Reviewed,
UniProtKB/Swiss-Prot Q92887 (MRP2_HUMAN)
Last modified
June 16, 2009.
Version 97.
History...
Clusters with 100%,
90%,
50% identity |
Documents (5) |
Third-party data |
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Names and origin
| Protein names | Recommended name: Canalicular multispecific organic anion transporter 1 Alternative name(s): ATP-binding cassette sub-family C member 2 Multidrug resistance-associated protein 2 Canalicular multidrug resistance protein | ||||
| Gene names |
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| 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 | 1545 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter. |
| Subcellular location | |
| Tissue specificity | Found on the apical membrane of polarized cells in liver, kidney and intestine. The highest expression is found in liver. |
| Involvement in disease | Defects in ABCC2 are the cause of Dubin-Johnson syndrome (DJS) [MIM:237500]. DJS is an autosomal recessive disorder characterized by conjugated hyperbilirubinemia, an increase in the urinary excretion of coproporphyrin isomer I, deposition of melanin-like pigment in hepatocytes, and prolonged retention of sulfobromophthalein, but otherwise normal liver function. Ref.5 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 |
| Sequence similarities | Belongs to the ABC transporter family. Conjugate transporter (TC 3.A.1.208) subfamily. [View classification] Contains 2 ABC transmembrane type-1 domains. Contains 2 ABC transporter domains. |
Ontologies
| Keywords | |
|---|---|
| Biological process | Transport |
| Cellular component | Membrane |
| Coding sequence diversity | Polymorphism |
| Disease | Disease mutation |
| Domain | Repeat Transmembrane |
| Ligand | ATP-binding Nucleotide-binding |
| PTM | Glycoprotein Phosphoprotein |
| Gene Ontology (GO) | |
| Biological process | transport Traceable author statement. Source: ProtInc |
| Cellular component | integral to plasma membrane Traceable author statement. Source: ProtInc |
| Molecular function | ATP binding Inferred from electronic annotation. Source: UniProtKB-KW ATPase activity, coupled to transmembrane movement of substancesTraceable author statement. Source: ProtInc organic anion transmembrane transporter activityTraceable author statement. Source: ProtInc |
| Complete GO annotation... | |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 1545 | 1545 | Canalicular multispecific organic anion transporter 1 | PRO_0000093356 | |||||
Regions | |||||||||
| Topological domain | 1 – 27 | 27 | Extracellular By similarity | ||||||
| Transmembrane | 28 – 48 | 21 | 1 By similarity | ||||||
| Topological domain | 49 – 68 | 20 | Cytoplasmic By similarity | ||||||
| Transmembrane | 69 – 89 | 21 | 2 By similarity | ||||||
| Topological domain | 90 – 93 | 4 | Extracellular By similarity | ||||||
| Transmembrane | 94 – 114 | 21 | 3 By similarity | ||||||
| Topological domain | 115 – 126 | 12 | Cytoplasmic By similarity | ||||||
| Transmembrane | 127 – 147 | 21 | 4 By similarity | ||||||
| Topological domain | 148 – 165 | 18 | Extracellular By similarity | ||||||
| Transmembrane | 166 – 186 | 21 | 5 By similarity | ||||||
| Topological domain | 187 – 313 | 127 | Cytoplasmic By similarity | ||||||
| Transmembrane | 314 – 334 | 21 | 6 By similarity | ||||||
| Topological domain | 335 – 360 | 26 | Extracellular By similarity | ||||||
| Transmembrane | 361 – 381 | 21 | 7 By similarity | ||||||
| Topological domain | 382 – 437 | 56 | Cytoplasmic By similarity | ||||||
| Transmembrane | 438 – 458 | 21 | 8 By similarity | ||||||
| Topological domain | 459 – 461 | 3 | Extracellular By similarity | ||||||
| Transmembrane | 462 – 482 | 21 | 9 By similarity | ||||||
| Topological domain | 483 – 544 | 62 | Cytoplasmic By similarity | ||||||
| Transmembrane | 545 – 565 | 21 | 10 By similarity | ||||||
| Topological domain | 566 – 587 | 22 | Extracellular By similarity | ||||||
| Transmembrane | 588 – 608 | 21 | 11 By similarity | ||||||
| Topological domain | 609 – 971 | 363 | Cytoplasmic By similarity | ||||||
| Transmembrane | 972 – 992 | 21 | 12 By similarity | ||||||
| Topological domain | 993 – 1033 | 41 | Extracellular By similarity | ||||||
| Transmembrane | 1034 – 1054 | 21 | 13 By similarity | ||||||
| Topological domain | 1055 – 1097 | 43 | Cytoplasmic By similarity | ||||||
| Transmembrane | 1098 – 1118 | 21 | 14 By similarity | ||||||
| Topological domain | 1119 | 1 | Extracellular By similarity | ||||||
| Transmembrane | 1120 – 1140 | 21 | 15 By similarity | ||||||
| Topological domain | 1141 – 1211 | 71 | Cytoplasmic By similarity | ||||||
| Transmembrane | 1212 – 1232 | 21 | 16 By similarity | ||||||
| Topological domain | 1233 – 1234 | 2 | Extracellular By similarity | ||||||
| Transmembrane | 1235 – 1255 | 21 | 17 By similarity | ||||||
| Topological domain | 1256 – 1545 | 290 | Cytoplasmic By similarity | ||||||
| Domain | 322 – 605 | 284 | ABC transmembrane type-1 1 | ||||||
| Domain | 637 – 861 | 225 | ABC transporter 1 | ||||||
| Domain | 979 – 1264 | 286 | ABC transmembrane type-1 2 | ||||||
| Domain | 1300 – 1534 | 235 | ABC transporter 2 | ||||||
| Nucleotide binding | 671 – 678 | 8 | ATP 1 Potential | ||||||
| Nucleotide binding | 1334 – 1341 | 8 | ATP 2 Potential | ||||||
Amino acid modifications | |||||||||
| Modified residue | 283 | 1 | Phosphoserine Ref.9 Ref.10 | ||||||
| Modified residue | 878 | 1 | Phosphoserine Ref.10 | ||||||
| Glycosylation | 7 | 1 | N-linked (GlcNAc...) Potential | ||||||
| Glycosylation | 12 | 1 | N-linked (GlcNAc...) Potential | ||||||
| Glycosylation | 1011 | 1 | N-linked (GlcNAc...) Potential | ||||||
Natural variations | |||||||||
| Natural variant | 39 | 1 | F → Y: dbSNP rs927344. Ref.6 | VAR_047152 | |||||
| Natural variant | 246 | 1 | M → L: dbSNP rs45462493. | VAR_029113 | |||||
| Natural variant | 281 | 1 | S → N: dbSNP rs56131651. Ref.14 | VAR_013324 | |||||
| Natural variant | 333 | 1 | D → G: dbSNP rs17222674. | VAR_020226 | |||||
| Natural variant | 353 | 1 | R → H: dbSNP rs7080681. | VAR_020227 | |||||
| Natural variant | 417 | 1 | V → I: dbSNP rs2273697. Ref.14 Ref.15 | VAR_013325 | |||||
| Natural variant | 495 | 1 | K → E: dbSNP rs17222561. | VAR_029115 | |||||
| Natural variant | 562 | 1 | F → L: dbSNP rs17216233. | VAR_029116 | |||||
| Natural variant | 670 | 1 | I → T | VAR_020228 | |||||
| Natural variant | 768 | 1 | R → W in DJS. dbSNP rs56199535. Ref.11 Ref.12 Ref.15 | VAR_000099 | |||||
| Natural variant | 789 | 1 | S → F: dbSNP rs56220353. Ref.15 | VAR_013326 | |||||
| Natural variant | 849 | 1 | L → R: dbSNP rs17222617. | VAR_020229 | |||||
| Natural variant | 982 | 1 | I → V: dbSNP rs17222554. | VAR_029117 | |||||
| Natural variant | 1036 | 1 | I → T: dbSNP rs45441199. | VAR_020230 | |||||
| Natural variant | 1063 | 1 | N → S: dbSNP rs17222540. | VAR_029118 | |||||
| Natural variant | 1150 | 1 | R → H in DJS; protein is properly localized at the plasma membrane, but transport activity is impaired. Ref.14 | VAR_013327 | |||||
| Natural variant | 1173 | 1 | I → F in DJS; low expression and mislocation to the endoplasmic reticulum. Ref.14 | VAR_013328 | |||||
| Natural variant | 1181 | 1 | R → L: dbSNP rs8187692. | VAR_020231 | |||||
| Natural variant | 1188 | 1 | V → E: dbSNP rs17222723. Ref.2 | VAR_020232 | |||||
| Natural variant | 1273 | 1 | T → A: dbSNP rs8187699. | VAR_024360 | |||||
| Natural variant | 1291 | 1 | P → L: dbSNP rs17216317. | VAR_020233 | |||||
| Natural variant | 1382 | 1 | Q → R in DJS. Ref.12 | VAR_010756 | |||||
| Natural variant | 1392 – 1393 | 2 | Missing in DJS; impaired maturation and intercompartmental trafficking. | VAR_013329 | |||||
| Natural variant | 1450 | 1 | A → T: dbSNP rs56296335. Ref.15 | VAR_013330 | |||||
| Natural variant | 1515 | 1 | C → Y: dbSNP rs8187710. Ref.2 | VAR_020234 | |||||
Experimental info | |||||||||
| Mutagenesis | 1254 | 1 | W → A or C: Fails to transport methotrexate, leukotriene C4 and estradiol glucuronide. Ref.8 | ||||||
| Mutagenesis | 1254 | 1 | W → F: Fails to transport methotrexate and leukotriene C4. Does not affect estradiol glucuronide transport. Ref.8 | ||||||
| Mutagenesis | 1254 | 1 | W → Y: Fails to transport methotrexate; reduces leukotriene C4 transport. Does not affect estradiol glucuronide transport. Ref.8 | ||||||
| Sequence conflict | 1430 | 1 | V → G in CAB45309. Ref.5 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "A human canalicular multispecific organic anion transporter (cMOAT) gene is overexpressed in cisplatin-resistant human cancer cell lines with decreased drug accumulation." Taniguchi K., Wada M., Kohno K., Nakamura T., Kawabe T., Kawakami M., Kagotani K., Okumura K., Akiyama S., Kuwano M. Cancer Res. 56:4124-4129(1996) [PubMed: 8797578] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. |
| [2] | Kool M., de Haas M., Ponne N.J., Paulusma C.C., Oude-Elferink R.P.J., Baas F., Borst P. Submitted (FEB-1996) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS GLU-1188 AND TYR-1515. |
| [3] | "cDNA cloning of the hepatocyte canalicular isoform of the multidrug resistance protein, cMrp, reveals a novel conjugate export pump deficient in hyperbilirubinemic mutant rats." Buechler M., Koenig J., Brom M., Kartenbeck J., Spring H., Horie T., Keppler D. J. Biol. Chem. 271:15091-15098(1996) [PubMed: 8662992] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. |
| [4] | Keppler D. Submitted (AUG-1996) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION. |
| [5] | "Exon-intron organization of the human multidrug-resistance protein 2 (MRP2) gene mutated in Dubin-Johnson syndrome." Tsujii H., Koenig J., Rost D., Stoeckel B., Leuschner U., Keppler D. Gastroenterology 117:653-660(1999) [PubMed: 10464142] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT DJS 1392-ARG-MET-1393 DEL. |
| [6] | "The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. Rogers J.Nature 429:375-381(2004) [PubMed: 15164054] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT TYR-39. |
| [7] | "Hepatic secretion of conjugated drugs and endogenous substances." Keppler D., Koenig J. Semin. Liver Dis. 20:265-272(2000) [PubMed: 11076395] [Abstract] Cited for: REVIEW. |
| [8] | "Mutation of Trp1254 in the multispecific organic anion transporter, multidrug resistance protein 2 (MRP2) (ABCC2), alters substrate specificity and results in loss of methotrexate transport activity." Ito K., Oleschuk C.J., Westlake C., Vasa M.Z., Deeley R.G., Cole S.P.C. J. Biol. Chem. 276:38108-38114(2001) [PubMed: 11500505] [Abstract] Cited for: MUTAGENESIS OF TRP-1254. |
| [9] | "Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-283, MASS SPECTROMETRY. |
| [10] | "A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-283 AND SER-878, MASS SPECTROMETRY. |
| [11] | "Mutations in the canilicular multispecific organic anion transporter (cMOAT) gene, a novel ABC transporter, in patients with hyperbilirubinemia II/Dubin-Johnson syndrome." Wada M., Toh S., Taniguchi K., Nakamura T., Uchiumi T., Kohno K., Yoshida I., Kimura A., Sakisaka S., Adachi Y., Kuwano M. Hum. Mol. Genet. 7:203-207(1998) [PubMed: 9425227] [Abstract] Cited for: VARIANT DJS TRP-768. |
| [12] | "Genomic structure of the canalicular multispecific organic anion-transporter gene (MRP2/cMOAT) and mutations in the ATP-binding-cassette region in Dubin-Johnson syndrome." Toh S., Wada M., Uchiumi T., Inokuchi A., Makino Y., Horie Y., Adachi Y., Sakisaka S., Kuwano M. Am. J. Hum. Genet. 64:739-746(1999) [PubMed: 10053008] [Abstract] Cited for: VARIANTS DJS TRP-768 AND ARG-1382. |
| [13] | "Impaired protein maturation of the conjugate export pump multidrug resistance protein 2 as a consequence of a deletion mutation in Dubin-Johnson syndrome." Keitel V., Kartenbeck J., Nies A.T., Spring H., Brom M., Keppler D. Hepatology 32:1317-1328(2000) [PubMed: 11093739] [Abstract] Cited for: CHARACTERIZATION OF VARIANT DJS 1392-ARG-MET-1393 DEL. |
| [14] | "Identification and functional analysis of two novel mutations in the multidrug resistance protein 2 gene in Israeli patients with Dubin-Johnson syndrome." Mor-Cohen R., Zivelin A., Rosenberg N., Shani M., Muallem S., Seligsohn U. J. Biol. Chem. 276:36923-36930(2001) [PubMed: 11477083] [Abstract] Cited for: VARIANTS DJS HIS-1150 AND PHE-1173, VARIANTS ASN-281 AND ILE-417. |
| [15] | "Polymorphism of the ABC transporter genes, MDR1, MRP1 and MRP2/cMOAT, in healthy Japanese subjects." Ito S., Ieiri I., Tanabe M., Suzuki A., Higuchi S., Otsubo K. Pharmacogenetics 11:175-184(2001) [PubMed: 11266082] [Abstract] Cited for: VARIANT DJS TRP-768, VARIANTS ILE-417; PHE-789 AND THR-1450. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| U63970 mRNA. Translation: AAB39892.1. U49248 mRNA. Translation: AAB09422.1. X96395 mRNA. Translation: CAA65259.2. AJ132244 AJ132314 Genomic DNA. Translation: CAB45309.1. AL392107, AL133353 Genomic DNA. Translation: CAI11010.1. AL133353, AL392107 Genomic DNA. Translation: CAI14502.1. | |
| IPI | IPI00023868. |
| PIR | S71841. |
| RefSeq | NP_000383.1. |
| UniGene | Hs.368243 |
3D structure databases | |
| HSSP | HSSP built from PDB template 1CKX based on UniProtKB Q00555. |
| ModBase | Search... |
Protein family/group databases | |
| TCDB | 3.A.1.208.2. ATP-binding cassette (ABC) superfamily. |
PTM databases | |
| PhosphoSite | Q92887. |
Proteomic databases | |
| PRIDE | Q92887. |
Genome annotation databases | |
| Ensembl | ENSG00000023839. Homo sapiens. [Contig view] |
| GeneID | 1244. |
| KEGG | hsa:1244. |
| NMPDR | fig|9606.3.peg.4488. |
Organism-specific databases | |
| GeneCards | GC10P101532. |
| H-InvDB | HIX0035426. |
| HGNC | HGNC:53. ABCC2. |
| MIM | 237500. phenotype. 601107. gene. |
| Orphanet | 234. Dubin-Johnson syndrome. |
| PharmGKB | PA116. |
| GenAtlas | Search... |
Phylogenomic databases | |
| HOGENOM | Q92887. |
| HOVERGEN | Q92887. |
Gene expression databases | |
| ArrayExpress | Q92887. |
| Bgee | Q92887. |
| CleanEx | HS_ABCC2. |
| GermOnline | ENSG00000023839. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR001140. ABC_TM_transpt. IPR003439. ABC_transporter-like. IPR017871. ABC_transporter_CS. IPR017940. ABC_transporter_type1. IPR003593. ATPase_AAA+_core. IPR005292. Multidrug-R_assoc_MRP. [Graphical view] |
| Pfam | PF00664. ABC_membrane. 2 hits. PF00005. ABC_tran. 2 hits. [Graphical view] |
| ProDom | PD000006. ABC_transporter. 2 hits. [Graphical view] [Entries sharing at least one domain] |
| SMART | SM00382. AAA. 2 hits. [Graphical view] |
| TIGRFAMs | TIGR00957. MRP_assoc_pro. 1 hit. |
| PROSITE | PS50929. ABC_TM1F. 2 hits. PS00211. ABC_TRANSPORTER_1. 1 hit. PS50893. ABC_TRANSPORTER_2. 2 hits. [Graphical view] |
| ProtoNet | Search... |
Other Resources | |
| DrugBank | DB00171. Adenosine triphosphate. DB00957. Norgestimate. DB00175. Pravastatin. DB01232. Saquinavir. DB01138. Sulfinpyrazone. |
| NextBio | 5071. |
| SOURCE | Search... |
Entry information
| Entry name | MRP2_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q92887 Secondary accession number(s): Q14022 Q9UMS2 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| Human chromosome 10 Human chromosome 10: 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


