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Protein

Transforming growth factor beta-1

Gene

Tgfb1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -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 (By similarity). Stimulates sustained production of collagen through the activation of CREB3L1 by regulated intramembrane proteolysis (RIP) (By similarity). 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. Mediates SMAD2/3 activation by inducing its phosphorylation and subsequent translocation to the nucleus. Can induce epithelial-to-mesenchymal transition (EMT) and cell migration in various cell types (By similarity).By similarity1 Publication

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionGrowth factor, Mitogen

Enzyme and pathway databases

ReactomeiR-RNO-114608 Platelet degranulation
R-RNO-202733 Cell surface interactions at the vascular wall
R-RNO-2129379 Molecules associated with elastic fibres
R-RNO-2173788 Downregulation of TGF-beta receptor signaling
R-RNO-2173789 TGF-beta receptor signaling activates SMADs
R-RNO-2173791 TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition)
R-RNO-3000170 Syndecan interactions
R-RNO-8941855 RUNX3 regulates CDKN1A transcription
R-RNO-8941858 Regulation of RUNX3 expression and activity
R-RNO-8951936 RUNX3 regulates p14-ARF

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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 1

Organism-specific databases

RGDi69051 Tgfb1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Extracellular matrix, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 29By similarityAdd BLAST29
ChainiPRO_000003377030 – 278Latency-associated peptideAdd BLAST249
ChainiPRO_0000033771279 – 390Transforming growth factor beta-1Add BLAST112

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi33Interchain (with C-1350 or C-1375 in LTBP1); in inactive formBy similarity
Glycosylationi82N-linked (GlcNAc...) asparagineBy similarity1
Glycosylationi136N-linked (GlcNAc...) asparagineBy similarity1
Glycosylationi176N-linked (GlcNAc...) asparagineBy similarity1
Disulfide bondi223Interchain (with C-225)By similarity
Disulfide bondi225Interchain (with C-223)By similarity
Disulfide bondi285 ↔ 294By similarity
Disulfide bondi293 ↔ 356By similarity
Disulfide bondi322 ↔ 387By similarity
Disulfide bondi326 ↔ 389By similarity
Disulfide bondi355InterchainBy similarity

Post-translational modificationi

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

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP17246
PRIDEiP17246

PTM databases

PhosphoSitePlusiP17246

Expressioni

Tissue specificityi

Abundant in the bone matrix.1 Publication

Gene expression databases

BgeeiENSRNOG00000020652
GenevisibleiP17246 RN

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. Interacts with CD109 and DPT. Interacts with ASPN. 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 (via processed form (LAP)) with HSP90AB1; inhibits latent TGFB1 activation (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

BioGridi248721, 1 interactor
DIPiDIP-6247N
STRINGi10116.ENSRNOP00000028051

Structurei

3D structure databases

ProteinModelPortaliP17246
SMRiP17246
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni30 – 74Straightjacket domainBy similarityAdd BLAST45
Regioni75 – 271Arm domainBy similarityAdd BLAST197

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi244 – 246Cell attachment siteSequence analysis3

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

eggNOGiKOG3900 Eukaryota
ENOG410XT8Z LUCA
GeneTreeiENSGT00910000143982
HOGENOMiHOG000290198
HOVERGENiHBG074115
InParanoidiP17246
KOiK13375
OMAiAENKYSQ
OrthoDBiEOG091G0BMM
PhylomeDBiP17246
TreeFamiTF318514

Family and domain databases

Gene3Di2.10.90.10, 1 hit
InterProiView protein in InterPro
IPR029034 Cystine-knot_cytokine
IPR001839 TGF-b_C
IPR001111 TGF-b_propeptide
IPR016319 TGF-beta
IPR015615 TGF-beta-rel
IPR003939 TGFb1
IPR017948 TGFb_CS
PANTHERiPTHR11848 PTHR11848, 1 hit
PfamiView protein in Pfam
PF00019 TGF_beta, 1 hit
PF00688 TGFb_propeptide, 1 hit
PIRSFiPIRSF001787 TGF-beta, 1 hit
PRINTSiPR01423 TGFBETA
PR01424 TGFBETA1
SMARTiView protein in SMART
SM00204 TGFB, 1 hit
SUPFAMiSSF57501 SSF57501, 1 hit
PROSITEiView protein in PROSITE
PS00250 TGF_BETA_1, 1 hit
PS51362 TGF_BETA_2, 1 hit

Sequencei

Sequence statusi: Complete.

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

P17246-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPPSGLRLLP LLLPLPWLLV LTPGRPAAGL STCKTIDMEL VKRKRIEAIR
60 70 80 90 100
GQILSKLRLA SPPSQGEVPP GPLPEAVLAL YNSTRDRVAG ESADPEPEPE
110 120 130 140 150
ADYYAKEVTR VLMVDRNNAI YDKTKDITHS IYMFFNTSDI REAVPEPPLL
160 170 180 190 200
SRAELRLQRF KSTVEQHVEL YQKYSNNSWR YLGNRLLTPT DTPEWLSFDV
210 220 230 240 250
TGVVRQWLNQ GDGIQGFRFS AHCSCDSKDN VLHVEINGIS PKRRGDLGTI
260 270 280 290 300
HDMNRPFLLL MATPLERAQH LHSSRHRRAL DTNYCFSSTE KNCCVRQLYI
310 320 330 340 350
DFRKDLGWKW IHEPKGYHAN FCLGPCPYIW SLDTQYSKVL ALYNQHNPGA
360 370 380 390
SASPCCVPQA LEPLPIVYYV GRKPKVEQLS NMIVRSCKCS
Length:390
Mass (Da):44,329
Last modified:August 1, 1990 - v1
Checksum:i5E21108ED50D853C
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X52498 mRNA Translation: CAA36741.1
AY550025 mRNA Translation: AAS55640.1
BC076380 mRNA Translation: AAH76380.1
PIRiS10219
RefSeqiNP_067589.1, NM_021578.2
UniGeneiRn.40136

Genome annotation databases

EnsembliENSRNOT00000028051; ENSRNOP00000028051; ENSRNOG00000020652
GeneIDi59086
KEGGirno:59086
UCSCiRGD:69051 rat

Similar proteinsi

Entry informationi

Entry nameiTGFB1_RAT
AccessioniPrimary (citable) accession number: P17246
Secondary accession number(s): Q53YM8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: August 1, 1990
Last modified: May 23, 2018
This is version 167 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

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