Q2M3G0 (ABCB5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
ATP-binding cassette sub-family B member 5

Alternative name(s):
ABCB5 P-gp
P-glycoprotein ABCB5

Gene names

Name:

ABCB5

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	812 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Plasma membrane transporter able to mediate efflux from cells of the rhodamine dye and of the therapeutic drug doxorubicin. Responsible for the resistance to doxorubicin of a subset of malignant melanomas. Ref.1 Ref.8 Ref.9
Subcellular location	Cell membrane; Multi-pass membrane protein Ref.1.
Tissue specificity	Expressed by CD133-expressing progenitor cells among epidermal melanocytes (at protein level). Widely expressed with specific expression in pigment cells. Also expressed in several malignant tissues. Ref.1 Ref.2
Miscellaneous	Depletion of ABCB5 by RNAi increases the sensitivity to several drugs of a subset of melanoma cells.
Sequence similarities	Belongs to the ABC transporter superfamily. ABCB family. Multidrug resistance exporter (TC 3.A.1.201) subfamily. [View classification] Contains 1 ABC transmembrane type-1 domain. Contains 2 ABC transporter domains.
Caution	Was named ABCB1 by some authors.
Sequence caution	The sequence AAN76500.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence AAQ03033.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Biological process	Transport
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat Transmembrane Transmembrane helix
Ligand	ATP-binding Nucleotide-binding
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	regulation of membrane potential Inferred from direct assay Ref.1. Source: UniProtKB
Cellular_component	Golgi membrane Inferred from Biological aspect of Ancestor. Source: RefGenome apical plasma membrane Inferred from Biological aspect of Ancestor. Source: RefGenome integral to plasma membrane Inferred from direct assay Ref.1. Source: UniProtKB intercellular canaliculus Inferred from Biological aspect of Ancestor. Source: RefGenome
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW ATPase activity, coupled to transmembrane movement of substances Inferred from Biological aspect of Ancestor. Source: RefGenome efflux transmembrane transporter activity Inferred from direct assay Ref.1. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q2M3G0-1)

Also known as: ABCB5beta;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q2M3G0-2)

Also known as: ABCB5alpha;

The sequence of this isoform differs from the canonical sequence as follows:
     125-131: ASKGRTT → DTPRYSF
     132-812: Missing.

Isoform 3 (identifier: Q2M3G0-3)

The sequence of this isoform differs from the canonical sequence as follows:
     125-126: AS → KK
     127-812: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 812	812	ATP-binding cassette sub-family B member 5		PRO_0000253575
Regions
	Topological domain	1 – 247	247	Extracellular Potential
	Transmembrane	248 – 268	21	Helical; Potential
	Topological domain	269 – 291	23	Cytoplasmic Potential
	Transmembrane	292 – 312	21	Helical; Potential
	Topological domain	313 – 381	69	Extracellular Potential
	Transmembrane	382 – 402	21	Helical; Potential
	Topological domain	403 – 471	69	Cytoplasmic Potential
	Transmembrane	472 – 492	21	Helical; Potential
	Topological domain	493 – 508	16	Extracellular Potential
	Transmembrane	509 – 529	21	Helical; Potential
	Topological domain	530 – 812	283	Cytoplasmic Potential
	Domain	2 – 177	176	ABC transporter 1
	Domain	247 – 535	289	ABC transmembrane type-1
	Domain	570 – 808	239	ABC transporter 2
	Nucleotide binding	605 – 612	8	ATP Potential
Natural variations
	Alternative sequence	125 – 131	7	ASKGRTT → DTPRYSF in isoform 2.		VSP_021075
	Alternative sequence	125 – 126	2	AS → KK in isoform 3.		VSP_045489
	Alternative sequence	127 – 812	686	Missing in isoform 3.		VSP_045490
	Alternative sequence	132 – 812	681	Missing in isoform 2.		VSP_021076
	Natural variant	115	1	K → E. Ref.2 Corresponds to variant rs2301641 [ dbSNP | Ensembl ].		VAR_028387
	Natural variant	224	1	K → R. Corresponds to variant rs13222448 [ dbSNP | Ensembl ].		VAR_028388
	Natural variant	230	1	E → V in a colorectal cancer sample; somatic mutation. Ref.10		VAR_035731
	Natural variant	435	1	A → T in a pancreatic ductal adenocarcinoma sample; somatic mutation. Ref.11		VAR_062662
	Natural variant	460	1	Q → H. Corresponds to variant rs35885925 [ dbSNP | Ensembl ].		VAR_033456
	Natural variant	470	1	A → T. Corresponds to variant rs17143304 [ dbSNP | Ensembl ].		VAR_028389
	Natural variant	525	1	E → K. Ref.1 Ref.2 Ref.6 Corresponds to variant rs6461515 [ dbSNP | Ensembl ].		VAR_028390
Experimental info
	Sequence conflict	132	1	I → M in AAN76500. Ref.1
	Sequence conflict	696	1	L → P in AAW31630. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (ABCB5beta) [UniParc]. Last modified October 5, 2010. Version 3. Checksum: 588E5F90AE305BE5	FASTA	812	89,832
	10 20 30 40 50 60 MVDENDIRAL NVRHYRDHIG VVSQEPVLFG TTISNNIKYG RDDVTDEEME RAAREANAYD 70 80 90 100 110 120 FIMEFPNKFN TLVGEKGAQM SGGQKQRIAI ARALVRNPKI LILDEATSAL DSESKSAVQA 130 140 150 160 170 180 ALEKASKGRT TIVVAHRLST IRSADLIVTL KDGMLAEKGA HAELMAKRGL YYSLVMSQDI 190 200 210 220 230 240 KKADEQMESM TYSTERKTNS LPLHSVKSIK SDFIDKAEES TQSKEISLPE VSLLKILKLN 250 260 270 280 290 300 KPEWPFVVLG TLASVLNGTV HPVFSIIFAK IITMFGNNDK TTLKHDAEIY SMIFVILGVI 310 320 330 340 350 360 CFVSYFMQGL FYGRAGEILT MRLRHLAFKA MLYQDIAWFD EKENSTGGLT TILAIDIAQI 370 380 390 400 410 420 QGATGSRIGV LTQNATNMGL SVIISFIYGW EMTFLILSIA PVLAVTGMIE TAAMTGFANK 430 440 450 460 470 480 DKQELKHAGK IATEALENIR TIVSLTREKA FEQMYEEMLQ TQHRNTSKKA QIIGSCYAFS 490 500 510 520 530 540 HAFIYFAYAA GFRFGAYLIQ AGRMTPEGMF IVFTAIAYGA MAIGETLVLA PEYSKAKSGA 550 560 570 580 590 600 AHLFALLEKK PNIDSRSQEG KKPDTCEGNL EFREVSFFYP CRPDVFILRG LSLSIERGKT 610 620 630 640 650 660 VAFVGSSGCG KSTSVQLLQR LYDPVQGQVL FDGVDAKELN VQWLRSQIAI VPQEPVLFNC 670 680 690 700 710 720 SIAENIAYGD NSRVVPLDEI KEAANAANIH SFIEGLPEKY NTQVGLKGAQ LSGGQKQRLA 730 740 750 760 770 780 IARALLQKPK ILLLDEATSA LDNDSEKVVQ HALDKARTGR TCLVVTHRLS AIQNADLIVV 790 800 810 LHNGKIKEQG THQELLRNRD IYFKLVNAQS VQ
	Isoform 2 (ABCB5alpha) [UniParc]. Checksum: 4F8BD88320C5CABE	FASTA	131	14,691
	10 20 30 40 50 60 MVDENDIRAL NVRHYRDHIG VVSQEPVLFG TTISNNIKYG RDDVTDEEME RAAREANAYD 70 80 90 100 110 120 FIMEFPNKFN TLVGEKGAQM SGGQKQRIAI ARALVRNPKI LILDEATSAL DSESKSAVQA 130 ALEKDTPRYS F
	Isoform 3 [UniParc]. Checksum: 37532E3C168CE6FA	FASTA	126	14,081
	10 20 30 40 50 60 MVDENDIRAL NVRHYRDHIG VVSQEPVLFG TTISNNIKYG RDDVTDEEME RAAREANAYD 70 80 90 100 110 120 FIMEFPNKFN TLVGEKGAQM SGGQKQRIAI ARALVRNPKI LILDEATSAL DSESKSAVQA ALEKKK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Regulation of progenitor cell fusion by ABCB5 P-glycoprotein, a novel human ATP-binding cassette transporter." Frank N.Y., Pendse S.S., Lapchak P.H., Margaryan A., Shlain D., Doeing C., Sayegh M.H., Frank M.H. J. Biol. Chem. 278:47156-47165(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, TOPOLOGY, TISSUE SPECIFICITY, VARIANT LYS-525. Tissue: Melanocyte and Melanoma.
[2]	"Principal 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 K.G., Szakacs G., Annereau J.-P., Rouzaud F., Liang X.-J., Valencia J.C., Nagineni C.N., Hooks J.J., Hearing V.J., Gottesman M.M. Pigment Cell Res. 18:102-112(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), VARIANTS GLU-115 AND LYS-525, TISSUE SPECIFICITY. Tissue: Melanoma.
[3]	"ABCB5 identifies a therapy-refractory tumor cell population in colorectal cancer patients." Wilson B.J., Schatton T., Zhan Q., Gasser M., Ma J., Saab K.R., Schanche R., Waaga-Gasser A.M., Gold J.S., Huang Q., Murphy G.F., Frank M.H., Frank N.Y. Cancer Res. 71:5307-5316(2011) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Colon adenocarcinoma.
[4]	"The DNA sequence of human chromosome 7." Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K. Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"Human chromosome 7: DNA sequence and biology." Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S. , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C. Science 300:767-772(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT LYS-525.
[7]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3). Tissue: Melanoma.
[8]	"Membrane transporters and channels: role of the transportome in cancer chemosensitivity and chemoresistance." Huang Y., Anderle P., Bussey K.J., Barbacioru C., Shankavaram U., Dai Z., Reinhold W.C., Papp A., Weinstein J.N., Sadee W. Cancer Res. 64:4294-4301(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[9]	"ABCB5-mediated doxorubicin transport and chemoresistance in human malignant melanoma." Frank N.Y., Margaryan A., Huang Y., Schatton T., Waaga-Gasser A.M., Gasser M., Sayegh M.H., Sadee W., Frank M.H. Cancer Res. 65:4320-4333(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[10]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] VAL-230.
[11]	"Core signaling pathways in human pancreatic cancers revealed by global genomic analyses." Jones S., Zhang X., Parsons D.W., Lin J.C., Leary R.J., Angenendt P., Mankoo P., Carter H., Kamiyama H., Jimeno A., Hong S.M., Fu B., Lin M.T., Calhoun E.S., Kamiyama M., Walter K., Nikolskaya T., Nikolsky Y. , Hartigan J., Smith D.R., Hidalgo M., Leach S.D., Klein A.P., Jaffee E.M., Goggins M., Maitra A., Iacobuzio-Donahue C., Eshleman J.R., Kern S.E., Hruban R.H., Karchin R., Papadopoulos N., Parmigiani G., Vogelstein B., Velculescu V.E., Kinzler K.W. Science 321:1801-1806(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] THR-435.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF319622 mRNA. Translation: AAN76500.1. Different initiation. AF399931 mRNA. Translation: AAQ03033.1. Different initiation. AY090613 mRNA. Translation: AAM09027.1. AY234788 mRNA. Translation: AAO73470.1. AY851364 mRNA. Translation: AAW31629.1. AY851365 mRNA. Translation: AAW31630.1. GU437216 mRNA. Translation: ADV32636.1. AC002486 Genomic DNA. No translation available. AC005060 Genomic DNA. No translation available. CH236948 Genomic DNA. Translation: EAL24273.1. CH471073 Genomic DNA. Translation: EAW93726.1. BC104894 mRNA. Translation: AAI04895.2. BC104920 mRNA. Translation: AAI04921.1. BC110370 mRNA. No translation available.
IPI	IPI00746222. IPI00747550. IPI00892563.
RefSeq	NP_001157413.1. NM_001163941.1. NP_001157414.1. NM_001163942.1. NP_001157465.1. NM_001163993.1. NP_848654.3. NM_178559.5.
UniGene	Hs.404102.
3D structure databases
HSSP	HSSP built from PDB template 2GHI based on UniProtKB Q7RBT4.
ProteinModelPortal	Q2M3G0.
SMR	Q2M3G0. Positions 2-197, 203-811.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q2M3G0. 1 interaction.
PTM databases
PhosphoSite	Q2M3G0.
Polymorphism databases
DMDM	308153645.
Proteomic databases
PaxDb	Q2M3G0.
PRIDE	Q2M3G0.
Protocols and materials databases
DNASU	340273.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000258738; ENSP00000258738; ENSG00000004846. ENST00000406935; ENSP00000383899; ENSG00000004846. ENST00000443026; ENSP00000406730; ENSG00000004846.
GeneID	340273.
KEGG	hsa:340273.
UCSC	uc003suv.4. human. uc003suw.4. human.
Organism-specific databases
CTD	340273.
GeneCards	GC07P020653.
H-InvDB	HIX0025281.
HGNC	HGNC:46. ABCB5.
HPA	HPA026975.
MIM	611785. gene.
neXtProt	NX_Q2M3G0.
PharmGKB	PA24387.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1132.
HOVERGEN	HBG080809.
InParanoid	Q2M3G0.
KO	K05660.
OrthoDB	EOG4WWRHP.
PhylomeDB	Q2M3G0.
Enzyme and pathway databases
Reactome	REACT_15518. Transmembrane transport of small molecules.
Gene expression databases
ArrayExpress	Q2M3G0.
Bgee	Q2M3G0.
CleanEx	HS_ABCB5.
Genevestigator	Q2M3G0.
GermOnline	ENSG00000004846. Homo sapiens.
Family and domain databases
InterPro	IPR003593. AAA+_ATPase. IPR003439. ABC_transporter-like. IPR017871. ABC_transporter_CS. IPR017940. ABC_transporter_type1. IPR001140. ABC_transptr_TM_dom. IPR011527. ABC_transptrTM_dom_typ1. [Graphical view]
Pfam	PF00664. ABC_membrane. 1 hit. PF00005. ABC_tran. 2 hits. [Graphical view]
SMART	SM00382. AAA. 2 hits. [Graphical view]
SUPFAM	SSF90123. ABC_TM_1. 1 hit.
PROSITE	PS50929. ABC_TM1F. 1 hit. PS00211. ABC_TRANSPORTER_1. 2 hits. PS50893. ABC_TRANSPORTER_2. 2 hits. [Graphical view]
ProtoNet	Search...
Other
ChEMBL	CHEMBL1772928.
GenomeRNAi	340273.
NextBio	97792.
SOURCE	Search...

Entry information

Entry name

ABCB5_HUMAN

Accession

Primary (citable) accession number: Q2M3G0
Secondary accession number(s): A4D131 , B5MD19, B7WPL1, F8QQP8, Q2M3I5, Q5I5Q7, Q5I5Q8, Q6KG50, Q6XFQ5, Q8IXA1

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 17, 2006
Last sequence update:	October 5, 2010
Last modified:	May 1, 2013
This is version 73 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.