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Q5CD18

- TGFR1_PIG

UniProt

Q5CD18 - TGFR1_PIG

Protein

TGF-beta receptor type-1

Gene

TGFBR1

Organism
Sus scrofa (Pig)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 80 (01 Oct 2014)
      Sequence version 1 (12 Apr 2005)
      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 By similarity.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei232 – 2321ATPPROSITE-ProRule annotation
    Active sitei333 – 3331Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi211 – 2199ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. metal ion binding Source: UniProtKB-KW
    3. receptor signaling protein serine/threonine kinase activity Source: InterPro
    4. transforming growth factor beta-activated receptor activity Source: InterPro

    GO - Biological processi

    1. apoptotic process Source: UniProtKB-KW
    2. cell differentiation Source: UniProtKB-KW
    3. regulation of growth Source: UniProtKB-KW

    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

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    TGF-beta receptor type-1 (EC:2.7.11.30)
    Short name:
    TGFR-1
    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 namesi
    Name:TGFBR1
    OrganismiSus scrofa (Pig)
    Taxonomic identifieri9823 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaSuinaSuidaeSus
    ProteomesiUP000008227: Unplaced

    Subcellular locationi

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

    GO - Cellular componenti

    1. integral component of membrane Source: UniProtKB-KW
    2. plasma membrane Source: UniProtKB-SubCell
    3. tight junction Source: UniProtKB-SubCell

    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 – 503474TGF-beta receptor type-1PRO_0000260305Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi41 – 411N-linked (GlcNAc...)Sequence Analysis
    Modified residuei165 – 1651PhosphoserineBy similarity
    Modified residuei185 – 1851Phosphothreonine; by TGFBR2By similarity
    Modified residuei186 – 1861Phosphothreonine; by TGFBR2By similarity
    Modified residuei187 – 1871Phosphoserine; by TGFBR2By similarity
    Modified residuei189 – 1891Phosphoserine; by TGFBR2By similarity
    Modified residuei191 – 1911Phosphoserine; by TGFBR2By similarity
    Cross-linki391 – 391Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity

    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

    Glycoprotein, Isopeptide bond, Phosphoprotein, Ubl conjugation

    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 (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.By similarity

    Structurei

    3D structure databases

    ProteinModelPortaliQ5CD18.
    SMRiQ5CD18. Positions 29-107, 171-500.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini30 – 12697ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini148 – 503356CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei127 – 14721HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini175 – 20430GSPROSITE-ProRule annotationAdd
    BLAST
    Domaini205 – 495291Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi193 – 1942FKBP1A-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.
    HOGENOMiHOG000230587.
    HOVERGENiHBG054502.
    KOiK04674.

    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]

    Sequences (2)i

    Sequence statusi: Complete.

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

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q5CD18-1) [UniParc]FASTAAdd to Basket

    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.

    « Hide

    MEVAAGAPRS RLLLFVLAAT ATLAPEATAF QCFCHLCTKD NFTCVTDGLC    50
    FVSVTETTDK VIHNSMCIAE IDLIPRDRPF VCAPSSKTGS VTTTYCCNQD 100
    HCNKIELPTV GPFPGKPPSG LGPVELAAVI AGPVCFVCIS LMLMVYICHN 150
    RTVIHHRVPN EEDPSLDRPF ISEGTTLKDL IYDMTTSGSG SGLPLLVQRT 200
    IARTIVLQES IGKGRFGEVW RGKWRGEEVA VKIFSSREER SWFREAEIYQ 250
    TVMLRHENIL GFIAADNKDN GTWTQLWLVS DYHEHGSLFD YLNRYTVTVE 300
    GMIKLALSTA SGLAHLHMEI VGTQGKPAIA HRDLKSKNIL VKKNGTCCIA 350
    DLGLAVRHDS ATDTIDIAPN HRVGTKRYMA PEVLDDSINM KHFESFKRAD 400
    IYAMGLVFWE IARRCSIGGI HEDYQLPYYD LVPSDPSVEE MRKVVCEQKL 450
    RPNIPNRWQS CEALRVMAKI MRECWYANGA ARLTALRIKK TLSQLSQQEG 500
    IKM 503
    Length:503
    Mass (Da):56,174
    Last modified:April 12, 2005 - v1
    Checksum:iCFA1EEC793401A4A
    GO
    Isoform 2 (identifier: Q5CD18-2) [UniParc]FASTAAdd to Basket

    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.

    Show »
    Length:499
    Mass (Da):55,775
    Checksum:i208EB1C35ED32918
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti8 – 81P → S.1 Publication
    Natural varianti417 – 4171I → V.1 Publication

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei111 – 1144Missing in isoform 2. 1 PublicationVSP_021594

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB182259 mRNA. Translation: BAD91022.1.
    AB182260 mRNA. Translation: BAD91023.1.
    RefSeqiNP_001033728.1. NM_001038639.1. [Q5CD18-1]
    UniGeneiSsc.23794.

    Genome annotation databases

    GeneIDi396665.
    KEGGissc:396665.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB182259 mRNA. Translation: BAD91022.1 .
    AB182260 mRNA. Translation: BAD91023.1 .
    RefSeqi NP_001033728.1. NM_001038639.1. [Q5CD18-1 ]
    UniGenei Ssc.23794.

    3D structure databases

    ProteinModelPortali Q5CD18.
    SMRi Q5CD18. Positions 29-107, 171-500.
    ModBasei Search...
    MobiDBi Search...

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 396665.
    KEGGi ssc:396665.

    Organism-specific databases

    CTDi 7046.

    Phylogenomic databases

    eggNOGi COG0515.
    HOGENOMi HOG000230587.
    HOVERGENi HBG054502.
    KOi K04674.

    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. "Structure and polymorphism analysis of transforming growth factor beta receptor 1 (TGFBR1) in pigs."
      Shimanuki S., Mikawa A., Miyake Y., Hamasima N., Mikawa S., Awata T.
      Biochem. Genet. 43:491-500(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), VARIANTS SER-8 AND VAL-417.
      Tissue: Testis.

    Entry informationi

    Entry nameiTGFR1_PIG
    AccessioniPrimary (citable) accession number: Q5CD18
    Secondary accession number(s): Q5CD19
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 28, 2006
    Last sequence update: April 12, 2005
    Last modified: October 1, 2014
    This is version 80 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