TGFB3_RAT
ID TGFB3_RAT Reviewed; 412 AA.
AC Q07258; Q56A31;
DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 2.
DT 03-AUG-2022, entry version 160.
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; Synonyms=Tgf-b3;
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=Wistar; TISSUE=Lung;
RX PubMed=7852342; DOI=10.1074/jbc.270.6.2722;
RA Wang J., Kuliszewski M., Yee W., Sedlackova L., Xu J., Tseu I., Post M.;
RT "Cloning and expression of glucocorticoid-induced genes in fetal rat lung
RT fibroblasts. Transforming growth factor-beta 3.";
RL J. Biol. Chem. 270:2722-2728(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 159-213.
RX PubMed=8509457; DOI=10.1083/jcb.121.6.1397;
RA McKinnon R.D., Piras G., Ida J., Dubois-Dalq M.;
RT "A role for TGF-beta in oligodendrocyte differentiation.";
RL J. Cell Biol. 121:1397-1407(1993).
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 (By similarity). 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 (By
CC similarity). Transforming growth factor beta-3: Interacts with TGF-beta
CC receptors (TGFBR1 and TGFBR2), leading to signal transduction (By
CC similarity). {ECO:0000250|UniProtKB:P01137,
CC ECO:0000250|UniProtKB:P04202, ECO:0000250|UniProtKB:P10600,
CC ECO:0000250|UniProtKB:P17125}.
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-293 by N6AMT1. {ECO:0000250|UniProtKB:P10600}.
CC -!- SIMILARITY: Belongs to the TGF-beta family. {ECO:0000305}.
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DR EMBL; U03491; AAA67915.1; -; mRNA.
DR EMBL; BC092195; AAH92195.1; -; mRNA.
DR EMBL; X71903; CAA50722.1; -; mRNA.
DR PIR; A55706; A55706.
DR RefSeq; NP_037306.1; NM_013174.2.
DR AlphaFoldDB; Q07258; -.
DR BMRB; Q07258; -.
DR SMR; Q07258; -.
DR STRING; 10116.ENSRNOP00000013516; -.
DR GlyGen; Q07258; 3 sites.
DR PhosphoSitePlus; Q07258; -.
DR PaxDb; Q07258; -.
DR Ensembl; ENSRNOT00000013516; ENSRNOP00000013516; ENSRNOG00000009867.
DR GeneID; 25717; -.
DR KEGG; rno:25717; -.
DR UCSC; RGD:3851; rat.
DR CTD; 7043; -.
DR RGD; 3851; Tgfb3.
DR eggNOG; KOG3900; Eukaryota.
DR GeneTree; ENSGT00940000155747; -.
DR HOGENOM; CLU_039840_0_0_1; -.
DR InParanoid; Q07258; -.
DR OMA; NNDLPNC; -.
DR OrthoDB; 643840at2759; -.
DR PhylomeDB; Q07258; -.
DR TreeFam; TF351793; -.
DR Reactome; R-RNO-114608; Platelet degranulation.
DR Reactome; R-RNO-2129379; Molecules associated with elastic fibres.
DR Reactome; R-RNO-2173789; TGF-beta receptor signaling activates SMADs.
DR PRO; PR:Q07258; -.
DR Proteomes; UP000002494; Chromosome 6.
DR Bgee; ENSRNOG00000009867; Expressed in pancreas and 19 other tissues.
DR Genevisible; Q07258; RN.
DR GO; GO:0009986; C:cell surface; IDA:RGD.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0031012; C:extracellular matrix; ISS:AgBase.
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; IDA:RGD.
DR GO; GO:0030141; C:secretory granule; IDA:RGD.
DR GO; GO:0030315; C:T-tubule; IDA:RGD.
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; IDA:RGD.
DR GO; GO:0050431; F:transforming growth factor beta binding; ISS:AgBase.
DR GO; GO:0005160; F:transforming growth factor beta receptor binding; TAS: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:AgBase.
DR GO; GO:0034714; F:type III transforming growth factor beta receptor binding; ISS:AgBase.
DR GO; GO:0007568; P:aging; IEP:RGD.
DR GO; GO:0009887; P:animal organ morphogenesis; ISO:RGD.
DR GO; GO:0030509; P:BMP signaling pathway; IBA:GO_Central.
DR GO; GO:0045216; P:cell-cell junction organization; ISS:AgBase.
DR GO; GO:0071363; P:cellular response to growth factor stimulus; ISO:RGD.
DR GO; GO:0070483; P:detection of hypoxia; ISS:AgBase.
DR GO; GO:0048565; P:digestive tract development; IEP:RGD.
DR GO; GO:0048702; P:embryonic neurocranium morphogenesis; IDA:RGD.
DR GO; GO:0060325; P:face morphogenesis; ISS:AgBase.
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:0001701; P:in utero embryonic development; ISO:RGD.
DR GO; GO:0048839; P:inner ear development; IEP:RGD.
DR GO; GO:0048286; P:lung alveolus development; ISO:RGD.
DR GO; GO:0030324; P:lung development; NAS:RGD.
DR GO; GO:0030879; P:mammary gland development; ISO:RGD.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:RGD.
DR GO; GO:0010936; P:negative regulation of macrophage cytokine production; ISS:AgBase.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISO:RGD.
DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; IDA:RGD.
DR GO; GO:1904706; P:negative regulation of vascular associated smooth muscle cell proliferation; ISO:RGD.
DR GO; GO:0043932; P:ossification involved in bone remodeling; ISS:AgBase.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:RGD.
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; ISS:AgBase.
DR GO; GO:0051491; P:positive regulation of filopodium assembly; ISO:RGD.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IDA:RGD.
DR GO; GO:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation; ISO:RGD.
DR GO; GO:0050714; P:positive regulation of protein secretion; ISO:RGD.
DR GO; GO:0060391; P:positive regulation of SMAD protein signal transduction; ISO:RGD.
DR GO; GO:0051496; P:positive regulation of stress fiber assembly; ISO:RGD.
DR GO; GO:1905075; P:positive regulation of tight junction disassembly; ISO:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:AgBase.
DR GO; GO:0042127; P:regulation of cell population proliferation; IBA:GO_Central.
DR GO; GO:0045601; P:regulation of endothelial cell differentiation; TAS:RGD.
DR GO; GO:0030856; P:regulation of epithelial cell differentiation; TAS:RGD.
DR GO; GO:0050678; P:regulation of epithelial cell proliferation; TAS:RGD.
DR GO; GO:0043627; P:response to estrogen; IDA:RGD.
DR GO; GO:0001666; P:response to hypoxia; IEP:RGD.
DR GO; GO:0034616; P:response to laminar fluid shear stress; IEP:RGD.
DR GO; GO:0032570; P:response to progesterone; ISS:AgBase.
DR GO; GO:0060021; P:roof of mouth development; ISO:RGD.
DR GO; GO:0007435; P:salivary gland morphogenesis; ISS:AgBase.
DR GO; GO:0062009; P:secondary palate development; ISS: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 GO; GO:0042060; P:wound healing; IEP: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; 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 2: Evidence at transcript 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..300
FT /note="Latency-associated peptide"
FT /evidence="ECO:0000250|UniProtKB:P01137"
FT /id="PRO_0000033802"
FT CHAIN 301..412
FT /note="Transforming growth factor beta-3"
FT /evidence="ECO:0000250|UniProtKB:P01137"
FT /id="PRO_0000033803"
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:0000250|UniProtKB:P10600"
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:0000250|UniProtKB:P10600"
FT DISULFID 315..378
FT /evidence="ECO:0000250|UniProtKB:P10600"
FT DISULFID 344..409
FT /evidence="ECO:0000250|UniProtKB:P10600"
FT DISULFID 348..411
FT /evidence="ECO:0000250|UniProtKB:P10600"
FT DISULFID 377
FT /note="Interchain"
FT /evidence="ECO:0000250|UniProtKB:P10600"
SQ SEQUENCE 412 AA; 47116 MW; 24FD7D899090AA9D CRC64;
MKMHLQRALV VLALLNLATV SLSLSTCTTL DFGHIKKKRV EAIRGQILSK LRLTSPPEPS
VMTHVPYQVL ALYNSTRELL EEMHGEREEG CTQETSESEY YAKEIHKFDM IQGLAEHNEL
AVCPKGITSK VFRFNVSSVE KNGTNLFRAE FRVLRVPNPS SKRTEQRIEL FQILRPDEHI
AKQRYIGGKN LPTRGTAEWL SFDVTDTVRE WLLRRESNLG LEISIHCPCH TFQPNGDILE
NVHEVMEIKF KGVDNEDDHG RGDLGRLKKQ KDHHNPHLIL MMIPPHRLDS PGQGGQRKKR
ALDTNYCFRN LEENCCVRPL YIDFRQDLGW KWVHEPKGYY ANFCSGPCPY LRSSDTTHST
VLGLYNTLNP EASASPCCVP QDLEPLTILY YVGRTPKVEQ LSNMVVKSCK CS
