======= CEACAM1 =======
== Gene Information ==
* **Official Symbol**: CEACAM1
* **Official Name**: CEA cell adhesion molecule 1
* **Aliases and Previous Symbols**: N/A
* **Entrez ID**: [[https://www.ncbi.nlm.nih.gov/gene/?term=634|634]]
* **UniProt**: [[https://www.uniprot.org/uniprot/P13688|P13688]]
* **Interactions**: [[https://thebiogrid.org/search.php?search=CEACAM1&organism=9606|BioGRID]]
* **PubMed articles**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20CEACAM1|Open PubMed]]
* **OMIM**: [[https://omim.org/entry/109770|Open OMIM]]
== Function Summary ==
* **Entrez Summary**: This gene encodes a member of the carcinoembryonic antigen (CEA) gene family, which belongs to the immunoglobulin superfamily. Two subgroups of the CEA family, the CEA cell adhesion molecules and the pregnancy-specific glycoproteins, are located within a 1.2 Mb cluster on the long arm of chromosome 19. Eleven pseudogenes of the CEA cell adhesion molecule subgroup are also found in the cluster. The encoded protein was originally described in bile ducts of liver as biliary glycoprotein. Subsequently, it was found to be a cell-cell adhesion molecule detected on leukocytes, epithelia, and endothelia. The encoded protein mediates cell adhesion via homophilic as well as heterophilic binding to other proteins of the subgroup. Multiple cellular activities have been attributed to the encoded protein, including roles in the differentiation and arrangement of tissue three-dimensional structure, angiogenesis, apoptosis, tumor suppression, metastasis, and the modulation of innate and adaptive immune responses. Multiple transcript variants encoding different isoforms have been reported, but the full-length nature of all variants has not been defined. [provided by RefSeq, May 2010].
* **UniProt Summary**: Isoform 1: Cell adhesion protein that mediates homophilic cell adhesion in a calcium-independent manner (By similarity). Plays a role as coinhibitory receptor in immune response, insulin action and functions also as an activator during angiogenesis (PubMed:18424730, PubMed:23696226, PubMed:25363763). Its coinhibitory receptor function is phosphorylation- and PTPN6 -dependent, which in turn, suppress signal transduction of associated receptors by dephosphorylation of their downstream effectors. Plays a role in immune response, of T cells, natural killer (NK) and neutrophils (PubMed:18424730, PubMed:23696226). Upon TCR/CD3 complex stimulation, inhibits TCR-mediated cytotoxicity by blocking granule exocytosis by mediating homophilic binding to adjacent cells, allowing interaction with and phosphorylation by LCK and interaction with the TCR/CD3 complex which recruits PTPN6 resulting in dephosphorylation of CD247 and ZAP70 (PubMed:18424730). Also inhibits T cell proliferation and cytokine production through inhibition of JNK cascade and plays a crucial role in regulating autoimmunity and anti-tumor immunity by inhibiting T cell through its interaction with HAVCR2 (PubMed:25363763). Upon natural killer (NK) cells activation, inhibit KLRK1-mediated cytolysis of CEACAM1-bearing tumor cells by trans-homophilic interactions with CEACAM1 on the target cell and lead to cis-interaction between CEACAM1 and KLRK1, allowing PTPN6 recruitment and then VAV1 dephosphorylation (PubMed:23696226). Upon neutrophils activation negatively regulates IL1B production by recruiting PTPN6 to a SYK-TLR4- CEACAM1 complex, that dephosphorylates SYK, reducing the production of reactive oxygen species (ROS) and lysosome disruption, which in turn, reduces the activity of the inflammasome. Downregulates neutrophil production by acting as a coinhibitory receptor for CSF3R by downregulating the CSF3R-STAT3 pathway through recruitment of PTPN6 that dephosphorylates CSF3R (By similarity). Also regulates insulin action by promoting INS clearance and regulating lipogenesis in liver through regulating insulin signaling (By similarity). Upon INS stimulation, undergoes phosphorylation by INSR leading to INS clearance by increasing receptor-mediated insulin endocytosis. This inernalization promotes interaction with FASN leading to receptor-mediated insulin degradation and to reduction of FASN activity leading to negative regulation of fatty acid synthesis. INSR-mediated phosphorylation also provokes a down-regulation of cell proliferation through SHC1 interaction resulting in decrease coupling of SHC1 to the MAPK3/ERK1-MAPK1/ERK2 and phosphatidylinositol 3-kinase pathways (By similarity). Functions as activator in angiogenesis by promoting blood vessel remodeling through endothelial cell differentiation and migration and in arteriogenesis by increasing the number of collateral arteries and collateral vessel calibers after ischemia. Also regulates vascular permeability through the VEGFR2 signaling pathway resulting in control of nitric oxide production (By similarity). Downregulates cell growth in response to EGF through its interaction with SHC1 that mediates interaction with EGFR resulting in decrease coupling of SHC1 to the MAPK3/ERK1-MAPK1/ERK2 pathway (By similarity). Negatively regulates platelet aggregation by decreasing platelet adhesion on type I collagen through the GPVI-FcRgamma complex (By similarity). Inhibits cell migration and cell scattering through interaction with FLNA; interfers with the interaction of FLNA with RALA (PubMed:16291724). Mediates bile acid transport activity in a phosphorylation dependent manner (By similarity). Negatively regulates osteoclastogenesis (By similarity). {ECO:0000250|UniProtKB:P16573, ECO:0000250|UniProtKB:P31809, ECO:0000269|PubMed:16291724, ECO:0000269|PubMed:18424730, ECO:0000269|PubMed:23696226, ECO:0000269|PubMed:25363763}.
|I-set|
|V-set|
|ig|
|insulin receptor internalization|
|granulocyte colony-stimulating factor signaling pathway|
|negative regulation of response to tumor cell|
|insulin catabolic process|
|regulation of cytotoxic T cell degranulation|
|negative regulation of natural killer cell mediated immune response to tumor cell|
|negative regulation of cytotoxic T cell degranulation|
|negative regulation of natural killer cell mediated cytotoxicity directed against tumor cell target|
|negative regulation of immune response to tumor cell|
|negative regulation of hepatocyte proliferation|
|regulation of homophilic cell adhesion|
|insulin metabolic process|
|negative regulation of T cell mediated cytotoxicity|
|common myeloid progenitor cell proliferation|
|negative regulation of granulocyte differentiation|
|regulation of blood vessel remodeling|
|regulation of natural killer cell mediated cytotoxicity directed against tumor cell target|
|regulation of natural killer cell mediated immune response to tumor cell|
|positive regulation of vasculogenesis|
|negative regulation of platelet aggregation|
|bile acid transmembrane transporter activity|
|negative regulation of vascular permeability|
|filamin binding|
|negative regulation of leukocyte degranulation|
|regulation of response to tumor cell|
|regulation of immune response to tumor cell|
|negative regulation of natural killer cell mediated cytotoxicity|
|regulation of vasculogenesis|
|regulation of hepatocyte proliferation|
|negative regulation of fatty acid biosynthetic process|
|negative regulation of natural killer cell mediated immunity|
|regulation of granulocyte differentiation|
|negative regulation of homotypic cell-cell adhesion|
|regulation of platelet aggregation|
|negative regulation of leukocyte mediated cytotoxicity|
|negative regulation of platelet activation|
|negative regulation of T cell mediated immunity|
|negative regulation of T cell receptor signaling pathway|
|negative regulation of cell killing|
|microvillus membrane|
|epiboly involved in wound healing|
|negative regulation of fatty acid metabolic process|
|negative regulation of regulated secretory pathway|
|regulation of homotypic cell-cell adhesion|
|wound healing, spreading of cells|
|protein tyrosine kinase binding|
|epiboly|
|negative regulation of antigen receptor-mediated signaling pathway|
|bile acid and bile salt transport|
|regulation of platelet activation|
|negative regulation of interleukin-1 production|
|regulation of endothelial cell differentiation|
|regulation of T cell mediated cytotoxicity|
|basal plasma membrane|
|negative regulation of exocytosis|
|negative regulation of animal organ morphogenesis|
|regulation of vascular permeability|
|negative regulation of lymphocyte mediated immunity|
|regulation of T cell receptor signaling pathway|
|negative regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains|
|transport vesicle membrane|
|regulation of natural killer cell mediated cytotoxicity|
|negative regulation of adaptive immune response|
|regulation of natural killer cell mediated immunity|
|regulation of fatty acid biosynthetic process|
|negative regulation of myeloid leukocyte differentiation|
|regulation of leukocyte degranulation|
|negative regulation of lipid biosynthetic process|
|negative regulation of leukocyte mediated immunity|
|morphogenesis of an epithelial sheet|
|negative regulation of blood coagulation|
|negative regulation of hemostasis|
|negative regulation of coagulation|
|negative regulation of innate immune response|
|lateral plasma membrane|
|receptor internalization|
|regulation of antigen receptor-mediated signaling pathway|
|adherens junction|
|regulation of sprouting angiogenesis|
|regulation of T cell mediated immunity|
|negative regulation of wound healing|
|regulation of tissue remodeling|
|tertiary granule membrane|
|negative regulation of myeloid cell differentiation|
|regulation of leukocyte mediated cytotoxicity|
|regulation of blood coagulation|
|regulation of hemostasis|
|regulation of coagulation|
|negative regulation of lipid metabolic process|
|regulation of epidermal growth factor receptor signaling pathway|
|protein phosphatase binding|
|negative regulation of response to wounding|
|regulation of fatty acid metabolic process|
|negative regulation of small molecule metabolic process|
|regulation of ERBB signaling pathway|
|specific granule membrane|
|negative regulation of response to biotic stimulus|
|kinase binding|
|integrin-mediated signaling pathway|
|regulation of interleukin-1 production|
|negative regulation of leukocyte differentiation|
|regulation of cell killing|
|receptor metabolic process|
|negative regulation of T cell activation|
|regulation of myeloid leukocyte differentiation|
|regulation of phosphatidylinositol 3-kinase signaling|
|negative regulation of immune effector process|
|negative regulation of leukocyte cell-cell adhesion|
|negative regulation of epithelial cell proliferation|
|T cell receptor complex|
|monocarboxylic acid transport|
|negative regulation of hemopoiesis|
|organic hydroxy compound transport|
|regulation of wound healing|
|regulation of epithelial cell differentiation|
|negative regulation of lymphocyte activation|
|regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains|
|negative regulation of immune response|
|regulation of lymphocyte mediated immunity|
|regulation of endothelial cell migration|
|protein dimerization activity|
|regulation of adaptive immune response|
|cellular response to insulin stimulus|
|regulation of regulated secretory pathway|
|regulation of response to wounding|
|homophilic cell adhesion via plasma membrane adhesion molecules|
|vascular process in circulatory system|
|cell-cell junction|
|regulation of cellular ketone metabolic process|
|negative regulation of cell-cell adhesion|
|negative regulation of leukocyte activation|
|positive regulation of vasculature development|
|regulation of lipid biosynthetic process|
|negative regulation of cell activation|
|calmodulin binding|
|negative regulation of secretion by cell|
|regulation of leukocyte mediated immunity|
|negative regulation of defense response|
|negative regulation of multi-organism process|
|regulation of epithelial cell migration|
|regulation of exocytosis|
|regulation of myeloid cell differentiation|
|negative regulation of protein kinase activity|
|response to insulin|
|negative regulation of secretion|
|receptor-mediated endocytosis|
|negative regulation of kinase activity|
|regulation of animal organ morphogenesis|
|cell-cell adhesion via plasma-membrane adhesion molecules|
|cellular response to peptide hormone stimulus|
|actin binding|
|negative regulation of cell adhesion|
|regulation of leukocyte differentiation|
|negative regulation of cytokine production|
|negative regulation of transferase activity|
|regulation of angiogenesis|
|organic acid transport|
|carboxylic acid transport|
|regulation of ERK1 and ERK2 cascade|
|regulation of leukocyte cell-cell adhesion|
|lipid transport|
|angiogenesis|
|regulation of T cell activation|
|apical plasma membrane|
|lipid localization|
|regulation of vasculature development|
|cellular response to peptide|
|regulation of epithelial cell proliferation|
|negative regulation of response to external stimulus|
|leukocyte migration|
|blood circulation|
|response to peptide hormone|
|circulatory system process|
|regulation of lipid metabolic process|
|regulation of cell-cell adhesion|
|negative regulation of protein phosphorylation|
|blood vessel morphogenesis|
|regulation of cell growth|
|regulation of small molecule metabolic process|
|morphogenesis of an epithelium|
|negative regulation of immune system process|
|negative regulation of phosphorylation|
|regulation of hemopoiesis|
|regulation of innate immune response|
|organic anion transport|
|regulation of immune effector process|
|response to peptide|
|wound healing|
|negative regulation of transport|
|blood vessel development|
|neutrophil degranulation|
|neutrophil activation involved in immune response|
|regulation of body fluid levels|
|neutrophil mediated immunity|
|neutrophil activation|
|granulocyte activation|
|cell-cell adhesion|
|vasculature development|
|leukocyte degranulation|
|regulation of lymphocyte activation|
|myeloid leukocyte mediated immunity|
|cardiovascular system development|
|myeloid cell activation involved in immune response|
|regulation of response to biotic stimulus|
|cell junction|
|regulation of vesicle-mediated transport|
|cell population proliferation|
|endocytosis|
|negative regulation of phosphate metabolic process|
|negative regulation of phosphorus metabolic process|
|tissue morphogenesis|
|response to wounding|
|anion transport|
|myeloid leukocyte activation|
|negative regulation of protein modification process|
|cellular response to organonitrogen compound|
|regulation of leukocyte activation|
|cellular response to hormone stimulus|
|cell surface|
|leukocyte activation involved in immune response|
|cell activation involved in immune response|
|regulation of cell activation|
|tube morphogenesis|
|cellular response to nitrogen compound|
|regulation of growth|
|cytokine-mediated signaling pathway|
|import into cell|
|negative regulation of cell population proliferation|
|regulation of cell adhesion|
|protein catabolic process|
|regulation of cytokine production|
|regulated exocytosis|
|negative regulation of cell differentiation|
|regulation of secretion by cell|
|regulation of MAPK cascade|
|molecular function|
|regulation of defense response|
|leukocyte mediated immunity|
|regulation of multi-organism process|
|negative regulation of catalytic activity|
|exocytosis|
|regulation of protein kinase activity|
|regulation of secretion|
|tube development|
|regulation of cell migration|
|circulatory system development|
|regulation of kinase activity|
|protein homodimerization activity|
|anatomical structure formation involved in morphogenesis|
|response to hormone|
|regulation of cell motility|
|leukocyte activation|
|cell adhesion|
|biological adhesion|
|negative regulation of developmental process|
|cell migration|
|positive regulation of cell differentiation|
|regulation of transferase activity|
|regulation of locomotion|
|regulation of cellular component movement|
|response to organonitrogen compound|
|secretion by cell|
|cellular response to cytokine stimulus|
|negative regulation of cellular protein metabolic process|
|export from cell|
|macromolecule catabolic process|
|cellular response to oxygen-containing compound|
|regulation of anatomical structure morphogenesis|
|organonitrogen compound catabolic process|
|identical protein binding|
|cell activation|
|cell motility|
|localization of cell|
|response to nitrogen compound|
|immune effector process|
|regulation of response to external stimulus|
|response to cytokine|
|negative regulation of protein metabolic process|
|epithelium development|
|secretion|
|negative regulation of molecular function|
|regulation of immune response|
|negative regulation of multicellular organismal process|
|cellular response to endogenous stimulus|
|negative regulation of signal transduction|
|locomotion|
|negative regulation of cell communication|
|negative regulation of signaling|
|positive regulation of developmental process|
|ion transport|
|integral component of plasma membrane|
|regulation of protein phosphorylation|
|response to endogenous stimulus|
|regulation of response to stress|
|negative regulation of cellular biosynthetic process|
|negative regulation of biosynthetic process|
|movement of cell or subcellular component|
|response to oxygen-containing compound|
|regulation of phosphorylation|
|regulation of cell population proliferation|
|negative regulation of response to stimulus|
|regulation of immune system process|
|positive regulation of multicellular organismal process|
|tissue development|
|organic substance catabolic process|
|regulation of phosphate metabolic process|
|regulation of phosphorus metabolic process|
|regulation of cell differentiation|
|regulation of intracellular signal transduction|
|regulation of protein modification process|
|regulation of transport|
|immune response|
|vesicle-mediated transport|
|system process|
|membrane|
\\
=== CRISPR Data ===
^Screen^Score^
|[[:results:exp114|A-196 10μM R03 exp114]]|1.88|
No correlation found to any other genes in chemogenomics.
Global Fraction of Cell Lines Where Essential: 0/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/26|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/16|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/16|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/9|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
== Essentiality in NALM6 ==
* **Essentiality Rank**: 13101
* **Expression level (log2 read counts)**: 2.39
{{:chemogenomics:nalm6 dist.png?nolink |}}