TGFB3_MOUSE
ID TGFB3_MOUSE Reviewed; 410 AA.
AC P17125;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1990, sequence version 1.
DT 03-AUG-2022, entry version 172.
DE RecName: Full=Transforming growth factor beta-3 proprotein;
DE Contains:
DE RecName: Full=Latency-associated peptide;
DE Short=LAP;
DE Contains:
DE RecName: Full=Transforming growth factor beta-3;
DE Short=TGF-beta-3;
DE Flags: Precursor;
GN Name=Tgfb3 {ECO:0000312|MGI:MGI:98727};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2628730; DOI=10.1210/mend-3-12-1926;
RA Miller D.A., Lee A., Matsui Y., Chen E.Y., Moses H.L., Derynck R.;
RT "Complementary DNA cloning of the murine transforming growth factor-beta 3
RT (TGF beta 3) precursor and the comparative expression of TGF beta 3 and TGF
RT beta 1 messenger RNA in murine embryos and adult tissues.";
RL Mol. Endocrinol. 3:1926-1934(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2206556; DOI=10.3109/08977199009108276;
RA Denhez F., Lafyatis R., Kondaiah P., Roberts A.B., Sporn M.B.;
RT "Cloning by polymerase chain reaction of a new mouse TGF-beta, mTGF-beta
RT 3.";
RL Growth Factors 3:139-146(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 285-410.
RC TISSUE=Testis;
RX PubMed=2069871;
RA Watrin F., Scotto L., Assoian R.K., Wolgemuth D.J.;
RT "Cell lineage specificity of expression of the murine transforming growth
RT factor beta 3 and transforming growth factor beta 1 genes.";
RL Cell Growth Differ. 2:77-83(1991).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=7493021; DOI=10.1038/ng1295-409;
RA Proetzel G., Pawlowski S.A., Wiles M.V., Yin M., Boivin G.P., Howles P.N.,
RA Ding J., Ferguson M.W., Doetschman T.;
RT "Transforming growth factor-beta 3 is required for secondary palate
RT fusion.";
RL Nat. Genet. 11:409-414(1995).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=7493022; DOI=10.1038/ng1295-415;
RA Kaartinen V., Voncken J.W., Shuler C., Warburton D., Bu D., Heisterkamp N.,
RA Groffen J.;
RT "Abnormal lung development and cleft palate in mice lacking TGF-beta 3
RT indicates defects of epithelial-mesenchymal interaction.";
RL Nat. Genet. 11:415-421(1995).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=10433915; DOI=10.1242/dev.126.17.3869;
RA Taya Y., O'Kane S., Ferguson M.W.;
RT "Pathogenesis of cleft palate in TGF-beta3 knockout mice.";
RL Development 126:3869-3879(1999).
RN [7]
RP FUNCTION, AND INTERACTION WITH LRRC32.
RX PubMed=28912269; DOI=10.1074/jbc.m117.797613;
RA Wu B.X., Li A., Lei L., Kaneko S., Wallace C., Li X., Li Z.;
RT "Glycoprotein A repetitions predominant (GARP) positively regulates
RT transforming growth factor (TGF) beta3 and is essential for mouse
RT palatogenesis.";
RL J. Biol. Chem. 292:18091-18097(2017).
CC -!- FUNCTION: Transforming growth factor beta-3 proprotein: Precursor of
CC the Latency-associated peptide (LAP) and Transforming growth factor
CC beta-3 (TGF-beta-3) chains, which constitute the regulatory and active
CC subunit of TGF-beta-3, respectively. {ECO:0000250|UniProtKB:P01137,
CC ECO:0000250|UniProtKB:P04202}.
CC -!- FUNCTION: [Latency-associated peptide]: Required to maintain the
CC Transforming growth factor beta-3 (TGF-beta-3) chain in a latent state
CC during storage in extracellular matrix (By similarity). Associates non-
CC covalently with TGF-beta-3 and regulates its activation via interaction
CC with 'milieu molecules', such as LTBP1 and LRRC32/GARP, that control
CC activation of TGF-beta-3 (PubMed:28912269). Interaction with integrins
CC results in distortion of the Latency-associated peptide chain and
CC subsequent release of the active TGF-beta-3 (By similarity).
CC {ECO:0000250|UniProtKB:P01137, ECO:0000250|UniProtKB:P04202,
CC ECO:0000269|PubMed:28912269}.
CC -!- FUNCTION: Transforming growth factor beta-3: Multifunctional protein
CC that regulates embryogenesis and cell differentiation and is required
CC in various processes such as secondary palate development
CC (PubMed:7493021, PubMed:7493022, PubMed:10433915, PubMed:28912269).
CC Activation into mature form follows different steps: following cleavage
CC of the proprotein in the Golgi apparatus, Latency-associated peptide
CC (LAP) and Transforming growth factor beta-3 (TGF-beta-3) chains remain
CC non-covalently linked rendering TGF-beta-3 inactive during storage in
CC extracellular matrix (By similarity). At the same time, LAP chain
CC interacts with 'milieu molecules', such as LTBP1 and LRRC32/GARP that
CC control activation of TGF-beta-3 and maintain it in a latent state
CC during storage in extracellular milieus (PubMed:28912269). TGF-beta-3
CC is released from LAP by integrins: integrin-binding results in
CC distortion of the LAP chain and subsequent release of the active TGF-
CC beta-3 (By similarity). Once activated following release of LAP, TGF-
CC beta-3 acts by binding to TGF-beta receptors (TGFBR1 and TGFBR2), which
CC transduce signal (By similarity). {ECO:0000250|UniProtKB:P01137,
CC ECO:0000250|UniProtKB:P04202, ECO:0000269|PubMed:10433915,
CC ECO:0000269|PubMed:28912269, ECO:0000269|PubMed:7493021,
CC ECO:0000269|PubMed:7493022}.
CC -!- SUBUNIT: Interacts with ASPN (By similarity). Latency-associated
CC peptide: Homodimer; disulfide-linked (By similarity). Latency-
CC associated peptide: Interacts with Transforming growth factor beta-3
CC (TGF-beta-3) chain; interaction is non-covalent and maintains (TGF-
CC beta-3) in a latent state (By similarity). Latency-associated peptide:
CC Interacts with LRRC32/GARP; leading to regulate activation of TGF-beta-
CC 3 and promote epithelial fusion during palate development
CC (PubMed:28912269). Latency-associated peptide: Interacts (via cell
CC attachment site) with integrins, leading to release of the active TGF-
CC beta-3 (By similarity). Transforming growth factor beta-3: Homodimer;
CC disulfide-linked (By similarity). Transforming growth factor beta-3:
CC Interacts with TGF-beta receptors (TGFBR1 and TGFBR2), leading to
CC signal transduction (By similarity). {ECO:0000250|UniProtKB:P01137,
CC ECO:0000250|UniProtKB:P04202, ECO:0000250|UniProtKB:P10600,
CC ECO:0000269|PubMed:28912269}.
CC -!- SUBCELLULAR LOCATION: [Latency-associated peptide]: Secreted,
CC extracellular space, extracellular matrix
CC {ECO:0000250|UniProtKB:P01137}.
CC -!- SUBCELLULAR LOCATION: [Transforming growth factor beta-3]: Secreted
CC {ECO:0000250|UniProtKB:P01137}.
CC -!- PTM: Transforming growth factor beta-3 proprotein: The precursor
CC proprotein is cleaved in the Golgi apparatus to form Transforming
CC growth factor beta-3 (TGF-beta-3) and Latency-associated peptide (LAP)
CC chains, which remain non-covalently linked, rendering TGF-beta-3
CC inactive. {ECO:0000250|UniProtKB:P01137}.
CC -!- PTM: Methylated at Gln-291 by N6AMT1. {ECO:0000250|UniProtKB:P10600}.
CC -!- DISRUPTION PHENOTYPE: Mice display a cleft palate caused by defects in
CC medial edge epithelial seam degeneration and palate fusion, leading to
CC death within the first day after birth. {ECO:0000269|PubMed:10433915,
CC ECO:0000269|PubMed:7493021, ECO:0000269|PubMed:7493022}.
CC -!- SIMILARITY: Belongs to the TGF-beta family. {ECO:0000305}.
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DR EMBL; M32745; AAA40422.1; -; mRNA.
DR PIR; A41397; A41397.
DR AlphaFoldDB; P17125; -.
DR BMRB; P17125; -.
DR SMR; P17125; -.
DR ComplexPortal; CPX-825; TGF-beta-3 complex.
DR ComplexPortal; CPX-826; TGF-beta-3-TGFR complex.
DR STRING; 10090.ENSMUSP00000003687; -.
DR GlyGen; P17125; 3 sites.
DR iPTMnet; P17125; -.
DR PhosphoSitePlus; P17125; -.
DR MaxQB; P17125; -.
DR PaxDb; P17125; -.
DR PeptideAtlas; P17125; -.
DR PRIDE; P17125; -.
DR ProteomicsDB; 263041; -.
DR MGI; MGI:98727; Tgfb3.
DR eggNOG; KOG3900; Eukaryota.
DR InParanoid; P17125; -.
DR PhylomeDB; P17125; -.
DR Reactome; R-MMU-114608; Platelet degranulation.
DR Reactome; R-MMU-2129379; Molecules associated with elastic fibres.
DR Reactome; R-MMU-2173789; TGF-beta receptor signaling activates SMADs.
DR ChiTaRS; Tgfb3; mouse.
DR PRO; PR:P17125; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; P17125; protein.
DR GO; GO:0009986; C:cell surface; ISO:MGI.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0031012; C:extracellular matrix; IDA:MGI.
DR GO; GO:0005615; C:extracellular space; ISO:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IC:ComplexPortal.
DR GO; GO:0030141; C:secretory granule; ISO:MGI.
DR GO; GO:0030315; C:T-tubule; ISO:MGI.
DR GO; GO:0099126; C:transforming growth factor beta complex; ISO:MGI.
DR GO; GO:0070021; C:transforming growth factor beta ligand-receptor complex; ISO:MGI.
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; ISS:AgBase.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0050431; F:transforming growth factor beta binding; ISS:AgBase.
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:AgBase.
DR GO; GO:0034714; F:type III transforming growth factor beta receptor binding; ISS:AgBase.
DR GO; GO:0009887; P:animal organ morphogenesis; IMP:MGI.
DR GO; GO:0030509; P:BMP signaling pathway; IBA:GO_Central.
DR GO; GO:0008283; P:cell population proliferation; IDA:MGI.
DR GO; GO:0045216; P:cell-cell junction organization; ISS:AgBase.
DR GO; GO:0071363; P:cellular response to growth factor stimulus; IDA:MGI.
DR GO; GO:0070483; P:detection of hypoxia; ISS:AgBase.
DR GO; GO:0048702; P:embryonic neurocranium morphogenesis; ISO:MGI.
DR GO; GO:0050673; P:epithelial cell proliferation; IDA:MGI.
DR GO; GO:0060325; P:face morphogenesis; IEP:UniProtKB.
DR GO; GO:0046847; P:filopodium assembly; IMP:MGI.
DR GO; GO:0010467; P:gene expression; IMP:MGI.
DR GO; GO:0001701; P:in utero embryonic development; IMP:MGI.
DR GO; GO:0048286; P:lung alveolus development; IMP:BHF-UCL.
DR GO; GO:0030879; P:mammary gland development; IDA:MGI.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISS:AgBase.
DR GO; GO:0050680; P:negative regulation of epithelial cell proliferation; IDA:MGI.
DR GO; GO:0010936; P:negative regulation of macrophage cytokine production; ISS:AgBase.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IMP:MGI.
DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; ISO:MGI.
DR GO; GO:1904706; P:negative regulation of vascular associated smooth muscle cell proliferation; ISO:MGI.
DR GO; GO:0051402; P:neuron apoptotic process; IMP:MGI.
DR GO; GO:0043932; P:ossification involved in bone remodeling; ISS:AgBase.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:MGI.
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:0008284; P:positive regulation of cell population proliferation; ISS:AgBase.
DR GO; GO:0032967; P:positive regulation of collagen biosynthetic process; ISS:AgBase.
DR GO; GO:0010718; P:positive regulation of epithelial to mesenchymal transition; IMP:BHF-UCL.
DR GO; GO:0051491; P:positive regulation of filopodium assembly; IMP:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; IDA:UniProtKB.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISO:MGI.
DR GO; GO:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation; IMP:BHF-UCL.
DR GO; GO:0050714; P:positive regulation of protein secretion; ISO:MGI.
DR GO; GO:0060391; P:positive regulation of SMAD protein signal transduction; IMP:BHF-UCL.
DR GO; GO:0051496; P:positive regulation of stress fiber assembly; ISO:MGI.
DR GO; GO:1905075; P:positive regulation of tight junction disassembly; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IGI:MGI.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:BHF-UCL.
DR GO; GO:0006468; P:protein phosphorylation; IC:ComplexPortal.
DR GO; GO:0042127; P:regulation of cell population proliferation; IBA:GO_Central.
DR GO; GO:0043627; P:response to estrogen; ISO:MGI.
DR GO; GO:0001666; P:response to hypoxia; ISS:AgBase.
DR GO; GO:0032570; P:response to progesterone; ISS:AgBase.
DR GO; GO:0060021; P:roof of mouth development; IMP:MGI.
DR GO; GO:0007435; P:salivary gland morphogenesis; ISS:AgBase.
DR GO; GO:0062009; P:secondary palate development; IMP:UniProtKB.
DR GO; GO:0060395; P:SMAD protein signal transduction; IBA:GO_Central.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; ISS:AgBase.
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; IPR015618; TGFB3.
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; PR01426; TGFBETA3.
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; Methylation; Mitogen; Reference proteome;
KW Secreted; Signal.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..298
FT /note="Latency-associated peptide"
FT /evidence="ECO:0000250|UniProtKB:P01137"
FT /id="PRO_0000033798"
FT CHAIN 299..410
FT /note="Transforming growth factor beta-3"
FT /evidence="ECO:0000250|UniProtKB:P01137"
FT /id="PRO_0000033799"
FT MOTIF 259..261
FT /note="Cell attachment site"
FT /evidence="ECO:0000250|UniProtKB:P01137"
FT MOD_RES 291
FT /note="N5-methylglutamine"
FT /evidence="ECO:0000250|UniProtKB:P10600"
FT CARBOHYD 72
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 133
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 140
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 305..314
FT /evidence="ECO:0000250|UniProtKB:P10600"
FT DISULFID 313..376
FT /evidence="ECO:0000250|UniProtKB:P10600"
FT DISULFID 342..407
FT /evidence="ECO:0000250|UniProtKB:P10600"
FT DISULFID 346..409
FT /evidence="ECO:0000250|UniProtKB:P10600"
FT DISULFID 375
FT /note="Interchain"
FT /evidence="ECO:0000250|UniProtKB:P10600"
SQ SEQUENCE 410 AA; 46885 MW; 250F7048CA432BD6 CRC64;
MHLQRALVVL ALLNLATISL SLSTCTTLDF GHIKKKRVEA IRGQILSKLR LTSPPEPSVM
THVPYQVLAL YNSTRELLEE MHGEREEGCT QETSESEYYA KEIHKFDMIQ GLAEHNELAV
CPKGITSKVF RFNVSSVEKN GTNLFRAEFR VLRVPNPSSK RTEQRIELFQ ILRPDEHIAK
QRYIGGKNLP TRGTAEWLSF DVTDTVREWL LRRESNLGLE ISIHCPCHTF QPNGDILENV
HEVMEIKFKG VDNEDDHGRG DLGRLKKQKD HHNPHLILMM IPPHRLDSPG QGSQRKKRAL
DTNYCFRNLE ENCCVRPLYI DFRQDLGWKW VHEPKGYYAN FCSGPCPYLR SADTTHSTVL
GLYNTLNPEA SASPCCVPQD LEPLTILYYV GRTPKVEQLS NMVVKSCKCS
