The reference OMIM entry for this protein is 611785

Atp-binding cassette, subfamily b, member 5; abcb5

DESCRIPTION

ABCB5 belongs to the ATP-binding cassette (ABC) transporter superfamily of integral membrane proteins. These proteins participate in ATP-dependent transmembrane transport of structurally diverse molecules ranging from small ions, sugars, and peptides to more complex organic molecules (Chen et al., 2005).

CLONING

By searching a database for homologs of ABCB1 (171050), followed by RT-PCR of RNA from human primary epidermal melanocytes and a malignant melanoma cell line, Frank et al. (2003) cloned ABCB5. The deduced 812-amino acid protein has 5 transmembrane helices flanked by both extracellular and intracellular ATP-binding domains. ABCB5 shares 54% and 56% amino acid identity with ABCB1 and ABCB4 (171060), respectively. RT-PCR detected ABCB5 in melanocytes and melanoma cells, but not in peripheral blood mononuclear cells or nonmelanoma tumor cell lines. Western blot analysis revealed an 89-kD endogenous ABCB5 protein in melanocytes and melanoma cells. Flow cytometry showed ABCB5 expressed on the cell surface of transfected breast cancer cells. By screening a melanoma cDNA library, Chen et al. (2005) cloned 2 ABCB5 splice variants, which they called ABCB5-alpha and -beta. ABCB5-alpha and -beta diverge after exon 6, with ABCB5-alpha including a seventh exon that encodes its 3-prime UTR, and ABCB5-beta including 14 more exons. The 131-amino acid ABCB5-alpha protein has a calculated molecular mass of 15 kD. It has an ABC signature motif and a Walker B consensus sequence, but no Walker A consensus sequence. In contrast, ABCB5-beta has an N-terminal ABC signature motif and Walker B motif, followed by 6 transmembrane domains and C-terminal Walker A, ABC signature, and Walker B motifs. RT-PCR detected preferential expression of both ABCB5-alpha and -beta in melanomas, with no expression in normal uterus, lung, or placenta. Northern blot analysis detected ABCB5 transcripts of 2.4 to 7.5 kb in melanoma cells, but not in any normal human tissues examined. RT-PCR showed expression of ABCB5-alpha and -beta in normal melanocytes and of ABCB5-beta in retinal pigment epithelial cells.

GENE FUNCTION

Frank et al. (2003) found that ABCB5, like ABCB1, induced rhodamine efflux in transfected breast cancer cell lines. ABCB5 was highly expressed in mono- and multinucleated human epidermal melanocytes with a CD133 (PROM1; 604365)-positive progenitor phenotype. Frank et al. (2003) showed that polyploid ABCB5-positive cells were generated by cell fusion, and this process was specifically enhanced by ABCB5 blockade. Multinucleated cell hybrids gave rise to mononucleated progeny, demonstrating that fusion contributed to culture growth and differentiation. Frank et al. (2005) showed that ABCB5 was expressed in clinical malignant melanomas and preferentially marked a subset of hyperpolarized tumor cells with a CD133-positive stem cell phenotype in malignant melanoma cultures and clinical melanomas. Blocking ABCB5 with anti-ABCB5 monoclonal antibody reversed doxorubicin resistance in a melanoma cell line and increased intracellular doxorubicin accumulation, indicating that ABCB5-mediated efflux was the mechanism of doxorubicin resistance in these cells. Expression of ABCB5 in a cancer cell line panel correlated significantly with tumor resistance to doxorubicin. Schatton et al. (2008) identified a subpopulation of tumor-initiating cells enriched for human malignant melanoma-initiating cells (MMIC) defined by expression of t ... More on the omim web site

Subscribe to this protein entry history

April 10, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).

Oct. 19, 2018: Protein entry updated
Automatic update: OMIM entry 611785 was added.