This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate a latency-associated peptide (LAP) and a ... See more...

Aliases for TGFB1 Gene

Aliases for TGFB1 Gene

  • Transforming Growth Factor Beta 1 2 3 5
  • Transforming Growth Factor Beta-1 Proprotein 3 4
  • Prepro-Transforming Growth Factor Beta-1 2 3
  • TGFB 3 4
  • Diaphyseal Dysplasia 1, Progressive 2
  • Transforming Growth Factor, Beta 1 2
  • Transforming Growth Factor Beta1 3
  • Latency-Associated Peptide 3
  • Camurati-Engelmann Disease 2
  • TGF-Beta-1 3
  • TGF-Beta1 3
  • IBDIMDE 3
  • TGFbeta 3
  • DPD1 3
  • CED 3
  • LAP 3

External Ids for TGFB1 Gene

Previous HGNC Symbols for TGFB1 Gene

  • TGFB
  • DPD1

Previous GeneCards Identifiers for TGFB1 Gene

  • GC19M042475
  • GC19M042227
  • GC19M046484
  • GC19M046528
  • GC19M041837
  • GC19M038268

Summaries for TGFB1 Gene

Entrez Gene Summary for TGFB1 Gene

  • This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate a latency-associated peptide (LAP) and a mature peptide, and is found in either a latent form composed of a mature peptide homodimer, a LAP homodimer, and a latent TGF-beta binding protein, or in an active form consisting solely of the mature peptide homodimer. The mature peptide may also form heterodimers with other TGFB family members. This encoded protein regulates cell proliferation, differentiation and growth, and can modulate expression and activation of other growth factors including interferon gamma and tumor necrosis factor alpha. This gene is frequently upregulated in tumor cells, and mutations in this gene result in Camurati-Engelmann disease. [provided by RefSeq, Aug 2016]

GeneCards Summary for TGFB1 Gene

TGFB1 (Transforming Growth Factor Beta 1) is a Protein Coding gene. Diseases associated with TGFB1 include Camurati-Engelmann Disease and Inflammatory Bowel Disease, Immunodeficiency, And Encephalopathy. Among its related pathways are Transcription Androgen Receptor nuclear signaling and p70S6K Signaling. Gene Ontology (GO) annotations related to this gene include protein homodimerization activity and enzyme binding. An important paralog of this gene is TGFB3.

UniProtKB/Swiss-Prot Summary for TGFB1 Gene

  • Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active subunit of TGF-beta-1, respectively.
  • Latency-associated peptide: Required to maintain the Transforming growth factor beta-1 (TGF-beta-1) chain in a latent state during storage in extracellular matrix (PubMed:28117447). Associates non-covalently with TGF-beta-1 and regulates its activation via interaction with 'milieu molecules', such as LTBP1, LRRC32/GARP and LRRC33/NRROS, that control activation of TGF-beta-1 (PubMed:2022183, PubMed:8617200, PubMed:8939931, PubMed:19750484, PubMed:22278742, PubMed:19651619). Interaction with LRRC33/NRROS regulates activation of TGF-beta-1 in macrophages and microglia (Probable). Interaction with LRRC32/GARP controls activation of TGF-beta-1 on the surface of activated regulatory T-cells (Tregs) (PubMed:19750484, PubMed:22278742, PubMed:19651619). Interaction with integrins (ITGAV:ITGB6 or ITGAV:ITGB8) results in distortion of the Latency-associated peptide chain and subsequent release of the active TGF-beta-1 (PubMed:22278742, PubMed:28117447).
  • Transforming growth factor beta-1: Multifunctional protein that regulates the growth and differentiation of various cell types and is involved in various processes, such as normal development, immune function, microglia function and responses to neurodegeneration (By similarity). Activation into mature form follows different steps: following cleavage of the proprotein in the Golgi apparatus, Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains remain non-covalently linked rendering TGF-beta-1 inactive during storage in extracellular matrix (PubMed:29109152). At the same time, LAP chain interacts with 'milieu molecules', such as LTBP1, LRRC32/GARP and LRRC33/NRROS that control activation of TGF-beta-1 and maintain it in a latent state during storage in extracellular milieus (PubMed:2022183, PubMed:8617200, PubMed:8939931, PubMed:19750484, PubMed:22278742, PubMed:19651619). TGF-beta-1 is released from LAP by integrins (ITGAV:ITGB6 or ITGAV:ITGB8): integrin-binding to LAP stabilizes an alternative conformation of the LAP bowtie tail and results in distortion of the LAP chain and subsequent release of the active TGF-beta-1 (PubMed:22278742, PubMed:28117447). Once activated following release of LAP, TGF-beta-1 acts by binding to TGF-beta receptors (TGFBR1 and TGFBR2), which transduce signal (PubMed:20207738). While expressed by many cells types, TGF-beta-1 only has a very localized range of action within cell environment thanks to fine regulation of its activation by Latency-associated peptide chain (LAP) and 'milieu molecules' (By similarity). Plays an important role in bone remodeling: acts as a potent stimulator of osteoblastic bone formation, causing chemotaxis, proliferation and differentiation in committed osteoblasts (By similarity). Can promote either T-helper 17 cells (Th17) or regulatory T-cells (Treg) lineage differentiation in a concentration-dependent manner (By similarity). At high concentrations, leads to FOXP3-mediated suppression of RORC and down-regulation of IL-17 expression, favoring Treg cell development (By similarity). At low concentrations in concert with IL-6 and IL-21, leads to expression of the IL-17 and IL-23 receptors, favoring differentiation to Th17 cells (By similarity). Stimulates sustained production of collagen through the activation of CREB3L1 by regulated intramembrane proteolysis (RIP) (PubMed:25310401). Mediates SMAD2/3 activation by inducing its phosphorylation and subsequent translocation to the nucleus (PubMed:25893292, PubMed:29483653). Can induce epithelial-to-mesenchymal transition (EMT) and cell migration in various cell types (PubMed:25893292).

Gene Wiki entry for TGFB1 Gene

Additional gene information for TGFB1 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for TGFB1 Gene

Genomics for TGFB1 Gene

GeneHancer (GH) Regulatory Elements for TGFB1 Gene

Promoters and enhancers for TGFB1 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around TGFB1 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the TGFB1 gene promoter:
  • AhR
  • AP-2gamma
  • Arnt
  • ATF6
  • MAZR
  • Nkx2-5
  • p53
  • PPAR-gamma1
  • PPAR-gamma2

Genomic Locations for TGFB1 Gene

Genomic Locations for TGFB1 Gene
chr19:41,301,587-41,353,933
(GRCh38/hg38)
Size:
52,347 bases
Orientation:
Minus strand
chr19:41,807,492-41,859,831
(GRCh37/hg19)
Size:
52,340 bases
Orientation:
Minus strand

Genomic View for TGFB1 Gene

Genes around TGFB1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
TGFB1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for TGFB1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for TGFB1 Gene

Proteins for TGFB1 Gene

  • Protein details for TGFB1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P01137-TGFB1_HUMAN
    Recommended name:
    Transforming growth factor beta-1 proprotein
    Protein Accession:
    P01137
    Secondary Accessions:
    • A8K792
    • Q9UCG4

    Protein attributes for TGFB1 Gene

    Size:
    390 amino acids
    Molecular mass:
    44341 Da
    Quaternary structure:
    • Homodimer; disulfide-linked (PubMed:20207738, PubMed:25209176, PubMed:28117447, PubMed:29109152). 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). May interact with THSD4; this interaction may lead to sequestration by FBN1 microfibril assembly and attenuation of TGFB signaling (By similarity). Interacts with CD109, DPT and ASPN (PubMed:9895299, PubMed:16754747, PubMed:17827158). Latency-associated peptide: Homodimer; disulfide-linked (PubMed:28117447, PubMed:29109152). Latency-associated peptide: Interacts with Transforming growth factor beta-1 (TGF-beta-1) chain; interaction is non-covalent and maintains (TGF-beta-1) in a latent state; each Latency-associated peptide (LAP) monomer interacts with TGF-beta-1 in the other monomer (PubMed:29109152). Latency-associated peptide: Interacts with LTBP1; leading to regulate activation of TGF-beta-1 (PubMed:2022183, PubMed:8617200, PubMed:8939931). Latency-associated peptide: Interacts with LRRC32/GARP; leading to regulate activation of TGF-beta-1 on the surface of activated regulatory T-cells (Tregs) (PubMed:19750484, PubMed:22278742, PubMed:19651619). Interacts with LRRC33/NRROS; leading to regulate activation of TGF-beta-1 in macrophages and microglia (Probable). Latency-associated peptide: Interacts (via cell attachment site) with integrins ITGAV and ITGB6 (ITGAV:ITGB6), leading to release of the active TGF-beta-1 (PubMed:22278742, PubMed:28117447). Latency-associated peptide: Interacts with NREP; the interaction results in a decrease in TGFB1 autoinduction (By similarity). Latency-associated peptide: Interacts with HSP90AB1; inhibits latent TGFB1 activation (PubMed:20599762). Transforming growth factor beta-1: Homodimer; disulfide-linked (PubMed:20207738, PubMed:25209176, PubMed:28117447, PubMed:29109152). Transforming growth factor beta-1: Interacts with TGF-beta receptors (TGFBR1 and TGFBR2), leading to signal transduction (PubMed:20207738).
    Miscellaneous:
    • TGF-beta-1 is inactivated by fresolimumab (also named GC1008), a monoclonal-neutralizing antibody.

    Three dimensional structures from OCA and Proteopedia for TGFB1 Gene

neXtProt entry for TGFB1 Gene

Post-translational modifications for TGFB1 Gene

  • Transforming growth factor beta-1 proprotein: The precursor proprotein is cleaved in the Golgi apparatus by FURIN to form Transforming growth factor beta-1 (TGF-beta-1) and Latency-associated peptide (LAP) chains, which remain non-covalently linked, rendering TGF-beta-1 inactive.
  • Latency-associated peptide: N-glycosylated (PubMed:3162913, PubMed:2493139, PubMed:28117447). Deglycosylation leads to activation of Transforming growth factor beta-1 (TGF-beta-1); mechanisms triggering deglycosylation-driven activation of TGF-beta-1 are however unclear (PubMed:2493139).
  • Glycosylation at Asn82, Asn136, and Asn176
  • Ubiquitination at Lys291
  • Modification sites at PhosphoSitePlus
  • Glycosylation from GlyConnect
    • TGFB1_HUMAN (1835)

Other Protein References for TGFB1 Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

  • Boster Bio Antibodies for TGFB1

Protein Products

Assay Products

No data available for DME Specific Peptides for TGFB1 Gene

Domains & Families for TGFB1 Gene

Gene Families for TGFB1 Gene

HGNC:
Human Protein Atlas (HPA):
  • Cancer-related genes
  • Candidate cardiovascular disease genes
  • Disease related genes
  • Plasma proteins
  • Predicted intracellular proteins
  • Predicted secreted proteins

Suggested Antigen Peptide Sequences for TGFB1 Gene

GenScript: Design optimal peptide antigens:
  • Transforming growth factor beta 1 (B2C8Z3_HUMAN)
  • Transforming growth factor beta 1 (Q49IK8_HUMAN)
  • Transforming growth factor beta 1 (Q49IL8_HUMAN)
  • Transforming growth factor beta 1 (Q7Z487_HUMAN)
  • Transforming growth factor beta 1 (Q7Z488_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P01137

UniProtKB/Swiss-Prot:

TGFB1_HUMAN :
  • Latency-associated peptide: The 'straitjacket' and 'arm' domains encircle the Transforming growth factor beta-1 (TGF-beta-1) monomers and are fastened together by strong bonding between Lys-56 and Tyr-103/Tyr-104.
  • Belongs to the TGF-beta family.
Domain:
  • Latency-associated peptide: The 'straitjacket' and 'arm' domains encircle the Transforming growth factor beta-1 (TGF-beta-1) monomers and are fastened together by strong bonding between Lys-56 and Tyr-103/Tyr-104.
  • Latency-associated peptide: The cell attachment site motif mediates binding to integrins (ITGAV:ITGB6 or ITGAV:ITGB8) (PubMed:28117447). The motif locates to a long loop in the arm domain called the bowtie tail (PubMed:28117447). Integrin-binding stabilizes an alternative conformation of the bowtie tail (PubMed:28117447). Activation by integrin requires force application by the actin cytoskeleton, which is resisted by the 'milieu molecules' (such as LTBP1, LRRC32/GARP and/or LRRC33/NRROS), resulting in distortion of the prodomain and release of the active TGF-beta-1 (PubMed:28117447).
Family:
  • Belongs to the TGF-beta family.
genes like me logo Genes that share domains with TGFB1: view

Function for TGFB1 Gene

Molecular function for TGFB1 Gene

UniProtKB/Swiss-Prot Function:
Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active subunit of TGF-beta-1, respectively.
UniProtKB/Swiss-Prot Function:
Latency-associated peptide: Required to maintain the Transforming growth factor beta-1 (TGF-beta-1) chain in a latent state during storage in extracellular matrix (PubMed:28117447). Associates non-covalently with TGF-beta-1 and regulates its activation via interaction with 'milieu molecules', such as LTBP1, LRRC32/GARP and LRRC33/NRROS, that control activation of TGF-beta-1 (PubMed:2022183, PubMed:8617200, PubMed:8939931, PubMed:19750484, PubMed:22278742, PubMed:19651619). Interaction with LRRC33/NRROS regulates activation of TGF-beta-1 in macrophages and microglia (Probable). Interaction with LRRC32/GARP controls activation of TGF-beta-1 on the surface of activated regulatory T-cells (Tregs) (PubMed:19750484, PubMed:22278742, PubMed:19651619). Interaction with integrins (ITGAV:ITGB6 or ITGAV:ITGB8) results in distortion of the Latency-associated peptide chain and subsequent release of the active TGF-beta-1 (PubMed:22278742, PubMed:28117447).
UniProtKB/Swiss-Prot Function:
Transforming growth factor beta-1: Multifunctional protein that regulates the growth and differentiation of various cell types and is involved in various processes, such as normal development, immune function, microglia function and responses to neurodegeneration (By similarity). Activation into mature form follows different steps: following cleavage of the proprotein in the Golgi apparatus, Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains remain non-covalently linked rendering TGF-beta-1 inactive during storage in extracellular matrix (PubMed:29109152). At the same time, LAP chain interacts with 'milieu molecules', such as LTBP1, LRRC32/GARP and LRRC33/NRROS that control activation of TGF-beta-1 and maintain it in a latent state during storage in extracellular milieus (PubMed:2022183, PubMed:8617200, PubMed:8939931, PubMed:19750484, PubMed:22278742, PubMed:19651619). TGF-beta-1 is released from LAP by integrins (ITGAV:ITGB6 or ITGAV:ITGB8): integrin-binding to LAP stabilizes an alternative conformation of the LAP bowtie tail and results in distortion of the LAP chain and subsequent release of the active TGF-beta-1 (PubMed:22278742, PubMed:28117447). Once activated following release of LAP, TGF-beta-1 acts by binding to TGF-beta receptors (TGFBR1 and TGFBR2), which transduce signal (PubMed:20207738). While expressed by many cells types, TGF-beta-1 only has a very localized range of action within cell environment thanks to fine regulation of its activation by Latency-associated peptide chain (LAP) and 'milieu molecules' (By similarity). Plays an important role in bone remodeling: acts as a potent stimulator of osteoblastic bone formation, causing chemotaxis, proliferation and differentiation in committed osteoblasts (By similarity). Can promote either T-helper 17 cells (Th17) or regulatory T-cells (Treg) lineage differentiation in a concentration-dependent manner (By similarity). At high concentrations, leads to FOXP3-mediated suppression of RORC and down-regulation of IL-17 expression, favoring Treg cell development (By similarity). At low concentrations in concert with IL-6 and IL-21, leads to expression of the IL-17 and IL-23 receptors, favoring differentiation to Th17 cells (By similarity). Stimulates sustained production of collagen through the activation of CREB3L1 by regulated intramembrane proteolysis (RIP) (PubMed:25310401). Mediates SMAD2/3 activation by inducing its phosphorylation and subsequent translocation to the nucleus (PubMed:25893292, PubMed:29483653). Can induce epithelial-to-mesenchymal transition (EMT) and cell migration in various cell types (PubMed:25893292).
GENATLAS Biochemistry:
transforming growth factor,beta 1,152.6kDa,homodimerizing,expressed by fibroblast,platelet,monocyte,chondrocyte,osteoblasts,stimulating articular chondrocyte cell growth through MAPK3 activation,including the latency associated peptide (LAP),involved in the growth inhibition suppression by the complex Rb/Bog,may be implicated in susceptibility to atherosclerosis,bone diseases or various forms of cancer,regarding the presence of particular alleles at the locus

LifeMap Function Summary for TGFB1 Gene

TGFB1 as growth factor is involved in stem cell differentiation protocols towards the derivation of the following cells:

Phenotypes From GWAS Catalog for TGFB1 Gene

Gene Ontology (GO) - Molecular Function for TGFB1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003823 antigen binding IPI 16754747
GO:0005114 type II transforming growth factor beta receptor binding IBA,IPI 1333888
GO:0005125 cytokine activity TAS 24263861
GO:0005160 transforming growth factor beta receptor binding IBA 21873635
GO:0005515 protein binding IPI 1326540
genes like me logo Genes that share ontologies with TGFB1: view
genes like me logo Genes that share phenotypes with TGFB1: view

Human Phenotype Ontology for TGFB1 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for TGFB1 Gene

MGI Knock Outs for TGFB1:

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for TGFB1

Clone Products

  • Addgene plasmids for TGFB1

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for TGFB1 Gene

Localization for TGFB1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for TGFB1 Gene

Latency-associated peptide: Secreted, extracellular space, extracellular matrix.
Transforming growth factor beta-1: Secreted.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for TGFB1 gene
Compartment Confidence
extracellular 5
nucleus 5
plasma membrane 4
golgi apparatus 4
cytosol 3
cytoskeleton 2
mitochondrion 1
peroxisome 1
endoplasmic reticulum 1
lysosome 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for TGFB1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region TAS --
GO:0005615 extracellular space IBA,IDA 19734317
GO:0005634 nucleus IDA 18040277
GO:0005737 cytoplasm IEA,IDA 18040277
GO:0005796 Golgi lumen TAS --
genes like me logo Genes that share ontologies with TGFB1: view

Pathways & Interactions for TGFB1 Gene

PathCards logo

SuperPathways for TGFB1 Gene

SuperPathway Contained pathways
1 Apoptotic Pathways in Synovial Fibroblasts
.85
.85
.84
.84
.74
.72
.66
.65
.64
.62
.61
.60
.57
.57
2 Loss of Function of SMAD2/3 in Cancer
3 GPCR Pathway
.73
.73
.62
.59
.58
.58
.55
4 ERK Signaling
.61
.61
.58
.51
.49
5 Nanog in Mammalian ESC Pluripotency
.61
.61
.59
.48
genes like me logo Genes that share pathways with TGFB1: view

Pathways by source for TGFB1 Gene

69 Qiagen pathways for TGFB1 Gene
  • 14-3-3 Induced Intracellular Signaling
  • Actin-Based Motility by Rho Family GTPases
  • Activation of cAMP-Dependent PKA
  • Activation of PKA through GPCR
  • Activation of PKC through GPCR
2 Cell Signaling Technology pathways for TGFB1 Gene
1 GeneTex pathway for TGFB1 Gene

Gene Ontology (GO) - Biological Process for TGFB1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription by RNA polymerase II IEA --
GO:0000165 MAPK cascade IMP 21147091
GO:0001570 vasculogenesis IEA,ISS --
GO:0001657 ureteric bud development IEA --
GO:0001666 response to hypoxia IEA --
genes like me logo Genes that share ontologies with TGFB1: view

Drugs & Compounds for TGFB1 Gene

(89) Drugs for TGFB1 Gene - From: DrugBank, PharmGKB, ClinicalTrials, ApexBio, DGIdb, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Aspirin Approved, Vet_approved Pharma Channel blocker 1403
Foreskin fibroblast (neonatal) Approved Pharma Target, agonist 0
Foreskin keratinocyte (neonatal) Approved Pharma Target, agonist 0
Hyaluronidase (ovine) Approved, Investigational Pharma Target, inhibitor 0
Terazosin Approved Pharma Target, inducer α1-adrenergic receptor antagonist 25

(49) Additional Compounds for TGFB1 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs

(2) ApexBio Compounds for TGFB1 Gene

Compound Action Cas Number
EW-7197 Selective inhibitor of TGF-β type I receptor kinase 1352608-82-2
ITD 1 The first selective TGFβ inhibitor 1099644-42-4
genes like me logo Genes that share compounds with TGFB1: view

Transcripts for TGFB1 Gene

mRNA/cDNA for TGFB1 Gene

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for TGFB1