Reviewed, UniProtKB/Swiss-Prot Q9UNQ0 (ABCG2_HUMAN)

Names and origin

Protein names

Recommended name:
    ATP-binding cassette sub-family G member 2
Alternative name(s):
    Placenta-specific ATP-binding cassette transporter
    Breast cancer resistance protein
    Mitoxantrone resistance-associated protein
    CDw338
    CD_antigen=CD338

Gene names

Name:	ABCG2
Synonyms:	ABCP, BCRP, BCRP1, MXR

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	655 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Xenobiotic transporter that may play an important role in the exclusion of xenobiotics from the brain. May be involved in brain-to-blood efflux. Appears to play a major role in the multidrug resistance phenotype of several cancer cell lines. When overexpressed, the transfected cells become resistant to mitoxantrone, daunorubicin and doxorubicin, display diminished intracellular accumulation of daunorubicin, and manifest an ATP-dependent increase in the efflux of rhodamine 123.
Subunit structure	Monomer or homodimer; disulfide-linked.
Subcellular location	Cell membrane; Multi-pass membrane protein.
Tissue specificity	Highly expressed in placenta. Low expression in small intestine, liver and colon.
Induction	Up-regulated in brain tumors.
Post-translational modification	Glycosylation-deficient ABCG2 is normally expressed and functional.
Sequence similarities	Belongs to the ABC transporter family. ABCG (White) subfamily. Contains 1 ABC transporter domain.
Sequence caution	AF093771 sequence differs from that shown. Reason: Frameshift at positions 486 and 586. AF093772 sequence differs from that shown. Reason: Frameshift at positions 386, 502 and 586.

Ontologies

Keywords
Biological process	Transport
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transmembrane
Ligand	ATP-binding Nucleotide-binding
PTM	Glycoprotein
Gene Ontology (GO)
Biological process	response to drug Ref.2 Traceable author statement. Source: ProtInc transport Ref.1 Traceable author statement. Source: ProtInc
Cellular component	integral to membrane Ref.1 Traceable author statement. Source: ProtInc
Molecular function	ATP binding Ref.1 Traceable author statement. Source: ProtInc protein homodimerization activity Inferred from direct assay. Source: UniProtKB xenobiotic-transporting ATPase activity Ref.2 Traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
PIM1	P11309-1	7	EBI-1569435,EBI-1018629

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9UNQ0-1)

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: Q9UNQ0-2)

The sequence of this isoform differs from the canonical sequence as follows:
     550-611: IFSGLLVNLT...PCNYATCTGE → VCWSISQPLH...MQHVLAKNIW
     612-655: Missing.

Notes: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view
Molecule processing
	Chain	1 – 655	655	ATP-binding cassette sub-family G member 2
Regions
	Topological domain	1 – 395	395	Cytoplasmic Potential
	Transmembrane	396 – 416	21	Potential
	Topological domain	417 – 428	12	Extracellular Potential
	Transmembrane	429 – 449	21	Potential
	Topological domain	450 – 477	28	Cytoplasmic Potential
	Transmembrane	478 – 498	21	Potential
	Topological domain	499 – 506	8	Extracellular Potential
	Transmembrane	507 – 527	21	Potential
	Topological domain	528 – 535	8	Cytoplasmic Potential
	Transmembrane	536 – 556	21	Potential
	Topological domain	557 – 630	74	Extracellular Potential
	Transmembrane	631 – 651	21	Potential
	Topological domain	652 – 655	4	Cytoplasmic Potential
	Domain	37 – 286	250	ABC transporter
	Nucleotide binding	80 – 87	8	ATP Potential
Sites
	Site	418	1	Not glycosylated
	Site	557	1	Not glycosylated
Amino acid modifications
	Glycosylation	596	1	N-linked (GlcNAc...)
	Disulfide bond	592 ↔ 608
	Disulfide bond	603		Interchain
Natural variations
	Alternative sequence	550 – 611	62	IFSGL…TCTGE → VCWSISQPLHLGCHGFSTSA FHDMDLRLCSIMNFWDKTSA QDSMQQETILVTMQHVLAKN IW in isoform 2.
	Alternative sequence	612 – 655	44	Missing in isoform 2.
	Natural variant	12	1	V → M: dbSNP rs2231137.
	Natural variant	141	1	Q → K Lower transport efficiency. dbSNP rs2231142.
	Natural variant	166	1	Q → E: dbSNP rs1061017.
	Natural variant	206	1	I → L
	Natural variant	208	1	F → S: dbSNP rs1061018.
	Natural variant	248	1	S → P: dbSNP rs3116448.
	Natural variant	296	1	D → H
	Natural variant	316	1	T → P
	Natural variant	431	1	F → L
	Natural variant	489	1	F → L
	Natural variant	528	1	A → T
	Natural variant	571	1	F → I: dbSNP rs9282571.
	Natural variant	590	1	N → Y
	Natural variant	620	1	D → N
Experimental info
	Mutagenesis	86	1	K → M: Inactive and altered subcellular location
	Mutagenesis	418	1	N → Q: No effect
	Mutagenesis	482	1	R → D: Decreases ATPase activity
	Mutagenesis	482	1	R → G, N, S or T: Increases ATPase activity
	Mutagenesis	482	1	R → K, I, M or Y: No change in ATPase activity
	Mutagenesis	482	1	R → T or Y: Decreases transport activity
	Mutagenesis	557	1	N → Q: No effect
	Mutagenesis	596	1	N → Q: Loss of glycosylation
	Sequence conflict	24	1	A → V in AAD09188. Ref.1
	Sequence conflict	24	1	A → V in AAP44087. Ref.7
	Sequence conflict	315 – 316	2	Missing in BAA92050. Ref.12
	Sequence conflict	390	1	G → V in AAH92408. Ref.11
	Sequence conflict	482	1	R → G in AF093771 and AF093772. Ref.13
	Sequence conflict	482	1	R → T in AAC97367. Ref.2
	Sequence conflict	484 – 485	2	LP → FT in AF093772. Ref.13
	Sequence conflict	501	1	P → A in AAG52982. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 10, 2005. Version 3. Checksum: A8AF66B96034C5A8	FASTA	655	72,314
	10 20 30 40 50 60 MSSSNVEVFI PVSQGNTNGF PATASNDLKA FTEGAVLSFH NICYRVKLKS GFLPCRKPVE 70 80 90 100 110 120 KEILSNINGI MKPGLNAILG PTGGGKSSLL DVLAARKDPS GLSGDVLING APRPANFKCN 130 140 150 160 170 180 SGYVVQDDVV MGTLTVRENL QFSAALRLAT TMTNHEKNER INRVIQELGL DKVADSKVGT 190 200 210 220 230 240 QFIRGVSGGE RKRTSIGMEL ITDPSILFLD EPTTGLDSST ANAVLLLLKR MSKQGRTIIF 250 260 270 280 290 300 SIHQPRYSIF KLFDSLTLLA SGRLMFHGPA QEALGYFESA GYHCEAYNNP ADFFLDIING 310 320 330 340 350 360 DSTAVALNRE EDFKATEIIE PSKQDKPLIE KLAEIYVNSS FYKETKAELH QLSGGEKKKK 370 380 390 400 410 420 ITVFKEISYT TSFCHQLRWV SKRSFKNLLG NPQASIAQII VTVVLGLVIG AIYFGLKNDS 430 440 450 460 470 480 TGIQNRAGVL FFLTTNQCFS SVSAVELFVV EKKLFIHEYI SGYYRVSSYF LGKLLSDLLP 490 500 510 520 530 540 MRMLPSIIFT CIVYFMLGLK PKADAFFVMM FTLMMVAYSA SSMALAIAAG QSVVSVATLL 550 560 570 580 590 600 MTICFVFMMI FSGLLVNLTT IASWLSWLQY FSIPRYGFTA LQHNEFLGQN FCPGLNATGN 610 620 630 640 650 NPCNYATCTG EEYLVKQGID LSPWGLWKNH VALACMIVIF LTIAYLKLLF LKKYS
	Isoform 2 [UniParc]. Checksum: 9F831226192A2D39		611	67,453
	10 20 30 40 50 60 MSSSNVEVFI PVSQGNTNGF PATASNDLKA FTEGAVLSFH NICYRVKLKS GFLPCRKPVE 70 80 90 100 110 120 KEILSNINGI MKPGLNAILG PTGGGKSSLL DVLAARKDPS GLSGDVLING APRPANFKCN 130 140 150 160 170 180 SGYVVQDDVV MGTLTVRENL QFSAALRLAT TMTNHEKNER INRVIQELGL DKVADSKVGT 190 200 210 220 230 240 QFIRGVSGGE RKRTSIGMEL ITDPSILFLD EPTTGLDSST ANAVLLLLKR MSKQGRTIIF 250 260 270 280 290 300 SIHQPRYSIF KLFDSLTLLA SGRLMFHGPA QEALGYFESA GYHCEAYNNP ADFFLDIING 310 320 330 340 350 360 DSTAVALNRE EDFKATEIIE PSKQDKPLIE KLAEIYVNSS FYKETKAELH QLSGGEKKKK 370 380 390 400 410 420 ITVFKEISYT TSFCHQLRWV SKRSFKNLLG NPQASIAQII VTVVLGLVIG AIYFGLKNDS 430 440 450 460 470 480 TGIQNRAGVL FFLTTNQCFS SVSAVELFVV EKKLFIHEYI SGYYRVSSYF LGKLLSDLLP 490 500 510 520 530 540 MRMLPSIIFT CIVYFMLGLK PKADAFFVMM FTLMMVAYSA SSMALAIAAG QSVVSVATLL 550 560 570 580 590 600 MTICFVFMMV CWSISQPLHL GCHGFSTSAF HDMDLRLCSI MNFWDKTSAQ DSMQQETILV 610 TMQHVLAKNI W

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A human placenta-specific ATP-binding cassette gene (ABCP) on chromosome 4q22 that is involved in multidrug resistance." Allikmets R., Schriml L.M., Hutchinson A., Romano-Spica V., Dean M. Cancer Res. 58:5337-5339(1998) [PubMed: 9850061] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS GLU-166 AND SER-208, TISSUE SPECIFICITY. Tissue: Placenta.
[2]	"A multidrug resistance transporter from human MCF-7 breast cancer cells." Doyle L.A., Yang W., Abruzzo L.V., Krogmann T., Gao Y., Rishi A.K., Ross D.D. Proc. Natl. Acad. Sci. U.S.A. 95:15665-15670(1998) [PubMed: 9861027] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY. Tissue: Mammary cancer.
[3]	Erratum Doyle L.A., Yang W., Abruzzo L.V., Krogmann T., Gao Y., Rishi A.K., Ross D.D. Proc. Natl. Acad. Sci. U.S.A. 96:2569-2569(1999)
[4]	"Breast cancer resistance protein constitutes a 140-kDa complex as a homodimer." Kage K., Tsukahara S., Sugiyama T., Asada S., Ishikawa E., Tsuruo T., Sugimoto Y. Submitted (MAR-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[5]	"Identification of breast cancer resistant protein/mitoxantrone resistance/placenta-specific, ATP-binding cassette transporter as a transporter of NB-506 and J-107088, topoisomerase I inhibitors with an indolocarbazole structure." Komatani H., Kotani H., Hara Y., Nakagawa R., Matsumoto M., Arakawa H., Nishimura S. Cancer Res. 61:2827-2832(2001) [PubMed: 11306452] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[6]	"The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype." Zhou S., Schuetz J.D., Bunting K.D., Colapietro A.M., Sampath J., Morris J.J., Lagutina I., Grosveld G.C., Osawa M., Nakauchi H., Sorrentino B.P. Nat. Med. 7:1028-1034(2001) [PubMed: 11533706] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[7]	"The expression and functional characterization of ABCG2 in brain endothelial cells and vessels." Zhang W., Mojsilovic-Petrovic J., Andrade M.F., Zhang H., Ball M., Stanimirovic D.B. FASEB J. 17:2085-2087(2003) [PubMed: 12958161] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, VARIANTS GLU-166 AND SER-208. Tissue: Brain endothelium.
[8]	Yoshikawa M., Yabuuchi H., Ikegami Y., Ishikawa T. Submitted (DEC-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT LYS-141.
[9]	"Cell line K562 resistant to Hoechst 33342." Sudarikov A., Makarik T., Andreeff M. Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT PRO-316.
[10]	SeattleSNPs program for genomic applications Submitted (SEP-2006) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS MET-12; LYS-141; HIS-296 AND THR-528.
[11]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), VARIANT LYS-141. Tissue: Pancreas and PNS.
[12]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 198-655 (ISOFORM 1). Tissue: Placenta.
[13]	"Molecular cloning of cDNAs which are highly overexpressed in mitoxantrone-resistant cells: demonstration of homology to ABC transport genes." Miyake K., Mickley L., Litman T., Zhan Z., Robey R.W., Cristensen B., Brangi M., Greenberger L., Dean M., Fojo T., Bates S.E. Cancer Res. 59:8-13(1999) [PubMed: 9892175] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 294-655 (ISOFORM 1).
[14]	"Role of ABCG1 and other ABCG family members in lipid metabolism." Schmitz G., Langmann T., Heimerl S. J. Lipid Res. 42:1513-1520(2001) [PubMed: 11590207] [Abstract] Cited for: REVIEW.
[15]	"N-linked glycosylation of the human ABC transporter ABCG2 on asparagine 596 is not essential for expression, transport activity, or trafficking to the plasma membrane." Diop N.K., Hrycyna C.A. Biochemistry 44:5420-5429(2005) [PubMed: 15807535] [Abstract] Cited for: SUBCELLULAR LOCATION, GLYCOSYLATION AT ASN-596, MUTAGENESIS OF ASN-418; ASN-557 AND ASN-596.
[16]	"Single amino acid (482) variants of the ABCG2 multidrug transporter: major differences in transport capacity and substrate recognition." Oezvegy-Laczka C., Koebloes G., Sarkadi B., Varadi A. Biochim. Biophys. Acta 1668:53-63(2005) [PubMed: 15670731] [Abstract] Cited for: MUTAGENESIS OF ARG-482.
[17]	"Effect of Walker A mutation (K86M) on oligomerization and surface targeting of the multidrug resistance transporter ABCG2." Henriksen U., Gether U., Litman T. J. Cell Sci. 118:1417-1426(2005) [PubMed: 15769853] [Abstract] Cited for: MUTAGENESIS OF LYS-86, SUBCELLULAR LOCATION, HOMODIMERIZATION.
[18]	"I