ID TGFB3_HUMAN Reviewed; 412 AA. AC P10600; Q8WV88; DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot. DT 01-JUL-1989, sequence version 1. DT 24-JAN-2024, entry version 237. 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; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=3164476; DOI=10.1073/pnas.85.13.4715; RA ten Dijke P., Hansen P., Iwata K., Pieler C., Foulkes J.G.; RT "Identification of another member of the transforming growth factor type RT beta gene family."; RL Proc. Natl. Acad. Sci. U.S.A. 85:4715-4719(1988). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Placenta; RX PubMed=3208746; DOI=10.1002/j.1460-2075.1988.tb03257.x; RA Derynck R., Lindquist P.B., Lee A., Wen D., Tamm J., Graycar J.L., Rhee L., RA Mason A.J., Miller D.A., Coffey R.J., Moses H.L., Chen E.Y.; RT "A new type of transforming growth factor-beta, TGF-beta 3."; RL EMBO J. 7:3737-3743(1988). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RA Madan A., Rowen L., Qin S., Dickhoff R., Shaffer T., James R., Abbasi N., RA Loretz C., Madan A., Dors M., Dahl T., Hall J., Lasky S., Hood L.; RT "Complete genomic sequence of human transforming growth factor-beta 3."; RL Submitted (NOV-1998) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RG NIEHS SNPs program; RL Submitted (AUG-2002) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT MET-60. RG SeattleSNPs variation discovery resource; RL Submitted (DEC-2002) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12508121; DOI=10.1038/nature01348; RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., RA Waterston R., Hood L., Weissenbach J.; RT "The DNA sequence and analysis of human chromosome 14."; RL Nature 421:601-607(2003). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Prostate; 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 [9] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-48 (ISOFORM 1/2). RX PubMed=1875922; DOI=10.1128/mcb.11.9.4306-4313.1991; RA Arrick B.A., Lee A.L., Grendell R.L., Derynck R.; RT "Inhibition of translation of transforming growth factor-beta 3 mRNA by its RT 5' untranslated region."; RL Mol. Cell. Biol. 11:4306-4313(1991). RN [10] RP INTERACTION WITH ASPN. RX PubMed=17827158; DOI=10.1074/jbc.m700522200; RA Nakajima M., Kizawa H., Saitoh M., Kou I., Miyazono K., Ikegawa S.; RT "Mechanisms for asporin function and regulation in articular cartilage."; RL J. Biol. Chem. 282:32185-32192(2007). RN [11] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 301-412, AND DISULFIDE BONDS. RX PubMed=8819159; DOI=10.1002/pro.5560050705; RA Mittl P.R.E., Priestle J.P., Cox D.A., McMaster G., Cerletti N., RA Gruetter M.G.; RT "The crystal structure of TGF-beta 3 and comparison to TGF-beta 2: RT implications for receptor binding."; RL Protein Sci. 5:1261-1271(1996). RN [12] RP INVOLVEMENT IN ARVD1. RX PubMed=15639475; DOI=10.1016/j.cardiores.2004.10.005; RA Beffagna G., Occhi G., Nava A., Vitiello L., Ditadi A., Basso C., Bauce B., RA Carraro G., Thiene G., Towbin J.A., Danieli G.A., Rampazzo A.; RT "Regulatory mutations in transforming growth factor-beta3 gene cause RT arrhythmogenic right ventricular cardiomyopathy type 1."; RL Cardiovasc. Res. 65:366-373(2005). RN [13] RP METHYLATION AT GLN-293, AND MUTAGENESIS OF GLN-293. RX PubMed=26797129; DOI=10.1074/jbc.m115.711952; RA Kusevic D., Kudithipudi S., Jeltsch A.; RT "Substrate specificity of the HEMK2 protein glutamine methyltransferase and RT identification of novel substrates."; RL J. Biol. Chem. 291:6124-6133(2016). RN [14] RP VARIANT LDS5 TYR-409, AND CHARACTERIZATION OF VARIANT LDS5 TYR-409. RX PubMed=23824657; DOI=10.1002/ajmg.a.36056; RA Rienhoff H.Y. Jr., Yeo C.Y., Morissette R., Khrebtukova I., Melnick J., RA Luo S., Leng N., Kim Y.J., Schroth G., Westwick J., Vogel H., McDonnell N., RA Hall J.G., Whitman M.; RT "A mutation in TGFB3 associated with a syndrome of low muscle mass, growth RT retardation, distal arthrogryposis and clinical features overlapping with RT Marfan and Loeys-Dietz syndrome."; RL Am. J. Med. Genet. A 161A:2040-2046(2013). 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 (By similarity). 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:0000250|UniProtKB:P17125}. 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 (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-3 (TGF- CC beta-3) chains remain non-covalently linked rendering TGF-beta-3 CC inactive during storage in extracellular matrix (By similarity). At the CC same time, LAP chain interacts with 'milieu molecules', such as LTBP1 CC and LRRC32/GARP that control activation of TGF-beta-3 and maintain it CC in a latent state during storage in extracellular milieus (By CC similarity). TGF-beta-3 is released from LAP by integrins: integrin- CC binding results in distortion of the LAP chain and subsequent release CC of the active TGF-beta-3 (By similarity). Once activated following CC release of LAP, TGF-beta-3 acts by binding to TGF-beta receptors CC (TGFBR1 and TGFBR2), which transduce signal (By similarity). CC {ECO:0000250|UniProtKB:P01137, ECO:0000250|UniProtKB:P04202, CC ECO:0000250|UniProtKB:P17125}. CC -!- SUBUNIT: Interacts with ASPN (PubMed:8819159). Latency-associated CC peptide: Homodimer; disulfide-linked. Latency-associated peptide: CC Interacts with Transforming growth factor beta-3 (TGF-beta-3) chain; CC interaction is non-covalent and maintains (TGF-beta-3) in a latent CC state (By similarity). Latency-associated peptide: Interacts with CC LRRC32/GARP; leading to regulate activation of TGF-beta-3 and promote CC epithelial fusion during palate development (By similarity). Latency- CC associated peptide: Interacts (via cell attachment site) with CC integrins, leading to release of the active TGF-beta-3 (By similarity). CC Transforming growth factor beta-3: Homodimer; disulfide-linked CC (PubMed:8819159). Transforming growth factor beta-3: Interacts with CC TGF-beta receptors (TGFBR1 and TGFBR2), leading to signal transduction CC (By similarity). {ECO:0000250|UniProtKB:P01137, CC ECO:0000250|UniProtKB:P04202, ECO:0000250|UniProtKB:P17125, CC ECO:0000269|PubMed:8819159}. CC -!- INTERACTION: CC P10600; P10600: TGFB3; NbExp=2; IntAct=EBI-1033020, EBI-1033020; CC P10600; P37173: TGFBR2; NbExp=8; IntAct=EBI-1033020, 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-3]: Secreted CC {ECO:0000250|UniProtKB:P01137}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P10600-1; Sequence=Displayed; CC Name=2; CC IsoId=P10600-2; Sequence=VSP_056285; 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-293 by N6AMT1. {ECO:0000269|PubMed:26797129}. CC -!- DISEASE: Arrhythmogenic right ventricular dysplasia, familial, 1 CC (ARVD1) [MIM:107970]: A congenital heart disease characterized by CC infiltration of adipose and fibrous tissue into the right ventricle and CC loss of myocardial cells, resulting in ventricular and supraventricular CC arrhythmias. {ECO:0000269|PubMed:15639475}. Note=The disease is caused CC by variants affecting the gene represented in this entry. CC -!- DISEASE: Loeys-Dietz syndrome 5 (LDS5) [MIM:615582]: A form of Loeys- CC Dietz syndrome, a syndrome with widespread systemic involvement CC characterized by arterial tortuosity and aneurysms, hypertelorism, and CC bifid uvula or cleft palate. LDS5 additional variable features include CC mitral valve disease, skeletal overgrowth, cervical spine instability, CC and clubfoot deformity. LDS5 patients do not manifest remarkable aortic CC or arterial tortuosity, and there is no strong evidence for early CC aortic dissection. {ECO:0000269|PubMed:23824657}. Note=The disease is CC caused by variants affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the TGF-beta family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=CAA33024.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/tgfb3/"; CC -!- WEB RESOURCE: Name=SeattleSNPs; CC URL="http://pga.gs.washington.edu/data/tgfb3/"; CC -!- WEB RESOURCE: Name=Wikipedia; Note=TGF beta-3 entry; CC URL="https://en.wikipedia.org/wiki/TGF_beta_3"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; J03241; AAA61161.1; -; mRNA. DR EMBL; X14149; CAA32362.1; -; mRNA. DR EMBL; X14885; CAA33024.1; ALT_INIT; Genomic_DNA. DR EMBL; X14886; CAA33024.1; JOINED; Genomic_DNA. DR EMBL; X14887; CAA33024.1; JOINED; Genomic_DNA. DR EMBL; X14888; CAA33024.1; JOINED; Genomic_DNA. DR EMBL; X14889; CAA33024.1; JOINED; Genomic_DNA. DR EMBL; X14890; CAA33024.1; JOINED; Genomic_DNA. DR EMBL; X14891; CAA33024.1; JOINED; Genomic_DNA. DR EMBL; AY140241; AAM96819.1; -; Genomic_DNA. DR EMBL; AY208161; AAO13495.1; -; Genomic_DNA. DR EMBL; BT007287; AAP35951.1; -; mRNA. DR EMBL; AF107885; AAC79727.1; -; Genomic_DNA. DR EMBL; BC018503; AAH18503.1; -; mRNA. DR CCDS; CCDS86415.1; -. [P10600-2] DR CCDS; CCDS9846.1; -. [P10600-1] DR PIR; A36169; A36169. DR RefSeq; NP_001316867.1; NM_001329938.1. [P10600-2] DR RefSeq; NP_001316868.1; NM_001329939.1. [P10600-1] DR RefSeq; NP_003230.1; NM_003239.4. [P10600-1] DR PDB; 1KTZ; X-ray; 2.15 A; A=301-412. DR PDB; 1TGJ; X-ray; 2.00 A; A=301-412. DR PDB; 1TGK; X-ray; 3.30 A; A=301-412. DR PDB; 2PJY; X-ray; 3.00 A; A=301-412. DR PDB; 3EO1; X-ray; 3.10 A; C/F/I/L=301-412. DR PDB; 4UM9; X-ray; 2.50 A; E/F=259-269. DR PDBsum; 1KTZ; -. DR PDBsum; 1TGJ; -. DR PDBsum; 1TGK; -. DR PDBsum; 2PJY; -. DR PDBsum; 3EO1; -. DR PDBsum; 4UM9; -. DR AlphaFoldDB; P10600; -. DR BMRB; P10600; -. DR SMR; P10600; -. DR BioGRID; 112901; 9. DR ComplexPortal; CPX-2544; TGF-beta-3-TGFR complex. DR ComplexPortal; CPX-606; TGF-beta-3 complex. DR CORUM; P10600; -. DR DIP; DIP-5937N; -. DR IntAct; P10600; 10. DR MINT; P10600; -. DR STRING; 9606.ENSP00000238682; -. DR ChEMBL; CHEMBL3712903; -. DR DrugBank; DB03316; 1,4-Dioxane. DR GlyConnect; 1837; 3 N-Linked glycans (1 site). DR GlyCosmos; P10600; 3 sites, 3 glycans. DR GlyGen; P10600; 4 sites, 3 N-linked glycans (1 site), 1 O-linked glycan (1 site). DR iPTMnet; P10600; -. DR PhosphoSitePlus; P10600; -. DR BioMuta; TGFB3; -. DR DMDM; 135684; -. DR jPOST; P10600; -. DR MassIVE; P10600; -. DR PaxDb; 9606-ENSP00000238682; -. DR PeptideAtlas; P10600; -. DR ProteomicsDB; 52617; -. [P10600-1] DR ProteomicsDB; 74762; -. DR ABCD; P10600; 54 sequenced antibodies. DR Antibodypedia; 4331; 580 antibodies from 39 providers. DR DNASU; 7043; -. DR Ensembl; ENST00000238682.8; ENSP00000238682.3; ENSG00000119699.8. [P10600-1] DR Ensembl; ENST00000556285.1; ENSP00000451110.1; ENSG00000119699.8. [P10600-2] DR Ensembl; ENST00000556674.2; ENSP00000502685.1; ENSG00000119699.8. [P10600-1] DR GeneID; 7043; -. DR KEGG; hsa:7043; -. DR MANE-Select; ENST00000238682.8; ENSP00000238682.3; NM_003239.5; NP_003230.1. DR UCSC; uc001xsc.3; human. [P10600-1] DR AGR; HGNC:11769; -. DR CTD; 7043; -. DR DisGeNET; 7043; -. DR GeneCards; TGFB3; -. DR GeneReviews; TGFB3; -. DR HGNC; HGNC:11769; TGFB3. DR HPA; ENSG00000119699; Low tissue specificity. DR MalaCards; TGFB3; -. DR MIM; 107970; phenotype. DR MIM; 190230; gene. DR MIM; 615582; phenotype. DR neXtProt; NX_P10600; -. DR OpenTargets; ENSG00000119699; -. DR Orphanet; 91387; Familial thoracic aortic aneurysm and aortic dissection. DR Orphanet; 293888; Inherited isolated arrhythmogenic cardiomyopathy, dominant-left variant. DR Orphanet; 293910; Inherited isolated arrhythmogenic cardiomyopathy, dominant-right variant. DR Orphanet; 293899; Inherited isolated arrhythmogenic ventricular dysplasia, biventricular variant. DR Orphanet; 60030; Loeys-Dietz syndrome. DR PharmGKB; PA36483; -. DR VEuPathDB; HostDB:ENSG00000119699; -. DR eggNOG; KOG3900; Eukaryota. DR GeneTree; ENSGT00940000155747; -. DR HOGENOM; CLU_039840_0_0_1; -. DR InParanoid; P10600; -. DR OMA; SHMKMYV; -. DR OrthoDB; 5390486at2759; -. DR PhylomeDB; P10600; -. DR TreeFam; TF351793; -. DR PathwayCommons; P10600; -. DR Reactome; R-HSA-114608; Platelet degranulation. DR Reactome; R-HSA-2129379; Molecules associated with elastic fibres. DR Reactome; R-HSA-2173789; TGF-beta receptor signaling activates SMADs. DR Reactome; R-HSA-3000178; ECM proteoglycans. DR SignaLink; P10600; -. DR SIGNOR; P10600; -. DR BioGRID-ORCS; 7043; 9 hits in 1157 CRISPR screens. DR ChiTaRS; TGFB3; human. DR EvolutionaryTrace; P10600; -. DR GeneWiki; Transforming_growth_factor,_beta_3; -. DR GenomeRNAi; 7043; -. DR Pharos; P10600; Tbio. DR PRO; PR:P10600; -. DR Proteomes; UP000005640; Chromosome 14. DR RNAct; P10600; Protein. DR Bgee; ENSG00000119699; Expressed in saphenous vein and 169 other cell types or tissues. DR ExpressionAtlas; P10600; baseline and differential. DR GO; GO:0009986; C:cell surface; IEA:Ensembl. DR GO; GO:0062023; C:collagen-containing extracellular matrix; IDA:BHF-UCL. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; IBA:GO_Central. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA. DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl. DR GO; GO:0005886; C:plasma membrane; IC:BHF-UCL. DR GO; GO:0031093; C:platelet alpha granule lumen; TAS:Reactome. DR GO; GO:0030315; C:T-tubule; IEA:Ensembl. 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; IDA:BHF-UCL. DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl. DR GO; GO:0050431; F:transforming growth factor beta binding; IDA:BHF-UCL. DR GO; GO:0034713; F:type I transforming growth factor beta receptor binding; IDA:BHF-UCL. DR GO; GO:0005114; F:type II transforming growth factor beta receptor binding; IDA:BHF-UCL. DR GO; GO:0034714; F:type III transforming growth factor beta receptor binding; IMP:AgBase. DR GO; GO:0045216; P:cell-cell junction organization; IDA:BHF-UCL. DR GO; GO:0070483; P:detection of hypoxia; IDA:BHF-UCL. DR GO; GO:0048565; P:digestive tract development; IEA:Ensembl. DR GO; GO:0048702; P:embryonic neurocranium morphogenesis; IEA:Ensembl. DR GO; GO:0060325; P:face morphogenesis; IMP:BHF-UCL. DR GO; GO:0007565; P:female pregnancy; IEA:Ensembl. DR GO; GO:0060364; P:frontal suture morphogenesis; IEA:Ensembl. DR GO; GO:0001701; P:in utero embryonic development; ISS:BHF-UCL. DR GO; GO:0048839; P:inner ear development; IEA:Ensembl. DR GO; GO:0048286; P:lung alveolus development; ISS:BHF-UCL. DR GO; GO:0030879; P:mammary gland development; ISS:BHF-UCL. DR GO; GO:0008285; P:negative regulation of cell population proliferation; IMP:BHF-UCL. DR GO; GO:0010936; P:negative regulation of macrophage cytokine production; IDA:DFLAT. DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISS:BHF-UCL. DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; IEA:Ensembl. DR GO; GO:1904706; P:negative regulation of vascular associated smooth muscle cell proliferation; IDA:BHF-UCL. DR GO; GO:0042476; P:odontogenesis; NAS:BHF-UCL. DR GO; GO:0043065; P:positive regulation of apoptotic process; ISS:BHF-UCL. DR GO; GO:0051781; P:positive regulation of cell division; IEA:UniProtKB-KW. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:BHF-UCL. DR GO; GO:0032967; P:positive regulation of collagen biosynthetic process; IMP:BHF-UCL. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:BHF-UCL. DR GO; GO:0010718; P:positive regulation of epithelial to mesenchymal transition; IDA:BHF-UCL. DR GO; GO:0051491; P:positive regulation of filopodium assembly; ISS:BHF-UCL. DR GO; GO:0043410; P:positive regulation of MAPK cascade; IEA:Ensembl. DR GO; GO:0050714; P:positive regulation of protein secretion; IDA:BHF-UCL. DR GO; GO:0060391; P:positive regulation of SMAD protein signal transduction; ISS:BHF-UCL. DR GO; GO:0051496; P:positive regulation of stress fiber assembly; IDA:BHF-UCL. DR GO; GO:1905075; P:positive regulation of tight junction disassembly; IDA:BHF-UCL. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:BHF-UCL. DR GO; GO:0042127; P:regulation of cell population proliferation; IBA:GO_Central. DR GO; GO:0043627; P:response to estrogen; IEA:Ensembl. DR GO; GO:0001666; P:response to hypoxia; IDA:BHF-UCL. DR GO; GO:0034616; P:response to laminar fluid shear stress; IEA:Ensembl. DR GO; GO:0032570; P:response to progesterone; IDA:BHF-UCL. DR GO; GO:0007435; P:salivary gland morphogenesis; IEP:BHF-UCL. DR GO; GO:0062009; P:secondary palate development; ISS:BHF-UCL. DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IDA:BHF-UCL. DR GO; GO:0042704; P:uterine wall breakdown; TAS:BHF-UCL. DR CDD; cd19386; TGF_beta_TGFB3; 1. DR Gene3D; 2.60.120.970; -; 1. DR Gene3D; 2.10.90.10; Cystine-knot cytokines; 1. DR IDEAL; IID00355; -. 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; TGF-BETA FAMILY; 1. DR PANTHER; PTHR11848:SF34; TRANSFORMING GROWTH FACTOR BETA-3 PROPROTEIN; 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; Cystine-knot cytokines; 1. DR PROSITE; PS00250; TGF_BETA_1; 1. DR PROSITE; PS51362; TGF_BETA_2; 1. DR Genevisible; P10600; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cardiomyopathy; KW Cleavage on pair of basic residues; Disease variant; Disulfide bond; KW Extracellular matrix; Glycoprotein; Growth factor; Methylation; Mitogen; KW Reference proteome; Secreted; Signal. FT SIGNAL 1..23 FT /evidence="ECO:0000255" FT CHAIN 24..300 FT /note="Latency-associated peptide" FT /evidence="ECO:0000250|UniProtKB:P01137" FT /id="PRO_0000033796" FT CHAIN 301..412 FT /note="Transforming growth factor beta-3" FT /evidence="ECO:0000250|UniProtKB:P01137" FT /id="PRO_0000033797" FT MOTIF 261..263 FT /note="Cell attachment site" FT /evidence="ECO:0000250|UniProtKB:P01137" FT MOD_RES 293 FT /note="N5-methylglutamine" FT /evidence="ECO:0000269|PubMed:26797129" FT CARBOHYD 74 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 135 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 142 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 307..316 FT /evidence="ECO:0000269|PubMed:8819159" FT DISULFID 315..378 FT /evidence="ECO:0000269|PubMed:8819159" FT DISULFID 344..409 FT /evidence="ECO:0000269|PubMed:8819159" FT DISULFID 348..411 FT /evidence="ECO:0000269|PubMed:8819159" FT DISULFID 377 FT /note="Interchain" FT /evidence="ECO:0000269|PubMed:8819159" FT VAR_SEQ 310..412 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334, ECO:0000303|Ref.6" FT /id="VSP_056285" FT VARIANT 60 FT /note="T -> M (in dbSNP:rs4252315)" FT /evidence="ECO:0000269|Ref.5" FT /id="VAR_016315" FT VARIANT 409 FT /note="C -> Y (in LDS5; hypomorphic mutation; results in FT impaired TGF-beta signaling; dbSNP:rs398122984)" FT /evidence="ECO:0000269|PubMed:23824657" FT /id="VAR_070924" FT MUTAGEN 293 FT /note="Q->R: Abolishes methylation by N6AMT1." FT /evidence="ECO:0000269|PubMed:26797129" FT HELIX 265..268 FT /evidence="ECO:0007829|PDB:4UM9" FT HELIX 304..309 FT /evidence="ECO:0007829|PDB:1TGJ" FT STRAND 314..318 FT /evidence="ECO:0007829|PDB:1TGJ" FT STRAND 321..323 FT /evidence="ECO:0007829|PDB:1TGJ" FT HELIX 324..328 FT /evidence="ECO:0007829|PDB:1TGJ" FT STRAND 333..335 FT /evidence="ECO:0007829|PDB:1TGJ" FT STRAND 337..340 FT /evidence="ECO:0007829|PDB:1TGJ" FT STRAND 343..346 FT /evidence="ECO:0007829|PDB:1TGJ" FT TURN 350..353 FT /evidence="ECO:0007829|PDB:1TGJ" FT HELIX 357..368 FT /evidence="ECO:0007829|PDB:1TGJ" FT HELIX 370..372 FT /evidence="ECO:0007829|PDB:3EO1" FT STRAND 377..380 FT /evidence="ECO:0007829|PDB:1TGJ" FT STRAND 382..392 FT /evidence="ECO:0007829|PDB:1TGJ" FT STRAND 395..406 FT /evidence="ECO:0007829|PDB:1TGJ" FT STRAND 408..412 FT /evidence="ECO:0007829|PDB:1TGJ" SQ SEQUENCE 412 AA; 47328 MW; 3CAD3548D3AEA178 CRC64; MKMHLQRALV VLALLNFATV SLSLSTCTTL DFGHIKKKRV EAIRGQILSK LRLTSPPEPT VMTHVPYQVL ALYNSTRELL EEMHGEREEG CTQENTESEY YAKEIHKFDM IQGLAEHNEL AVCPKGITSK VFRFNVSSVE KNRTNLFRAE FRVLRVPNPS SKRNEQRIEL FQILRPDEHI AKQRYIGGKN LPTRGTAEWL SFDVTDTVRE WLLRRESNLG LEISIHCPCH TFQPNGDILE NIHEVMEIKF KGVDNEDDHG RGDLGRLKKQ KDHHNPHLIL MMIPPHRLDN PGQGGQRKKR ALDTNYCFRN LEENCCVRPL YIDFRQDLGW KWVHEPKGYY ANFCSGPCPY LRSADTTHST VLGLYNTLNP EASASPCCVP QDLEPLTILY YVGRTPKVEQ LSNMVVKSCK CS //