TGFB1_CHICK
ID TGFB1_CHICK Reviewed; 391 AA.
AC P09531; A0A1D5PM67;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 10-OCT-2018, sequence version 3.
DT 03-AUG-2022, entry version 124.
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 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 [LARGE SCALE GENOMIC DNA].
RC STRAIN=Red jungle fowl;
RX PubMed=15592404; DOI=10.1038/nature03154;
RA Hillier L.W., Miller W., Birney E., Warren W., Hardison R.C., Ponting C.P.,
RA Bork P., Burt D.W., Groenen M.A.M., Delany M.E., Dodgson J.B.,
RA Chinwalla A.T., Cliften P.F., Clifton S.W., Delehaunty K.D., Fronick C.,
RA Fulton R.S., Graves T.A., Kremitzki C., Layman D., Magrini V.,
RA McPherson J.D., Miner T.L., Minx P., Nash W.E., Nhan M.N., Nelson J.O.,
RA Oddy L.G., Pohl C.S., Randall-Maher J., Smith S.M., Wallis J.W.,
RA Yang S.-P., Romanov M.N., Rondelli C.M., Paton B., Smith J., Morrice D.,
RA Daniels L., Tempest H.G., Robertson L., Masabanda J.S., Griffin D.K.,
RA Vignal A., Fillon V., Jacobbson L., Kerje S., Andersson L.,
RA Crooijmans R.P., Aerts J., van der Poel J.J., Ellegren H., Caldwell R.B.,
RA Hubbard S.J., Grafham D.V., Kierzek A.M., McLaren S.R., Overton I.M.,
RA Arakawa H., Beattie K.J., Bezzubov Y., Boardman P.E., Bonfield J.K.,
RA Croning M.D.R., Davies R.M., Francis M.D., Humphray S.J., Scott C.E.,
RA Taylor R.G., Tickle C., Brown W.R.A., Rogers J., Buerstedde J.-M.,
RA Wilson S.A., Stubbs L., Ovcharenko I., Gordon L., Lucas S., Miller M.M.,
RA Inoko H., Shiina T., Kaufman J., Salomonsen J., Skjoedt K., Wong G.K.-S.,
RA Wang J., Liu B., Wang J., Yu J., Yang H., Nefedov M., Koriabine M.,
RA Dejong P.J., Goodstadt L., Webber C., Dickens N.J., Letunic I., Suyama M.,
RA Torrents D., von Mering C., Zdobnov E.M., Makova K., Nekrutenko A.,
RA Elnitski L., Eswara P., King D.C., Yang S.-P., Tyekucheva S.,
RA Radakrishnan A., Harris R.S., Chiaromonte F., Taylor J., He J.,
RA Rijnkels M., Griffiths-Jones S., Ureta-Vidal A., Hoffman M.M., Severin J.,
RA Searle S.M.J., Law A.S., Speed D., Waddington D., Cheng Z., Tuzun E.,
RA Eichler E., Bao Z., Flicek P., Shteynberg D.D., Brent M.R., Bye J.M.,
RA Huckle E.J., Chatterji S., Dewey C., Pachter L., Kouranov A.,
RA Mourelatos Z., Hatzigeorgiou A.G., Paterson A.H., Ivarie R., Brandstrom M.,
RA Axelsson E., Backstrom N., Berlin S., Webster M.T., Pourquie O.,
RA Reymond A., Ucla C., Antonarakis S.E., Long M., Emerson J.J., Betran E.,
RA Dupanloup I., Kaessmann H., Hinrichs A.S., Bejerano G., Furey T.S.,
RA Harte R.A., Raney B., Siepel A., Kent W.J., Haussler D., Eyras E.,
RA Castelo R., Abril J.F., Castellano S., Camara F., Parra G., Guigo R.,
RA Bourque G., Tesler G., Pevzner P.A., Smit A., Fulton L.A., Mardis E.R.,
RA Wilson R.K.;
RT "Sequence and comparative analysis of the chicken genome provide unique
RT perspectives on vertebrate evolution.";
RL Nature 432:695-716(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 18-391.
RC STRAIN=White leghorn;
RX PubMed=2464131; DOI=10.1210/mend-2-12-1186;
RA Jakowlew S.B., Dillard P.J., Sporn M.B., Roberts A.B.;
RT "Complementary deoxyribonucleic acid cloning of a messenger ribonucleic
RT acid encoding transforming growth factor beta 4 from chicken embryo
RT chondrocytes.";
RL Mol. Endocrinol. 2:1186-1195(1988).
RN [3]
RP SEQUENCE REVISION.
RX PubMed=1353860; DOI=10.1210/mend.6.6.1353860;
RA Burt D.W., Jakowlew S.B.;
RT "Correction: a new interpretation of a chicken transforming growth factor-
RT beta 4 complementary DNA.";
RL Mol. Endocrinol. 6:989-992(1992).
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-45 and
CC Tyr-93/Trp-94. {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; M31160; AAB05637.1; -; mRNA.
DR PIR; A41918; A41918.
DR AlphaFoldDB; P09531; -.
DR SMR; P09531; -.
DR VEuPathDB; HostDB:geneid_100873157; -.
DR InParanoid; P09531; -.
DR OrthoDB; 643840at2759; -.
DR PhylomeDB; P09531; -.
DR Proteomes; UP000000539; Unplaced.
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:0005114; F:type II transforming growth factor beta receptor binding; IBA:GO_Central.
DR GO; GO:0034714; F:type III transforming growth factor beta receptor binding; IBA:GO_Central.
DR GO; GO:0030509; P:BMP signaling pathway; IBA:GO_Central.
DR GO; GO:0051781; P:positive regulation of cell division; IEA:UniProtKB-KW.
DR GO; GO:0046881; P:positive regulation of follicle-stimulating hormone secretion; IEP:AgBase.
DR GO; GO:0033686; P:positive regulation of luteinizing hormone secretion; IEP:AgBase.
DR GO; GO:0014008; P:positive regulation of microglia differentiation; ISS:UniProtKB.
DR GO; GO:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation; IBA:GO_Central.
DR GO; GO:0042327; P:positive regulation of phosphorylation; IEP:AgBase.
DR GO; GO:0042701; P:progesterone secretion; IEP:AgBase.
DR GO; GO:0042127; P:regulation of cell population proliferation; IBA:GO_Central.
DR GO; GO:0050708; P:regulation of protein secretion; IEP:AgBase.
DR GO; GO:0060395; P:SMAD protein signal transduction; IBA:GO_Central.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IBA:GO_Central.
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..18
FT /evidence="ECO:0000255"
FT CHAIN 19..277
FT /note="Latency-associated peptide"
FT /evidence="ECO:0000250|UniProtKB:P01137"
FT /id="PRO_0000033774"
FT CHAIN 278..391
FT /note="Transforming growth factor beta-1"
FT /evidence="ECO:0000250|UniProtKB:P01137"
FT /id="PRO_0000033775"
FT REGION 19..63
FT /note="Straightjacket domain"
FT /evidence="ECO:0000250|UniProtKB:P07200"
FT REGION 64..270
FT /note="Arm domain"
FT /evidence="ECO:0000250|UniProtKB:P07200"
FT REGION 221..249
FT /note="Bowtie tail"
FT /evidence="ECO:0000250|UniProtKB:P01137"
FT MOTIF 241..243
FT /note="Cell attachment site"
FT /evidence="ECO:0000255"
FT CARBOHYD 71
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 126
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 171
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 22
FT /note="Interchain (with C-? in LTBP1 TB3 domain); in
FT inactive form"
FT /evidence="ECO:0000250|UniProtKB:P07200"
FT DISULFID 218
FT /note="Interchain (with C-220)"
FT /evidence="ECO:0000250|UniProtKB:P01137"
FT DISULFID 220
FT /note="Interchain (with C-218)"
FT /evidence="ECO:0000250|UniProtKB:P01137"
FT DISULFID 284..295
FT /evidence="ECO:0000250|UniProtKB:P01137"
FT DISULFID 294..357
FT /evidence="ECO:0000250|UniProtKB:P01137"
FT DISULFID 323..388
FT /evidence="ECO:0000250|UniProtKB:P01137"
FT DISULFID 327..390
FT /evidence="ECO:0000250|UniProtKB:P01137"
FT DISULFID 356
FT /note="Interchain"
FT /evidence="ECO:0000250|UniProtKB:P01137"
FT CONFLICT 110
FT /note="P -> A (in Ref. 2; AAB05637)"
FT CONFLICT 130..138
FT /note="VRAEVGGRA -> ARRGGRPT (in Ref. 2; AAB05637)"
FT CONFLICT 228
FT /note="D -> E (in Ref. 2; AAB05637)"
SQ SEQUENCE 391 AA; 44437 MW; FB34D6A4BC4B0B93 CRC64;
MDPSPLLALL LLLGAARALS TCQRLDLEAA KKKRIEAVRG QILSKLRLTA PPPASETPPR
PLPDDVRALY NSTQELLKQR ARLRPPPDGP DEYWAKELRR IPMETTWDGP MEHWQPQSHS
IFFVFNVSRV RAEVGGRALL HRAELRMLRQ KAAADSAGTE QRLELYQGYG NASWRYLHGR
SVRATADDEW LSFDVTDAVH QWLSGSELLG VFKLSVHCPC EMGPGHADEM RISIEGFEQQ
RGDMQSIAKK HRRVPYVLAM ALPAERANEL HSARRRRDLD TDYCFGPGTD EKNCCVRPLY
IDFRKDLQWK WIHEPKGYMA NFCMGPCPYI WSADTQYTKV LALYNQHNPG ASAAPCCVPQ
TLDPLPIIYY VGRNVRVEQL SNMVVRACKC S
