TDGF1_HUMAN
ID TDGF1_HUMAN Reviewed; 188 AA.
AC P13385; Q8TCC1;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1990, sequence version 1.
DT 03-AUG-2022, entry version 190.
DE RecName: Full=Teratocarcinoma-derived growth factor 1;
DE AltName: Full=Cripto-1 growth factor;
DE Short=CRGF;
DE AltName: Full=Epidermal growth factor-like cripto protein CR1;
DE Flags: Precursor;
GN Name=TDGF1; Synonyms=CRIPTO;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2792079; DOI=10.1002/j.1460-2075.1989.tb03605.x;
RA Ciccodicola A., Dono R., Obici S., Zollo M., Persico M.G.;
RT "Molecular characterization of a gene of the 'EGF family' expressed in
RT undifferentiated human NTERA2 teratocarcinoma cells.";
RL EMBO J. 8:1987-1991(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1882841;
RA Dono R., Montuori N., Rocchi M., de Ponti-Zilli L., Ciccodicola A.,
RA Persico M.G.;
RT "Isolation and characterization of the CRIPTO autosomal gene and its X-
RT linked related sequence.";
RL Am. J. Hum. Genet. 49:555-565(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ALA-22.
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ALA-22.
RC TISSUE=Brain, and Kidney;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP PROTEIN SEQUENCE OF 31-45.
RX PubMed=15340161; DOI=10.1110/ps.04682504;
RA Zhang Z., Henzel W.J.;
RT "Signal peptide prediction based on analysis of experimentally verified
RT cleavage sites.";
RL Protein Sci. 13:2819-2824(2004).
RN [7]
RP INTERACTION WITH ACVR1B, AND FUNCTION.
RX PubMed=11909953; DOI=10.1128/mcb.22.8.2586-2597.2002;
RA Bianco C., Adkins H.B., Wechselberger C., Seno M., Normanno N., De Luca A.,
RA Sun Y., Khan N., Kenney N., Ebert A., Williams K.P., Sanicola M.,
RA Salomon D.S.;
RT "Cripto-1 activates nodal- and ALK4-dependent and -independent signaling
RT pathways in mammary epithelial Cells.";
RL Mol. Cell. Biol. 22:2586-2597(2002).
RN [8]
RP DISULFIDE BONDS.
RX PubMed=12919325; DOI=10.1046/j.1432-1033.2003.03749.x;
RA Foley S.F., Van Vlijmen H.W., Boynton R.E., Adkins H.B., Cheung A.E.,
RA Singh J., Sanicola M., Young C.N., Wen D.;
RT "The CRIPTO/FRL-1/CRYPTIC (CFC) domain of human Cripto.";
RL Eur. J. Biochem. 270:3610-3618(2003).
RN [9]
RP SUBCELLULAR LOCATION, GPI-ANCHOR AT ASP-150, AND MUTAGENESIS OF TYR-188.
RX PubMed=18930707; DOI=10.1016/j.bbamem.2008.09.011;
RA Watanabe K., Nagaoka T., Strizzi L., Mancino M., Gonzales M., Bianco C.,
RA Salomon D.S.;
RT "Characterization of the glycosylphosphatidylinositol-anchor signal
RT sequence of human Cryptic with a hydrophilic extension.";
RL Biochim. Biophys. Acta 1778:2671-2681(2008).
RN [10]
RP TISSUE SPECIFICITY.
RX PubMed=18835250; DOI=10.1016/j.bbrc.2008.09.113;
RA Sun C., Orozco O., Olson D.L., Choi E., Garber E., Tizard R., Szak S.,
RA Sanicola M., Carulli J.P.;
RT "CRIPTO3, a presumed pseudogene, is expressed in cancer.";
RL Biochem. Biophys. Res. Commun. 377:215-220(2008).
RN [11]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=27881714; DOI=10.1083/jcb.201605121;
RA Lee G.H., Fujita M., Takaoka K., Murakami Y., Fujihara Y., Kanzawa N.,
RA Murakami K.I., Kajikawa E., Takada Y., Saito K., Ikawa M., Hamada H.,
RA Maeda Y., Kinoshita T.;
RT "A GPI processing phospholipase A2, PGAP6, modulates Nodal signaling in
RT embryos by shedding CRIPTO.";
RL J. Cell Biol. 215:705-718(2016).
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
CC (PubMed:27881714). Could play a role in the determination of the
CC epiblastic cells that subsequently give rise to the mesoderm
CC (PubMed:11909953). {ECO:0000269|PubMed:11909953,
CC ECO:0000269|PubMed:27881714}.
CC -!- SUBUNIT: Interacts with the activin type-1 receptor ACVR1B.
CC {ECO:0000269|PubMed:11909953}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:18930707,
CC ECO:0000269|PubMed:27881714}; Lipid-anchor, GPI-anchor
CC {ECO:0000269|PubMed:18930707, ECO:0000269|PubMed:27881714}. Secreted
CC {ECO:0000269|PubMed:27881714}. Note=Released from the cell membrane by
CC GPI cleavage. {ECO:0000269|PubMed:27881714}.
CC -!- TISSUE SPECIFICITY: Preferentially expressed in gastric and colorectal
CC carcinomas than in their normal counterparts. Expressed in breast and
CC lung. {ECO:0000269|PubMed:18835250}.
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:0000269|PubMed:27881714}.
CC -!- SIMILARITY: Belongs to the EGF-CFC (Cripto-1/FRL1/Cryptic) family.
CC {ECO:0000305}.
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DR EMBL; X14253; CAA32467.1; -; mRNA.
DR EMBL; M96955; AAA61134.1; -; Genomic_DNA.
DR EMBL; AC104304; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471055; EAW64773.1; -; Genomic_DNA.
DR EMBL; BC022393; AAH22393.1; -; mRNA.
DR EMBL; BC067844; AAH67844.1; -; mRNA.
DR CCDS; CCDS2742.1; -.
DR PIR; B39787; A30362.
DR RefSeq; NP_001167607.1; NM_001174136.1.
DR RefSeq; NP_003203.1; NM_003212.3.
DR AlphaFoldDB; P13385; -.
DR BioGRID; 112856; 72.
DR IntAct; P13385; 28.
DR MINT; P13385; -.
DR STRING; 9606.ENSP00000296145; -.
DR ChEMBL; CHEMBL3713025; -.
DR GlyGen; P13385; 1 site.
DR BioMuta; TDGF1; -.
DR DMDM; 117473; -.
DR EPD; P13385; -.
DR jPOST; P13385; -.
DR MassIVE; P13385; -.
DR PaxDb; P13385; -.
DR PeptideAtlas; P13385; -.
DR PRIDE; P13385; -.
DR ProteomicsDB; 52909; -.
DR Antibodypedia; 35134; 666 antibodies from 38 providers.
DR DNASU; 6997; -.
DR Ensembl; ENST00000296145.6; ENSP00000296145.5; ENSG00000241186.10.
DR GeneID; 6997; -.
DR KEGG; hsa:6997; -.
DR MANE-Select; ENST00000296145.6; ENSP00000296145.5; NM_003212.4; NP_003203.1.
DR UCSC; uc003cpv.4; human.
DR CTD; 6997; -.
DR DisGeNET; 6997; -.
DR GeneCards; TDGF1; -.
DR GeneReviews; TDGF1; -.
DR HGNC; HGNC:11701; TDGF1.
DR HPA; ENSG00000241186; Tissue enhanced (kidney, lymphoid tissue).
DR MalaCards; TDGF1; -.
DR MIM; 187395; gene+phenotype.
DR neXtProt; NX_P13385; -.
DR OpenTargets; ENSG00000241186; -.
DR Orphanet; 93925; Alobar holoprosencephaly.
DR Orphanet; 93924; Lobar holoprosencephaly.
DR Orphanet; 280200; Microform holoprosencephaly.
DR Orphanet; 93926; Midline interhemispheric variant of holoprosencephaly.
DR Orphanet; 220386; Semilobar holoprosencephaly.
DR Orphanet; 280195; Septopreoptic holoprosencephaly.
DR PharmGKB; PA36420; -.
DR VEuPathDB; HostDB:ENSG00000241186; -.
DR eggNOG; KOG1217; Eukaryota.
DR GeneTree; ENSGT00940000159076; -.
DR InParanoid; P13385; -.
DR OMA; PMGIQNS; -.
DR OrthoDB; 1387592at2759; -.
DR PhylomeDB; P13385; -.
DR TreeFam; TF333187; -.
DR PathwayCommons; P13385; -.
DR Reactome; R-HSA-1181150; Signaling by NODAL.
DR Reactome; R-HSA-1433617; Regulation of signaling by NODAL.
DR Reactome; R-HSA-2892247; POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation.
DR SignaLink; P13385; -.
DR SIGNOR; P13385; -.
DR BioGRID-ORCS; 6997; 401 hits in 1038 CRISPR screens.
DR ChiTaRS; TDGF1; human.
DR GeneWiki; Teratocarcinoma-derived_growth_factor_1; -.
DR GenomeRNAi; 6997; -.
DR Pharos; P13385; Tbio.
DR PRO; PR:P13385; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; P13385; protein.
DR Bgee; ENSG00000241186; Expressed in adrenal tissue and 89 other tissues.
DR ExpressionAtlas; P13385; baseline and differential.
DR Genevisible; P13385; HS.
DR GO; GO:0031225; C:anchored component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; IBA:GO_Central.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0019897; C:extrinsic component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0045121; C:membrane raft; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0070697; F:activin receptor binding; IBA:GO_Central.
DR GO; GO:0008083; F:growth factor activity; IDA:UniProtKB.
DR GO; GO:0038100; F:nodal binding; IBA:GO_Central.
DR GO; GO:0005102; F:signaling receptor binding; IDA:UniProtKB.
DR GO; GO:0048856; P:anatomical structure development; IBA:GO_Central.
DR GO; GO:0008595; P:anterior/posterior axis specification, embryo; ISS:UniProtKB.
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:0030154; P:cell differentiation; TAS:UniProtKB.
DR GO; GO:0002042; P:cell migration involved in sprouting angiogenesis; IMP:UniProtKB.
DR GO; GO:0071364; P:cellular response to epidermal growth factor stimulus; IDA:UniProtKB.
DR GO; GO:0044344; P:cellular response to fibroblast growth factor stimulus; IDA:UniProtKB.
DR GO; GO:0035729; P:cellular response to hepatocyte growth factor stimulus; IDA:UniProtKB.
DR GO; GO:0071346; P:cellular response to interferon-gamma; IDA:UniProtKB.
DR GO; GO:0071354; P:cellular response to interleukin-6; IDA:UniProtKB.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IDA:UniProtKB.
DR GO; GO:0007368; P:determination of left/right symmetry; IBA:GO_Central.
DR GO; GO:0009792; P:embryo development ending in birth or egg hatching; TAS:UniProtKB.
DR GO; GO:0007507; P:heart development; IDA:UniProtKB.
DR GO; GO:0030879; P:mammary gland development; TAS:UniProtKB.
DR GO; GO:0001763; P:morphogenesis of a branching structure; TAS:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:0038092; P:nodal signaling pathway; IBA:GO_Central.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:UniProtKB.
DR GO; GO:0030335; P:positive regulation of cell migration; IDA:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:MGI.
DR GO; GO:0010595; P:positive regulation of endothelial cell migration; IDA:UniProtKB.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; IDA:MGI.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IDA:UniProtKB.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IDA:UniProtKB.
DR GO; GO:0009966; P:regulation of signal transduction; IDA:UniProtKB.
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 Cell membrane; Direct protein sequencing; Disulfide bond; EGF-like domain;
KW Glycoprotein; GPI-anchor; Growth factor; Lipoprotein; Membrane;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..30
FT /evidence="ECO:0000269|PubMed:15340161"
FT CHAIN 31..150
FT /note="Teratocarcinoma-derived growth factor 1"
FT /id="PRO_0000007503"
FT PROPEP 151..188
FT /note="Removed in mature form"
FT /id="PRO_0000395410"
FT DOMAIN 78..107
FT /note="EGF-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT LIPID 150
FT /note="GPI-anchor amidated aspartate"
FT /evidence="ECO:0000269|PubMed:18930707"
FT CARBOHYD 79
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 82..89
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 83..95
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 97..106
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 115..133
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076,
FT ECO:0000269|PubMed:12919325"
FT DISULFID 128..149
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076,
FT ECO:0000269|PubMed:12919325"
FT DISULFID 131..140
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076,
FT ECO:0000269|PubMed:12919325"
FT VARIANT 22
FT /note="V -> A (in dbSNP:rs11130097)"
FT /evidence="ECO:0000269|PubMed:15489334, ECO:0000269|Ref.4"
FT /id="VAR_024262"
FT VARIANT 43
FT /note="Y -> D (in dbSNP:rs2293025)"
FT /id="VAR_021903"
FT VARIANT 111
FT /note="R -> G (in dbSNP:rs34501971)"
FT /id="VAR_048975"
FT MUTAGEN 188
FT /note="Y->YVVVVV: Alters the localization and decreases the
FT biological activity."
FT /evidence="ECO:0000269|PubMed:18930707"
SQ SEQUENCE 188 AA; 21169 MW; AEE8727D0F27D886 CRC64;
MDCRKMARFS YSVIWIMAIS KVFELGLVAG LGHQEFARPS RGYLAFRDDS IWPQEEPAIR
PRSSQRVPPM GIQHSKELNR TCCLNGGTCM LGSFCACPPS FYGRNCEHDV RKENCGSVPH
DTWLPKKCSL CKCWHGQLRC FPQAFLPGCD GLVMDEHLVA SRTPELPPSA RTTTFMLVGI
CLSIQSYY
