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P38438

- TGFR2_RAT

UniProt

P38438 - TGFR2_RAT

Protein

TGF-beta receptor type-2

Gene

Tgfbr2

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 127 (01 Oct 2014)
      Sequence version 1 (01 Oct 1994)
      Previous versions | rss
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    Functioni

    Transmembrane serine/threonine kinase forming with the TGF-beta type I serine/threonine kinase receptor, TGFBR1, 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 TGFRB1 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 By similarity.By similarity

    Catalytic activityi

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

    Cofactori

    Magnesium or manganese.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei277 – 2771ATPPROSITE-ProRule annotation
    Active sitei379 – 3791Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi250 – 2589ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. glycosaminoglycan binding Source: Ensembl
    3. metal ion binding Source: UniProtKB-KW
    4. mitogen-activated protein kinase kinase kinase binding Source: RGD
    5. protein binding Source: BHF-UCL
    6. protein heterodimerization activity Source: RGD
    7. protein homodimerization activity Source: RGD
    8. receptor signaling protein serine/threonine kinase activity Source: InterPro
    9. transforming growth factor beta receptor activity, type II Source: RGD

    GO - Biological processi

    1. activation of protein kinase activity Source: Ensembl
    2. aging Source: RGD
    3. brain development Source: Ensembl
    4. bronchus morphogenesis Source: Ensembl
    5. cartilage development Source: Ensembl
    6. common-partner SMAD protein phosphorylation Source: RGD
    7. digestive tract development Source: RGD
    8. embryo implantation Source: RGD
    9. embryonic cranial skeleton morphogenesis Source: Ensembl
    10. embryonic hemopoiesis Source: Ensembl
    11. gastrulation Source: Ensembl
    12. heart development Source: Ensembl
    13. in utero embryonic development Source: Ensembl
    14. lens development in camera-type eye Source: Ensembl
    15. lens fiber cell apoptotic process Source: Ensembl
    16. lung development Source: RGD
    17. lung lobe morphogenesis Source: Ensembl
    18. mammary gland morphogenesis Source: Ensembl
    19. myeloid dendritic cell differentiation Source: Ensembl
    20. negative regulation of cardiac muscle cell proliferation Source: RGD
    21. negative regulation of cell proliferation Source: RGD
    22. organ morphogenesis Source: RGD
    23. organ regeneration Source: RGD
    24. palate development Source: Ensembl
    25. pathway-restricted SMAD protein phosphorylation Source: Ensembl
    26. patterning of blood vessels Source: Ensembl
    27. peptidyl-serine phosphorylation Source: Ensembl
    28. peptidyl-threonine phosphorylation Source: Ensembl
    29. positive regulation of B cell tolerance induction Source: Ensembl
    30. positive regulation of epithelial cell migration Source: Ensembl
    31. positive regulation of mesenchymal cell proliferation Source: Ensembl
    32. positive regulation of NK T cell differentiation Source: Ensembl
    33. positive regulation of reactive oxygen species metabolic process Source: Ensembl
    34. positive regulation of skeletal muscle tissue regeneration Source: RGD
    35. positive regulation of smooth muscle cell proliferation Source: RGD
    36. positive regulation of T cell tolerance induction Source: Ensembl
    37. positive regulation of tolerance induction to self antigen Source: Ensembl
    38. receptor-mediated endocytosis Source: RGD
    39. response to cholesterol Source: Ensembl
    40. response to drug Source: Ensembl
    41. response to estrogen Source: RGD
    42. response to glucose Source: RGD
    43. response to hypoxia Source: RGD
    44. response to mechanical stimulus Source: RGD
    45. response to nutrient Source: RGD
    46. response to organic cyclic compound Source: RGD
    47. response to organic substance Source: RGD
    48. response to steroid hormone Source: RGD
    49. smoothened signaling pathway Source: Ensembl
    50. trachea formation Source: Ensembl
    51. transforming growth factor beta receptor signaling pathway Source: RGD
    52. vasculogenesis Source: RGD
    53. wound healing 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_194652. TGFBR2 MSI Frameshift 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-2 (EC:2.7.11.30)
    Short name:
    TGFR-2
    Alternative name(s):
    TGF-beta type II receptor
    Transforming growth factor-beta receptor type II
    Short name:
    TGF-beta receptor type II
    Short name:
    TbetaR-II
    Gene namesi
    Name:Tgfbr2
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Chromosome 8

    Organism-specific databases

    RGDi69651. Tgfbr2.

    Subcellular locationi

    GO - Cellular componenti

    1. caveola Source: MGI
    2. cell surface Source: RGD
    3. cytoplasm Source: RGD
    4. cytosol Source: RGD
    5. external side of plasma membrane Source: Ensembl
    6. integral component of plasma membrane Source: RGD
    7. membrane raft Source: MGI
    8. transforming growth factor beta receptor homodimeric complex Source: RGD

    Keywords - Cellular componenti

    Cell membrane, Membrane

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2323Sequence AnalysisAdd
    BLAST
    Chaini24 – 567544TGF-beta receptor type-2PRO_0000024429Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi51 ↔ 84By similarity
    Disulfide bondi54 ↔ 71By similarity
    Disulfide bondi61 ↔ 67By similarity
    Glycosylationi70 – 701N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi77 ↔ 101By similarity
    Glycosylationi94 – 941N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi121 ↔ 136By similarity
    Disulfide bondi138 ↔ 143By similarity
    Modified residuei548 – 5481PhosphoserineBy similarity
    Modified residuei553 – 5531PhosphoserineBy similarity

    Post-translational modificationi

    Phosphorylated on a Ser/Thr residue in the cytoplasmic domain.

    Keywords - PTMi

    Disulfide bond, Glycoprotein, Phosphoprotein

    Proteomic databases

    PaxDbiP38438.
    PRIDEiP38438.

    Expressioni

    Gene expression databases

    ArrayExpressiP38438.
    GenevestigatoriP38438.

    Interactioni

    Subunit structurei

    Homodimer. 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 TGFRB1 and TGFRB2 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 DAXX. Interacts with TCTEX1D4. Interacts with ZFYVE9; ZFYVE9 recruits SMAD2 and SMAD3 to the TGF-beta receptor By similarity. Interacts with and is activated by SCUBE3; this interaction does not affect TGFB1-binding to TGFBR2 By similarity. Interacts with VPS39; this interaction is independent of the receptor kinase activity and of the presence of TGF-beta By similarity.By similarity

    Protein-protein interaction databases

    BioGridi249668. 1 interaction.
    IntActiP38438. 1 interaction.
    STRINGi10116.ENSRNOP00000017950.

    Structurei

    3D structure databases

    ProteinModelPortaliP38438.
    SMRiP38438. Positions 40-159.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini24 – 166143ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini188 – 567380CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei167 – 18721HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini244 – 546303Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Contains 1 protein kinase domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Signal, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiCOG0515.
    GeneTreeiENSGT00560000076906.
    HOGENOMiHOG000231495.
    HOVERGENiHBG104975.
    KOiK04388.
    OMAiWETSKPR.
    OrthoDBiEOG7JHM5B.
    PhylomeDBiP38438.

    Family and domain databases

    InterProiIPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR008271. Ser/Thr_kinase_AS.
    IPR000333. TGFB_receptor.
    IPR017194. Transform_growth_fac-b_typ-2.
    IPR015013. Transforming_GF_b_rcpt_2_ecto.
    [Graphical view]
    PANTHERiPTHR23255. PTHR23255. 1 hit.
    PfamiPF08917. ecTbetaR2. 1 hit.
    PF00069. Pkinase. 1 hit.
    [Graphical view]
    PIRSFiPIRSF037393. TGFRII. 1 hit.
    PRINTSiPR00653. ACTIVIN2R.
    SUPFAMiSSF56112. SSF56112. 1 hit.
    PROSITEiPS00107. 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.

    P38438-1 [UniParc]FASTAAdd to Basket

    « Hide

    MGRGLLRGLW PLHIVLWTRI ASTIPPHVPK SVNSDLMAGD NSGAVKLPQL    50
    CKFCDVTLST CDNQKSCMSN CSVTSICEKP QEVCVAVWRK NDKNITLETV 100
    CHDPKFTYHG FTLEDATSPT CVMKEKKRAG ETFFMCSCNT EECNDYIIFN 150
    EEYTTSSPDL LLVIIQVTGV SLLPPLGIAI AVIAIFYCYR VHRQQKLSPS 200
    WESSKPRKLM DFSDNCAIIL EDDRSDISST CANNINHNTE LLPIELDTLV 250
    GKGRFAEVYK AKLKQNTSEQ FETVAVKIFP YEEYSSWKTE KDIFSDINLK 300
    HENILQFLTA EERKTEMGKQ YWLITAFHAK GNLQEYLTRH VISWEDLRKL 350
    GSSLARGIAH LHSDHTPCGR PKMPIVHRDL KSSNILVKND LTCCLCDFGL 400
    SLRLDPTLSV DDLANSGQVG TARYMAPEVL ESRMNLENME SFKQTDVYSM 450
    ALVLWEMTSR CNAVGEVKDY EPPFGSKVRE HPCVESMKDN VLRDRGRPEI 500
    PSFWLNHQGI QIVCETLTEC WDHDPEARLT AQCVAERFSE LEHPDRLSGR 550
    SCSQEKIPED GSLNTTK 567
    Length:567
    Mass (Da):64,241
    Last modified:October 1, 1994 - v1
    Checksum:iEC1D7642A51A3B75
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti388 – 3892KN → RS in AAB29352. (PubMed:8264154)Curated
    Sequence conflicti403 – 4031R → G in AAB29352. (PubMed:8264154)Curated
    Sequence conflicti405 – 4051D → S in AAB29352. (PubMed:8264154)Curated
    Sequence conflicti477 – 4771K → R in AAB29352. (PubMed:8264154)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L09653 mRNA. Translation: AAA42237.1.
    S67770 mRNA. Translation: AAB29352.2.
    PIRiJN0459.
    RefSeqiNP_112394.3. NM_031132.3.
    UniGeneiRn.9954.

    Genome annotation databases

    EnsembliENSRNOT00000037883; ENSRNOP00000035501; ENSRNOG00000013265.
    GeneIDi81810.
    KEGGirno:81810.
    UCSCiRGD:69651. rat.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L09653 mRNA. Translation: AAA42237.1 .
    S67770 mRNA. Translation: AAB29352.2 .
    PIRi JN0459.
    RefSeqi NP_112394.3. NM_031132.3.
    UniGenei Rn.9954.

    3D structure databases

    ProteinModelPortali P38438.
    SMRi P38438. Positions 40-159.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 249668. 1 interaction.
    IntActi P38438. 1 interaction.
    STRINGi 10116.ENSRNOP00000017950.

    Proteomic databases

    PaxDbi P38438.
    PRIDEi P38438.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSRNOT00000037883 ; ENSRNOP00000035501 ; ENSRNOG00000013265 .
    GeneIDi 81810.
    KEGGi rno:81810.
    UCSCi RGD:69651. rat.

    Organism-specific databases

    CTDi 7048.
    RGDi 69651. Tgfbr2.

    Phylogenomic databases

    eggNOGi COG0515.
    GeneTreei ENSGT00560000076906.
    HOGENOMi HOG000231495.
    HOVERGENi HBG104975.
    KOi K04388.
    OMAi WETSKPR.
    OrthoDBi EOG7JHM5B.
    PhylomeDBi P38438.

    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_194652. TGFBR2 MSI Frameshift 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

    NextBioi 615691.
    PROi P38438.

    Gene expression databases

    ArrayExpressi P38438.
    Genevestigatori P38438.

    Family and domain databases

    InterProi IPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR008271. Ser/Thr_kinase_AS.
    IPR000333. TGFB_receptor.
    IPR017194. Transform_growth_fac-b_typ-2.
    IPR015013. Transforming_GF_b_rcpt_2_ecto.
    [Graphical view ]
    PANTHERi PTHR23255. PTHR23255. 1 hit.
    Pfami PF08917. ecTbetaR2. 1 hit.
    PF00069. Pkinase. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF037393. TGFRII. 1 hit.
    PRINTSi PR00653. ACTIVIN2R.
    SUPFAMi SSF56112. SSF56112. 1 hit.
    PROSITEi PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Molecular characterization of rat transforming growth factor-beta type II receptor."
      Tsuchida K., Lewis K.A., Mathews L.S., Vale W.W.
      Biochem. Biophys. Res. Commun. 191:790-795(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Strain: Sprague-Dawley.
      Tissue: Pituitary.
    2. "Rat mesangial cell hypertrophy in response to transforming growth factor-beta 1."
      Choi M.E., Kim E.G., Huang Q., Ballermann B.J.
      Kidney Int. 44:948-958(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].

    Entry informationi

    Entry nameiTGFR2_RAT
    AccessioniPrimary (citable) accession number: P38438
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 1, 1994
    Last sequence update: October 1, 1994
    Last modified: October 1, 2014
    This is version 127 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