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P80204 (TGFR1_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 130. 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):
Serine/threonine-protein kinase receptor R4
Short name=SKR4
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
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length501 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. Ref.2

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 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. Interacts (unphosphorylated) with FKBP1A; prevents TGFBR1 phosphorylation by TGFBR2 and stabilizes it in the inactive conformation. Ref.2

Subcellular location

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

Tissue specificity

Urogenital ridge, testis, ovary, brain and lungs.

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_processaging

Inferred from expression pattern PubMed 12051734. Source: RGD

apoptotic process

Inferred from electronic annotation. Source: UniProtKB-KW

cell differentiation

Inferred from electronic annotation. Source: UniProtKB-KW

digestive tract development

Inferred from expression pattern PubMed 12815632. Source: RGD

embryo development

Inferred from expression pattern PubMed 17428384. Source: RGD

embryo implantation

Inferred from expression pattern PubMed 16426643. Source: RGD

lung development

Inferred from expression pattern PubMed 10835329. Source: RGD

negative regulation of endothelial cell differentiation

Inferred from mutant phenotype PubMed 17450384. Source: RGD

organ regeneration

Inferred from expression pattern PubMed 9699514. Source: RGD

protein autophosphorylation

Inferred from mutant phenotype PubMed 8272871. Source: RGD

protein phosphorylation

Inferred from mutant phenotype PubMed 17505012. Source: RGD

regulation of growth

Inferred from electronic annotation. Source: UniProtKB-KW

response to electrical stimulus

Inferred from expression pattern PubMed 16682418. Source: RGD

response to estrogen

Inferred from direct assay PubMed 12097811. Source: RGD

response to hypoxia

Inferred from expression pattern PubMed 18760335. Source: RGD

response to organic cyclic compound

Inferred from expression pattern PubMed 12890451. Source: RGD

response to prostaglandin E

Inferred from expression pattern PubMed 12890451. Source: RGD

response to toxic substance

Inferred from expression pattern PubMed 16682418. Source: RGD

transforming growth factor beta receptor signaling pathway

Inferred from mutant phenotype PubMed 17505012PubMed 18684975PubMed 8272871. Source: RGD

   Cellular_componentapical plasma membrane

Inferred from direct assay PubMed 10590020. Source: RGD

basolateral plasma membrane

Inferred from direct assay PubMed 10590020. Source: RGD

caveola

Inferred from direct assay PubMed 17878231. Source: MGI

membrane raft

Inferred from direct assay PubMed 17878231. Source: MGI

protein complex

Inferred from direct assay PubMed 16617054. Source: RGD

tight junction

Inferred from electronic annotation. Source: UniProtKB-SubCell

transforming growth factor beta receptor homodimeric complex

Inferred by curator PubMed 18684975. Source: RGD

   Molecular_functionATP binding

Inferred from mutant phenotype PubMed 17505012. Source: RGD

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein complex binding

Inferred from physical interaction PubMed 16617054. Source: RGD

protein heterodimerization activity

Inferred from mutant phenotype PubMed 8272871. Source: RGD

protein serine/threonine kinase activity

Inferred from mutant phenotype PubMed 8272871. Source: RGD

transforming growth factor beta binding

Inferred from direct assay PubMed 8272871. Source: RGD

transforming growth factor beta receptor activity, type I

Inferred from mutant phenotype PubMed 17505012PubMed 18684975PubMed 8272871. Source: RGD

ubiquitin protein ligase binding

Inferred from physical interaction PubMed 17347560. Source: RGD

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2929 By similarity
Chain30 – 501472TGF-beta receptor type-1
PRO_0000024425

Regions

Topological domain30 – 12495Extracellular Potential
Transmembrane125 – 14521Helical; Potential
Topological domain146 – 501356Cytoplasmic Potential
Domain173 – 20230GS
Domain203 – 493291Protein kinase
Nucleotide binding209 – 2179ATP By similarity
Motif191 – 1922FKBP1A-binding

Sites

Active site3311Proton acceptor By similarity
Binding site2301ATP By similarity

Amino acid modifications

Modified residue1631Phosphoserine By similarity
Modified residue1831Phosphothreonine; by TGFBR2 By similarity
Modified residue1841Phosphothreonine; by TGFBR2 By similarity
Modified residue1851Phosphoserine; by TGFBR2 By similarity
Modified residue1871Phosphoserine; by TGFBR2 By similarity
Modified residue1891Phosphoserine; 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 ↔ 94 By similarity
Disulfide bond95 ↔ 100 By similarity
Cross-link389Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.3

Sequences

Sequence LengthMass (Da)Tools
P80204 [UniParc].

Last modified October 1, 1993. Version 1.
Checksum: EAD7F8D37E456102

FASTA50156,000
        10         20         30         40         50         60 
MEAASAALRR CLLLIVLVAA ATLLPGAKAL QCFCHLCTKD NFTCETDGLC FVSVTETTDK 

        70         80         90        100        110        120 
VIHNSMCIAE IDLIPRDRPF VCAPSSKTGA VTYCCNQDHC NKIELPTTGP FSEKQSAGLG 

       130        140        150        160        170        180 
PVELAAVIAG PVCFVCIALM LMVYICHNRT VIHHRVPNEE DPSLDRPFIS EGTTLKDLIY 

       190        200        210        220        230        240 
DMTTSGSGSG LPLLVQRTIA RTIVLQESIG KGRFGEVWRG KWRGEEVAVK IFSSREERSW 

       250        260        270        280        290        300 
FREAEIYQTV MLRHENILGF IAADNKDNGT WTQLWLVSDY HEHGSLFDYL NRYTVTVEGM 

       310        320        330        340        350        360 
IKLALSTASG LAHLHMEIVG TQGKPAIAHR DLKSKNILVK KNGTCCIADL GLAVRHDSAT 

       370        380        390        400        410        420 
DTIDIAPNHR VGTKRYMAPE VLDDSINMKH FESFKRADIY AMGLVFWEIA RRCSIGGIHE 

       430        440        450        460        470        480 
DYQLPYYDLV PSDPSVEEMR KVVCEQKLRP NIPNRWQSCE ALRVMAKIMR ECWYANGAAR 

       490        500 
LTALRIKKTL SQLSQQEGIK M 

« Hide

References

[1]"Developmental expression of four novel serine/threonine kinase receptors homologous to the activin/transforming growth factor-beta type II receptor family."
He W.-W., Gustafson M.L., Hirobe S., Donahoe P.K.
Dev. Dyn. 196:133-142(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: Sprague-Dawley.
Tissue: Urogenital ridge.
[2]"The immunophilin FKBP12 functions as a common inhibitor of the TGF beta family type I receptors."
Wang T., Li B.Y., Danielson P.D., Shah P.C., Rockwell S., Lechleider R.J., Martin J., Manganaro T., Donahoe P.K.
Cell 86:435-444(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH FKBP1A, ENZYME REGULATION.
[3]"The type I TGF-beta receptor is covalently modified and regulated by sumoylation."
Kang J.S., Saunier E.F., Akhurst R.J., Derynck R.
Nat. Cell Biol. 10:654-664(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: SUMOYLATION AT LYS-389.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L26110 mRNA. Translation: AAA83216.1.
UniGeneRn.44402.

3D structure databases

ProteinModelPortalP80204.
SMRP80204. Positions 29-105, 169-498.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActP80204. 4 interactions.
STRING10116.ENSRNOP00000009452.

Proteomic databases

PaxDbP80204.
PRIDEP80204.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000009452; ENSRNOP00000009452; ENSRNOG00000007036.
UCSCRGD:3852. rat.

Organism-specific databases

RGD3852. Tgfbr1.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00730000110337.
HOGENOMHOG000230587.
HOVERGENHBG054502.
InParanoidP80204.
OMACKPAIAH.
OrthoDBEOG7Q8CN3.
PhylomeDBP80204.
TreeFamTF314724.

Enzyme and pathway databases

BRENDA2.7.10.2. 5301.

Gene expression databases

GenevestigatorP80204.

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

PROP80204.

Entry information

Entry nameTGFR1_RAT
AccessionPrimary (citable) accession number: P80204
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1993
Last sequence update: October 1, 1993
Last modified: April 16, 2014
This is version 130 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