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Transforming growth factor beta-3 proprotein [Cleaved into: Latency-associated peptide (LAP); Transforming growth factor beta-3 (TGF-beta-3)]

 TGFB3_RAT               Reviewed;         412 AA.
Q07258; Q56A31;
01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
01-FEB-1996, sequence version 2.
16-OCT-2019, entry version 149.
RecName: Full=Transforming growth factor beta-3 proprotein;
Contains:
RecName: Full=Latency-associated peptide;
Short=LAP;
Contains:
RecName: Full=Transforming growth factor beta-3;
Short=TGF-beta-3;
Flags: Precursor;
Name=Tgfb3; Synonyms=Tgf-b3;
Rattus norvegicus (Rat).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Rattus.
NCBI_TaxID=10116;
[1]
NUCLEOTIDE SEQUENCE [MRNA].
STRAIN=Wistar; TISSUE=Lung;
PubMed=7852342; DOI=10.1074/jbc.270.6.2722;
Wang J., Kuliszewski M., Yee W., Sedlackova L., Xu J., Tseu I.,
Post M.;
"Cloning and expression of glucocorticoid-induced genes in fetal rat
lung fibroblasts. Transforming growth factor-beta 3.";
J. Biol. Chem. 270:2722-2728(1995).
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Brain;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[3]
NUCLEOTIDE SEQUENCE [MRNA] OF 159-213.
PubMed=8509457; DOI=10.1083/jcb.121.6.1397;
McKinnon R.D., Piras G., Ida J., Dubois-Dalq M.;
"A role for TGF-beta in oligodendrocyte differentiation.";
J. Cell Biol. 121:1397-1407(1993).
-!- FUNCTION: Transforming growth factor beta-3 proprotein: Precursor
of the Latency-associated peptide (LAP) and Transforming growth
factor beta-3 (TGF-beta-3) chains, which constitute the regulatory
and active subunit of TGF-beta-3, respectively.
{ECO:0000250|UniProtKB:P01137, ECO:0000250|UniProtKB:P04202}.
-!- FUNCTION: Latency-associated peptide: Required to maintain the
Transforming growth factor beta-3 (TGF-beta-3) chain in a latent
state during storage in extracellular matrix (By similarity).
Associates non-covalently with TGF-beta-3 and regulates its
activation via interaction with 'milieu molecules', such as LTBP1
and LRRC32/GARP, that control activation of TGF-beta-3 (By
similarity). Interaction with integrins results in distortion of
the Latency-associated peptide chain and subsequent release of the
active TGF-beta-3 (By similarity). {ECO:0000250|UniProtKB:P01137,
ECO:0000250|UniProtKB:P04202, ECO:0000250|UniProtKB:P17125}.
-!- FUNCTION: Transforming growth factor beta-3: Multifunctional
protein that regulates embryogenesis and cell differentiation and
is required in various processes such as secondary palate
development (By similarity). Activation into mature form follows
different steps: following cleavage of the proprotein in the Golgi
apparatus, Latency-associated peptide (LAP) and Transforming
growth factor beta-3 (TGF-beta-3) chains remain non-covalently
linked rendering TGF-beta-3 inactive during storage in
extracellular matrix (By similarity). At the same time, LAP chain
interacts with 'milieu molecules', such as LTBP1 and LRRC32/GARP
that control activation of TGF-beta-3 and maintain it in a latent
state during storage in extracellular milieus (By similarity).
TGF-beta-3 is released from LAP by integrins: integrin-binding
results in distortion of the LAP chain and subsequent release of
the active TGF-beta-3 (By similarity). Once activated following
release of LAP, TGF-beta-3 acts by binding to TGF-beta receptors
(TGFBR1 and TGFBR2), which transduce signal (By similarity).
{ECO:0000250|UniProtKB:P01137, ECO:0000250|UniProtKB:P04202,
ECO:0000250|UniProtKB:P17125}.
-!- SUBUNIT: Interacts with ASPN (By similarity). Latency-associated
peptide: Homodimer; disulfide-linked. Latency-associated peptide:
Interacts with Transforming growth factor beta-3 (TGF-beta-3)
chain; interaction is non-covalent and maintains (TGF-beta-3) in a
latent state (By similarity). Latency-associated peptide:
Interacts with LRRC32/GARP; leading to regulate activation of TGF-
beta-3 and promote epithelial fusion during palate development (By
similarity). Latency-associated peptide: Interacts (via cell
attachment site) with integrins, leading to release of the active
TGF-beta-3 (By similarity). Transforming growth factor beta-3:
Homodimer; disulfide-linked (By similarity). Transforming growth
factor beta-3: Interacts with TGF-beta receptors (TGFBR1 and
TGFBR2), leading to signal transduction (By similarity).
{ECO:0000250|UniProtKB:P01137, ECO:0000250|UniProtKB:P04202,
ECO:0000250|UniProtKB:P10600, ECO:0000250|UniProtKB:P17125}.
-!- SUBCELLULAR LOCATION: Latency-associated peptide: Secreted,
extracellular space, extracellular matrix
{ECO:0000250|UniProtKB:P01137}.
-!- SUBCELLULAR LOCATION: Transforming growth factor beta-3: Secreted
{ECO:0000250|UniProtKB:P01137}.
-!- PTM: Transforming growth factor beta-3 proprotein: The precursor
proprotein is cleaved in the Golgi apparatus to form Transforming
growth factor beta-3 (TGF-beta-3) and Latency-associated peptide
(LAP) chains, which remain non-covalently linked, rendering TGF-
beta-3 inactive. {ECO:0000250|UniProtKB:P01137}.
-!- PTM: Methylated at Gln-293 by N6AMT1.
{ECO:0000250|UniProtKB:P10600}.
-!- SIMILARITY: Belongs to the TGF-beta family. {ECO:0000305}.
-----------------------------------------------------------------------
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EMBL; U03491; AAA67915.1; -; mRNA.
EMBL; BC092195; AAH92195.1; -; mRNA.
EMBL; X71903; CAA50722.1; -; mRNA.
PIR; A55706; A55706.
RefSeq; NP_037306.1; NM_013174.2.
STRING; 10116.ENSRNOP00000013516; -.
PhosphoSitePlus; Q07258; -.
PaxDb; Q07258; -.
PRIDE; Q07258; -.
Ensembl; ENSRNOT00000013516; ENSRNOP00000013516; ENSRNOG00000009867.
GeneID; 25717; -.
KEGG; rno:25717; -.
UCSC; RGD:3851; rat.
CTD; 7043; -.
RGD; 3851; Tgfb3.
eggNOG; KOG3900; Eukaryota.
eggNOG; ENOG410XT8Z; LUCA.
GeneTree; ENSGT00940000155747; -.
HOGENOM; HOG000290198; -.
InParanoid; Q07258; -.
KO; K13377; -.
OMA; FANFCSG; -.
OrthoDB; 184308at2759; -.
PhylomeDB; Q07258; -.
TreeFam; TF351793; -.
Reactome; R-RNO-114608; Platelet degranulation.
Reactome; R-RNO-2129379; Molecules associated with elastic fibres.
PRO; PR:Q07258; -.
Proteomes; UP000002494; Chromosome 6.
Bgee; ENSRNOG00000009867; Expressed in 10 organ(s), highest expression level in heart.
Genevisible; Q07258; RN.
GO; GO:0009986; C:cell surface; IDA:RGD.
GO; GO:0062023; C:collagen-containing extracellular matrix; IEA:Ensembl.
GO; GO:0005737; C:cytoplasm; IDA:RGD.
GO; GO:0031012; C:extracellular matrix; ISS:AgBase.
GO; GO:0005615; C:extracellular space; IDA:RGD.
GO; GO:0043025; C:neuronal cell body; IDA:RGD.
GO; GO:0005634; C:nucleus; IDA:RGD.
GO; GO:0030141; C:secretory granule; IDA:RGD.
GO; GO:0030315; C:T-tubule; IDA:RGD.
GO; GO:0005125; F:cytokine activity; IBA:GO_Central.
GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
GO; GO:0042802; F:identical protein binding; ISS:AgBase.
GO; GO:0046982; F:protein heterodimerization activity; IDA:RGD.
GO; GO:0050431; F:transforming growth factor beta binding; ISS:AgBase.
GO; GO:0005160; F:transforming growth factor beta receptor binding; IBA:GO_Central.
GO; GO:0034713; F:type I transforming growth factor beta receptor binding; ISS:AgBase.
GO; GO:0005114; F:type II transforming growth factor beta receptor binding; ISS:AgBase.
GO; GO:0034714; F:type III transforming growth factor beta receptor binding; ISS:AgBase.
GO; GO:0000187; P:activation of MAPK activity; IDA:RGD.
GO; GO:0007568; P:aging; IEP:RGD.
GO; GO:0030509; P:BMP signaling pathway; IBA:GO_Central.
GO; GO:0048468; P:cell development; IBA:GO_Central.
GO; GO:0045216; P:cell-cell junction organization; ISS:AgBase.
GO; GO:0070483; P:detection of hypoxia; ISS:AgBase.
GO; GO:0048565; P:digestive tract development; IEP:RGD.
GO; GO:0048702; P:embryonic neurocranium morphogenesis; IDA:RGD.
GO; GO:0060325; P:face morphogenesis; ISS:AgBase.
GO; GO:0007565; P:female pregnancy; IEP:RGD.
GO; GO:0060364; P:frontal suture morphogenesis; IEP:RGD.
GO; GO:0048839; P:inner ear development; IEP:RGD.
GO; GO:0030324; P:lung development; NAS:RGD.
GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:RGD.
GO; GO:0010936; P:negative regulation of macrophage cytokine production; ISS:AgBase.
GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; IDA:RGD.
GO; GO:1904706; P:negative regulation of vascular smooth muscle cell proliferation; IEA:Ensembl.
GO; GO:0043932; P:ossification involved in bone remodeling; ISS:AgBase.
GO; GO:0043065; P:positive regulation of apoptotic process; IDA:RGD.
GO; GO:0030501; P:positive regulation of bone mineralization; ISS:AgBase.
GO; GO:0051781; P:positive regulation of cell division; IEA:UniProtKB-KW.
GO; GO:0008284; P:positive regulation of cell population proliferation; ISS:BHF-UCL.
GO; GO:0032967; P:positive regulation of collagen biosynthetic process; ISS:AgBase.
GO; GO:0010718; P:positive regulation of epithelial to mesenchymal transition; ISS:AgBase.
GO; GO:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation; IBA:GO_Central.
GO; GO:0050714; P:positive regulation of protein secretion; IEA:Ensembl.
GO; GO:0051496; P:positive regulation of stress fiber assembly; IEA:Ensembl.
GO; GO:1905075; P:positive regulation of tight junction disassembly; IEA:Ensembl.
GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:AgBase.
GO; GO:0042981; P:regulation of apoptotic process; IBA:GO_Central.
GO; GO:0042127; P:regulation of cell population proliferation; IBA:GO_Central.
GO; GO:0045601; P:regulation of endothelial cell differentiation; TAS:RGD.
GO; GO:0030856; P:regulation of epithelial cell differentiation; TAS:RGD.
GO; GO:0050678; P:regulation of epithelial cell proliferation; TAS:RGD.
GO; GO:0043408; P:regulation of MAPK cascade; IBA:GO_Central.
GO; GO:0043627; P:response to estrogen; IDA:RGD.
GO; GO:0001666; P:response to hypoxia; IEP:RGD.
GO; GO:0034616; P:response to laminar fluid shear stress; IEP:RGD.
GO; GO:0032570; P:response to progesterone; ISS:AgBase.
GO; GO:0007435; P:salivary gland morphogenesis; ISS:AgBase.
GO; GO:0062009; P:secondary palate development; ISS:UniProtKB.
GO; GO:0060395; P:SMAD protein signal transduction; IBA:GO_Central.
GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; ISS:AgBase.
GO; GO:0042060; P:wound healing; IEP:RGD.
Gene3D; 2.10.90.10; -; 1.
InterPro; IPR029034; Cystine-knot_cytokine.
InterPro; IPR001839; TGF-b_C.
InterPro; IPR001111; TGF-b_propeptide.
InterPro; IPR016319; TGF-beta.
InterPro; IPR015615; TGF-beta-rel.
InterPro; IPR015618; TGFB3.
InterPro; IPR017948; TGFb_CS.
PANTHER; PTHR11848; PTHR11848; 1.
Pfam; PF00019; TGF_beta; 1.
Pfam; PF00688; TGFb_propeptide; 1.
PIRSF; PIRSF001787; TGF-beta; 1.
PRINTS; PR01423; TGFBETA.
PRINTS; PR01426; TGFBETA3.
SMART; SM00204; TGFB; 1.
SUPFAM; SSF57501; SSF57501; 1.
PROSITE; PS00250; TGF_BETA_1; 1.
PROSITE; PS51362; TGF_BETA_2; 1.
2: Evidence at transcript level;
Cleavage on pair of basic residues; Complete proteome; Disulfide bond;
Extracellular matrix; Glycoprotein; Growth factor; Methylation;
Mitogen; Reference proteome; Secreted; Signal.
SIGNAL 1 23 {ECO:0000255}.
CHAIN 24 300 Latency-associated peptide.
{ECO:0000250|UniProtKB:P01137}.
/FTId=PRO_0000033802.
CHAIN 301 412 Transforming growth factor beta-3.
{ECO:0000250|UniProtKB:P01137}.
/FTId=PRO_0000033803.
MOTIF 261 263 Cell attachment site.
{ECO:0000250|UniProtKB:P01137}.
MOD_RES 293 293 N5-methylglutamine.
{ECO:0000250|UniProtKB:P10600}.
CARBOHYD 74 74 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 135 135 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 142 142 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
DISULFID 307 316 {ECO:0000250|UniProtKB:P10600}.
DISULFID 315 378 {ECO:0000250|UniProtKB:P10600}.
DISULFID 344 409 {ECO:0000250|UniProtKB:P10600}.
DISULFID 348 411 {ECO:0000250|UniProtKB:P10600}.
DISULFID 377 377 Interchain.
{ECO:0000250|UniProtKB:P10600}.
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


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Related Genes :
[TGFB3] Transforming growth factor beta-3 proprotein [Cleaved into: Latency-associated peptide (LAP); Transforming growth factor beta-3 (TGF-beta-3)]
[TGFB1 TGFB] Transforming growth factor beta-1 proprotein [Cleaved into: Latency-associated peptide (LAP); Transforming growth factor beta-1 (TGF-beta-1)]
[Tgfb1] Transforming growth factor beta-1 proprotein [Cleaved into: Latency-associated peptide (LAP); Transforming growth factor beta-1 (TGF-beta-1)]
[TGFB1] Transforming growth factor beta-1 proprotein [Cleaved into: Latency-associated peptide (LAP); Transforming growth factor beta-1 (TGF-beta-1)]
[Tgfb1] Transforming growth factor beta-1 proprotein [Cleaved into: Latency-associated peptide (LAP); Transforming growth factor beta-1 (TGF-beta-1)]
[TGFB1] Transforming growth factor beta-1 proprotein [Cleaved into: Latency-associated peptide (LAP); Transforming growth factor beta-1 (TGF-beta-1)]
[TGFB1] Transforming growth factor beta-1 proprotein [Cleaved into: Latency-associated peptide (LAP); Transforming growth factor beta-1 (TGF-beta-1)]
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[TGFB1] Transforming growth factor beta-1 proprotein [Cleaved into: Latency-associated peptide (LAP); Transforming growth factor beta-1 (TGF-beta-1)]
[TGFB1] Transforming growth factor beta-1 proprotein [Cleaved into: Latency-associated peptide (LAP); Transforming growth factor beta-1 (TGF-beta-1)]
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[TGFB1] Transforming growth factor beta-1 proprotein [Cleaved into: Latency-associated peptide (LAP); Transforming growth factor beta-1 (TGF-beta-1)]
[TGFB2] Transforming growth factor beta-2 proprotein (Cetermin) (Glioblastoma-derived T-cell suppressor factor) (G-TSF) [Cleaved into: Latency-associated peptide (LAP); Transforming growth factor beta-2 (TGF-beta-2)]
[TGFB2] Transforming growth factor beta-2 proprotein [Cleaved into: Latency-associated peptide (LAP); Transforming growth factor beta-2 (TGF-beta-2)]
[TGFB1] Transforming growth factor beta-1 proprotein [Cleaved into: Latency-associated peptide (LAP); Transforming growth factor beta-1 (TGF-beta-1)]
[Tgfbr3] Transforming growth factor beta receptor type 3 (TGF-beta receptor type 3) (TGFR-3) (Betaglycan) (Transforming growth factor beta receptor III) (TGF-beta receptor type III)
[Lefty1 Ebaf Lefty Stra3 Tgfb4] Left-right determination factor 1 (Protein lefty-1) (Lefty protein) (Stimulated by retinoic acid gene 3 protein) (Transforming growth factor beta-4) (TGF-beta-4)
[TGFBR2] TGF-beta receptor type-2 (TGFR-2) (EC 2.7.11.30) (TGF-beta type II receptor) (Transforming growth factor-beta receptor type II) (TGF-beta receptor type II) (TbetaR-II)
[TGFBR1 ALK5 SKR4] TGF-beta receptor type-1 (TGFR-1) (EC 2.7.11.30) (Activin A receptor type II-like protein kinase of 53kD) (Activin receptor-like kinase 5) (ALK-5) (ALK5) (Serine/threonine-protein kinase receptor R4) (SKR4) (TGF-beta type I receptor) (Transforming growth factor-beta receptor type I) (TGF-beta receptor type I) (TbetaR-I)
[MAP3K7 TAK1] Mitogen-activated protein kinase kinase kinase 7 (EC 2.7.11.25) (Transforming growth factor-beta-activated kinase 1) (TGF-beta-activated kinase 1)
[Map3k7 Tak1] Mitogen-activated protein kinase kinase kinase 7 (EC 2.7.11.25) (Transforming growth factor-beta-activated kinase 1) (TGF-beta-activated kinase 1)
[TGFBR1] TGF-beta receptor type-1 (TGFR-1) (EC 2.7.11.30) (TGF-beta type I receptor) (Transforming growth factor-beta receptor type I) (TGF-beta receptor type I) (TbetaR-I)
[Tgfbr1] TGF-beta receptor type-1 (TGFR-1) (EC 2.7.11.30) (Serine/threonine-protein kinase receptor R4) (SKR4) (TGF-beta type I receptor) (Transforming growth factor-beta receptor type I) (TGF-beta receptor type I) (TbetaR-I)
[TGFBR1] TGF-beta receptor type-1 (TGFR-1) (EC 2.7.11.30) (TGF-beta type I receptor) (Transforming growth factor-beta receptor type I) (TGF-beta receptor type I) (TbetaR-I)
[Tgfbr1] TGF-beta receptor type-1 (TGFR-1) (EC 2.7.11.30) (ESK2) (Transforming growth factor-beta receptor type I) (TGF-beta receptor type I) (TbetaR-I)
[LEFTY2 EBAF LEFTA LEFTYA TGFB4 PSEC0024] Left-right determination factor 2 (Endometrial bleeding-associated factor) (Left-right determination factor A) (Protein lefty-2) (Protein lefty-A) (Transforming growth factor beta-4) (TGF-beta-4)
[Nrros Lrrc33] Transforming growth factor beta activator LRRC33 (Leucine-rich repeat-containing protein 33) (Negative regulator of reactive oxygen species)
[LTBP4] Latent-transforming growth factor beta-binding protein 4 (LTBP-4)
[TGFBI BIGH3] Transforming growth factor-beta-induced protein ig-h3 (Beta ig-h3) (Kerato-epithelin) (RGD-containing collagen-associated protein) (RGD-CAP)
[LTBP2 C14orf141 LTBP3] Latent-transforming growth factor beta-binding protein 2 (LTBP-2)

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