Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Transforming growth factor beta-1

Gene

Tgfb1

Organism
Mus musculus (Mouse)
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 (PubMed:18368049).2 Publications

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Growth factor, Mitogen

Enzyme and pathway databases

ReactomeiREACT_27166. Transcriptional Regulation of Adipocyte Differentiation in 3T3-L1 Pre-adipocytes.
REACT_294284. TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition).
REACT_294789. Downregulation of TGF-beta receptor signaling.
REACT_297798. TGF-beta receptor signaling activates SMADs.
REACT_307071. Platelet degranulation.
REACT_309805. Transcriptional regulation of white adipocyte differentiation.
REACT_326610. Syndecan interactions.
REACT_332220. Molecules associated with elastic fibres.
REACT_354321. ECM proteoglycans.

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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:98725. Tgfb1.

Subcellular locationi

GO - Cellular componenti

  • axon Source: Ensembl
  • blood microparticle Source: AgBase
  • cell surface Source: BHF-UCL
  • cytoplasm Source: UniProtKB
  • extracellular space Source: BHF-UCL
  • microvillus Source: Ensembl
  • neuronal cell body Source: Ensembl
  • nucleus Source: UniProtKB
  • proteinaceous extracellular matrix Source: MGI
  • secretory granule Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Extracellular matrix, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2929By similarityAdd
BLAST
Chaini30 – 278249Latency-associated peptidePRO_0000033766Add
BLAST
Chaini279 – 390112Transforming growth factor beta-1PRO_0000033767Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi33 – 33Interchain (with C-1350 or C-1375 in LTBP1); in inactive formBy similarity
Glycosylationi82 – 821N-linked (GlcNAc...)By similarity
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 ↔ 294By similarity
Disulfide bondi293 ↔ 356By similarity
Disulfide bondi322 ↔ 387By similarity
Disulfide bondi326 ↔ 389By similarity
Disulfide bondi355 – 355InterchainBy 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

MaxQBiP04202.
PaxDbiP04202.
PRIDEiP04202.

PTM databases

PhosphoSiteiP04202.

Miscellaneous databases

PMAP-CutDBP04202.

Expressioni

Gene expression databases

BgeeiP04202.
CleanExiMM_TGFB1.
ExpressionAtlasiP04202. baseline and differential.
GenevisibleiP04202. MM.

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). Interacts with CD109 and DPT. Interacts with ASPN (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. Latency-associated peptide interacts with NREP; the interaction results in a decrease in TGFB1 autoinduction.By similarity4 Publications

Protein-protein interaction databases

BioGridi204157. 4 interactions.
DIPiDIP-48640N.
STRINGi10090.ENSMUSP00000002678.

Structurei

3D structure databases

ProteinModelPortaliP04202.
SMRiP04202. Positions 30-390.
ModBaseiSearch...
MobiDBiSearch...

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.
GeneTreeiENSGT00760000119112.
HOGENOMiHOG000290198.
HOVERGENiHBG074115.
InParanoidiP04202.
KOiK13375.
OMAiSHSIYMF.
OrthoDBiEOG70GMFT.
PhylomeDBiP04202.
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.

P04202-1 [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 YEKTKDISHS IYMFFNTSDI REAVPEPPLL
160 170 180 190 200
SRAELRLQRL KSSVEQHVEL YQKYSNNSWR YLGNRLLTPT DTPEWLSFDV
210 220 230 240 250
TGVVRQWLNQ GDGIQGFRFS AHCSCDSKDN KLHVEINGIS 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):44,310
Last modified:March 20, 1987 - v1
Checksum:i4381A51B711D689E
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M13177 mRNA. Translation: AAA40423.1.
L42462
, L42456, L42457, L42458, L42459, L42460, L42461 Genomic DNA. Translation: AAB00138.1.
AJ009862 mRNA. Translation: CAA08900.1.
BC013738 mRNA. Translation: AAH13738.1.
CCDSiCCDS20993.1.
PIRiA01396. WFMS2.
RefSeqiNP_035707.1. NM_011577.1.
UniGeneiMm.248380.

Genome annotation databases

EnsembliENSMUST00000002678; ENSMUSP00000002678; ENSMUSG00000002603.
GeneIDi21803.
KEGGimmu:21803.
UCSCiuc009ftq.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M13177 mRNA. Translation: AAA40423.1.
L42462
, L42456, L42457, L42458, L42459, L42460, L42461 Genomic DNA. Translation: AAB00138.1.
AJ009862 mRNA. Translation: CAA08900.1.
BC013738 mRNA. Translation: AAH13738.1.
CCDSiCCDS20993.1.
PIRiA01396. WFMS2.
RefSeqiNP_035707.1. NM_011577.1.
UniGeneiMm.248380.

3D structure databases

ProteinModelPortaliP04202.
SMRiP04202. Positions 30-390.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi204157. 4 interactions.
DIPiDIP-48640N.
STRINGi10090.ENSMUSP00000002678.

PTM databases

PhosphoSiteiP04202.

Proteomic databases

MaxQBiP04202.
PaxDbiP04202.
PRIDEiP04202.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000002678; ENSMUSP00000002678; ENSMUSG00000002603.
GeneIDi21803.
KEGGimmu:21803.
UCSCiuc009ftq.1. mouse.

Organism-specific databases

CTDi7040.
MGIiMGI:98725. Tgfb1.

Phylogenomic databases

eggNOGiNOG279949.
GeneTreeiENSGT00760000119112.
HOGENOMiHOG000290198.
HOVERGENiHBG074115.
InParanoidiP04202.
KOiK13375.
OMAiSHSIYMF.
OrthoDBiEOG70GMFT.
PhylomeDBiP04202.
TreeFamiTF318514.

Enzyme and pathway databases

ReactomeiREACT_27166. Transcriptional Regulation of Adipocyte Differentiation in 3T3-L1 Pre-adipocytes.
REACT_294284. TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition).
REACT_294789. Downregulation of TGF-beta receptor signaling.
REACT_297798. TGF-beta receptor signaling activates SMADs.
REACT_307071. Platelet degranulation.
REACT_309805. Transcriptional regulation of white adipocyte differentiation.
REACT_326610. Syndecan interactions.
REACT_332220. Molecules associated with elastic fibres.
REACT_354321. ECM proteoglycans.

Miscellaneous databases

NextBioi301176.
PMAP-CutDBP04202.
PROiP04202.
SOURCEiSearch...

Gene expression databases

BgeeiP04202.
CleanExiMM_TGFB1.
ExpressionAtlasiP04202. baseline and differential.
GenevisibleiP04202. MM.

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. "The murine transforming growth factor-beta precursor."
    Derynck R., Jarrett J.A., Chen E.Y., Goeddel D.V.
    J. Biol. Chem. 261:4377-4379(1986) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "Molecular organization of the gene encoding murine transforming growth factor beta 1."
    Guron C., Sudarshan C., Raghow R.
    Gene 165:325-326(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: BALB/c.
  3. "Transforming growth factor-beta 1 sequence and expression: no difference between NOD/Lt and C57Bl/6 mouse strains."
    Poirot L., Benoist C., Mathis D.
    Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: C57BL/6 and NOD/LT.
    Tissue: Spleen.
  4. "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].
    Strain: FVB/N.
    Tissue: Mammary tumor.
  5. "P311 binds to the latency associated protein and downregulates the expression of TGF-beta1 and TGF-beta2."
    Paliwal S., Shi J., Dhru U., Zhou Y., Schuger L.
    Biochem. Biophys. Res. Commun. 315:1104-1109(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH NREP.
  6. "Developmentally regulated expression of mouse HtrA3 and its role as an inhibitor of TGF-beta signaling."
    Tocharus J., Tsuchiya A., Kajikawa M., Ueta Y., Oka C., Kawaichi M.
    Dev. Growth Differ. 46:257-274(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HTRA3.
  7. Cited for: INTERACTION WITH HTRA1.
  8. "TGF-beta-induced Foxp3 inhibits T(H)17 cell differentiation by antagonizing RORgammat function."
    Zhou L., Lopes J.E., Chong M.M., Ivanov I.I., Min R., Victora G.D., Shen Y., Du J., Rubtsov Y.P., Rudensky A.Y., Ziegler S.F., Littman D.R.
    Nature 453:236-240(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  9. "ADAMTSL6beta protein rescues fibrillin-1 microfibril disorder in a Marfan syndrome mouse model through the promotion of fibrillin-1 assembly."
    Saito M., Kurokawa M., Oda M., Oshima M., Tsutsui K., Kosaka K., Nakao K., Ogawa M., Manabe R., Suda N., Ganjargal G., Hada Y., Noguchi T., Teranaka T., Sekiguchi K., Yoneda T., Tsuji T.
    J. Biol. Chem. 286:38602-38613(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH THSD4.
  10. "Protein phosphatase 5 modulates SMAD3 function in the transforming growth factor-? pathway."
    Bruce D.L., Macartney T., Yong W., Shou W., Sapkota G.P.
    Cell. Signal. 24:1999-2006(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.

Entry informationi

Entry nameiTGFB1_MOUSE
AccessioniPrimary (citable) accession number: P04202
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 20, 1987
Last sequence update: March 20, 1987
Last modified: July 22, 2015
This is version 171 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. 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.