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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 protein 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)DescriptionActionsGraphical viewLength
Binding sitei277ATPPROSITE-ProRule annotation1
Active sitei379Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi250 – 258ATPPROSITE-ProRule annotation9

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
  • animal organ morphogenesis Source: RGD
  • animal organ regeneration 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 looping 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
  • Notch signaling pathway Source: Ensembl
  • outflow tract morphogenesis Source: Ensembl
  • 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 epithelial to mesenchymal transition involved in endocardial cushion formation 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
  • ventricular septum morphogenesis Source: Ensembl
  • 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.
ReactomeiR-RNO-2173788. Downregulation of TGF-beta receptor signaling.
R-RNO-2173789. TGF-beta receptor signaling activates SMADs.
R-RNO-2173791. TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition).

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
Proteomesi
  • UP000002494 Componenti: Chromosome 8

Organism-specific databases

RGDi69651. Tgfbr2.

Subcellular locationi

  • Cell membrane By similarity; Single-pass type I membrane protein By similarity
  • Membrane raft By similarity

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini24 – 166ExtracellularSequence analysisAdd BLAST143
Transmembranei167 – 187HelicalSequence analysisAdd BLAST21
Topological domaini188 – 567CytoplasmicSequence analysisAdd BLAST380

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)DescriptionActionsGraphical viewLength
Signal peptidei1 – 23Sequence analysisAdd BLAST23
ChainiPRO_000002442924 – 567TGF-beta receptor type-2Add BLAST544

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi51 ↔ 84By similarity
Disulfide bondi54 ↔ 71By similarity
Disulfide bondi61 ↔ 67By similarity
Glycosylationi70N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi77 ↔ 101By similarity
Glycosylationi94N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi121 ↔ 136By similarity
Disulfide bondi138 ↔ 143By similarity
Modified residuei409PhosphoserineBy similarity1
Modified residuei548PhosphoserineCombined sources1
Modified residuei553PhosphoserineBy similarity1

Post-translational modificationi

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

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiP38438.
PRIDEiP38438.

PTM databases

iPTMnetiP38438.
PhosphoSitePlusiP38438.

Expressioni

Gene expression databases

BgeeiENSRNOG00000013265.
ExpressionAtlasiP38438. differential.
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

GO - Molecular functioni

  • mitogen-activated protein kinase kinase kinase binding Source: RGD
  • protein heterodimerization activity Source: RGD
  • protein homodimerization activity Source: RGD

Protein-protein interaction databases

BioGridi249668. 1 interactor.
IntActiP38438. 1 interactor.
STRINGi10116.ENSRNOP00000035501.

Structurei

3D structure databases

ProteinModelPortaliP38438.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini244 – 546Protein kinasePROSITE-ProRule annotationAdd BLAST303

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3653. Eukaryota.
ENOG410XS2Z. LUCA.
GeneTreeiENSGT00760000118876.
HOGENOMiHOG000231495.
HOVERGENiHBG104975.
InParanoidiP38438.
KOiK04388.
OMAiTRHIISW.
OrthoDBiEOG091G03YO.
PhylomeDBiP38438.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
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.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PIRSFiPIRSF037393. TGFRII. 1 hit.
PRINTSiPR00653. ACTIVIN2R.
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
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)DescriptionActionsGraphical viewLength
Sequence conflicti388 – 389KN → RS in AAB29352 (PubMed:8264154).Curated2
Sequence conflicti403R → G in AAB29352 (PubMed:8264154).Curated1
Sequence conflicti405D → S in AAB29352 (PubMed:8264154).Curated1
Sequence conflicti477K → R in AAB29352 (PubMed:8264154).Curated1

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.164421.
Rn.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.164421.
Rn.9954.

3D structure databases

ProteinModelPortaliP38438.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi249668. 1 interactor.
IntActiP38438. 1 interactor.
STRINGi10116.ENSRNOP00000035501.

PTM databases

iPTMnetiP38438.
PhosphoSitePlusiP38438.

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

eggNOGiKOG3653. Eukaryota.
ENOG410XS2Z. LUCA.
GeneTreeiENSGT00760000118876.
HOGENOMiHOG000231495.
HOVERGENiHBG104975.
InParanoidiP38438.
KOiK04388.
OMAiTRHIISW.
OrthoDBiEOG091G03YO.
PhylomeDBiP38438.

Enzyme and pathway databases

BRENDAi2.7.10.2. 5301.
ReactomeiR-RNO-2173788. Downregulation of TGF-beta receptor signaling.
R-RNO-2173789. TGF-beta receptor signaling activates SMADs.
R-RNO-2173791. TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition).

Miscellaneous databases

PROiP38438.

Gene expression databases

BgeeiENSRNOG00000013265.
ExpressionAtlasiP38438. differential.
GenevisibleiP38438. RN.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
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.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PIRSFiPIRSF037393. TGFRII. 1 hit.
PRINTSiPR00653. ACTIVIN2R.
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
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...

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: November 30, 2016
This is version 148 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

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 one 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.