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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 (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 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)DescriptionActionsGraphical viewLength
Mutagenesisi103Y → A, K or T: Results in spontaneous, non integrin-dependent activation. 1 Publication1
Mutagenesisi104Y → A, C, S or T: Results in spontaneous, non integrin-dependent activation. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 29By similarityAdd BLAST29
ChainiPRO_000003376830 – 278Latency-associated peptideAdd BLAST249
ChainiPRO_0000033769279 – 390Transforming growth factor beta-1Add BLAST112

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi33Interchain (with C-? in LTBP1 TB3 domain); in inactive form1 Publication
Glycosylationi82N-linked (GlcNAc...)1 Publication1
Glycosylationi136N-linked (GlcNAc...)By similarity1
Glycosylationi176N-linked (GlcNAc...)By similarity1
Disulfide bondi223Interchain (with C-225)1 Publication
Disulfide bondi225Interchain (with C-223)1 Publication
Disulfide bondi285 ↔ 2941 Publication
Disulfide bondi293 ↔ 3561 Publication
Disulfide bondi322 ↔ 3871 Publication
Disulfide bondi326 ↔ 3891 Publication
Disulfide bondi355Interchain1 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.
PRIDEiP07200.

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 interactors.
STRINGi9823.ENSSSCP00000003267.

Structurei

Secondary structure

1390
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi31 – 57Combined sources27
Helixi75 – 85Combined sources11
Beta strandi89 – 91Combined sources3
Beta strandi106 – 112Combined sources7
Turni118 – 124Combined sources7
Beta strandi130 – 135Combined sources6
Helixi137 – 143Combined sources7
Beta strandi144 – 146Combined sources3
Turni147 – 149Combined sources3
Beta strandi152 – 159Combined sources8
Beta strandi166 – 173Combined sources8
Beta strandi175 – 177Combined sources3
Beta strandi179 – 187Combined sources9
Beta strandi195 – 199Combined sources5
Helixi201 – 209Combined sources9
Beta strandi215 – 221Combined sources7
Beta strandi223 – 228Combined sources6
Beta strandi231 – 236Combined sources6
Beta strandi251 – 254Combined sources4
Beta strandi256 – 262Combined sources7
Helixi265 – 269Combined sources5
Turni282 – 287Combined sources6
Beta strandi292 – 296Combined sources5
Beta strandi299 – 301Combined sources3
Helixi302 – 306Combined sources5
Beta strandi310 – 313Combined sources4
Beta strandi315 – 318Combined sources4
Beta strandi321 – 324Combined sources4
Turni329 – 331Combined sources3
Helixi337 – 342Combined sources6
Beta strandi348 – 353Combined sources6
Beta strandi355 – 358Combined sources4
Beta strandi360 – 370Combined sources11
Beta strandi373 – 384Combined sources12
Beta strandi387 – 390Combined sources4

3D structure databases

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

Family & Domainsi

Region

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

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi244 – 246Cell attachment site3

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)DescriptionActionsGraphical viewLength
Sequence conflicti6 – 7LR → PG in CAA30933 (PubMed:3166520).Curated2
Sequence conflicti180R → G in CAA30933 (PubMed:3166520).Curated1
Sequence conflicti237N → NA in CAA30933 (PubMed:3166520).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti114L → V.3 Publications1

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
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3RJRX-ray3.05A/B/C/D30-390[»]
ProteinModelPortaliP07200.
SMRiP07200.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

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

Proteomic databases

PaxDbiP07200.
PRIDEiP07200.

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...

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: November 30, 2016
This is version 139 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.