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P01137

- TGFB1_HUMAN

UniProt

P01137 - TGFB1_HUMAN

Protein

Transforming growth factor beta-1

Gene

TGFB1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 198 (01 Oct 2014)
      Sequence version 2 (01 Feb 1991)
      Previous versions | rss
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    Functioni

    Multifunctional protein that controls proliferation, differentiation and other functions in many cell types. Many cells synthesize TGFB1 and have specific receptors for it. It positively and negatively regulates many other growth factors. It plays an important role in bone remodeling as it is a potent stimulator of osteoblastic bone formation, causing chemotaxis, proliferation and differentiation in committed osteoblasts.

    GO - Molecular functioni

    1. antigen binding Source: UniProt
    2. cytokine activity Source: AgBase
    3. enzyme binding Source: BHF-UCL
    4. glycoprotein binding Source: UniProt
    5. protein binding Source: UniProtKB
    6. type II transforming growth factor beta receptor binding Source: BHF-UCL

    GO - Biological processi

    1. active induction of host immune response by virus Source: Reactome
    2. adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains Source: Ensembl
    3. aging Source: Ensembl
    4. ATP biosynthetic process Source: BHF-UCL
    5. blood coagulation Source: Reactome
    6. branch elongation involved in mammary gland duct branching Source: Ensembl
    7. cell-cell junction organization Source: BHF-UCL
    8. cell cycle arrest Source: BHF-UCL
    9. cell growth Source: InterPro
    10. cellular calcium ion homeostasis Source: Ensembl
    11. cellular response to dexamethasone stimulus Source: Ensembl
    12. cellular response to organic cyclic compound Source: UniProtKB
    13. cellular response to transforming growth factor beta stimulus Source: BHF-UCL
    14. chondrocyte differentiation Source: UniProtKB
    15. common-partner SMAD protein phosphorylation Source: UniProtKB
    16. connective tissue replacement involved in inflammatory response wound healing Source: BHF-UCL
    17. defense response to fungus, incompatible interaction Source: Ensembl
    18. digestive tract development Source: Ensembl
    19. embryo development Source: Ensembl
    20. endoderm development Source: Ensembl
    21. epidermal growth factor receptor signaling pathway Source: BHF-UCL
    22. epithelial to mesenchymal transition Source: Ensembl
    23. evasion or tolerance of host defenses by virus Source: BHF-UCL
    24. extracellular matrix assembly Source: BHF-UCL
    25. extracellular matrix organization Source: Reactome
    26. extrinsic apoptotic signaling pathway Source: BHF-UCL
    27. face morphogenesis Source: Ensembl
    28. female pregnancy Source: Ensembl
    29. frontal suture morphogenesis Source: Ensembl
    30. germ cell migration Source: Ensembl
    31. hematopoietic progenitor cell differentiation Source: UniProtKB
    32. hyaluronan catabolic process Source: UniProtKB
    33. inflammatory response Source: UniProtKB
    34. inner ear development Source: Ensembl
    35. lens fiber cell differentiation Source: Ensembl
    36. lipopolysaccharide-mediated signaling pathway Source: UniProtKB
    37. lymph node development Source: UniProtKB
    38. macrophage derived foam cell differentiation Source: BHF-UCL
    39. mammary gland branching involved in thelarche Source: Ensembl
    40. MAPK cascade Source: UniProtKB
    41. mitotic cell cycle checkpoint Source: BHF-UCL
    42. modulation by virus of host morphology or physiology Source: Reactome
    43. mononuclear cell proliferation Source: Ensembl
    44. myelination Source: Ensembl
    45. myeloid dendritic cell differentiation Source: Ensembl
    46. negative regulation of blood vessel endothelial cell migration Source: BHF-UCL
    47. negative regulation of cell-cell adhesion Source: BHF-UCL
    48. negative regulation of cell cycle Source: HGNC
    49. negative regulation of cell growth Source: BHF-UCL
    50. negative regulation of cell proliferation Source: BHF-UCL
    51. negative regulation of DNA replication Source: BHF-UCL
    52. negative regulation of epithelial cell proliferation Source: BHF-UCL
    53. negative regulation of extracellular matrix disassembly Source: BHF-UCL
    54. negative regulation of fat cell differentiation Source: UniProtKB
    55. negative regulation of gene expression Source: BHF-UCL
    56. negative regulation of hyaluronan biosynthetic process Source: UniProtKB
    57. negative regulation of immune response Source: Ensembl
    58. negative regulation of macrophage cytokine production Source: DFLAT
    59. negative regulation of mitotic cell cycle Source: BHF-UCL
    60. negative regulation of myoblast differentiation Source: UniProtKB
    61. negative regulation of neuroblast proliferation Source: Ensembl
    62. negative regulation of ossification Source: Ensembl
    63. negative regulation of phagocytosis Source: Ensembl
    64. negative regulation of protein phosphorylation Source: BHF-UCL
    65. negative regulation of release of sequestered calcium ion into cytosol Source: Ensembl
    66. negative regulation of skeletal muscle tissue development Source: UniProtKB
    67. negative regulation of T cell proliferation Source: Ensembl
    68. negative regulation of transcription, DNA-templated Source: UniProtKB
    69. negative regulation of transcription from RNA polymerase II promoter Source: Ensembl
    70. negative regulation of transforming growth factor beta receptor signaling pathway Source: Reactome
    71. organ regeneration Source: Ensembl
    72. ossification involved in bone remodeling Source: BHF-UCL
    73. pathway-restricted SMAD protein phosphorylation Source: BHF-UCL
    74. phosphate-containing compound metabolic process Source: BHF-UCL
    75. platelet activation Source: Reactome
    76. platelet degranulation Source: Reactome
    77. positive regulation of apoptotic process Source: Ensembl
    78. positive regulation of blood vessel endothelial cell migration Source: BHF-UCL
    79. positive regulation of bone mineralization Source: BHF-UCL
    80. positive regulation of branching involved in ureteric bud morphogenesis Source: Ensembl
    81. positive regulation of cell cycle arrest Source: Ensembl
    82. positive regulation of cell division Source: UniProtKB-KW
    83. positive regulation of cell migration Source: BHF-UCL
    84. positive regulation of cell proliferation Source: BHF-UCL
    85. positive regulation of cellular protein metabolic process Source: BHF-UCL
    86. positive regulation of chemotaxis Source: BHF-UCL
    87. positive regulation of collagen biosynthetic process Source: BHF-UCL
    88. positive regulation of epithelial cell proliferation Source: Ensembl
    89. positive regulation of epithelial to mesenchymal transition Source: BHF-UCL
    90. positive regulation of exit from mitosis Source: Ensembl
    91. positive regulation of extracellular matrix assembly Source: BHF-UCL
    92. positive regulation of fibroblast migration Source: BHF-UCL
    93. positive regulation of gene expression Source: UniProtKB
    94. positive regulation of histone acetylation Source: Ensembl
    95. positive regulation of histone deacetylation Source: Ensembl
    96. positive regulation of interleukin-17 production Source: BHF-UCL
    97. positive regulation of isotype switching to IgA isotypes Source: MGI
    98. positive regulation of MAP kinase activity Source: BHF-UCL
    99. positive regulation of NAD+ ADP-ribosyltransferase activity Source: BHF-UCL
    100. positive regulation of NF-kappaB transcription factor activity Source: Ensembl
    101. positive regulation of odontogenesis Source: Ensembl
    102. positive regulation of pathway-restricted SMAD protein phosphorylation Source: BHF-UCL
    103. positive regulation of peptidyl-serine phosphorylation Source: BHF-UCL
    104. positive regulation of peptidyl-threonine phosphorylation Source: BHF-UCL
    105. positive regulation of phosphatidylinositol 3-kinase activity Source: BHF-UCL
    106. positive regulation of protein complex assembly Source: BHF-UCL
    107. positive regulation of protein dephosphorylation Source: BHF-UCL
    108. positive regulation of protein import into nucleus Source: BHF-UCL
    109. positive regulation of protein kinase B signaling Source: BHF-UCL
    110. positive regulation of protein phosphorylation Source: BHF-UCL
    111. positive regulation of protein secretion Source: BHF-UCL
    112. positive regulation of SMAD protein import into nucleus Source: BHF-UCL
    113. positive regulation of smooth muscle cell differentiation Source: Ensembl
    114. positive regulation of superoxide anion generation Source: BHF-UCL
    115. positive regulation of transcription, DNA-templated Source: UniProtKB
    116. positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
    117. positive regulation of transcription regulatory region DNA binding Source: BHF-UCL
    118. positive regulation vascular endothelial growth factor production Source: BHF-UCL
    119. protein export from nucleus Source: UniProtKB
    120. protein import into nucleus, translocation Source: UniProtKB
    121. protein kinase B signaling Source: UniProtKB
    122. protein phosphorylation Source: UniProtKB
    123. receptor catabolic process Source: BHF-UCL
    124. regulation of binding Source: UniProtKB
    125. regulation of blood vessel remodeling Source: BHF-UCL
    126. regulation of branching involved in mammary gland duct morphogenesis Source: Ensembl
    127. regulation of cartilage development Source: Ensembl
    128. regulation of cell migration Source: BHF-UCL
    129. regulation of DNA binding Source: UniProtKB
    130. regulation of miRNA metabolic process Source: BHF-UCL
    131. regulation of protein import into nucleus Source: UniProtKB
    132. regulation of sodium ion transport Source: Ensembl
    133. regulation of striated muscle tissue development Source: UniProtKB
    134. regulation of transforming growth factor beta receptor signaling pathway Source: BHF-UCL
    135. regulatory T cell differentiation Source: Ensembl
    136. response to cholesterol Source: BHF-UCL
    137. response to drug Source: Ensembl
    138. response to estradiol Source: BHF-UCL
    139. response to glucose Source: Ensembl
    140. response to hypoxia Source: Ensembl
    141. response to laminar fluid shear stress Source: Ensembl
    142. response to progesterone Source: BHF-UCL
    143. response to radiation Source: Ensembl
    144. response to vitamin D Source: Ensembl
    145. response to wounding Source: BHF-UCL
    146. salivary gland morphogenesis Source: BHF-UCL
    147. SMAD protein complex assembly Source: BHF-UCL
    148. SMAD protein import into nucleus Source: BHF-UCL
    149. T cell homeostasis Source: Ensembl
    150. tolerance induction to self antigen Source: Ensembl
    151. transforming growth factor beta receptor signaling pathway Source: BHF-UCL
    152. ureteric bud development Source: Ensembl
    153. viral life cycle Source: Reactome

    Keywords - Molecular functioni

    Growth factor, Mitogen

    Enzyme and pathway databases

    ReactomeiREACT_120726. TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition).
    REACT_120727. Downregulation of TGF-beta receptor signaling.
    REACT_120850. TGF-beta receptor signaling activates SMADs.
    REACT_150331. Molecules associated with elastic fibres.
    REACT_163906. ECM proteoglycans.
    REACT_163942. Syndecan interactions.
    REACT_169103. SMAD2/3 Phosphorylation Motif Mutants in Cancer.
    REACT_169165. SMAD2/3 MH2 Domain Mutants in Cancer.
    REACT_169192. TGFBR2 MSI Frameshift Mutants in Cancer.
    REACT_169263. TGFBR1 KD Mutants in Cancer.
    REACT_169440. TGFBR2 Kinase Domain Mutants in Cancer.
    REACT_169445. TGFBR1 LBD Mutants in Cancer.
    REACT_27161. Transcriptional regulation of white adipocyte differentiation.
    REACT_6213. Influenza Virus Induced Apoptosis.
    SignaLinkiP01137.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Transforming growth factor beta-1
    Short name:
    TGF-beta-1
    Cleaved into the following chain:
    Gene namesi
    Name:TGFB1
    Synonyms:TGFB
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 19

    Organism-specific databases

    HGNCiHGNC:11766. TGFB1.

    Subcellular locationi

    Secretedextracellular spaceextracellular matrix 1 Publication

    GO - Cellular componenti

    1. axon Source: Ensembl
    2. blood microparticle Source: UniProt
    3. cell surface Source: BHF-UCL
    4. cytoplasm Source: BHF-UCL
    5. extracellular region Source: Reactome
    6. extracellular space Source: BHF-UCL
    7. Golgi lumen Source: Reactome
    8. neuronal cell body Source: Ensembl
    9. nucleus Source: BHF-UCL
    10. plasma membrane Source: Reactome
    11. platelet alpha granule lumen Source: Reactome
    12. proteinaceous extracellular matrix Source: UniProtKB

    Keywords - Cellular componenti

    Extracellular matrix, Secreted

    Pathology & Biotechi

    Involvement in diseasei

    Camurati-Engelmann disease (CE) [MIM:131300]: Autosomal dominant disorder characterized by hyperostosis and sclerosis of the diaphyses of long bones. The disease typically presents in early childhood with pain, muscular weakness and waddling gait, and in some cases other features such as exophthalmos, facial paralysis, hearing difficulties and loss of vision.3 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti81 – 811Y → H in CE; leads to TGF-beta-1 intracellular accumulation. 1 Publication
    VAR_017607
    Natural varianti218 – 2181R → C in CE; higher levels of active TGF-beta-1 in the culture medium; enhances osteoclast formation in vitro. 2 Publications
    VAR_017608
    Natural varianti218 – 2181R → H in CE. 1 Publication
    VAR_017609
    Natural varianti222 – 2221H → D in CE; sporadic case; higher levels of active TGF-beta-1 in the culture medium.
    VAR_017610
    Natural varianti223 – 2231C → G in CE. 1 Publication
    VAR_067303
    Natural varianti223 – 2231C → R in CE. 1 Publication
    VAR_067304
    Natural varianti225 – 2251C → R in CE; higher levels of active TGF-beta-1 in the culture medium. 2 Publications
    VAR_017611

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    MIMi131300. phenotype.
    Orphaneti1328. Camurati-Engelmann disease.
    586. Cystic fibrosis.
    PharmGKBiPA350.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 29291 PublicationAdd
    BLAST
    Chaini30 – 278249Latency-associated peptidePRO_0000033762Add
    BLAST
    Chaini279 – 390112Transforming growth factor beta-1PRO_0000033763Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi33 – 33Interchain (with C-1359 or C-1384 in LTBP1); in inactive formBy similarity
    Glycosylationi82 – 821N-linked (GlcNAc...)2 Publications
    Glycosylationi136 – 1361N-linked (GlcNAc...)By similarity
    Glycosylationi176 – 1761N-linked (GlcNAc...)By similarity
    Disulfide bondi223 – 223Interchain (with C-225)By similarity
    Disulfide bondi225 – 225Interchain (with C-223)By similarity
    Disulfide bondi285 ↔ 294
    Disulfide bondi293 ↔ 356
    Disulfide bondi322 ↔ 387
    Disulfide bondi326 ↔ 389
    Disulfide bondi355 – 355Interchain

    Post-translational modificationi

    Glycosylated.2 Publications
    The precursor is cleaved into mature TGF-beta-1 and LAP, which remains non-covalently linked to mature TGF-beta-1 rendering it inactive.

    Keywords - PTMi

    Cleavage on pair of basic residues, Disulfide bond, Glycoprotein

    Proteomic databases

    MaxQBiP01137.
    PaxDbiP01137.
    PRIDEiP01137.

    2D gel databases

    OGPiP01137.

    PTM databases

    PhosphoSiteiP01137.

    Expressioni

    Tissue specificityi

    Highly expressed in bone. Abundantly expressed in articular cartilage and chondrocytes and is increased in osteoarthritis (OA). Colocalizes with ASPN in chondrocytes within OA lesions of articular cartilage.2 Publications

    Inductioni

    Activated in vitro at pH below 3.5 and over 12.5.

    Gene expression databases

    ArrayExpressiP01137.
    BgeeiP01137.
    CleanExiHS_TGFB1.
    GenevestigatoriP01137.

    Organism-specific databases

    HPAiCAB000361.
    HPA047516.

    Interactioni

    Subunit structurei

    Homodimer; disulfide-linked, or heterodimer with TGFB2 By similarity. Secreted and stored as a biologically inactive form in the extracellular matrix in a 290 kDa complex (large latent TGF-beta1 complex) containing the TGFB1 homodimer, the latency-associated peptide (LAP), and the latent TGFB1 binding protein-1 (LTBP1). The complex without LTBP1 is known as the'small latent TGF-beta1 complex'. Dissociation of the TGFB1 from LAP is required for growth factor activation and biological activity. Release of the large latent TGF-beta1 complex from the extracellular matrix is carried out by the matrix metalloproteinase MMP3 By similarity. May interact with THSD4; this interaction may lead to sequestration by FBN1 microfibril assembly and attenuation of TGFB signaling. Interacts with the serine proteases, HTRA1 and HTRA3: the interaction with either inhibits TGFB1-mediated signaling. The HTRA protease activity is required for this inhibition By similarity. Latency-associated peptide interacts with NREP; the interaction results in a decrease in TGFB1 autoinduction By similarity. Interacts with CD109, DPT and ASPN.By similarity3 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    APPP050673EBI-779636,EBI-77613
    DIP2AQ146892EBI-779636,EBI-2564275
    ENGP178132EBI-779636,EBI-2834630
    FSTL1Q128412EBI-779636,EBI-2349801
    TGFBR1P368972EBI-779636,EBI-1027557
    TGFBR2P371736EBI-779636,EBI-296151
    TGFBR3Q031672EBI-779636,EBI-2852679
    TGFBR3Q909982EBI-779636,EBI-6620843From a different organism.
    THBS1P079962EBI-779636,EBI-2530274

    Protein-protein interaction databases

    BioGridi112898. 32 interactions.
    DIPiDIP-5934N.
    IntActiP01137. 21 interactions.
    MINTiMINT-6806111.
    STRINGi9606.ENSP00000221930.

    Structurei

    Secondary structure

    1
    390
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi282 – 2854
    Beta strandi291 – 2966
    Beta strandi299 – 3013
    Helixi302 – 3065
    Beta strandi311 – 3133
    Beta strandi315 – 3184
    Beta strandi321 – 3244
    Beta strandi330 – 3323
    Helixi335 – 34612
    Beta strandi347 – 3493
    Beta strandi356 – 37015
    Beta strandi373 – 38917

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1KLANMR-A/B279-390[»]
    1KLCNMR-A/B279-390[»]
    1KLDNMR-A/B279-390[»]
    3KFDX-ray3.00A/B/C/D279-390[»]
    ProteinModelPortaliP01137.
    SMRiP01137. Positions 30-390.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP01137.

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni30 – 7445Straightjacket domainBy similarityAdd
    BLAST
    Regioni75 – 271197Arm domainBy similarityAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi244 – 2463Cell attachment siteSequence Analysis

    Domaini

    The 'straitjacket' and 'arm' domains encircle the growth factor monomers and are fastened together by strong bonding between Lys-56 and Tyr-103/Tyr-104. Activation of TGF-beta1 requires the binding of integrin alpha-V to an RGD sequence in the prodomain and exertion of force on this domain, which is held in the extracellular matrix by latent TGF-beta binding proteins. The sheer physical force unfastens the straitjacket and releases the active growth factor dimer By similarity.By similarity

    Sequence similaritiesi

    Belongs to the TGF-beta family.Curated

    Keywords - Domaini

    Signal

    Phylogenomic databases

    eggNOGiNOG279949.
    HOGENOMiHOG000290198.
    HOVERGENiHBG074115.
    InParanoidiP01137.
    KOiK13375.
    PhylomeDBiP01137.
    TreeFamiTF318514.

    Family and domain databases

    Gene3Di2.10.90.10. 1 hit.
    InterProiIPR029034. Cystine-knot_cytokine.
    IPR001839. TGF-b_C.
    IPR001111. TGF-b_N.
    IPR016319. TGF-beta.
    IPR015615. TGF-beta-rel.
    IPR003939. TGFb1.
    IPR017948. TGFb_CS.
    [Graphical view]
    PANTHERiPTHR11848. PTHR11848. 1 hit.
    PfamiPF00019. TGF_beta. 1 hit.
    PF00688. TGFb_propeptide. 1 hit.
    [Graphical view]
    PIRSFiPIRSF001787. TGF-beta. 1 hit.
    PRINTSiPR01423. TGFBETA.
    PR01424. TGFBETA1.
    SMARTiSM00204. TGFB. 1 hit.
    [Graphical view]
    SUPFAMiSSF57501. SSF57501. 1 hit.
    PROSITEiPS00250. TGF_BETA_1. 1 hit.
    PS51362. TGF_BETA_2. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

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

    P01137-1 [UniParc]FASTAAdd to Basket

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    MPPSGLRLLL LLLPLLWLLV LTPGRPAAGL STCKTIDMEL VKRKRIEAIR    50
    GQILSKLRLA SPPSQGEVPP GPLPEAVLAL YNSTRDRVAG ESAEPEPEPE 100
    ADYYAKEVTR VLMVETHNEI YDKFKQSTHS IYMFFNTSEL REAVPEPVLL 150
    SRAELRLLRL KLKVEQHVEL YQKYSNNSWR YLSNRLLAPS DSPEWLSFDV 200
    TGVVRQWLSR GGEIEGFRLS AHCSCDSRDN TLQVDINGFT TGRRGDLATI 250
    HGMNRPFLLL MATPLERAQH LQSSRHRRAL DTNYCFSSTE KNCCVRQLYI 300
    DFRKDLGWKW IHEPKGYHAN FCLGPCPYIW SLDTQYSKVL ALYNQHNPGA 350
    SAAPCCVPQA LEPLPIVYYV GRKPKVEQLS NMIVRSCKCS 390
    Length:390
    Mass (Da):44,341
    Last modified:February 1, 1991 - v2
    Checksum:i75391614250288FE
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti159 – 1591R → RR in CAA26580. (PubMed:3861940)Curated

    Polymorphismi

    In post-menopausal Japanese women, the frequency of Leu-10 is higher in subjects with osteoporosis than in controls.

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti10 – 101L → P Associated with higher bone mineral density and lower frequency of vertebral fractures in Japanese post-menopausal women. 3 Publications
    Corresponds to variant rs1800470 [ dbSNP | Ensembl ].
    VAR_016171
    Natural varianti25 – 251R → P.1 Publication
    Corresponds to variant rs1800471 [ dbSNP | Ensembl ].
    VAR_016172
    Natural varianti81 – 811Y → H in CE; leads to TGF-beta-1 intracellular accumulation. 1 Publication
    VAR_017607
    Natural varianti218 – 2181R → C in CE; higher levels of active TGF-beta-1 in the culture medium; enhances osteoclast formation in vitro. 2 Publications
    VAR_017608
    Natural varianti218 – 2181R → H in CE. 1 Publication
    VAR_017609
    Natural varianti222 – 2221H → D in CE; sporadic case; higher levels of active TGF-beta-1 in the culture medium.
    VAR_017610
    Natural varianti223 – 2231C → G in CE. 1 Publication
    VAR_067303
    Natural varianti223 – 2231C → R in CE. 1 Publication
    VAR_067304
    Natural varianti225 – 2251C → R in CE; higher levels of active TGF-beta-1 in the culture medium. 2 Publications
    VAR_017611
    Natural varianti263 – 2631T → I.
    Corresponds to variant rs1800472 [ dbSNP | Ensembl ].
    VAR_016173

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X05839
    , X05840, X05843, X05844, X05849, X05850 Genomic DNA. Translation: CAA29283.1.
    X02812 mRNA. Translation: CAA26580.1.
    BT007245 mRNA. Translation: AAP35909.1.
    AK291907 mRNA. Translation: BAF84596.1.
    CH471126 Genomic DNA. Translation: EAW57032.1.
    BC001180 mRNA. Translation: AAH01180.1.
    BC000125 mRNA. Translation: AAH00125.1.
    BC022242 mRNA. Translation: AAH22242.1.
    M38449 mRNA. Translation: AAA36735.1.
    CCDSiCCDS33031.1.
    PIRiA27513. WFHU2.
    RefSeqiNP_000651.3. NM_000660.5.
    UniGeneiHs.645227.

    Genome annotation databases

    EnsembliENST00000221930; ENSP00000221930; ENSG00000105329.
    GeneIDi7040.
    KEGGihsa:7040.
    UCSCiuc002oqh.2. human.

    Polymorphism databases

    DMDMi135674.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Web resourcesi

    Wikipedia

    TGF beta-1 entry

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X05839
    , X05840 , X05843 , X05844 , X05849 , X05850 Genomic DNA. Translation: CAA29283.1 .
    X02812 mRNA. Translation: CAA26580.1 .
    BT007245 mRNA. Translation: AAP35909.1 .
    AK291907 mRNA. Translation: BAF84596.1 .
    CH471126 Genomic DNA. Translation: EAW57032.1 .
    BC001180 mRNA. Translation: AAH01180.1 .
    BC000125 mRNA. Translation: AAH00125.1 .
    BC022242 mRNA. Translation: AAH22242.1 .
    M38449 mRNA. Translation: AAA36735.1 .
    CCDSi CCDS33031.1.
    PIRi A27513. WFHU2.
    RefSeqi NP_000651.3. NM_000660.5.
    UniGenei Hs.645227.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1KLA NMR - A/B 279-390 [» ]
    1KLC NMR - A/B 279-390 [» ]
    1KLD NMR - A/B 279-390 [» ]
    3KFD X-ray 3.00 A/B/C/D 279-390 [» ]
    ProteinModelPortali P01137.
    SMRi P01137. Positions 30-390.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 112898. 32 interactions.
    DIPi DIP-5934N.
    IntActi P01137. 21 interactions.
    MINTi MINT-6806111.
    STRINGi 9606.ENSP00000221930.

    Chemistry

    BindingDBi P01137.
    ChEMBLi CHEMBL1795178.
    DrugBanki DB00070. Hyaluronidase.

    PTM databases

    PhosphoSitei P01137.

    Polymorphism databases

    DMDMi 135674.

    2D gel databases

    OGPi P01137.

    Proteomic databases

    MaxQBi P01137.
    PaxDbi P01137.
    PRIDEi P01137.

    Protocols and materials databases

    DNASUi 7040.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000221930 ; ENSP00000221930 ; ENSG00000105329 .
    GeneIDi 7040.
    KEGGi hsa:7040.
    UCSCi uc002oqh.2. human.

    Organism-specific databases

    CTDi 7040.
    GeneCardsi GC19M041837.
    GeneReviewsi TGFB1.
    H-InvDB HIX0015152.
    HGNCi HGNC:11766. TGFB1.
    HPAi CAB000361.
    HPA047516.
    MIMi 131300. phenotype.
    190180. gene.
    neXtProti NX_P01137.
    Orphaneti 1328. Camurati-Engelmann disease.
    586. Cystic fibrosis.
    PharmGKBi PA350.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG279949.
    HOGENOMi HOG000290198.
    HOVERGENi HBG074115.
    InParanoidi P01137.
    KOi K13375.
    PhylomeDBi P01137.
    TreeFami TF318514.

    Enzyme and pathway databases

    Reactomei REACT_120726. TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition).
    REACT_120727. Downregulation of TGF-beta receptor signaling.
    REACT_120850. TGF-beta receptor signaling activates SMADs.
    REACT_150331. Molecules associated with elastic fibres.
    REACT_163906. ECM proteoglycans.
    REACT_163942. Syndecan interactions.
    REACT_169103. SMAD2/3 Phosphorylation Motif Mutants in Cancer.
    REACT_169165. SMAD2/3 MH2 Domain Mutants in Cancer.
    REACT_169192. TGFBR2 MSI Frameshift Mutants in Cancer.
    REACT_169263. TGFBR1 KD Mutants in Cancer.
    REACT_169440. TGFBR2 Kinase Domain Mutants in Cancer.
    REACT_169445. TGFBR1 LBD Mutants in Cancer.
    REACT_27161. Transcriptional regulation of white adipocyte differentiation.
    REACT_6213. Influenza Virus Induced Apoptosis.
    SignaLinki P01137.

    Miscellaneous databases

    ChiTaRSi TGFB1. human.
    EvolutionaryTracei P01137.
    GeneWikii TGF_beta_1.
    GenomeRNAii 7040.
    NextBioi 27507.
    PROi P01137.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P01137.
    Bgeei P01137.
    CleanExi HS_TGFB1.
    Genevestigatori P01137.

    Family and domain databases

    Gene3Di 2.10.90.10. 1 hit.
    InterProi IPR029034. Cystine-knot_cytokine.
    IPR001839. TGF-b_C.
    IPR001111. TGF-b_N.
    IPR016319. TGF-beta.
    IPR015615. TGF-beta-rel.
    IPR003939. TGFb1.
    IPR017948. TGFb_CS.
    [Graphical view ]
    PANTHERi PTHR11848. PTHR11848. 1 hit.
    Pfami PF00019. TGF_beta. 1 hit.
    PF00688. TGFb_propeptide. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF001787. TGF-beta. 1 hit.
    PRINTSi PR01423. TGFBETA.
    PR01424. TGFBETA1.
    SMARTi SM00204. TGFB. 1 hit.
    [Graphical view ]
    SUPFAMi SSF57501. SSF57501. 1 hit.
    PROSITEi PS00250. TGF_BETA_1. 1 hit.
    PS51362. TGF_BETA_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Intron-exon structure of the human transforming growth factor-beta precursor gene."
      Derynck R., Rhee L., Chen E.Y., van Tilburg A.
      Nucleic Acids Res. 15:3188-3189(1987) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    2. "Human transforming growth factor-beta complementary DNA sequence and expression in normal and transformed cells."
      Derynck R., Jarrett J.A., Chen E.Y., Eaton D.H., Bell J.R., Assoian R.K., Roberts A.B., Sporn M.B., Goeddel D.V.
      Nature 316:701-705(1985) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS PRO-10 AND PRO-25.
    3. "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
      Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
      Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    4. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    6. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Duodenum and Eye.
    7. "Cloning and expression of the gene for human transforming growth factor-beta in Escherichia coli."
      Urushizaki Y., Niitsu Y., Terui T., Koshida Y., Mahara K., Kohgo Y., Urushizaki I., Takahashi Y., Ito H.
      Tumor Res. 22:41-55(1987)
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 279-390.
      Tissue: Carcinoma.
    8. "Recombinant human transforming growth factor-beta 1: expression by Chinese hamster ovary cells, isolation, and characterization."
      Bourdrel L., Lin C.-H., Lauren S.L., Elmore R.H., Sugarman B.J., Hu S., Westcott K.R.
      Protein Expr. Purif. 4:130-140(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 279-329.
      Tissue: Urinary bladder carcinoma.
    9. "Cellular receptors for type beta transforming growth factor. Ligand binding and affinity labeling in human and rodent cell lines."
      Massague J., Like B.
      J. Biol. Chem. 260:2636-2645(1985) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 279-301.
    10. "Latent high molecular weight complex of transforming growth factor beta 1. Purification from human platelets and structural characterization."
      Miyazono K., Hellman U., Wernstedt C., Heldin C.H.
      J. Biol. Chem. 263:6407-6415(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 30-42 AND 279-290, CHARACTERIZATION.
    11. "Latent transforming growth factor-beta: structural features and mechanisms of activation."
      Munger J.S., Harpel J.G., Gleizes P.E., Mazzieri R., Nunes I., Rifkin D.B.
      Kidney Int. 51:1376-1382(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.
    12. "Dermatopontin interacts with transforming growth factor beta and enhances its biological activity."
      Okamoto O., Fujiwara S., Abe M., Sato Y.
      Biochem. J. 337:537-541(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH DPT.
    13. "Differential gene expression of cultured human osteoblasts."
      Shur I., Lokiec F., Bleiberg I., Benayahu D.
      J. Cell. Biochem. 83:547-553(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY.
    14. "Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry."
      Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D.
      J. Proteome Res. 4:2070-2080(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-82.
      Tissue: Plasma.
    15. "Identification of CD109 as part of the TGF-beta receptor system in human keratinocytes."
      Finnson K.W., Tam B.Y.Y., Liu K., Marcoux A., Lepage P., Roy S., Bizet A.A., Philip A.
      FASEB J. 20:1525-1527(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH CD109.
    16. "Elucidation of N-glycosylation sites on human platelet proteins: a glycoproteomic approach."
      Lewandrowski U., Moebius J., Walter U., Sickmann A.
      Mol. Cell. Proteomics 5:226-233(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-82.
      Tissue: Platelet.
    17. "Mechanisms for asporin function and regulation in articular cartilage."
      Nakajima M., Kizawa H., Saitoh M., Kou I., Miyazono K., Ikegawa S.
      J. Biol. Chem. 282:32185-32192(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH ASPN.
    18. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    19. "Transforming growth factor beta 1: NMR signal assignments of the recombinant protein expressed and isotopically enriched using Chinese hamster ovary cells."
      Archer S.J., Bax A., Roberts A.B., Sporn M.B., Ogawa Y., Piez K.A., Weatherbee J.A., Tsang M.L.-S., Lucas R., Zheng B.-L., Wenker J., Torchia D.A.
      Biochemistry 32:1152-1163(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR OF 279-390.
    20. "Transforming growth factor beta 1: secondary structure as determined by heteronuclear magnetic resonance spectroscopy."
      Archer S.J., Bax A., Roberts A.B., Sporn M.B., Ogawa Y., Piez K.A., Weatherbee J.A., Tsang M.L.-S., Lucas R., Zheng B.-L., Wenker J., Torchia D.A.
      Biochemistry 32:1164-1171(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR OF 279-390.
    21. "Transforming growth factor beta 1: three-dimensional structure in solution and comparison with the X-ray structure of transforming growth factor beta 2."
      Hinck A.P., Archer S.J., Qian S.W., Roberts A.B., Sporn M.B., Weatherbee J.A., Tsang M.L.-S., Lucas R., Zheng B.-L., Wenker J., Torchia D.A.
      Biochemistry 35:8517-8534(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR OF 279-390.
    22. "Association of a polymorphism of the transforming growth factor-beta1 gene with genetic susceptibility to osteoporosis in postmenopausal Japanese women."
      Yamada Y., Miyauchi A., Goto J., Takagi Y., Okuizumi H., Kanematsu M., Hase M., Takai H., Harada A., Ikeda K.
      J. Bone Miner. Res. 13:1569-1576(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT PRO-10.
    23. Cited for: VARIANTS CE CYS-218; HIS-218 AND ARG-225.
    24. "Mutations in the gene encoding the latency-associated peptide of TGF-beta 1 cause Camurati-Engelmann disease."
      Janssens K., Gershoni-Baruch R., Guanabens N., Migone N., Ralston S., Bonduelle M., Lissens W., Van Maldergem L., Vanhoenacker F., Verbruggen L., Van Hul W.
      Nat. Genet. 26:273-275(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS CE HIS-81; CYS-218 AND ARG-225.
    25. "A catalog of 106 single-nucleotide polymorphisms (SNPs) and 11 other types of variations in genes for transforming growth factor-beta1 (TGF-beta1) and its signaling pathway."
      Watanabe Y., Kinoshita A., Yamada T., Ohta T., Kishino T., Matsumoto N., Ishikawa M., Niikawa N., Yoshiura K.
      J. Hum. Genet. 47:478-483(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT PRO-10.
    26. "Transforming growth factor-beta-1 mutations in Camurati-Engelmann disease lead to increased signaling by altering either activation or secretion of the mutant protein."
      Janssens K., ten Dijke P., Ralston S.H., Bergmann C., Van Hul W.
      J. Biol. Chem. 278:7718-7724(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: CHARACTERIZATION OF VARIANTS CE HIS-81; CYS-218; ASP-222 AND ARG-225.
    27. "A mutation affecting the latency-associated peptide of TGFbeta1 in Camurati-Engelmann disease enhances osteoclast formation in vitro."
      McGowan N.W., MacPherson H., Janssens K., Van Hul W., Frith J.C., Fraser W.D., Ralston S.H., Helfrich M.H.
      J. Clin. Endocrinol. Metab. 88:3321-3326(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: CHARACTERIZATION OF VARIANT CE CYS-218.
    28. "TGFB1 mutations in four new families with Camurati-Engelmann disease: confirmation of independently arising LAP-domain-specific mutations."
      Kinoshita A., Fukumaki Y., Shirahama S., Miyahara A., Nishimura G., Haga N., Namba A., Ueda H., Hayashi H., Ikegawa S., Seidel J., Niikawa N., Yoshiura K.
      Am. J. Med. Genet. 127A:104-107(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS CE GLY-223 AND ARG-223.

    Entry informationi

    Entry nameiTGFB1_HUMAN
    AccessioniPrimary (citable) accession number: P01137
    Secondary accession number(s): A8K792, Q9UCG4
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 21, 1986
    Last sequence update: February 1, 1991
    Last modified: October 1, 2014
    This is version 198 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 19
      Human chromosome 19: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3