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O46680 (TGFR1_BOVIN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 112. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·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):
TGF-beta type I receptor
Transforming growth factor-beta receptor type I
Short name=TGF-beta receptor type I
Short name=TbetaR-I
Gene names
Name:TGFBR1
OrganismBos taurus (Bovine) [Reference proteome]
Taxonomic identifier9913 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos

Protein attributes

Sequence length499 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at transcript 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
   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 electronic annotation. Source: Ensembl

anterior/posterior pattern specification

Inferred from electronic annotation. Source: Ensembl

apoptotic process

Inferred from electronic annotation. Source: UniProtKB-KW

artery morphogenesis

Inferred from electronic annotation. Source: Ensembl

blastocyst development

Inferred from electronic annotation. Source: Ensembl

cellular response to transforming growth factor beta stimulus

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

collagen fibril organization

Inferred from electronic annotation. Source: Ensembl

embryonic cranial skeleton morphogenesis

Inferred from electronic annotation. Source: Ensembl

endothelial cell migration

Inferred from electronic annotation. Source: Ensembl

epithelial to mesenchymal transition

Inferred from electronic annotation. Source: Ensembl

germ cell migration

Inferred from electronic annotation. Source: Ensembl

heart development

Inferred from electronic annotation. Source: Ensembl

kidney development

Inferred from electronic annotation. Source: Ensembl

lens development in camera-type eye

Inferred from electronic annotation. Source: Ensembl

negative regulation of apoptotic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of chondrocyte differentiation

Inferred from electronic annotation. Source: Ensembl

negative regulation of endothelial cell proliferation

Inferred from electronic annotation. Source: Ensembl

negative regulation of extrinsic apoptotic signaling pathway

Inferred from electronic annotation. Source: Ensembl

neuron fate commitment

Inferred from electronic annotation. Source: Ensembl

palate development

Inferred from electronic annotation. Source: Ensembl

parathyroid gland development

Inferred from electronic annotation. Source: Ensembl

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 electronic annotation. Source: Ensembl

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 electronic annotation. Source: Ensembl

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 electronic annotation. Source: Ensembl

regulation of protein binding

Inferred from electronic annotation. Source: Ensembl

regulation of protein ubiquitination

Inferred from electronic annotation. Source: Ensembl

response to cholesterol

Inferred from electronic annotation. Source: Ensembl

thymus development

Inferred from electronic annotation. Source: Ensembl

transforming growth factor beta receptor signaling pathway

Inferred from sequence or structural similarity. Source: AgBase

   Cellular_componentintegral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

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

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

transforming growth factor beta receptor activity, type I

Inferred from sequence or structural similarity. Source: AgBase

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2929 By similarity
Chain30 – 499470TGF-beta receptor type-1
PRO_0000254657

Regions

Topological domain30 – 12293Extracellular Potential
Transmembrane123 – 14321Helical; Potential
Topological domain144 – 499356Cytoplasmic Potential
Domain171 – 20030GS
Domain201 – 491291Protein kinase
Nucleotide binding207 – 2159ATP By similarity
Motif189 – 1902FKBP1A-binding

Sites

Active site3291Proton acceptor By similarity
Binding site2281ATP By similarity

Amino acid modifications

Modified residue1611Phosphoserine By similarity
Modified residue1811Phosphothreonine; by TGFBR2 By similarity
Modified residue1821Phosphothreonine; by TGFBR2 By similarity
Modified residue1831Phosphoserine; by TGFBR2 By similarity
Modified residue1851Phosphoserine; by TGFBR2 By similarity
Modified residue1871Phosphoserine; 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-link387Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity

Sequences

Sequence LengthMass (Da)Tools
O46680 [UniParc].

Last modified June 1, 1998. Version 1.
Checksum: 7FA311693CA938CD

FASTA49955,814
        10         20         30         40         50         60 
MEAAAATPRP RLFLLMLAAA ATLVPEATPL QCFCHLCTKD NFTCVTDGLC FVSVTETTDK 

        70         80         90        100        110        120 
VIHNSMCIAE IDLIPRDRPF VCAPSSKTGS ITTTYCCNQD HCNKIELPTV GKPSSGLGPV 

       130        140        150        160        170        180 
ELAAVIAGPV CFVCISLMLM VYICHNRTVI HHRVPNEEDP SLDRPFISEG TTLKDLIYDM 

       190        200        210        220        230        240 
TTSGSGSGLP LLVQRTIART IVLQESIGKG RFGEVWRGKW RGEEVAVKIF SSREERSWFR 

       250        260        270        280        290        300 
EAEIYQTVML RHENILGFIA ADNKDNGTWT QLWLVSDYHE HGSLFDYLNR YTVTVEGMIK 

       310        320        330        340        350        360 
LALSTASGLA HLHMEIVGTQ GKPAIAHRDL KSKNILVKKN GTCCIADLGL AVRHDSATDT 

       370        380        390        400        410        420 
IDIAPNHRVG TKRYMAPEVL DDSINMKHFE SFKRADIYAM GLVFWEVARR CSIGGIHEDY 

       430        440        450        460        470        480 
QLPYYDLVPS DPSVEEMRKV VCEQKLRPNI PNRWQSCEAL RVMAKIMREC WYANGAARLT 

       490 
ALRIKKTLSQ LSQQEGIKM 

« Hide

References

[1]"Molecular cloning, genetic mapping, and developmental expression of a bovine transforming growth factor beta (TGF-beta) type I receptor."
Roelen B.A.J., Van Eijk M.J.T., Van Rooijen M.A., Bevers M.M., Larson J.H., Lewin H.A., Mummery C.L.
Mol. Reprod. Dev. 49:1-9(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Placenta.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U97485 mRNA. Translation: AAC02717.1.
RefSeqNP_777046.1. NM_174621.2.
UniGeneBt.91785.

3D structure databases

ProteinModelPortalO46680.
SMRO46680. Positions 30-107, 167-496.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9913.ENSBTAP00000024010.

Proteomic databases

PRIDEO46680.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSBTAT00000024010; ENSBTAP00000024010; ENSBTAG00000018035.
GeneID282382.
KEGGbta:282382.

Organism-specific databases

CTD7046.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00730000110337.
HOGENOMHOG000230587.
HOVERGENHBG054502.
InParanoidO46680.
KOK04674.
OMALYICHNR.
OrthoDBEOG7Q8CN3.
TreeFamTF314724.

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

NextBio20806171.

Entry information

Entry nameTGFR1_BOVIN
AccessionPrimary (citable) accession number: O46680
Entry history
Integrated into UniProtKB/Swiss-Prot: October 31, 2006
Last sequence update: June 1, 1998
Last modified: April 16, 2014
This is version 112 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