TGFB1_RAT
ID TGFB1_RAT Reviewed; 390 AA.
AC P17246; Q53YM8;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1990, sequence version 1.
DT 03-AUG-2022, entry version 190.
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Heart;
RX PubMed=2349108; DOI=10.1093/nar/18.10.3059;
RA Qian S.W., Kondaiah P., Roberts A.B., Sporn M.B.;
RT "cDNA cloning by PCR of rat transforming growth factor beta-1.";
RL Nucleic Acids Res. 18:3059-3059(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RA Dai W.-J., Jiang H.-C., Fu S.-B.;
RT "Open reading frame sequence of rat TGF beta 1.";
RL Submitted (FEB-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP SUBUNIT.
RX PubMed=11907708; DOI=10.1007/s002230010032;
RA Maeda S., Dean D.D., Gomez R., Schwartz Z., Boyan B.D.;
RT "The first stage of transforming growth factor beta1 activation is release
RT of the large latent complex from the extracellular matrix of growth plate
RT chondrocytes by matrix vesicle stromelysin-1 (MMP-3).";
RL Calcif. Tissue Int. 70:54-65(2002).
RN [5]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=2070682;
RA Mundy G.R.;
RT "The effects of TGF-beta on bone.";
RL Ciba Found. Symp. 157:137-143(1991).
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 (By similarity). At the
CC same time, LAP chain interacts with 'milieu molecules', such as LTBP1,
CC LRRC32/GARP and LRRC33/NRROS that control activation of TGF-beta-1 and
CC maintain it in a latent state during storage in extracellular milieus.
CC TGF-beta-1 is released from LAP by integrins (ITGAV:ITGB6 or
CC ITGAV:ITGB8): integrin-binding to LAP stabilizes an alternative
CC conformation of the LAP bowtie tail and results in distortion of the
CC LAP chain and subsequent release of the active TGF-beta-1 (By
CC similarity). Once activated following release of LAP, TGF-beta-1 acts
CC by binding to TGF-beta receptors (TGFBR1 and TGFBR2), which transduce
CC signal (By similarity). While expressed by many cells types, TGF-beta-1
CC only has a very localized range of action within cell environment
CC thanks to fine regulation of its activation by Latency-associated
CC peptide chain (LAP) and 'milieu molecules' (PubMed:2070682). 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 (PubMed:2070682). Can promote
CC either T-helper 17 cells (Th17) or regulatory T-cells (Treg) lineage
CC differentiation in a concentration-dependent manner (By similarity). At
CC high concentrations, leads to FOXP3-mediated suppression of RORC and
CC down-regulation of IL-17 expression, favoring Treg cell development (By
CC similarity). At low concentrations in concert with IL-6 and IL-21,
CC leads to expression of the IL-17 and IL-23 receptors, favoring
CC differentiation to Th17 cells (By similarity). Stimulates sustained
CC production of collagen through the activation of CREB3L1 by regulated
CC intramembrane proteolysis (RIP). Mediates SMAD2/3 activation by
CC inducing its phosphorylation and subsequent translocation to the
CC nucleus. Can induce epithelial-to-mesenchymal transition (EMT) and cell
CC migration in various cell types (By similarity).
CC {ECO:0000250|UniProtKB:P01137, ECO:0000250|UniProtKB:P04202,
CC ECO:0000269|PubMed:2070682}.
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 -!- 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 -!- TISSUE SPECIFICITY: Abundant in the bone matrix.
CC {ECO:0000269|PubMed:2070682}.
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:0000250|UniProtKB:P07200}.
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. Activation by integrin requires force application by the actin
CC cytoskeleton, which is resisted by the 'milieu molecules' (such as
CC LTBP1, LRRC32/GARP and/or LRRC33/NRROS), resulting in distortion of the
CC prodomain and release of the active TGF-beta-1.
CC {ECO:0000250|UniProtKB:P01137}.
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}.
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DR EMBL; X52498; CAA36741.1; -; mRNA.
DR EMBL; AY550025; AAS55640.1; -; mRNA.
DR EMBL; BC076380; AAH76380.1; -; mRNA.
DR PIR; S10219; S10219.
DR RefSeq; NP_067589.1; NM_021578.2.
DR AlphaFoldDB; P17246; -.
DR SMR; P17246; -.
DR BioGRID; 248721; 1.
DR DIP; DIP-6247N; -.
DR STRING; 10116.ENSRNOP00000028051; -.
DR GlyGen; P17246; 3 sites.
DR PhosphoSitePlus; P17246; -.
DR jPOST; P17246; -.
DR PaxDb; P17246; -.
DR PRIDE; P17246; -.
DR Ensembl; ENSRNOT00000028051; ENSRNOP00000028051; ENSRNOG00000020652.
DR GeneID; 59086; -.
DR KEGG; rno:59086; -.
DR UCSC; RGD:69051; rat.
DR CTD; 7040; -.
DR RGD; 69051; Tgfb1.
DR eggNOG; KOG3900; Eukaryota.
DR GeneTree; ENSGT00940000160457; -.
DR HOGENOM; CLU_039840_0_0_1; -.
DR InParanoid; P17246; -.
DR OMA; YIWDAEN; -.
DR OrthoDB; 643840at2759; -.
DR PhylomeDB; P17246; -.
DR TreeFam; TF318514; -.
DR Reactome; R-RNO-114608; Platelet degranulation.
DR Reactome; R-RNO-202733; Cell surface interactions at the vascular wall.
DR Reactome; R-RNO-2129379; Molecules associated with elastic fibres.
DR Reactome; R-RNO-2173788; Downregulation of TGF-beta receptor signaling.
DR Reactome; R-RNO-2173789; TGF-beta receptor signaling activates SMADs.
DR Reactome; R-RNO-2173791; TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition).
DR Reactome; R-RNO-3000170; Syndecan interactions.
DR Reactome; R-RNO-8941855; RUNX3 regulates CDKN1A transcription.
DR Reactome; R-RNO-8941858; Regulation of RUNX3 expression and activity.
DR PRO; PR:P17246; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000020652; Expressed in spleen and 18 other tissues.
DR Genevisible; P17246; RN.
DR GO; GO:0030424; C:axon; IDA:RGD.
DR GO; GO:0072562; C:blood microparticle; ISS:AgBase.
DR GO; GO:0009986; C:cell surface; IDA:BHF-UCL.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0031012; C:extracellular matrix; ISO:RGD.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0030141; C:secretory granule; IDA:RGD.
DR GO; GO:0099126; C:transforming growth factor beta complex; ISO:RGD.
DR GO; GO:0003823; F:antigen binding; ISS:AgBase.
DR GO; GO:0005125; F:cytokine activity; IBA:GO_Central.
DR GO; GO:0019899; F:enzyme binding; ISO:RGD.
DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; IPI:RGD.
DR GO; GO:0047485; F:protein N-terminus binding; IMP:RGD.
DR GO; GO:0043539; F:protein serine/threonine kinase activator activity; ISO:RGD.
DR GO; GO:0044877; F:protein-containing complex binding; IDA:RGD.
DR GO; GO:0005160; F:transforming growth factor beta receptor binding; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0007568; P:aging; IEP:RGD.
DR GO; GO:0031100; P:animal organ regeneration; IMP:RGD.
DR GO; GO:0003180; P:aortic valve morphogenesis; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0060435; P:bronchiole development; ISO:RGD.
DR GO; GO:0001775; P:cell activation; ISO:RGD.
DR GO; GO:0016477; P:cell migration; ISS:UniProtKB.
DR GO; GO:0000902; P:cell morphogenesis; ISO:RGD.
DR GO; GO:0008283; P:cell population proliferation; ISO:RGD.
DR GO; GO:0045216; P:cell-cell junction organization; ISS:UniProtKB.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; ISO:RGD.
DR GO; GO:0071549; P:cellular response to dexamethasone stimulus; IDA:UniProtKB.
DR GO; GO:0071363; P:cellular response to growth factor stimulus; ISO:RGD.
DR GO; GO:1990314; P:cellular response to insulin-like growth factor stimulus; IEP:RGD.
DR GO; GO:0071479; P:cellular response to ionizing radiation; IEP:RGD.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEP:RGD.
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; ISO:RGD.
DR GO; GO:0002062; P:chondrocyte differentiation; ISS:UniProtKB.
DR GO; GO:0002069; P:columnar/cuboidal epithelial cell maturation; ISO:RGD.
DR GO; GO:0007182; P:common-partner SMAD protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0061448; P:connective tissue development; ISO:RGD.
DR GO; GO:0050832; P:defense response to fungus; IDA:RGD.
DR GO; GO:0048565; P:digestive tract development; IEP:RGD.
DR GO; GO:1990402; P:embryonic liver development; ISO:RGD.
DR GO; GO:0070166; P:enamel mineralization; ISO:RGD.
DR GO; GO:0007492; P:endoderm development; ISO:RGD.
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; IDA:RGD.
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; ISO:RGD.
DR GO; GO:0007565; P:female pregnancy; IEP:RGD.
DR GO; GO:0060364; P:frontal suture morphogenesis; IEP:RGD.
DR GO; GO:0010467; P:gene expression; ISO:RGD.
DR GO; GO:0008354; P:germ cell migration; ISO:RGD.
DR GO; GO:0007507; P:heart development; ISO:RGD.
DR GO; GO:0003179; P:heart valve morphogenesis; ISO:RGD.
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:AgBase.
DR GO; GO:0048839; P:inner ear development; IEP:RGD.
DR GO; GO:0061520; P:Langerhans cell differentiation; IEA:Ensembl.
DR GO; GO:0070306; P:lens fiber cell differentiation; ISO:RGD.
DR GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0097421; P:liver regeneration; IEP:RGD.
DR GO; GO:0048286; P:lung alveolus development; ISO:RGD.
DR GO; GO:0030324; P:lung development; TAS:RGD.
DR GO; GO:0048535; P:lymph node development; ISO:RGD.
DR GO; GO:0060744; P:mammary gland branching involved in thelarche; ISO:RGD.
DR GO; GO:0030879; P:mammary gland development; ISO:RGD.
DR GO; GO:0000165; P:MAPK cascade; ISS:UniProtKB.
DR GO; GO:0031293; P:membrane protein intracellular domain proteolysis; ISS:UniProtKB.
DR GO; GO:0032943; P:mononuclear cell proliferation; ISO:RGD.
DR GO; GO:0001763; P:morphogenesis of a branching structure; IDA:RGD.
DR GO; GO:0046716; P:muscle cell cellular homeostasis; ISO:RGD.
DR GO; GO:0042552; P:myelination; IMP:RGD.
DR GO; GO:0043011; P:myeloid dendritic cell differentiation; ISO:RGD.
DR GO; GO:0070168; P:negative regulation of biomineral tissue development; ISO:RGD.
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:0045596; P:negative regulation of cell differentiation; ISO:RGD.
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:0045918; P:negative regulation of cytolysis; ISO:RGD.
DR GO; GO:0050680; P:negative regulation of epithelial cell proliferation; IDA:RGD.
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:0050777; P:negative regulation of immune response; IDA:RGD.
DR GO; GO:0032700; P:negative regulation of interleukin-17 production; ISO:RGD.
DR GO; GO:0010936; P:negative regulation of macrophage cytokine production; ISS:AgBase.
DR GO; GO:1903799; P:negative regulation of miRNA maturation; ISO:RGD.
DR GO; GO:1902894; P:negative regulation of miRNA transcription; ISO:RGD.
DR GO; GO:0060965; P:negative regulation of miRNA-mediated gene silencing; ISO:RGD.
DR GO; GO:0045662; P:negative regulation of myoblast differentiation; ISS:UniProtKB.
DR GO; GO:0007406; P:negative regulation of neuroblast proliferation; IDA:RGD.
DR GO; GO:0030279; P:negative regulation of ossification; ISO:RGD.
DR GO; GO:0050765; P:negative regulation of phagocytosis; IDA:RGD.
DR GO; GO:1903077; P:negative regulation of protein localization to plasma membrane; ISO:RGD.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0051280; P:negative regulation of release of sequestered calcium ion into cytosol; IDA:RGD.
DR GO; GO:0048642; P:negative regulation of skeletal muscle tissue development; ISS:UniProtKB.
DR GO; GO:0050868; P:negative regulation of T cell activation; ISO:RGD.
DR GO; GO:0042130; P:negative regulation of T cell proliferation; ISO:RGD.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0001843; P:neural tube closure; ISO:RGD.
DR GO; GO:0021915; P:neural tube development; ISO:RGD.
DR GO; GO:0007219; P:Notch signaling pathway; ISO:RGD.
DR GO; GO:0042475; P:odontogenesis of dentin-containing tooth; IEP:RGD.
DR GO; GO:0014003; P:oligodendrocyte development; ISO:RGD.
DR GO; GO:0043932; P:ossification involved in bone remodeling; ISS:AgBase.
DR GO; GO:0030316; P:osteoclast differentiation; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:RGD.
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:0090190; P:positive regulation of branching involved in ureteric bud morphogenesis; IMP:UniProtKB.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; ISO:RGD.
DR GO; GO:2000727; P:positive regulation of cardiac muscle cell differentiation; ISO:RGD.
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; IMP:RGD.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IDA:RGD.
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:0031536; P:positive regulation of exit from mitosis; IDA:RGD.
DR GO; GO:0010763; P:positive regulation of fibroblast migration; ISS:UniProtKB.
DR GO; GO:0048146; P:positive regulation of fibroblast proliferation; ISO:RGD.
DR GO; GO:0010628; P:positive regulation of gene expression; ISS:UniProtKB.
DR GO; GO:0035066; P:positive regulation of histone acetylation; ISO:RGD.
DR GO; GO:0031065; P:positive regulation of histone deacetylation; ISO:RGD.
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:1903800; P:positive regulation of miRNA maturation; ISO:RGD.
DR GO; GO:1902895; P:positive regulation of miRNA transcription; ISO:RGD.
DR GO; GO:0071677; P:positive regulation of mononuclear cell migration; IMP:RGD.
DR GO; GO:1901666; P:positive regulation of NAD+ ADP-ribosyltransferase activity; ISS:UniProtKB.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IDA:RGD.
DR GO; GO:0042482; P:positive regulation of odontogenesis; ISO:RGD.
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:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; ISO:RGD.
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:1900182; P:positive regulation of protein localization to nucleus; ISO:RGD.
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; ISO:RGD.
DR GO; GO:1904894; P:positive regulation of receptor signaling pathway via STAT; ISO:RGD.
DR GO; GO:0045591; P:positive regulation of regulatory T cell differentiation; ISO:RGD.
DR GO; GO:0060391; P:positive regulation of SMAD protein signal transduction; ISS:AgBase.
DR GO; GO:0051152; P:positive regulation of smooth muscle cell differentiation; IDA:MGI.
DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; ISO:RGD.
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:0043117; P:positive regulation of vascular permeability; ISO:RGD.
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; IDA:CACAO.
DR GO; GO:0032801; P:receptor catabolic process; ISS:UniProtKB.
DR GO; GO:2000249; P:regulation of actin cytoskeleton reorganization; ISO:RGD.
DR GO; GO:0051098; P:regulation of binding; ISO:RGD.
DR GO; GO:0060762; P:regulation of branching involved in mammary gland duct morphogenesis; ISO:RGD.
DR GO; GO:0061035; P:regulation of cartilage development; ISO:RGD.
DR GO; GO:0051726; P:regulation of cell cycle; ISO:RGD.
DR GO; GO:0001558; P:regulation of cell growth; TAS:RGD.
DR GO; GO:0042127; P:regulation of cell population proliferation; ISO:RGD.
DR GO; GO:0051101; P:regulation of DNA binding; ISO:RGD.
DR GO; GO:0010468; P:regulation of gene expression; ISO:RGD.
DR GO; GO:0032667; P:regulation of interleukin-23 production; ISO:RGD.
DR GO; GO:0042306; P:regulation of protein import into nucleus; ISO:RGD.
DR GO; GO:0045589; P:regulation of regulatory T cell differentiation; ISO:RGD.
DR GO; GO:0060390; P:regulation of SMAD protein signal transduction; ISS:UniProtKB.
DR GO; GO:0002028; P:regulation of sodium ion transport; ISO:RGD.
DR GO; GO:0016202; P:regulation of striated muscle tissue development; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0070723; P:response to cholesterol; ISS:UniProtKB.
DR GO; GO:0032355; P:response to estradiol; IEP:RGD.
DR GO; GO:0009749; P:response to glucose; IEP:RGD.
DR GO; GO:0001666; P:response to hypoxia; IEP:RGD.
DR GO; GO:0035902; P:response to immobilization stress; IEP:RGD.
DR GO; GO:0034616; P:response to laminar fluid shear stress; IEP:RGD.
DR GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
DR GO; GO:0010033; P:response to organic substance; IDA:RGD.
DR GO; GO:0032570; P:response to progesterone; ISS:UniProtKB.
DR GO; GO:0009314; P:response to radiation; IEP:RGD.
DR GO; GO:1902074; P:response to salt; IEP:RGD.
DR GO; GO:0033280; P:response to vitamin D; IEP:RGD.
DR GO; GO:0009611; P:response to wounding; ISS:AgBase.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
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; ISO:RGD.
DR GO; GO:0042110; P:T cell activation; ISO:RGD.
DR GO; GO:0030217; P:T cell differentiation; ISO:RGD.
DR GO; GO:0043029; P:T cell homeostasis; ISO:RGD.
DR GO; GO:0042098; P:T cell proliferation; IEA:Ensembl.
DR GO; GO:0002513; P:tolerance induction to self antigen; ISO:RGD.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IEP:RGD.
DR GO; GO:1905313; P:transforming growth factor beta receptor signaling pathway involved in heart development; ISO:RGD.
DR GO; GO:0001657; P:ureteric bud development; ISO:RGD.
DR GO; GO:0001570; P:vasculogenesis; ISO:RGD.
DR GO; GO:0055010; P:ventricular cardiac muscle tissue morphogenesis; ISO:RGD.
DR GO; GO:0042060; P:wound healing; IMP:RGD.
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 Cleavage on pair of basic residues; 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:0000250|UniProtKB:P01137"
FT /id="PRO_0000033770"
FT CHAIN 279..390
FT /note="Transforming growth factor beta-1"
FT /evidence="ECO:0000250|UniProtKB:P01137"
FT /id="PRO_0000033771"
FT REGION 30..74
FT /note="Straightjacket domain"
FT /evidence="ECO:0000250|UniProtKB:P07200"
FT REGION 75..271
FT /note="Arm domain"
FT /evidence="ECO:0000250|UniProtKB:P07200"
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:0000255"
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:0000255"
FT CARBOHYD 136
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 176
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 33
FT /note="Interchain (with C-1359 or C-1384 in LTBP1); in
FT inactive form"
FT /evidence="ECO:0000250|UniProtKB:P07200"
FT DISULFID 223
FT /note="Interchain (with C-225)"
FT /evidence="ECO:0000250|UniProtKB:P01137"
FT DISULFID 225
FT /note="Interchain (with C-223)"
FT /evidence="ECO:0000250|UniProtKB:P01137"
FT DISULFID 285..294
FT /evidence="ECO:0000250|UniProtKB:P01137"
FT DISULFID 293..356
FT /evidence="ECO:0000250|UniProtKB:P01137"
FT DISULFID 322..387
FT /evidence="ECO:0000250|UniProtKB:P01137"
FT DISULFID 326..389
FT /evidence="ECO:0000250|UniProtKB:P01137"
FT DISULFID 355
FT /note="Interchain"
FT /evidence="ECO:0000250|UniProtKB:P01137"
SQ SEQUENCE 390 AA; 44329 MW; 5E21108ED50D853C CRC64;
MPPSGLRLLP LLLPLPWLLV LTPGRPAAGL STCKTIDMEL VKRKRIEAIR GQILSKLRLA
SPPSQGEVPP GPLPEAVLAL YNSTRDRVAG ESADPEPEPE ADYYAKEVTR VLMVDRNNAI
YDKTKDITHS IYMFFNTSDI REAVPEPPLL SRAELRLQRF KSTVEQHVEL YQKYSNNSWR
YLGNRLLTPT DTPEWLSFDV TGVVRQWLNQ GDGIQGFRFS AHCSCDSKDN VLHVEINGIS
PKRRGDLGTI HDMNRPFLLL MATPLERAQH LHSSRHRRAL DTNYCFSSTE KNCCVRQLYI
DFRKDLGWKW IHEPKGYHAN FCLGPCPYIW SLDTQYSKVL ALYNQHNPGA SASPCCVPQA
LEPLPIVYYV GRKPKVEQLS NMIVRSCKCS
