ABCB5 (ATP-binding cassette, sub-family B (MDR/TAP), member 5)

2009-07-01   Xiang Jiao , Tobias Sjöblom 

Department of Genetics, Pathology, Uppsala University, Uppsala, Sweden

Identity

HGNC
LOCATION
7p21.1
LOCUSID
ALIAS
ABCB5alpha,ABCB5beta,EST422562
FUSION GENES

DNA/RNA

Atlas Image
ABCB5 gene on chromosome 7p.

Description

The gene encompasses 108081 bp of DNA with 19 exons.

Transcription

ABCB5 encodes a 2784 bp mRNA. The coding region consists of exon 4-19, while exon 1-3 and 3 part of exon 19 are non-coding.

Proteins

Description

Only 2 isoforms, ABCB5alpha and ABCB5beta have been studied so far. ABCB5 P-gp (isoform 1, also known as ABCB5beta) contains 812 amino acids (P-gp is short for "permeability glycoprotein"). ABCB5alpha contains only 131 amino acids.

Expression

ABCB5 is reported to be expressed in many different tissues, including brain, intestine, kidney, mammary gland, testis and skin. Besides, ABCB5 has a significantly higher expression level in malignant melanomas than in benign melanocytes.

Localisation

ABCB5 P-gp is located in the plasma membrane, with 5 transmembrane helices flanked by both extracellular and intracellular ATP-binding domains.

Function

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. ABCB5 mediates melanoma doxorubicin resistance via its function as a doxorubicin efflux transporter. In addition, ABCB5 P-gp can regulate progenitor cell fusion. However, ABCB5alpha alone may be non-functional.

Homology

ABCB5 shares 54% and 56% amino acid identity with ABCB1 and ABCB4, respectively.

Implicated in

Entity name
Malignant melanoma
Note
Tissue microarray showed that primary and metastatic malignant melanomas expressed significantly more ABCB5 protein than benign melanocytic nevi, thick primary melanomas more than thin primary melanomas, and melanomas metastatic to lymph nodes more than primary lesions. Melanoma cell subpopulations identified by expression of ABCB5 were enriched for human malignant-melanoma-initiating cells (MMIC). Besides, ABCB5 also mediates chemoresistance in human malignant melanoma.
Entity name
Chemoresistance in human malignant melanoma
Oncogenesis
ABCB5 P-gp mediates melanoma doxorubicin resistance via its function as a doxorubicin efflux transporter.

Bibliography

Pubmed IDLast YearTitleAuthors
157603392005Principal expression of two mRNA isoforms (ABCB 5alpha and ABCB 5beta ) of the ATP-binding cassette transporter gene ABCB 5 in melanoma cells and melanocytes.Chen KG et al
114353972001The human ATP-binding cassette (ABC) transporter superfamily.Dean M et al
158998242005ABCB5-mediated doxorubicin transport and chemoresistance in human malignant melanoma.Frank NY et al
129601492003Regulation of progenitor cell fusion by ABCB5 P-glycoprotein, a novel human ATP-binding cassette transporter.Frank NY et al
182026602008Identification of cells initiating human melanomas.Schatton T et al

Other Information

Locus ID:

NCBI: 340273
MIM: 611785
HGNC: 46
Ensembl: ENSG00000004846

Variants:

dbSNP: 340273
ClinVar: 340273
TCGA: ENSG00000004846
COSMIC: ABCB5

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000004846ENST00000258738Q2M3G0
ENSG00000004846ENST00000404938Q2M3G0
ENSG00000004846ENST00000406935Q2M3G0
ENSG00000004846ENST00000441315H7C165
ENSG00000004846ENST00000443026Q2M3G0
ENSG00000004846ENST00000443026A0A024RA03

Expression (GTEx)

0
1

Pathways

PathwaySourceExternal ID
ABC transportersKEGGko02010
ABC transportersKEGGhsa02010
Transmembrane transport of small moleculesREACTOMER-HSA-382551
ABC-family proteins mediated transportREACTOMER-HSA-382556

PharmGKB

Entity IDNameTypeEvidenceAssociationPKPDPMIDs
PA447215Psychotic DisordersDiseaseClinicalAnnotationassociatedPD25647612
PA449841haloperidolChemicalClinicalAnnotation, MultilinkAnnotationassociatedPD25647612, 27023437

References

Pubmed IDYearTitleCitations
212124112011VEGFR-1 expressed by malignant melanoma-initiating cells is required for tumor growth.64
206823182011Granulin-epithelin precursor and ATP-dependent binding cassette (ABC)B5 regulate liver cancer cell chemoresistance.49
228654552012CD133+ melanoma subpopulations contribute to perivascular niche morphogenesis and tumorigenicity through vasculogenic mimicry.42
207299122010Tenascin-C promotes melanoma progression by maintaining the ABCB5-positive side population.41
209507862010A genome-wide study reveals copy number variants exclusive to childhood obesity cases.41
256894832015The c-MYC-ABCB5 axis plays a pivotal role in 5-fluorouracil resistance in human colon cancer cells.20
223930602012The helicase HAGE expressed by malignant melanoma-initiating cells is required for tumor cell proliferation in vivo.15
245257372014The helicase HAGE prevents interferon-α-induced PML expression in ABCB5+ malignant melanoma-initiating cells by promoting the expression of SOCS1.9
254497862015CD133⁺ melanoma subpopulation acquired resistance to caffeic acid phenethyl ester-induced apoptosis is attributed to the elevated expression of ABCB5: significance for melanoma treatment.8
282819732017ABCB5-ZEB1 Axis Promotes Invasion and Metastasis in Breast Cancer Cells.8

Citation

Xiang Jiao ; Tobias Sjöblom

ABCB5 (ATP-binding cassette, sub-family B (MDR/TAP), member 5)

Atlas Genet Cytogenet Oncol Haematol. 2009-07-01

Online version: http://atlasgeneticsoncology.org/gene/44305/abcb5