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FLASH GENE
Symbol TDGF1 contributors: mct - updated : 22-11-2016
HGNC name teratocarcinoma-derived growth factor 1
HGNC id 11701
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
6 - 2174 - 188 - 2013 23129342
6 - 1784 - 172 - 2013 23129342
EXPRESSION
Type restricted
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Nervousbrain   moderately
Urinarykidney   moderately
cell lineage undifferentiated cells
cell lines gastric and colorectal carcinomas cell lines
fluid/secretion
at STAGE
physiological period embryo
Text embryonic tissue
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • one EGF-like domain and a six cysteine (CFC) motifs
  • three tandem LEF1 binding sites
  • conjugated MetalloP
    HOMOLOGY
    interspecies ortholog to murine Cripto
    homolog to C.elegans c49g7.11
    intraspecies paralog to CFC1
    Homologene
    FAMILY
  • epidermal growth factor-cripto FRL1 cryptic (EGF-CFC) gene family
  • CATEGORY protooncogene , signaling growth factor
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
    text exhibits pericellular characteristics of a GPI-anchored protein in that it can be localized to lipid raft domains on the plasma membrane
    basic FUNCTION
  • playing a role in the determination of the epiblastic cells that subsequently give rise to the mesoderm
  • implicated in midline forebrain and left-right axis development
  • can activate mitogen-activated protein kinase (MAPK), AKT and c-src intracellular signaling pathways independently of Nodal and ALK4
  • function as a ligand through a Nodal/ALK4-independent signaling pathway that involves binding to glypican-1 and the subsequent activation through SRC of phosphoinositol-3 kinase/Akt and ras/mitogen-activated protein kinase intracellular pathways
  • may be involved in stem cell maintenance
  • can stimulate endothelial cell sprouting through direct cell-cell interaction, and may contribute to endothelial cell migration and possibly tumor angiogenesis
  • angiogenic and oncogenic effects might be enhanced by its shedding and shedding of TDGF1 could be a potential target for cancer therapy
  • glycosylphosphatidylinositol-anchored signaling protein with important roles during embryonic development, stem cell function and cancer progression
  • plays a key role in stem cell biology and during early embryonic development
  • with HSPA5 bind at the cell surface to enhance tumor growth via the inhibition of TGF-beta signaling
  • capable of signaling through the Nodal pathway
  • plays critical roles during embryogenesis and has been implicated in promoting the growth and spread of tumors
  • facilitates Nodal signaling and inhibits activin signaling by forming receptor complexes with these ligands that are structurally and functionally similar
  • with HSPA5, cooperatively regulate signaling via activin-A, activin-B, TGFB-1 and NODAL
  • both TDGF1 and CFC1 function non-cell-autonomously during normal development
  • plays a role in the malignant transformation of the oral mucosa and is involved in the tumorigenesis and progression of oral squamous cell carcinoma by promoting the growth and migration of malignant cells
  • may play a role during developmental EMT, and it may also be involved in the reprogramming of differentiated tumor cells into cancer stem cells through the induction of an EMT program
  • is implicated in multiple cellular events, including cell proliferation, motility and angiogenesis, through the activation of an intricate network of signaling pathways
  • is the key GPI anchored protein whose altered function results likely in an holoprosencephaly-like phenotype
  • TDGF1 and its cell-surface receptor HSPA5 are regulators of stem cell behavior in isolated fetal and adult mammary epithelial cells
  • is a multifunctional embryonic protein that is re-expressed during inflammation, wound repair, and malignant transformation
  • mediate cell growth, migration, invasion, and induce epithelial to mesenchymal transition (EMT)
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS development
    text germ line formation, correct positioning in anteroposterior axis (mouse)
  • acting as a ligand and coreceptor in the signaling pathway for then TGF beta ligand NODAL
  • PATHWAY
    metabolism
    signaling signal transduction
  • Wnt signaling pathway
  • signaling by the TGFB1 morphogen NODAL and its co-receptor TDGF1 is active during a crucial window of male germ cell development
  • a component
  • forms a cell surface complex with the HSP70 family member glucose-regulated protein-78 (HSPA5)
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • co-receptor for the morphogen NODAL (strongly expressed in undifferentiated cells and rapidly down-regulated during retinoic acid-induced differentiation)
  • co-receptor for NODAL, that can activate Nodal-dependent and Nodal-independent signaling pathways
  • modulates myogenic cell determination and promotes proliferation by antagonizing the TGFB1 ligand myostatin (MSTN)
  • MEF2C regulates outflow tract alignment and transcriptional control of TDGF1
  • cell & other
    REGULATION
    repressed by SNAI1 (SNAI1 represses TDGF1 gene by direct transcriptional interaction and it co-ordinately regulates likely cell fate decisions during development and could be causal of cancers)
    Other regulated by Wnt signaling pathway
    ASSOCIATED DISORDERS
    corresponding disease(s) HPEL1
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   deletion    
    in colon carcinoma, hepatoma cell lines and primary colon cancers
    constitutional germinal mutation      
    associated with developmental defects
    tumoral     --over  
    in several different types of human carcinomas with a differential modulation in embryonal and colon cancer cells by two different members of the TGF-beta family
    tumoral     --over  
    contributes to aggressiveness and poor prognosis of hepatocellular carcinoma
    constitutional       loss of function
    have been shown to result in holoprosencephaly
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • may be an attractive target in the diagnosis, prognosis and therapy of several types of human cancer
  • Therapy target
    SystemTypeDisorderPubmed
    cancer  
    disrupting the TDGF1/HSPA5 binding interface blocks oncogenic TDGF1 signaling and may have important therapeutic value in the treatment of cancer
    ANIMAL & CELL MODELS