Descriptions

MRP2 (Multidrug resistance-associated protein 2) is an efflux transporter for organic anions, expressed in hepatocyte canalicular membranes. It plays a role in exporting bilirubin glucuronide, a breakdown product of heme. The structural analysis of rat Mrp2 (rMrp2) reveals an autoinhibited state where the regulatory domain (R-domain) is folded within the transmembrane domain cavity, preventing substrate binding and NBD:NBD interface formation. Phosphorylation of the R-domain by intracellular kinases relieves autoinhibition, enhancing rMrp2 transport activity. The drug-bound state of rMrp2 shows two probenecid binding sites, suggesting a dynamic interplay with autoinhibition and providing insights into drug modulation of MRP2 activity.

Autoinhibitory domains (AIDs)

Target domain

322-603 (Transmembrane domain 1);978-1262 (Transmembrane domain 2)

Relief mechanism

PTM

Assay

Accessory elements

No accessory elements

Autoinhibited structure

Activated structure

1 structures for Q8VI47

Entry ID Method Resolution Chain Position Source
AF-Q8VI47-F1 Predicted AlphaFoldDB

112 variants for Q8VI47

Variant ID(s) Position Change Description Diseaes Association Provenance
rs3389543522 26 F>S No EVA
rs3389535175 47 L>F No EVA
rs3389449356 77 L>S No EVA
rs1132208267 92 Q>K No EVA
rs3389498512 118 H>Q No EVA
rs252393281 119 C>F No EVA
rs3389534345 121 Q>* No EVA
rs3389536840 122 C>Y No EVA
rs3409213631 142 G>D No EVA
rs31000153 162 T>A No EVA
rs244307689 186 S>P No EVA
rs260701983 187 S>R No EVA
rs246718080 203 V>I No EVA
rs212331316 228 I>V No EVA
rs8250832 231 N>K No EVA
rs8250834 242 K>E No EVA
rs3389507415 245 M>K No EVA
rs3389556635 268 E>K No EVA
rs31264106 270 T>P No EVA
rs3389498538 279 S>N No EVA
rs3389489477 279 S>R No EVA
rs8242072 290 S>A No EVA
rs3389520732 295 K>R No EVA
rs3389543576 296 K>N No EVA
rs8242071 299 A>V No EVA
rs3389507393 301 K>* No EVA
rs3389541406 310 K>R No EVA
rs226391102 330 H>Y No EVA
rs3410685664 349 K>R No EVA
rs3389535244 359 Y>N No EVA
rs3389550835 359 Y>S No EVA
rs214541690 367 S>A No EVA
rs3389543529 372 Q>K No EVA
rs3389556685 401 K>M No EVA
rs3409336795 405 L>Q No EVA
rs3389540763 426 S>P No EVA
rs8250863 479 A>T No EVA
rs3389543566 496 R>S No EVA
rs3389449354 509 I>T No EVA
rs3389449339 516 E>D No EVA
rs3389534375 530 E>D No EVA
rs8250508 542 T>A No EVA
rs238217120 549 H>Q No EVA
rs3389489540 575 E>D No EVA
rs8250768 592 A>S No EVA
rs226347603 600 S>L No EVA
rs3389540748 609 D>G No EVA
rs30368996 613 Q>R No EVA
rs3389541421 711 G>V No EVA
rs3389449350 719 F>L No EVA
rs238277034 724 D>N No EVA
rs261463374 730 R>Q No EVA
rs3407275833 761 G>V No EVA
rs8250869 791 T>A No EVA
rs8250871 864 S>L No EVA
rs213029040 865 G>E No EVA
rs3389536888 869 E>A No EVA
rs257387723 873 D>N No EVA
rs3389556629 913 R>L No EVA
rs262142834 921 R>H No EVA
rs37789542 927 S>N No EVA
rs256639614 942 E>K No EVA
rs256639614 942 E>Q No EVA
rs3389556650 973 G>V No EVA
rs8250622 985 V>I No EVA
rs8250623 994 T>S No EVA
rs258088036 1008 Q>L No EVA
rs1132926624 1015 P>S No EVA
rs8237005 1037 L>F No EVA
rs8237006 1049 N>D No EVA
rs3412978476 1067 M>I No EVA
rs3412866974 1068 S>C No EVA
rs3389541381 1072 T>I No EVA
rs8242054 1097 L>F No EVA
rs3389498534 1103 C>Y No EVA
rs3389449312 1114 I>N No EVA
rs8250639 1133 V>I No EVA
rs3389543508 1135 V>M No EVA
rs3389553545 1150 D>H No EVA
rs3389535106 1160 H>N No EVA
rs3389536886 1162 S>N No EVA
rs3389489544 1186 K>* No EVA
rs37663858 1223 L>F No EVA
rs225143801 1260 V>A No EVA
rs3389553577 1290 A>V No EVA
rs3409336803 1334 T>N No EVA
rs3409095543 1335 G>* No EVA
rs3407275888 1336 A>D No EVA
rs3409175940 1336 A>T No EVA
rs3408221531 1341 L>H No EVA
rs259382066 1357 I>T No EVA
rs3389449400 1369 H>Y No EVA
rs3389540770 1371 L>P No EVA
rs3389546088 1373 G>W No EVA
rs3389553518 1375 L>Q No EVA
rs3389556617 1386 S>C No EVA
rs3389508609 1389 L>M No EVA
rs3389508628 1432 G>D No EVA
rs8250824 1440 R>K No EVA
rs3389508646 1442 L>V No EVA
rs260246846 1451 R>Q No EVA
rs3389520711 1454 K>Q No EVA
rs3389508659 1480 E>D No EVA
rs3389520752 1495 T>I No EVA
rs3389508676 1509 K>N No EVA
rs3408221539 1514 G>S No EVA
rs3409175941 1516 P>S No EVA
rs3407275911 1517 E>* No EVA
rs3409336792 1517 E>A No EVA
rs3409374891 1518 E>G No EVA
rs3409175890 1520 L>P No EVA
rs3389535240 1536 E>K No EVA

No associated diseases with Q8VI47

6 regional properties for Q8VI47

Type Name Position InterPro Accession
domain ABC transporter-like, ATP-binding domain 635 - 859 IPR003439-1
domain ABC transporter-like, ATP-binding domain 1298 - 1532 IPR003439-2
domain AAA+ ATPase domain 661 - 836 IPR003593-1
domain AAA+ ATPase domain 1324 - 1509 IPR003593-2
domain ABC transporter type 1, transmembrane domain 322 - 603 IPR011527-1
domain ABC transporter type 1, transmembrane domain 977 - 1262 IPR011527-2

Functions

Description
EC Number 7.6.2.2 Linked to the hydrolysis of a nucleoside triphosphate
Subcellular Localization
  • Apical cell membrane ; Multi-pass membrane protein
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

7 GO annotations of cellular component

Name Definition
apical plasma membrane The region of the plasma membrane located at the apical end of the cell.
brush border membrane The portion of the plasma membrane surrounding the brush border.
cell surface The external part of the cell wall and/or plasma membrane.
intercellular canaliculus An extremely narrow tubular channel located between adjacent cells. An instance of this is the secretory canaliculi occurring between adjacent parietal cells in the gastric mucosa of vertebrates.
intracellular canaliculus An apical plasma membrane part that forms a narrow enfolded luminal membrane channel, lined with numerous microvilli, that appears to extend into the cytoplasm of the cell. A specialized network of intracellular canaliculi is a characteristic feature of parietal cells of the gastric mucosa in vertebrates.
membrane A lipid bilayer along with all the proteins and protein complexes embedded in it and attached to it.
plasma membrane The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.

7 GO annotations of molecular function

Name Definition
ABC-type glutathione S-conjugate transporter activity Catalysis of the reaction
ABC-type xenobiotic transporter activity Catalysis of the reaction
ATP binding Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
ATP hydrolysis activity Catalysis of the reaction
ATPase-coupled transmembrane transporter activity Primary active transporter of a solute across a membrane, via the reaction
bilirubin transmembrane transporter activity Enables the transfer of bilirubin from one side of a membrane to the other. Bilirubin is a linear tetrapyrrole produced in the reticuloendothelial system from biliverdin and transported to the liver as a complex with serum albumin. In the liver, bilirubin is converted to bilirubin bisglucuronide, which is excreted in the bile.
protein domain specific binding Binding to a specific domain of a protein.

21 GO annotations of biological process

Name Definition
antibiotic metabolic process The chemical reactions and pathways involving an antibiotic, a substance produced by or derived from certain fungi, bacteria, and other organisms, that can destroy or inhibit the growth of other microorganisms.
benzylpenicillin metabolic process The chemical reactions and pathways involving benzylpenicillin.
bile acid and bile salt transport The directed movement of bile acid and bile salts into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore.
bilirubin transport The directed movement of bilirubin into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore.
canalicular bile acid transport Enables the transfer of bile acid from one side of a hepatocyte plasma membrane into a bile canaliculus. Bile canaliculi are the thin tubes formed by hepatocyte membranes. Bile acids are any of a group of steroid carboxylic acids occurring in bile, where they are present as the sodium salts of their amides with glycine or taurine.
detoxification of mercury ion Any process that reduce or remove the toxicity of mercuric ion. These include transport of mercury away from sensitive areas and to compartments or complexes whose purpose is sequestration of mercury ion and/or reduction of mercury ion (Hg) to metallic mercury (Hg).
intracellular chloride ion homeostasis A homeostatic process involved in the maintenance of a steady state level of chloride ions within a cell.
leukotriene transport The directed movement of leukotrienes into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore. Leukotrienes are linear C20 endogenous metabolites of arachidonic acid (icosa-5,8,11,14-tetraenoic acid) containing a terminal carboxy function and four or more double bonds (three or more of which are conjugated) as well as other functional groups.
mercury ion transport The directed movement of mercury (Hg) ions into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore.
negative regulation of gene expression Any process that decreases the frequency, rate or extent of gene expression. Gene expression is the process in which a gene's coding sequence is converted into a mature gene product (protein or RNA).
organic anion transport The directed movement of organic anions into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore. Organic anions are atoms or small molecules with a negative charge which contain carbon in covalent linkage.
prostaglandin transport The directed movement of prostaglandins into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore.
response to estrogen Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of stimulus by an estrogen, C18 steroid hormones that can stimulate the development of female sexual characteristics.
response to xenobiotic stimulus Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus from a xenobiotic, a compound foreign to the organim exposed to it. It may be synthesized by another organism (like ampicilin) or it can be a synthetic chemical.
thyroid hormone transport The directed movement of thyroid hormone into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore.
transepithelial transport The directed movement of a substance from one side of an epithelium to the other.
transmembrane transport The process in which a solute is transported across a lipid bilayer, from one side of a membrane to the other.
xenobiotic catabolic process The chemical reactions and pathways resulting in the breakdown of a xenobiotic compound, a compound foreign to the organim exposed to it. It may be synthesized by another organism (like ampicilin) or it can be a synthetic chemical.
xenobiotic detoxification by transmembrane export across the plasma membrane A process that reduces or removes the toxicity of a xenobiotic by exporting it outside the cell.
xenobiotic transmembrane transport The process in which a xenobiotic, a compound foreign to the organim exposed to it, is transported across a membrane. It may be synthesized by another organism (like ampicilin) or it can be a synthetic chemical.
xenobiotic transport across blood-brain barrier The directed movement of a xenobiotic through the blood-brain barrier.

25 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
P14772 BPT1 Bile pigment transporter 1 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) PR
Q8HXQ5 ABCC1 Multidrug resistance-associated protein 1 Bos taurus (Bovine) PR
Q2QLE5 CFTR Cystic fibrosis transmembrane conductance regulator Pan troglodytes (Chimpanzee) PR
P91660 Rh5 Probable multidrug resistance-associated protein lethal(2)03659 Drosophila melanogaster (Fruit fly) PR
P13569 CFTR Cystic fibrosis transmembrane conductance regulator Homo sapiens (Human) PR
O15439 ABCC4 ATP-binding cassette sub-family C member 4 Homo sapiens (Human) PR
Q96J66 ABCC11 ATP-binding cassette sub-family C member 11 Homo sapiens (Human) PR
O15438 ABCC3 ATP-binding cassette sub-family C member 3 Homo sapiens (Human) PR
O95255 ABCC6 ATP-binding cassette sub-family C member 6 Homo sapiens (Human) PR
P33527 ABCC1 Multidrug resistance-associated protein 1 Homo sapiens (Human) PR
Q92887 ABCC2 ATP-binding cassette sub-family C member 2 Homo sapiens (Human) SS
B2RX12 Abcc3 ATP-binding cassette sub-family C member 3 Mus musculus (Mouse) PR
O35379 Abcc1 Multidrug resistance-associated protein 1 Mus musculus (Mouse) PR
Q80WJ6 Abcc12 ATP-binding cassette sub-family C member 12 Mus musculus (Mouse) PR
P26361 Cftr Cystic fibrosis transmembrane conductance regulator Mus musculus (Mouse) PR
Q6PQZ2 CFTR Cystic fibrosis transmembrane conductance regulator Sus scrofa (Pig) PR
Q6Y306 Abcc12 ATP-binding cassette sub-family C member 12 Rattus norvegicus (Rat) PR
Q8CG09 Abcc1 Multidrug resistance-associated protein 1 Rattus norvegicus (Rat) PR
Q63120 Abcc2 ATP-binding cassette sub-family C member 2 Rattus norvegicus (Rat) EV
Q00553 CFTR Cystic fibrosis transmembrane conductance regulator Macaca mulatta (Rhesus macaque) PR
Q9SKX0 ABCC13 ABC transporter C family member 13 Arabidopsis thaliana (Mouse-ear cress) PR
Q8VZZ4 ABCC6 ABC transporter C family member 6 Arabidopsis thaliana (Mouse-ear cress) PR
Q9M1C7 ABCC9 ABC transporter C family member 9 Arabidopsis thaliana (Mouse-ear cress) PR
Q9C8G9 ABCC1 ABC transporter C family member 1 Arabidopsis thaliana (Mouse-ear cress) PR
Q9C8H0 ABCC12 ABC transporter C family member 12 Arabidopsis thaliana (Mouse-ear cress) PR
10 20 30 40 50 60
MDEFCNSTFW NLSLLKSPEA DLPLCFEQTV LVWIPLGFLW LLAPWQLYRI YRSRTKRFAI
70 80 90 100 110 120
TKFYLAKQVF VVCLLILAAI DLSLALTEDT GQATIPPVKY TNPILYLCTW LLVLVIQHCR
130 140 150 160 170 180
QCCIQKNSWF LSMFWILSLL CGIFQFQTLI RALLQDSKSN MTYSCLFFVS YGFQIVILIL
190 200 210 220 230 240
SAFSESSDST HAPSATASFL SSVTFSWYDS TVLKGYKHPL TIEDVWDIEE NLKAKSLTSK
250 260 270 280 290 300
FKTIMTKDLQ KARQALQRRL KKSQQSPEGT SHGLTKKQSQ SQDVLVLEDS KKKKKKSEAT
310 320 330 340 350 360
KDFPKSWLVK ALFKTFYVVI LKSFILKLAH DILLFLNPQL LKFLIGFVKD PDSYPWVGYI
370 380 390 400 410 420
YAILMFSVTL IQSFFLQCYF QFCFVLGMTV RTTIIASVYK KALTLSNLAR RQYTIGETVN
430 440 450 460 470 480
LMSVDSQKLM DVTNYIHLLW SSVLQIALSI FFLWRELGPS ILAGVGLMVL LVPVNGVLAT
490 500 510 520 530 540
KIRKIQVQNM KNKDKRLKIM NEILSGIKIL KYFAWEPSFK EQVNSIRKKE LRNLLRFSQL
550 560 570 580 590 600
QTILIFILHL TPTLVSVITF SVYVLVDSQN VLNAEKAFTS ITLFNILRFP LAMLPMVISS
610 620 630 640 650 660
VIQASVSVDR LEQYLGSDDL DLSAIRHVCH FDKAVQFSEA SFTWDRDLEA TIQDVNLDIK
670 680 690 700 710 720
PGQLVAVVGT VGSGKSSLIS AMLGEMENVH GHITIKGSIA YVPQQAWIQN GTIKDNILFG
730 740 750 760 770 780
SEYDEKKYQR VIEACALLPD LEMLPGGDMA EIGEKGINLS GGQKHRVSLA RATYQDADIY
790 800 810 820 830 840
ILDDPLSAVD THVGKHIFNK VVGPNGLLSG KTRILVTHGI HFLPQVDEIV VLGKGTILEK
850 860 870 880 890 900
GSYSDLMDKK GVFAKNWKTF MKHSGPEGEA TVDNDSEEED GDCGLIPTVE EIPDDAASLT
910 920 930 940 950 960
MRRENSLRRT LSRSSRSGSR RGKSLKSSLK IKSVNALNKK EEVVKGQKLI KKEFVETGKV
970 980 990 1000 1010 1020
KFSIYLKYLQ AVGWWSLLFI VIFYVLNYVA FIGTNLWLSA WTSDSEKQNG TDNSPSQRDM
1030 1040 1050 1060 1070 1080
RIGVFGALGI AQGIFLLSSS LWSIYACRNA SKTLHRQLLT NILRAPMSFF DTTPTGRIVN
1090 1100 1110 1120 1130 1140
RFAGDISTVD DTLPQTLRSW LLCFFGIVST LVMICMATPI FIIIIIPLSI LYVSVQVFYV
1150 1160 1170 1180 1190 1200
ATSRQLRRLD SVTKSPIYSH FSETVSGLPV IRAFEHQQRF LANSEKQIDT NQKCVFSWIT
1210 1220 1230 1240 1250 1260
SNRWLAIRLE LVGNLIVFCS ALLLVIYKNS LTGDTVGFVL SNALNITQTL NWLVRMTSEV
1270 1280 1290 1300 1310 1320
ETNIVAVERI NEYINVDNEA PWVTDKKPPA DWPKKGEIQF NNYQVRYRPE LDLVLKGITC
1330 1340 1350 1360 1370 1380
NIKSTEKVGV VGRTGAGKSS LTNCLFRILE SAGGQIIIDG IDIASIGLHD LRGRLTIIPQ
1390 1400 1410 1420 1430 1440
DPILFSGNLR MNLDPFNKYS DEEIWRALEL AHLKSFVAGL QLGLLHEVTE GGDNLSIGQR
1450 1460 1470 1480 1490 1500
QLLCLGRAVL RKSKILVLDE ATAAVDLETD SLIQTTIRNE FSQCTVITIA HRLHTIMDSD
1510 1520 1530 1540
KIMVLDSGKI VEYGSPEELL SNMGPFYLMA KEAGIESVNH TEL