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FLASH GENE

Symbol

CEACAM1

contributors: mct/npt/pgu - updated : 09-11-2015

HGNC name	carcinoembryonic antigen-related cell adhesion molecule 1 (biliary glycoprotein)
HGNC id	1814

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular vessels         Digestive choledoque           intestine large intestine colon   highly   intestine small intestine     highly Endocrine parathyroid       highly Reproductive male system male genital tract epididymis     Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial absorptive excretory digestive epithelium     Epithelial barrier/lining uroepithelium     Epithelial secretory glandular exocrine

cells

System Cell Pubmed Species Stage Rna symbol Digestive epithelial cell Reproductive epididymal cell Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	N-terminal GXXXG dimerization sequences and IgV-like domain followed by up to three IgC-like domains
	four Ig extracellular domains
	a long cytoplasmic tail (71 AAs) with immunoreceptor tyrosine based inhibitory motifs (ITIM), having a functional role in regulation of beta-catenin activity , but does not play a significant role in promoting CEACAM1 dimerization
	a transmembrane domain responsible for the CDC42-induced targeting at cell-cell contacts, and might be a driving force for the establishment of the basal state dimers
	C-terminal tyrosine residues shown in related studies to stabilize transmembrane domain helix-helix interactions

conjugated

GlycoP

HOMOLOGY

interspecies

homolog to murine Ceacam1

intraspecies

homolog to carcinoembryonic antigen

Homologene

FAMILY	immunoglobulin superfamily
	CEA subfamily

CATEGORY

adhesion , antigen

SUBCELLULAR LOCALIZATION

plasma membrane

basic FUNCTION	regulating insulin clearance in the liver
	suppressor of tumor by inhibiting tumor angiogenesis
	playing an important role in epithelial cell signaling and functions
	mediates homophilic intercellular interactions that influence cellular growth, immune cell activation, and tissue morphogenesis
	confers a phosphatidylinositol 3-kinase- and Akt-dependent survival signal that inhibits mitochondrion-dependent apoptosis of monocytes
	functions as a key regulator of contact-dependent control of cell survival, differentiation, and growth
	unique mediator that restricts tumor growth whereas increasing metastatic potential
	altered splicing of CEACAM1 may play an important role in tumorogenesis
	is capable of binding to itself in a trans-homophilic manner and has been demonstrated to mediate aggregation of a variety of cell types
	immunoglobulin-like cell surface co-receptor expressed on epithelial, hematopoietic and endothelial cells
	PECAM1 and CEACAM1 play essential roles in vascular sprouting
	creates a pro-angiogenic tumor microenvironment that supports tumor vessel maturation
	coexpression of CEACAM1 and TGFB increased from nonneoplastic to neoplastic lesions and may be related with tumor progression via promoting tumorous angiogenesis
	role as an important regulator of key processes in cutaneous wound healing
	participates in pivotal cellular and immunological processes and is involved in cancer
	multifunctional Ig-like cell adhesion molecule expressed by epithelial cells in many organs
	functions as an adhesion inhibitor and a migration promoter, and an inhibitor of cell-matrix adhesion
	inhibit cell-matrix adhesion and promote cell motility and CDH2 is a crucial protein involved in the processes
	might play a part in the EMT process of tumor cells

CELLULAR PROCESS

cell organization/biogenesis

PHYSIOLOGICAL PROCESS

text	angiogenesis

PATHWAY

metabolism

signaling

a component

exists as an equilibrium of cis-monomers and cis-homodimers on the surface of human epithelium-derived cells

INTERACTION

DNA

RNA

small molecule

protein	IFNG has two important effects on the expression levels of the CEA family molecules in colon epithelial cells: direct upregulation of CEACAM1 and promotion of cell differentiation resulting in increased expression of CEA and CEACAM6 and decreased expression of CEACAM7
	first direct target of SOX9 identified in the colon epithelium (SOX9 upregulates CEACAM1 in colonic cells)
	functional link between CEACAM1 and the KDR/AKT1/eNOS-mediated vascular permeability pathway
	interaction of actin with CEACAM1 receptor in liposomes is Ca2+- and phospholipid-dependent
	CEACAM1 serves as a heterophilic ligand for HAVCR2 that is required for its ability to mediate T-cell inhibition, and this interaction has a crucial role in regulating autoimmunity and anti-tumour immunity

cell & other

REGULATION

activated by	CD98 independently of integrins
	SOX9 (transcriptional activation of the CEACAM1)

Other	increased by VEGF and stimulating microvascular angiogenesis
	regulated by androgen (may be one of the mechanisms by which androgen regulates prostatic function)

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --low   in colorectal carcinoma tumoral     --over   in some tumors such as non-small cell lung cancer tumoral   LOH     in prostate carcinoma constitutional     --over   associated to prolonged survival and increased tube formation when they were stimulated with vascular endothelial growth factor (VEGF) tumoral     --over   on tumors correlates with poor prognosis and high risk of metastasis tumoral     --over   in lung cancer and malignant melanoma

Susceptibility

to risk of infection by the receptor-targeting pathogens

Variant & Polymorphism other	distinct polymorphisms have the potential to decrease or increase the risk of infection by the receptor-targeting pathogens

Candidate gene
Marker	melanoma biomarker
	potential marker of metastatic carcinoma and advanced carcinoma, and may contribute to tumor cell EMT
Therapy target
	System Type Disorder Pubmed cancer skin   in malignant melanoma cancer     targeting the endothelial up-regulation of CEACAM1 might be promising for antiangiogenic tumor therapy

ANIMAL & CELL MODELS

Ceacam1-/- mice exhibit a significant increase in basal vascular permeability related to increased basal Akt and endothelial nitric oxide synthase (eNOS) activation in primary murine lung endothelial cells