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Transforming growth factor beta-1 proprotein (TGF-beta-5) [Cleaved into: Latency-associated peptide (LAP); Transforming growth factor beta-1 (TGF-beta-1)]

 TGFB1_XENLA             Reviewed;         382 AA.
P16176; A1L2V0;
01-APR-1990, integrated into UniProtKB/Swiss-Prot.
01-APR-1990, sequence version 1.
17-JUN-2020, entry version 102.
RecName: Full=Transforming growth factor beta-1 proprotein;
AltName: Full=TGF-beta-5 {ECO:0000303|PubMed:2295601};
Contains:
RecName: Full=Latency-associated peptide;
Short=LAP;
Contains:
RecName: Full=Transforming growth factor beta-1;
Short=TGF-beta-1;
Flags: Precursor;
Name=tgfb1;
Xenopus laevis (African clawed frog).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
NCBI_TaxID=8355;
[1]
NUCLEOTIDE SEQUENCE [MRNA].
PubMed=2295601;
Kondaiah P., Sands M.J., Smith J.M., Fields A., Roberts A.B., Sporn M.B.,
Melton D.A.;
"Identification of a novel transforming growth factor-beta (TGF-beta 5)
mRNA in Xenopus laevis.";
J. Biol. Chem. 265:1089-1093(1990).
[2]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Vempati U.D., Kondaiah P.;
Submitted (AUG-1997) to the EMBL/GenBank/DDBJ databases.
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Thymus;
NIH - Xenopus Gene Collection (XGC) project;
Submitted (DEC-2006) to the EMBL/GenBank/DDBJ databases.
-!- FUNCTION: Transforming growth factor beta-1 proprotein: Precursor of
the Latency-associated peptide (LAP) and Transforming growth factor
beta-1 (TGF-beta-1) chains, which constitute the regulatory and active
subunit of TGF-beta-1, respectively. {ECO:0000250|UniProtKB:P01137}.
-!- FUNCTION: [Latency-associated peptide]: Required to maintain the
Transforming growth factor beta-1 (TGF-beta-1) chain in a latent state
during storage in extracellular matrix. Associates non-covalently with
TGF-beta-1 and regulates its activation via interaction with 'milieu
molecules', such as LTBP1, LRRC32/GARP and LRRC33/NRROS, that control
activation of TGF-beta-1. Interaction with integrins (ITGAV:ITGB6 or
ITGAV:ITGB8) results in distortion of the Latency-associated peptide
chain and subsequent release of the active TGF-beta-1.
{ECO:0000250|UniProtKB:P01137}.
-!- FUNCTION: Transforming growth factor beta-1: Multifunctional protein
that regulates the growth and differentiation of various cell types and
is involved in various processes, such as normal development, immune
function, microglia function and responses to neurodegeneration (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-1 (TGF-
beta-1) chains remain non-covalently linked rendering TGF-beta-1
inactive during storage in extracellular matrix. At the same time, LAP
chain interacts with 'milieu molecules', such as ltbp1, lrrc32/garp and
lrrc33/nrros that control activation of TGF-beta-1 and maintain it in a
latent state during storage in extracellular milieus. TGF-beta-1 is
released from LAP by integrins (ITGAV:ITGB6 or ITGAV:ITGB8): integrin-
binding to LAP stabilizes an alternative conformation of the LAP bowtie
tail and results in distortion of the LAP chain and subsequent release
of the active TGF-beta-1. Once activated following release of LAP, TGF-
beta-1 acts by binding to TGF-beta receptors (tgfbr1 and tgfbr2), which
transduce signal (By similarity). While expressed by many cells types,
TGF-beta-1 only has a very localized range of action within cell
environment thanks to fine regulation of its activation by Latency-
associated peptide chain (LAP) and 'milieu molecules'. Plays an
important role in bone remodeling: acts as a potent stimulator of
osteoblastic bone formation. Can promote either T-helper 17 cells
(Th17) or regulatory T-cells (Treg) lineage differentiation in a
concentration-dependent manner (By similarity). Can induce epithelial-
to-mesenchymal transition (EMT) and cell migration in various cell
types (By similarity). {ECO:0000250|UniProtKB:P01137,
ECO:0000250|UniProtKB:P04202}.
-!- SUBUNIT: Latency-associated peptide: Homodimer; disulfide-linked.
Latency-associated peptide: Interacts with Transforming growth factor
beta-1 (TGF-beta-1) chain; interaction is non-covalent and maintains
(TGF-beta-1) in a latent state; each Latency-associated peptide (LAP)
monomer interacts with TGF-beta-1 in the other monomer. Transforming
growth factor beta-1: Homodimer; disulfide-linked. Transforming growth
factor beta-1: Interacts with TGF-beta receptors (tgfbr1 and tgfbr2),
leading to signal transduction. {ECO:0000250|UniProtKB:P01137}.
-!- SUBCELLULAR LOCATION: [Latency-associated peptide]: Secreted,
extracellular space, extracellular matrix
{ECO:0000250|UniProtKB:P01137}.
-!- SUBCELLULAR LOCATION: [Transforming growth factor beta-1]: Secreted
{ECO:0000250|UniProtKB:P01137}.
-!- DOMAIN: [Latency-associated peptide]: The 'straitjacket' and 'arm'
domains encircle the Transforming growth factor beta-1 (TGF-beta-1)
monomers and are fastened together by strong bonding between Lys-53 and
Tyr-99/Tyr-100. {ECO:0000250|UniProtKB:P07200}.
-!- DOMAIN: [Latency-associated peptide]: The cell attachment site motif
mediates binding to integrins (ITGAV:ITGB6 or ITGAV:ITGB8). The motif
locates to a long loop in the arm domain called the bowtie tail.
Integrin-binding stabilizes an alternative conformation of the bowtie
tail. Activation by integrin requires force application by the actin
cytoskeleton, which is resisted by the 'milieu molecules' (such as
ltbp1, lrrc32/garp and/or lrrc33/nrros), resulting in distortion of the
prodomain and release of the active TGF-beta-1.
{ECO:0000250|UniProtKB:P01137}.
-!- PTM: Transforming growth factor beta-1 proprotein: The precursor
proprotein is cleaved in the Golgi apparatus to form Transforming
growth factor beta-1 (TGF-beta-1) and Latency-associated peptide (LAP)
chains, which remain non-covalently linked, rendering TGF-beta-1
inactive. {ECO:0000250|UniProtKB:P01137}.
-!- SIMILARITY: Belongs to the TGF-beta family. {ECO:0000305}.
---------------------------------------------------------------------------
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EMBL; J05180; AAA49968.1; -; mRNA.
EMBL; AF009335; AAB64441.1; -; Genomic_DNA.
EMBL; AF009331; AAB64441.1; JOINED; Genomic_DNA.
EMBL; AF009332; AAB64441.1; JOINED; Genomic_DNA.
EMBL; AF009333; AAB64441.1; JOINED; Genomic_DNA.
EMBL; AF009334; AAB64441.1; JOINED; Genomic_DNA.
EMBL; BC129720; AAI29721.1; -; mRNA.
PIR; A34929; B61036.
RefSeq; NP_001081330.1; NM_001087861.1.
SMR; P16176; -.
PRIDE; P16176; -.
GeneID; 397778; -.
KEGG; xla:397778; -.
CTD; 397778; -.
Xenbase; XB-GENE-865765; tgfb1.
KO; K13375; -.
OMA; MAKEPEP; -.
OrthoDB; 643840at2759; -.
GO; GO:0005615; C:extracellular space; IEA:InterPro.
GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
GO; GO:0005160; F:transforming growth factor beta receptor binding; IEA:InterPro.
GO; GO:0051781; P:positive regulation of cell division; IEA:UniProtKB-KW.
GO; GO:0014008; P:positive regulation of microglia differentiation; ISS:UniProtKB.
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; IPR003939; TGFb1.
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; PR01424; TGFBETA1.
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; Disulfide bond; Extracellular matrix;
Glycoprotein; Growth factor; Mitogen; Secreted; Signal.
SIGNAL 1..21
/evidence="ECO:0000255"
CHAIN 22..270
/note="Latency-associated peptide"
/evidence="ECO:0000250|UniProtKB:P01137"
/id="PRO_0000445549"
CHAIN 271..382
/note="Transforming growth factor beta-1"
/evidence="ECO:0000250|UniProtKB:P01137"
/id="PRO_0000033777"
REGION 22..65
/note="Straightjacket domain"
/evidence="ECO:0000250|UniProtKB:P07200"
REGION 66..263
/note="Arm domain"
/evidence="ECO:0000250|UniProtKB:P07200"
REGION 218..242
/note="Bowtie tail"
/evidence="ECO:0000250|UniProtKB:P01137"
MOTIF 234..236
/note="Cell attachment site"
/evidence="ECO:0000255"
CARBOHYD 73
/note="N-linked (GlcNAc...) asparagine"
/evidence="ECO:0000255"
CARBOHYD 123
/note="N-linked (GlcNAc...) asparagine"
/evidence="ECO:0000255"
CARBOHYD 166
/note="N-linked (GlcNAc...) asparagine"
/evidence="ECO:0000255"
DISULFID 25
/note="Interchain (with C-? in LTBP1 TB3 domain); in
inactive form"
/evidence="ECO:0000250|UniProtKB:P07200"
DISULFID 215
/note="Interchain (with C-217)"
/evidence="ECO:0000250|UniProtKB:P01137"
DISULFID 217
/note="Interchain (with C-215)"
/evidence="ECO:0000250|UniProtKB:P01137"
DISULFID 277..286
/evidence="ECO:0000250|UniProtKB:P01137"
DISULFID 285..348
/evidence="ECO:0000250|UniProtKB:P01137"
DISULFID 314..379
/evidence="ECO:0000250|UniProtKB:P01137"
DISULFID 318..381
/evidence="ECO:0000250|UniProtKB:P01137"
DISULFID 347
/note="Interchain"
/evidence="ECO:0000250|UniProtKB:P01137"
SEQUENCE 382 AA; 44201 MW; 1034621C917AAE15 CRC64;
MEVLWMLLVL LVLHLSSLAM SLSTCKAVDM EEVRKRRIEA IRGQILSKLK LDKTPDVDSE
KMTVPSEAIF LYNSTLEVIR EKATREEEHV GHDQNIQDYY AKQVYRFESI TELEDHEFKF
KFNASHVREN VGMNSLLHHA ELRMYKKQTD KNMDQRMELF WKYQENGTTH SRYLESKYIT
PVTDDEWMSF DVTKTVNEWL KRAEENEQFG LQPACKCPTP QAKDIDIEGF PALRGDLASL
SSKENTKPYL MITSMPAERI DTVTSSRKKR GVGQEYCFGN NGPNCCVKPL YINFRKDLGW
KWIHEPKGYE ANYCLGNCPY IWSMDTQYSK VLSLYNQNNP GASISPCCVP DVLEPLPIIY
YVGRTAKVEQ LSNMVVRSCN CS


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Related Genes :
[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)]
[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)]
[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)]
[TGFB3] Transforming growth factor beta-3 proprotein [Cleaved into: Latency-associated peptide (LAP); Transforming growth factor beta-3 (TGF-beta-3)]
[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)]
[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)
[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) (TGF-beta type I receptor) (Transforming growth factor-beta receptor type I) (TGF-beta receptor type I) (TbetaR-I)
[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)
[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)
[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)
[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)
[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)
[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)
[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)
[tgfb1] Transforming growth factor beta-1 proprotein (TGF-beta-5) [Cleaved into: Latency-associated peptide (LAP); Transforming growth factor beta-1 (TGF-beta-1)]
[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)
[tgfb1] Transforming growth factor beta-1 proprotein [Cleaved into: Latency-associated peptide (LAP); Transforming growth factor beta-1 (TGF-beta-1)]

Bibliography :