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Q62312 (TGFR2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 137. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
TGF-beta receptor type-2

Short name=TGFR-2
EC=2.7.11.30
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 names
Name:Tgfbr2
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length592 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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 By similarity.

Catalytic activity

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

Cofactor

Magnesium or manganese By similarity.

Subunit structure

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.

Subcellular location

Cell membrane; Single-pass type I membrane protein.

Tissue specificity

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

Post-translational modification

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

Sequence similarities

Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. TGFB receptor subfamily.

Contains 1 protein kinase domain.

Ontologies

Keywords
   Biological processApoptosis
Differentiation
Growth regulation
   Cellular componentCell membrane
Membrane
   Coding sequence diversityAlternative splicing
   DomainSignal
Transmembrane
Transmembrane helix
   LigandATP-binding
Magnesium
Manganese
Metal-binding
Nucleotide-binding
   Molecular functionKinase
Receptor
Serine/threonine-protein kinase
Transferase
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processactivation of protein kinase activity

Inferred from direct assay PubMed 16806156. Source: MGI

aging

Inferred from electronic annotation. Source: Ensembl

brain development

Inferred from mutant phenotype PubMed 12975342. Source: BHF-UCL

bronchus development

Inferred from mutant phenotype PubMed 18990706. Source: MGI

bronchus morphogenesis

Inferred from mutant phenotype PubMed 18990706. Source: MGI

cartilage development

Inferred from mutant phenotype PubMed 18498113. Source: UniProtKB

common-partner SMAD protein phosphorylation

Inferred from electronic annotation. Source: Ensembl

digestive tract development

Inferred from electronic annotation. Source: Ensembl

embryo implantation

Inferred from electronic annotation. Source: Ensembl

embryonic cranial skeleton morphogenesis

Inferred from mutant phenotype PubMed 12975342. Source: BHF-UCL

embryonic hemopoiesis

Inferred from mutant phenotype PubMed 12975342. Source: BHF-UCL

gastrulation

Inferred from mutant phenotype PubMed 10030593. Source: MGI

heart development

Inferred from mutant phenotype PubMed 16332365PubMed 17078885. Source: MGI

in utero embryonic development

Inferred from mutant phenotype PubMed 10030593PubMed 18990706. Source: MGI

lens development in camera-type eye

Inferred from mutant phenotype PubMed 11641223. Source: MGI

lens fiber cell apoptotic process

Inferred from direct assay PubMed 11641223. Source: MGI

lung development

Inferred from mutant phenotype PubMed 18990706. Source: MGI

lung lobe morphogenesis

Inferred from mutant phenotype PubMed 18990706. Source: MGI

lung morphogenesis

Inferred from mutant phenotype PubMed 18990706. Source: MGI

mammary gland morphogenesis

Inferred from mutant phenotype PubMed 15781643. Source: MGI

myeloid dendritic cell differentiation

Inferred from mutant phenotype PubMed 17938236. Source: MGI

negative regulation of cardiac muscle cell proliferation

Inferred from electronic annotation. Source: Ensembl

organ regeneration

Inferred from electronic annotation. Source: Ensembl

palate development

Inferred from mutant phenotype PubMed 12975342. Source: BHF-UCL

pathway-restricted SMAD protein phosphorylation

Inferred from electronic annotation. Source: Ensembl

patterning of blood vessels

Inferred from mutant phenotype PubMed 17078885. Source: MGI

peptidyl-serine phosphorylation

Inferred from electronic annotation. Source: Ensembl

peptidyl-threonine phosphorylation

Inferred from electronic annotation. Source: Ensembl

positive regulation of B cell tolerance induction

Inferred from mutant phenotype PubMed 16973387. Source: MGI

positive regulation of NK T cell differentiation

Inferred from mutant phenotype PubMed 16973387. Source: MGI

positive regulation of T cell tolerance induction

Inferred from mutant phenotype PubMed 16973387. Source: MGI

positive regulation of epithelial cell migration

Inferred from mutant phenotype PubMed 11641223. Source: MGI

positive regulation of mesenchymal cell proliferation

Inferred from mutant phenotype PubMed 12975342. Source: BHF-UCL

positive regulation of reactive oxygen species metabolic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of skeletal muscle tissue regeneration

Inferred from electronic annotation. Source: Ensembl

positive regulation of smooth muscle cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of tolerance induction to self antigen

Inferred from mutant phenotype PubMed 16973387. Source: MGI

protein phosphorylation

Traceable author statement PubMed 11893733. Source: MGI

receptor-mediated endocytosis

Inferred from electronic annotation. Source: Ensembl

regulation of cell proliferation

Inferred from mutant phenotype PubMed 12975342PubMed 15781643. Source: MGI

response to cholesterol

Inferred from direct assay PubMed 17878231. Source: BHF-UCL

response to drug

Inferred from electronic annotation. Source: Ensembl

response to estrogen

Inferred from electronic annotation. Source: Ensembl

response to glucose

Inferred from electronic annotation. Source: Ensembl

response to mechanical stimulus

Inferred from electronic annotation. Source: Ensembl

response to nutrient

Inferred from electronic annotation. Source: Ensembl

smoothened signaling pathway

Inferred from mutant phenotype PubMed 18990706. Source: MGI

trachea formation

Inferred from mutant phenotype PubMed 18990706. Source: MGI

trachea morphogenesis

Inferred from mutant phenotype PubMed 18990706. Source: MGI

transforming growth factor beta receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

vasculogenesis

Inferred from mutant phenotype PubMed 12975342. Source: BHF-UCL

wound healing

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcaveola

Inferred from sequence orthology PubMed 17878231. Source: MGI

cytosol

Inferred from electronic annotation. Source: Ensembl

external side of plasma membrane

Inferred from direct assay PubMed 16973387. Source: MGI

integral component of plasma membrane

Inferred from electronic annotation. Source: Ensembl

membrane raft

Inferred from sequence orthology PubMed 17878231. Source: MGI

receptor complex

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

SMAD binding

Inferred from direct assay PubMed 12773577. Source: BHF-UCL

glycosaminoglycan binding

Inferred from electronic annotation. Source: Ensembl

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

receptor signaling protein serine/threonine kinase activity

Inferred from electronic annotation. Source: InterPro

transforming growth factor beta binding

Inferred from physical interaction PubMed 17878231. Source: MGI

transforming growth factor beta receptor activity, type II

Inferred from electronic annotation. Source: InterPro

transforming growth factor beta-activated receptor activity

Inferred from genetic interaction PubMed 17878231. Source: MGI

Complete GO annotation...

Binary interactions

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform RII-2 (identifier: Q62312-1)

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.
Isoform RII-1 (identifier: Q62312-2)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2323 Potential
Chain24 – 592569TGF-beta receptor type-2
PRO_0000024427

Regions

Topological domain24 – 184161Extracellular Potential
Transmembrane185 – 21430Helical; Potential
Topological domain215 – 592378Cytoplasmic Potential
Domain269 – 569301Protein kinase
Nucleotide binding275 – 2839ATP By similarity

Sites

Active site4041Proton acceptor By similarity
Binding site3021ATP By similarity

Amino acid modifications

Modified residue5731Phosphoserine By similarity
Modified residue5781Phosphoserine Ref.4
Glycosylation481N-linked (GlcNAc...) Potential
Glycosylation951N-linked (GlcNAc...) Potential
Glycosylation1191N-linked (GlcNAc...) Potential
Disulfide bond76 ↔ 109 By similarity
Disulfide bond79 ↔ 96 By similarity
Disulfide bond86 ↔ 92 By similarity
Disulfide bond102 ↔ 126 By similarity
Disulfide bond146 ↔ 161 By similarity
Disulfide bond163 ↔ 168 By similarity

Natural variations

Alternative sequence32 – 5625Missing in isoform RII-1.
VSP_004955
Alternative sequence571F → V in isoform RII-1.
VSP_004956

Experimental info

Sequence conflict81G → A in AAB30100. Ref.2
Sequence conflict1171D → N in AAB30100. Ref.2
Sequence conflict3541A → R in AAB30100. Ref.2
Sequence conflict440 – 4434NSGQ → KQRE in AAB30100. Ref.2
Sequence conflict4861C → W in AAB30100. Ref.2
Sequence conflict5061H → P in AAB30100. Ref.2
Sequence conflict569 – 5702PE → MD in AAB30100. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform RII-2 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: 1A12D58550921F5E

FASTA59267,122
        10         20         30         40         50         60 
MGRGLLRGLW PLHIVLWTRI ASTIPPHVPK SDVEMEAQKD ASIHLSCNRT IHPLKHFNSD 

        70         80         90        100        110        120 
VMASDNGGAV KLPQLCKFCD VRLSTCDNQK SCMSNCSITA ICEKPHEVCV AVWRKNDKNI 

       130        140        150        160        170        180 
TLETVCHDPK LTYHGFTLED AASPKCVMKE KKRAGETFFM CACNMEECND YIIFSEEYTT 

       190        200        210        220        230        240 
SSPDLLLVII QVTGVSLLPP LGIAIAVIII FYCYRVHRQQ KLSPSWESSK PRKLMDFSDN 

       250        260        270        280        290        300 
CAIILEDDRS DISSTCANNI NHNTELLPIE LDTLVGKGRF AEVYKAKLKQ NTSEQFETVA 

       310        320        330        340        350        360 
VKIFPYEEYS SWKTEKDIFS DINLKHENIL QFLTAEERKT ELGKQYWLIT AFHAKGNLQE 

       370        380        390        400        410        420 
YLTRHVISWE DLRKLGSSLA RGIAHLHSDH TPCGRPKMPI VHRDLKSSNI LVKNDLTCCL 

       430        440        450        460        470        480 
CDFGLSLRLD PTLSVDDLAN SGQVGTARYM APEVLESRMN LENVESFKQT DVYSMALVLW 

       490        500        510        520        530        540 
EMTSRCNAVG EVKDYEPPFG SKVREHPCVE SMKDSVLRDR GRPEIPSFWL NHQGIQIVCE 

       550        560        570        580        590 
TLTECWDHDP EARLTAQCVA ERFSELEHPE RLSGRSCSQE KIPEDGSLNT TK 

« Hide

Isoform RII-1 [UniParc].

Checksum: 4C66067ADA84F986
Show »

FASTA56764,219

References

« Hide 'large scale' references
[1]"Cloning of an isoform of mouse TGF-beta type II receptor gene."
Suzuki A., Shioda N., Maeda T., Tada M., Ueno N.
FEBS Lett. 355:19-22(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING.
Tissue: Brain.
[2]"The murine type II TGF-beta receptor has a coincident embryonic expression and binding preference for TGF-beta 1."
Lawler S., Candia A.F., Ebner R., Shum L., Lopez A.R., Moses H.L., Wright C.V., Derynck R.
Development 120:165-175(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM RII-2).
Tissue: Olfactory epithelium.
[4]"The phagosomal proteome in interferon-gamma-activated macrophages."
Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P.
Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-578, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D32072 mRNA. Translation: BAA06840.1.
S69114 mRNA. Translation: AAB30100.2.
BC052629 mRNA. No translation available.
PIRS51371.
RefSeqNP_033397.3. NM_009371.3.
UniGeneMm.172346.

3D structure databases

ProteinModelPortalQ62312.
SMRQ62312. Positions 73-178, 269-564.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid204164. 2 interactions.
DIPDIP-44605N.
IntActQ62312. 8 interactions.
MINTMINT-5181700.

PTM databases

PhosphoSiteQ62312.

Proteomic databases

PaxDbQ62312.
PRIDEQ62312.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000035014; ENSMUSP00000035014; ENSMUSG00000032440. [Q62312-2]
ENSMUST00000061101; ENSMUSP00000062333; ENSMUSG00000032440. [Q62312-1]
GeneID21813.
KEGGmmu:21813.
UCSCuc009rys.2. mouse. [Q62312-1]
uc009ryt.2. mouse. [Q62312-2]

Organism-specific databases

CTD7048.
MGIMGI:98729. Tgfbr2.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00560000076906.
HOGENOMHOG000231495.
HOVERGENHBG104975.
InParanoidQ62312.
KOK04388.
OMAWETSKPR.
OrthoDBEOG7JHM5B.
PhylomeDBQ62312.
TreeFamTF314724.

Enzyme and pathway databases

BRENDA2.7.10.2. 3474.

Gene expression databases

ArrayExpressQ62312.
BgeeQ62312.
CleanExMM_TGFBR2.
GenevestigatorQ62312.

Family and domain databases

InterProIPR011009. 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]
PANTHERPTHR23255:SF10. PTHR23255:SF10. 1 hit.
PfamPF08917. ecTbetaR2. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
PIRSFPIRSF037393. TGFRII. 1 hit.
PRINTSPR00653. ACTIVIN2R.
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSTGFBR2. mouse.
NextBio301206.
PROQ62312.
SOURCESearch...

Entry information

Entry nameTGFR2_MOUSE
AccessionPrimary (citable) accession number: Q62312
Secondary accession number(s): Q63947
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1996
Last modified: April 16, 2014
This is version 137 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot