TGFB1_ONCMY
ID TGFB1_ONCMY Reviewed; 382 AA.
AC O93449; Q91217;
DT 16-JAN-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 25-MAY-2022, entry version 79.
DE RecName: Full=Transforming growth factor beta-1 proprotein;
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 Oncorhynchus mykiss (Rainbow trout) (Salmo gairdneri).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Protacanthopterygii; Salmoniformes;
OC Salmonidae; Salmoninae; Oncorhynchus.
OX NCBI_TaxID=8022;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Leukocyte;
RX PubMed=10227481; DOI=10.1016/s0145-305x(98)00051-2;
RA Daniels G.D., Secombes C.J.;
RT "Genomic organisation of rainbow trout, Oncorhynchus mykiss TGF-beta.";
RL Dev. Comp. Immunol. 23:139-147(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE, AND TISSUE SPECIFICITY.
RC TISSUE=Leukocyte;
RX PubMed=9722928; DOI=10.1006/cyto.1997.0334;
RA Hardie L.J., Laing K.J., Daniels G.D., Grabowski P.S., Cunningham C.,
RA Secombes C.J.;
RT "Isolation of the first piscine transforming growth factor beta gene:
RT analysis reveals tissue specific expression and a potential regulatory
RT sequence in rainbow trout (Oncorhynchus mykiss).";
RL Cytokine 10:555-563(1998).
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. Interacts with EFEMP2 (By similarity).
CC {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 -!- TISSUE SPECIFICITY: Expressed in blood leukocytes, kidney macrophages,
CC brain, gill and spleen but not in liver. {ECO:0000269|PubMed:9722928}.
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-54 and
CC Tyr-101/Phe-102. {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; AJ007836; CAA07707.1; -; Genomic_DNA.
DR EMBL; X99303; CAA67685.1; -; mRNA.
DR AlphaFoldDB; O93449; -.
DR SMR; O93449; -.
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 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; Secreted; Signal.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..271
FT /note="Latency-associated peptide"
FT /evidence="ECO:0000250|UniProtKB:P01137"
FT /id="PRO_0000445551"
FT CHAIN 272..382
FT /note="Transforming growth factor beta-1"
FT /evidence="ECO:0000250|UniProtKB:P01137"
FT /id="PRO_0000033781"
FT REGION 23..68
FT /note="Straightjacket domain"
FT /evidence="ECO:0000250|UniProtKB:P07200"
FT REGION 69..264
FT /note="Arm domain"
FT /evidence="ECO:0000250|UniProtKB:P07200"
FT REGION 218..243
FT /note="Bowtie tail"
FT /evidence="ECO:0000250|UniProtKB:P01137"
FT MOTIF 235..237
FT /note="Cell attachment site"
FT /evidence="ECO:0000255"
FT CARBOHYD 76
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 116
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 125
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 26
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 278..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"
FT CONFLICT 237
FT /note="N -> D (in Ref. 2; CAA67685)"
FT /evidence="ECO:0000305"
FT CONFLICT 345
FT /note="Q -> H (in Ref. 2; CAA67685)"
FT /evidence="ECO:0000305"
FT CONFLICT 371..372
FT /note="LS -> VP (in Ref. 2; CAA67685)"
FT /evidence="ECO:0000305"
FT CONFLICT 377
FT /note="K -> M (in Ref. 2; CAA67685)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 382 AA; 44137 MW; 93BD4D3540084B92 CRC64;
MRAVCLMLTA LLMLEYVCRS DTMSTCKSLD LELVKRKRIE AIRGQILSKL RLPKEPEIDQ
EGDTEEVPAS LMSIYNSTVE LSEEQVHTYI PSTQDAEEEA YFAKEVHKFN MKQSENTSKH
QILFNMSEMR SVLGTDRLLS QAELRLLIKN HGLLDDSEQR LELYRGVGDK ARYLKSHFVS
KEWANRWVSF DVTQTLNEWL QGAGEEQGFQ LKLPCDCGKP MEEFRFKISG MNKLRGNTET
LAMKMPSKPH ILLMSLPVER HSQLSSRKKR QTTTEEICSD KSESCCVRKL YIDFRKDLGW
KWIHEPTGYF ANYCIGPCTY IWNTENKYSQ VLALYKHHNP GASAQPCCVP QVLEPLPIIY
YVGRQHKVEQ LSNMIVKSCR CS
