TGFB1_XENLA
ID TGFB1_XENLA Reviewed; 382 AA.
AC P16176; A1L2V0;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1990, sequence version 1.
DT 03-AUG-2022, entry version 108.
DE RecName: Full=Transforming growth factor beta-1 proprotein;
DE AltName: Full=TGF-beta-5 {ECO:0000303|PubMed:2295601};
DE Contains:
DE RecName: Full=Latency-associated peptide;
DE Short=LAP;
DE Contains:
DE RecName: Full=Transforming growth factor beta-1;
DE Short=TGF-beta-1;
DE Flags: Precursor;
GN Name=tgfb1;
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2295601; DOI=10.1016/s0021-9258(19)40162-2;
RA Kondaiah P., Sands M.J., Smith J.M., Fields A., Roberts A.B., Sporn M.B.,
RA Melton D.A.;
RT "Identification of a novel transforming growth factor-beta (TGF-beta 5)
RT mRNA in Xenopus laevis.";
RL J. Biol. Chem. 265:1089-1093(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Vempati U.D., Kondaiah P.;
RL Submitted (AUG-1997) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Thymus;
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (DEC-2006) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Transforming growth factor beta-1 proprotein: Precursor of
CC the Latency-associated peptide (LAP) and Transforming growth factor
CC beta-1 (TGF-beta-1) chains, which constitute the regulatory and active
CC subunit of TGF-beta-1, respectively. {ECO:0000250|UniProtKB:P01137}.
CC -!- FUNCTION: [Latency-associated peptide]: Required to maintain the
CC Transforming growth factor beta-1 (TGF-beta-1) chain in a latent state
CC during storage in extracellular matrix. Associates non-covalently with
CC TGF-beta-1 and regulates its activation via interaction with 'milieu
CC molecules', such as LTBP1, LRRC32/GARP and LRRC33/NRROS, that control
CC activation of TGF-beta-1. Interaction with integrins (ITGAV:ITGB6 or
CC ITGAV:ITGB8) results in distortion of the Latency-associated peptide
CC chain and subsequent release of the active TGF-beta-1.
CC {ECO:0000250|UniProtKB:P01137}.
CC -!- FUNCTION: Transforming growth factor beta-1: Multifunctional protein
CC that regulates the growth and differentiation of various cell types and
CC is involved in various processes, such as normal development, immune
CC function, microglia function and responses to neurodegeneration (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-1 (TGF-
CC beta-1) chains remain non-covalently linked rendering TGF-beta-1
CC inactive during storage in extracellular matrix. At the same time, LAP
CC chain interacts with 'milieu molecules', such as ltbp1, lrrc32/garp and
CC lrrc33/nrros that control activation of TGF-beta-1 and maintain it in a
CC latent state during storage in extracellular milieus. TGF-beta-1 is
CC released from LAP by integrins (ITGAV:ITGB6 or ITGAV:ITGB8): integrin-
CC binding to LAP stabilizes an alternative conformation of the LAP bowtie
CC tail and results in distortion of the LAP chain and subsequent release
CC of the active TGF-beta-1. Once activated following release of LAP, TGF-
CC beta-1 acts by binding to TGF-beta receptors (tgfbr1 and tgfbr2), which
CC transduce signal (By similarity). While expressed by many cells types,
CC TGF-beta-1 only has a very localized range of action within cell
CC environment thanks to fine regulation of its activation by Latency-
CC associated peptide chain (LAP) and 'milieu molecules'. Plays an
CC important role in bone remodeling: acts as a potent stimulator of
CC osteoblastic bone formation. Can promote either T-helper 17 cells
CC (Th17) or regulatory T-cells (Treg) lineage differentiation in a
CC concentration-dependent manner (By similarity). Can induce epithelial-
CC to-mesenchymal transition (EMT) and cell migration in various cell
CC types (By similarity). {ECO:0000250|UniProtKB:P01137,
CC ECO:0000250|UniProtKB:P04202}.
CC -!- SUBUNIT: Latency-associated peptide: Homodimer; disulfide-linked.
CC Latency-associated peptide: Interacts with Transforming growth factor
CC beta-1 (TGF-beta-1) chain; interaction is non-covalent and maintains
CC (TGF-beta-1) in a latent state; each Latency-associated peptide (LAP)
CC monomer interacts with TGF-beta-1 in the other monomer. Transforming
CC growth factor beta-1: Homodimer; disulfide-linked. Transforming growth
CC factor beta-1: Interacts with TGF-beta receptors (tgfbr1 and tgfbr2),
CC leading to signal transduction. {ECO:0000250|UniProtKB:P01137}.
CC -!- SUBCELLULAR LOCATION: [Latency-associated peptide]: Secreted,
CC extracellular space, extracellular matrix
CC {ECO:0000250|UniProtKB:P01137}.
CC -!- SUBCELLULAR LOCATION: [Transforming growth factor beta-1]: Secreted
CC {ECO:0000250|UniProtKB:P01137}.
CC -!- DOMAIN: [Latency-associated peptide]: The 'straitjacket' and 'arm'
CC domains encircle the Transforming growth factor beta-1 (TGF-beta-1)
CC monomers and are fastened together by strong bonding between Lys-53 and
CC Tyr-99/Tyr-100. {ECO:0000250|UniProtKB:P07200}.
CC -!- DOMAIN: [Latency-associated peptide]: The cell attachment site motif
CC mediates binding to integrins (ITGAV:ITGB6 or ITGAV:ITGB8). The motif
CC locates to a long loop in the arm domain called the bowtie tail.
CC Integrin-binding stabilizes an alternative conformation of the bowtie
CC tail. Activation by integrin requires force application by the actin
CC cytoskeleton, which is resisted by the 'milieu molecules' (such as
CC ltbp1, lrrc32/garp and/or lrrc33/nrros), resulting in distortion of the
CC prodomain and release of the active TGF-beta-1.
CC {ECO:0000250|UniProtKB:P01137}.
CC -!- PTM: Transforming growth factor beta-1 proprotein: The precursor
CC proprotein is cleaved in the Golgi apparatus to form Transforming
CC growth factor beta-1 (TGF-beta-1) and Latency-associated peptide (LAP)
CC chains, which remain non-covalently linked, rendering TGF-beta-1
CC inactive. {ECO:0000250|UniProtKB:P01137}.
CC -!- SIMILARITY: Belongs to the TGF-beta family. {ECO:0000305}.
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DR EMBL; J05180; AAA49968.1; -; mRNA.
DR EMBL; AF009335; AAB64441.1; -; Genomic_DNA.
DR EMBL; AF009331; AAB64441.1; JOINED; Genomic_DNA.
DR EMBL; AF009332; AAB64441.1; JOINED; Genomic_DNA.
DR EMBL; AF009333; AAB64441.1; JOINED; Genomic_DNA.
DR EMBL; AF009334; AAB64441.1; JOINED; Genomic_DNA.
DR EMBL; BC129720; AAI29721.1; -; mRNA.
DR PIR; A34929; B61036.
DR RefSeq; NP_001081330.1; NM_001087861.1.
DR AlphaFoldDB; P16176; -.
DR SMR; P16176; -.
DR PRIDE; P16176; -.
DR DNASU; 397778; -.
DR GeneID; 397778; -.
DR KEGG; xla:397778; -.
DR CTD; 397778; -.
DR Xenbase; XB-GENE-865765; tgfb1.L.
DR OMA; LALEYMC; -.
DR OrthoDB; 643840at2759; -.
DR Proteomes; UP000186698; Chromosome 8L.
DR Bgee; 397778; Expressed in spleen and 14 other tissues.
DR GO; GO:0005615; C:extracellular space; IEA:InterPro.
DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR GO; GO:0005160; F:transforming growth factor beta receptor binding; IEA:InterPro.
DR GO; GO:0051781; P:positive regulation of cell division; IEA:UniProtKB-KW.
DR GO; GO:0014008; P:positive regulation of microglia differentiation; ISS:UniProtKB.
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; IPR003939; TGFb1.
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; PR01424; TGFBETA1.
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..270
FT /note="Latency-associated peptide"
FT /evidence="ECO:0000250|UniProtKB:P01137"
FT /id="PRO_0000445549"
FT CHAIN 271..382
FT /note="Transforming growth factor beta-1"
FT /evidence="ECO:0000250|UniProtKB:P01137"
FT /id="PRO_0000033777"
FT REGION 22..65
FT /note="Straightjacket domain"
FT /evidence="ECO:0000250|UniProtKB:P07200"
FT REGION 66..263
FT /note="Arm domain"
FT /evidence="ECO:0000250|UniProtKB:P07200"
FT REGION 218..242
FT /note="Bowtie tail"
FT /evidence="ECO:0000250|UniProtKB:P01137"
FT MOTIF 234..236
FT /note="Cell attachment site"
FT /evidence="ECO:0000255"
FT CARBOHYD 73
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 123
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 166
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 25
FT /note="Interchain (with C-? in LTBP1 TB3 domain); in
FT inactive form"
FT /evidence="ECO:0000250|UniProtKB:P07200"
FT DISULFID 215
FT /note="Interchain (with C-217)"
FT /evidence="ECO:0000250|UniProtKB:P01137"
FT DISULFID 217
FT /note="Interchain (with C-215)"
FT /evidence="ECO:0000250|UniProtKB:P01137"
FT DISULFID 277..286
FT /evidence="ECO:0000250|UniProtKB:P01137"
FT DISULFID 285..348
FT /evidence="ECO:0000250|UniProtKB:P01137"
FT DISULFID 314..379
FT /evidence="ECO:0000250|UniProtKB:P01137"
FT DISULFID 318..381
FT /evidence="ECO:0000250|UniProtKB:P01137"
FT DISULFID 347
FT /note="Interchain"
FT /evidence="ECO:0000250|UniProtKB:P01137"
SQ 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
