CEACAM family

Members

CEA	CEACAM5, CD66e
CEACAM1	CD66a, Cell-CAM 105, BGP, biliary glycoprotein, NCA-160
CEACAM3	CD66d, CGM1
CEACAM4	CGM7
CEACAM6	CD66c, NCA, NCA-90, CGM6
CEACAM7	CGM2
CEACAM8	CD66b, CGM6, CGM8, NCA-95

Note: The carcinoembryonic antigen (CEA) family nomenclature has recently been redefined¹, ².

Family

Immunoglobulin superfamily

Structure

Molecular weights
Amino acids	CEA	702
	CEACAM1	526
	CEACAM3	252
	CEACAM6	344
	CEACAM8	349
Polypeptide	CEA	76795
	CEACAM1	57560
	CEACAM3	27077
	CEACAM6	37161
	CEACAM8	38154
SDS-PAGE reduced	CEA	180–200 kDa
	CEACAM1	140–180 kDa
	CEACAM3	35 kDa
	CEACAM6	90–95 kDa
	CEACAM8	95–100 kDa
Carbohydrate
N-linked sites	CEA	28
	CEACAM1	20
	CEACAM3	2
	CEACAM6	12
	CEACAM8	11
O-linked sites
Gene location	19q13.1–19q13.2
Gene structure	The CEA family comprises at least 28 separate genes.

Alternative forms

CEACAM1, CEACAM3 and CEACAM7 are alternatively spliced. The largest isoforms are shown here.

Structure

The human CEA family is part of a cluster of at least 28 genes divided into two functional groups. By genomic mapping, the CEACAM subgroup contains seven members and the PSG (pregnancy-specific glycoprotein) subgroup of secreted molecules contains 11 members. The remaining genes are thought to be pseudogenes¹. Within the best characterized CEACAM members, CEACAM1 and CEACAM3 encode type 1 transmembrane proteins while CEACAM8, CEACAM6 and CEA are GPI anchored in the membrane. All members possess an N-terminal V-type Ig domain followed by between 0 and 6 C2-type Ig domains. Apart from CEACAM3, the extracellular domains are extensively N-glycosylated. CEACAM1 and CEACAM3 have putative tyrosine phosphorylation sites in their cytoplasmic domains, which could bind signalling components such as the tyrosine phosphatases SHP-1 and SHP-2; CEACAM1 can associate with the cytoplasmic tyrosine kinases Src, Lyn and Hck³, ⁴. Alternative splicing results in CEACAM1, 3 and 7 isoforms with varying numbers of Ig domains and/or shorter cytoplasmic domains¹. Further structural and sequence information on other CEACAM family members and members of the PSG family can be found in refs 1 and 2.

Ligands

The CEACAM family can mediate homophilic cell–cell adhesion and in certain combinations, heterophilic interactions with other family members⁵. Binding is via the V-type domain⁶, ⁷. In addition, CEACAM1 and CEACAM6 have been reported to bind E-selectin, CEACAM1 and CEACAM3 can act as a receptors for Neisseria gonorrhoeae and Neisseria meningitidis ⁸, murine CEACAM1 and CEACAM2 are receptors for murine coronaviruses⁹, and CEACAM6 can bind galectins.

Function

Binding assays indicate a role for CEACAM family members in mediating adhesion between granulocytes and/or between granulocytes and epithelial cells, and as microbial receptors. In addition, signalling via CEACAM1 and CEACAM3 cytoplasmic domains⁴ may regulate the adhesive activity of the β₂ integrins¹⁰ and the cytolytic function of intraepithelial lymphocytes¹¹. Different splice variants of CEACAM1 and 3 display different bacterial tropism and invasion⁴. Importantly, members of the CEACAM family are strongly down-regulated in malignancies, implicating these receptors as putative tumour suppressors⁴. It should be noted that Cell-CAM 105 originally identified in rats and described as a homophilic adhesion molecule involved in the formation and maintenance of hepatocyte polarization and exhibiting ecto-ATPase activity¹²,¹³, is CEACAM1.

Distribution

CEACAM1 and CEACAM6 are abundant on granulocytes and epithelial cells, CEACAM8 and CEACAM3 are restricted to granulocytes, and CEA is mostly found on epithelial cells.

Disease association

OMIM CEA, 114890; CEACAMl, 109770; CEACAM6, 163980.

CEACAM1 and CEA are strongly down-regulated in colon and other carcinomas. Evidence that CEACAM proteins can act as tumour suppressors comes from studies in which transfection of CEACAM1 in carcinoma cells resulted in an inhibition of tumour development in nude mice and conversely down-regulation in benign cells resulted in increased tumourigenicity⁴. CEA levels in serum are used routinely as clinical markers in the diagnosis and serial monitoring of cancer patients for recurrent disease or response to therapy.

Knockout

MGI:1347245 (CEACAM1)

Amino acid sequence of human CEA

In CEA the C-terminus is proteolytically cleaved and a GPI anchor attached. However, the site of cleavage has not been unambigously determined.

Amino acid sequence of human CEACAM1

Amino acid sequence of human CEACAM3

Amino acid sequence of human CEACAM6

The sequences sequences underlined and in italics are cleaved off to form mature CEACAM6 and a GPI anchor is added.

Amino acid sequence of human CEACAM8

The sequences sequences underlined and in italics are cleaved off to form mature CEACAM8 and a GPI anchor is added.

Database accession

	EMBL/GenBank	SwissProt
CEA	M17303	P06731
CEACAM1	X16354	P13688
CEACAM3	L00692	P40198
CEACAM6	M29541	P40199
CEACAM8	X52378	P31997