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FLASH GENE
Symbol TGFB1 contributors: mct/shn - updated : 03-07-2016
HGNC name transforming growth factor, beta 1
HGNC id 11766
Corresponding disease
DPD1 Camurati-Engelmann disease
Location 19q13.2      Physical location : 41.836.812 - 41.859.831
Synonym name
  • latency-associated peptide
  • TGF-beta 1 protein
  • TGF-beta-1
  • Camurati-Engelmann disease
  • transforming growth factor beta-1
  • Synonym symbol(s) TGFB, CED, LAP, TGFbeta, DPD1
    DNA
    TYPE functioning gene
    STRUCTURE 23.02 kb     7 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Map cen - D19S718 - D19S400 - TGFB1 - D19S198 - D19S423 - qter
    Physical map
    CYP2T2P 19q13.2 cytochrome P450, family 2, subfamily T, polypeptide 2 pseudogene CYP2F1P 19q13.2 cytochrome P450, family 2, subfamily F, polypeptide 1 pseudogene CYP2A6 19q13.2 cytochrome P450, family 2, subfamily A, polypeptide 6 CYP2A7 19q13.2 cytochrome P450, family 2, subfamily A, polypeptide 7 CYP2G1 19q13.2 cytochrome P450, family 2, subfamily G, polypeptide 1 pseudogene CYP2A7P1 19q13.2 cytochrome P450, family 2, subfamily A, polypeptide 7 pseudogene 1 CYP2B7 19q13.2 cytochrome P450, family 2, subfamily B, polypeptide 7 pseudogene CYP2B6 19q13.2 cytochrome P450, family 2, subfamily B, polypeptide 6 CYP2G2 19pter-p13.3 cytochrome P450, family 2, subfamily G, polypeptide 2 CYP2A13 19q13.2 cytochrome P450, family 2, subfamily A, polypeptide 13 CYP2F1 19q13.2 cytochrome P450, family 2, subfamily F, polypeptide 1 CYP2T3P 19q13.32 cytochrome P450, family 2, subfamily T, polypeptide 3 pseudogene CYP2S1 19q13.1 cytochrome P450, family 2, subfamily S, polypeptide 1 AXL 19q13.1 AXL receptor tyrosine kinase E1B-AP5 19q13.31 E1B-55kDa-associated protein 5 MGC20255 19q13.31 hypothetical protein MGC20255 TGFB1 19q13.2 transforming growth factor, beta 1 (Camurati-Engelmann disease) MGC4093 19q13.31 hypothetical protein MGC4093 RRP46 19q13.1 exosome component Rrp46 BCKDHA 19q13.2 branched chain keto acid dehydrogenase E1, alpha polypeptide (maple syrup urine disease) BGALT15 19q13.31 beta galactosyltransferase BGALT15 FLJ10241 19q13.31 hypothetical protein FLJ10241 LOC388543 19 LOC388543 LOC283855 19q13.31 similar to tropomyosin 3 PLEKHA3P1 19 pleckstrin homology domain-containing, family A member 3 pseudogene 1 R29124_1 19q13.31 hypothetical protein R29124_1 CEACAMP3 19q13.2 carcinoembryonic antigen-related cell adhesion molecule pseudogene 3 CEACAM4 19q13.2 carcinoembryonic antigen-related cell adhesion molecule 4 CEACAM7 19q13.2 carcinoembryonic antigen-related cell adhesion molecule 7 CEACAM5 19q13.2 carcinoembryonic antigen-related cell adhesion molecule 5 CEACAM6 19q13.2 carcinoembryonic antigen-related cell adhesion molecule 6 (non-specific cross reacting antigen) CEACAM3 19q13.2 carcinoembryonic antigen-related cell adhesion molecule 3
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    7 - 2217 - 390 - - 12489179
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    blood / hematopoieticspleen   highly
    Cardiovascularheart   moderately
    Digestiveliver   moderately
    Endocrinepancreas   highly
    Nervousbrain   highly
    Reproductivefemale systemplacenta  moderately Homo sapiens
     male systemprostate  highly
    Respiratorylung   moderately
    Skin/Tegumentskin    
    Urinarykidney   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoieticbone marrow   
    Connectivebone   
    Epithelialbarrier/lining   
    Epithelialsecretoryglandularendocrine 
    Lymphoid    
    cells
    SystemCellPubmedSpeciesStageRna symbol
     chondrocyte
     fibroblast
    Blood/Hematopoieticmonocyte
    Blood/Hematopoieticplatelet
    Skeletonosteoblast
    cell lineage
    cell lines HEP-G2, TuWi, A172, T24, A431, MCF-7, KB, HT1080, Daudi, Molt-4, PBL-unind, and PL-ind (
    fluid/secretion
    at STAGE
    physiological period embryo
    Text developing cartilage
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • prodomains of TGFB1 and TGFB3 contain an RGD motif that is recognized by alpha5 integrins
  • a signal peptide
  • EGF repeats
  • two latency associated peptide (LAP) domains with two disulfide cysteine bonds
  • a C terminal TGFB sequence
  • mono polymer homomer , dimer
    isoforms Precursor
    HOMOLOGY
    interspecies ortholog to Tgfb1, Rattus norvegicus
    ortholog to Tgfb1, Mus musculus
    ortholog to TGFB1, Pan troglodytes
    intraspecies homolog to TGFB3
    Homologene
    FAMILY
  • TGF beta family
  • CATEGORY regulatory , signaling growth factor
    SUBCELLULAR LOCALIZATION extracellular
    text
  • stored in the extracellular matrix as a latent complex with its prodomain
  • basic FUNCTION
  • stimulating articular chondrocyte cell growth through MAPK3 activation
  • upregulatory factor of CYP19 in human osteoblast-like cells
  • involved in the growth inhibition suppression by the complex Rb/Bog (RBBP9)
  • recruitement and proliferation of osteoblasts and chondrocytes
  • inducing apoptosis in endothelial cells (promoting endothelial cell expression of FGF2, which up-regulates VEGF synthesis)
  • repressing CBFA1 (RUNX2) and osteocalcin genes through the mediation of MADH3
  • playing a pivotal role in the regulation of vasculogenesis and angiogenesis
  • stimulating the phosphorylation of AKT1 and extracellular signal-regulated kinase 1/2 (ERK1/2)
  • enhancing VEGF synthesis via the AKT1 and ERK1/2 activation
  • regulating the expression and intracellular distribution of NFATC1 during early stages of osteoclast differentiation
  • a key regulator of the brain's responses to injury and inflammation (
  • an important modifier of amyloid deposition in vivo and might promote microglial processes that inhibit the accumulation of Abeta in the brain parenchyma (
  • stimulates chondrocyte differentiation and inhibited adipocyte differentiation of hMSCs in vitro Human bone marrow stromal cells (
  • enhances tumor growth and metastasis in the late stages of cancer progression
  • TGFB1-TGFBR1-MAPK signaling in tumor cells promotes tumor angiogenesis
  • role in mediating ovarian oncogenesis by enhancing metastatic potential (
  • functions to couple bone resorption and formation
  • role in the regulation of thyroid function and growth
  • modifier of the course of the monogenic disease cystic fibrosis
  • initiates signaling pathways to fate naive neurites into axons, and directs axon establishment in developing neurons
  • TGFbeta signaling is required to induce CKI (cyclin-dependent kinase inhibitors) expression and cellular senescence and suppress tumor recurrence
  • key factor that establishes oncogene addiction of T-cell lymphomas (interaction between MYC and ZBTB17 is required to antagonize TGFbeta-dependent autocrine signaling during lymphoma formation and maintenance)
  • its antiproliferative activity is essential for maintaining normal tissue homeostasis and is lost in many types of tumors
  • might act in the disassembly of capillaries observed during luteal regression
  • might be responsible for the fascin overexpression in some metastatic tumors
  • promoted fascin expression in spindle tumor cells, implicating that cytokines in the tumor microenvironment could affect fascin expression
  • activates JNK signaling pathway and may be partly responsible for the downregulation of keratocan and lumican expression in activated corneal keratocytes during corneal stromal wound healing (
  • fundamental regulator of immune cell development and function
  • PDGFA and TGFB1 regulate acute respiratory distress syndrome (ARDS)-associated lung fibrosis through distinct signaling pathway-mediated activation of fibrosis-related proteins
  • CELLULAR PROCESS cell life, proliferation/growth
    cell life, antiapoptosis
    nucleotide, transcription, regulation
    cell organization/biogenesis
    PHYSIOLOGICAL PROCESS development , ossification
    PATHWAY
    metabolism
    signaling signal transduction
  • via the SMAD (SMAD2 or SMAD3-SMAD4) complex
  • central pathway involving MMP14 and TGFbeta that mediates vessel stability and vascular response to tissue injury
  • TGFB1-FGF9-PITX2 signaling cascade regulates cranial neural crest cell proliferation during palate formation
  • TGFB1-SMAD4-FGF6 signaling cascade plays a crucial role in myogenic cell fate determination and lineage progression during tongue myogenesis
  • a component
  • forming latent complexes through association to macroglobular alpha 2, and latent TGF beta binding proteins (LTBPs)
  • homodimer, disulfide linked
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • Endoglin (
  • Thrombospondin, TSP (
  • pregnancy zone protein, PZP (
  • biglycan, decorin and fibromodulin (
  • betaglycan (
  • macrophage inflammatory protein-1 alpha, MIP1 (
  • alpha subunit of p21(RAS) farnesyltransferase (FNTA) (
  • Dermatopontin (
  • integrin alpha v beta 6 (
  • Type IIA procollagen (
  • activin receptor-like kinase 1, ALK1 (
  • Latent TGF-beta binding protein-1, LTBP-1
  • rhBMP-2 (
  • death-domain associated protein, DAXX (
  • vitronectin (
  • Latent TGF-beta binding protein-3, LTBP-3 (
  • Abeta-(1-40) (
  • Vasorin (
  • cell surface hyaluronidase Hyal-2 (
  • BMP3
  • TGFB1 signals via IRS2 in kidney epithelial cells
  • WFIKKN1 and WFIKKN2 proteins are antagonists of MSTN and GDF11, but in the case of TGFB1, BMP2 and BMP4 they function as growth factor binding proteins
  • CD109, a GPI-anchored protein, is a TGFB1 co-receptor and a negative regulator of TGFB1 signaling
  • induces SIK1 levels via a direct transcriptional mechanism that implicates the SMAD proteins)
  • non-neural function of PICK1 is an important negative regulator of TGFB1 signaling
  • CITED2 functions as a molecular switch of TGFA and TGFB1-induced growth control
  • AXL expression is induced by TGFB1 during Langerhans cells (LCs) differentiation and LC precursors acquire AXL early during differentiation
  • BAG1 may regulate TGFB1 expression, a key cytokine in normal colonic tissue homoeostasis
  • BAG1 is a repressor of TGFB1, suggesting a new role for BAG1 in colorectal tumorigenesis
  • NR2F2 interacts with SMAD4 to modulate TGFB1 signalling
  • PRRX1 regulates TGFB1 ligand expression in preadipocytes and thereby modulates adipogenesis
  • induction of ANGPTL2 by TGFB1 was dependent on the SMAD3 protein which binds to the SMAD Binding Element (SBE) region located on the ANGPTL2 promoter)
  • crosstalk between the TGFB1 and TP53 pathways defines a major node of regulation in the cellular stress response, enhancing drug resistance
  • TGFB1 induced expression of transcription factors MAFK and BACH1
  • SMAD2 and SMAD3 were redundantly essential for TGFB1 signaling to induce histone modifications for IL9 transcription
  • SMAD2 might regulate TGFB1-dependent cellular responses mediated by TGFB1 signaling inhibition
  • SMAD2 and SMAD3 interact with each other to mediate transforming growth factor-beta (TGFB1)-triggered signaling transduction
  • TGFB1 increased the association of SLC6A4 with the soluble STX3 and promoted exocytosis of SLC6A4
  • CAV1-positive early endosomes may act as a multifunctional device for TGFB1 signaling and TGFB1 receptor recycling and degradation
  • CD109, a glycosylphosphatidylinositol (GPI)-anchored protein, is a novel TGFB1 co-receptor that negatively regulates TGFB1 signalling and responses
  • TGFB1 may be key in controlling the glycosylation of IgA1, in part via the downregulation of C1GALT1 and C1GALT1C1
  • cell & other
    REGULATION
    activated by metalloproteinase-9, MMP9 (
    integrin alpha v beta 6 (
    Thrombospondin-1 (
    Other Secreted protein acidic and rich in cysteine, SPARC (
    ASSOCIATED DISORDERS
    corresponding disease(s) DPD1
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in lymphomas
    Susceptibility
  • to atherosclerosis
  • to progressive diabetic nephropathy with hypertension, hypertensive complications
  • to diabetic retinopathy
  • to obesity (
  • to chronic obstructive pulmonary disease by cigarettes smockers
  • stimulates fibrosis in Duchenne muscular dystrophy (
  • a key determinants of carcinoma cell behavior (
  • TGF-beta hyperresponsiveness observed in scleroderma (
  • Circulating TGF-beta1 concentrations are elevated in Marfan syndrome (
  • increased TGF-beta1 has been found in the central nervous system of patients with Alzheimer's disease, and may be a risk factor for developing Alzheimer's disease(
  • Variant & Polymorphism SNP , other
  • R25P
  • SNP in the promoter region increasing the risk of chronic obstructive pulmonary disease by cigarettes smockers
  • CC homozygote in codon 10 are at higher risk of developing high myopia
  • a modifier of Cystic fibrosis lung disease (
  • Candidate gene could be a modifier gene in cystic fibrosis (codon 10 CC genotype)
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    osteoarticularboneothers
    modulation of TGF-beta1 activity could be an effective treatment for bone remodeling diseases
    cardiovascular  
    TGFB signaling pathway as the primary pharmacological target for the development of new treatment strategies for arterial wall anomalies and osteoarthritis
    dermatologyskin 
    targeting TGFB1 downstream via the profibrotic mediator NOX4 could be a potential anti-fibrotic therapy
    respiratorylung 
    treatments with both PDGFA and TGFB1 antagonists may result in a better anti-fibrotic outcome for acute lung injury (ALI)-induced lung fibrosis
    ANIMAL & CELL MODELS
  • TGF-beta1 induces amyloid-beta deposition in cerebral blood vessels and meninges of aged transgenic mice overexpressing this cytokine from astrocytes (
  • overexpression of TGF-beta1 may initiate or promote amyloidogenesis in Alzheimer's disease (
  • Transgenic mice overexpressing a constitutively active human TGF-beta1 developed fibrosis of the liver, kidney, and adipose tissue, and exhibited a severe reduction in body fat (
  • transgenic mice that overexpress active TGF-beta1 predominantly in the odontoblasts show a significant reduction in the tooth mineralization, defective dentin formation, and a relatively high branching of dentinal tubules (
  • Tgfb1(-/-) survival to birth, in addition to dependence on embryonic Tgfbkm2 genotype, also depends on maternal effects (
  • lack of TGF-beta1 expression in neonatal Tgfb1(-/-) mice results in a widespread increase in degenerating neurons accompanied by reduced expression of synaptophysin and laminin and a prominent microgliosis (
  • TGF-beta1 deficiency in adult Tgfb1(-/+) mice results in increased neuronal susceptibility to excitotoxic injury (
  • transgenic mice expressing wild-type TGFbeta1 in the epidermis developed inflammatory skin lesions, with gross appearance of psoriasis-like plaques, generalized scaly erythema, and Koebner's phenomenon (
  • increased TGF-beta signaling may contribute to the multisystem pathogenesis of mitral valve prolapse, including the development of myxomatous changes of the atrioventricular valves (
  • Specific inactivation of TGFbeta signaling in neural crest stem cells results in cardiovascular defects and thymic, parathyroid, and craniofacial anomalies (
  • aortic aneurysm in a mouse model of Marfan syndrome is associated with increased TGF-beta signaling (
  • male Tgfb1 null mice demonstrate complete inability to mate with females, associated with failure to initiate and/or sustain successful penile intromission or ejaculation
  • mice carrying a Camurati-Engelmann disease-derived mutant TGFB1 show progressive diaphyseal dysplasia (