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Protein

TGF-beta receptor type-2

Gene

Tgfbr2

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

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 (By similarity).By similarity

Catalytic activityi

ATP + [receptor-protein] = ADP + [receptor-protein] phosphate.

Cofactori

Mg2+By similarity, Mn2+By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei277 – 2771ATPPROSITE-ProRule annotation
Active sitei379 – 3791Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi250 – 2589ATPPROSITE-ProRule annotation

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • glycosaminoglycan binding Source: Ensembl
  • metal ion binding Source: UniProtKB-KW
  • mitogen-activated protein kinase kinase kinase binding Source: RGD
  • protein heterodimerization activity Source: RGD
  • protein homodimerization activity Source: RGD
  • receptor signaling protein serine/threonine kinase activity Source: InterPro
  • transforming growth factor beta receptor activity, type II Source: RGD

GO - Biological processi

  • activation of protein kinase activity Source: Ensembl
  • aging Source: RGD
  • brain development Source: Ensembl
  • bronchus morphogenesis Source: Ensembl
  • common-partner SMAD protein phosphorylation Source: RGD
  • digestive tract development Source: RGD
  • embryo implantation Source: RGD
  • embryonic cranial skeleton morphogenesis Source: Ensembl
  • embryonic hemopoiesis Source: Ensembl
  • gastrulation Source: Ensembl
  • growth plate cartilage chondrocyte growth Source: Ensembl
  • heart development Source: Ensembl
  • in utero embryonic development Source: Ensembl
  • lens development in camera-type eye Source: Ensembl
  • lens fiber cell apoptotic process Source: Ensembl
  • lung development Source: RGD
  • lung lobe morphogenesis Source: Ensembl
  • mammary gland morphogenesis Source: Ensembl
  • myeloid dendritic cell differentiation Source: Ensembl
  • negative regulation of cardiac muscle cell proliferation Source: RGD
  • negative regulation of cell proliferation Source: RGD
  • organ morphogenesis Source: RGD
  • organ regeneration Source: RGD
  • palate development Source: Ensembl
  • pathway-restricted SMAD protein phosphorylation Source: Ensembl
  • patterning of blood vessels Source: Ensembl
  • peptidyl-serine phosphorylation Source: Ensembl
  • peptidyl-threonine phosphorylation Source: Ensembl
  • positive regulation of angiogenesis Source: Ensembl
  • positive regulation of B cell tolerance induction Source: Ensembl
  • positive regulation of epithelial cell migration Source: Ensembl
  • positive regulation of mesenchymal cell proliferation Source: Ensembl
  • positive regulation of NK T cell differentiation Source: Ensembl
  • positive regulation of reactive oxygen species metabolic process Source: Ensembl
  • positive regulation of skeletal muscle tissue regeneration Source: RGD
  • positive regulation of smooth muscle cell proliferation Source: RGD
  • positive regulation of T cell tolerance induction Source: Ensembl
  • positive regulation of tolerance induction to self antigen Source: Ensembl
  • receptor-mediated endocytosis Source: RGD
  • regulation of gene expression Source: Ensembl
  • response to cholesterol Source: Ensembl
  • response to drug Source: Ensembl
  • response to estrogen Source: RGD
  • response to glucose Source: RGD
  • response to hypoxia Source: RGD
  • response to mechanical stimulus Source: RGD
  • response to nutrient Source: RGD
  • response to organic cyclic compound Source: RGD
  • response to organic substance Source: RGD
  • response to steroid hormone Source: RGD
  • smoothened signaling pathway Source: Ensembl
  • trachea formation Source: Ensembl
  • transforming growth factor beta receptor signaling pathway Source: RGD
  • vasculogenesis Source: RGD
  • wound healing Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Receptor, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Apoptosis, Differentiation, Growth regulation

Keywords - Ligandi

ATP-binding, Magnesium, Manganese, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.2. 5301.
ReactomeiREACT_294475. TGF-beta receptor signaling activates SMADs.
REACT_308893. TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition).
REACT_336534. Downregulation of TGF-beta receptor signaling.

Names & Taxonomyi

Protein namesi
Recommended name:
TGF-beta receptor type-2 (EC:2.7.11.30)
Short name:
TGFR-2
Alternative name(s):
TGF-beta type II receptor
Transforming growth factor-beta receptor type II
Short name:
TGF-beta receptor type II
Short name:
TbetaR-II
Gene namesi
Name:Tgfbr2
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494 Componenti: Chromosome 8

Organism-specific databases

RGDi69651. Tgfbr2.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini24 – 166143ExtracellularSequence AnalysisAdd
BLAST
Transmembranei167 – 18721HelicalSequence AnalysisAdd
BLAST
Topological domaini188 – 567380CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  • caveola Source: MGI
  • cell surface Source: RGD
  • cytoplasm Source: RGD
  • cytosol Source: RGD
  • external side of plasma membrane Source: Ensembl
  • integral component of plasma membrane Source: RGD
  • membrane raft Source: MGI
  • transforming growth factor beta receptor homodimeric complex Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2323Sequence AnalysisAdd
BLAST
Chaini24 – 567544TGF-beta receptor type-2PRO_0000024429Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi51 ↔ 84By similarity
Disulfide bondi54 ↔ 71By similarity
Disulfide bondi61 ↔ 67By similarity
Glycosylationi70 – 701N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi77 ↔ 101By similarity
Glycosylationi94 – 941N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi121 ↔ 136By similarity
Disulfide bondi138 ↔ 143By similarity
Modified residuei548 – 5481PhosphoserineBy similarity
Modified residuei553 – 5531PhosphoserineBy similarity

Post-translational modificationi

Phosphorylated on a Ser/Thr residue in the cytoplasmic domain.

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiP38438.
PRIDEiP38438.

Expressioni

Gene expression databases

ExpressionAtlasiP38438. baseline.
GenevisibleiP38438. RN.

Interactioni

Subunit structurei

Homodimer. Heterohexamer; TGFB1, TGFB2 and TGFB3 homodimeric ligands assemble a functional receptor composed of two TGFBR1 and TGFBR2 heterodimers to form a ligand-receptor heterohexamer. The respective affinity of TGFRB1 and TGFRB2 for the ligands may modulate the kinetics of assembly of the receptor and may explain the different biological activities of TGFB1, TGFB2 and TGFB3. Interacts with DAXX. Interacts with TCTEX1D4. Interacts with ZFYVE9; ZFYVE9 recruits SMAD2 and SMAD3 to the TGF-beta receptor (By similarity). Interacts with and is activated by SCUBE3; this interaction does not affect TGFB1-binding to TGFBR2 (By similarity). Interacts with VPS39; this interaction is independent of the receptor kinase activity and of the presence of TGF-beta (By similarity).By similarity

Protein-protein interaction databases

BioGridi249668. 1 interaction.
IntActiP38438. 1 interaction.
STRINGi10116.ENSRNOP00000035501.

Structurei

3D structure databases

ProteinModelPortaliP38438.
SMRiP38438. Positions 40-159.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini244 – 546303Protein kinasePROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00760000118876.
HOGENOMiHOG000231495.
HOVERGENiHBG104975.
InParanoidiP38438.
KOiK04388.
OMAiTRHIISW.
OrthoDBiEOG7JHM5B.
PhylomeDBiP38438.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
IPR000333. TGFB_receptor.
IPR017194. Transform_growth_fac-b_typ-2.
IPR015013. Transforming_GF_b_rcpt_2_ecto.
[Graphical view]
PANTHERiPTHR23255. PTHR23255. 1 hit.
PfamiPF08917. ecTbetaR2. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
PIRSFiPIRSF037393. TGFRII. 1 hit.
PRINTSiPR00653. ACTIVIN2R.
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P38438-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGRGLLRGLW PLHIVLWTRI ASTIPPHVPK SVNSDLMAGD NSGAVKLPQL
60 70 80 90 100
CKFCDVTLST CDNQKSCMSN CSVTSICEKP QEVCVAVWRK NDKNITLETV
110 120 130 140 150
CHDPKFTYHG FTLEDATSPT CVMKEKKRAG ETFFMCSCNT EECNDYIIFN
160 170 180 190 200
EEYTTSSPDL LLVIIQVTGV SLLPPLGIAI AVIAIFYCYR VHRQQKLSPS
210 220 230 240 250
WESSKPRKLM DFSDNCAIIL EDDRSDISST CANNINHNTE LLPIELDTLV
260 270 280 290 300
GKGRFAEVYK AKLKQNTSEQ FETVAVKIFP YEEYSSWKTE KDIFSDINLK
310 320 330 340 350
HENILQFLTA EERKTEMGKQ YWLITAFHAK GNLQEYLTRH VISWEDLRKL
360 370 380 390 400
GSSLARGIAH LHSDHTPCGR PKMPIVHRDL KSSNILVKND LTCCLCDFGL
410 420 430 440 450
SLRLDPTLSV DDLANSGQVG TARYMAPEVL ESRMNLENME SFKQTDVYSM
460 470 480 490 500
ALVLWEMTSR CNAVGEVKDY EPPFGSKVRE HPCVESMKDN VLRDRGRPEI
510 520 530 540 550
PSFWLNHQGI QIVCETLTEC WDHDPEARLT AQCVAERFSE LEHPDRLSGR
560
SCSQEKIPED GSLNTTK
Length:567
Mass (Da):64,241
Last modified:October 1, 1994 - v1
Checksum:iEC1D7642A51A3B75
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti388 – 3892KN → RS in AAB29352 (PubMed:8264154).Curated
Sequence conflicti403 – 4031R → G in AAB29352 (PubMed:8264154).Curated
Sequence conflicti405 – 4051D → S in AAB29352 (PubMed:8264154).Curated
Sequence conflicti477 – 4771K → R in AAB29352 (PubMed:8264154).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L09653 mRNA. Translation: AAA42237.1.
S67770 mRNA. Translation: AAB29352.2.
PIRiJN0459.
RefSeqiNP_112394.3. NM_031132.3.
UniGeneiRn.9954.

Genome annotation databases

EnsembliENSRNOT00000037883; ENSRNOP00000035501; ENSRNOG00000013265.
GeneIDi81810.
KEGGirno:81810.
UCSCiRGD:69651. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L09653 mRNA. Translation: AAA42237.1.
S67770 mRNA. Translation: AAB29352.2.
PIRiJN0459.
RefSeqiNP_112394.3. NM_031132.3.
UniGeneiRn.9954.

3D structure databases

ProteinModelPortaliP38438.
SMRiP38438. Positions 40-159.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi249668. 1 interaction.
IntActiP38438. 1 interaction.
STRINGi10116.ENSRNOP00000035501.

Proteomic databases

PaxDbiP38438.
PRIDEiP38438.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000037883; ENSRNOP00000035501; ENSRNOG00000013265.
GeneIDi81810.
KEGGirno:81810.
UCSCiRGD:69651. rat.

Organism-specific databases

CTDi7048.
RGDi69651. Tgfbr2.

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00760000118876.
HOGENOMiHOG000231495.
HOVERGENiHBG104975.
InParanoidiP38438.
KOiK04388.
OMAiTRHIISW.
OrthoDBiEOG7JHM5B.
PhylomeDBiP38438.

Enzyme and pathway databases

BRENDAi2.7.10.2. 5301.
ReactomeiREACT_294475. TGF-beta receptor signaling activates SMADs.
REACT_308893. TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition).
REACT_336534. Downregulation of TGF-beta receptor signaling.

Miscellaneous databases

NextBioi615691.
PROiP38438.

Gene expression databases

ExpressionAtlasiP38438. baseline.
GenevisibleiP38438. RN.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
IPR000333. TGFB_receptor.
IPR017194. Transform_growth_fac-b_typ-2.
IPR015013. Transforming_GF_b_rcpt_2_ecto.
[Graphical view]
PANTHERiPTHR23255. PTHR23255. 1 hit.
PfamiPF08917. ecTbetaR2. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
PIRSFiPIRSF037393. TGFRII. 1 hit.
PRINTSiPR00653. ACTIVIN2R.
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Molecular characterization of rat transforming growth factor-beta type II receptor."
    Tsuchida K., Lewis K.A., Mathews L.S., Vale W.W.
    Biochem. Biophys. Res. Commun. 191:790-795(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: Sprague-Dawley.
    Tissue: Pituitary.
  2. "Rat mesangial cell hypertrophy in response to transforming growth factor-beta 1."
    Choi M.E., Kim E.G., Huang Q., Ballermann B.J.
    Kidney Int. 44:948-958(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].

Entry informationi

Entry nameiTGFR2_RAT
AccessioniPrimary (citable) accession number: P38438
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1994
Last sequence update: October 1, 1994
Last modified: July 22, 2015
This is version 135 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.