Reviewed,
UniProtKB/Swiss-Prot Q9UNQ0 (ABCG2_HUMAN)
Last modified
June 16, 2009.
Version 97.
History...
Clusters with 100%,
90%,
50% identity |
Documents (6) |
Third-party data |
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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 |
| ||||
| 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. Ref.7 |
| Subunit structure | |
| Subcellular location | |
| Tissue specificity | Highly expressed in placenta. Low expression in small intestine, liver and colon. Ref.1 Ref.2 |
| 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 transmembrane type-2 domain. Contains 1 ABC transporter domain. |
| Sequence caution | The sequence AF093771 differs from that shown. Reason: Frameshift at positions 486 and 586. The sequence AF093772 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 | Disulfide bond Glycoprotein |
| Gene Ontology (GO) | |
| Biological process | response to drug Ref.2 Traceable author statement. Source: ProtInc transport Ref.1Traceable author statement. Source: ProtInc |
| Cellular component | integral to membrane Ref.1 Traceable author statement. Source: ProtInc plasma membraneInferred from electronic annotation. Source: UniProtKB-SubCell |
| Molecular function | ATP binding Ref.1 Traceable author statement. Source: ProtInc protein homodimerization activityInferred from direct assay. Source: UniProtKB xenobiotic-transporting ATPase activity Ref.2Traceable author statement. Source: ProtInc |
| Complete GO annotation... | |
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. | ||||||
| Note: No experimental confirmation available. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||||
Molecule processing | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 655 | 655 | ATP-binding cassette sub-family G member 2 | PRO_0000093386 | |||||||
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 | ||||||||
| Domain | 389 – 651 | 263 | ABC transmembrane type-2 | ||||||||
| 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...) Ref.15 | ||||||||
| Disulfide bond | 592 ↔ 608 | Ref.18 | |||||||||
| Disulfide bond | 603 | Interchain Ref.18 | |||||||||
Natural variations | |||||||||||
| Alternative sequence | 550 – 611 | 62 | IFSGL…TCTGE → VCWSISQPLHLGCHGFSTSA FHDMDLRLCSIMNFWDKTSA QDSMQQETILVTMQHVLAKN IW in isoform 2. | VSP_014232 | |||||||
| Alternative sequence | 612 – 655 | 44 | Missing in isoform 2. | VSP_014233 | |||||||
| Natural variant | 12 | 1 | V → M: dbSNP rs2231137. Ref.11 Ref.19 Ref.21 Ref.22 | VAR_020779 | |||||||
| Natural variant | 141 | 1 | Q → K Lower transport efficiency. dbSNP rs2231142. Ref.11 Ref.19 Ref.21 Ref.22 Ref.8 Ref.12 | VAR_020780 | |||||||
| Natural variant | 166 | 1 | Q → E: dbSNP rs1061017. Ref.7 Ref.1 | VAR_022704 | |||||||
| Natural variant | 206 | 1 | I → L Ref.21 | VAR_022705 | |||||||
| Natural variant | 208 | 1 | F → S: dbSNP rs1061018. Ref.7 Ref.1 | VAR_022706 | |||||||
| Natural variant | 248 | 1 | S → P: dbSNP rs3116448. | VAR_022707 | |||||||
| Natural variant | 296 | 1 | D → H Ref.11 | VAR_030357 | |||||||
| Natural variant | 316 | 1 | T → P Ref.9 | VAR_022443 | |||||||
| Natural variant | 431 | 1 | F → L Ref.20 | VAR_018349 | |||||||
| Natural variant | 489 | 1 | F → L Ref.20 | VAR_018350 | |||||||
| Natural variant | 528 | 1 | A → T Ref.11 | VAR_030358 | |||||||
| Natural variant | 571 | 1 | F → I: dbSNP rs9282571. | VAR_022708 | |||||||
| Natural variant | 590 | 1 | N → Y Ref.21 | VAR_035355 | |||||||
| Natural variant | 620 | 1 | D → N Ref.22 | VAR_022709 | |||||||
Experimental info | |||||||||||
| Mutagenesis | 86 | 1 | K → M: Inactive and altered subcellular location. Ref.17 | ||||||||
| Mutagenesis | 418 | 1 | N → Q: No effect. Ref.15 | ||||||||
| Mutagenesis | 482 | 1 | R → D: Decreases ATPase activity. Ref.16 | ||||||||
| Mutagenesis | 482 | 1 | R → G, N, S or T: Increases ATPase activity. Ref.16 | ||||||||
| Mutagenesis | 482 | 1 | R → K, I, M or Y: No change in ATPase activity. Ref.16 | ||||||||
| Mutagenesis | 482 | 1 | R → T or Y: Decreases transport activity. Ref.16 | ||||||||
| Mutagenesis | 557 | 1 | N → Q: No effect. Ref.15 | ||||||||
| Mutagenesis | 596 | 1 | N → Q: Loss of glycosylation. Ref.15 | ||||||||
| 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.10 | ||||||||
| Sequence conflict | 390 | 1 | G → V in AAH92408. Ref.12 | ||||||||
| Sequence conflict | 482 | 1 | R → G in AF093771. Ref.13 | ||||||||
| Sequence conflict | 482 | 1 | R → G in 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
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References
| « Hide '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] | "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. Sugano S.Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Hippocampus and Placenta. |
| [11] | SeattleSNPs variation discovery resource 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. |
| [12] | "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. |
| [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] | "Intramolecular disulfide bond is a critical check point determining degradative fates of ATP-binding cassette (ABC) transporter ABCG2 protein." Wakabayashi K., Nakagawa H., Tamura A., Koshiba S., Hoshijima K., Komada M., Ishikawa T. J. Biol. Chem. 282:27841-27846(2007) [PubMed: 17686774] [Abstract] Cited for: SUBUNIT, DISULFIDE BONDS. |
| [19] | "Catalog of 605 single-nucleotide polymorphisms (SNPs) among 13 genes encoding human ATP-binding cassette transporters: ABCA4, ABCA7, ABCA8, ABCD1, ABCD3, ABCD4, ABCE1, ABCF1, ABCG1, ABCG2, ABCG4, ABCG5, and ABCG8." Iida A., Saito S., Sekine A., Mishima C., Kitamura Y., Kondo K., Harigae S., Osawa S., Nakamura Y. J. Hum. Genet. 47:285-310(2002) [PubMed: 12111378] [Abstract] Cited for: VARIANTS MET-12 AND LYS-141. |
| [20] | "Eight novel single nucleotide polymorphisms in ABCG2/BCRP in Japanese cancer patients administered irinotacan." Itoda M., Saito Y., Shirao K., Minami H., Ohtsu A., Yoshida T., Saijo N., Suzuki H., Sugiyama Y., Ozawa S., Sawada J. Drug Metab. Pharmacokinet. 18:212-217(2003) [PubMed: 15618737] [Abstract] Cited for: VARIANTS LEU-431 AND LEU-489. |
| [21] | "Natural allelic variants of breast cancer resistance protein (BCRP) and their relationship to BCRP expression in human intestine." Zamber C.P., Lamba J.K., Yasuda K., Farnum J., Thummel K., Schuetz J.D., Schuetz E.G. Pharmacogenetics 13:19-28(2003) [PubMed: 12544509] [Abstract] Cited for: VARIANTS MET-12; LYS-141; LEU-206 AND TYR-590. |
| [22] | "Single nucleotide polymorphisms modify the transporter activity of ABCG2." Morisaki K., Robey R.W., Oezvegy-Laczka C., Honjo Y., Polgar O., Steadman K., Sarkadi B., Bates S.E. Cancer Chemother. Pharmacol. 56:161-172(2005) [PubMed: 15838659] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS MET-12; LYS-141 AND ASN-620. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| AF103796 mRNA. Translation: AAD09188.1. AF098951 mRNA. Translation: AAC97367.1. AB056867 mRNA. Translation: BAB39212.1. AB051855 mRNA. Translation: BAB46933.1. AY017168 mRNA. Translation: AAG52982.1. AY289766 mRNA. Translation: AAP44087.1. AY288307 mRNA. Translation: AAP31310.1. AF463519 mRNA. Translation: AAO14617.1. AY333755 mRNA. Translation: AAQ92941.1. AY333756 mRNA. Translation: AAQ92942.1. AK002040 mRNA. Translation: BAA92050.1. AK290000 mRNA. Translation: BAF82689.1. DQ996467 Genomic DNA. Translation: ABI97388.1. BC021281 mRNA. Translation: AAH21281.1. BC092408 mRNA. Translation: AAH92408.1. AF093771 mRNA. No translation available. AF093772 mRNA. No translation available. | |
| IPI | IPI00298214. IPI00607625. |
| RefSeq | NP_004818.2. |
| UniGene | Hs.480218 |
3D structure databases | |
| ModBase | Search... |
Protein-protein interaction databases | |
| DIP | DIP:29162N. |
| IntAct | Q9UNQ0. 2 interactions. |
Protein family/group databases | |
| TCDB | 3.A.1.204.3. ATP-binding cassette (ABC) superfamily. |
PTM databases | |
| PhosphoSite | Q9UNQ0. |
Proteomic databases | |
| PRIDE | Q9UNQ0. |
Genome annotation databases | |
| Ensembl | ENSG00000118777. Homo sapiens. [Contig view] |
| GeneID | 9429. |
| KEGG | hsa:9429. |
Organism-specific databases | |
| GeneCards | GC04M089314. |
| H-InvDB | HIX0019250. |
| HGNC | HGNC:74. ABCG2. |
| MIM | 603756. gene. |
| PharmGKB | PA390. |
| GenAtlas | Search... |
Phylogenomic databases | |
| HOVERGEN | Q9UNQ0. |
| OMA | Q9UNQ0. AQIIVTV. |
Enzyme and pathway databases | |
| Pathway_Interaction_DB | hif1_tfpathway. HIF-1-alpha transcription factor network. |
Gene expression databases | |
| ArrayExpress | Q9UNQ0. |
| Bgee | Q9UNQ0. |
| GermOnline | ENSG00000118777. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR013525. ABC_2_trans. IPR003439. ABC_transporter-like. IPR017871. ABC_transporter_CS. IPR003593. ATPase_AAA+_core. [Graphical view] |
| Pfam | PF01061. ABC2_membrane. 1 hit. PF00005. ABC_tran. 1 hit. [Graphical view] |
| ProDom | PD000006. ABC_transporter. 1 hit. [Graphical view] [Entries sharing at least one domain] |
| SMART | SM00382. AAA. 1 hit. [Graphical view] |
| PROSITE | PS51012. ABC_TM2. False negative. PS00211. ABC_TRANSPORTER_1. False negative. PS50893. ABC_TRANSPORTER_2. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other Resources | |
| DrugBank | DB00619. Imatinib. DB01204. Mitoxantrone. DB00622. Nicardipine. DB01054. Nitrendipine. DB01098. Rosuvastatin. DB01232. Saquinavir. DB01030. Topotecan. |
| NextBio | 35322. |
| SOURCE | Search... |
Entry information
| Entry name | ABCG2_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q9UNQ0 Secondary accession number(s): A0A1W3 Q9NUS0 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| Human cell differentiation molecules CD nomenclature of surface proteins of human leucocytes and list of entries |
| Human chromosome 4 Human chromosome 4: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with


