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P80204

- TGFR1_RAT

UniProt

P80204 - TGFR1_RAT

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
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    • History
      Entry version 134 (01 Oct 2014)
      Sequence version 1 (01 Oct 1993)
      Previous versions | rss
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    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

    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-SubCell
    7. transforming growth factor beta receptor homodimeric complex Source: RGD

    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

    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.
    GeneTreeiENSGT00730000110337.
    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

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    MEAASAALRR CLLLIVLVAA ATLLPGAKAL QCFCHLCTKD NFTCETDGLC    50
    FVSVTETTDK VIHNSMCIAE IDLIPRDRPF VCAPSSKTGA VTYCCNQDHC 100
    NKIELPTTGP FSEKQSAGLG PVELAAVIAG PVCFVCIALM LMVYICHNRT 150
    VIHHRVPNEE DPSLDRPFIS EGTTLKDLIY DMTTSGSGSG LPLLVQRTIA 200
    RTIVLQESIG KGRFGEVWRG KWRGEEVAVK IFSSREERSW FREAEIYQTV 250
    MLRHENILGF IAADNKDNGT WTQLWLVSDY HEHGSLFDYL NRYTVTVEGM 300
    IKLALSTASG LAHLHMEIVG TQGKPAIAHR DLKSKNILVK KNGTCCIADL 350
    GLAVRHDSAT DTIDIAPNHR VGTKRYMAPE VLDDSINMKH FESFKRADIY 400
    AMGLVFWEIA RRCSIGGIHE DYQLPYYDLV PSDPSVEEMR KVVCEQKLRP 450
    NIPNRWQSCE ALRVMAKIMR ECWYANGAAR LTALRIKKTL SQLSQQEGIK 500
    M 501
    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.
    UniGeneiRn.44402.

    Genome annotation databases

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

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L26110 mRNA. Translation: AAA83216.1 .
    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 .
    UCSCi RGD:3852. rat.

    Organism-specific databases

    RGDi 3852. Tgfbr1.

    Phylogenomic databases

    eggNOGi COG0515.
    GeneTreei ENSGT00730000110337.
    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

    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 1, 2014
    This is version 134 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