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Protein

Transforming growth factor beta-1

Gene

TGFB1

Organism
Sus scrofa (Pig)
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. 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

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Growth factor, Mitogen

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
OrganismiSus scrofa (Pig)
Taxonomic identifieri9823 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaSuinaSuidaeSus
Proteomesi
  • UP000008227 Componenti: Unplaced

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Extracellular matrix, Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi103 – 1031Y → A, K or T: Results in spontaneous, non integrin-dependent activation. 1 Publication
Mutagenesisi104 – 1041Y → A, C, S or T: Results in spontaneous, non integrin-dependent activation. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2929By similarityAdd
BLAST
Chaini30 – 278249Latency-associated peptidePRO_0000033768Add
BLAST
Chaini279 – 390112Transforming growth factor beta-1PRO_0000033769Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi33 – 33Interchain (with C-? in LTBP1 TB3 domain); in inactive form1 Publication
Glycosylationi82 – 821N-linked (GlcNAc...)1 Publication
Glycosylationi136 – 1361N-linked (GlcNAc...)By similarity
Glycosylationi176 – 1761N-linked (GlcNAc...)By similarity
Disulfide bondi223 – 223Interchain (with C-225)1 Publication
Disulfide bondi225 – 225Interchain (with C-223)1 Publication
Disulfide bondi285 ↔ 2941 Publication
Disulfide bondi293 ↔ 3561 Publication
Disulfide bondi322 ↔ 3871 Publication
Disulfide bondi326 ↔ 3891 Publication
Disulfide bondi355 – 355Interchain1 Publication

Post-translational modificationi

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

PaxDbiP07200.

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. 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).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
Emilin1Q99K412EBI-907660,EBI-906561From a different organism.
TGFBR2P371732EBI-907660,EBI-296151From a different organism.

GO - Molecular functioni

Protein-protein interaction databases

DIPiDIP-35732N.
IntActiP07200. 3 interactions.
STRINGi9823.ENSSSCP00000003267.

Structurei

Secondary structure

1
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi31 – 5727Combined sources
Helixi75 – 8511Combined sources
Beta strandi89 – 913Combined sources
Beta strandi106 – 1127Combined sources
Turni118 – 1247Combined sources
Beta strandi130 – 1356Combined sources
Helixi137 – 1437Combined sources
Beta strandi144 – 1463Combined sources
Turni147 – 1493Combined sources
Beta strandi152 – 1598Combined sources
Beta strandi166 – 1738Combined sources
Beta strandi175 – 1773Combined sources
Beta strandi179 – 1879Combined sources
Beta strandi195 – 1995Combined sources
Helixi201 – 2099Combined sources
Beta strandi215 – 2217Combined sources
Beta strandi223 – 2286Combined sources
Beta strandi231 – 2366Combined sources
Beta strandi251 – 2544Combined sources
Beta strandi256 – 2627Combined sources
Helixi265 – 2695Combined sources
Turni282 – 2876Combined sources
Beta strandi292 – 2965Combined sources
Beta strandi299 – 3013Combined sources
Helixi302 – 3065Combined sources
Beta strandi310 – 3134Combined sources
Beta strandi315 – 3184Combined sources
Beta strandi321 – 3244Combined sources
Turni329 – 3313Combined sources
Helixi337 – 3426Combined sources
Beta strandi348 – 3536Combined sources
Beta strandi355 – 3584Combined sources
Beta strandi360 – 37011Combined sources
Beta strandi373 – 38412Combined sources
Beta strandi387 – 3904Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3RJRX-ray3.05A/B/C/D30-390[»]
ProteinModelPortaliP07200.
SMRiP07200. Positions 279-390.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni30 – 7445Straightjacket domainAdd
BLAST
Regioni75 – 271197Arm domainAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi244 – 2463Cell attachment site

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 (PubMed:21677751).1 Publication

Sequence similaritiesi

Belongs to the TGF-beta family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG3900. Eukaryota.
ENOG410XT8Z. LUCA.
HOGENOMiHOG000290198.
HOVERGENiHBG074115.
InParanoidiP07200.
KOiK13375.

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.

P07200-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPPSGLRLLP LLLPLLWLLV LTPGRPAAGL STCKTIDMEL VKRKRIEAIR
60 70 80 90 100
GQILSKLRLA SPPSQGDVPP GPLPEAVLAL YNSTRDRVAG ESVEPEPEPE
110 120 130 140 150
ADYYAKEVTR VLMLESGNQI YDKFKGTPHS LYMLFNTSEL REAVPEPVLL
160 170 180 190 200
SRAELRLLRL KLKVEQHVEL YQKYSNDSWR YLSNRLLAPS DSPEWLSFDV
210 220 230 240 250
TGVVRQWLTR REAIEGFRLS AHCSCDSKDN TLHVEINGFN SGRRGDLATI
260 270 280 290 300
HGMNRPFLLL MATPLERAQH LHSSRHRRAL DTNYCFSSTE KNCCVRQLYI
310 320 330 340 350
DFRKDLGWKW IHEPKGYHAN FCLGPCPYIW SLDTQYSKVL ALYNQHNPGA
360 370 380 390
SAAPCCVPQA LEPLPIVYYV GRKPKVEQLS NMIVRSCKCS
Length:390
Mass (Da):44,294
Last modified:April 1, 1988 - v1
Checksum:iA6E2C3659FC384E6
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti6 – 72LR → PG in CAA30933 (PubMed:3166520).Curated
Sequence conflicti180 – 1801R → G in CAA30933 (PubMed:3166520).Curated
Sequence conflicti237 – 2371N → NA in CAA30933 (PubMed:3166520).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti114 – 1141L → V.3 Publications

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y00111 mRNA. Translation: CAA68291.1.
M23703 mRNA. Translation: AAA64616.1.
X12373 mRNA. Translation: CAA30933.1.
AF461808 mRNA. Translation: AAL57902.1.
PIRiA27512.
S01413.
RefSeqiNP_999180.1. NM_214015.1.
UniGeneiSsc.76.

Genome annotation databases

GeneIDi397078.
KEGGissc:397078.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y00111 mRNA. Translation: CAA68291.1.
M23703 mRNA. Translation: AAA64616.1.
X12373 mRNA. Translation: CAA30933.1.
AF461808 mRNA. Translation: AAL57902.1.
PIRiA27512.
S01413.
RefSeqiNP_999180.1. NM_214015.1.
UniGeneiSsc.76.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3RJRX-ray3.05A/B/C/D30-390[»]
ProteinModelPortaliP07200.
SMRiP07200. Positions 279-390.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-35732N.
IntActiP07200. 3 interactions.
STRINGi9823.ENSSSCP00000003267.

Proteomic databases

PaxDbiP07200.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi397078.
KEGGissc:397078.

Organism-specific databases

CTDi7040.

Phylogenomic databases

eggNOGiKOG3900. Eukaryota.
ENOG410XT8Z. LUCA.
HOGENOMiHOG000290198.
HOVERGENiHBG074115.
InParanoidiP07200.
KOiK13375.

Miscellaneous databases

ChiTaRSiTGFB1. pig.

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

  1. "Sequence of the porcine transforming growth factor-beta precursor."
    Derynck R., Rhee L.
    Nucleic Acids Res. 15:3187-3187(1987) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Ovary.
  2. "cDNA cloning of porcine transforming growth factor-beta 1 mRNAs. Evidence for alternate splicing and polyadenylation."
    Kondaiah P., van Obberghen-Schilling E., Ludwig R.L., Dhar R., Sporn M.B., Roberts A.B.
    J. Biol. Chem. 263:18313-18317(1988) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT VAL-114.
    Strain: Miniature swine.
  3. "Nucleotide sequence of chicken transforming growth factor-beta 1 (TGF-beta 1)."
    Jakowlew S.B., Dillard P.J., Sporn M.B., Roberts A.B.
    Nucleic Acids Res. 16:8730-8730(1988) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT VAL-114.
  4. Jakowlew S.B.
    Unpublished observations (MAR-1996)
    Cited for: SHOWS THAT SEQUENCE DESCRIBED IN PUBMED:3166520 ORIGINATES FROM PIG.
  5. "Polymorphism in the porcine transforming growth factor-beta1 gene."
    Wimmers K., Chomdej S., Ponsuksili S., Schellander K.
    Anim. Genet. 33:234-235(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT VAL-114.
  6. "The transforming growth factor-beta system, a complex pattern of cross-reactive ligands and receptors."
    Cheifetz S., Weatherbee J.A., Tsang M.L.S., Anderson J.K., Mole J.E., Lucas R., Massague J.
    Cell 48:409-415(1987) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 279-322.
  7. Cited for: X-RAY CRYSTALLOGRAPHY (3.05 ANGSTROMS) OF 30-390 OF MUTANT SER-33, SUBUNIT, GLYCOSYLATION AT ASN-82, DISULFIDE BONDS, MUTAGENESIS OF TYR-103 AND TYR-104, ACTIVATION MECHANISM.

Entry informationi

Entry nameiTGFB1_PIG
AccessioniPrimary (citable) accession number: P07200
Secondary accession number(s): P08832
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1988
Last sequence update: April 1, 1988
Last modified: March 16, 2016
This is version 136 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Caution

PubMed:3166520 sequence which was said to originate from chicken, seems (Ref. 4) to originate from pig.Curated

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

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 one 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.