CD243 MDR-1 (multidrug resistance protein 1), P-gp (P-glycoprotein), ABC-B1 (ATP-binding cassette, subfamily B member 1), GP170
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 3 glycoprotein, 12 span
Hematopoietic Cell
Progenitor Cell
Stem Cell
Colon
Tumor Cell
Small intestine
Brain
Kidney
Liver
Endothelial Cell
Epithelial Cell
Ovarian cancer
Breast
170 / 170

Expression
CD243 is expressed on stem and progenitor cells and by endothelial and epithelial cells of many tissues.  The P-glycoprotein (P-gp) product of the CD243 gene is expressed in small intestine, brain, colon, kidney, liver and adrenal, with very low levels of expression in most tissues.  Normal peripheral blood and bone marrow cells express very low amounts of P-gp, but it is expressed on practically all hematopoietic progenitor cells with the highest levels on pluripotent stem cells.  Expression can be markedly elevated in various malignancies including breast and ovarian carcinomas.  Low expressions

Structure
MOLECULAR FAMILY NAME: Belongs to the multidrug resistant subfamily, ABC family.

CD243 is a multi-pass type-3, 12 span 1280 aa glycoprotein.  It contains an extracellular domain, 12 transmembrane domains which contains 2 type-1 ABC transmembrane domains, 2 ABC transporter domains, 2 ATP binding sites at 434 aa and 1077 aa and 3 potential N-linked glycosylation sites and a N- and C-terminal cytoplasmic domain.  CD243 belongs to the ATP-binding cassette (ABC) transport proteins superfamily that includes the product of the cystic fibrosis gene (CFTR), the Plasmodium falciparum multidrug resistance protein (pfMDR) and a large number of bacterial periplasmic transport proteins.  ABC proteins transport various molecules across extra- and intra-cellular membranes.  ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White).  This glycoprotein is a member of MDR/TAP subfamily which is involved in multidrug resistance.  

CD243 consists of 2 halves which share a high degree of sequence similarity.  The genomic organization of CD243 suggests that this gene arose by fusion of 2 related, but independently evolved genes, rather than by gene duplication.  Each half of the protein consists of a short hydrophilic N-terminal sequence, a long hydrophobic region containing 6 transmembrane segments, and a relatively hydrophilic region containing an ATP binding cassette of about 200 aa.  The CD243  gene contains 28 introns, of which 26 interrupt the protein coding sequence.

MOLECULAR MASS
Cell Type Unreduced Reduced
170 kDa

POST-TRANSCRIPTIONAL MODIFICATION: No information.

POST-TRANSLATIONAL MODIFICATION: No information.


Ligands
LIGANDS AND MOLECULES ASSOCIATED WITH CD243: No information.

Function
CD243 is an ATP-dependent efflux transporter capable of effluxing a variety of structurally and pharmacologically unrelated neutral and positively charged hydrophobic compounds that are potentially toxic to the cell.  CD243 influences the uptake, tissue distribution and elimination of P-gp transported drugs and toxins.  P-gp has been shown to utilize ATP to pump hydrophobic drugs out of cells, thus decreasing their intracellular concentration and hence their toxicity.  The CD243 gene is amplified in multidrug-resistant cell lines. However the actual physiological role of P-gp is not clear, although recent evidence suggests 2 possibilities that are not mutually exclusive.  The 1st possibility is that P-gp appears to be a flippase which translocates, or "flips", phospholipids from the inner leaflet to the lipid bilayer to the outer leaflet, or visa versa, to maintain the asymmetric distribution of different phospholipids in cell membranes.  The flippase model would explain how P-gp can export a wide range of drugs but not most normal cellular constituents. Hydrophobic drug molecules could initially intercalate into the inner leaflet of the bilayer, then interact with P-gp and be "flipped" from the inner to the other leaflet and subsequently into the aqueous phase. The 2nd possibility is that P-gp appears to regulate cell volume by modulating the activity of an endogenous chloride channel, rather than being itself an ion channel.

BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD243 IN INTACT ANIMAL

CD243 is a useful marker in evaluating potential drug resistance of tumors and is a prognostic indicator for various tumors.  CD243 is responsible for decreased drug accumulation in multidrug-resistant cells and often mediates the development of resistance to anticancer drugs.  CD243 expression renders tumor cells resistant to hydrophobic agents such as chemotherapeutic agents such as vinblasline and adriamycin.  Parenchymal cells in several normal tissues express P-glycoprotein in the secretory domain of the plasma membrane such as bile canaliculus of hepatocytes, brush border of proximal tubular and small intestional cells.  Over expression of CD243 has been correlated with tumor aggressiveness and worse prognosis in a number of human neoplasms like myeloid leukemia.  CD243 is expressed at blood-brain barriers, including brain-brain barrier, blood-testis barrier, blood-placenta barrier and blood-ocular barrier.  At these sites CD243 acts to prevent accumulation of harmful substances by effluxing them out of the cell.  Expression of CD243 is high in the intestine, particularly in the ileum and colon, which suggests CD243 limits availability of orally administered drugs.  Single nucleotide polymorphisms can affect CD243 transport capabilities.  For example, patients with resistant epilepsy are likely to have the C3435T polymorphism, and position emisson tomography (PET) imaging showed lower delivery of an anti-epilepsy drug to the brain than in other genotypes.

Comments
CD243 is a useful marker in evaluating potential drug resistance of tumors and is a prognostic indicator for various tumors.

MOLECULAR INTERACTIONS -
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD243: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD243: No information.


Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 5243P08183
MouseA33719P06795M14757
RatP43245M81855
Antibodies

Revised June 25, 2008


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