMLEG00000042351.
GeneTree; ENSGT00940000157527; -.
OMA; HQGIQTV; -.
Proteomes; UP000233140; Whole Genome Shotgun Assembly.
GO; GO:0005901; C:caveola; IEA:Ensembl.
GO; GO:0009897; C:external side of plasma membrane; IEA:Ensembl.
GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
GO; GO:0043235; C:receptor complex; IEA:Ensembl.
GO; GO:0005524; F:ATP binding; IEA:UniProtKB-UniRule.
GO; GO:0005539; F:glycosaminoglycan binding; IEA:Ensembl.
GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
GO; GO:0046332; F:SMAD binding; IEA:Ensembl.
GO; GO:0050431; F:transforming growth factor beta binding; IEA:Ensembl.
GO; GO:0005026; F:transforming growth factor beta receptor activity, type II; IEA:UniProtKB-UniRule.
GO; GO:0034713; F:type I transforming growth factor beta receptor binding; IEA:Ensembl.
GO; GO:0032147; P:activation of protein kinase activity; IEA:Ensembl.
GO; GO:0007420; P:brain development; IEA:Ensembl.
GO; GO:0001569; P:branching involved in blood vessel morphogenesis; IEA:Ensembl.
GO; GO:0060434; P:bronchus morphogenesis; IEA:Ensembl.
GO; GO:0003214; P:cardiac left ventricle morphogenesis; IEA:Ensembl.
GO; GO:0048701; P:embryonic cranial skeleton morphogenesis; IEA:Ensembl.
GO; GO:0035162; P:embryonic hemopoiesis; IEA:Ensembl.
GO; GO:0003274; P:endocardial cushion fusion; IEA:Ensembl.
GO; GO:0007369; P:gastrulation; IEA:Ensembl.
GO; GO:0003430; P:growth plate cartilage chondrocyte growth; IEA:Ensembl.
GO; GO:0001947; P:heart looping; IEA:Ensembl.
GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
GO; GO:1905317; P:inferior endocardial cushion morphogenesis; IEA:Ensembl.
GO; GO:0002088; P:lens development in camera-type eye; IEA:Ensembl.
GO; GO:1990086; P:lens fiber cell apoptotic process; IEA:Ensembl.
GO; GO:0060463; P:lung lobe morphogenesis; IEA:Ensembl.
GO; GO:0060443; P:mammary gland morphogenesis; IEA:Ensembl.
GO; GO:0003149; P:membranous septum morphogenesis; IEA:Ensembl.
GO; GO:1990428; P:miRNA transport; IEA:Ensembl.
GO; GO:0043011; P:myeloid dendritic cell differentiation; IEA:Ensembl.
GO; GO:0007219; P:Notch signaling pathway; IEA:Ensembl.
GO; GO:0003148; P:outflow tract septum morphogenesis; IEA:Ensembl.
GO; GO:0060389; P:pathway-restricted SMAD protein phosphorylation; IEA:Ensembl.
GO; GO:0018105; P:peptidyl-serine phosphorylation; IEA:Ensembl.
GO; GO:0018107; P:peptidyl-threonine phosphorylation; IEA:Ensembl.
GO; GO:0045766; P:positive regulation of angiogenesis; IEA:Ensembl.
GO; GO:0002663; P:positive regulation of B cell tolerance induction; IEA:Ensembl.
GO; GO:2000563; P:positive regulation of CD4-positive, alpha-beta T cell proliferation; IEA:Ensembl.
GO; GO:0010634; P:positive regulation of epithelial cell migration; IEA:Ensembl.
GO; GO:1905007; P:positive regulation of epithelial to mesenchymal transition involved in endocardial cushion formation; IEA:Ensembl.
GO; GO:0002053; P:positive regulation of mesenchymal cell proliferation; IEA:Ensembl.
GO; GO:0051138; P:positive regulation of NK T cell differentiation; IEA:Ensembl.
GO; GO:2000379; P:positive regulation of reactive oxygen species metabolic process; IEA:Ensembl.
GO; GO:0002666; P:positive regulation of T cell tolerance induction; IEA:Ensembl.
GO; GO:0002651; P:positive regulation of tolerance induction to self antigen; IEA:Ensembl.
GO; GO:0010468; P:regulation of gene expression; IEA:Ensembl.
GO; GO:0040008; P:regulation of growth; IEA:UniProtKB-KW.
GO; GO:0070723; P:response to cholesterol; IEA:Ensembl.
GO; GO:0042493; P:response to drug; IEA:Ensembl.
GO; GO:0062009; P:secondary palate development; IEA:Ensembl.
GO; GO:0007224; P:smoothened signaling pathway; IEA:Ensembl.
GO; GO:0060440; P:trachea formation; IEA:Ensembl.
GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IEA:Ensembl.
GO; GO:0003186; P:tricuspid valve morphogenesis; IEA:Ensembl.
GO; GO:0001570; P:vasculogenesis; IEA:Ensembl.
InterPro; IPR011009; Kinase-like_dom_sf.
InterPro; IPR000719; Prot_kinase_dom.
InterPro; IPR017441; Protein_kinase_ATP_BS.
InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
InterPro; IPR008271; Ser/Thr_kinase_AS.
InterPro; IPR000333; TGFB_receptor.
InterPro; IPR017194; Transform_growth_fac-b_typ-2.
InterPro; IPR015013; Transforming_GF_b_rcpt_2_ecto.
PANTHER; PTHR23255; PTHR23255; 1.
Pfam; PF08917; ecTbetaR2; 1.
Pfam; PF07714; Pkinase_Tyr; 1.
PIRSF; PIRSF037393; TGFRII; 1.
PRINTS; PR00653; ACTIVIN2R.
SMART; SM00220; S_TKc; 1.
SUPFAM; SSF56112; SSF56112; 1.
PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
3: Inferred from homology;
Apoptosis {ECO:0000256|PIRNR:PIRNR037393};
ATP-binding {ECO:0000256|PIRNR:PIRNR037393, ECO:0000256|PIRSR:PIRSR037393-
2, ECO:0000256|RuleBase:RU361271, ECO:0000256|SAAS:SAAS00138218};
Cell membrane {ECO:0000256|PIRNR:PIRNR037393};
Differentiation {ECO:0000256|PIRNR:PIRNR037393};
Disulfide bond {ECO:0000256|PIRSR:PIRSR037393-3};
Growth regulation {ECO:0000256|PIRNR:PIRNR037393};
Kinase {ECO:0000256|PIRNR:PIRNR037393, ECO:0000256|RuleBase:RU361271,
ECO:0000256|SAAS:SAAS00138186};
Magnesium {ECO:0000256|PIRNR:PIRNR037393, ECO:0000256|RuleBase:RU361271};
Manganese {ECO:0000256|PIRNR:PIRNR037393, ECO:0000256|RuleBase:RU361271};
Membrane {ECO:0000256|PIRNR:PIRNR037393, ECO:0000256|RuleBase:RU361271,
ECO:0000256|SAAS:SAAS00488859};
Metal-binding {ECO:0000256|PIRNR:PIRNR037393,
ECO:0000256|RuleBase:RU361271};
Nucleotide-binding {ECO:0000256|PIRNR:PIRNR037393,
ECO:0000256|PIRSR:PIRSR037393-2, ECO:0000256|RuleBase:RU361271,
ECO:0000256|SAAS:SAAS00138218};
Receptor {ECO:0000256|PIRNR:PIRNR037393, ECO:0000256|RuleBase:RU361271,
ECO:0000256|SAAS:SAAS00138179};
Reference proteome {ECO:0000313|Proteomes:UP000233140};
Serine/threonine-protein kinase {ECO:0000256|PIRNR:PIRNR037393,
ECO:0000256|RuleBase:RU361271, ECO:0000256|SAAS:SAAS00138186};
Transferase {ECO:0000256|PIRNR:PIRNR037393, ECO:0000256|RuleBase:RU361271,
ECO:0000256|SAAS:SAAS00138186};
Transmembrane {ECO:0000256|RuleBase:RU361271,
ECO:0000256|SAAS:SAAS00488859};
Transmembrane helix {ECO:0000256|RuleBase:RU361271,
ECO:0000256|SAAS:SAAS00488859}.
TRANSMEM 153..182
/note="Helical"
/evidence="ECO:0000256|RuleBase:RU361271"
DOMAIN 237..537
/note="Protein kinase"
/evidence="ECO:0000259|PROSITE:PS50011"
NP_BIND 243..251
/note="ATP"
/evidence="ECO:0000256|PIRSR:PIRSR037393-2"
ACT_SITE 372
/note="Proton acceptor"
/evidence="ECO:0000256|PIRSR:PIRSR037393-1"
BINDING 270
/note="ATP"
/evidence="ECO:0000256|PIRSR:PIRSR037393-2"
DISULFID 44..77
/evidence="ECO:0000256|PIRSR:PIRSR037393-3"
DISULFID 47..64
/evidence="ECO:0000256|PIRSR:PIRSR037393-3"
DISULFID 54..60
/evidence="ECO:0000256|PIRSR:PIRSR037393-3"
DISULFID 70..94
/evidence="ECO:0000256|PIRSR:PIRSR037393-3"
DISULFID 114..129
/evidence="ECO:0000256|PIRSR:PIRSR037393-3"
DISULFID 131..136
/evidence="ECO:0000256|PIRSR:PIRSR037393-3"
SEQUENCE 560 AA; 63697 MW; CFF0E2ECF805D0C2 CRC64;
VEMEAQKGEM ICPSCNRTAH PLRHSNNDMM VTDNNGAVKF PQLCKFCDVR FSTCDNQKSC
LSNCSITSIC EKPQEVCVAV WRKNDENITL ETVCHDPKLP YHDFILEDAA SPKCIMKEKK
KPGETFFMCS CSSDECNDNI IFSEEYNTSN PDLLLVIFQV TGISLLPPLG VAISVIIIFY
CYRVNRQQKL SSSWEAGKPR KLMDFSEHCA IILEDDRSDI SSTCANNINH NTELLPIELD
TLVGKGRFAE VYKAKLKQNT SEQFETVAVK IFPYEEYASW KTEKDIFSDI NLKHENILQF
LTAEERKTEL GKQYWLITAF HAKGNLQEYL TRHVISWEDL RKLGSSLARG IAHLHSDHTP
CGRPKMPIVH RDLKSSNILV KNDLTCCLCD FGLSLRLDPT LSVDDLANSG QVGTARYMAP
EVLESRMNLE NVESFKQTDV YSMALVLWEM TSRCNAVGEV KDYEPPFGSK VREHPCVESM
KDNVLRDRGR PEIPSFWLNH QGIQMVCETL TECWDHDPEA RLTAQCVAER FSELEHLDRL
SGRSCSEEKI PEDGSLNTTK


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