P13385 (TDGF1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Teratocarcinoma-derived growth factor 1

Alternative name(s):
Cripto-1 growth factor
Short name=CRGF
Epidermal growth factor-like cripto protein CR1

Gene names

Name:	TDGF1
Synonyms:	CRIPTO

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	188 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Could play a role in the determination of the epiblastic cells that subsequently give rise to the mesoderm. Ref.7
Subunit structure	Interacts with the activin type-1 receptor ACVR1B. Ref.7
Subcellular location	Cell membrane; Lipid-anchor › GPI-anchor Ref.9.
Tissue specificity	Preferentially expressed in gastric and colorectal carcinomas than in their normal counterparts. Expressed in breast and lung. Ref.10
Sequence similarities	Contains 1 EGF-like domain.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Domain	EGF-like domain Signal
Molecular function	Growth factor
PTM	Disulfide bond GPI-anchor Glycoprotein Lipoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	BMP signaling pathway Inferred from electronic annotation. Source: Compara activation of MAPK activity Inferred from direct assay PubMed 9013573. Source: UniProtKB anterior/posterior axis specification, embryo Inferred from sequence or structural similarity. Source: UniProtKB canonical Wnt receptor signaling pathway Inferred from electronic annotation. Source: Compara cardiac muscle cell differentiation Inferred from electronic annotation. Source: Compara cell differentiation Traceable author statement PubMed 11857442. Source: UniProtKB cell migration involved in sprouting angiogenesis Inferred from mutant phenotype PubMed 17720976. Source: UniProtKB cellular response to epidermal growth factor stimulus Inferred from direct assay PubMed 17720976. Source: UniProtKB cellular response to fibroblast growth factor stimulus Inferred from direct assay PubMed 17720976. Source: UniProtKB cellular response to hepatocyte growth factor stimulus Inferred from direct assay PubMed 17720976. Source: UniProtKB cellular response to interferon-gamma Inferred from direct assay PubMed 17720976. Source: UniProtKB cellular response to interleukin-6 Inferred from direct assay PubMed 17720976. Source: UniProtKB cellular response to tumor necrosis factor Inferred from direct assay PubMed 17720976. Source: UniProtKB gastrulation Inferred from electronic annotation. Source: Compara heart development Inferred from direct assay PubMed 9576836. Source: UniProtKB in utero embryonic development Inferred from electronic annotation. Source: Compara mammary gland development Traceable author statement PubMed 11857442. Source: UniProtKB morphogenesis of a branching structure Traceable author statement PubMed 10070255. Source: UniProtKB negative regulation of apoptotic process Inferred from direct assay PubMed 10493495. Source: UniProtKB negative regulation of transforming growth factor beta receptor signaling pathway Inferred from electronic annotation. Source: Compara peptidyl-serine phosphorylation Inferred from direct assay PubMed 10493495. Source: UniProtKB positive regulation of cell proliferation Traceable author statement PubMed 11857442. Source: UniProtKB positive regulation of cell-matrix adhesion Inferred from electronic annotation. Source: Compara positive regulation of endothelial cell migration Inferred from direct assay PubMed 17720976. Source: UniProtKB positive regulation of fibroblast proliferation Inferred from electronic annotation. Source: Compara positive regulation of peptidyl-tyrosine phosphorylation Inferred from direct assay PubMed 10493495. Source: UniProtKB positive regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara vasculogenesis Inferred from electronic annotation. Source: Compara
Cellular_component	Golgi apparatus Inferred from electronic annotation. Source: Compara anchored to membrane Inferred from electronic annotation. Source: UniProtKB-KW apical plasma membrane Inferred from direct assay PubMed 17720976. Source: UniProtKB cell surface Inferred from direct assay PubMed 12925698. Source: UniProtKB extracellular space Inferred from direct assay PubMed 17720976. Source: UniProtKB extrinsic to plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB membrane raft Inferred from direct assay PubMed 17720976. Source: UniProtKB nucleus Inferred from electronic annotation. Source: Compara perinuclear region of cytoplasm Inferred from electronic annotation. Source: Compara
Molecular_function	growth factor activity Inferred from direct assay PubMed 12925698. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 30	30	Ref.6
	Chain	31 – 150	120	Teratocarcinoma-derived growth factor 1		PRO_0000007503
	Propeptide	151 – 188	38	Removed in mature form		PRO_0000395410
Regions
	Domain	78 – 107	30	EGF-like
Amino acid modifications
	Lipidation	150	1	GPI-anchor amidated aspartate Ref.9
	Glycosylation	79	1	N-linked (GlcNAc...) Potential
	Disulfide bond	82 ↔ 89		By similarity
	Disulfide bond	83 ↔ 95		By similarity
	Disulfide bond	97 ↔ 106		By similarity
	Disulfide bond	115 ↔ 133		Ref.8
	Disulfide bond	128 ↔ 149		Ref.8
	Disulfide bond	131 ↔ 140		Ref.8
Natural variations
	Natural variant	22	1	V → A. Ref.4 Ref.5 Corresponds to variant rs11130097 [ dbSNP | Ensembl ].		VAR_024262
	Natural variant	43	1	Y → D. Corresponds to variant rs2293025 [ dbSNP | Ensembl ].		VAR_021903
	Natural variant	111	1	R → G. Corresponds to variant rs34501971 [ dbSNP | Ensembl ].		VAR_048975
Experimental info
	Mutagenesis	188	1	Y → YVVVVV: Alters the localization and decreases the biological activity. Ref.9

Sequences

	Sequence		Length	Mass (Da)
	P13385 [UniParc]. Last modified January 1, 1990. Version 1. Checksum: AEE8727D0F27D886	FASTA	188	21,169
	10 20 30 40 50 60 MDCRKMARFS YSVIWIMAIS KVFELGLVAG LGHQEFARPS RGYLAFRDDS IWPQEEPAIR 70 80 90 100 110 120 PRSSQRVPPM GIQHSKELNR TCCLNGGTCM LGSFCACPPS FYGRNCEHDV RKENCGSVPH 130 140 150 160 170 180 DTWLPKKCSL CKCWHGQLRC FPQAFLPGCD GLVMDEHLVA SRTPELPPSA RTTTFMLVGI CLSIQSYY

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular characterization of a gene of the 'EGF family' expressed in undifferentiated human NTERA2 teratocarcinoma cells." Ciccodicola A., Dono R., Obici S., Zollo M., Persico M.G. EMBO J. 8:1987-1991(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Isolation and characterization of the CRIPTO autosomal gene and its X-linked related sequence." Dono R., Montuori N., Rocchi M., de Ponti-Zilli L., Ciccodicola A., Persico M.G. Am. J. Hum. Genet. 49:555-565(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"The DNA sequence, annotation and analysis of human chromosome 3." Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A. Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT ALA-22.
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ALA-22. Tissue: Brain and Kidney.
[6]	"Signal peptide prediction based on analysis of experimentally verified cleavage sites." Zhang Z., Henzel W.J. Protein Sci. 13:2819-2824(2004) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 31-45.
[7]	"Cripto-1 activates nodal- and ALK4-dependent and -independent signaling pathways in mammary epithelial Cells." Bianco C., Adkins H.B., Wechselberger C., Seno M., Normanno N., De Luca A., Sun Y., Khan N., Kenney N., Ebert A., Williams K.P., Sanicola M., Salomon D.S. Mol. Cell. Biol. 22:2586-2597(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ACVR1B, FUNCTION.
[8]	"The CRIPTO/FRL-1/CRYPTIC (CFC) domain of human Cripto." Foley S.F., Van Vlijmen H.W., Boynton R.E., Adkins H.B., Cheung A.E., Singh J., Sanicola M., Young C.N., Wen D. Eur. J. Biochem. 270:3610-3618(2003) [PubMed] [Europe PMC] [Abstract] Cited for: DISULFIDE BONDS.
[9]	"Characterization of the glycosylphosphatidylinositol-anchor signal sequence of human Cryptic with a hydrophilic extension." Watanabe K., Nagaoka T., Strizzi L., Mancino M., Gonzales M., Bianco C., Salomon D.S. Biochim. Biophys. Acta 1778:2671-2681(2008) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, GPI-ANCHOR, MUTAGENESIS OF TYR-188.
[10]	"CRIPTO3, a presumed pseudogene, is expressed in cancer." Sun C., Orozco O., Olson D.L., Choi E., Garber E., Tizard R., Szak S., Sanicola M., Carulli J.P. Biochem. Biophys. Res. Commun. 377:215-220(2008) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X14253 mRNA. Translation: CAA32467.1. M96955 Genomic DNA. Translation: AAA61134.1. AC104304 Genomic DNA. No translation available. CH471055 Genomic DNA. Translation: EAW64773.1. BC022393 mRNA. Translation: AAH22393.1. BC067844 mRNA. Translation: AAH67844.1.
IPI	IPI00008499.
PIR	A30362. B39787.
RefSeq	NP_001167607.1. NM_001174136.1. NP_003203.1. NM_003212.3.
UniGene	Hs.385870.
3D structure databases
ProteinModelPortal	P13385.
ModBase	Search...
Protein-protein interaction databases
IntAct	P13385. 8 interactions.
MINT	MINT-1386411.
STRING	9606.ENSP00000296145.
Polymorphism databases
DMDM	117473.
Proteomic databases
PaxDb	P13385.
PRIDE	P13385.
Protocols and materials databases
DNASU	6997.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000296145; ENSP00000296145; ENSG00000241186.
GeneID	6997.
KEGG	hsa:6997.
UCSC	uc003cpv.3. human.
Organism-specific databases
CTD	6997.
GeneCards	GC03P046616.
HGNC	HGNC:11701. TDGF1.
MIM	187395. gene+phenotype.
neXtProt	NX_P13385.
Orphanet	93925. Alobar holoprosencephaly. 93924. Lobar holoprosencephaly. 280200. Microform holoprosencephaly. 93926. Midline interhemispheric variant of holoprosencephaly. 220386. Semilobar holoprosencephaly. 280195. Septopreoptic holoprosencephaly.
PharmGKB	PA36420.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG320031.
HOGENOM	HOG000145523.
HOVERGEN	HBG054705.
InParanoid	P13385.
OMA	NCEHDVR.
OrthoDB	EOG4G1MHG.
PhylomeDB	P13385.
Enzyme and pathway databases
Pathway_Interaction_DB	glypican_1pathway. Glypican 1 network.
Reactome	REACT_111045. Developmental Biology.
Gene expression databases
ArrayExpress	P13385.
Bgee	P13385.
CleanEx	HS_TDGF1.
Genevestigator	P13385.
GermOnline	ENSG00000163828. Homo sapiens.
Family and domain databases
InterPro	IPR017047. Cripto_growth_factor. IPR019011. Cryptic/Cripto_CFC-dom. IPR000742. EG-like_dom. IPR013032. EGF-like_CS. [Graphical view]
Pfam	PF09443. CFC. 1 hit. [Graphical view]
PIRSF	PIRSF036301. Cripto_growth_factor. 1 hit.
SMART	SM00181. EGF. 1 hit. [Graphical view]
PROSITE	PS00022. EGF_1. 1 hit. PS01186. EGF_2. False negative. PS50026. EGF_3. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	TDGF1. human.
GenomeRNAi	6997.
NextBio	27331.
SOURCE	Search...

Entry information

Entry name

TDGF1_HUMAN

Accession

Primary (citable) accession number: P13385
Secondary accession number(s): Q8TCC1

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 1, 1990
Last sequence update:	January 1, 1990
Last modified:	May 1, 2013
This is version 125 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.