TDGF1_MOUSE
ID TDGF1_MOUSE Reviewed; 171 AA.
AC P51865;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Teratocarcinoma-derived growth factor;
DE AltName: Full=Cripto growth factor;
DE AltName: Full=Epidermal growth factor-like Cripto protein;
DE Flags: Precursor;
GN Name=Tdgf1; Synonyms=Cripto;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C57BL/6J; TISSUE=Embryo;
RX PubMed=7916676; DOI=10.1242/dev.118.4.1157;
RA Dono R., Scalera L., Pacifico F., Acampora D., Persico M.G., Simeone A.;
RT "The murine cripto gene: expression during mesoderm induction and early
RT heart morphogenesis.";
RL Development 118:1157-1168(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 135-171.
RC STRAIN=129/Sv;
RX PubMed=8661720; DOI=10.1007/s003359900100;
RA Liguori G., Tucci M., Montuori N., Dono R., Lago C.T., Pacifico A.F.,
RA Persico M.G.;
RT "Characterization of the mouse Tdgf1 gene and Tdgf pseudogenes.";
RL Mamm. Genome 7:344-348(1996).
RN [3]
RP SUBCELLULAR LOCATION, AND GPI-ANCHOR.
RX PubMed=10640699; DOI=10.1016/s0925-4773(99)00235-x;
RA Minchiotti G., Parisi S., Liguori G., Signore M., Lania G., Adamson E.D.,
RA Lago C.T., Persico M.G.;
RT "Membrane-anchorage of Cripto protein by glycosylphosphatidylinositol and
RT its distribution during early mouse development.";
RL Mech. Dev. 90:133-142(2000).
RN [4]
RP STRUCTURE BY NMR OF 96-134, DISULFIDE BONDS, AND MUTAGENESIS OF TRP-107.
RX PubMed=17125258; DOI=10.1021/jm060772r;
RA Calvanese L., Saporito A., Marasco D., D'Auria G., Minchiotti G.,
RA Pedone C., Paolillo L., Falcigno L., Ruvo M.;
RT "Solution structure of mouse Cripto CFC domain and its inactive variant
RT Trp107Ala.";
RL J. Med. Chem. 49:7054-7062(2006).
CC -!- FUNCTION: GPI-anchored cell membrane protein involved in Nodal
CC signaling. Cell-associated Tdgf1 acts as a Nodal coreceptor in cis.
CC Shedding of Tdgf1 by Tmem8a modulates Nodal signaling by allowing
CC soluble Tdgf1 to act as a Nodal coreceptor on other cells. Could play a
CC role in the determination of the epiblastic cells that subsequently
CC give rise to the mesoderm. {ECO:0000250|UniProtKB:P13385}.
CC -!- SUBUNIT: Interacts with the activin type-1 receptor ACVR1B.
CC {ECO:0000250}.
CC -!- INTERACTION:
CC P51865; Q9W6I6: lft1; Xeno; NbExp=2; IntAct=EBI-15529529, EBI-15529806;
CC P51865; O13144: ndr1; Xeno; NbExp=2; IntAct=EBI-15529529, EBI-15529595;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10640699};
CC Lipid-anchor, GPI-anchor {ECO:0000269|PubMed:10640699}. Secreted
CC {ECO:0000250|UniProtKB:P13385}. Note=Released from the cell membrane by
CC GPI cleavage. {ECO:0000250|UniProtKB:P13385}.
CC -!- TISSUE SPECIFICITY: Expressed at low level in specific organs of the
CC adult animal such as spleen, heart, lung and brain. During
CC gastrulation, expressed in the forming mesoderm. In later stages of the
CC developing heart, expression is restricted to the truncus arteriosus.
CC -!- DEVELOPMENTAL STAGE: First expressed prior to the onset of gastrulation
CC (early streak stage), then continues throughout embryonic development.
CC -!- PTM: The GPI-anchor is attached to the protein in the endoplasmic
CC reticulum and serves to target the protein to the cell surface. There,
CC it is processed by GPI processing phospholipase A2 (Tmem8a), removing
CC an acyl-chain at the sn-2 position of GPI and releasing Tdgf1 as a
CC lysophosphatidylinositol-bearing form, which is further cleaved by
CC phospholipase D (Gpld1) into a soluble form.
CC {ECO:0000250|UniProtKB:P13385}.
CC -!- SIMILARITY: Belongs to the EGF-CFC (Cripto-1/FRL1/Cryptic) family.
CC {ECO:0000305}.
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DR EMBL; M87321; AAA37459.1; -; mRNA.
DR EMBL; X94083; CAA63827.1; -; Genomic_DNA.
DR CCDS; CCDS40783.1; -.
DR PIR; I49612; I49612.
DR PDB; 2J5H; NMR; -; A=96-134.
DR PDBsum; 2J5H; -.
DR AlphaFoldDB; P51865; -.
DR BMRB; P51865; -.
DR SMR; P51865; -.
DR DIP; DIP-46063N; -.
DR IntAct; P51865; 4.
DR STRING; 10090.ENSMUSP00000035075; -.
DR GlyGen; P51865; 1 site.
DR PaxDb; P51865; -.
DR PRIDE; P51865; -.
DR MGI; MGI:98658; Tdgf1.
DR eggNOG; KOG1217; Eukaryota.
DR InParanoid; P51865; -.
DR PhylomeDB; P51865; -.
DR EvolutionaryTrace; P51865; -.
DR PRO; PR:P51865; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; P51865; protein.
DR GO; GO:0031225; C:anchored component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016324; C:apical plasma membrane; ISO:MGI.
DR GO; GO:0009986; C:cell surface; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IDA:MGI.
DR GO; GO:0019897; C:extrinsic component of plasma membrane; IDA:MGI.
DR GO; GO:0005794; C:Golgi apparatus; IDA:MGI.
DR GO; GO:0045121; C:membrane raft; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0070697; F:activin receptor binding; IBA:GO_Central.
DR GO; GO:0015026; F:coreceptor activity; IDA:UniProtKB.
DR GO; GO:0008083; F:growth factor activity; ISO:MGI.
DR GO; GO:0038100; F:nodal binding; IPI:UniProtKB.
DR GO; GO:0005102; F:signaling receptor binding; ISO:MGI.
DR GO; GO:0070698; F:type I activin receptor binding; IPI:UniProtKB.
DR GO; GO:0017147; F:Wnt-protein binding; IPI:UniProtKB.
DR GO; GO:0048856; P:anatomical structure development; IBA:GO_Central.
DR GO; GO:0009948; P:anterior/posterior axis specification; IGI:MGI.
DR GO; GO:0008595; P:anterior/posterior axis specification, embryo; IMP:MGI.
DR GO; GO:0009952; P:anterior/posterior pattern specification; IBA:GO_Central.
DR GO; GO:0001568; P:blood vessel development; IBA:GO_Central.
DR GO; GO:0055007; P:cardiac muscle cell differentiation; IMP:MGI.
DR GO; GO:0030154; P:cell differentiation; TAS:UniProtKB.
DR GO; GO:0007368; P:determination of left/right symmetry; IBA:GO_Central.
DR GO; GO:0048144; P:fibroblast proliferation; IMP:MGI.
DR GO; GO:0007369; P:gastrulation; IGI:MGI.
DR GO; GO:0007507; P:heart development; IDA:UniProtKB.
DR GO; GO:0001701; P:in utero embryonic development; IMP:MGI.
DR GO; GO:0001763; P:morphogenesis of a branching structure; IDA:UniProtKB.
DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; IGI:MGI.
DR GO; GO:0038092; P:nodal signaling pathway; IMP:UniProtKB.
DR GO; GO:0030335; P:positive regulation of cell migration; IDA:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0001954; P:positive regulation of cell-matrix adhesion; IMP:MGI.
DR GO; GO:0048146; P:positive regulation of fibroblast proliferation; IMP:MGI.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IGI:MGI.
DR GO; GO:0010762; P:regulation of fibroblast migration; IMP:MGI.
DR GO; GO:0009966; P:regulation of signal transduction; IDA:MGI.
DR GO; GO:0001570; P:vasculogenesis; IMP:MGI.
DR InterPro; IPR017047; Cripto_growth_factor.
DR InterPro; IPR019011; Cryptic/Cripto_CFC-dom.
DR InterPro; IPR000742; EGF-like_dom.
DR Pfam; PF09443; CFC; 1.
DR PIRSF; PIRSF036301; Cripto_growth_factor; 1.
DR PROSITE; PS00022; EGF_1; 1.
DR PROSITE; PS50026; EGF_3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Disulfide bond; EGF-like domain; Glycoprotein;
KW GPI-anchor; Growth factor; Lipoprotein; Membrane; Reference proteome;
KW Secreted; Signal.
FT SIGNAL 1..17
FT /evidence="ECO:0000255"
FT CHAIN 18..134
FT /note="Teratocarcinoma-derived growth factor"
FT /id="PRO_0000007504"
FT PROPEP 135..171
FT /note="Removed in mature form"
FT /evidence="ECO:0000250"
FT /id="PRO_0000395411"
FT DOMAIN 62..91
FT /note="EGF-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT LIPID 134
FT /note="GPI-anchor amidated aspartate"
FT /evidence="ECO:0000250"
FT CARBOHYD 63
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 66..73
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 67..79
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 81..90
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 99..117
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076,
FT ECO:0000269|PubMed:17125258"
FT DISULFID 112..133
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076,
FT ECO:0000269|PubMed:17125258"
FT DISULFID 115..124
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076,
FT ECO:0000269|PubMed:17125258"
FT MUTAGEN 107
FT /note="W->A: Unable to bind Cripto receptor."
FT /evidence="ECO:0000269|PubMed:17125258"
FT STRAND 119..121
FT /evidence="ECO:0007829|PDB:2J5H"
FT STRAND 127..130
FT /evidence="ECO:0007829|PDB:2J5H"
SQ SEQUENCE 171 AA; 18754 MW; C52051AEACDB5380 CRC64;
MGYFSSSVVL LVAISSAFEF GPVAGRDLAI RDNSIWDQKE PAVRDRSFQF VPSVGIQNSK
SLNKTCCLNG GTCILGSFCA CPPSFYGRNC EHDVRKEHCG SILHGTWLPK KCSLCRCWHG
QLHCLPQTFL PGCDGHVMDQ DLKASRTPCQ TPSVTTTFML AGACLFLDMK V
