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P80204

- TGFR1_RAT

UniProt

P80204 - TGFR1_RAT

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Protein

TGF-beta receptor type-1

Gene

Tgfbr1

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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).By similarity

Catalytic activityi

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

Cofactori

Magnesium or manganese.By similarity

Enzyme regulationi

Kept in an inactive conformation by FKBP1A preventing receptor activation in absence of ligand. CD109 is another inhibitor of the receptor.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei230 – 2301ATPPROSITE-ProRule annotation
Active sitei331 – 3311Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi209 – 2179ATPPROSITE-ProRule annotation

GO - Molecular functioni

  1. ATP binding Source: RGD
  2. metal ion binding Source: UniProtKB-KW
  3. protein complex binding Source: RGD
  4. protein heterodimerization activity Source: RGD
  5. protein serine/threonine kinase activity Source: RGD
  6. receptor signaling protein serine/threonine kinase activity Source: InterPro
  7. transforming growth factor beta binding Source: RGD
  8. transforming growth factor beta receptor activity, type I Source: RGD
  9. ubiquitin protein ligase binding Source: RGD

GO - Biological processi

  1. aging Source: RGD
  2. apoptotic process Source: UniProtKB-KW
  3. cell differentiation Source: UniProtKB-KW
  4. digestive tract development Source: RGD
  5. embryo implantation Source: RGD
  6. lung development Source: RGD
  7. negative regulation of endothelial cell differentiation Source: RGD
  8. organ regeneration Source: RGD
  9. protein autophosphorylation Source: RGD
  10. protein phosphorylation Source: RGD
  11. regulation of growth Source: UniProtKB-KW
  12. response to electrical stimulus Source: RGD
  13. response to estrogen Source: RGD
  14. response to hypoxia Source: RGD
  15. response to organic cyclic compound Source: RGD
  16. response to prostaglandin E Source: RGD
  17. response to toxic substance Source: RGD
  18. transforming growth factor beta receptor signaling pathway Source: RGD
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. 5301.
ReactomeiREACT_194641. Downregulation of TGF-beta receptor signaling.
REACT_194651. SMAD2/3 MH2 Domain Mutants in Cancer.
REACT_194657. TGFBR1 KD Mutants in Cancer.
REACT_194661. TGFBR2 Kinase Domain Mutants in Cancer.
REACT_194677. TGF-beta receptor signaling activates SMADs.
REACT_194682. SMAD2/3 Phosphorylation Motif Mutants in Cancer.
REACT_198828. TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition).

Names & Taxonomyi

Protein namesi
Recommended name:
TGF-beta receptor type-1 (EC:2.7.11.30)
Short name:
TGFR-1
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 namesi
Name:Tgfbr1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Chromosome 5

Organism-specific databases

RGDi3852. Tgfbr1.

Subcellular locationi

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

GO - Cellular componenti

  1. apical plasma membrane Source: RGD
  2. basolateral plasma membrane Source: RGD
  3. caveola Source: MGI
  4. membrane raft Source: MGI
  5. protein complex Source: RGD
  6. tight junction Source: UniProtKB-KW
  7. transforming growth factor beta receptor homodimeric complex Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Membrane, Tight junction

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2929By similarityAdd
BLAST
Chaini30 – 501472TGF-beta receptor type-1PRO_0000024425Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi32 ↔ 50By similarity
Disulfide bondi34 ↔ 37By similarity
Glycosylationi41 – 411N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi44 ↔ 67By similarity
Disulfide bondi82 ↔ 94By similarity
Disulfide bondi95 ↔ 100By similarity
Modified residuei163 – 1631PhosphoserineBy similarity
Modified residuei183 – 1831Phosphothreonine; by TGFBR2By similarity
Modified residuei184 – 1841Phosphothreonine; by TGFBR2By similarity
Modified residuei185 – 1851Phosphoserine; by TGFBR2By similarity
Modified residuei187 – 1871Phosphoserine; by TGFBR2By similarity
Modified residuei189 – 1891Phosphoserine; by TGFBR2By similarity
Cross-linki389 – 389Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)

Post-translational modificationi

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).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).By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiP80204.
PRIDEiP80204.

Expressioni

Tissue specificityi

Urogenital ridge, testis, ovary, brain and lungs.

Gene expression databases

ExpressionAtlasiP80204. baseline and differential.
GenevestigatoriP80204.

Interactioni

Subunit structurei

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.By similarity1 Publication

Protein-protein interaction databases

IntActiP80204. 4 interactions.
STRINGi10116.ENSRNOP00000009452.

Structurei

3D structure databases

ProteinModelPortaliP80204.
SMRiP80204. Positions 29-105, 169-498.
ModBaseiSearch...
MobiDBiSearch...

Topological domain

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini30 – 12495ExtracellularSequence AnalysisAdd
BLAST
Topological domaini146 – 501356CytoplasmicSequence AnalysisAdd
BLAST

Transmembrane

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei125 – 14521HelicalSequence AnalysisAdd
BLAST

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini173 – 20230GSPROSITE-ProRule annotationAdd
BLAST
Domaini203 – 493291Protein kinasePROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi191 – 1922FKBP1A-binding

Sequence similaritiesi

Contains 1 GS domain.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00760000118876.
HOGENOMiHOG000230587.
HOVERGENiHBG054502.
InParanoidiP80204.
OMAiCKPAIAH.
OrthoDBiEOG7Q8CN3.
PhylomeDBiP80204.
TreeFamiTF314724.

Family and domain databases

InterProiIPR000472. 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.
IPR000333. TGFB_receptor.
[Graphical view]
PANTHERiPTHR23255. PTHR23255. 1 hit.
PfamiPF01064. Activin_recp. 1 hit.
PF00069. Pkinase. 1 hit.
PF08515. TGF_beta_GS. 1 hit.
[Graphical view]
SMARTiSM00467. GS. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS51256. GS. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

P80204-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MEAASAALRR CLLLIVLVAA ATLLPGAKAL QCFCHLCTKD NFTCETDGLC
60 70 80 90 100
FVSVTETTDK VIHNSMCIAE IDLIPRDRPF VCAPSSKTGA VTYCCNQDHC
110 120 130 140 150
NKIELPTTGP FSEKQSAGLG PVELAAVIAG PVCFVCIALM LMVYICHNRT
160 170 180 190 200
VIHHRVPNEE DPSLDRPFIS EGTTLKDLIY DMTTSGSGSG LPLLVQRTIA
210 220 230 240 250
RTIVLQESIG KGRFGEVWRG KWRGEEVAVK IFSSREERSW FREAEIYQTV
260 270 280 290 300
MLRHENILGF IAADNKDNGT WTQLWLVSDY HEHGSLFDYL NRYTVTVEGM
310 320 330 340 350
IKLALSTASG LAHLHMEIVG TQGKPAIAHR DLKSKNILVK KNGTCCIADL
360 370 380 390 400
GLAVRHDSAT DTIDIAPNHR VGTKRYMAPE VLDDSINMKH FESFKRADIY
410 420 430 440 450
AMGLVFWEIA RRCSIGGIHE DYQLPYYDLV PSDPSVEEMR KVVCEQKLRP
460 470 480 490 500
NIPNRWQSCE ALRVMAKIMR ECWYANGAAR LTALRIKKTL SQLSQQEGIK

M
Length:501
Mass (Da):56,000
Last modified:October 1, 1993 - v1
Checksum:iEAD7F8D37E456102
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
L26110 mRNA. Translation: AAA83216.1.
RefSeqiXP_006238092.2. XM_006238030.2.
UniGeneiRn.44402.

Genome annotation databases

EnsembliENSRNOT00000009452; ENSRNOP00000009452; ENSRNOG00000007036.
GeneIDi29591.
UCSCiRGD:3852. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
L26110 mRNA. Translation: AAA83216.1 .
RefSeqi XP_006238092.2. XM_006238030.2.
UniGenei Rn.44402.

3D structure databases

ProteinModelPortali P80204.
SMRi P80204. Positions 29-105, 169-498.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

IntActi P80204. 4 interactions.
STRINGi 10116.ENSRNOP00000009452.

Proteomic databases

PaxDbi P80204.
PRIDEi P80204.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSRNOT00000009452 ; ENSRNOP00000009452 ; ENSRNOG00000007036 .
GeneIDi 29591.
UCSCi RGD:3852. rat.

Organism-specific databases

RGDi 3852. Tgfbr1.

Phylogenomic databases

eggNOGi COG0515.
GeneTreei ENSGT00760000118876.
HOGENOMi HOG000230587.
HOVERGENi HBG054502.
InParanoidi P80204.
OMAi CKPAIAH.
OrthoDBi EOG7Q8CN3.
PhylomeDBi P80204.
TreeFami TF314724.

Enzyme and pathway databases

BRENDAi 2.7.10.2. 5301.
Reactomei REACT_194641. Downregulation of TGF-beta receptor signaling.
REACT_194651. SMAD2/3 MH2 Domain Mutants in Cancer.
REACT_194657. TGFBR1 KD Mutants in Cancer.
REACT_194661. TGFBR2 Kinase Domain Mutants in Cancer.
REACT_194677. TGF-beta receptor signaling activates SMADs.
REACT_194682. SMAD2/3 Phosphorylation Motif Mutants in Cancer.
REACT_198828. TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition).

Miscellaneous databases

PROi P80204.

Gene expression databases

ExpressionAtlasi P80204. baseline and differential.
Genevestigatori P80204.

Family and domain databases

InterProi IPR000472. 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.
IPR000333. TGFB_receptor.
[Graphical view ]
PANTHERi PTHR23255. PTHR23255. 1 hit.
Pfami PF01064. Activin_recp. 1 hit.
PF00069. Pkinase. 1 hit.
PF08515. TGF_beta_GS. 1 hit.
[Graphical view ]
SMARTi SM00467. GS. 1 hit.
[Graphical view ]
SUPFAMi SSF56112. SSF56112. 1 hit.
PROSITEi PS51256. GS. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  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.

Entry informationi

Entry nameiTGFR1_RAT
AccessioniPrimary (citable) accession number: P80204
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1993
Last sequence update: October 1, 1993
Last modified: October 29, 2014
This is version 135 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. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3