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Q64729 (TGFR1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 139. 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-1

Short name=TGFR-1
EC=2.7.11.30
Alternative name(s):
ESK2
Transforming growth factor-beta receptor type I
Short name=TGF-beta receptor type I
Short name=TbetaR-I
Gene names
Name:Tgfbr1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length503 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 II serine/threonine kinase receptor, TGFBR2, 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 TGFBR1 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. For instance, TGFBR1 induces TRAF6 autoubiquitination which in turn results in MAP3K7 ubiquitination and activation to trigger apoptosis. Also regulates epithelial to mesenchymal transition through a SMAD-independent signaling pathway through PARD6A phosphorylation and activation By similarity.

Catalytic activity

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

Cofactor

Magnesium or manganese By similarity.

Enzyme regulation

Kept in an inactive conformation by FKBP1A preventing receptor activation in absence of ligand. CD109 is another inhibitor of the receptor By similarity.

Subunit structure

Homodimer; in the endoplasmic reticulum but also at the cell membrane. 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 TGBRB1 and TGFBR2 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 CD109; inhibits TGF-beta receptor activation in keratinocytes. Interacts with RBPMS. Interacts (unphosphorylated) with FKBP1A; prevents TGFBR1 phosphorylation by TGFBR2 and stabilizes it in the inactive conformation. Interacts with SMAD2, SMAD3 and ZFYVE9; ZFYVE9 recruits SMAD2 and SMAD3 to the TGF-beta receptor. Interacts with TRAF6 and MAP3K7; induces MAP3K7 activation by TRAF6. Interacts with PARD6A; involved in TGF-beta induced epithelial to mesenchymal transition. Interacts with SMAD7, NEDD4L, SMURF1 and SMURF2; SMAD7 recruits NEDD4L, SMURF1 and SMURF2 to the TGF-beta receptor By similarity. Interacts with USP15 and VPS39 By similarity.

Subcellular location

Cell membrane; Single-pass type I membrane protein By similarity. Cell junctiontight junction By similarity.

Post-translational modification

Phosphorylated at basal levels in the absence of ligand. Activated upon phosphorylation by TGFBR2, mainly in the GS domain. Phosphorylation in the GS domain abrogates FKBP1A-binding By similarity.

N-Glycosylated By similarity.

Ubiquitinated; undergoes ubiquitination catalyzed by several E3 ubiquitin ligases including SMURF1, SMURF2 and NEDD4L2. Results in the proteasomal and/or lysosomal degradation of the receptor thereby negatively regulating its activity. Deubiquitinated by USP15, leading to stabilization of the protein and enhanced TGF-beta signal By similarity.

Sequence similarities

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

Contains 1 GS domain.

Contains 1 protein kinase domain.

Ontologies

Keywords
   Biological processApoptosis
Differentiation
Growth regulation
   Cellular componentCell junction
Cell membrane
Membrane
Tight junction
   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
Isopeptide bond
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processactivation of MAPKK activity

Inferred from electronic annotation. Source: Ensembl

angiogenesis

Inferred from mutant phenotype PubMed 11285230. Source: MGI

anterior/posterior pattern specification

Inferred from genetic interaction PubMed 16845371. Source: MGI

apoptotic process

Inferred from electronic annotation. Source: UniProtKB-KW

artery morphogenesis

Inferred from mutant phenotype PubMed 17078885. Source: MGI

blastocyst development

Inferred from direct assay PubMed 9921650. Source: MGI

cellular response to transforming growth factor beta stimulus

Inferred from direct assay PubMed 19494318. Source: BHF-UCL

collagen fibril organization

Inferred from mutant phenotype PubMed 15993878. Source: MGI

embryo development

Inferred from mutant phenotype PubMed 14729481PubMed 16344855. Source: MGI

embryonic cranial skeleton morphogenesis

Inferred from mutant phenotype PubMed 16806156. Source: MGI

endothelial cell migration

Inferred from mutant phenotype PubMed 11285230. Source: MGI

epithelial to mesenchymal transition

Inferred from electronic annotation. Source: Ensembl

germ cell migration

Inferred from mutant phenotype PubMed 15993878. Source: MGI

heart development

Inferred from mutant phenotype PubMed 17078885. Source: MGI

in utero embryonic development

Inferred from mutant phenotype PubMed 11285230PubMed 14729481PubMed 17078885. Source: MGI

kidney development

Inferred from genetic interaction PubMed 16845371. Source: MGI

lens development in camera-type eye

Inferred from mutant phenotype PubMed 11641223. Source: MGI

negative regulation of apoptotic process

Inferred from mutant phenotype PubMed 16806156PubMed 17078885. Source: MGI

negative regulation of chondrocyte differentiation

Inferred from mutant phenotype PubMed 19494318. Source: BHF-UCL

negative regulation of endothelial cell proliferation

Inferred from genetic interaction PubMed 21832243. Source: MGI

negative regulation of extrinsic apoptotic signaling pathway

Inferred from electronic annotation. Source: Ensembl

neuron fate commitment

Inferred from mutant phenotype PubMed 15744664. Source: MGI

palate development

Inferred from mutant phenotype PubMed 16806156. Source: MGI

parathyroid gland development

Inferred from mutant phenotype PubMed 17078885. Source: MGI

pathway-restricted SMAD protein phosphorylation

Inferred from electronic annotation. Source: Ensembl

peptidyl-serine phosphorylation

Inferred from electronic annotation. Source: Ensembl

peptidyl-threonine phosphorylation

Inferred from electronic annotation. Source: Ensembl

pharyngeal system development

Inferred from mutant phenotype PubMed 17078885. Source: MGI

positive regulation of SMAD protein import into nucleus

Inferred from electronic annotation. Source: Ensembl

positive regulation of apoptotic signaling pathway

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell growth

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of cellular component movement

Inferred from electronic annotation. Source: Ensembl

positive regulation of filopodium assembly

Inferred from mutant phenotype PubMed 16806156. Source: MGI

positive regulation of pathway-restricted SMAD protein phosphorylation

Inferred from electronic annotation. Source: Ensembl

positive regulation of protein kinase B signaling

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription, DNA-templated

Inferred from electronic annotation. Source: Ensembl

post-embryonic development

Inferred from mutant phenotype PubMed 16806156. Source: MGI

regulation of gene expression

Inferred from mutant phenotype PubMed 16806156. Source: MGI

regulation of protein binding

Inferred from mutant phenotype PubMed 16601693. Source: MGI

regulation of protein ubiquitination

Inferred from electronic annotation. Source: Ensembl

response to cholesterol

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

skeletal system development

Inferred from genetic interaction PubMed 16845371. Source: MGI

skeletal system morphogenesis

Inferred from genetic interaction PubMed 16845371. Source: MGI

thymus development

Inferred from mutant phenotype PubMed 17078885. Source: MGI

transforming growth factor beta receptor signaling pathway

Inferred from direct assay PubMed 14580334PubMed 15820682. Source: MGI

   Cellular_componentcaveola

Inferred from sequence orthology PubMed 17878231. Source: MGI

endosome

Inferred from direct assay PubMed 21266196. Source: UniProt

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

membrane raft

Inferred from sequence orthology PubMed 17878231. Source: MGI

receptor complex

Inferred from electronic annotation. Source: Ensembl

tight junction

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

SMAD binding

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

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

transforming growth factor beta binding

Inferred from physical interaction PubMed 17878231. Source: MGI

transforming growth factor beta receptor activity, type I

Inferred from electronic annotation. Source: Ensembl

transforming growth factor beta-activated receptor activity

Inferred from direct assay PubMed 15820682. Source: MGI

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Cdh5P552842EBI-2899393,EBI-7087433
DLG5Q8TDM63EBI-2899393,EBI-715138From a different organism.
Shc1P98083-23EBI-2899393,EBI-1019301

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q64729-1)

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 2 (identifier: Q64729-2)

The sequence of this isoform differs from the canonical sequence as follows:
     111-114: Missing.
Note: May be due to a competing donnor splice site.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2929 By similarity
Chain30 – 503474TGF-beta receptor type-1
PRO_0000024424

Regions

Topological domain30 – 12697Extracellular Potential
Transmembrane127 – 14721Helical; Potential
Topological domain148 – 503356Cytoplasmic Potential
Domain175 – 20430GS
Domain205 – 495291Protein kinase
Nucleotide binding211 – 2199ATP By similarity
Motif193 – 1942FKBP1A-binding

Sites

Active site3331Proton acceptor By similarity
Binding site2321ATP By similarity

Amino acid modifications

Modified residue1651Phosphoserine By similarity
Modified residue1851Phosphothreonine; by TGFBR2 By similarity
Modified residue1861Phosphothreonine; by TGFBR2 By similarity
Modified residue1871Phosphoserine; by TGFBR2 By similarity
Modified residue1891Phosphoserine; by TGFBR2 By similarity
Modified residue1911Phosphoserine; by TGFBR2 By similarity
Glycosylation411N-linked (GlcNAc...) Potential
Disulfide bond32 ↔ 50 By similarity
Disulfide bond34 ↔ 37 By similarity
Disulfide bond44 ↔ 67 By similarity
Disulfide bond82 ↔ 96 By similarity
Disulfide bond97 ↔ 102 By similarity
Cross-link391Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity

Natural variations

Alternative sequence111 – 1144Missing in isoform 2.
VSP_021593

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: BB8BB6D2261793AF

FASTA50356,179
        10         20         30         40         50         60 
MEAAAAAPRR PQLLIVLVAA ATLLPGAKAL QCFCHLCTKD NFTCETDGLC FVSVTETTDK 

        70         80         90        100        110        120 
VIHNSMCIAE IDLIPRDRPF VCAPSSKTGA VTTTYCCNQD HCNKIELPTT GPFSEKQSAG 

       130        140        150        160        170        180 
LGPVELAAVI AGPVCFVCIA LMLMVYICHN RTVIHHRVPN EEDPSLDRPF ISEGTTLKDL 

       190        200        210        220        230        240 
IYDMTTSGSG SGLPLLVQRT IARTIVLQES IGKGRFGEVW RGKWRGEEVA VKIFSSREER 

       250        260        270        280        290        300 
SWFREAEIYQ TVMLRHENIL GFIAADNKDN GTWTQLWLVS DYHEHGSLFD YLNRYTVTVE 

       310        320        330        340        350        360 
GMIKLALSTA SGLAHLHMEI VGTQGKPAIA HRDLKSKNIL VKKNGTCCIA DLGLAVRHDS 

       370        380        390        400        410        420 
ATDTIDIAPN HRVGTKRYMA PEVLDDSINM KHFESFKRAD IYAMGLVFWE IARRCSIGGI 

       430        440        450        460        470        480 
HEDYQLPYYD LVPSDPSVEE MRKVVCEQKL RPNIPNRWQS CEALRVMAKI MRECWYANGA 

       490        500 
ARLTALRIKK TLSQLSQQEG IKM 

« Hide

Isoform 2 [UniParc].

Checksum: 914DE6236B689C1C
Show »

FASTA49955,790

References

« Hide 'large scale' references
[1]"Molecular cloning of a mouse counterpart for human TGF-beta type I receptor."
Tomoda T., Kudoh T., Noma T., Nakazawa A., Muramatsu M.-A., Arai K.
Biochem. Biophys. Res. Commun. 198:1054-1062(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Brain and Testis.
[2]"A mouse TGF-beta type I receptor that requires type II receptor for ligand binding."
Suzuki A., Shioda N., Maeda T., Tada M., Ueno N.
Biochem. Biophys. Res. Commun. 198:1063-1069(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
Tissue: Brain.
[3]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[4]"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 1).
Strain: C57BL/6.
Tissue: Brain.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D28526 mRNA. Translation: BAA05878.1.
D25540 mRNA. Translation: BAA05023.1.
AL772232, AL772150 Genomic DNA. Translation: CAM13897.1.
AL772150, AL772232 Genomic DNA. Translation: CAM24923.1.
BC063260 mRNA. Translation: AAH63260.1.
PIRJC2061.
JC2062.
RefSeqNP_033396.1. NM_009370.2.
UniGeneMm.197552.

3D structure databases

ProteinModelPortalQ64729.
SMRQ64729. Positions 27-110, 175-500.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid204163. 9 interactions.
DIPDIP-42262N.
IntActQ64729. 9 interactions.
MINTMINT-1341331.

Chemistry

ChEMBLCHEMBL2021750.

PTM databases

PhosphoSiteQ64729.

Proteomic databases

PRIDEQ64729.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000007757; ENSMUSP00000007757; ENSMUSG00000007613. [Q64729-1]
ENSMUST00000044234; ENSMUSP00000048501; ENSMUSG00000007613. [Q64729-2]
GeneID21812.
KEGGmmu:21812.
UCSCuc008sun.1. mouse. [Q64729-1]
uc008suo.1. mouse. [Q64729-2]

Organism-specific databases

CTD7046.
MGIMGI:98728. Tgfbr1.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00730000110337.
HOGENOMHOG000230587.
HOVERGENHBG054502.
InParanoidQ64729.
KOK04674.
OMALYICHNR.
OrthoDBEOG7Q8CN3.
PhylomeDBQ64729.
TreeFamTF314724.

Enzyme and pathway databases

BRENDA2.7.10.2. 3474.

Gene expression databases

ArrayExpressQ64729.
BgeeQ64729.
CleanExMM_TGFBR1.
GenevestigatorQ64729.

Family and domain databases

InterProIPR000472. Activin_rcpt.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
IPR003605. TGF_beta_rcpt_GS.
[Graphical view]
PfamPF01064. Activin_recp. 1 hit.
PF00069. Pkinase. 1 hit.
PF08515. TGF_beta_GS. 1 hit.
[Graphical view]
SMARTSM00467. GS. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS51256. GS. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSTGFBR1. mouse.
NextBio301202.
PROQ64729.
SOURCESearch...

Entry information

Entry nameTGFR1_MOUSE
AccessionPrimary (citable) accession number: Q64729
Secondary accession number(s): A2AJN0
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: November 1, 1996
Last modified: April 16, 2014
This is version 139 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