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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
DNA
TYPE functioning gene
SPECIAL FEATURE component of a cluster
STRUCTURE 21.20 kb     9 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Promoter
Binding site
text structure SOX9-binding sequences in the human CEACAM1 promoter
MAPPING cloned Y linked N status confirmed
Map see CEA@
RNA
TRANSCRIPTS type messenger
text
  • two regulatory cis-acting elements required for the alternative splicing of CEACAM1 (PMID: 18507857)
  • 7 CEACAM1a splice variants expressed by the small intestinal epithelium (PMID: 19358828)
    • identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    9 splicing 3528 54 526 - 2011 21413011
  • CEACAM1-L , CEACAM1-4L
  • having three IgC-like domains (A1-B-A2) and a 76-amino acid cytoplasmic domain
  • dramatic differences between the ratios of S:L isoforms in normal breast tissues versus breast cancer
  • two immunoreceptor-tyrosine based inhibitory motifs (ITIMs) in the long cytoplasmic domain that generally transmit inhibitory signals
  • promoted invasion and migration
  • CEACAM1-L dominance is associated with metastasis and shorter survival of the patients with colorectal cancer
    • 8 splicing 3475 47 464 - 2011 21669871
  • CEACAM1-S lacking exon 7, CEACAM1-4S
  • has a 10-amino acid cytoplasmic domain
  • dramatic differences between the ratios of S:L isoforms in normal breast tissues versus breast cancer
  • lacks ITIM sequences in the short cytoplasmic domain but can send signals to trigger actin cytoskeleton reorganization
  • cytoplasmic domain short isoform
  • sufficient to induce lumen formation when expressed in the breast cancer cell line
  • can recruit cytosolic proteins in a phospholipid- and calcium-specific manner
  • transmembrane domain is an important determinant of CEACAM1-4S functionality
  • CAMK2D was able to phosphorylate a synthetic peptide corresponding to the cytoplasmic domain of CEACAM1-S
    • - - - - - - 2009 19358828
    - - - - - - 2009 19358828
    - - - - - - 2009 19358828
    major secreted isoform due to the soluble/secreted CEACAM1a with a frameshift sequence in the C-terminus
    7 - 3187 - 368 - 2009 19358828
    8 - 3240 - 430 - 2009 19358828
    9 - 3333 - 461 - 2009 19358828
    8 - 3470 - 468 - 2009 19358828
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularvessels    
    Digestivecholedoque    
     intestinelarge intestinecolon highly
     intestinesmall intestine  highly
    Endocrineparathyroid   highly
    Reproductivemale systemmale genital tractepididymis   Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialabsorptive excretorydigestive epithelium  
    Epithelialbarrier/lininguroepithelium  
    Epithelialsecretoryglandularexocrine 
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Digestiveepithelial cell
    Reproductiveepididymal 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)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein 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
    SystemTypeDisorderPubmed
    cancerskin 
    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