CD338 ABCG2 (ATP-binding cassette sub-family G (WHITE) member 2), CDw338, BCRP, BCRP1, ABCP, MRX, MXR, MXR1, BMDP, ABC15, EST157481, MGC102821
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 3 glycoprotein, 6 span
Stem Cell
Placenta
Hematopoietic Cell
Small intestine
Skeletal muscle
Liver
Heart
Pancreas
Brain
Epithelium
Endothelium
72 / 72

Expression
CD338 is expressed by a subpopulation of hematopoietic stem cells as well as stem cell from a variety of other tissues including skeletal muscle, liver, heart, pancreas.  CD338 is strongly expressed in placenta syncytiotrophoblasts the apical membrane of small intestinal epithelium, the liver canalicular membrane and the luminal surface of brain microvascular endothelium, particularly in the putamen, substanria nigra, pituitary and thalamus. 




Structure
MOLECULAR FAMILY NAME: Belongs to the ATP-binding cassette transport family.

CD338 is a multi-pass type-3 6 span integral 655 aa glycoprotein.  It contains an extracellular domain which contains 3 potential N-linked glycosylation sites which are located in the loops of the membrane-spanning domain (MSD), a transmembrane which contains 3 potential N-linked glycosylation sites and a 395 aa intracellular C-terminus cytoplasmic domain which contains a nucleotide binding domain followed by a MSD.  CD338 is predicited to form disulphide-linked homodimers or homotetramers.  In eukaryotes, CD338 genes encode 4 domains that include 2 conserved ATP-binding domains and 2 domains with multiple transmembrane segements.  The proteins transport various molecules across extra- and intra-cellular membranes.  CD338 genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20,White).  This protein is a member of the White family. 

MOLECULAR MASS

POST-TRANSCRIPTIONAL MODIFICATION

Alternative splicing yields 2 different isoforms. 

POST-TRANSLATIONAL MODIFICATION

CD338 has 3 N-linked glycosylation sites.

Ligands
LIGANDS AND MOLECULE ASSOCIATED WITH CD338

CD338 is disulfide-linked.



Function
The ATP-binding cassette (ABC) superfamily of membrane transporters is one of the largest protein classes known and is involved in the trafficking of biologic molecules and is involved in the transport of molecules across cell membranes.  CD338 acts as a xenobiotic efflux transport protein that can transport chemotherapeutic drugs, organic anions and a variety of toxic chemicals across the cell membrane using ATP hydrolysis to drive the efflux process against a concentrated gradient.  The normal sites of CD338 expression are tissues involved in absorption, distribution and elimination of drugs which indicates a role for CD338 in drug disposition potentially providing protection against cytotoxic substrates.  The function of CD338 in human stem cells is unclear.  Studies of CD338-/- mice have shown that CD338 expression not only provides protection against exogenous cytotoxic substrates but also protects against the effects of hypoxia by preventing the intracellular accumulation of heme, which is toxic to mitochondria.


BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD338 IN INTACT ANIMAL

CD338 can be used as a marker to select for stem cells, potentially enriching stem cells with greater resistance to cytoxic substrates and hypoxia.  CD338 inhibitors are used in conjunction with cytotoxic drugs as part of chemotherapy for various cancers.  CD338 functions as a xenobiotic transport  and overexpression can render cells resistant to several drugs used in chemotherapy such as mitoxantrone, daunorubicin and doxorubicin.   It likely serves as a cellular defense mechanism in response to mitoxantrone and anthracycline exposure.  CD338 is also known as the breast cancer resistance protein, however it does not appear to be a major contributor to drug reisistance in breast cancers.  There have been studies that indicate thatcd338 may contribute to drug resistance in some subgroups of leukemia patients.  Expression of CD338 is upregulated in human glioblastomas and is often found to be elveated in gastric, hepatocellular, endometrial, colon and small cell lung carcinomas and melanoma.  Significant expression of this protein has been observed in the placenta, which may suggest a potential role for this molecule in placenta tissue.  


Comments
MOLECULAR INTERACTIONS-
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD338: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD338: No information.

ADDITIONAL INSIGHTS

For further information see Zhou, S. et al (2001) Nat, Med. 7: 1028-1034.


Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 9429Q9UNQ0
Antibodies

Revised June 25, 2008


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