TGFB3_CHICK
ID TGFB3_CHICK Reviewed; 412 AA.
AC P16047;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 29-AUG-2001, sequence version 2.
DT 03-AUG-2022, entry version 140.
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 Gallus gallus (Chicken).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Phasianinae; Gallus.
OX NCBI_TaxID=9031;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3211158; DOI=10.1210/mend-2-8-747;
RA Jakowlew S.B., Dillard P.J., Kondaiah P., Sporn M.B., Roberts A.B.;
RT "Complementary deoxyribonucleic acid cloning of a novel transforming growth
RT factor-beta messenger ribonucleic acid from chick embryo chondrocytes.";
RL Mol. Endocrinol. 2:747-755(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=White leghorn;
RX PubMed=7865129; DOI=10.1089/dna.1995.14.111;
RA Burt D.W., Dey B.R., Paton I.R., Morrice D.R., Law A.S.;
RT "The chicken transforming growth factor-beta 3 gene: genomic structure,
RT transcriptional analysis, and chromosomal location.";
RL DNA Cell Biol. 14:111-123(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-117.
RC STRAIN=White leghorn; TISSUE=Blood;
RX PubMed=1840616; DOI=10.1677/jme.0.0070175;
RA Burt D.W., Dey B.R., Paton I.R.;
RT "Comparative analysis of human and chicken transforming growth factor-beta
RT 2 and -beta 3 promoters.";
RL J. Mol. Endocrinol. 7:175-183(1991).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-117.
RX PubMed=1406706; DOI=10.1210/mend.6.8.1406706;
RA Jakowlew S.B., Lechleider R., Geiser A.G., Kim S.J., Santa-Coloma T.A.,
RA Cubert J., Sporn M.B., Roberts A.B.;
RT "Identification and characterization of the chicken transforming growth
RT factor-beta 3 promoter.";
RL Mol. Endocrinol. 6:1285-1298(1992).
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: Latency-associated peptide: Homodimer; disulfide-linked.
CC Latency-associated peptide: Interacts with Transforming growth factor
CC beta-3 (TGF-beta-3) chain; interaction is non-covalent and maintains
CC (TGF-beta-3) in a latent state (By similarity). Latency-associated
CC peptide: Interacts (via cell attachment site) with integrins, leading
CC to release of the active TGF-beta-3 (By similarity). Transforming
CC growth factor beta-3: Homodimer; disulfide-linked (By similarity).
CC Transforming growth factor beta-3: Interacts with TGF-beta receptors
CC (TGFBR1 and TGFBR2), leading to signal transduction (By similarity).
CC {ECO:0000250|UniProtKB:P01137, ECO:0000250|UniProtKB:P04202,
CC ECO:0000250|UniProtKB:P10600}.
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; M31154; AAA49089.1; -; mRNA.
DR EMBL; X58127; CAA41128.2; -; Genomic_DNA.
DR EMBL; X60055; CAA41128.2; JOINED; Genomic_DNA.
DR EMBL; X60091; CAA41128.2; JOINED; Genomic_DNA.
DR EMBL; X60090; CAA41128.2; JOINED; Genomic_DNA.
DR EMBL; S46000; AAB23575.1; -; Genomic_DNA.
DR PIR; A34939; A34939.
DR RefSeq; NP_990785.1; NM_205454.1.
DR AlphaFoldDB; P16047; -.
DR SMR; P16047; -.
DR STRING; 9031.ENSGALP00000036912; -.
DR PaxDb; P16047; -.
DR GeneID; 396438; -.
DR KEGG; gga:396438; -.
DR CTD; 7043; -.
DR VEuPathDB; HostDB:geneid_396438; -.
DR eggNOG; KOG3900; Eukaryota.
DR InParanoid; P16047; -.
DR OrthoDB; 643840at2759; -.
DR PhylomeDB; P16047; -.
DR PRO; PR:P16047; -.
DR Proteomes; UP000000539; Unplaced.
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:0060317; P:cardiac epithelial to mesenchymal transition; IMP:DFLAT.
DR GO; GO:0001775; P:cell activation; TAS:AgBase.
DR GO; GO:0045216; P:cell-cell junction organization; ISS:AgBase.
DR GO; GO:0070483; P:detection of hypoxia; ISS:AgBase.
DR GO; GO:0048566; P:embryonic digestive tract development; IEP:AgBase.
DR GO; GO:0003198; P:epithelial to mesenchymal transition involved in endocardial cushion formation; TAS:DFLAT.
DR GO; GO:0060325; P:face morphogenesis; ISS:AgBase.
DR GO; GO:0090131; P:mesenchyme migration; IMP:DFLAT.
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:0007399; P:nervous system development; TAS: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:0030335; P:positive regulation of cell migration; TAS:AgBase.
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; IMP:DFLAT.
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:0060395; P:SMAD protein signal transduction; IBA:GO_Central.
DR GO; GO:0048536; P:spleen development; IEP:AgBase.
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..23
FT /evidence="ECO:0000255"
FT CHAIN 24..300
FT /note="Latency-associated peptide"
FT /evidence="ECO:0000250|UniProtKB:P01137"
FT /id="PRO_0000033804"
FT CHAIN 301..412
FT /note="Transforming growth factor beta-3"
FT /evidence="ECO:0000250|UniProtKB:P01137"
FT /id="PRO_0000033805"
FT MOTIF 261..263
FT /note="Cell attachment site"
FT /evidence="ECO:0000250|UniProtKB:P01137"
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"
FT CONFLICT 323..326
FT /note="ELPT -> DFRQ (in Ref. 1; AAA49089)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 412 AA; 47078 MW; 1CAB883170069D55 CRC64;
MKMYAQRALV LLSLLSFATV SLALSSCTTL DLEHIKKKRV EAIRGQILSK LRLTSPPESV
GPAHVPYQIL ALYNSTRELL EEMEEEKEES CSQENTESEY YAKEIHKFDM IQGLPEHNEL
GICPKGVTSN VFRFNVSSAE KNSTNLFRAE FRVLRVPNPS SKRSEQRIEL FQILRPDEHI
AKQRYLSGRN VQTRGSPEWL SFDVTDTVRE WLLHRESNLG LEISIHCPCH TFQPNGDILE
NLHEVLEIKF KGIDSEDDYG RGDLGRLKKQ KDLHNPHLIL MMLPPHRLES PTLGGQRKKR
ALDTNYCFRN LEENCCVRPL YIELPTDLGW KWVHEPKGYF ANFCSGPCPY LRSADTTHST
VLGLYNTLNP EASASPCCVP QDLEPLTILY YVGRTPKVEQ LSNMVVKSCK CS
