CEACAM1

Summary

CEACAM1 (CEA cell adhesion molecule 1, HGNC:1814) is a protein-coding gene on chromosome 19q13.2, encoding Cell adhesion molecule CEACAM1 (P13688). Cell adhesion protein that mediates homophilic cell adhesion in a calcium-independent manner.

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.

Source: NCBI Gene 634 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 54 total
• MANE Select transcript: NM_001712

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1814
Approved symbol	CEACAM1
Name	CEA cell adhesion molecule 1
Location	19q13.2
Locus type	gene with protein product
Status	Approved
Aliases	BGP1, CD66a
Ensembl gene	ENSG00000079385
Ensembl biotype	protein_coding
OMIM	109770
Entrez	634

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 13 protein_coding, 5 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000161559, ENST00000344391, ENST00000352591, ENST00000358394, ENST00000377806, ENST00000403136, ENST00000403444, ENST00000403461, ENST00000465051, ENST00000471298, ENST00000485605, ENST00000488639, ENST00000599389, ENST00000600172, ENST00000676851, ENST00000867317, ENST00000867318, ENST00000867319, ENST00000926894

RefSeq mRNA: 6 — MANE Select: NM_001712 NM_001024912, NM_001184813, NM_001184815, NM_001184816, NM_001205344, NM_001712

CCDS: CCDS12609, CCDS46089, CCDS54272, CCDS54273, CCDS54274

Canonical transcript exons

ENST00000161559 — 9 exons

Exon	Start	End
ENSE00000709025	42518948	42519235
ENSE00002485635	42507306	42509228
ENSE00003483283	42512350	42512479
ENSE00003515306	42527041	42527400
ENSE00003564498	42521924	42522202
ENSE00003580694	42511576	42511628
ENSE00003582496	42510889	42510920
ENSE00003586678	42521267	42521521
ENSE00003658731	42528311	42528481

Expression profiles

Bgee: expression breadth ubiquitous, 222 present calls, max score 99.47.

FANTOM5 (CAGE): breadth broad, TPM avg 7.4439 / max 1077.2409, expressed in 587 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
181201	7.4439	587

Top tissues by expression

289 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
ileal mucosa	UBERON:0000331	99.47	gold quality
mucosa of transverse colon	UBERON:0004991	99.34	gold quality
colonic mucosa	UBERON:0000317	99.31	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.19	gold quality
rectum	UBERON:0001052	98.67	gold quality
metanephros cortex	UBERON:0010533	98.10	gold quality
minor salivary gland	UBERON:0001830	96.93	gold quality
lower esophagus mucosa	UBERON:0035834	96.66	gold quality
esophagus mucosa	UBERON:0002469	96.12	gold quality
saliva-secreting gland	UBERON:0001044	96.11	gold quality
jejunal mucosa	UBERON:0000399	95.81	gold quality
mouth mucosa	UBERON:0003729	95.33	gold quality
esophagus squamous epithelium	UBERON:0006920	95.09	gold quality
epithelium of esophagus	UBERON:0001976	94.52	gold quality
duodenum	UBERON:0002114	94.33	gold quality
bone marrow	UBERON:0002371	94.04	gold quality
bone marrow cell	CL:0002092	94.02	gold quality
vermiform appendix	UBERON:0001154	93.79	gold quality
transverse colon	UBERON:0001157	93.39	gold quality
oral cavity	UBERON:0000167	93.24	gold quality
parotid gland	UBERON:0001831	93.17	gold quality
right lobe of liver	UBERON:0001114	92.86	gold quality
trabecular bone tissue	UBERON:0002483	92.73	gold quality
right adrenal gland	UBERON:0001233	92.50	gold quality
pharyngeal mucosa	UBERON:0000355	92.34	gold quality
right adrenal gland cortex	UBERON:0035827	91.99	gold quality
squamous epithelium	UBERON:0006914	91.71	gold quality
cervix squamous epithelium	UBERON:0006922	91.52	silver quality
adult mammalian kidney	UBERON:0000082	91.36	gold quality
liver	UBERON:0002107	91.20	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-9801	yes	1887.99
E-GEOD-125970	yes	23.46
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, CTNNB1, EBF1, HNF4A, IRF1, IRF2, NFKB1, RELA, SOX9, SP1, SP2, TXK, USF1, USF2

miRNA regulators (miRDB)

77 targeting CEACAM1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-5682	99.89	72.56	1005
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-3919	99.87	69.45	2489

Literature-anchored findings (GeneRIF, showing 40)

• The expression ratio of the long-form and the short-form generated from CEACAM1 (C-CAM1) mRNA by alternative splicing differs significantly in primary NSCLC tissues. (PMID:10955775)
• ability of N. gonorrhoeae to up-regulate its epithelial receptor CEACAM1 through NF-kappaB suggests an important mechanism allowing efficient bacterial colonization during the initial infection process. (PMID:11751883)
• The expression of CD66a observed on NK cells from patients with malignant melanoma suggest the existence of a class I MHC-independent inhibitory mechanism of defense used by these cells to evade attack by CD66a-positive NK cells. (PMID:11884449)
• Quaternary structure of coronavirus spikes in complex with carcinoembryonic antigen-related cell adhesion molecule cellular receptors (PMID:11912215)
• Only the long cytoplasmic domain isoform of CEACAM1 is expressed in human granulocytes, B cells, and T cells, since GPI-linked CEA-related proteins have functionally replaced the short cytoplasmic domains in the human. (PMID:11994468)
• High CEACAM 1 expression is associated with development of metastasis in primary cutaneous malignant melanoma patients (PMID:12011132)
• inhibition of prostate tumor angiogenesis by the tumor suppressor CEACAM1 (PMID:12122002)
• Role of CEACAM1 protein in the inhibition of activated decidual lymphocyte functions. (PMID:12370272)
• CEACAM1-4S mediates apoptosis and reverts mammary carcinoma cells to a normal morphogenic phenotype in a 3D culture. (PMID:12522268)
• CEACAM1 has a role in internalizing bacteria to epithelial cells (PMID:12571236)
• CEACAM1, a cell-cell adhesion molecule, directly associates with annexin II (PMID:14522961)
• cholesterol is an essential membrane fusion cofactor that can act with or without CEACAMs to promote murine hepatitis virus entry (PMID:14990688)
• The long and short cytoplasmic tails of CEACAM1 serve as inhibitory and costimulatory receptors, respectively, in T cell regulation. (PMID:15004154)
• CEACAM1-4L (long), but not the -4S (short)isoform inhibits IL-2 production in transfected Jurkat cells, while CEACAM1-4S, but not the -4L isoform inhibits proliferation in transfected Kit-225 cells. (PMID:15004155)
• the N-domain of CEACAM1 does not show evidence of recombination (PMID:15184366)
• The sequential digestions clearly identified several different Lewis x glycan epitopes, which may modulate the cell adhesive functions of CEACAM1 (PMID:15317738)
• The amino-terminal end of CEACAM1 interacts with CEACAM5, but not with CEACAM6. Both CEACAM1 and CEACAM5 contain the Arg and Gln residues in positions 43 and 44, respectively, whereas CEACAM6 contains 43-Ser and 44-Leu. (PMID:15356119)
• CEACAM1 and alpha(v)beta(3) integrin are functionally interconnected with respect to the invasive growth of melanomas (PMID:15509546)
• constitutive expression of CEACAM1 in microvascular endothelial cells switches them to an angiogenic phenotype, whereas CEACAM1 silencing apparently abrogates the VEGF-induced morphogenetic effects during capillary formation (PMID:15536067)
• failure of the maturing colon cell to express CEACAM1 is likely to contribute to the development of hyperplastic lesions (PMID:15568039)
• role in developing of hyperplastic polyps leading to colon cancer (PMID:15602572)
• CEACAM1 is up-regulated in endothelial cells of angiogenic blood vessels. This in turn is involved in the switch from noninvasive and nonvascularized to invasive and vascularized bladder cancer. (PMID:15604255)
• transmembrane CEACAM1-L expressed on endothelial cells is implicated in the activation phase of angiogenesis by affecting the cytoskeleton architecture and integrin-mediated signaling (PMID:15687237)
• Heterophilic interactions of carcinoembryonic antigen and CEACAM1 inhibit killing by natural killer (NK) cells. The N-terminal domain of CEACAM1 is crucial but not sufficient for both CEACAM1-CEACAM1 homophilic and CEACAM1-CEA heterophilic interactions. (PMID:15905509)
• OPN and CEACAM1 may act as a functional complex involved in the regulation of placental invasiveness. (PMID:15956076)
• Data show that variants of Neisseria gonorrhoeae that bind to human carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) 1 and 6 failed to induce detachment and, instead, promoted enhanced host cell adhesion to the ECM. (PMID:16115956)
• Binding of DC-SIGN to both CEACAM1 and Mac-1 is required to establish cellular interactions with neutrophils. (PMID:16246332)
• findings suggest that CEACAM1 participates in immune regulation in physiological conditions and in pathological conditions, such as inflammation, autoimmune disease, and cancer (PMID:16282604)
• The expression of CEACAM1-L led to an increased phosphorylation of focal adhesions and to altered cytoskeletal rearrangements during monolayer wound healing assays. (PMID:16291724)
• first report demonstrating that activators of PKC are able to specifically induce the expression of CEACAM1 in human carcinoma cells (PMID:16332726)
• data show that disappearance of epithelial CEACAM1 in PIN is accompanied by its upregulation in adjacent vasculature which apparently correlates with vascular destabilization and increased vascularization of prostate cancer (PMID:16568082)
• study shows the expression pattern of osteopontin in cellular populations of normal endometrium and in endometrial carcinoma and its correlation with the expression of CEACAM1 (PMID:16633066)
• This Review considers the evidence for CEACAM1 involvement in immunity, with emphasis on its functions as a regulatory co-receptor for both lymphoid and myeloid cell types. (PMID:16724098)
• CEACAM1 may be an interesting progression marker in squamous intraepithelial lesions and cervical cancer, in particular due to reported immunoregulatory properties. (PMID:16924126)
• the N-terminal domain of human CEACAM1 contains the binding target of the opacity proteins during invasion of Neisseria meningitidis and N. gonorrhoeae (PMID:16929097)
• studies imply that distinct polymorphisms in human epithelial CEACAMs have the potential to decrease or increase the risk of infection by the receptor-targeting pathogens (PMID:16953805)
• CEACAM1 functions as a key regulator of contact-dependent control of cell survival, differentiation, and growth by controlling both ERK/MEK and PI3K/Akt pathways (PMID:17071610)
• High expression of CD66a was significantly correlated with tumor invasion, stage, and pre-operation serum carcinoembryonic antigen level. (PMID:17143599)
• In conclusion, M. catarrhalis induced apoptosis in pulmonary epithelial cells–a process that was triggered by interaction between CEACAM1 and UspA1. (PMID:17471435)
• Phosphorylation mimic mutants at either Thr457 or Ser459 (or both), but not null mutants in CEACAM1-4S were able to restore glandular lumen formation. (PMID:17546042)

Cross-species orthologs

0 orthologs

Paralogs (24): CEACAM21 (ENSG00000007129), CEACAM7 (ENSG00000007306), CEACAM6 (ENSG00000086548), CEACAM4 (ENSG00000105352), CEACAM5 (ENSG00000105388), PSG8 (ENSG00000124467), CEACAM8 (ENSG00000124469), HEPACAM (ENSG00000165478), PSG6 (ENSG00000170848), CEACAM3 (ENSG00000170956), PSG9 (ENSG00000183668), CEACAM19 (ENSG00000186567), HEPACAM2 (ENSG00000188175), PSG5 (ENSG00000204941), CEACAM18 (ENSG00000213822), CEACAM16 (ENSG00000213892), VSTM5 (ENSG00000214376), PSG3 (ENSG00000221826), PSG7 (ENSG00000221878), PSG1 (ENSG00000231924), PSG2 (ENSG00000242221), PSG11 (ENSG00000243130), PSG4 (ENSG00000243137), CEACAM20 (ENSG00000273777)

Protein

Protein identifiers

Cell adhesion molecule CEACAM1 — P13688 (reviewed: P13688)

Alternative names: Biliary glycoprotein 1, Carcinoembryonic antigen-related cell adhesion molecule 1

All UniProt accessions (4): P13688, A0A7I2V3A7, M0R109, M0R2K4

UniProt curated annotations — full annotation on UniProt →

Function. Cell adhesion protein that mediates homophilic cell adhesion in a calcium-independent manner. Plays a role as coinhibitory receptor in immune response, insulin action and also functions as an activator during angiogenesis. 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. 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. 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. 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. 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. Down-regulates neutrophil production by acting as a coinhibitory receptor for CSF3R by down-regulating the CSF3R-STAT3 pathway through recruitment of PTPN6 that dephosphorylates CSF3R. Also regulates insulin action by promoting INS clearance and regulating lipogenesis in liver through regulating insulin signaling. 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. 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. Down-regulates 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. Negatively regulates platelet aggregation by decreasing platelet adhesion on type I collagen through the GPVI-FcRgamma complex. Inhibits cell migration and cell scattering through interaction with FLNA; interferes with the interaction of FLNA with RALA. Mediates bile acid transport activity in a phosphorylation dependent manner. Negatively regulates osteoclastogenesis. Cell adhesion protein that mediates homophilic cell adhesion in a calcium-independent manner. Promotes populations of T cells regulating IgA production and secretion associated with control of the commensal microbiota and resistance to enteropathogens.

Subunit / interactions. Monomer. Oligomer. Heterodimer. Homodimer. Cis-dimer/oligomer (via Ig-like C2-type and/or via cytoplasmic domains); induced by trans-homophilic cell adhesion through an allosteric mechanism transmitted by the Ig-like V-type domain, and is regulated by intracellular calcium and calmodulin. Interacts (via cytoplasmic domain) with calmodulin in a calcium dependent manner; reduces homophilic cell adhesion through dissociation of dimer. Isoform 1 interacts (via cytoplasmic domain) with PTPN11 (preferentially) and PTPN6; cis-homodimer form is preferred; this interaction is decreased by formation of Isoform 1 /Isoform 8 cis-heterodimers and is dependent on the monomer/dimer equilibrium; this interaction is phosphorylation-dependent. Isoform 1 interacts with LYN. Isoform 1 interacts (via cytoplasmic domain) with SRC (via SH2 domain); this interaction is regulated by trans-homophilic cell adhesion. Isoform 1 interacts (via cytoplasmic domain) with LCK; mediates phosphorylation at Tyr-493 and Tyr-520 resulting in PTPN6 association. Isoform 1 interacts with PTPN6; this interaction is phosphorylation-dependent and causes a profound decrease in TCR stimulation-induced CD247 and ZAP70 phosphorylation. Isoform 1 interacts with TCR/CD3 complex through TCR beta chain and CD3E; colocalizes at the cell surface and upon stimulation of the TCR/CD3 complex recruits PTPN6 in the TCR/CD3 complex, resulting in dephosphorylation of CD247 and ZAP70. Isoform 1 interacts (via cytoplasmic domain) with SHC1 (via SH2 domain); SHC1 mediates interaction with INSR or EGFR in a Ser-508 phosphorylation-dependent manner. Isoform 1 interacts with EGFR; the interaction is indirect. Isoform 1 interacts with CSF3R; down-regulates the CSF3R-STAT3 pathway through recruitment of PTPN6 that dephosphorylates CSF3R. Isoform 1 (phosphorylated form) interacts with TLR4 and SYK; recruits PTPN6 that dephosphorylates SYK, reducing the production of reactive oxygen species (ROS) and lysosome disruption, leading to a reduction of the inflammasome activity. Isoform 1 interacts with FLNA; inhibits cell migration and cell scattering by interfering with the interaction of FLNA with RALA. Isoform 1 interacts (via cytoplasmic domain) with PXN; the interaction is phosphotyrosyl-dependent. Isoform 1 interacts with KLRK1; recruits PTPN6 that dephosphorylates VAV1. Isoform 1 interacts with CEACAM8. Isoform 1 interacts with FASN; this interaction is insulin and phosphorylation-dependent; reduces fatty-acid synthase activity. Interacts (via Ig-like V-type) with HAVCR2 (via Ig-like V-type); facilitates the maturation and cell surface expression of HAVCR2 thereby regulating T cell tolerance induction. Isoform 8 interacts (via the cytoplasmic domain) with ANXA2; this interaction is regulated by phosphorylation and appears in the AIIt complex. Interacts (via Lewis X moieties) with CD209 (via C-type lectin domain); this interaction is regulated by the glycosylation pattern of CEACAM1 on cell types and regulates contact between dendritic cells and neutrophils.

Subcellular location. Cell membrane. Lateral cell membrane. Apical cell membrane. Basal cell membrane. Cell junction. Adherens junction Secreted Secreted Secreted Cell membrane Cell membrane Cell membrane Cell membrane. Cytoplasmic vesicle. Secretory vesicle membrane. Adherens junction Cell projection. Microvillus membrane.

Tissue specificity. Expressed in columnar epithelial cells of the colon (at protein level). The predominant forms expressed by T cells are those containing a long cytoplasmic domain. Expressed in granulocytes and lymphocytes. Leukocytes only express isoforms 6 and isoform 1.

Post-translational modifications. Phosphorylated on serine and tyrosine. Isoform 1 is phosphorylated on tyrosine by Src family kinases like SRC and LCK and by receptor like CSF3R, EGFR and INSR upon stimulation. Phosphorylated at Ser-508; mediates activity. Phosphorylated at Tyr-493; regulates activity. Phosphorylated at Tyr-493 by EGFR and INSR upon stimulation; this phosphorylation is Ser-508-phosphorylation-dependent; mediates cellular internalization; increases interaction with downstream proteins like SHC1 and FASN. Phosphorylated at Tyr-493 and Tyr-520 by LCK; mediates PTPN6 association and is regulated by homophilic ligation of CEACAM1 in the absence of T cell activation. Phosphorylated at Tyr-520; mediates interaction with PTPN11. Phosphorylated on serine and threonine.

Domain organisation. Ig-like V-type domain mediates trans-homophilic cell adhesion through homodimerization and this active process is regulated by tyrosine kinase, PTPN11 and PTPN6. Ig-like C2-type and/or cytoplasmic domains mediate cis-dimer/oligomer.

Induction. Induced in primary T cells by activation with IL-2.

Miscellaneous. Pseudophosphorylated double mutant Thr-457->Asp and Ser-459->Asp. The single mutant Ser-459->Asp mutant highly binds with ANXA2.

Similarity. Belongs to the immunoglobulin superfamily. CEA family.

Isoforms (11)

UniProt ID	Names	Canonical?
P13688-1	1, BGPa, CEACAM1-4L, TM1-CEA	yes
P13688-2	2, BGPg, CEACAM1-4C1
P13688-3	3, BGPh, CEACAM1-3
P13688-4	4, BGPi, CEACAM1-3C2
P13688-5	5, BGPy, CEACAM1-3AL
P13688-6	6, BGPb, CEACAM1-3L, TM2-CEA
P13688-7	7, BGPx, CEACAM1-1L
P13688-8	8, BGPc, CEACAM1-4S, TM3-CEA
P13688-9	9, BGPz, CEACAM1-3AS
P13688-10	10
P13688-11	11, BGPd, CEACAM1-3S

RefSeq proteins (6): NP_001020083, NP_001171742, NP_001171744, NP_001171745, NP_001192273, NP_001703* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003598	Ig_sub2	Domain
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013106	Ig_V-set	Domain
IPR013151	Immunoglobulin_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR050831	CEA_cell_adhesion	Family

Pfam: PF00047, PF07686, PF13895, PF13927

UniProt features (85 total): glycosylation site 20, splice variant 14, strand 9, region of interest 6, mutagenesis site 6, sequence conflict 5, modified residue 4, domain 4, sequence variant 4, disulfide bond 3, compositionally biased region 2, topological domain 2, helix 2, signal peptide 1, chain 1, transmembrane region 1, turn 1

Structure

Experimental structures (PDB)

18 structures.

PDB	Method	Resolution (Å)
7MU8	X-RAY DIFFRACTION	1.7
6XO1	X-RAY DIFFRACTION	1.76
6XNO	X-RAY DIFFRACTION	1.9
6XNW	X-RAY DIFFRACTION	1.9
4QXW	X-RAY DIFFRACTION	2.04
9U94	ELECTRON MICROSCOPY	2.11
2GK2	X-RAY DIFFRACTION	2.2
7RPP	X-RAY DIFFRACTION	2.2
4WHD	X-RAY DIFFRACTION	2.5
6GBH	X-RAY DIFFRACTION	2.59
6AW2	X-RAY DIFFRACTION	2.68
9GH5	ELECTRON MICROSCOPY	2.7
6GBG	X-RAY DIFFRACTION	2.8
9GH6	ELECTRON MICROSCOPY	3
8CXJ	X-RAY DIFFRACTION	3.05
6XNT	X-RAY DIFFRACTION	3.1
6V3P	X-RAY DIFFRACTION	3.25
5DZL	X-RAY DIFFRACTION	3.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P13688-F1	81.51	0.65

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (4): 35, 493, 508, 520

Disulfide bonds (3): 167–215, 259–299, 348–396

Glycosylation sites (20): 104, 111, 115, 152, 182, 197, 208, 224, 232, 254, 274, 288, 292, 302, 309, 345, 351, 363, 378, 405

Mutagenesis-validated functional residues (6):

Position	Phenotype
76	impairs interaction with havcr2.
77–78	doesn’t affect cell surface expression. impairs phosphorylation.
81	impairs interaction with havcr2.
457	decreases the binding to anxa2.
493	impairs phosphorylation; when associated with f-520.
520	impairs phosphorylation; when associated with f-493.

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-1566977	Fibronectin matrix formation
R-HSA-202733	Cell surface interactions at the vascular wall
R-HSA-6798695	Neutrophil degranulation
R-HSA-9854909	Regulation of MITF-M dependent genes involved in invasion
R-HSA-109582	Hemostasis
R-HSA-1266738	Developmental Biology
R-HSA-1474244	Extracellular matrix organization
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-9730414	MITF-M-regulated melanocyte development
R-HSA-9856651	MITF-M-dependent gene expression

MSigDB gene sets: 527 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_T_CELL_RECEPTOR_SIGNALING_PATHWAY, GOBP_NEGATIVE_REGULATION_OF_EPITHELIAL_CELL_PROLIFERATION, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_REGULATION_OF_HEPATOCYTE_PROLIFERATION, GOBP_REGULATION_OF_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_VASCULOGENESIS, GOBP_HEPATICOBILIARY_SYSTEM_DEVELOPMENT, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, WANG_CLIM2_TARGETS_UP, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_GLAND_MORPHOGENESIS

GO Biological Process (39): angiogenesis (GO:0001525), regulation of cell growth (GO:0001558), blood vessel development (GO:0001568), negative regulation of T cell mediated cytotoxicity (GO:0001915), regulation of immune system process (GO:0002682), negative regulation of natural killer cell mediated cytotoxicity directed against tumor cell target (GO:0002859), negative regulation of protein kinase activity (GO:0006469), cell adhesion (GO:0007155), homophilic cell-cell adhesion (GO:0007156), signal transduction (GO:0007165), integrin-mediated signaling pathway (GO:0007229), regulation of endothelial cell migration (GO:0010594), bile acid and bile salt transport (GO:0015721), cell migration (GO:0016477), regulation of cell migration (GO:0030334), negative regulation of granulocyte differentiation (GO:0030853), negative regulation of interleukin-1 production (GO:0032692), cellular response to insulin stimulus (GO:0032869), common myeloid progenitor cell proliferation (GO:0035726), insulin receptor internalization (GO:0038016), granulocyte colony-stimulating factor signaling pathway (GO:0038158), regulation of epidermal growth factor receptor signaling pathway (GO:0042058), negative regulation of vascular permeability (GO:0043116), negative regulation of cytotoxic T cell degranulation (GO:0043318), wound healing, spreading of cells (GO:0044319), regulation of endothelial cell differentiation (GO:0045601), negative regulation of fatty acid biosynthetic process (GO:0045717), negative regulation of T cell receptor signaling pathway (GO:0050860), negative regulation of lipid biosynthetic process (GO:0051055), regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051896), regulation of blood vessel remodeling (GO:0060312), regulation of ERK1 and ERK2 cascade (GO:0070372), negative regulation of platelet aggregation (GO:0090331), obsolete cell-cell adhesion via plasma-membrane adhesion molecules (GO:0098742), insulin catabolic process (GO:1901143), regulation of homophilic cell adhesion (GO:1903385), regulation of sprouting angiogenesis (GO:1903670), negative regulation of hepatocyte proliferation (GO:2000346), positive regulation of vasculogenesis (GO:2001214)

GO Molecular Function (11): actin binding (GO:0003779), calmodulin binding (GO:0005516), bile acid transmembrane transporter activity (GO:0015125), kinase binding (GO:0019900), protein phosphatase binding (GO:0019903), filamin binding (GO:0031005), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), protein dimerization activity (GO:0046983), protein tyrosine kinase binding (GO:1990782), protein binding (GO:0005515)

GO Cellular Component (19): plasma membrane (GO:0005886), cell-cell junction (GO:0005911), adherens junction (GO:0005912), basal plasma membrane (GO:0009925), cell surface (GO:0009986), membrane (GO:0016020), apical plasma membrane (GO:0016324), lateral plasma membrane (GO:0016328), cell junction (GO:0030054), transport vesicle membrane (GO:0030658), microvillus membrane (GO:0031528), specific granule membrane (GO:0035579), extracellular exosome (GO:0070062), tertiary granule membrane (GO:0070821), extracellular region (GO:0005576), cytoplasmic vesicle (GO:0031410), T cell receptor complex (GO:0042101), cell projection (GO:0042995), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Extracellular matrix organization	1
Hemostasis	1
Innate Immune System	1
MITF-M-dependent gene expression	1
Immune System	1
Developmental Biology	1
MITF-M-regulated melanocyte development	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
protein binding	3
cellular process	2
cytoskeletal protein binding	2
plasma membrane region	2
secretory granule membrane	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
cell growth	1
regulation of growth	1
regulation of cellular component organization	1
vasculature development	1
anatomical structure development	1
negative regulation of leukocyte mediated cytotoxicity	1
T cell mediated cytotoxicity	1
regulation of T cell mediated cytotoxicity	1
negative regulation of T cell mediated immunity	1
immune system process	1
regulation of biological process	1
natural killer cell mediated cytotoxicity directed against tumor cell target	1
negative regulation of natural killer cell mediated immune response to tumor cell	1
regulation of natural killer cell mediated cytotoxicity directed against tumor cell target	1
negative regulation of natural killer cell mediated cytotoxicity	1
negative regulation of protein phosphorylation	1
protein kinase activity	1
negative regulation of kinase activity	1
regulation of protein kinase activity	1
cell-cell adhesion	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cell surface receptor signaling pathway	1
regulation of cell migration	1
endothelial cell migration	1
lipid transport	1
monocarboxylic acid transport	1
organic hydroxy compound transport	1
cell motility	1
cell migration	1

Protein interactions and networks

STRING

2092 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CEACAM1	HAVCR2	Q8TDQ0	994
CEACAM1	CEACAM5	P06731	880
CEACAM1	LGALS9	O00182	806
CEACAM1	CD209	Q9NNX6	801
CEACAM1	LGALS9B	Q3B8N2	796
CEACAM1	LGALS9C	Q6DKI2	796
CEACAM1	POLDIP2	Q9Y2S7	794
CEACAM1	PTPN11	Q06124	746
CEACAM1	CEACAM6	P40199	723
CEACAM1	HMGB1	P09429	679
CEACAM1	ERV3-1	Q14264	671
CEACAM1	PDCD1	Q15116	667
CEACAM1	ERVFRD-1	P60508	666
CEACAM1	ACE2	Q9BYF1	614
CEACAM1	ITGB3	P05106	605

IntAct

45 interactions, top by confidence:

A	B	Type	Score
CEACAM1	CEACAM1	psi-mi:“MI:0915”(physical association)	0.790
CEACAM1	CEACAM1	psi-mi:“MI:0407”(direct interaction)	0.790
CEACAM8	CEACAM1	psi-mi:“MI:0915”(physical association)	0.710
CEACAM1	CEACAM8	psi-mi:“MI:0915”(physical association)	0.710
CEACAM8	CEACAM1	psi-mi:“MI:0407”(direct interaction)	0.710
uspa1	CEACAM1	psi-mi:“MI:0407”(direct interaction)	0.690
CEACAM1	uspa1	psi-mi:“MI:0407”(direct interaction)	0.690
opaH	CEACAM1	psi-mi:“MI:0407”(direct interaction)	0.610
CEACAM1	opaH	psi-mi:“MI:0407”(direct interaction)	0.610
CEACAM1	CEACAM6	psi-mi:“MI:0915”(physical association)	0.610
CEACAM5	CEACAM1	psi-mi:“MI:0915”(physical association)	0.610
CEACAM1	CEACAM5	psi-mi:“MI:0407”(direct interaction)	0.610
CEACAM6	CEACAM1	psi-mi:“MI:0407”(direct interaction)	0.610
HAVCR2	CEACAM1	psi-mi:“MI:0915”(physical association)	0.590

BioGRID (22): ANXA2 (Affinity Capture-MS), ANXA2 (Reconstituted Complex), CEACAM8 (Reconstituted Complex), CEACAM1 (Affinity Capture-Western), PTPN11 (Affinity Capture-Western), CEACAM1 (Reconstituted Complex), PXN (Affinity Capture-Western), CEACAM21 (Negative Genetic), CEACAM1 (Co-fractionation), CEACAM1 (Co-fractionation), CEACAM1 (Co-fractionation), CEACAM1 (Co-fractionation), CEACAM6 (Reconstituted Complex), CEACAM1 (Reconstituted Complex), CARTPT (Reconstituted Complex)

ESM2 similar proteins: A0A0K2S4Q6, A6NI73, B6A8C7, O75019, O75022, O75023, O75871, O76036, P0C191, P13688, P24071, P31994, P40198, P43629, P43630, P59901, P97484, Q08708, Q14943, Q28110, Q3KPI0, Q496F6, Q6GTX8, Q6ISS4, Q6PI73, Q6UX52, Q810J1, Q863H2, Q8C567, Q8IYS5, Q8K249, Q8MJZ2, Q8MJZ7, Q8N149, Q8N423, Q8N6C8, Q8N743, Q8NHJ6, Q8NHK3, Q8NHL6

Diamond homologs: A0A0B4J1L0, D3ZQE1, E9QA28, O75871, P06731, P11464, P11465, P13688, P16573, P31809, P31997, P40198, P40199, Q00887, Q00888, Q00889, Q13046, Q14002, Q15238, Q16557, Q2WEN9, Q3KPI0, Q3UKK2, Q61400, Q63111, Q810J1, Q925P2, Q9D2Z1, Q9UQ72, Q9UQ74, Q0E9H9, Q6UY09, A8MTB9, A0A140LHF2, Q8BFR2, Q8N475, Q9PWR4, P35329, Q4VAH7, Q7TPB4

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
CAMK2D	up-regulates	CEACAM1	phosphorylation
SRC	“up-regulates activity”	CEACAM1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 17 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Cell surface interactions at the vascular wall	5	43.3×	5e-06
Hemostasis	5	16.4×	3e-04

GO biological processes:

GO term	Partners	Fold	FDR
heterophilic cell-cell adhesion	5	140.4×	2e-08

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

54 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	31
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1309 predictions. Top by Δscore:

Variant	Effect	Δscore
19:42512344:TCATA:T	donor_loss	1.0000
19:42512345:CATA:C	donor_loss	1.0000
19:42512346:ATAC:A	donor_loss	1.0000
19:42512347:TACCT:T	donor_loss	1.0000
19:42512352:G:A	donor_gain	1.0000
19:42512476:TTAT:T	acceptor_gain	1.0000
19:42512477:TAT:T	acceptor_gain	1.0000
19:42512478:AT:A	acceptor_gain	1.0000
19:42512478:ATC:A	acceptor_loss	1.0000
19:42512480:C:CC	acceptor_gain	1.0000
19:42512480:C:CG	acceptor_loss	1.0000
19:42512485:A:AC	acceptor_gain	1.0000
19:42512485:A:C	acceptor_gain	1.0000
19:42522198:CTCCG:C	acceptor_gain	1.0000
19:42522200:CCG:C	acceptor_gain	1.0000
19:42522201:CG:C	acceptor_gain	1.0000
19:42522201:CGC:C	acceptor_gain	1.0000
19:42527033:ATACT:A	donor_loss	1.0000
19:42527037:TCACG:T	donor_loss	1.0000
19:42527038:CA:C	donor_loss	1.0000
19:42527039:A:AC	donor_gain	1.0000
19:42527040:C:CC	donor_gain	1.0000
19:42527040:CG:C	donor_gain	1.0000
19:42509394:CAT:C	acceptor_gain	0.9900
19:42509396:T:TC	acceptor_gain	0.9900
19:42510921:C:CC	acceptor_gain	0.9900
19:42512475:ATTAT:A	acceptor_gain	0.9900
19:42512484:CA:C	acceptor_gain	0.9900
19:42518946:A:AC	donor_gain	0.9900
19:42518947:C:CC	donor_gain	0.9900

AlphaMissense

3441 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:42519119:A:G	W359R	0.986
19:42519119:A:T	W359R	0.986
19:42519007:C:G	C396S	0.984
19:42519008:A:T	C396S	0.984
19:42519117:C:A	W359C	0.984
19:42519117:C:G	W359C	0.984
19:42521412:C:A	W271C	0.981
19:42521412:C:G	W271C	0.981
19:42521414:A:G	W271R	0.979
19:42521414:A:T	W271R	0.979
19:42521329:C:G	C299S	0.978
19:42521330:A:T	C299S	0.978
19:42519157:A:G	L346P	0.975
19:42521330:A:G	C299R	0.975
19:42519151:C:G	C348S	0.974
19:42519152:A:T	C348S	0.974
19:42527266:A:G	W67R	0.972
19:42527266:A:T	W67R	0.972
19:42521450:A:G	C259R	0.970
19:42527145:A:G	L107P	0.969
19:42521336:A:C	Y297D	0.968
19:42521448:G:C	C259W	0.968
19:42527264:C:A	W67C	0.966
19:42527264:C:G	W67C	0.966
19:42521455:A:G	L257P	0.965
19:42521328:G:C	C299W	0.964
19:42521329:C:T	C299Y	0.964
19:42521449:C:T	C259Y	0.964
19:42519152:A:G	C348R	0.962
19:42519014:A:C	Y394D	0.961

dbSNP variants (sampled 300 via entrez): RS1000071357 (19:42516705 GAACAA>G), RS1000297387 (19:42509632 G>T), RS1000677126 (19:42525216 G>A), RS1000726265 (19:42525547 C>G,T), RS1000733613 (19:42518804 C>T), RS1001181779 (19:42522338 G>A), RS1001293230 (19:42514949 A>G), RS1001397200 (19:42521950 C>T), RS1001529931 (19:42517075 G>A), RS1001593076 (19:42523400 T>C), RS1001684515 (19:42507429 C>T), RS1001862038 (19:42515693 T>A), RS1001949679 (19:42526774 G>A), RS1001977472 (19:42522396 T>C), RS1002034608 (19:42529067 G>C)

Disease associations

OMIM: gene MIM:109770 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

79 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, increases methylation	4
Cisplatin	affects expression, affects cotreatment, increases expression	3
Aflatoxin B1	increases expression, affects expression	3
dinophysistoxin 1	increases expression	2
azaspiracid	increases expression	2
Resveratrol	increases expression	2
Acetaminophen	decreases expression	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Camptothecin	increases expression	2
Formaldehyde	decreases expression, increases expression	2
Mustard Gas	increases expression, increases secretion	2
Silicon Dioxide	decreases expression, increases expression	2
Tetrachlorodibenzodioxin	decreases expression, affects cotreatment, increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Tretinoin	increases expression	2
Valproic Acid	decreases methylation, increases expression	2
Cyclosporine	decreases expression	2
aristolochic acid I	increases expression	1
afuresertib	increases expression	1
3,19-(2-bromobenzylidene)andrographolide	decreases response to substance, increases expression	1
dicrotophos	increases expression	1
methyleugenol	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
cobaltiprotoporphyrin	decreases expression, decreases reaction, decreases secretion	1
kojic acid	decreases expression	1
trichostatin A	increases expression	1
pyrazolo(3,4-d)pyrimidine	affects expression	1
3,4-dichloroaniline	increases expression	1
beta-lapachone	increases expression	1

Cellosaurus cell lines

9 cell lines: 4 cancer cell line, 4 transformed cell line, 1 spontaneously immortalized cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1ET	Abcam A-549 CEACAM1 KO 2	Cancer cell line	Male
CVCL_B2MB	Abcam A-549 CEACAM1 KO 1	Cancer cell line	Male
CVCL_C0DZ	A549-CEACAM1-4L	Cancer cell line	Male
CVCL_C0EF	HEK293-CEACAM1-dN-Fc	Transformed cell line	Female
CVCL_C0EG	HEK293-CEACAM1-Fc	Transformed cell line	Female
CVCL_C0EH	HEK293-CEACAM1-N-Fc	Transformed cell line	Female
CVCL_C515	MM46 CEA1-2	Cancer cell line	Female
CVCL_D9BU	Ubigene HEK293 CEACAM1 KO	Transformed cell line	Female
CVCL_E6PV	Genomeditech CHO-K1 H_CEACAM1(CD66a)	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.