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Protein

Transforming growth factor beta-1

Gene

TGFB1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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. Can promote either T-helper 17 cells (Th17) or regulatory T-cells (Treg) lineage differentiation in a concentration-dependent manner. At high concentrations, leads to FOXP3-mediated suppression of RORC and down-regulation of IL-17 expression, favoring Treg cell development. 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

GO - Molecular functioni

  • antigen binding Source: UniProtKB
  • cytokine activity Source: AgBase
  • enzyme binding Source: BHF-UCL
  • glycoprotein binding Source: UniProtKB
  • type III transforming growth factor beta receptor binding Source: AgBase
  • type II transforming growth factor beta receptor binding Source: BHF-UCL
  • type I transforming growth factor beta receptor binding Source: AgBase

GO - Biological processi

  • active induction of host immune response by virus Source: Reactome
  • adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains Source: Ensembl
  • aging Source: Ensembl
  • ATP biosynthetic process Source: BHF-UCL
  • blood coagulation Source: Reactome
  • branch elongation involved in mammary gland duct branching Source: Ensembl
  • cell-cell junction organization Source: BHF-UCL
  • cell cycle arrest Source: BHF-UCL
  • cell development Source: GO_Central
  • cell growth Source: InterPro
  • cellular calcium ion homeostasis Source: Ensembl
  • cellular response to dexamethasone stimulus Source: Ensembl
  • cellular response to organic cyclic compound Source: UniProtKB
  • cellular response to transforming growth factor beta stimulus Source: BHF-UCL
  • chondrocyte differentiation Source: UniProtKB
  • common-partner SMAD protein phosphorylation Source: UniProtKB
  • connective tissue replacement involved in inflammatory response wound healing Source: BHF-UCL
  • defense response to fungus, incompatible interaction Source: Ensembl
  • digestive tract development Source: Ensembl
  • endoderm development Source: Ensembl
  • epidermal growth factor receptor signaling pathway Source: BHF-UCL
  • epithelial to mesenchymal transition Source: Ensembl
  • evasion or tolerance of host defenses by virus Source: BHF-UCL
  • extracellular matrix assembly Source: BHF-UCL
  • extracellular matrix organization Source: Reactome
  • extrinsic apoptotic signaling pathway Source: BHF-UCL
  • face morphogenesis Source: Ensembl
  • female pregnancy Source: Ensembl
  • frontal suture morphogenesis Source: Ensembl
  • germ cell migration Source: Ensembl
  • hematopoietic progenitor cell differentiation Source: UniProtKB
  • hyaluronan catabolic process Source: UniProtKB
  • inflammatory response Source: UniProtKB
  • inner ear development Source: Ensembl
  • lens fiber cell differentiation Source: Ensembl
  • lipopolysaccharide-mediated signaling pathway Source: UniProtKB
  • lymph node development Source: UniProtKB
  • macrophage derived foam cell differentiation Source: BHF-UCL
  • mammary gland branching involved in thelarche Source: Ensembl
  • MAPK cascade Source: UniProtKB
  • mitotic cell cycle checkpoint Source: BHF-UCL
  • modulation by virus of host morphology or physiology Source: Reactome
  • mononuclear cell proliferation Source: Ensembl
  • myelination Source: Ensembl
  • myeloid dendritic cell differentiation Source: Ensembl
  • negative regulation of blood vessel endothelial cell migration Source: BHF-UCL
  • negative regulation of cell-cell adhesion Source: BHF-UCL
  • negative regulation of cell cycle Source: HGNC
  • negative regulation of cell differentiation Source: CACAO
  • negative regulation of cell growth Source: BHF-UCL
  • negative regulation of cell proliferation Source: BHF-UCL
  • negative regulation of DNA replication Source: BHF-UCL
  • negative regulation of epithelial cell proliferation Source: BHF-UCL
  • negative regulation of extracellular matrix disassembly Source: BHF-UCL
  • negative regulation of fat cell differentiation Source: UniProtKB
  • negative regulation of gene expression Source: BHF-UCL
  • negative regulation of gene silencing by miRNA Source: BHF-UCL
  • negative regulation of hyaluronan biosynthetic process Source: UniProtKB
  • negative regulation of interleukin-17 production Source: Ensembl
  • negative regulation of macrophage cytokine production Source: DFLAT
  • negative regulation of mitotic cell cycle Source: BHF-UCL
  • negative regulation of myoblast differentiation Source: UniProtKB
  • negative regulation of neuroblast proliferation Source: Ensembl
  • negative regulation of ossification Source: Ensembl
  • negative regulation of phagocytosis Source: Ensembl
  • negative regulation of protein phosphorylation Source: BHF-UCL
  • negative regulation of release of sequestered calcium ion into cytosol Source: Ensembl
  • negative regulation of skeletal muscle tissue development Source: UniProtKB
  • negative regulation of T cell proliferation Source: Ensembl
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • negative regulation of transcription from RNA polymerase II promoter Source: Ensembl
  • negative regulation of transforming growth factor beta receptor signaling pathway Source: Reactome
  • oligodendrocyte development Source: Ensembl
  • organ regeneration Source: Ensembl
  • ossification involved in bone remodeling Source: BHF-UCL
  • pathway-restricted SMAD protein phosphorylation Source: BHF-UCL
  • phosphate-containing compound metabolic process Source: BHF-UCL
  • platelet activation Source: Reactome
  • platelet degranulation Source: Reactome
  • positive regulation of apoptotic process Source: Ensembl
  • positive regulation of blood vessel endothelial cell migration Source: BHF-UCL
  • positive regulation of bone mineralization Source: BHF-UCL
  • positive regulation of branching involved in ureteric bud morphogenesis Source: Ensembl
  • positive regulation of cell cycle arrest Source: Ensembl
  • positive regulation of cell migration Source: BHF-UCL
  • positive regulation of cell proliferation Source: BHF-UCL
  • positive regulation of cellular protein metabolic process Source: BHF-UCL
  • positive regulation of chemotaxis Source: BHF-UCL
  • positive regulation of collagen biosynthetic process Source: BHF-UCL
  • positive regulation of epithelial cell proliferation Source: Ensembl
  • positive regulation of epithelial to mesenchymal transition Source: BHF-UCL
  • positive regulation of exit from mitosis Source: Ensembl
  • positive regulation of extracellular matrix assembly Source: BHF-UCL
  • positive regulation of fibroblast migration Source: BHF-UCL
  • positive regulation of gene expression Source: UniProtKB
  • positive regulation of histone acetylation Source: Ensembl
  • positive regulation of histone deacetylation Source: Ensembl
  • positive regulation of interleukin-17 production Source: BHF-UCL
  • positive regulation of isotype switching to IgA isotypes Source: MGI
  • positive regulation of MAP kinase activity Source: BHF-UCL
  • positive regulation of NAD+ ADP-ribosyltransferase activity Source: BHF-UCL
  • positive regulation of NF-kappaB transcription factor activity Source: Ensembl
  • positive regulation of odontogenesis Source: Ensembl
  • positive regulation of pathway-restricted SMAD protein phosphorylation Source: BHF-UCL
  • positive regulation of peptidyl-serine phosphorylation Source: BHF-UCL
  • positive regulation of peptidyl-threonine phosphorylation Source: BHF-UCL
  • positive regulation of phosphatidylinositol 3-kinase activity Source: BHF-UCL
  • positive regulation of protein complex assembly Source: BHF-UCL
  • positive regulation of protein dephosphorylation Source: BHF-UCL
  • positive regulation of protein import into nucleus Source: BHF-UCL
  • positive regulation of protein kinase B signaling Source: BHF-UCL
  • positive regulation of protein phosphorylation Source: BHF-UCL
  • positive regulation of protein secretion Source: BHF-UCL
  • positive regulation of SMAD protein import into nucleus Source: BHF-UCL
  • positive regulation of smooth muscle cell differentiation Source: Ensembl
  • positive regulation of superoxide anion generation Source: BHF-UCL
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • positive regulation of transcription regulatory region DNA binding Source: BHF-UCL
  • positive regulation of vascular endothelial growth factor production Source: BHF-UCL
  • protein export from nucleus Source: UniProtKB
  • protein import into nucleus, translocation Source: UniProtKB
  • protein kinase B signaling Source: UniProtKB
  • protein phosphorylation Source: UniProtKB
  • receptor catabolic process Source: BHF-UCL
  • regulation of actin cytoskeleton reorganization Source: Ensembl
  • regulation of apoptotic process Source: GO_Central
  • regulation of binding Source: UniProtKB
  • regulation of blood vessel remodeling Source: BHF-UCL
  • regulation of branching involved in mammary gland duct morphogenesis Source: Ensembl
  • regulation of cartilage development Source: Ensembl
  • regulation of cell migration Source: BHF-UCL
  • regulation of DNA binding Source: UniProtKB
  • regulation of interleukin-23 production Source: Ensembl
  • regulation of protein import into nucleus Source: UniProtKB
  • regulation of sodium ion transport Source: Ensembl
  • regulation of striated muscle tissue development Source: UniProtKB
  • regulation of transforming growth factor beta receptor signaling pathway Source: BHF-UCL
  • regulatory T cell differentiation Source: Ensembl
  • response to cholesterol Source: BHF-UCL
  • response to drug Source: Ensembl
  • response to estradiol Source: BHF-UCL
  • response to glucose Source: Ensembl
  • response to hypoxia Source: Ensembl
  • response to laminar fluid shear stress Source: Ensembl
  • response to progesterone Source: BHF-UCL
  • response to radiation Source: Ensembl
  • response to vitamin D Source: Ensembl
  • response to wounding Source: BHF-UCL
  • salivary gland morphogenesis Source: BHF-UCL
  • SMAD protein complex assembly Source: BHF-UCL
  • SMAD protein import into nucleus Source: BHF-UCL
  • SMAD protein signal transduction Source: GO_Central
  • T cell homeostasis Source: Ensembl
  • tolerance induction to self antigen Source: Ensembl
  • transforming growth factor beta receptor signaling pathway Source: BHF-UCL
  • ureteric bud development Source: Ensembl
  • viral life cycle Source: Reactome
Complete GO annotation...

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_318. Platelet degranulation.
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 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:11766. TGFB1.

Subcellular locationi

GO - Cellular componenti

  • axon Source: Ensembl
  • blood microparticle Source: UniProtKB
  • cell surface Source: BHF-UCL
  • cytoplasm Source: BHF-UCL
  • extracellular region Source: Reactome
  • extracellular space Source: BHF-UCL
  • Golgi lumen Source: Reactome
  • neuronal cell body Source: Ensembl
  • nucleus Source: BHF-UCL
  • plasma membrane Source: Reactome
  • platelet alpha granule lumen Source: Reactome
  • proteinaceous extracellular matrix Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Extracellular matrix, Secreted

Pathology & Biotechi

Involvement in diseasei

Camurati-Engelmann disease (CAEND)3 Publications

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionAn 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.

See also OMIM:131300
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti81 – 811Y → H in CAEND; leads to TGF-beta-1 intracellular accumulation. 2 Publications
VAR_017607
Natural varianti218 – 2181R → C in CAEND; higher levels of active TGF-beta-1 in the culture medium; enhances osteoclast formation in vitro. 4 Publications
VAR_017608
Natural varianti218 – 2181R → H in CAEND. 1 Publication
VAR_017609
Natural varianti222 – 2221H → D in CAEND; sporadic case; higher levels of active TGF-beta-1 in the culture medium. 1 Publication
VAR_017610
Natural varianti223 – 2231C → G in CAEND. 1 Publication
VAR_067303
Natural varianti223 – 2231C → R in CAEND. 1 Publication
VAR_067304
Natural varianti225 – 2251C → R in CAEND; higher levels of active TGF-beta-1 in the culture medium. 3 Publications
VAR_017611

Keywords - Diseasei

Disease mutation

Organism-specific databases

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

Chemistry

DrugBankiDB00070. Hyaluronidase.

Polymorphism and mutation databases

BioMutaiTGFB1.
DMDMi135674.

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

BgeeiP01137.
CleanExiHS_TGFB1.
ExpressionAtlasiP01137. baseline and differential.
GenevisibleiP01137. HS.

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
MEOX2A4D1273EBI-779636,EBI-10172134
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. 42 interactions.
DIPiDIP-5934N.
IntActiP01137. 58 interactions.
MINTiMINT-6806111.
STRINGi9606.ENSP00000221930.

Structurei

Secondary structure

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

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1KLANMR-A/B279-390[»]
1KLCNMR-A/B279-390[»]
1KLDNMR-A/B279-390[»]
3KFDX-ray3.00A/B/C/D279-390[»]
4KV5X-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

« Hide

        10         20         30         40         50
MPPSGLRLLL LLLPLLWLLV LTPGRPAAGL STCKTIDMEL VKRKRIEAIR
60 70 80 90 100
GQILSKLRLA SPPSQGEVPP GPLPEAVLAL YNSTRDRVAG ESAEPEPEPE
110 120 130 140 150
ADYYAKEVTR VLMVETHNEI YDKFKQSTHS IYMFFNTSEL REAVPEPVLL
160 170 180 190 200
SRAELRLLRL KLKVEQHVEL YQKYSNNSWR YLSNRLLAPS DSPEWLSFDV
210 220 230 240 250
TGVVRQWLSR GGEIEGFRLS AHCSCDSRDN TLQVDINGFT TGRRGDLATI
260 270 280 290 300
HGMNRPFLLL MATPLERAQH LQSSRHRRAL DTNYCFSSTE KNCCVRQLYI
310 320 330 340 350
DFRKDLGWKW IHEPKGYHAN FCLGPCPYIW SLDTQYSKVL ALYNQHNPGA
360 370 380 390
SAAPCCVPQA LEPLPIVYYV GRKPKVEQLS NMIVRSCKCS
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 CAEND; leads to TGF-beta-1 intracellular accumulation. 2 Publications
VAR_017607
Natural varianti218 – 2181R → C in CAEND; higher levels of active TGF-beta-1 in the culture medium; enhances osteoclast formation in vitro. 4 Publications
VAR_017608
Natural varianti218 – 2181R → H in CAEND. 1 Publication
VAR_017609
Natural varianti222 – 2221H → D in CAEND; sporadic case; higher levels of active TGF-beta-1 in the culture medium. 1 Publication
VAR_017610
Natural varianti223 – 2231C → G in CAEND. 1 Publication
VAR_067303
Natural varianti223 – 2231C → R in CAEND. 1 Publication
VAR_067304
Natural varianti225 – 2251C → R in CAEND; higher levels of active TGF-beta-1 in the culture medium. 3 Publications
VAR_017611
Natural varianti263 – 2631T → I.
Corresponds to variant rs1800472 [ dbSNP | Ensembl ].
VAR_016173

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Wikipedia

TGF beta-1 entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1KLANMR-A/B279-390[»]
1KLCNMR-A/B279-390[»]
1KLDNMR-A/B279-390[»]
3KFDX-ray3.00A/B/C/D279-390[»]
4KV5X-ray3.00A/B/C/D279-390[»]
ProteinModelPortaliP01137.
SMRiP01137. Positions 30-390.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112898. 42 interactions.
DIPiDIP-5934N.
IntActiP01137. 58 interactions.
MINTiMINT-6806111.
STRINGi9606.ENSP00000221930.

Chemistry

BindingDBiP01137.
ChEMBLiCHEMBL1795178.
DrugBankiDB00070. Hyaluronidase.

PTM databases

PhosphoSiteiP01137.

Polymorphism and mutation databases

BioMutaiTGFB1.
DMDMi135674.

2D gel databases

OGPiP01137.

Proteomic databases

MaxQBiP01137.
PaxDbiP01137.
PRIDEiP01137.

Protocols and materials databases

DNASUi7040.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi7040.
GeneCardsiGC19M041837.
GeneReviewsiTGFB1.
H-InvDBHIX0015152.
HGNCiHGNC:11766. TGFB1.
HPAiCAB000361.
HPA047516.
MIMi131300. phenotype.
190180. gene.
neXtProtiNX_P01137.
Orphaneti1328. Camurati-Engelmann disease.
586. Cystic fibrosis.
PharmGKBiPA350.
GenAtlasiSearch...

Phylogenomic databases

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

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_318. Platelet degranulation.
REACT_6213. Influenza Virus Induced Apoptosis.
SignaLinkiP01137.

Miscellaneous databases

ChiTaRSiTGFB1. human.
EvolutionaryTraceiP01137.
GeneWikiiTGF_beta_1.
GenomeRNAii7040.
NextBioi27507.
PROiP01137.
SOURCEiSearch...

Gene expression databases

BgeeiP01137.
CleanExiHS_TGFB1.
ExpressionAtlasiP01137. baseline and differential.
GenevisibleiP01137. HS.

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]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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 CAEND 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 CAEND 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 CAEND 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 CAEND 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 CAEND 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: July 22, 2015
This is version 208 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.