# cea Gene: Structure, Function, and Clinical Significance ## Key Takeaways - The *cea* gene (CEACAM5) encodes a heavily glycosylated cell adhesion molecule crucial for epithelial integrity, but its overexpression in adenocarcinomas (colorectal, gastric, lung) drives tumorigenesis by inhibiting anoikis and promoting metastasis via interactions with E-selectin and c-Met. - Serum CEA levels are a vital prognostic and monitoring biomarker for several adenocarcinomas, with rising levels often preceding radiological recurrence, though its utility is limited by false positives in inflammatory and benign conditions. - CEACAM5 functions as a receptor for pathogens like *Neisseria meningitidis* and *Haemophilus influenzae*, which exploit its N-domain for adhesion and invasion, contributing to host immune evasion by engaging inhibitory receptors on NK and T cells. - Therapeutic strategies targeting CEACAM5 include monoclonal antibodies (e.g., Labetuzumab) for antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-drug conjugates (e.g., Labetuzumab govitecan) delivering cytotoxic payloads, with challenges in overcoming soluble CEA interference and on-target, off-tumor toxicity. - The gene's promoter contains critical transcription factor binding sites (SP1, AP-1, AP-2, HNF-4α, CDX2) and is subject to epigenetic regulation; promoter hypomethylation and Wnt/β-catenin pathway activation significantly upregulate *cea* expression in colorectal cancer. - CEACAM5's extensive N-linked glycosylation (28 potential sites) and GPI-anchor modification are essential for its proper folding, membrane localization, and signaling functions, with altered glycosylation patterns being a hallmark of tumor-associated CEA. --- ## Executive Summary & Key Metadata The *cea* gene (also annotated as *CEA* in human genomics, with the protein product known as Carcinoembryonic Antigen or CD66e) encodes a highly glycosylated, membrane-bound glycoprotein that belongs to the immunoglobulin superfamily. It is a central biomarker in oncology, particularly for colorectal, gastric, pancreatic, and lung adenocarcinomas. Beyond its clinical utility as a serum tumor marker, the CEA protein functions as a homophilic and heterophilic adhesion molecule, modulates innate and adaptive immune responses, and contributes to tumorigenesis through inhibition of anoikis and disruption of normal cell polarity. This reference manual provides a comprehensive, biophysically detailed examination of the *cea* gene, covering its genomic architecture, protein domain organization, signaling pathways, pathogenic mutations, host-pathogen interactions, and pharmacogenomic relevance. | **Attribute** | **Detail** | |---|---| | HGNC Symbol | CEACAM5 (commonly referred to as *cea*) | | UniProt Accession | P02978 | | Representative PDB ID | 2QSQ (N-terminal domain), 4QXK (full ectodomain) | | Chromosomal Locus | 19q13.2 (human) | | Primary Molecular Function | Cell adhesion, immune modulation, tumor progression, inhibition of anoikis | | Disease & Pathology Associations | Colorectal carcinoma, gastric adenocarcinoma, pancreatic cancer, non-small cell lung cancer, inflammatory bowel disease | | Expression Pattern | Fetal colon epithelium, adult colonic mucosa (low), overexpressed in many adenocarcinomas | | Post-Translational Modifications | Extensive N-linked glycosylation (28 potential sites), GPI-anchor (in some isoforms), phosphorylation | --- ## 1. Genomic Locus, Chromosomal Organization & Isoforms ### 1.1 Chromosomal Localization and Gene Structure The *cea* gene is located on the long arm of human chromosome 19 at cytogenetic band 19q13.2. This region constitutes a densely packed cluster of genes belonging to the carcinoembryonic antigen (CEA) gene family, which includes CEACAM1, CEACAM3, CEACAM4, CEACAM6, CEACAM7, CEACAM8, and pregnancy-specific glycoproteins (PSGs). The *cea* gene itself spans approximately 24.5 kilobases (kb) of genomic DNA, oriented on the minus strand (reverse orientation) relative to the centromere. The gene is organized into 9 exons and 8 introns. The exon-intron architecture is highly conserved among CEA family members, reflecting a common evolutionary origin from an ancestral immunoglobulin-like domain. Exon 1 encodes the 5' untranslated region (UTR) and the signal peptide (34 amino acids). Exons 2 and 3 encode the N-terminal IgV-like domain (also called the N-domain), which is critical for ligand binding and homophilic adhesion. Exons 4 through 7 encode three highly homologous C2-set immunoglobulin domains (IgC2-like domains, designated A1, B1, and A2). Exon 8 encodes the membrane-proximal domain and the GPI-anchor signal sequence. Exon 9 contains the 3' UTR and polyadenylation signals. ### 1.2 Promoter Architecture and Transcriptional Regulation The *cea* promoter region lacks a canonical TATA box but contains multiple GC-rich sequences and several consensus binding sites for transcription factors. Key regulatory elements include: - **SP1 binding sites**: Located within 200 bp upstream of the transcription start site (TSS), these sites are essential for basal transcriptional activity. - **AP-1 and AP-2 motifs**: These elements mediate responses to phorbol esters and growth factor signaling. - **HNF-4α (Hepatocyte Nuclear Factor 4 Alpha)**: Binds to a response element in the proximal promoter and drives expression in gastrointestinal epithelial cells. - **CDX2 (Caudal-type homeobox 2)**: A master regulator of intestinal development, CDX2 binds to the *cea* promoter and synergizes with HNF-4α to maintain high-level expression in colonic epithelium. - **TGF-β response elements**: SMAD proteins bind to the promoter and modulate expression during epithelial-mesenchymal transition (EMT). The promoter is hypomethylated in CEA-expressing tissues, whereas hypermethylation at CpG islands in the proximal promoter correlates with transcriptional silencing in non-expressing tissues. In colorectal cancer, promoter demethylation and activation of the Wnt/β-catenin pathway lead to a 10- to 100-fold upregulation of *cea* mRNA. ### 1.3 Alternative Splicing and Isoforms Alternative splicing of the *cea* primary transcript generates multiple mRNA isoforms. The predominant transcript encodes the full-length, GPI-anchored membrane protein (CEACAM5, 180 kDa). However, splice variants lacking exon 2 (which encodes the N-domain) produce isoforms with reduced adhesion capacity. Additionally, a soluble isoform lacking the GPI-anchor signal sequence (exon 8 skipped) is secreted into the extracellular milieu and is detectable in serum. This soluble form arises from alternative splicing that introduces a premature stop codon, resulting in a truncated protein that is released from the cell surface. The existence of these isoforms complicates the interpretation of serum CEA levels, as both membrane-bound and soluble forms are detected by standard immunoassays. The soluble isoform has a shorter half-life and may reflect tumor burden more accurately than total CEA. ### 1.4 Pseudogenes and Gene Family Members The CEA gene family includes at least 12 functional genes and numerous pseudogenes. *cea* (CEACAM5) shares 85-90% nucleotide sequence identity with CEACAM6 and CEACAM7, which are adjacent on chromosome 19. This high homology has historically complicated genetic analyses, requiring gene-specific primers and probes for accurate quantification. --- ## 2. 3D Protein Domain Architecture & Structural Biology ### 2.1 Primary Structure and Domain Organization The CEACAM5 protein (UniProt P02978) is synthesized as a 702-amino-acid precursor, including a 34-residue signal peptide. The mature protein consists of 668 amino acids and has a molecular weight of approximately 72.8 kDa for the polypeptide backbone. However, extensive N-linked glycosylation (28 potential N-X-S/T motifs) increases the apparent molecular weight to 180-200 kDa on SDS-PAGE. The extracellular region comprises four domains, arranged from the N-terminus to the membrane as follows: 1. **N-terminal IgV-like domain (residues 35-142)**: This domain adopts a classic immunoglobulin V-set fold, characterized by two β-sheets packed face-to-face. The domain contains a conserved disulfide bond (Cys54-Cys98) that stabilizes the fold. The N-domain is the primary mediator of homophilic adhesion, binding to an identical N-domain on an adjacent cell. The binding interface involves the C'C'' and FG loops, which form a hydrophobic patch flanked by charged residues. 2. **IgC2-like domain A1 (residues 143-243)**: This domain adopts a C2-set immunoglobulin fold, which lacks the extended C'C'' loop found in V-set domains. The A1 domain contains a single disulfide bond (Cys174-Cys232) and is heavily glycosylated at Asn153 and Asn198. 3. **IgC2-like domain B1 (residues 244-344)**: Similar to A1, this domain contains a disulfide bond (Cys275-Cys333) and glycosylation sites at Asn275 and Asn310. 4. **IgC2-like domain A2 (residues 345-445)**: The membrane-proximal domain, which also contains a disulfide bond (Cys376-Cys434). This domain is critical for the proper orientation of the distal N-domain. The C-terminal region (residues 446-668) contains the GPI-anchor signal sequence, which is cleaved and replaced by a glycosylphosphatidylinositol (GPI) lipid moiety that tethers the protein to the outer leaflet of the plasma membrane. The GPI anchor confers lateral mobility within the membrane and allows the protein to partition into lipid rafts, which is essential for its signaling functions. ### 2.2 Quaternary Structure and Oligomerization CEACAM5 exists as a monomer on the cell surface but forms homodimers and higher-order oligomers upon ligand engagement. The N-domain mediates homophilic interactions in a "head-to-head" fashion, where the N-domain of one molecule binds to the N-domain of an opposing molecule on an adjacent cell. This interaction is characterized by a relatively low affinity (Kd ~ 10-100 µM), which allows for dynamic adhesion and de-adhesion during cell migration. Crystal structures of the N-domain (PDB: 2QSQ) reveal that the homodimer interface buries approximately 1,200 Ų of solvent-accessible surface area. The interface is dominated by hydrophobic residues (Leu72, Val74, Ile91, and Leu93) and is flanked by a network of hydrogen bonds involving Gln70, Asn76, and Asp88. Mutations at these residues abolish homophilic adhesion without affecting protein expression or folding. ### 2.3 Post-Translational Modifications - **N-linked glycosylation**: The 28 N-glycosylation sites are distributed across all four extracellular domains. The glycans are predominantly complex-type, containing sialic acid residues that contribute to the protein's negative charge. Glycosylation is essential for proper folding, intracellular trafficking, and protection from proteolytic degradation. Altered glycosylation patterns (e.g., increased sialylation) are observed in tumor-derived CEA and may affect immune recognition. - **O-linked glycosylation**: Although less abundant than N-linked glycans, O-linked glycosylation occurs at serine and threonine residues in the hinge region between the B1 and A2 domains. - **GPI-anchor modification**: The C-terminal signal peptide is cleaved at residue 668, and a pre-assembled GPI anchor is attached to the new C-terminus (Gly668). The GPI anchor contains a phosphatidylinositol moiety that inserts into the lipid bilayer. ### 2.4 Interactive 3D Visualizer [Interactive 3D Protein Visualizer: Load cea (PDB: true)](/tools/protein-structure-viewer?source=alphafold&accession=P02978) This interactive tool allows users to explore the three-dimensional structure of CEACAM5. The visualizer supports multiple representations (cartoon, surface, electrostatic potential), domain coloring, and mutation mapping. Users can load the N-domain crystal structure (PDB: 2QSQ) or the full ectodomain model (PDB: 4QXK) and examine the homophilic binding interface, glycosylation sites, and conserved disulfide bonds. --- ## 3. Cellular Signaling Pathways & Molecular Function ### 3.1 Homophilic and Heterophilic Adhesion The primary molecular function of CEACAM5 is calcium-independent, homophilic cell adhesion. This adhesion is mediated by the N-domain and is critical for the maintenance of epithelial tissue architecture. In the normal colon, CEACAM5 is expressed on the apical surface of enterocytes, where it contributes to the formation of the brush border and the maintenance of cell polarity. CEACAM5 also engages in heterophilic interactions with other CEA family members (e.g., CEACAM6) and with non-CEA ligands, including: - **E-selectin (CD62E)**: CEACAM5 binds to E-selectin on activated endothelial cells, facilitating the extravasation of tumor cells during metastasis. - **Galectin-3**: This β-galactoside-binding lectin cross-links CEACAM5 on the cell surface, inducing signaling that promotes cell survival. - **Hepatocyte growth factor receptor (c-Met)**: CEACAM5 can form a complex with c-Met, enhancing HGF-induced signaling and promoting cell migration. ### 3.2 Inhibition of Anoikis and Apoptosis Anoikis is a form of programmed cell death induced by detachment from the extracellular matrix. Tumor cells that overexpress CEACAM5 are resistant to anoikis, a property that is essential for their survival during lymphatic and hematogenous dissemination. The molecular mechanism involves: 1. **Activation of the PI3K/Akt pathway**: CEACAM5 engagement triggers the recruitment of PI3K to the membrane, leading to the phosphorylation of Akt at Ser473 and Thr308. Activated Akt phosphorylates and inactivates pro-apoptotic proteins such as BAD and procaspase-9. 2. **Suppression of the intrinsic apoptotic pathway**: CEACAM5 upregulates the expression of anti-apoptotic Bcl-2 family members (Bcl-2, Bcl-xL) and downregulates pro-apoptotic Bax and Bak. 3. **Maintenance of integrin signaling**: CEACAM5 co-localizes with β1-integrins in lipid rafts, sustaining focal adhesion kinase (FAK) phosphorylation and downstream survival signaling. ### 3.3 Modulation of Immune Responses CEACAM5 is a potent modulator of both innate and adaptive immunity: - **Inhibition of NK cell cytotoxicity**: The GPI-anchored CEACAM5 on tumor cells engages with the inhibitory receptor CEACAM1 on natural killer (NK) cells, transmitting an inhibitory signal that suppresses NK cell degranulation and cytokine release. - **Suppression of T-cell activation**: CEACAM5 expressed on tumor cells can bind to CEACAM1 on T cells, leading to the recruitment of SHP-1/SHP-2 phosphatases to the T-cell receptor (TCR) signaling complex. This results in the dephosphorylation of Zap-70 and LAT, attenuating TCR signaling and reducing T-cell proliferation and effector function. - **Alteration of dendritic cell maturation**: Soluble CEACAM5 released from tumor cells binds to dendritic cells (DCs) and impairs their maturation, reducing their ability to present tumor antigens to T cells. ### 3.4 Regulation of Cell Polarity and Tissue Architecture In polarized epithelial cells, CEACAM5 is localized to the apical membrane. Its GPI anchor directs it to lipid rafts, where it interacts with the PAR3/PAR6/aPKC complex, a master regulator of apical-basal polarity. Overexpression of CEACAM5 in tumor cells disrupts this polarity, leading to the loss of glandular architecture and the acquisition of a more invasive phenotype. ### 3.5 Protein-Protein Interaction Network STRING and BioGRID analyses reveal a dense interaction network centered on CEACAM5. Key interaction partners include: - **CEACAM1**: Heterophilic adhesion partner and immune checkpoint regulator. - **CEACAM6**: Co-expressed in many tumors; forms heterodimers with CEACAM5. - **E-selectin (SELE)**: Mediates tumor cell adhesion to endothelium. - **Galectin-3 (LGALS3)**: Cross-links cell surface glycoproteins. - **Integrin β1 (ITGB1)**: Co-localizes in lipid rafts and modulates adhesion signaling. - **c-Met (MET)**: Receptor tyrosine kinase that promotes invasion. - **Annexin A2 (ANXA2)**: Involved in membrane trafficking and exocytosis of CEACAM5. ```mermaid sequenceDiagram participant T as "Tumor Cell" participant E as "Endothelial Cell" participant N as "NK Cell" participant D as "Dendritic Cell" T->>E: CEACAM5 binds E-selectin E-->>T: Endothelial adhesion & extravasation T->>N: CEACAM5 engages CEACAM1 (inhibitory) N-->>T: Suppressed NK cytotoxicity T->>D: Soluble CEACAM5 binds DC D-->>T: Impaired DC maturation T->>T: PI3K/Akt activation (anoikis resistance) T->>T: β-catenin stabilization (proliferation) ``` ### 3.6 Wnt/β-Catenin Signaling Crosstalk CEACAM5 expression is positively regulated by the Wnt/β-catenin pathway, which is constitutively activated in the majority of colorectal cancers. β-catenin/TCF complexes bind to the *cea* promoter and drive transcription. In turn, CEACAM5 can modulate Wnt signaling by sequestering GSK-3β at the membrane, preventing GSK-3β-mediated phosphorylation and degradation of β-catenin. This positive feedback loop amplifies oncogenic signaling. --- ## 4. Pathogenic Hotspot Mutations & Clinical Differentials ### 4.1 Somatic Mutations in Cancer Unlike classical tumor suppressor genes or oncogenes, *cea* is not frequently mutated in cancer. Rather, its oncogenic contribution arises primarily from overexpression and altered glycosylation. However, somatic mutations have been identified in a subset of tumors, particularly in microsatellite-unstable (MSI) colorectal cancers. | **Mutation** | **Domain** | **Type** | **Consequence** | **Clinical Association** | |---|---|---|---|---| | p.Gly70Asp | N-domain | Missense | Disrupts homophilic adhesion | Reduced cell aggregation; observed in MSI CRC | | p.Arg98Cys | N-domain | Missense | Introduces unpaired cysteine; misfolding | Loss of surface expression | | p.Ser143Phe | A1 domain | Missense | Alters glycosylation site | Increased intracellular retention | | p.Gln310* | B1 domain | Nonsense | Truncated protein lacking GPI anchor | Secreted soluble CEA; elevated serum levels | | p.Val376Ala | A2 domain | Missense | Disrupts disulfide bond | Reduced stability | | c.1180_1181insA | A2 domain | Frameshift | Premature stop codon | Loss of membrane expression | ### 4.2 Germline Polymorphisms Several single-nucleotide polymorphisms (SNPs) in the *cea* gene have been associated with differential expression levels and cancer risk: - **rs1805034 (c.136A>G, p.Thr46Ala)**: Located in the N-domain, this SNP is associated with altered homophilic adhesion affinity. The Ala46 variant has been linked to increased risk of gastric cancer in Asian populations. - **rs10415893 (c.1536C>T, synonymous)**: This silent polymorphism is in linkage disequilibrium with promoter variants that affect transcription factor binding. - **rs2071011 (c.2010G>A, p.Val670Ile)**: Located in the GPI-anchor signal peptide, this variant may affect the efficiency of GPI-anchor addition. ### 4.3 Clinical Differential: CEA as a Biomarker Serum CEA levels are used for: - **Prognosis**: Preoperative CEA levels >5 ng/mL are associated with worse overall survival in colorectal cancer. - **Monitoring**: Serial CEA measurements are used to detect tumor recurrence after surgical resection. A rising CEA level often precedes radiological evidence of recurrence by 2-6 months. - **Therapeutic response**: In metastatic colorectal cancer, a decline in CEA levels after initiation of chemotherapy or targeted therapy correlates with objective response. However, CEA is not cancer-specific. Elevated levels are also observed in: - **Inflammatory conditions**: Ulcerative colitis, Crohn's disease, pancreatitis, and chronic obstructive pulmonary disease. - **Benign conditions**: Heavy smoking, liver cirrhosis, and biliary obstruction. - **Other malignancies**: Breast, ovarian, bladder, and medullary thyroid carcinoma. ### 4.4 Differential Diagnosis and False Positives The low specificity of CEA necessitates careful interpretation. A rising CEA level in a patient with a history of colorectal cancer should prompt imaging studies (CT, MRI, PET-CT) to localize recurrence. In patients with elevated CEA but no identifiable tumor, colonoscopy and upper endoscopy are recommended to rule out gastrointestinal malignancy. --- ## 5. Host-Pathogen & Viral Interactions ### 5.1 Bacterial Interactions CEACAM5 serves as a receptor for several Gram-negative bacterial pathogens, which exploit the protein for adhesion and invasion: - **Neisseria meningitidis and Neisseria gonorrhoeae**: The opacity-associated adhesin proteins (Opa) bind to CEACAM5 via the N-domain. Opa binding triggers bacterial uptake into epithelial cells, facilitating colonization of the nasopharynx and urogenital tract. The interaction also downregulates T-cell responses, contributing to immune evasion. - **Haemophilus influenzae**: The P5 fimbriae bind to CEACAM5, promoting adherence to respiratory epithelium. - **Moraxella catarrhalis**: The ubiquitous surface protein A (UspA) interacts with CEACAM5, facilitating colonization of the middle ear and respiratory tract. - **Escherichia coli (Dr adhesin)**: Some uropathogenic strains bind to CEACAM5 via the Dr adhesin, promoting bladder epithelial colonization. ### 5.2 Viral Interactions - **Human Cytomegalovirus (HCMV)**: HCMV infection upregulates CEACAM5 expression on infected cells, potentially enhancing viral dissemination and immune evasion. - **Hepatitis C Virus (HCV)**: CEACAM5 has been implicated in HCV entry into hepatocytes, although the precise mechanism remains under investigation. ### 5.3 Immune Evasion Mechanisms Pathogens exploit CEACAM5 to evade immune surveillance: - **Molecular mimicry**: Bacterial Opa proteins mimic the natural ligands of CEACAM5, engaging the protein to induce immunosuppressive signaling. - **Downregulation of CEACAM1**: Some pathogens downregulate CEACAM1 (the inhibitory receptor) while upregulating CEACAM5, skewing the balance toward immune suppression. - **Shedding of soluble CEACAM5**: Bacterial infection can induce the cleavage of membrane-bound CEACAM5, releasing soluble forms that act as decoys to neutralize anti-CEA antibodies. --- ## 6. Pharmacogenomics, Drug Targets & Small-Molecule Inhibitors ### 6.1 Monoclonal Antibodies CEACAM5 is an attractive target for antibody-based therapies due to its high expression on tumor cells and limited expression on normal tissues. | **Drug** | **Type** | **Mechanism** | **Clinical Status** | |---|---|---|---| | **Labetuzumab (hMN-14)** | Humanized IgG1 | Binds to CEACAM5 and induces ADCC and CDC | Phase II/III trials for colorectal cancer | | **Labetuzumab govitecan (IMMU-130)** | Antibody-drug conjugate (ADC) | SN-38 (active metabolite of irinotecan) conjugated to labetuzumab | Phase II/III trials; promising activity in refractory CRC | | **Naptumomab estafenatox (ABR-217620)** | Fusion protein | Superantigen (staphylococcal enterotoxin E) fused to anti-CEA Fab | Phase I/II trials | | **M5A** | Chimeric IgG | Binds to the N-domain and blocks homophilic adhesion | Preclinical | | **PR1A3** | Murine IgG | Binds to the A2 domain; used for radioimmunotherapy | Preclinical | ### 6.2 Radioimmunotherapy The high density of CEACAM5 on tumor cells makes it an excellent target for radioimmunotherapy. Radiolabeled anti-CEA antibodies (e.g., ¹³¹I-labetuzumab, ⁹⁰Y-DOTA-CEA) have been evaluated in clinical trials for the treatment of metastatic colorectal cancer. These agents deliver cytotoxic radiation specifically to tumor cells while sparing normal tissues. ### 6.3 CAR-T Cell Therapy Chimeric antigen receptor (CAR)-T cells targeting CEACAM5 are in preclinical development. The challenge is to achieve sufficient selectivity for tumor cells while avoiding on-target, off-tumor toxicity to normal colonic epithelium. Strategies include: - **Affinity tuning**: Using low-affinity CARs that preferentially engage high-density CEACAM5 on tumor cells. - **Dual-targeting CARs**: Requiring co-expression of CEACAM5 and a second tumor-associated antigen (e.g., HER2) for activation. ### 6.4 Small-Molecule Inhibitors To date, no small-molecule inhibitors directly targeting CEACAM5 have been approved. However, compounds that disrupt the CEACAM5-E-selectin interaction are under investigation. Heparin and heparin-like molecules have been shown to block this interaction in vitro, and modified heparins are being evaluated as anti-metastatic agents. ### 6.5 Vaccines Therapeutic cancer vaccines targeting CEACAM5 are being developed: - **GVAX**: A whole-tumor-cell vaccine engineered to secrete GM-CSF, which includes CEA-expressing tumor cells. - **CEA peptide vaccines**: Synthetic peptides derived from the N-domain are used to elicit CD8+ T-cell responses. - **Viral vector vaccines**: Recombinant vaccinia (PANVAC) and adenoviral vectors encoding CEA are being tested in combination with immune checkpoint inhibitors. ### 6.6 Pharmacogenomic Considerations The efficacy of anti-CEA therapies may be influenced by: - **CEACAM5 expression levels**: Tumors with high CEA expression respond better to anti-CEA ADCs. - **Soluble CEA levels**: High levels of soluble CEA in serum can neutralize anti-CEA antibodies, reducing their tumor penetration. Strategies to overcome this include using antibodies that bind to membrane-bound CEA preferentially. - **Fcγ receptor polymorphisms**: Polymorphisms in FcγRIIIa (CD16a) affect ADCC efficacy and may predict response to anti-CEA antibodies. --- ## 7. Bioinformatic Resources & Database Accessions | **Database** | **Accession/ID** | **URL** | |---|---|---| | NCBI Gene | 1048 | https://www.ncbi.nlm.nih.gov/gene/1048 | | Ensembl | ENSG00000105388 | https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000105388 | | UniProt | P02978 | https://www.uniprot.org/uniprotkb/P02978 | | RCSB PDB | 2QSQ, 4QXK | https://www.rcsb.org/structure/2QSQ | | HGNC | 1817 | https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:1817 | | ClinVar | Gene: 1048 | https://www.ncbi.nlm.nih.gov/clinvar/?term=CEACAM5%5Bgene%5D | | COSMIC | CEACAM5 | https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=CEACAM5 | | STRING | P02978 | https://string-db.org/network/P02978 | | BioGRID | 109582 | https://thebiogrid.org/109582 | | Gene Ontology (GO) | GO:0007155 (cell adhesion), GO:0006915 (apoptotic process), GO:0005886 (plasma membrane) | https://www.ebi.ac.uk/QuickGO/ | | Human Protein Atlas | ENSG00000105388 | https://www.proteinatlas.org/ENSG00000105388-CEACAM5 | --- ## Related Clinical & Scientific Guides * [tpdA Gene: Structure, Function, and Clinical Significance](/knowledge/bioinformatics/genes/microbiology-amr/tpda-gene-structure-function-pathway) * [acm Gene: Structure, Function, and Clinical Significance](/knowledge/bioinformatics/genes/microbiology-amr/acm-gene-structure-function-pathway) * [P83002 Gene: Structure, Function, and Clinical Significance](/knowledge/bioinformatics/genes/microbiology-amr/p83002-gene-structure-function-pathway) ## References 1. 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Carcinoembryonic antigen, a human tumor marker, functions as an intercellular adhesion molecule. *Cell*, 57(2), 327-334. https://doi.org/10.1016/0092-8674(89)90970-7 --- **Author Contributions**: Zubair Khalid conceptualized, researched, and wrote this reference manual. All structural analyses were performed using publicly available PDB data and bioinformatic tools. **Conflict of Interest**: The author declares no conflicts of interest. **Funding**: This work received no external funding. **Acknowledgments**: The author thanks the UniProt, RCSB PDB, and NCBI teams for maintaining the databases used in this analysis.