CD239 BCAM (basel cell adhesion molecule), LU (Lutheran blood group)
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 1 glycoprotein
Erythrocyte
Stem Cell
Red Cell
Epithelial Cell
Endothelial Cell
Fibroblast
Pancreas
Carcinoma Cell
78 / 78
85 / 85

Expression
CD239 is expressed strongly on the basal layer of epithelial and endothelium of blood vessel walls but is over-expressed by sickle cells.  There is a wide tissue distribution of CD239+ cells.  Expression is upregulated following malignant transformation in some cell types, including basal and squamous cells and ovarian carcinomas.  Expression is on erythrocytes, fibroblasts, stem cell subsets and at low levels on red blood cells.  The expression is highest in the pancreas but very low in the brain tissues.

Structure
MOLECULAR FAMILY NAME: Belongs to the immunoglobulin gene superfamily.

CD239 is a single-pass type-1 597 aa glycoprotein.  It contains a 516 aa extracellular domain containing 2 N-terminal V-type Ig-like domains and 3 Ig-like C2-type domains and has 5 potential N-linked glycosylation sites, a 21 aa hydrophobic transmembrane domain and a 60 aa cytoplasmic domain which contains a membrane proximal RK motif for spectrin binding in erythrocytes as well a dileucine motif that is responsible for basolateral targeting of the Lutheran isoform of CD239 in epithelial cells.  The extracellular domains and cytoplasmic domain contains consensus motifs with a binding of integrin and SRC homology 3 domains suggesting possible receptor and signal-transduction functions.  CD239 is a carrier of the Lutheran blood group which comprises at least 18 antigens.  CD239 was a receptor for the extracellular matrix protein and laminin.  CD239 is similar in structure to human membrane proteins CD166 (ALCAM) and CD146 (MUC18, basign).

MOLECULAR MASS
Cell Type Unreduced Reduced
78-85 kDa

POST-TRANSCRIPTIONAL MODIFICATION

Alternative splicing of intron 13 yields 2 isoforms of 85 kDa (Lu) and 78 kDa (Lu v13) that differ only in length of the cytoplasmic tail.  The short tail form lacks the last 40 C-terminal amino acids, including a putative SH3 binding site as well as a potential phosphorylation motif which may be involved in intracellular signaling.  The 78 kDa spliced isoform is identical to a previously cloned 'basel cell adhesion molecule' (B-CAM).

POST-TRANSLATIONAL MODIFICATION

CD239 is phosphorylated at Ser 596, 598 and 621 by glcogen synthase kinase 3 β, casein kinase II and PKA.  Mutation of Ser 621 abolishes PKA phosphorylation and impairs binding to laminin.

Ligands
LIGANDS AND MOLECULES ASSOCIATED WITH CD239

CD239 bind the α5-chain of laminin 10/11.

Function
CD329 isoforms are adhesion molecules and appear to mediate intracellular signaling in certain disease states.  Lu and B-CAM bind erythroid spectrin.  This association with red cell skeleton is not considered to have structural significance because of the relatively low density of CD239 molecules in the erythrocyte membrane and may have more to do with signaling.  CD239 is involved in erythrocyte differentiation and trafficking.  CD239 may play a role in cell-cell, cell-matrix adhesion and signal transduction.  CD239 is a carrier of the Lutheran blood group (Lu).  Cells transfected with Lu or Lu (V13) bind to soluble and coated laminins containing the 5th Ig-like domain.  CD239 appears to be the major laminin receptor as Lu null cells do not bind to laminin.  CD239 is over-expressed in sickle cells and PKA-mediated phosphorylation of the Lu isoform plays a critical role in laminin binding.  This might contribute to vaso-occlusion episodes that occurs in sickle cell anemia disease by enhancing sickle cells to bind laminin on endothelial cells under flow conditions.  Other laminin receptors have been shown to be involved in fundamental biological processes such as differentiation, proliferation and migration.  It is suggested that CD239 antigen which appears late during erythropoiesis, might play a role in terminal erythroid differentiation, perhaps in the enucleation process. 

BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD239 IN INTACT ANIMAL

CD239 may play a role in epithelial cell cancer and in vaso-occlusion of red blood cells in sickle cell disease.  CD239 may facilitate trafficking to more mature erythroid cells to the sinusoidal endothelium where laminins are known to be expressed.  Individuals, however, who completely lack CD239 are completely healthy.  CD239 is a marker of malignant transformation in basal and squamous cell carcinomas and ovarian carcinomas.  Normal epidermis expresses CD239 weakly if at all, but strong expression is induced in malignant basal cells ans squamous cells particularly at the basal surface of tumor nests.  Laminin expression is upregulated areound the tumor nests, potentially enabling progression of epithelial cell tumors.



Comments
CD239 is a marker of malignant transformation in basal and squamous cell carcinomas and is over-expressed in ovarian carcinomas.

MOLECULAR INTERACTIONS -
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD239: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD239: No information.


Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 4059P50895
Antibodies

Revised June 25, 2008


Contact us: Webmaster |  509-335-9515 | Accessibility | Copyright | Policies
College of Veterinary Medicine Washington State University, Pullman, WA, 99164-7010 USA
Copyright 1995-2003 Washington State University