TGFB3_PIG
ID TGFB3_PIG Reviewed; 409 AA.
AC P15203;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1990, sequence version 1.
DT 03-AUG-2022, entry version 132.
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 Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Ovary;
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).
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 -!- SIMILARITY: Belongs to the TGF-beta family. {ECO:0000305}.
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DR EMBL; X14150; CAA32363.1; -; mRNA.
DR PIR; S01825; S01825.
DR RefSeq; NP_999363.1; NM_214198.1.
DR AlphaFoldDB; P15203; -.
DR BMRB; P15203; -.
DR SMR; P15203; -.
DR STRING; 9823.ENSSSCP00000030885; -.
DR PaxDb; P15203; -.
DR Ensembl; ENSSSCT00015109301; ENSSSCP00015046449; ENSSSCG00015080409.
DR GeneID; 397400; -.
DR KEGG; ssc:397400; -.
DR CTD; 7043; -.
DR eggNOG; KOG3900; Eukaryota.
DR HOGENOM; CLU_039840_0_0_1; -.
DR InParanoid; P15203; -.
DR Reactome; R-SSC-114608; Platelet degranulation.
DR Reactome; R-SSC-2129379; Molecules associated with elastic fibres.
DR Reactome; R-SSC-2173789; TGF-beta receptor signaling activates SMADs.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Unplaced.
DR Genevisible; P15203; SS.
DR GO; GO:0031012; C:extracellular matrix; ISS:AgBase.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
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: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:0030509; P:BMP signaling pathway; IBA:GO_Central.
DR GO; GO:0045216; P:cell-cell junction organization; ISS:AgBase.
DR GO; GO:0070483; P:detection of hypoxia; ISS:AgBase.
DR GO; GO:0060325; P:face morphogenesis; ISS:AgBase.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISS:AgBase.
DR GO; GO:0010936; P:negative regulation of macrophage cytokine production; ISS:AgBase.
DR GO; GO:0043932; P:ossification involved in bone remodeling; ISS:AgBase.
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:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation; IBA:GO_Central.
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:0001666; P:response to hypoxia; ISS:AgBase.
DR GO; GO:0032570; P:response to progesterone; ISS:AgBase.
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 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; Mitogen; Reference proteome; Secreted; Signal.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..297
FT /note="Latency-associated peptide"
FT /evidence="ECO:0000250|UniProtKB:P01137"
FT /id="PRO_0000033800"
FT CHAIN 298..409
FT /note="Transforming growth factor beta-3"
FT /evidence="ECO:0000250|UniProtKB:P01137"
FT /id="PRO_0000033801"
FT MOTIF 259..261
FT /note="Cell attachment site"
FT /evidence="ECO:0000250|UniProtKB:P01137"
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 304..313
FT /evidence="ECO:0000250|UniProtKB:P10600"
FT DISULFID 312..375
FT /evidence="ECO:0000250|UniProtKB:P10600"
FT DISULFID 341..406
FT /evidence="ECO:0000250|UniProtKB:P10600"
FT DISULFID 345..408
FT /evidence="ECO:0000250|UniProtKB:P10600"
FT DISULFID 374
FT /note="Interchain"
FT /evidence="ECO:0000250|UniProtKB:P10600"
SQ SEQUENCE 409 AA; 46814 MW; B4900235B5CC955E CRC64;
MHLQRALVVL ALLNFATVSL SMSTCTTLDF DHIKRKRVEA IRGQILSKLR LTSPPDPSML
ANIPTQVLDL YNSTRELLEE VHGERGDDCT QENTESEYYA KEIYKFDMIQ GLEEHNDLAV
CPKGITSKIF RFNVSSVEKN ETNLFRAEFR VLRMPNPSSK RSEQRIELFQ ILQPDEHIAK
QRYIDGKNLP TRGAAEWLSF DVTDTVREWL LRRESNLGLE ISIHCPCHTF QPNGDILENI
QEVMEIKFKG VDSEDDPGRG DLGRLKKKKE HSPHLILMMI PPDRLDNPGL GAQRKKRALD
TNYCFRNLEE NCCVRPLYID FRQDLGWKWV HEPKGYYANF CSGPCPYLRS ADTTHSSVLG
LYNTLNPEAS ASPCCVPQDL EPLTILYYVG RTAKVEQLSN MVVKSCKCS
