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Junior Blood Group System

JR
Gene locus - ABCG2
Alleles

Introduction

Recent studies of Saison et al. (Nature Genetics, 2012, 44:131-2) and Zelinski et al. (Nature Genetics, 2012, 44:174-7) provided the first molecular evidence and the basis for the long known high incidence antigen to change its status from a private antigen to a new blood group system, named Junior, JR or Jr(a). Anti-Jr(a) antibody appears in blood of individuals who are negative for this blood group, and this antibody, although occurring rarely in world populations, may cause acute hemolytic reactions and may be responsible for fatal hemolytic disease of the fetus and newborn (HDFN). A cat erythrocyte protein, orthologous to ABCG2, was imunoprecipitated with a monoclonal antibody to Jr(a) antigen and identified by mass spectrometry; this protein as well as chromosomal analysis of SNPs from DNA of Jr(a-) vs. Jr(a+) individuals, were important tools in elucidating the nature of the gene and the molecular basis for this blood group system. Individuals bearing the Jr(a-) blood group phenotype are rare in all world populations with the exception of Japan and European Gypsies.

The genes

The JR protein is encoded by the ABCG2 gene, a member of the large family (48 genes) of ABC (ATP binding cassette) transporters. ABCG2 is an abbreviation for ATP-binding cassette, sub-family G (white; because of the Drosophila White mutation), member 2 (Homo sapiens). The gene is also known as ATP-binding cassette transporter G, or Breast Cancer Resistance Protein or BCRP. Its locus resides on chromosome 4q22.1. It is organized in 16 exons and spans 66 kb. ABCG2-encoded protein usually resides in extra- and intra-cellular membranes of various tissues and is highly expressed in the placenta. Proteins of this family function as homodimers and their main function is transport across membranes against high concentration gradients using ATP hydrolysis as the main source of energy. The molecular weight of ABCG2 is ~70 kDa and it contains ~655 residues. More generally, ABCG2 is a half-size transporter with three membrane-spanning segments and contains a single ATP-binding cassette located near its amino terminal end.

Function of proteins

The proteins play an important role in protecting the organism against toxic substances by restricting absorption and facilitating elimination. They transport a wide variety of drugs and do not require glutathione for transport of electroneutral amphipathic compounds. They confer multidrug resistance for a wide variety of drugs posing a problem in chemotherapy.

Tissue distribution

ABCG2 proteins are highly expressed in the placenta and also in the blood brain barrier. They are found in hepatocytes, proximal tubular kidney cells, hematopoietic stem cells and mature erythrocytes. They are present in venous and capillary cells in walls of almost all tissues.

Disease association

The presence of Jr(a) antibody, such as in Jr(a-) individuals, can cause hemolytic transfusion reactions, and may lead to hemolytic disease of fetus and newborn. No other health problems have been documented, so far, in individuals lacking this antigen, and mice lacking the gene develop normally and have a normal life span. Drug resistance in cancer treatment is associated with the protein function as a multidrug transporter.

About the alleles

Even though over 1000 SNPs of human ABCG2 are documented in the NCBI dbSNP database, here we will document mostly those that result in change of blood group phenotype, such as those associated with Jr(a-). Most of the latter seem to result from the recessive inheritance of ABCG2 null mutations caused by frameshift or nonsense mutations. The reference sequence for cDNA is the Genbank sequence with acc. no. NM_004827.1, and the one used for amino acid residue changes has acc. no. NP_004818.1.

Other database IDs and links

NCBI genes
9429 for ABCG2
Uniprot ID
Q9UNQ0 for ABCG2
Genbank proteins
NP_004818.2 for ABCG2
Gene nomenclature database ID
74 for ABCG2
Genbank nucleic acids
NM_004827.2 for ABCG2
NCBI homologenes for homologs and orthologs
55852 for ABCG2
NCBI dbSNP for single nucleotide polymorphisms
9429 for ABCG2
OMIM ID - at Online Mendelian Inheritance in Man
603756 for ABCG2

Literature

P. Borst and R. Oude Elferink. Mammalian ABC transporters In health and disease. Ann. Rev. Biochem. 2002, 71;537-592; Saison et al. Null alleles of ABCG2 encoding the breast cancer resistance protein define the new blood group system Junior. Nature Genetics. 2012, 44:174-177; Zelinski et al. ABCG2 null alleles define the JR(a-) blood group phenotype. Nature Genetics. 2012, 44:131-132.

New PubMed entries with the terms Junior and blood from the last 30 days.
NCBI Book Sections with the terms Junior and blood.

Contributors

Olga O. Blumenfeld, Dept. of Biochemistry, Albert Einstein College of Medicine, New York, N.Y., 10461.

Contributors for specific alleles are listed with the alleles.

Links


Updated 2014-03-24 19:26:42.650
 
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