TGFB3_HUMAN
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 03-AUG-2022, entry version 229.
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";
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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 GlyGen; P10600; 3 sites, 3 N-linked glycans (1 site).
DR iPTMnet; P10600; -.
DR PhosphoSitePlus; P10600; -.
DR BioMuta; TGFB3; -.
DR DMDM; 135684; -.
DR jPOST; P10600; -.
DR MassIVE; P10600; -.
DR PaxDb; P10600; -.
DR PeptideAtlas; P10600; -.
DR PRIDE; P10600; -.
DR ProteomicsDB; 52617; -. [P10600-1]
DR ProteomicsDB; 74762; -.
DR ABCD; P10600; 1 sequenced antibody.
DR Antibodypedia; 4331; 486 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 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; 293899; Familial isolated arrhythmogenic ventricular dysplasia, biventricular form.
DR Orphanet; 293888; Familial isolated arrhythmogenic ventricular dysplasia, left dominant form.
DR Orphanet; 293910; Familial isolated arrhythmogenic ventricular dysplasia, right dominant form.
DR Orphanet; 91387; Familial thoracic aortic aneurysm and aortic dissection.
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; NNDLPNC; -.
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; 8 hits in 1079 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 167 other tissues.
DR ExpressionAtlas; P10600; baseline and differential.
DR Genevisible; P10600; HS.
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:0005634; C:nucleus; 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:0099126; C:transforming growth factor beta complex; IPI:ComplexPortal.
DR GO; GO:0070021; C:transforming growth factor beta ligand-receptor complex; IPI:ComplexPortal.
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:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0030509; P:BMP signaling pathway; IBA:GO_Central.
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:0043932; P:ossification involved in bone remodeling; IEP:BHF-UCL.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISS:BHF-UCL.
DR GO; GO:0030501; P:positive regulation of bone mineralization; IEP: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: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:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation; ISS:BHF-UCL.
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:0045893; P:positive regulation of transcription, DNA-templated; IDA: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:0060395; P:SMAD protein signal transduction; IBA:GO_Central.
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 GO; GO:0042060; P:wound healing; IEA:Ensembl.
DR Gene3D; 2.10.90.10; -; 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; 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 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
