TGFB1_PIG
ID TGFB1_PIG Reviewed; 390 AA.
AC P07200; K7GQZ2; P08832;
DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot.
DT 10-OCT-2018, sequence version 2.
DT 03-AUG-2022, entry version 173.
DE RecName: Full=Transforming growth factor beta-1 proprotein;
DE Contains:
DE RecName: Full=Latency-associated peptide;
DE Short=LAP;
DE Contains:
DE RecName: Full=Transforming growth factor beta-1;
DE Short=TGF-beta-1;
DE Flags: Precursor;
GN Name=TGFB1;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Ovary;
RX PubMed=3470708; DOI=10.1093/nar/15.7.3187;
RA Derynck R., Rhee L.;
RT "Sequence of the porcine transforming growth factor-beta precursor.";
RL Nucleic Acids Res. 15:3187-3187(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT LEU-114.
RC STRAIN=Miniature swine;
RX PubMed=2461367; DOI=10.1016/s0021-9258(19)81361-3;
RA Kondaiah P., van Obberghen-Schilling E., Ludwig R.L., Dhar R., Sporn M.B.,
RA Roberts A.B.;
RT "cDNA cloning of porcine transforming growth factor-beta 1 mRNAs. Evidence
RT for alternate splicing and polyadenylation.";
RL J. Biol. Chem. 263:18313-18317(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3166520; DOI=10.1093/nar/16.17.8730;
RA Jakowlew S.B., Dillard P.J., Sporn M.B., Roberts A.B.;
RT "Nucleotide sequence of chicken transforming growth factor-beta 1 (TGF-beta
RT 1).";
RL Nucleic Acids Res. 16:8730-8730(1988).
RN [4]
RP SHOWS THAT SEQUENCE DESCRIBED IN PUBMED:3166520 ORIGINATES FROM PIG.
RA Jakowlew S.B.;
RL Unpublished observations (MAR-1996).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=12030934; DOI=10.1046/j.1365-2052.2002.t01-4-00876.x;
RA Wimmers K., Chomdej S., Ponsuksili S., Schellander K.;
RT "Polymorphism in the porcine transforming growth factor-beta1 gene.";
RL Anim. Genet. 33:234-235(2002).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Duroc {ECO:0000312|Ensembl:ENSSSCP00000030317};
RG Porcine genome sequencing project;
RL Submitted (NOV-2009) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP PROTEIN SEQUENCE OF 279-322.
RX PubMed=2879635; DOI=10.1016/0092-8674(87)90192-9;
RA Cheifetz S., Weatherbee J.A., Tsang M.L.S., Anderson J.K., Mole J.E.,
RA Lucas R., Massague J.;
RT "The transforming growth factor-beta system, a complex pattern of cross-
RT reactive ligands and receptors.";
RL Cell 48:409-415(1987).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (3.05 ANGSTROMS) OF 30-390 OF MUTANT SER-33, SUBUNIT,
RP GLYCOSYLATION AT ASN-82 AND ASN-136, DISULFIDE BONDS, MUTAGENESIS OF
RP TYR-103 AND TYR-104, AND ACTIVATION MECHANISM.
RX PubMed=21677751; DOI=10.1038/nature10152;
RA Shi M., Zhu J., Wang R., Chen X., Mi L., Walz T., Springer T.A.;
RT "Latent TGF-beta structure and activation.";
RL Nature 474:343-349(2011).
RN [9] {ECO:0007744|PDB:5VQF}
RP X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) OF 30-390, AND DISULFIDE BONDS.
RX PubMed=29109152; DOI=10.1074/jbc.m117.809657;
RA Zhao B., Xu S., Dong X., Lu C., Springer T.A.;
RT "Prodomain-growth factor swapping in the structure of pro-TGF-beta1.";
RL J. Biol. Chem. 293:1579-1589(2018).
CC -!- FUNCTION: Transforming growth factor beta-1 proprotein: Precursor of
CC the Latency-associated peptide (LAP) and Transforming growth factor
CC beta-1 (TGF-beta-1) chains, which constitute the regulatory and active
CC subunit of TGF-beta-1, respectively. {ECO:0000250|UniProtKB:P01137}.
CC -!- FUNCTION: [Latency-associated peptide]: Required to maintain the
CC Transforming growth factor beta-1 (TGF-beta-1) chain in a latent state
CC during storage in extracellular matrix. Associates non-covalently with
CC TGF-beta-1 and regulates its activation via interaction with 'milieu
CC molecules', such as LTBP1, LRRC32/GARP and LRRC33/NRROS, that control
CC activation of TGF-beta-1. Interaction with LRRC33/NRROS regulates
CC activation of TGF-beta-1 in macrophages and microglia. Interaction with
CC LRRC32/GARP controls activation of TGF-beta-1 on the surface of
CC activated regulatory T-cells (Tregs). Interaction with integrins
CC (ITGAV:ITGB6 or ITGAV:ITGB8) results in distortion of the Latency-
CC associated peptide chain and subsequent release of the active TGF-beta-
CC 1. {ECO:0000250|UniProtKB:P01137}.
CC -!- FUNCTION: [Transforming growth factor beta-1]: Multifunctional protein
CC that regulates the growth and differentiation of various cell types and
CC is involved in various processes, such as normal development, immune
CC function, microglia function and responses to neurodegeneration (By
CC similarity). Activation into mature form follows different steps:
CC following cleavage of the proprotein in the Golgi apparatus, Latency-
CC associated peptide (LAP) and Transforming growth factor beta-1 (TGF-
CC beta-1) chains remain non-covalently linked rendering TGF-beta-1
CC inactive during storage in extracellular matrix. At the same time, LAP
CC chain interacts with 'milieu molecules', such as LTBP1, LRRC32/GARP and
CC LRRC33/NRROS that control activation of TGF-beta-1 and maintain it in a
CC latent state during storage in extracellular milieus. TGF-beta-1 is
CC released from LAP by integrins (ITGAV:ITGB6 or ITGAV:ITGB8): integrin-
CC binding to LAP stabilizes an alternative conformation of the LAP bowtie
CC tail and results in distortion of the LAP chain and subsequent release
CC of the active TGF-beta-1. Once activated following release of LAP, TGF-
CC beta-1 acts by binding to TGF-beta receptors (TGFBR1 and TGFBR2), which
CC transduce signal (By similarity). While expressed by many cells types,
CC TGF-beta-1 only has a very localized range of action within cell
CC environment thanks to fine regulation of its activation by Latency-
CC associated peptide chain (LAP) and 'milieu molecules'. Plays an
CC important role in bone remodeling: acts as a potent stimulator of
CC osteoblastic bone formation, causing chemotaxis, proliferation and
CC differentiation in committed osteoblasts. Can promote either T-helper
CC 17 cells (Th17) or regulatory T-cells (Treg) lineage differentiation in
CC a concentration-dependent manner. At high concentrations, leads to
CC FOXP3-mediated suppression of RORC and down-regulation of IL-17
CC expression, favoring Treg cell development. At low concentrations in
CC concert with IL-6 and IL-21, leads to expression of the IL-17 and IL-23
CC receptors, favoring differentiation to Th17 cells (By similarity).
CC Stimulates sustained production of collagen through the activation of
CC CREB3L1 by regulated intramembrane proteolysis (RIP). Mediates SMAD2/3
CC activation by inducing its phosphorylation and subsequent translocation
CC to the nucleus. Can induce epithelial-to-mesenchymal transition (EMT)
CC and cell migration in various cell types (By similarity).
CC {ECO:0000250|UniProtKB:P01137, ECO:0000250|UniProtKB:P04202}.
CC -!- SUBUNIT: Homodimer; disulfide-linked. Interacts with the serine
CC proteases, HTRA1 and HTRA3: the interaction with either inhibits TGFB1-
CC mediated signaling and the HTRA protease activity is required for this
CC inhibition. May interact with THSD4; this interaction may lead to
CC sequestration by FBN1 microfibril assembly and attenuation of TGFB
CC signaling. Interacts with CD109, DPT and ASPN. Interacts with EFEMP2.
CC Interacts with TSKU; the interaction contributes to regulation of the
CC hair cycle. {ECO:0000250|UniProtKB:P01137,
CC ECO:0000250|UniProtKB:P04202}.
CC -!- SUBUNIT: [Latency-associated peptide]: Homodimer; disulfide-linked.
CC Interacts with transforming growth factor beta-1 (TGF-beta-1) chain;
CC interaction is non-covalent and maintains TGF-beta-1 in a latent state;
CC each latency-associated peptide (LAP) monomer interacts with TGF-beta-1
CC in the other monomer. Interacts with LTBP1; leading to regulation of
CC TGF-beta-1 activation. Interacts with LRRC32/GARP; leading to
CC regulation of TGF-beta-1 activation on the surface of activated
CC regulatory T-cells (Tregs). Interacts with LRRC33/NRROS; leading to
CC regulation of TGF-beta-1 activation in macrophages and microglia.
CC Interacts (via cell attachment site) with integrins ITGAV and ITGB6
CC (ITGAV:ITGB6), leading to release of the active TGF-beta-1. Interacts
CC with NREP; the interaction results in a decrease in TGFB1
CC autoinduction. Interacts with HSP90AB1; inhibits latent TGFB1
CC activation. {ECO:0000250|UniProtKB:P01137,
CC ECO:0000250|UniProtKB:P04202}.
CC -!- SUBUNIT: [Transforming growth factor beta-1]: Homodimer; disulfide-
CC linked. Interacts with TGF-beta receptors (TGFBR1 and TGFBR2), leading
CC to signal transduction. {ECO:0000250|UniProtKB:P01137}.
CC -!- INTERACTION:
CC P07200; P07200: TGFB1; NbExp=2; IntAct=EBI-907660, EBI-907660;
CC P07200; Q99K41: Emilin1; Xeno; NbExp=2; IntAct=EBI-907660, EBI-906561;
CC P07200; P37173: TGFBR2; Xeno; NbExp=2; IntAct=EBI-907660, EBI-296151;
CC -!- SUBCELLULAR LOCATION: [Latency-associated peptide]: Secreted,
CC extracellular space, extracellular matrix
CC {ECO:0000250|UniProtKB:P01137}.
CC -!- SUBCELLULAR LOCATION: [Transforming growth factor beta-1]: Secreted
CC {ECO:0000250|UniProtKB:P01137}.
CC -!- DOMAIN: [Latency-associated peptide]: The 'straitjacket' and 'arm'
CC domains encircle the Transforming growth factor beta-1 (TGF-beta-1)
CC monomers and are fastened together by strong bonding between Lys-56 and
CC Tyr-103/Tyr-104. {ECO:0000269|PubMed:21677751}.
CC -!- DOMAIN: [Latency-associated peptide]: The cell attachment site motif
CC mediates binding to integrins (ITGAV:ITGB6 or ITGAV:ITGB8). The motif
CC locates to a long loop in the arm domain called the bowtie tail.
CC Integrin-binding stabilizes an alternative conformation of the bowtie
CC tail (PubMed:21677751). Activation by integrin requires force
CC application by the actin cytoskeleton, which is resisted by the 'milieu
CC molecules' (such as LTBP1, LRRC32/GARP and/or LRRC33/NRROS), resulting
CC in distortion of the prodomain and release of the active TGF-beta-1 (By
CC similarity). {ECO:0000250|UniProtKB:P01137,
CC ECO:0000269|PubMed:21677751}.
CC -!- PTM: Transforming growth factor beta-1 proprotein: The precursor
CC proprotein is cleaved in the Golgi apparatus by FURIN to form
CC Transforming growth factor beta-1 (TGF-beta-1) and Latency-associated
CC peptide (LAP) chains, which remain non-covalently linked, rendering
CC TGF-beta-1 inactive. {ECO:0000250|UniProtKB:P01137}.
CC -!- PTM: [Latency-associated peptide]: N-glycosylated. Deglycosylation
CC leads to activation of Transforming growth factor beta-1 (TGF-beta-1);
CC mechanisms triggering deglycosylation-driven activation of TGF-beta-1
CC are however unclear. {ECO:0000250|UniProtKB:P01137}.
CC -!- SIMILARITY: Belongs to the TGF-beta family. {ECO:0000305}.
CC -!- CAUTION: PubMed:3166520 sequence which was said to originate from
CC chicken. It however seems to originate from pig.
CC {ECO:0000305|PubMed:3166520, ECO:0000305|Ref.4}.
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DR EMBL; Y00111; CAA68291.1; -; mRNA.
DR EMBL; M23703; AAA64616.1; -; mRNA.
DR EMBL; X12373; CAA30933.1; -; mRNA.
DR EMBL; AF461808; AAL57902.1; -; mRNA.
DR EMBL; AEMK02000041; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR PIR; A27512; A27512.
DR PIR; S01413; S01413.
DR RefSeq; NP_999180.2; NM_214015.2.
DR PDB; 3RJR; X-ray; 3.05 A; A/B/C/D=30-390.
DR PDB; 5VQF; X-ray; 2.90 A; A/B/C/D=30-390.
DR PDB; 6UJA; EM; 3.30 A; D=30-390.
DR PDBsum; 3RJR; -.
DR PDBsum; 5VQF; -.
DR PDBsum; 6UJA; -.
DR AlphaFoldDB; P07200; -.
DR SMR; P07200; -.
DR DIP; DIP-35732N; -.
DR IntAct; P07200; 3.
DR STRING; 9823.ENSSSCP00000003267; -.
DR iPTMnet; P07200; -.
DR PaxDb; P07200; -.
DR PRIDE; P07200; -.
DR Ensembl; ENSSSCT00000036469; ENSSSCP00000030317; ENSSSCG00000003017.
DR Ensembl; ENSSSCT00015109974; ENSSSCP00015046877; ENSSSCG00015080792.
DR Ensembl; ENSSSCT00025026430; ENSSSCP00025011191; ENSSSCG00025019487.
DR Ensembl; ENSSSCT00030029290; ENSSSCP00030013147; ENSSSCG00030021126.
DR Ensembl; ENSSSCT00035051620; ENSSSCP00035020698; ENSSSCG00035038894.
DR Ensembl; ENSSSCT00040094188; ENSSSCP00040041585; ENSSSCG00040068791.
DR Ensembl; ENSSSCT00045055664; ENSSSCP00045038824; ENSSSCG00045032593.
DR Ensembl; ENSSSCT00050031315; ENSSSCP00050013072; ENSSSCG00050023190.
DR Ensembl; ENSSSCT00055017714; ENSSSCP00055013996; ENSSSCG00055009042.
DR Ensembl; ENSSSCT00060095738; ENSSSCP00060041409; ENSSSCG00060070125.
DR Ensembl; ENSSSCT00065016364; ENSSSCP00065006672; ENSSSCG00065012270.
DR Ensembl; ENSSSCT00070003600; ENSSSCP00070002984; ENSSSCG00070001924.
DR GeneID; 397078; -.
DR KEGG; ssc:397078; -.
DR CTD; 7040; -.
DR VGNC; VGNC:98656; TGFB1.
DR eggNOG; KOG3900; Eukaryota.
DR GeneTree; ENSGT00940000160457; -.
DR HOGENOM; CLU_039840_1_0_1; -.
DR InParanoid; P07200; -.
DR OMA; YIWDAEN; -.
DR OrthoDB; 643840at2759; -.
DR ChiTaRS; TGFB1; pig.
DR Proteomes; UP000008227; Chromosome 6.
DR Proteomes; UP000314985; Chromosome 6.
DR Bgee; ENSSSCG00000003017; Expressed in blood and 42 other tissues.
DR GO; GO:0072562; C:blood microparticle; ISS:AgBase.
DR GO; GO:0009986; C:cell surface; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0031012; C:extracellular matrix; ISS:UniProtKB.
DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0003823; F:antigen binding; ISS:AgBase.
DR GO; GO:0005125; F:cytokine activity; IBA:GO_Central.
DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0043539; F:protein serine/threonine kinase activator activity; IEA:Ensembl.
DR GO; GO:0034713; F:type I transforming growth factor beta receptor binding; ISS:AgBase.
DR GO; GO:0005114; F:type II transforming growth factor beta receptor binding; ISS:UniProtKB.
DR GO; GO:0034714; F:type III transforming growth factor beta receptor binding; ISS:AgBase.
DR GO; GO:0002460; P:adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains; IEA:Ensembl.
DR GO; GO:0003180; P:aortic valve morphogenesis; IEA:Ensembl.
DR GO; GO:0006754; P:ATP biosynthetic process; ISS:UniProtKB.
DR GO; GO:0030509; P:BMP signaling pathway; IBA:GO_Central.
DR GO; GO:0060751; P:branch elongation involved in mammary gland duct branching; IEA:Ensembl.
DR GO; GO:0060435; P:bronchiole development; IEA:Ensembl.
DR GO; GO:0016477; P:cell migration; ISS:UniProtKB.
DR GO; GO:0000902; P:cell morphogenesis; IEA:Ensembl.
DR GO; GO:0045216; P:cell-cell junction organization; ISS:UniProtKB.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; IEA:Ensembl.
DR GO; GO:0071479; P:cellular response to ionizing radiation; IEA:Ensembl.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; ISS:UniProtKB.
DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; ISS:AgBase.
DR GO; GO:0098586; P:cellular response to virus; IEA:Ensembl.
DR GO; GO:0002062; P:chondrocyte differentiation; ISS:UniProtKB.
DR GO; GO:0002069; P:columnar/cuboidal epithelial cell maturation; IEA:Ensembl.
DR GO; GO:0007182; P:common-partner SMAD protein phosphorylation; ISS:UniProtKB.
DR GO; GO:1990402; P:embryonic liver development; IEA:Ensembl.
DR GO; GO:0070166; P:enamel mineralization; IEA:Ensembl.
DR GO; GO:0007492; P:endoderm development; IEA:Ensembl.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0050673; P:epithelial cell proliferation; IEA:Ensembl.
DR GO; GO:0001837; P:epithelial to mesenchymal transition; ISS:UniProtKB.
DR GO; GO:0085029; P:extracellular matrix assembly; ISS:UniProtKB.
DR GO; GO:0097191; P:extrinsic apoptotic signaling pathway; ISS:UniProtKB.
DR GO; GO:0060325; P:face morphogenesis; IEA:Ensembl.
DR GO; GO:0010467; P:gene expression; IEA:Ensembl.
DR GO; GO:0008354; P:germ cell migration; IEA:Ensembl.
DR GO; GO:0002244; P:hematopoietic progenitor cell differentiation; ISS:UniProtKB.
DR GO; GO:0030214; P:hyaluronan catabolic process; ISS:UniProtKB.
DR GO; GO:0006954; P:inflammatory response; ISS:UniProtKB.
DR GO; GO:0061520; P:Langerhans cell differentiation; IEA:Ensembl.
DR GO; GO:0070306; P:lens fiber cell differentiation; IEA:Ensembl.
DR GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0048286; P:lung alveolus development; IEA:Ensembl.
DR GO; GO:0048535; P:lymph node development; ISS:UniProtKB.
DR GO; GO:0060744; P:mammary gland branching involved in thelarche; IEA:Ensembl.
DR GO; GO:0000165; P:MAPK cascade; ISS:UniProtKB.
DR GO; GO:0031293; P:membrane protein intracellular domain proteolysis; ISS:UniProtKB.
DR GO; GO:0046716; P:muscle cell cellular homeostasis; IEA:Ensembl.
DR GO; GO:0070168; P:negative regulation of biomineral tissue development; IEA:Ensembl.
DR GO; GO:0043537; P:negative regulation of blood vessel endothelial cell migration; ISS:UniProtKB.
DR GO; GO:0045786; P:negative regulation of cell cycle; ISS:UniProtKB.
DR GO; GO:0030308; P:negative regulation of cell growth; ISS:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:0022408; P:negative regulation of cell-cell adhesion; ISS:UniProtKB.
DR GO; GO:0050680; P:negative regulation of epithelial cell proliferation; ISS:UniProtKB.
DR GO; GO:0045599; P:negative regulation of fat cell differentiation; ISS:UniProtKB.
DR GO; GO:0010629; P:negative regulation of gene expression; ISS:BHF-UCL.
DR GO; GO:1900126; P:negative regulation of hyaluronan biosynthetic process; ISS:UniProtKB.
DR GO; GO:0032700; P:negative regulation of interleukin-17 production; IEA:Ensembl.
DR GO; GO:0010936; P:negative regulation of macrophage cytokine production; ISS:AgBase.
DR GO; GO:0045662; P:negative regulation of myoblast differentiation; ISS:UniProtKB.
DR GO; GO:0030279; P:negative regulation of ossification; IEA:Ensembl.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0048642; P:negative regulation of skeletal muscle tissue development; ISS:UniProtKB.
DR GO; GO:0042130; P:negative regulation of T cell proliferation; IEA:Ensembl.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0001843; P:neural tube closure; IEA:Ensembl.
DR GO; GO:0007219; P:Notch signaling pathway; IEA:Ensembl.
DR GO; GO:0014003; P:oligodendrocyte development; IEA:Ensembl.
DR GO; GO:0043932; P:ossification involved in bone remodeling; ISS:AgBase.
DR GO; GO:0030316; P:osteoclast differentiation; IEA:Ensembl.
DR GO; GO:0060389; P:pathway-restricted SMAD protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0006796; P:phosphate-containing compound metabolic process; ISS:UniProtKB.
DR GO; GO:0055091; P:phospholipid homeostasis; IEA:Ensembl.
DR GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; ISS:UniProtKB.
DR GO; GO:0030501; P:positive regulation of bone mineralization; ISS:AgBase.
DR GO; GO:0051781; P:positive regulation of cell division; IEA:UniProtKB-KW.
DR GO; GO:0030335; P:positive regulation of cell migration; ISS:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:0050921; P:positive regulation of chemotaxis; ISS:UniProtKB.
DR GO; GO:0032967; P:positive regulation of collagen biosynthetic process; ISS:UniProtKB.
DR GO; GO:0010718; P:positive regulation of epithelial to mesenchymal transition; ISS:UniProtKB.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
DR GO; GO:0010763; P:positive regulation of fibroblast migration; ISS:UniProtKB.
DR GO; GO:0048146; P:positive regulation of fibroblast proliferation; IEA:Ensembl.
DR GO; GO:0010628; P:positive regulation of gene expression; ISS:UniProtKB.
DR GO; GO:0035066; P:positive regulation of histone acetylation; IEA:Ensembl.
DR GO; GO:0031065; P:positive regulation of histone deacetylation; IEA:Ensembl.
DR GO; GO:0032740; P:positive regulation of interleukin-17 production; ISS:UniProtKB.
DR GO; GO:0048298; P:positive regulation of isotype switching to IgA isotypes; ISS:AgBase.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; ISS:UniProtKB.
DR GO; GO:0014008; P:positive regulation of microglia differentiation; ISS:UniProtKB.
DR GO; GO:1901666; P:positive regulation of NAD+ ADP-ribosyltransferase activity; ISS:UniProtKB.
DR GO; GO:0042482; P:positive regulation of odontogenesis; IEA:Ensembl.
DR GO; GO:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; ISS:UniProtKB.
DR GO; GO:0010800; P:positive regulation of peptidyl-threonine phosphorylation; ISS:UniProtKB.
DR GO; GO:0043552; P:positive regulation of phosphatidylinositol 3-kinase activity; ISS:UniProtKB.
DR GO; GO:0035307; P:positive regulation of protein dephosphorylation; ISS:UniProtKB.
DR GO; GO:0042307; P:positive regulation of protein import into nucleus; ISS:AgBase.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; ISS:UniProtKB.
DR GO; GO:0051247; P:positive regulation of protein metabolic process; ISS:UniProtKB.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0050714; P:positive regulation of protein secretion; ISS:UniProtKB.
DR GO; GO:0031334; P:positive regulation of protein-containing complex assembly; ISS:UniProtKB.
DR GO; GO:1903911; P:positive regulation of receptor clustering; IEA:Ensembl.
DR GO; GO:0045591; P:positive regulation of regulatory T cell differentiation; IEA:Ensembl.
DR GO; GO:0060391; P:positive regulation of SMAD protein signal transduction; ISS:AgBase.
DR GO; GO:2000648; P:positive regulation of stem cell proliferation; IEA:Ensembl.
DR GO; GO:0032930; P:positive regulation of superoxide anion generation; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:AgBase.
DR GO; GO:2000679; P:positive regulation of transcription regulatory region DNA binding; ISS:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0006611; P:protein export from nucleus; ISS:UniProtKB.
DR GO; GO:0043491; P:protein kinase B signaling; ISS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0032801; P:receptor catabolic process; ISS:UniProtKB.
DR GO; GO:2000249; P:regulation of actin cytoskeleton reorganization; IEA:Ensembl.
DR GO; GO:0051098; P:regulation of binding; ISS:UniProtKB.
DR GO; GO:0060762; P:regulation of branching involved in mammary gland duct morphogenesis; IEA:Ensembl.
DR GO; GO:0061035; P:regulation of cartilage development; IEA:Ensembl.
DR GO; GO:0042127; P:regulation of cell population proliferation; IBA:GO_Central.
DR GO; GO:0051101; P:regulation of DNA binding; ISS:UniProtKB.
DR GO; GO:0032667; P:regulation of interleukin-23 production; IEA:Ensembl.
DR GO; GO:0042306; P:regulation of protein import into nucleus; ISS:UniProtKB.
DR GO; GO:0060390; P:regulation of SMAD protein signal transduction; ISS:UniProtKB.
DR GO; GO:0002028; P:regulation of sodium ion transport; IEA:Ensembl.
DR GO; GO:0016202; P:regulation of striated muscle tissue development; ISS:UniProtKB.
DR GO; GO:0017015; P:regulation of transforming growth factor beta receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0045066; P:regulatory T cell differentiation; IEA:Ensembl.
DR GO; GO:0070723; P:response to cholesterol; ISS:UniProtKB.
DR GO; GO:0032355; P:response to estradiol; ISS:UniProtKB.
DR GO; GO:0032570; P:response to progesterone; ISS:UniProtKB.
DR GO; GO:0009611; P:response to wounding; ISS:AgBase.
DR GO; GO:0007435; P:salivary gland morphogenesis; ISS:AgBase.
DR GO; GO:0007183; P:SMAD protein complex assembly; ISS:UniProtKB.
DR GO; GO:0060395; P:SMAD protein signal transduction; IBA:GO_Central.
DR GO; GO:0072089; P:stem cell proliferation; IEA:Ensembl.
DR GO; GO:0043129; P:surfactant homeostasis; IEA:Ensembl.
DR GO; GO:0043029; P:T cell homeostasis; IEA:Ensembl.
DR GO; GO:0042098; P:T cell proliferation; IEA:Ensembl.
DR GO; GO:0002513; P:tolerance induction to self antigen; IEA:Ensembl.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:1905313; P:transforming growth factor beta receptor signaling pathway involved in heart development; IEA:Ensembl.
DR GO; GO:0001657; P:ureteric bud development; IEA:Ensembl.
DR GO; GO:0001570; P:vasculogenesis; IEA:Ensembl.
DR GO; GO:0055010; P:ventricular cardiac muscle tissue morphogenesis; IEA:Ensembl.
DR Gene3D; 2.10.90.10; -; 1.
DR InterPro; IPR029034; Cystine-knot_cytokine.
DR InterPro; IPR001839; TGF-b_C.
DR InterPro; IPR001111; TGF-b_propeptide.
DR InterPro; IPR016319; TGF-beta.
DR InterPro; IPR015615; TGF-beta-rel.
DR InterPro; IPR003939; TGFb1.
DR InterPro; IPR017948; TGFb_CS.
DR PANTHER; PTHR11848; PTHR11848; 1.
DR Pfam; PF00019; TGF_beta; 1.
DR Pfam; PF00688; TGFb_propeptide; 1.
DR PIRSF; PIRSF001787; TGF-beta; 1.
DR PRINTS; PR01423; TGFBETA.
DR PRINTS; PR01424; TGFBETA1.
DR SMART; SM00204; TGFB; 1.
DR SUPFAM; SSF57501; SSF57501; 1.
DR PROSITE; PS00250; TGF_BETA_1; 1.
DR PROSITE; PS51362; TGF_BETA_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cleavage on pair of basic residues;
KW Direct protein sequencing; Disulfide bond; Extracellular matrix;
KW Glycoprotein; Growth factor; Mitogen; Reference proteome; Secreted; Signal.
FT SIGNAL 1..29
FT /evidence="ECO:0000250|UniProtKB:P01137"
FT CHAIN 30..278
FT /note="Latency-associated peptide"
FT /evidence="ECO:0000305|PubMed:2879635"
FT /id="PRO_0000033768"
FT CHAIN 279..390
FT /note="Transforming growth factor beta-1"
FT /evidence="ECO:0000305|PubMed:2879635"
FT /id="PRO_0000033769"
FT REGION 30..74
FT /note="Straightjacket domain"
FT /evidence="ECO:0000269|PubMed:21677751"
FT REGION 75..271
FT /note="Arm domain"
FT /evidence="ECO:0000269|PubMed:21677751"
FT REGION 226..252
FT /note="Bowtie tail"
FT /evidence="ECO:0000250|UniProtKB:P01137"
FT MOTIF 244..246
FT /note="Cell attachment site"
FT /evidence="ECO:0000269|PubMed:21677751"
FT SITE 278..279
FT /note="Cleavage; by FURIN"
FT /evidence="ECO:0000250|UniProtKB:P01137"
FT CARBOHYD 82
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:21677751,
FT ECO:0007744|PDB:3RJR"
FT CARBOHYD 136
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:21677751,
FT ECO:0007744|PDB:3RJR"
FT CARBOHYD 176
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 33
FT /note="Interchain (with C-? in LTBP1 TB3 domain); in
FT inactive form"
FT /evidence="ECO:0000269|PubMed:21677751"
FT DISULFID 223
FT /note="Interchain (with C-225)"
FT /evidence="ECO:0000269|PubMed:21677751,
FT ECO:0000269|PubMed:29109152, ECO:0007744|PDB:3RJR,
FT ECO:0007744|PDB:5VQF"
FT DISULFID 225
FT /note="Interchain (with C-223)"
FT /evidence="ECO:0000269|PubMed:21677751,
FT ECO:0000269|PubMed:29109152, ECO:0007744|PDB:3RJR,
FT ECO:0007744|PDB:5VQF"
FT DISULFID 285..294
FT /evidence="ECO:0000269|PubMed:21677751,
FT ECO:0000269|PubMed:29109152, ECO:0007744|PDB:3RJR,
FT ECO:0007744|PDB:5VQF"
FT DISULFID 293..356
FT /evidence="ECO:0000269|PubMed:21677751,
FT ECO:0000269|PubMed:29109152, ECO:0007744|PDB:3RJR,
FT ECO:0007744|PDB:5VQF"
FT DISULFID 322..387
FT /evidence="ECO:0000269|PubMed:21677751,
FT ECO:0000269|PubMed:29109152, ECO:0007744|PDB:3RJR,
FT ECO:0007744|PDB:5VQF"
FT DISULFID 326..389
FT /evidence="ECO:0000269|PubMed:21677751,
FT ECO:0000269|PubMed:29109152, ECO:0007744|PDB:3RJR,
FT ECO:0007744|PDB:5VQF"
FT DISULFID 355
FT /note="Interchain"
FT /evidence="ECO:0000269|PubMed:21677751,
FT ECO:0000269|PubMed:29109152, ECO:0007744|PDB:3RJR,
FT ECO:0007744|PDB:5VQF"
FT VARIANT 114
FT /note="V -> L"
FT /evidence="ECO:0000269|PubMed:3470708"
FT MUTAGEN 103
FT /note="Y->A,K,T: Results in spontaneous, non integrin-
FT dependent activation."
FT /evidence="ECO:0000269|PubMed:21677751"
FT MUTAGEN 104
FT /note="Y->A,C,S,T: Results in spontaneous, non integrin-
FT dependent activation."
FT /evidence="ECO:0000269|PubMed:21677751"
FT CONFLICT 6..7
FT /note="LR -> PG (in Ref. 3; CAA30933)"
FT /evidence="ECO:0000305"
FT CONFLICT 180
FT /note="R -> G (in Ref. 3; CAA30933)"
FT /evidence="ECO:0000305"
FT CONFLICT 237
FT /note="N -> NA (in Ref. 3; CAA30933)"
FT /evidence="ECO:0000305"
FT HELIX 32..56
FT /evidence="ECO:0007829|PDB:5VQF"
FT HELIX 75..85
FT /evidence="ECO:0007829|PDB:5VQF"
FT STRAND 89..91
FT /evidence="ECO:0007829|PDB:3RJR"
FT STRAND 106..112
FT /evidence="ECO:0007829|PDB:5VQF"
FT STRAND 116..119
FT /evidence="ECO:0007829|PDB:5VQF"
FT TURN 120..126
FT /evidence="ECO:0007829|PDB:5VQF"
FT STRAND 130..136
FT /evidence="ECO:0007829|PDB:5VQF"
FT HELIX 137..143
FT /evidence="ECO:0007829|PDB:5VQF"
FT STRAND 144..146
FT /evidence="ECO:0007829|PDB:3RJR"
FT HELIX 147..149
FT /evidence="ECO:0007829|PDB:5VQF"
FT STRAND 150..159
FT /evidence="ECO:0007829|PDB:5VQF"
FT STRAND 166..172
FT /evidence="ECO:0007829|PDB:5VQF"
FT STRAND 175..177
FT /evidence="ECO:0007829|PDB:5VQF"
FT STRAND 180..187
FT /evidence="ECO:0007829|PDB:5VQF"
FT STRAND 194..199
FT /evidence="ECO:0007829|PDB:5VQF"
FT HELIX 201..209
FT /evidence="ECO:0007829|PDB:5VQF"
FT STRAND 213..221
FT /evidence="ECO:0007829|PDB:5VQF"
FT STRAND 224..228
FT /evidence="ECO:0007829|PDB:5VQF"
FT STRAND 231..235
FT /evidence="ECO:0007829|PDB:5VQF"
FT HELIX 245..248
FT /evidence="ECO:0007829|PDB:6UJA"
FT STRAND 251..254
FT /evidence="ECO:0007829|PDB:3RJR"
FT STRAND 257..262
FT /evidence="ECO:0007829|PDB:5VQF"
FT HELIX 265..267
FT /evidence="ECO:0007829|PDB:5VQF"
FT HELIX 282..285
FT /evidence="ECO:0007829|PDB:5VQF"
FT STRAND 291..296
FT /evidence="ECO:0007829|PDB:5VQF"
FT STRAND 299..301
FT /evidence="ECO:0007829|PDB:5VQF"
FT TURN 302..306
FT /evidence="ECO:0007829|PDB:5VQF"
FT STRAND 310..313
FT /evidence="ECO:0007829|PDB:5VQF"
FT STRAND 315..318
FT /evidence="ECO:0007829|PDB:5VQF"
FT STRAND 321..323
FT /evidence="ECO:0007829|PDB:5VQF"
FT HELIX 329..331
FT /evidence="ECO:0007829|PDB:5VQF"
FT STRAND 332..334
FT /evidence="ECO:0007829|PDB:5VQF"
FT HELIX 337..340
FT /evidence="ECO:0007829|PDB:5VQF"
FT HELIX 341..345
FT /evidence="ECO:0007829|PDB:5VQF"
FT TURN 348..350
FT /evidence="ECO:0007829|PDB:5VQF"
FT STRAND 351..353
FT /evidence="ECO:0007829|PDB:5VQF"
FT STRAND 355..370
FT /evidence="ECO:0007829|PDB:5VQF"
FT STRAND 373..384
FT /evidence="ECO:0007829|PDB:5VQF"
FT STRAND 386..390
FT /evidence="ECO:0007829|PDB:5VQF"
SQ SEQUENCE 390 AA; 44280 MW; A9FC32859BA6AF06 CRC64;
MPPSGLRLLP LLLPLLWLLV LTPGRPAAGL STCKTIDMEL VKRKRIEAIR GQILSKLRLA
SPPSQGDVPP GPLPEAVLAL YNSTRDRVAG ESVEPEPEPE ADYYAKEVTR VLMVESGNQI
YDKFKGTPHS LYMLFNTSEL REAVPEPVLL SRAELRLLRL KLKVEQHVEL YQKYSNDSWR
YLSNRLLAPS DSPEWLSFDV TGVVRQWLTR REAIEGFRLS AHCSCDSKDN TLHVEINGFN
SGRRGDLATI HGMNRPFLLL MATPLERAQH LHSSRHRRAL DTNYCFSSTE KNCCVRQLYI
DFRKDLGWKW IHEPKGYHAN FCLGPCPYIW SLDTQYSKVL ALYNQHNPGA SAAPCCVPQA
LEPLPIVYYV GRKPKVEQLS NMIVRSCKCS
