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Protein

TGF-beta receptor type-2

Gene

Tgfbr2

Organism
Mus musculus (Mouse)
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 sitei302ATPPROSITE-ProRule annotation1
Active sitei404Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi275 – 283ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

  • activation of protein kinase activity Source: MGI
  • aging Source: Ensembl
  • animal organ regeneration Source: Ensembl
  • apoptotic process Source: MGI
  • atrioventricular valve morphogenesis Source: BHF-UCL
  • brain development Source: BHF-UCL
  • bronchus development Source: MGI
  • bronchus morphogenesis Source: MGI
  • cardiac left ventricle morphogenesis Source: BHF-UCL
  • cartilage development Source: UniProtKB
  • common-partner SMAD protein phosphorylation Source: Ensembl
  • digestive tract development Source: Ensembl
  • embryo implantation Source: Ensembl
  • embryonic cranial skeleton morphogenesis Source: BHF-UCL
  • embryonic hemopoiesis Source: BHF-UCL
  • endocardial cushion fusion Source: BHF-UCL
  • gastrulation Source: MGI
  • growth plate cartilage chondrocyte growth Source: MGI
  • growth plate cartilage development Source: MGI
  • heart development Source: MGI
  • heart looping Source: BHF-UCL
  • in utero embryonic development Source: MGI
  • lens development in camera-type eye Source: MGI
  • lens fiber cell apoptotic process Source: MGI
  • lung development Source: MGI
  • lung lobe morphogenesis Source: MGI
  • lung morphogenesis Source: MGI
  • mammary gland morphogenesis Source: MGI
  • membranous septum morphogenesis Source: BHF-UCL
  • myeloid dendritic cell differentiation Source: MGI
  • negative regulation of cardiac muscle cell proliferation Source: Ensembl
  • Notch signaling pathway Source: MGI
  • outflow tract morphogenesis Source: BHF-UCL
  • outflow tract septum morphogenesis Source: BHF-UCL
  • palate development Source: BHF-UCL
  • pathway-restricted SMAD protein phosphorylation Source: MGI
  • patterning of blood vessels Source: MGI
  • peptidyl-serine phosphorylation Source: MGI
  • peptidyl-threonine phosphorylation Source: MGI
  • positive regulation of angiogenesis Source: MGI
  • positive regulation of B cell tolerance induction Source: MGI
  • positive regulation of epithelial cell migration Source: MGI
  • positive regulation of epithelial to mesenchymal transition Source: MGI
  • positive regulation of epithelial to mesenchymal transition involved in endocardial cushion formation Source: BHF-UCL
  • positive regulation of mesenchymal cell proliferation Source: BHF-UCL
  • positive regulation of NK T cell differentiation Source: MGI
  • positive regulation of reactive oxygen species metabolic process Source: MGI
  • positive regulation of skeletal muscle tissue regeneration Source: Ensembl
  • positive regulation of smooth muscle cell proliferation Source: Ensembl
  • positive regulation of T cell tolerance induction Source: MGI
  • positive regulation of tolerance induction to self antigen Source: MGI
  • protein phosphorylation Source: MGI
  • receptor-mediated endocytosis Source: Ensembl
  • regulation of cell proliferation Source: MGI
  • regulation of gene expression Source: MGI
  • response to cholesterol Source: BHF-UCL
  • response to drug Source: MGI
  • response to estrogen Source: Ensembl
  • response to glucose Source: Ensembl
  • response to hypoxia Source: Ensembl
  • response to mechanical stimulus Source: Ensembl
  • response to nutrient Source: Ensembl
  • response to steroid hormone Source: Ensembl
  • smoothened signaling pathway Source: MGI
  • trachea formation Source: MGI
  • trachea morphogenesis Source: MGI
  • transforming growth factor beta receptor signaling pathway Source: MGI
  • tricuspid valve morphogenesis Source: BHF-UCL
  • vasculogenesis Source: BHF-UCL
  • ventricular septum morphogenesis Source: BHF-UCL
  • wound healing Source: Ensembl
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. 3474.
ReactomeiR-MMU-2173788. Downregulation of TGF-beta receptor signaling.
R-MMU-2173789. TGF-beta receptor signaling activates SMADs.
R-MMU-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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 9

Organism-specific databases

MGIiMGI:98729. 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 – 184ExtracellularSequence analysisAdd BLAST161
Transmembranei185 – 214HelicalSequence analysisAdd BLAST30
Topological domaini215 – 592CytoplasmicSequence analysisAdd BLAST378

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 23Sequence analysisAdd BLAST23
ChainiPRO_000002442724 – 592TGF-beta receptor type-2Add BLAST569

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi48N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi76 ↔ 109By similarity
Disulfide bondi79 ↔ 96By similarity
Disulfide bondi86 ↔ 92By similarity
Glycosylationi95N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi102 ↔ 126By similarity
Glycosylationi119N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi146 ↔ 161By similarity
Disulfide bondi163 ↔ 168By similarity
Modified residuei434PhosphoserineCombined sources1
Modified residuei573PhosphoserineBy similarity1
Modified residuei578PhosphoserineCombined sources1

Post-translational modificationi

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

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ62312.
PRIDEiQ62312.

PTM databases

iPTMnetiQ62312.
PhosphoSitePlusiQ62312.

Expressioni

Tissue specificityi

Widely expressed in adult. Expressed primarily in mesenchyme and epidermis of the midgestational fetus.

Gene expression databases

BgeeiENSMUSG00000032440.
CleanExiMM_TGFBR2.
ExpressionAtlasiQ62312. baseline and differential.
GenevisibleiQ62312. MM.

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

Binary interactionsi

WithEntry#Exp.IntActNotes
Cdh5P552844EBI-2899332,EBI-7087433
DLG5Q8TDM63EBI-2899332,EBI-715138From a different organism.
Shc1P98083-12EBI-2899332,EBI-7533258
Shc1P98083-23EBI-2899332,EBI-1019301

GO - Molecular functioni

  • SMAD binding Source: BHF-UCL
  • transforming growth factor beta binding Source: MGI
  • type I transforming growth factor beta receptor binding Source: MGI

Protein-protein interaction databases

BioGridi204164. 4 interactors.
DIPiDIP-44605N.
IntActiQ62312. 8 interactors.
MINTiMINT-5181700.
STRINGi10090.ENSMUSP00000062333.

Structurei

3D structure databases

ProteinModelPortaliQ62312.
SMRiQ62312.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini269 – 569Protein kinasePROSITE-ProRule annotationAdd BLAST301

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.
InParanoidiQ62312.
KOiK04388.
OMAiTRHIISW.
OrthoDBiEOG091G03YO.
PhylomeDBiQ62312.
TreeFamiTF314724.

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. 2 hits.
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]

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform RII-2 (identifier: Q62312-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MGRGLLRGLW PLHIVLWTRI ASTIPPHVPK SDVEMEAQKD ASIHLSCNRT
60 70 80 90 100
IHPLKHFNSD VMASDNGGAV KLPQLCKFCD VRLSTCDNQK SCMSNCSITA
110 120 130 140 150
ICEKPHEVCV AVWRKNDKNI TLETVCHDPK LTYHGFTLED AASPKCVMKE
160 170 180 190 200
KKRAGETFFM CACNMEECND YIIFSEEYTT SSPDLLLVII QVTGVSLLPP
210 220 230 240 250
LGIAIAVIII FYCYRVHRQQ KLSPSWESSK PRKLMDFSDN CAIILEDDRS
260 270 280 290 300
DISSTCANNI NHNTELLPIE LDTLVGKGRF AEVYKAKLKQ NTSEQFETVA
310 320 330 340 350
VKIFPYEEYS SWKTEKDIFS DINLKHENIL QFLTAEERKT ELGKQYWLIT
360 370 380 390 400
AFHAKGNLQE YLTRHVISWE DLRKLGSSLA RGIAHLHSDH TPCGRPKMPI
410 420 430 440 450
VHRDLKSSNI LVKNDLTCCL CDFGLSLRLD PTLSVDDLAN SGQVGTARYM
460 470 480 490 500
APEVLESRMN LENVESFKQT DVYSMALVLW EMTSRCNAVG EVKDYEPPFG
510 520 530 540 550
SKVREHPCVE SMKDSVLRDR GRPEIPSFWL NHQGIQIVCE TLTECWDHDP
560 570 580 590
EARLTAQCVA ERFSELEHPE RLSGRSCSQE KIPEDGSLNT TK
Length:592
Mass (Da):67,122
Last modified:November 1, 1996 - v1
Checksum:i1A12D58550921F5E
GO
Isoform RII-1 (identifier: Q62312-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     32-56: Missing.
     57-57: F → V

Show »
Length:567
Mass (Da):64,219
Checksum:i4C66067ADA84F986
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti8G → A in AAB30100 (PubMed:8119124).Curated1
Sequence conflicti117D → N in AAB30100 (PubMed:8119124).Curated1
Sequence conflicti354A → R in AAB30100 (PubMed:8119124).Curated1
Sequence conflicti440 – 443NSGQ → KQRE in AAB30100 (PubMed:8119124).Curated4
Sequence conflicti486C → W in AAB30100 (PubMed:8119124).Curated1
Sequence conflicti506H → P in AAB30100 (PubMed:8119124).Curated1
Sequence conflicti569 – 570PE → MD in AAB30100 (PubMed:8119124).Curated2

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_00495532 – 56Missing in isoform RII-1. CuratedAdd BLAST25
Alternative sequenceiVSP_00495657F → V in isoform RII-1. Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D32072 mRNA. Translation: BAA06840.1.
S69114 mRNA. Translation: AAB30100.2.
BC052629 mRNA. No translation available.
CCDSiCCDS23601.1. [Q62312-1]
CCDS23602.1. [Q62312-2]
PIRiS51371.
RefSeqiNP_033397.3. NM_009371.3. [Q62312-1]
UniGeneiMm.172346.

Genome annotation databases

EnsembliENSMUST00000035014; ENSMUSP00000035014; ENSMUSG00000032440. [Q62312-2]
ENSMUST00000061101; ENSMUSP00000062333; ENSMUSG00000032440. [Q62312-1]
GeneIDi21813.
KEGGimmu:21813.
UCSCiuc009rys.2. mouse. [Q62312-1]
uc009ryt.2. mouse. [Q62312-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D32072 mRNA. Translation: BAA06840.1.
S69114 mRNA. Translation: AAB30100.2.
BC052629 mRNA. No translation available.
CCDSiCCDS23601.1. [Q62312-1]
CCDS23602.1. [Q62312-2]
PIRiS51371.
RefSeqiNP_033397.3. NM_009371.3. [Q62312-1]
UniGeneiMm.172346.

3D structure databases

ProteinModelPortaliQ62312.
SMRiQ62312.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi204164. 4 interactors.
DIPiDIP-44605N.
IntActiQ62312. 8 interactors.
MINTiMINT-5181700.
STRINGi10090.ENSMUSP00000062333.

PTM databases

iPTMnetiQ62312.
PhosphoSitePlusiQ62312.

Proteomic databases

PaxDbiQ62312.
PRIDEiQ62312.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000035014; ENSMUSP00000035014; ENSMUSG00000032440. [Q62312-2]
ENSMUST00000061101; ENSMUSP00000062333; ENSMUSG00000032440. [Q62312-1]
GeneIDi21813.
KEGGimmu:21813.
UCSCiuc009rys.2. mouse. [Q62312-1]
uc009ryt.2. mouse. [Q62312-2]

Organism-specific databases

CTDi7048.
MGIiMGI:98729. Tgfbr2.

Phylogenomic databases

eggNOGiKOG3653. Eukaryota.
ENOG410XS2Z. LUCA.
GeneTreeiENSGT00760000118876.
HOGENOMiHOG000231495.
HOVERGENiHBG104975.
InParanoidiQ62312.
KOiK04388.
OMAiTRHIISW.
OrthoDBiEOG091G03YO.
PhylomeDBiQ62312.
TreeFamiTF314724.

Enzyme and pathway databases

BRENDAi2.7.10.2. 3474.
ReactomeiR-MMU-2173788. Downregulation of TGF-beta receptor signaling.
R-MMU-2173789. TGF-beta receptor signaling activates SMADs.
R-MMU-2173791. TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition).

Miscellaneous databases

ChiTaRSiTgfbr2. mouse.
PROiQ62312.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000032440.
CleanExiMM_TGFBR2.
ExpressionAtlasiQ62312. baseline and differential.
GenevisibleiQ62312. MM.

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. 2 hits.
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_MOUSE
AccessioniPrimary (citable) accession number: Q62312
Secondary accession number(s): Q63947
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1996
Last modified: November 2, 2016
This is version 161 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. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. 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.