Entrez Summary: This gene encodes a member of the signal peptide, complement subcomponents C1r/C1s, Uegf, bone morphogenetic protein-1 and epidermal growth factor-like domain containing protein family. Overexpression of this gene in human embryonic kidney cells results in secretion of a glycosylated form of the protein that forms oligomers and tethers to the cell surface. This gene is upregulated in lung cancer tumor tissue compared to healthy tissue and is associated with loss of the epithelial marker E-cadherin and with increased expression of vimentin, a mesenchymal marker. In addition, the protein encoded by this gene is a transforming growth factor beta receptor ligand, and when secreted by cancer cells, it can be cleaved in vitro to release the N-terminal epidermal growth factor-like repeat domain and the C-terminal complement subcomponents C1r/C1s domain. Both the full length protein and C-terminal fragment can bind to the transforming growth factor beta type II receptor to promote the epithelial-mesenchymal transition and tumor angiogenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014].
UniProt Summary: Binds to TGFBR2 and activates TGFB signaling. In lung cancer cells, could serve as an endogenous autocrine and paracrine ligand of TGFBR2, which could regulate TGFBR2 signaling and hence modulate epithelial-mesenchymal transition and cancer progression. {ECO:0000269|PubMed:21441952}.
Pfam DomainsGO Terms
Pfam Domains
GCC2 GCC3
EGF
EGF 3
CUB
cEGF
EGF CA
GO Terms
positive regulation of smoothened signaling pathway
extracellular matrix disassembly
regulation of smoothened signaling pathway
protein heterooligomerization
protein homooligomerization
extracellular matrix organization
extracellular structure organization
cellular component disassembly
protein complex oligomerization
cell surface
calcium ion binding
protein-containing complex assembly
extracellular space
positive regulation of signal transduction
positive regulation of cell communication
positive regulation of signaling
protein-containing complex subunit organization
CRISPR Data
Compound HitMost Correlated Genes in ChemogenomicsTissues where Essential in the Avana Dataset (DepMap 20Q1)