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Multidrug resistance-associated protein 6 (ATP-binding cassette sub-family C member 6) (Anthracycline resistance-associated protein) (Multi-specific organic anion transporter E) (MOAT-E)

 MRP6_HUMAN              Reviewed;        1503 AA.
O95255; A2RRN8; A8KIG6; A8Y988; E7ESW8; P78420; Q8TCY8; Q9UMZ7;
30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
24-NOV-2009, sequence version 2.
22-NOV-2017, entry version 191.
RecName: Full=Multidrug resistance-associated protein 6;
AltName: Full=ATP-binding cassette sub-family C member 6;
AltName: Full=Anthracycline resistance-associated protein;
AltName: Full=Multi-specific organic anion transporter E;
Short=MOAT-E;
Name=ABCC6; Synonyms=ARA, MRP6;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT VAL-848.
PubMed=10424734; DOI=10.1038/sj.bjc.6690527;
Belinsky M.G., Kruh G.D.;
"MOAT-E (ARA) is a full-length MRP/cMOAT subfamily transporter
expressed in kidney and liver.";
Br. J. Cancer 80:1342-1349(1999).
[2]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS TRP-64 AND
VAL-848.
PubMed=9892204;
Kool M., van der Linden M., de Haas M., Baas F., Borst P.;
"Expression of human MRP6, a homologue of the multidrug resistance
protein gene MRP1, in tissues and cancer cells.";
Cancer Res. 59:175-182(1999).
[3]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
PubMed=11431746; DOI=10.1053/jhep.2001.25545;
Lian Z., Liu J., Pan J., Tufan N.L.S., Zhu M., Arbuthnot P., Kew M.,
Clayton M.M., Feitelson M.A.;
"A cellular gene up-regulated by hepatitis B virus-encoded X antigen
promotes hepatocellular growth and survival.";
Hepatology 34:146-157(2001).
[4]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3), VARIANTS VAL-319 AND
VAL-848, AND ALTERNATIVE SPLICING.
TISSUE=Liver;
PubMed=21318057; DOI=10.1155/2008/912478;
Armentano M.F., Ostuni A., Infantino V., Iacobazzi V.,
Castiglione Morelli M.A., Bisaccia F.;
"Identification of a new splice variant of the human ABCC6
transporter.";
Biochem. Res. Int. 2008:912478-912478(2008).
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANTS TRP-64 AND
VAL-848.
PubMed=10493829; DOI=10.1006/geno.1999.5927;
Loftus B.J., Kim U.-J., Sneddon V.P., Kalush F., Brandon R.,
Fuhrmann J., Mason T., Crosby M.L., Barnstead M., Cronin L.,
Mays A.D., Cao Y., Xu R.X., Kang H.-L., Mitchell S., Eichler E.E.,
Harris P.C., Venter J.C., Adams M.D.;
"Genome duplications and other features in 12 Mb of DNA sequence from
human chromosome 16p and 16q.";
Genomics 60:295-308(1999).
[6]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=15616553; DOI=10.1038/nature03187;
Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X.,
Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A.,
Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J.,
Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L.,
Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A.,
Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D.,
Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J.,
Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I.,
Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W.,
Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A.,
Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S.,
Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L.,
Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A.,
Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L.,
Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N.,
Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M.,
Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L.,
Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D.,
Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P.,
Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M.,
Rubin E.M., Pennacchio L.A.;
"The sequence and analysis of duplication-rich human chromosome 16.";
Nature 432:988-994(2004).
[7]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND
VARIANTS ALA-614; GLN-632 AND VAL-848.
TISSUE=Retinoblastoma;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[8]
FUNCTION, AND CHARACTERIZATION OF VARIANTS PXE PHE-1298; ARG-1302 AND
SER-1321.
PubMed=11880368; DOI=10.1074/jbc.M110918200;
Ilias A., Urban Z., Seidl T.L., Le Saux O., Sinko E., Boyd C.D.,
Sarkadi B., Varadi A.;
"Loss of ATP-dependent transport activity in pseudoxanthoma elasticum-
associated mutants of human ABCC6 (MRP6).";
J. Biol. Chem. 277:16860-16867(2002).
[9]
REVIEW, AND VARIANT PXE PRO-455.
PubMed=11427982; DOI=10.1016/S1471-4914(00)01869-4;
Uitto J., Pulkkinen L., Ringpfeil F.;
"Molecular genetics of pseudoxanthoma elasticum: a metabolic disorder
at the environment-genome interface?";
Trends Mol. Med. 7:13-17(2001).
[10]
SUBCELLULAR LOCATION, TOPOLOGY, AND GLYCOSYLATION AT ASN-15.
PubMed=12901863; DOI=10.1016/S0006-291X(03)01349-4;
Sinko E., Ilias A., Ujhelly O., Homolya L., Scheffer G.L.,
Bergen A.A., Sarkadi B., Varadi A.;
"Subcellular localization and N-glycosylation of human ABCC6,
expressed in MDCKII cells.";
Biochem. Biophys. Res. Commun. 308:263-269(2003).
[11]
SUBCELLULAR LOCATION.
PubMed=23625951; DOI=10.1161/CIRCRESAHA.111.300194;
Pomozi V., Le Saux O., Brampton C., Apana A., Ilias A., Szeri F.,
Martin L., Monostory K., Paku S., Sarkadi B., Szakacs G., Varadi A.;
"ABCC6 is a basolateral plasma membrane protein.";
Circ. Res. 112:E148-E151(2013).
[12]
FUNCTION (ISOFORM 2), INDUCTION (ISOFORM 2), AND SUBCELLULAR LOCATION
(ISOFORM 2).
PubMed=23912081; DOI=10.1016/j.febslet.2013.07.042;
Ostuni A., Lara P., Armentano M.F., Miglionico R., Salvia A.M.,
Monnich M., Carmosino M., Lasorsa F.M., Monne M., Nilsson I.,
Bisaccia F.;
"The hepatitis B x antigen anti-apoptotic effector URG7 is localized
to the endoplasmic reticulum membrane.";
FEBS Lett. 587:3058-3062(2013).
[13]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1286, AND IDENTIFICATION
BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Liver;
PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D.,
Wang L., Ye M., Zou H.;
"An enzyme assisted RP-RPLC approach for in-depth analysis of human
liver phosphoproteome.";
J. Proteomics 96:253-262(2014).
[14]
VARIANT GLN-1268.
PubMed=10913334; DOI=10.1006/bbrc.2000.3101;
Germain D.P., Perdu J., Remones V., Jeunemaitre X.;
"Homozygosity for the R1268Q mutation in MRP6, the pseudoxanthoma
elasticum gene, is not disease-causing.";
Biochem. Biophys. Res. Commun. 274:297-301(2000).
[15]
VARIANT TRP-64.
PubMed=11058917;
DOI=10.1002/1098-1004(200011)16:5<449::AID-HUMU24>3.0.CO;2-O;
Germain D.P., Perdu J., Remones V., Manzoni K., Jeunemaitre X.;
"Identification of two polymorphisms (c189G>C; c190T>C) in exon 2 of
the human MRP6 gene (ABCC6) by screening of Pseudoxanthoma elasticum
patients: possible sequence correction?";
Hum. Mutat. 16:449-449(2000).
[16]
VARIANT PXE CYS-1339, AND VARIANT GLN-632.
PubMed=10954200; DOI=10.1007/s001090000114;
Struk B., Cai L., Zaech S., Ji W., Chung J., Lumsden A., Stumm M.,
Huber M., Schaen L., Kim C.-A., Goldsmith L.A., Viljoen D.,
Figuera L.E., Fuchs W., Munier F., Ramesar R., Hohl D., Richards R.,
Neldner K.H., Lindpaintner K.;
"Mutations of the gene encoding the transmembrane transporter protein
ABC-C6 cause pseudoxanthoma elasticum.";
J. Mol. Med. 78:282-286(2000).
[17]
VARIANTS PXE PRO-1114; GLN-1138 AND TRP-1314, AND VARIANT ALA-614.
PubMed=10835642; DOI=10.1038/76102;
Le Saux O., Urban Z., Tschuch C., Csiszar K., Bacchelli B.,
Quaglino D., Pasquali-Ronchetti I., Pope F.M., Richards A., Terry S.,
Bercovitch L., de Paepe A., Boyd C.D.;
"Mutations in a gene encoding an ABC transporter cause pseudoxanthoma
elasticum.";
Nat. Genet. 25:223-227(2000).
[18]
VARIANT PXE TRP-1138, AND VARIANT GLN-1268.
PubMed=10811882; DOI=10.1073/pnas.100041297;
Ringpfeil F., Lebwohl M.G., Christiano A.M., Uitto J.;
"Pseudoxanthoma elasticum: mutations in the MRP6 gene encoding a
transmembrane ATP-binding cassette (ABC) transporter.";
Proc. Natl. Acad. Sci. U.S.A. 97:6001-6006(2000).
[19]
VARIANTS PXE LYS-411; GLN-518; SER-568; PRO-673; GLN-765; PRO-1114;
TRP-1121; PRO-1138; GLN-1138; ASP-1203; PHE-1298; ILE-1301; ARG-1302;
PRO-1303; GLN-1314; TRP-1314; SER-1321; CYS-1339; HIS-1347; ASN-1361
AND THR-1424, AND VARIANTS ASP-61; ARG-207; GLY-265; GLU-281; VAL-319;
LYS-497; ALA-614; GLN-632; HIS-953; CYS-1241 AND GLN-1268.
PubMed=11536079; DOI=10.1086/323704;
Le Saux O., Beck K., Sachsinger C., Silvestri C., Treiber C.,
Goering H.H.H., Johnson E.W., De Paepe A., Pope F.M.,
Pasquali-Ronchetti I., Bercovitch L., Terry S., Boyd C.D.;
"A spectrum of ABCC6 mutations is responsible for pseudoxanthoma
elasticum.";
Am. J. Hum. Genet. 69:749-764(2001).
[20]
VARIANTS PXE 60-ARG--TYR-62 DEL; ARG-364 AND ARG-1354, AND VARIANT
GLY-265.
PubMed=11702217; DOI=10.1007/s004390100582;
Pulkkinen L., Nakano A., Ringpfeil F., Uitto J.;
"Identification of ABCC6 pseudogenes on human chromosome 16p:
implications for mutation detection in pseudoxanthoma elasticum.";
Hum. Genet. 109:356-365(2001).
[21]
VARIANTS ALA-614; GLN-632 AND GLN-1268.
PubMed=11776382; DOI=10.1007/s100380170003;
Wang J., Near S., Young K., Connelly P.W., Hegele R.A.;
"ABCC6 gene polymorphism associated with variation in plasma
lipoproteins.";
J. Hum. Genet. 46:699-705(2001).
[22]
VARIANT PXE CYS-1459.
PubMed=15098239; DOI=10.1002/ajmg.a.20632;
Plomp A.S., Hu X., de Jong P.T., Bergen A.A.;
"Does autosomal dominant pseudoxanthoma elasticum exist?";
Am. J. Med. Genet. A 126:403-412(2004).
[23]
VARIANTS PXE ARG-364; LYS-411; GLY-440; GLN-518; CYS-600; MET-810;
PRO-820; CYS-1114; MET-1130; GLN-1138; CYS-1339; SER-1346 AND
LYS-1400.
PubMed=15459974; DOI=10.1002/humu.9284;
Gheduzzi D., Guidetti R., Anzivino C., Tarugi P., Di Leo E.,
Quaglino D., Ronchetti I.P.;
"ABCC6 mutations in Italian families affected by pseudoxanthoma
elasticum (PXE).";
Hum. Mutat. 24:438-439(2004).
[24]
VARIANTS PXE VAL-74 DEL; 363-GLN--ARG-373 DEL; GLY-391; GLN-518;
ASP-766; MET-1130; GLN-1138 HIS-1238; PRO-1335 AND LYS-1400.
PubMed=15086542; DOI=10.1111/j.0022-202X.2004.22312.x;
Chassaing N., Martin L., Mazereeuw J., Barrie L., Nizard S.,
Bonafe J.L., Calvas P., Hovnanian A.;
"Novel ABCC6 mutations in pseudoxanthoma elasticum.";
J. Invest. Dermatol. 122:608-613(2004).
[25]
VARIANTS PXE 60-ARG--TYR-62 DEL; GLU-129; ARG-317; ARG-355; ARG-364;
ASP-370; GLY-391; GLY-398; HIS-495; GLN-518; SER-551; VAL-594;
PRO-677; TRP-760; GLN-765; GLN-807; TRP-807; GLU-1056; PHE-1036 DEL;
PHE-1048 DEL; CYS-1114; LEU-1121; GLN-1138; TRP-1138; GLN-1164;
CYS-1221; TRP-1235; ARG-1302; PRO-1303; GLN-1314; CYS-1339; LEU-1339
AND TRP-1357, AND VARIANTS THR-78; LYS-125; VAL-158; GLY-265; GLU-281;
VAL-319; ILE-514; ALA-614; GLN-632; LYS-724; VAL-742; ILE-946;
TRP-1064 AND GLN-1268.
PubMed=16086317; DOI=10.1002/humu.20206;
Miksch S., Lumsden A., Guenther U.P., Foernzler D., Christen-Zach S.,
Daugherty C., Ramesar R.K., Lebwohl M., Hohl D., Neldner K.H.,
Lindpaintner K., Richards R.I., Struk B.;
"Molecular genetics of pseudoxanthoma elasticum: type and frequency of
mutations in ABCC6.";
Hum. Mutat. 26:235-248(2005).
[26]
VARIANTS PXE 60-ARG--TYR-62 DEL; ARG-317; ARG-364; TRP-382; GLY-391;
ASN-392; HIS-463 HIS-495; GLN-518; PRO-535; SER-568; CYS-600; CYS-663;
PRO-698; ASP-699; PRO-726; LYS-751; ARG-755; TRP-760; GLN-765;
ASN-777; MET-811; SER-881; ILE-944; THR-950; ARG-992; CYS-1114;
MET-1130; ALA-1133; GLN-1138; TRP-1138; THR-1139; GLN-1164; CYS-1221;
HIS-1221; ILE-1226; PHE-1298; ARG-1302; PRO-1303; GLN-1314; TRP-1314;
GLN-1335; CYS-1339; HIS-1339 AND THR-1342.
PubMed=17617515; DOI=10.1136/jmg.2007.051094;
Pfendner E.G., Vanakker O.M., Terry S.F., Vourthis S., McAndrew P.E.,
McClain M.R., Fratta S., Marais A.S., Hariri S., Coucke P.J.,
Ramsay M., Viljoen D., Terry P.F., De Paepe A., Uitto J.,
Bercovitch L.G.;
"Mutation detection in the ABCC6 gene and genotype-phenotype analysis
in a large international case series affected by pseudoxanthoma
elasticum.";
J. Med. Genet. 44:621-628(2007).
[27]
VARIANT [LARGE SCALE ANALYSIS] GLN-1268.
PubMed=18987736; DOI=10.1038/nature07485;
Ley T.J., Mardis E.R., Ding L., Fulton B., McLellan M.D., Chen K.,
Dooling D., Dunford-Shore B.H., McGrath S., Hickenbotham M., Cook L.,
Abbott R., Larson D.E., Koboldt D.C., Pohl C., Smith S., Hawkins A.,
Abbott S., Locke D., Hillier L.W., Miner T., Fulton L., Magrini V.,
Wylie T., Glasscock J., Conyers J., Sander N., Shi X., Osborne J.R.,
Minx P., Gordon D., Chinwalla A., Zhao Y., Ries R.E., Payton J.E.,
Westervelt P., Tomasson M.H., Watson M., Baty J., Ivanovich J.,
Heath S., Shannon W.D., Nagarajan R., Walter M.J., Link D.C.,
Graubert T.A., DiPersio J.F., Wilson R.K.;
"DNA sequencing of a cytogenetically normal acute myeloid leukaemia
genome.";
Nature 456:66-72(2008).
[28]
VARIANTS PXE GLN-518; PRO-726; GLN-1138; ARG-1302; PRO-1335 AND
CYS-1339, AND VARIANTS THR-78; GLY-265; MET-417; ALA-614; GLN-632;
LEU-724; VAL-742; VAL-848 AND ILE-946.
PubMed=19339160; DOI=10.1016/j.jdermsci.2009.02.008;
Ramsay M., Greenberg T., Lombard Z., Labrum R., Lubbe S., Aron S.,
Marais A.S., Terry S., Bercovitch L., Viljoen D.;
"Spectrum of genetic variation at the ABCC6 locus in South Africans:
Pseudoxanthoma elasticum patients and healthy individuals.";
J. Dermatol. Sci. 54:198-204(2009).
[29]
VARIANTS PXE GLN-765 AND LYS-1406.
PubMed=20034067; DOI=10.1002/ajmg.a.33162;
Le Boulanger G., Labreze C., Croue A., Schurgers L.J., Chassaing N.,
Wittkampf T., Rutsch F., Martin L.;
"An unusual severe vascular case of pseudoxanthoma elasticum
presenting as generalized arterial calcification of infancy.";
Am. J. Med. Genet. A 152:118-123(2010).
[30]
VARIANTS GACI2 ARG-355; GLY-391; PHE-590; PHE-1036 DEL; CYS-1114;
HIS-1221 AND TRP-1314.
PubMed=22209248; DOI=10.1016/j.ajhg.2011.11.020;
Nitschke Y., Baujat G., Botschen U., Wittkampf T., du Moulin M.,
Stella J., Le Merrer M., Guest G., Lambot K.,
Tazarourte-Pinturier M.F., Chassaing N., Roche O., Feenstra I.,
Loechner K., Deshpande C., Garber S.J., Chikarmane R., Steinmann B.,
Shahinyan T., Martorell L., Davies J., Smith W.E., Kahler S.G.,
McCulloch M., Wraige E., Loidi L., Hohne W., Martin L., Hadj-Rabia S.,
Terkeltaub R., Rutsch F.;
"Generalized arterial calcification of infancy and pseudoxanthoma
elasticum can be caused by mutations in either ENPP1 or ABCC6.";
Am. J. Hum. Genet. 90:25-39(2012).
[31]
VARIANTS PXE THR-78 AND LYS-125, VARIANTS HIS-4; GLU-9; SER-21;
GLN-64; THR-90; GLN-419; PRO-605; GLY-709; THR-834; PRO-948 AND
THR-1442, CHARACTERIZATION OF VARIANTS HIS-4; GLU-9; SER-21; GLN-64;
THR-90; GLN-419; PRO-605; GLY-709; THR-834; PRO-948 AND THR-1442, AND
CHARACTERIZATION OF VARIANTS PXE THR-78 AND LYS-125.
PubMed=25615550; DOI=10.1038/jid.2015.10;
Jin L., Jiang Q., Wu Z., Shao C., Zhou Y., Yang L., Uitto J., Wang G.;
"Genetic heterogeneity of pseudoxanthoma elasticum: the chinese
signature profile of ABCC6 and ENPP1 mutations.";
J. Invest. Dermatol. 135:1294-1302(2015).
-!- FUNCTION: Isoform 1: May participate directly in the active
transport of drugs into subcellular organelles or influence drug
distribution indirectly. Transports glutathione conjugates as
leukotriene-c4 (LTC4) and N-ethylmaleimide S-glutathione (NEM-GS).
{ECO:0000269|PubMed:11880368}.
-!- FUNCTION: Isoform 2: Inhibits TNF-alpha-mediated apoptosis through
blocking one or more caspases. {ECO:0000269|PubMed:23912081}.
-!- SUBCELLULAR LOCATION: Isoform 1: Basolateral cell membrane
{ECO:0000269|PubMed:12901863, ECO:0000269|PubMed:23625951}; Multi-
pass membrane protein {ECO:0000255}.
-!- SUBCELLULAR LOCATION: Isoform 2: Endoplasmic reticulum membrane
{ECO:0000269|PubMed:23912081}; Single-pass membrane protein
{ECO:0000255}.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=3;
Name=1;
IsoId=O95255-1; Sequence=Displayed;
Name=2; Synonyms=URG7;
IsoId=O95255-2; Sequence=VSP_047315, VSP_047316;
Name=3; Synonyms=Delta19Delta24;
IsoId=O95255-3; Sequence=VSP_057077, VSP_057078;
Note=May function as a a half transporter.;
-!- TISSUE SPECIFICITY: Expressed in kidney and liver. Very low
expression in other tissues.
-!- INDUCTION: Isoform 2 is induced by HBV x antigen upon hepatitis B
viral infection. {ECO:0000269|PubMed:23912081}.
-!- DISEASE: Pseudoxanthoma elasticum (PXE) [MIM:264800]: A
multisystem disorder characterized by accumulation of mineralized
and fragmented elastic fibers in the skin, vascular walls, and
Burch membrane in the eye. Clinically, patients exhibit
characteristic lesions of the posterior segment of the eye
including peau d'orange, angioid streaks, and choroidal
neovascularizations, of the skin including soft, ivory colored
papules in a reticular pattern that predominantly affect the neck
and large flexor surfaces, and of the cardiovascular system with
peripheral and coronary arterial occlusive disease as well as
gastrointestinal bleedings. {ECO:0000269|PubMed:10811882,
ECO:0000269|PubMed:10835642, ECO:0000269|PubMed:10954200,
ECO:0000269|PubMed:11427982, ECO:0000269|PubMed:11536079,
ECO:0000269|PubMed:11702217, ECO:0000269|PubMed:11880368,
ECO:0000269|PubMed:15086542, ECO:0000269|PubMed:15098239,
ECO:0000269|PubMed:15459974, ECO:0000269|PubMed:16086317,
ECO:0000269|PubMed:17617515, ECO:0000269|PubMed:19339160,
ECO:0000269|PubMed:20034067, ECO:0000269|PubMed:25615550}.
Note=The disease is caused by mutations affecting the gene
represented in this entry. Homozygous or compound heterozygous
ABCC6 mutations have been found in the overwhelming majority of
cases. Individuals carrying heterozygous mutations express limited
manifestations of the pseudoxanthoma elasticum phenotype.
-!- DISEASE: Arterial calcification of infancy, generalized, 2 (GACI2)
[MIM:614473]: A severe autosomal recessive disorder characterized
by calcification of the internal elastic lamina of muscular
arteries and stenosis due to myointimal proliferation. The
disorder is often fatal within the first 6 months of life because
of myocardial ischemia resulting in refractory heart failure.
{ECO:0000269|PubMed:22209248}. Note=The disease is caused by
mutations affecting the gene represented in this entry.
-!- SIMILARITY: Belongs to the ABC transporter superfamily. ABCC
family. Conjugate transporter (TC 3.A.1.208) subfamily.
{ECO:0000305}.
-!- SEQUENCE CAUTION:
Sequence=AAC15785.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
-!- WEB RESOURCE: Name=Mutations of the ABCC6 gene; Note=Retina
International's Scientific Newsletter;
URL="http://www.retina-international.org/files/sci-news/abcc6mut.htm";
-!- WEB RESOURCE: Name=ABCMdb; Note=Database for mutations in ABC
proteins;
URL="http://abcmutations.hegelab.org/proteinDetails?uniprot_id=O95255";
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EMBL; AF168791; AAD51293.1; -; mRNA.
EMBL; AF076622; AAC79696.1; -; mRNA.
EMBL; AY078405; AAL83711.1; -; mRNA.
EMBL; AM711638; CAN84639.1; -; mRNA.
EMBL; AM774324; CAO81806.1; -; mRNA.
EMBL; U91318; AAC15785.1; ALT_SEQ; Genomic_DNA.
EMBL; AC136624; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; BC050733; AAH50733.1; -; mRNA.
EMBL; BC131732; AAI31733.1; -; mRNA.
CCDS; CCDS10568.1; -. [O95255-1]
CCDS; CCDS58430.1; -. [O95255-2]
RefSeq; NP_001072996.1; NM_001079528.3. [O95255-2]
RefSeq; NP_001162.4; NM_001171.5.
UniGene; Hs.442182; -.
ProteinModelPortal; O95255; -.
SMR; O95255; -.
BioGrid; 106863; 5.
IntAct; O95255; 5.
STRING; 9606.ENSP00000205557; -.
ChEMBL; CHEMBL2073661; -.
DrugBank; DB00515; Cisplatin.
DrugBank; DB00970; Dactinomycin.
DrugBank; DB00694; Daunorubicin.
DrugBank; DB00997; Doxorubicin.
DrugBank; DB00773; Etoposide.
DrugBank; DB00328; Indomethacin.
DrugBank; DB01032; Probenecid.
DrugBank; DB01138; Sulfinpyrazone.
DrugBank; DB00444; Teniposide.
DrugBank; DB00570; Vinblastine.
TCDB; 3.A.1.208.10; the atp-binding cassette (abc) superfamily.
iPTMnet; O95255; -.
PhosphoSitePlus; O95255; -.
BioMuta; ABCC6; -.
MaxQB; O95255; -.
PaxDb; O95255; -.
PeptideAtlas; O95255; -.
PRIDE; O95255; -.
Ensembl; ENST00000205557; ENSP00000205557; ENSG00000091262. [O95255-1]
Ensembl; ENST00000456970; ENSP00000405002; ENSG00000091262. [O95255-3]
Ensembl; ENST00000575728; ENSP00000461686; ENSG00000091262. [O95255-2]
Ensembl; ENST00000600761; ENSP00000481979; ENSG00000275331. [O95255-2]
Ensembl; ENST00000622290; ENSP00000483331; ENSG00000091262. [O95255-3]
GeneID; 368; -.
KEGG; hsa:368; -.
UCSC; uc002den.5; human. [O95255-1]
CTD; 368; -.
DisGeNET; 368; -.
EuPathDB; HostDB:ENSG00000091262.14; -.
GeneCards; ABCC6; -.
GeneReviews; ABCC6; -.
H-InvDB; HIX0026937; -.
H-InvDB; HIX0038600; -.
HGNC; HGNC:57; ABCC6.
HPA; HPA038105; -.
MalaCards; ABCC6; -.
MIM; 264800; phenotype.
MIM; 603234; gene.
MIM; 614473; phenotype.
neXtProt; NX_O95255; -.
OpenTargets; ENSG00000091262; -.
Orphanet; 51608; Generalized arterial calcification of infancy.
Orphanet; 758; Pseudoxanthoma elasticum.
PharmGKB; PA58; -.
eggNOG; KOG0054; Eukaryota.
eggNOG; COG1132; LUCA.
GeneTree; ENSGT00880000137856; -.
HOVERGEN; HBG108314; -.
InParanoid; O95255; -.
KO; K05669; -.
OMA; TVWLTTM; -.
OrthoDB; EOG091G00IN; -.
PhylomeDB; O95255; -.
TreeFam; TF105199; -.
Reactome; R-HSA-382556; ABC-family proteins mediated transport.
Reactome; R-HSA-5690338; Defective ABCC6 causes pseudoxanthoma elasticum (PXE).
ChiTaRS; ABCC6; human.
GeneWiki; ABCC6; -.
GenomeRNAi; 368; -.
PRO; PR:O95255; -.
Proteomes; UP000005640; Chromosome 16.
Bgee; ENSG00000091262; -.
CleanEx; HS_ABCC6; -.
ExpressionAtlas; O95255; baseline and differential.
Genevisible; O95255; HS.
GO; GO:0016324; C:apical plasma membrane; IEA:Ensembl.
GO; GO:0016323; C:basolateral plasma membrane; IEA:UniProtKB-SubCell.
GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
GO; GO:0016328; C:lateral plasma membrane; IEA:Ensembl.
GO; GO:0005634; C:nucleus; IDA:HPA.
GO; GO:0005886; C:plasma membrane; IDA:HPA.
GO; GO:0005524; F:ATP binding; TAS:ProtInc.
GO; GO:0042626; F:ATPase activity, coupled to transmembrane movement of substances; TAS:ProtInc.
GO; GO:0043225; F:ATPase-coupled anion transmembrane transporter activity; TAS:Reactome.
GO; GO:0005215; F:transporter activity; TAS:ProtInc.
GO; GO:0042493; P:response to drug; TAS:ProtInc.
GO; GO:0055085; P:transmembrane transport; TAS:Reactome.
GO; GO:0006810; P:transport; TAS:ProtInc.
GO; GO:0007601; P:visual perception; IEA:UniProtKB-KW.
Gene3D; 1.20.1560.10; -; 2.
InterPro; IPR003593; AAA+_ATPase.
InterPro; IPR011527; ABC1_TM_dom.
InterPro; IPR036640; ABC1_TM_sf.
InterPro; IPR003439; ABC_transporter-like.
InterPro; IPR017871; ABC_transporter_CS.
InterPro; IPR030239; ABCC6.
InterPro; IPR005292; Multidrug-R_assoc.
InterPro; IPR027417; P-loop_NTPase.
PANTHER; PTHR24223:SF339; PTHR24223:SF339; 1.
Pfam; PF00664; ABC_membrane; 2.
Pfam; PF00005; ABC_tran; 2.
SMART; SM00382; AAA; 2.
SUPFAM; SSF52540; SSF52540; 2.
SUPFAM; SSF90123; SSF90123; 2.
TIGRFAMs; TIGR00957; MRP_assoc_pro; 1.
PROSITE; PS50929; ABC_TM1F; 2.
PROSITE; PS00211; ABC_TRANSPORTER_1; 2.
PROSITE; PS50893; ABC_TRANSPORTER_2; 2.
1: Evidence at protein level;
Alternative splicing; ATP-binding; Cell membrane; Complete proteome;
Disease mutation; Endoplasmic reticulum; Glycoprotein; Membrane;
Nucleotide-binding; Phosphoprotein; Polymorphism; Reference proteome;
Repeat; Sensory transduction; Transmembrane; Transmembrane helix;
Transport; Vision.
CHAIN 1 1503 Multidrug resistance-associated protein
6.
/FTId=PRO_0000093366.
TOPO_DOM 1 31 Extracellular. {ECO:0000250}.
TRANSMEM 32 52 Helical; Name=1. {ECO:0000255|PROSITE-
ProRule:PRU00441}.
TOPO_DOM 53 72 Cytoplasmic. {ECO:0000250}.
TRANSMEM 73 93 Helical; Name=2. {ECO:0000255|PROSITE-
ProRule:PRU00441}.
TOPO_DOM 94 98 Extracellular. {ECO:0000250}.
TRANSMEM 99 119 Helical; Name=3. {ECO:0000255|PROSITE-
ProRule:PRU00441}.
TOPO_DOM 120 131 Cytoplasmic. {ECO:0000250}.
TRANSMEM 132 149 Helical; Name=4. {ECO:0000255|PROSITE-
ProRule:PRU00441}.
TOPO_DOM 150 167 Extracellular. {ECO:0000250}.
TRANSMEM 168 188 Helical; Name=5. {ECO:0000255|PROSITE-
ProRule:PRU00441}.
TOPO_DOM 189 302 Cytoplasmic. {ECO:0000250}.
TRANSMEM 303 323 Helical; Name=6. {ECO:0000255|PROSITE-
ProRule:PRU00441}.
TOPO_DOM 324 349 Extracellular. {ECO:0000250}.
TRANSMEM 350 370 Helical; Name=7. {ECO:0000255|PROSITE-
ProRule:PRU00441}.
TOPO_DOM 371 426 Cytoplasmic. {ECO:0000250}.
TRANSMEM 427 447 Helical; Name=8. {ECO:0000255|PROSITE-
ProRule:PRU00441}.
TOPO_DOM 448 450 Extracellular. {ECO:0000250}.
TRANSMEM 451 471 Helical; Name=9. {ECO:0000255|PROSITE-
ProRule:PRU00441}.
TOPO_DOM 472 533 Cytoplasmic. {ECO:0000250}.
TRANSMEM 534 554 Helical; Name=10. {ECO:0000255|PROSITE-
ProRule:PRU00441}.
TOPO_DOM 555 575 Extracellular. {ECO:0000250}.
TRANSMEM 576 596 Helical; Name=11. {ECO:0000255|PROSITE-
ProRule:PRU00441}.
TOPO_DOM 597 939 Cytoplasmic. {ECO:0000250}.
TRANSMEM 940 960 Helical; Name=12. {ECO:0000255|PROSITE-
ProRule:PRU00441}.
TOPO_DOM 961 997 Extracellular. {ECO:0000250}.
TRANSMEM 998 1018 Helical; Name=13. {ECO:0000255|PROSITE-
ProRule:PRU00441}.
TOPO_DOM 1019 1061 Cytoplasmic. {ECO:0000250}.
TRANSMEM 1062 1082 Helical; Name=14. {ECO:0000255|PROSITE-
ProRule:PRU00441}.
TOPO_DOM 1083 1083 Extracellular. {ECO:0000250}.
TRANSMEM 1084 1104 Helical; Name=15. {ECO:0000255|PROSITE-
ProRule:PRU00441}.
TOPO_DOM 1105 1175 Cytoplasmic. {ECO:0000250}.
TRANSMEM 1176 1196 Helical; Name=16. {ECO:0000255|PROSITE-
ProRule:PRU00441}.
TOPO_DOM 1197 1198 Extracellular. {ECO:0000250}.
TRANSMEM 1199 1219 Helical; Name=17. {ECO:0000255|PROSITE-
ProRule:PRU00441}.
TOPO_DOM 1220 1503 Cytoplasmic. {ECO:0000250}.
DOMAIN 311 593 ABC transmembrane type-1 1.
{ECO:0000255|PROSITE-ProRule:PRU00441}.
DOMAIN 629 853 ABC transporter 1. {ECO:0000255|PROSITE-
ProRule:PRU00434}.
DOMAIN 947 1228 ABC transmembrane type-1 2.
{ECO:0000255|PROSITE-ProRule:PRU00441}.
DOMAIN 1265 1499 ABC transporter 2. {ECO:0000255|PROSITE-
ProRule:PRU00434}.
NP_BIND 663 670 ATP 1. {ECO:0000255|PROSITE-
ProRule:PRU00434}.
NP_BIND 1299 1306 ATP 2. {ECO:0000255|PROSITE-
ProRule:PRU00434}.
MOD_RES 1286 1286 Phosphoserine.
{ECO:0000244|PubMed:24275569}.
CARBOHYD 15 15 N-linked (GlcNAc...) asparagine.
{ECO:0000305|PubMed:12901863}.
VAR_SEQ 75 99 LGFALIVLCTSSVAVALWKIQQGTP -> AAIPGSLEPGNV
RGRQGTGWNLVKS (in isoform 2).
{ECO:0000303|PubMed:11431746,
ECO:0000303|PubMed:15489334}.
/FTId=VSP_047315.
VAR_SEQ 100 1503 Missing (in isoform 2).
{ECO:0000303|PubMed:11431746,
ECO:0000303|PubMed:15489334}.
/FTId=VSP_047316.
VAR_SEQ 806 871 TRILVTHALHILPQADWIIVLANGAIAEMGSYQELLQRKGA
LMCLLDQARQPGDRGEGETEPGTST -> KQNLGPAPRTPE
APLQAGGPSLDARGPSSQSLRRTVPLQKPRQRFLWMTLTGQ
DGQQERTASNTAG (in isoform 3).
{ECO:0000303|PubMed:21318057}.
/FTId=VSP_057077.
VAR_SEQ 872 1503 Missing (in isoform 3).
{ECO:0000303|PubMed:21318057}.
/FTId=VSP_057078.
VARIANT 4 4 P -> H (found in patient with putative
diagnosis of PXE; uncertain pathological
significance; loss-of-function mutation;
localization comparable to wild-type).
{ECO:0000269|PubMed:25615550}.
/FTId=VAR_072803.
VARIANT 9 9 A -> E (found in patient with putative
diagnosis of PXE; uncertain pathological
significance; loss-of-function mutation;
localization comparable to wild-type).
{ECO:0000269|PubMed:25615550}.
/FTId=VAR_072804.
VARIANT 21 21 P -> S (found in patient with putative
diagnosis of PXE; uncertain pathological
significance; loss-of-function mutation;
localization comparable to wild-type).
{ECO:0000269|PubMed:25615550}.
/FTId=VAR_072805.
VARIANT 60 62 Missing (in PXE; autosomal recessive).
{ECO:0000269|PubMed:11702217,
ECO:0000269|PubMed:16086317,
ECO:0000269|PubMed:17617515}.
/FTId=VAR_013363.
VARIANT 61 61 G -> D (in dbSNP:rs72657696).
{ECO:0000269|PubMed:11536079}.
/FTId=VAR_013364.
VARIANT 64 64 R -> Q (found in patient with putative
diagnosis of PXE; uncertain pathological
significance; localization comparable to
wild-type; dbSNP:rs777566074).
{ECO:0000269|PubMed:25615550}.
/FTId=VAR_072806.
VARIANT 64 64 R -> W (in dbSNP:rs557180313).
{ECO:0000269|PubMed:10493829,
ECO:0000269|PubMed:11058917,
ECO:0000269|PubMed:9892204}.
/FTId=VAR_013365.
VARIANT 74 74 Missing (in PXE).
{ECO:0000269|PubMed:15086542}.
/FTId=VAR_067840.
VARIANT 78 78 A -> T (in PXE; dbSNP:rs2856597).
{ECO:0000269|PubMed:16086317,
ECO:0000269|PubMed:19339160,
ECO:0000269|PubMed:25615550}.
/FTId=VAR_067841.
VARIANT 90 90 A -> T (found in patient with putative
diagnosis of PXE; uncertain pathological
significance).
{ECO:0000269|PubMed:25615550}.
/FTId=VAR_072807.
VARIANT 125 125 E -> K (in PXE; loss-of-function
mutation; localization comparable to
wild-type; dbSNP:rs3853814).
{ECO:0000269|PubMed:16086317,
ECO:0000269|PubMed:25615550}.
/FTId=VAR_067842.
VARIANT 129 129 G -> E (in PXE; autosomal recessive;
dbSNP:rs72653753).
{ECO:0000269|PubMed:16086317}.
/FTId=VAR_067843.
VARIANT 158 158 A -> V (in dbSNP:rs2606921).
{ECO:0000269|PubMed:16086317}.
/FTId=VAR_067844.
VARIANT 207 207 G -> R (in dbSNP:rs72657697).
{ECO:0000269|PubMed:11536079}.
/FTId=VAR_013366.
VARIANT 265 265 R -> G (in dbSNP:rs72657698).
{ECO:0000269|PubMed:11536079,
ECO:0000269|PubMed:11702217,
ECO:0000269|PubMed:16086317,
ECO:0000269|PubMed:19339160}.
/FTId=VAR_013367.
VARIANT 281 281 K -> E (in dbSNP:rs4780606).
{ECO:0000269|PubMed:11536079,
ECO:0000269|PubMed:16086317}.
/FTId=VAR_013368.
VARIANT 317 317 S -> R (in PXE; autosomal recessive;
dbSNP:rs78678589).
{ECO:0000269|PubMed:16086317,
ECO:0000269|PubMed:17617515}.
/FTId=VAR_067845.
VARIANT 319 319 I -> V (in dbSNP:rs72657699).
{ECO:0000269|PubMed:11536079,
ECO:0000269|PubMed:16086317,
ECO:0000269|PubMed:21318057}.
/FTId=VAR_013369.
VARIANT 355 355 L -> R (in GACI2 and PXE; autosomal
recessive; dbSNP:rs72653758).
{ECO:0000269|PubMed:16086317,
ECO:0000269|PubMed:22209248}.
/FTId=VAR_067846.
VARIANT 363 373 Missing (in PXE).
{ECO:0000269|PubMed:15086542}.
/FTId=VAR_067847.
VARIANT 364 364 T -> R (in PXE; autosomal recessive;
dbSNP:rs72653759).
{ECO:0000269|PubMed:11702217,
ECO:0000269|PubMed:15459974,
ECO:0000269|PubMed:16086317,
ECO:0000269|PubMed:17617515}.
/FTId=VAR_013370.
VARIANT 370 370 N -> D (in PXE; autosomal recessive;
dbSNP:rs72653760).
{ECO:0000269|PubMed:16086317}.
/FTId=VAR_067848.
VARIANT 382 382 R -> W (in PXE; dbSNP:rs72653761).
{ECO:0000269|PubMed:17617515}.
/FTId=VAR_067849.
VARIANT 391 391 R -> G (in GACI2 and PXE; autosomal
recessive; dbSNP:rs72653762).
{ECO:0000269|PubMed:15086542,
ECO:0000269|PubMed:16086317,
ECO:0000269|PubMed:17617515,
ECO:0000269|PubMed:22209248}.
/FTId=VAR_067850.
VARIANT 392 392 K -> N (in PXE; dbSNP:rs72653763).
{ECO:0000269|PubMed:17617515}.
/FTId=VAR_067851.
VARIANT 398 398 S -> G (in PXE; autosomal recessive;
dbSNP:rs72653764).
{ECO:0000269|PubMed:16086317}.
/FTId=VAR_067852.
VARIANT 411 411 N -> K (in PXE; autosomal dominant;
dbSNP:rs9930886).
{ECO:0000269|PubMed:11536079,
ECO:0000269|PubMed:15459974}.
/FTId=VAR_013371.
VARIANT 417 417 V -> M (in dbSNP:rs768869262).
{ECO:0000269|PubMed:19339160}.
/FTId=VAR_067853.
VARIANT 419 419 R -> Q (found in patient with putative
diagnosis of PXE; uncertain pathological
significance; loss-of-function mutation;
localization comparable to wild-type;
dbSNP:rs772434460).
{ECO:0000269|PubMed:25615550}.
/FTId=VAR_072808.
VARIANT 440 440 C -> G (in PXE; autosomal recessive;
dbSNP:rs72653766).
{ECO:0000269|PubMed:15459974}.
/FTId=VAR_067854.
VARIANT 455 455 A -> P (in PXE; autosomal dominant;
dbSNP:rs67996819).
{ECO:0000269|PubMed:11427982}.
/FTId=VAR_013372.
VARIANT 463 463 L -> H (in PXE; dbSNP:rs72653767).
/FTId=VAR_067855.
VARIANT 495 495 L -> H (in PXE; autosomal recessive;
dbSNP:rs72653769).
{ECO:0000269|PubMed:16086317,
ECO:0000269|PubMed:17617515}.
/FTId=VAR_067856.
VARIANT 497 497 N -> K (in dbSNP:rs72653770).
{ECO:0000269|PubMed:11536079}.
/FTId=VAR_013373.
VARIANT 514 514 V -> I (in dbSNP:rs59157279).
{ECO:0000269|PubMed:16086317}.
/FTId=VAR_067857.
VARIANT 518 518 R -> Q (in PXE; autosomal recessive;
dbSNP:rs72653772).
{ECO:0000269|PubMed:11536079,
ECO:0000269|PubMed:15086542,
ECO:0000269|PubMed:15459974,
ECO:0000269|PubMed:16086317,
ECO:0000269|PubMed:17617515,
ECO:0000269|PubMed:19339160}.
/FTId=VAR_013374.
VARIANT 535 535 S -> P (in PXE; dbSNP:rs72653773).
{ECO:0000269|PubMed:17617515}.
/FTId=VAR_067858.
VARIANT 551 551 F -> S (in PXE; autosomal recessive;
dbSNP:rs72653774).
{ECO:0000269|PubMed:16086317}.
/FTId=VAR_067859.
VARIANT 568 568 F -> S (in PXE; autosomal dominant;
dbSNP:rs66864704).
{ECO:0000269|PubMed:11536079,
ECO:0000269|PubMed:17617515}.
/FTId=VAR_013375.
VARIANT 590 590 S -> F (in GACI2; dbSNP:rs537233133).
{ECO:0000269|PubMed:22209248}.
/FTId=VAR_067860.
VARIANT 594 594 A -> V (in PXE; autosomal recessive;
dbSNP:rs72653776).
{ECO:0000269|PubMed:16086317}.
/FTId=VAR_067861.
VARIANT 600 600 R -> C (in PXE; autosomal recessive;
dbSNP:rs72653777).
{ECO:0000269|PubMed:15459974,
ECO:0000269|PubMed:17617515}.
/FTId=VAR_067862.
VARIANT 605 605 L -> P (found in patient with putative
diagnosis of PEX; uncertain pathological
significance; mutant protein is retained
in the cytoplasm; dbSNP:rs768271196).
{ECO:0000269|PubMed:25615550}.
/FTId=VAR_072809.
VARIANT 614 614 V -> A (in dbSNP:rs12931472).
{ECO:0000269|PubMed:10835642,
ECO:0000269|PubMed:11536079,
ECO:0000269|PubMed:11776382,
ECO:0000269|PubMed:15489334,
ECO:0000269|PubMed:16086317,
ECO:0000269|PubMed:19339160}.
/FTId=VAR_011490.
VARIANT 632 632 H -> Q (in dbSNP:rs8058694).
{ECO:0000269|PubMed:10954200,
ECO:0000269|PubMed:11536079,
ECO:0000269|PubMed:11776382,
ECO:0000269|PubMed:15489334,
ECO:0000269|PubMed:16086317,
ECO:0000269|PubMed:19339160}.
/FTId=VAR_013376.
VARIANT 663 663 G -> C (in PXE; dbSNP:rs72653780).
{ECO:0000269|PubMed:17617515}.
/FTId=VAR_067863.
VARIANT 665 665 V -> A (in dbSNP:rs4341770).
/FTId=VAR_055477.
VARIANT 673 673 L -> P (in PXE; autosomal dominant;
dbSNP:rs67470842).
{ECO:0000269|PubMed:11536079}.
/FTId=VAR_013377.
VARIANT 677 677 L -> P (in PXE; autosomal recessive;
dbSNP:rs72653782).
{ECO:0000269|PubMed:16086317}.
/FTId=VAR_067864.
VARIANT 698 698 Q -> P (in PXE; dbSNP:rs72653783).
{ECO:0000269|PubMed:17617515}.
/FTId=VAR_067865.
VARIANT 699 699 E -> D (in PXE; dbSNP:rs72653784).
{ECO:0000269|PubMed:17617515}.
/FTId=VAR_067866.
VARIANT 709 709 E -> G (found in patient with putative
diagnosis of PEX; uncertain pathological
significance; loss-of-function mutation;
localization comparable to wild-type).
{ECO:0000269|PubMed:25615550}.
/FTId=VAR_072810.
VARIANT 724 724 R -> K (in dbSNP:rs58073789).
{ECO:0000269|PubMed:16086317}.
/FTId=VAR_067867.
VARIANT 724 724 R -> L. {ECO:0000269|PubMed:19339160}.
/FTId=VAR_067868.
VARIANT 726 726 L -> P (in PXE; dbSNP:rs72653785).
{ECO:0000269|PubMed:17617515,
ECO:0000269|PubMed:19339160}.
/FTId=VAR_067869.
VARIANT 742 742 I -> V (in dbSNP:rs59593133).
{ECO:0000269|PubMed:16086317,
ECO:0000269|PubMed:19339160}.
/FTId=VAR_067870.
VARIANT 751 751 M -> K (in PXE; dbSNP:rs72653786).
{ECO:0000269|PubMed:17617515}.
/FTId=VAR_067871.
VARIANT 755 755 G -> R (in PXE; dbSNP:rs72653787).
{ECO:0000269|PubMed:17617515}.
/FTId=VAR_067872.
VARIANT 760 760 R -> W (in PXE; autosomal recessive;
dbSNP:rs72653788).
{ECO:0000269|PubMed:16086317,
ECO:0000269|PubMed:17617515}.
/FTId=VAR_067873.
VARIANT 765 765 R -> Q (in PXE; autosomal dominant and
autosomal recessive; dbSNP:rs67561842).
{ECO:0000269|PubMed:11536079,
ECO:0000269|PubMed:16086317,
ECO:0000269|PubMed:17617515,
ECO:0000269|PubMed:20034067}.
/FTId=VAR_013378.
VARIANT 766 766 A -> D (in PXE; autosomal recessive;
dbSNP:rs72653789).
{ECO:0000269|PubMed:15086542}.
/FTId=VAR_067874.
VARIANT 777 777 D -> N (in PXE; dbSNP:rs72653790).
{ECO:0000269|PubMed:17617515}.
/FTId=VAR_067875.
VARIANT 807 807 R -> Q (in PXE; autosomal recessive;
dbSNP:rs72653794).
{ECO:0000269|PubMed:16086317}.
/FTId=VAR_067876.
VARIANT 807 807 R -> W (in PXE; autosomal recessive;
dbSNP:rs72653793).
{ECO:0000269|PubMed:16086317}.
/FTId=VAR_067877.
VARIANT 810 810 V -> M (in PXE; autosomal recessive;
dbSNP:rs72653795).
{ECO:0000269|PubMed:15459974}.
/FTId=VAR_067878.
VARIANT 811 811 T -> M (in PXE; dbSNP:rs72653796).
{ECO:0000269|PubMed:17617515}.
/FTId=VAR_067879.
VARIANT 820 820 A -> P (in PXE; autosomal recessive;
dbSNP:rs72653797).
{ECO:0000269|PubMed:15459974}.
/FTId=VAR_067880.
VARIANT 834 834 M -> T (found in patient with putative
diagnosis of PEX; uncertain pathological
significance; loss-of-function mutation;
localization comparable to wild-type).
{ECO:0000269|PubMed:25615550}.
/FTId=VAR_072811.
VARIANT 848 848 M -> V (in dbSNP:rs6416668).
{ECO:0000269|PubMed:10424734,
ECO:0000269|PubMed:10493829,
ECO:0000269|PubMed:15489334,
ECO:0000269|PubMed:19339160,
ECO:0000269|PubMed:21318057,
ECO:0000269|PubMed:9892204}.
/FTId=VAR_059108.
VARIANT 881 881 R -> S (in PXE; dbSNP:rs72653800).
{ECO:0000269|PubMed:17617515}.
/FTId=VAR_067881.
VARIANT 944 944 T -> I (in PXE; dbSNP:rs72653801).
{ECO:0000269|PubMed:17617515}.
/FTId=VAR_067882.
VARIANT 946 946 L -> I (in dbSNP:rs61340537).
{ECO:0000269|PubMed:16086317,
ECO:0000269|PubMed:19339160}.
/FTId=VAR_067883.
VARIANT 948 948 L -> P (found in patient with putative
diagnosis of PEX; uncertain pathological
significance; loss-of-function mutation;
localization comparable to wild-type).
{ECO:0000269|PubMed:25615550}.
/FTId=VAR_072812.
VARIANT 950 950 A -> T (in PXE; dbSNP:rs72657689).
{ECO:0000269|PubMed:17617515}.
/FTId=VAR_067884.
VARIANT 953 953 L -> H (in dbSNP:rs72657700).
{ECO:0000269|PubMed:11536079}.
/FTId=VAR_013379.
VARIANT 992 992 G -> R (in PXE; dbSNP:rs72657692).
{ECO:0000269|PubMed:17617515}.
/FTId=VAR_067885.
VARIANT 1036 1036 Missing (in GACI2 and PXE; autosomal
recessive). {ECO:0000269|PubMed:16086317,
ECO:0000269|PubMed:22209248}.
/FTId=VAR_067886.
VARIANT 1048 1048 Missing (in PXE; autosomal recessive).
{ECO:0000269|PubMed:16086317}.
/FTId=VAR_067887.
VARIANT 1056 1056 D -> E (in PXE; dbSNP:rs72657694).
{ECO:0000269|PubMed:16086317}.
/FTId=VAR_067888.
VARIANT 1064 1064 R -> W (in dbSNP:rs41278174).
{ECO:0000269|PubMed:16086317}.
/FTId=VAR_067889.
VARIANT 1097 1097 L -> I (in dbSNP:rs60707953).
/FTId=VAR_060988.
VARIANT 1114 1114 R -> C (in GACI2 and PXE; autosomal
recessive; dbSNP:rs63749794).
{ECO:0000269|PubMed:15459974,
ECO:0000269|PubMed:16086317,
ECO:0000269|PubMed:17617515,
ECO:0000269|PubMed:22209248}.
/FTId=VAR_067890.
VARIANT 1114 1114 R -> P (in PXE; autosomal recessive;
dbSNP:rs63750427).
{ECO:0000269|PubMed:10835642,
ECO:0000269|PubMed:11536079}.
/FTId=VAR_011491.
VARIANT 1121 1121 S -> L (in PXE; dbSNP:rs63750987).
{ECO:0000269|PubMed:16086317}.
/FTId=VAR_067891.
VARIANT 1121 1121 S -> W (in PXE; autosomal dominant;
dbSNP:rs63750987).
{ECO:0000269|PubMed:11536079}.
/FTId=VAR_013380.
VARIANT 1130 1130 T -> M (in PXE; autosomal recessive;
dbSNP:rs63750459).
{ECO:0000269|PubMed:15086542,
ECO:0000269|PubMed:15459974,
ECO:0000269|PubMed:17617515}.
/FTId=VAR_067892.
VARIANT 1133 1133 G -> A (in PXE; dbSNP:rs63750473).
{ECO:0000269|PubMed:17617515}.
/FTId=VAR_067893.
VARIANT 1138 1138 R -> P (in PXE; autosomal dominant;
dbSNP:rs60791294).
{ECO:0000269|PubMed:11536079}.
/FTId=VAR_013381.
VARIANT 1138 1138 R -> Q (in PXE; autosomal recessive;
dbSNP:rs60791294).
{ECO:0000269|PubMed:10835642,
ECO:0000269|PubMed:11536079,
ECO:0000269|PubMed:15459974,
ECO:0000269|PubMed:16086317,
ECO:0000269|PubMed:17617515,
ECO:0000269|PubMed:19339160}.
/FTId=VAR_011492.
VARIANT 1138 1138 R -> W (in PXE; autosomal recessive;
dbSNP:rs28939701).
{ECO:0000269|PubMed:10811882,
ECO:0000269|PubMed:16086317,
ECO:0000269|PubMed:17617515}.
/FTId=VAR_011493.
VARIANT 1139 1139 A -> T (in PXE; dbSNP:rs63750146).
{ECO:0000269|PubMed:17617515}.
/FTId=VAR_067894.
VARIANT 1164 1164 R -> Q (in PXE; autosomal recessive;
dbSNP:rs63750457).
{ECO:0000269|PubMed:16086317,
ECO:0000269|PubMed:17617515}.
/FTId=VAR_067895.
VARIANT 1203 1203 G -> D (in PXE; autosomal dominant;
dbSNP:rs63750607).
{ECO:0000269|PubMed:11536079}.
/FTId=VAR_013382.
VARIANT 1221 1221 R -> C (in PXE; autosomal recessive;
dbSNP:rs63751215).
{ECO:0000269|PubMed:16086317,
ECO:0000269|PubMed:17617515}.
/FTId=VAR_067896.
VARIANT 1221 1221 R -> H (in GACI2; dbSNP:rs63751001).
{ECO:0000269|PubMed:17617515,
ECO:0000269|PubMed:22209248}.
/FTId=VAR_067897.
VARIANT 1226 1226 L -> I (in PXE; dbSNP:rs63750125).
{ECO:0000269|PubMed:17617515}.
/FTId=VAR_067898.
VARIANT 1235 1235 R -> W (in PXE; autosomal recessive;
dbSNP:rs63750402).
{ECO:0000269|PubMed:16086317}.
/FTId=VAR_067899.
VARIANT 1238 1238 D -> H (in PXE; pseudodominant;
dbSNP:rs63749796).
{ECO:0000269|PubMed:15086542}.
/FTId=VAR_067900.
VARIANT 1241 1241 W -> C (in dbSNP:rs72657701).
{ECO:0000269|PubMed:11536079}.
/FTId=VAR_013383.
VARIANT 1268 1268 R -> Q (associated with lower plasma
triglycerides and higher plasma HDL
cholesterol; dbSNP:rs2238472).
{ECO:0000269|PubMed:10811882,
ECO:0000269|PubMed:10913334,
ECO:0000269|PubMed:11536079,
ECO:0000269|PubMed:11776382,
ECO:0000269|PubMed:16086317,
ECO:0000269|PubMed:18987736}.
/FTId=VAR_011494.
VARIANT 1298 1298 V -> F (in PXE; autosomal dominant;
abolishes LTC4 and NEM-GS transport;
dbSNP:rs63751325).
{ECO:0000269|PubMed:11536079,
ECO:0000269|PubMed:11880368,
ECO:0000269|PubMed:17617515}.
/FTId=VAR_013384.
VARIANT 1301 1301 T -> I (in PXE; autosomal dominant;
dbSNP:rs63750494).
{ECO:0000269|PubMed:11536079}.
/FTId=VAR_013385.
VARIANT 1302 1302 G -> R (in PXE; autosomal dominant and
autosomal recessive; abolishes LTC4 and
NEM-GS transport; dbSNP:rs63749856).
{ECO:0000269|PubMed:11536079,
ECO:0000269|PubMed:11880368,
ECO:0000269|PubMed:16086317,
ECO:0000269|PubMed:17617515,
ECO:0000269|PubMed:19339160}.
/FTId=VAR_013386.
VARIANT 1303 1303 A -> P (in PXE; autosomal dominant and
autosomal recessive; dbSNP:rs63750410).
{ECO:0000269|PubMed:11536079,
ECO:0000269|PubMed:16086317,
ECO:0000269|PubMed:17617515}.
/FTId=VAR_013387.
VARIANT 1314 1314 R -> Q (in PXE; autosomal dominant and
autosomal recessive; dbSNP:rs63751086).
{ECO:0000269|PubMed:11536079,
ECO:0000269|PubMed:16086317,
ECO:0000269|PubMed:17617515}.
/FTId=VAR_013388.
VARIANT 1314 1314 R -> W (in GACI2 and PXE; autosomal
recessive; dbSNP:rs63750759).
{ECO:0000269|PubMed:10835642,
ECO:0000269|PubMed:11536079,
ECO:0000269|PubMed:17617515,
ECO:0000269|PubMed:22209248}.
/FTId=VAR_011495.
VARIANT 1321 1321 G -> S (in PXE; autosomal dominant;
abolishes LTC4 and NEM-GS transport;
dbSNP:rs63749823).
{ECO:0000269|PubMed:11536079,
ECO:0000269|PubMed:11880368}.
/FTId=VAR_013389.
VARIANT 1335 1335 L -> P (in PXE; autosomal recessive;
dbSNP:rs63750414).
{ECO:0000269|PubMed:15086542,
ECO:0000269|PubMed:19339160}.
/FTId=VAR_067901.
VARIANT 1335 1335 L -> Q (in PXE; dbSNP:rs63750414).
{ECO:0000269|PubMed:17617515}.
/FTId=VAR_067902.
VARIANT 1339 1339 R -> C (in PXE; autosomal recessive;
dbSNP:rs28939702).
{ECO:0000269|PubMed:10954200,
ECO:0000269|PubMed:11536079,
ECO:0000269|PubMed:15459974,
ECO:0000269|PubMed:16086317,
ECO:0000269|PubMed:17617515,
ECO:0000269|PubMed:19339160}.
/FTId=VAR_013390.
VARIANT 1339 1339 R -> H (in PXE; autosomal recessive;
dbSNP:rs63750622).
{ECO:0000269|PubMed:17617515}.
/FTId=VAR_067904.
VARIANT 1339 1339 R -> L (in PXE; autosomal recessive;
dbSNP:rs63750622).
{ECO:0000269|PubMed:16086317}.
/FTId=VAR_067903.
VARIANT 1346 1346 P -> S (in PXE; autosomal recessive;
dbSNP:rs63751112).
{ECO:0000269|PubMed:15459974}.
/FTId=VAR_067905.
VARIANT 1347 1347 Q -> H (in PXE; autosomal dominant;
dbSNP:rs63751111).
{ECO:0000269|PubMed:11536079}.
/FTId=VAR_013391.
VARIANT 1354 1354 G -> R (in PXE; autosomal recessive;
dbSNP:rs63750018).
{ECO:0000269|PubMed:11702217}.
/FTId=VAR_013392.
VARIANT 1357 1357 R -> W (in PXE; autosomal recessive;
dbSNP:rs63750428).
{ECO:0000269|PubMed:16086317}.
/FTId=VAR_067906.
VARIANT 1361 1361 D -> N (in PXE; autosomal dominant;
dbSNP:rs58695352).
{ECO:0000269|PubMed:11536079}.
/FTId=VAR_013393.
VARIANT 1400 1400 E -> K (in PXE; autosomal recessive;
dbSNP:rs63751241).
{ECO:0000269|PubMed:15086542,
ECO:0000269|PubMed:15459974}.
/FTId=VAR_067907.
VARIANT 1406 1406 Q -> K (in PXE; autosomal recessive;
dbSNP:rs387906859).
{ECO:0000269|PubMed:20034067}.
/FTId=VAR_067908.
VARIANT 1424 1424 I -> T (in PXE; autosomal dominant;
dbSNP:rs63750295).
{ECO:0000269|PubMed:11536079}.
/FTId=VAR_013394.
VARIANT 1442 1442 A -> T (found in patient with putative
diagnosis of PEX; uncertain pathological
significance).
{ECO:0000269|PubMed:25615550}.
/FTId=VAR_072813.
VARIANT 1459 1459 R -> C (in PXE; putative autosomal
dominant; dbSNP:rs72547524).
{ECO:0000269|PubMed:15098239}.
/FTId=VAR_067909.
CONFLICT 6 6 E -> Q (in Ref. 4; CAO81806).
{ECO:0000305}.
CONFLICT 377 377 L -> P (in Ref. 1; AAD51293).
{ECO:0000305}.
CONFLICT 401 401 R -> K (in Ref. 4; CAO81806).
{ECO:0000305}.
CONFLICT 986 986 L -> P (in Ref. 4; CAO81806).
{ECO:0000305}.
CONFLICT 1274 1274 Y -> C (in Ref. 1; AAD51293).
{ECO:0000305}.
CONFLICT 1455 1455 L -> P (in Ref. 1; AAD51293).
{ECO:0000305}.
SEQUENCE 1503 AA; 164906 MW; 2107BE13B1547B39 CRC64;
MAAPAEPCAG QGVWNQTEPE PAATSLLSLC FLRTAGVWVP PMYLWVLGPI YLLFIHHHGR
GYLRMSPLFK AKMVLGFALI VLCTSSVAVA LWKIQQGTPE APEFLIHPTV WLTTMSFAVF
LIHTERKKGV QSSGVLFGYW LLCFVLPATN AAQQASGAGF QSDPVRHLST YLCLSLVVAQ
FVLSCLADQP PFFPEDPQQS NPCPETGAAF PSKATFWWVS GLVWRGYRRP LRPKDLWSLG
RENSSEELVS RLEKEWMRNR SAARRHNKAI AFKRKGGSGM KAPETEPFLR QEGSQWRPLL
KAIWQVFHST FLLGTLSLII SDVFRFTVPK LLSLFLEFIG DPKPPAWKGY LLAVLMFLSA
CLQTLFEQQN MYRLKVLQMR LRSAITGLVY RKVLALSSGS RKASAVGDVV NLVSVDVQRL
TESVLYLNGL WLPLVWIVVC FVYLWQLLGP SALTAIAVFL SLLPLNFFIS KKRNHHQEEQ
MRQKDSRARL TSSILRNSKT IKFHGWEGAF LDRVLGIRGQ ELGALRTSGL LFSVSLVSFQ
VSTFLVALVV FAVHTLVAEN AMNAEKAFVT LTVLNILNKA QAFLPFSIHS LVQARVSFDR
LVTFLCLEEV DPGVVDSSSS GSAAGKDCIT IHSATFAWSQ ESPPCLHRIN LTVPQGCLLA
VVGPVGAGKS SLLSALLGEL SKVEGFVSIE GAVAYVPQEA WVQNTSVVEN VCFGQELDPP
WLERVLEACA LQPDVDSFPE GIHTSIGEQG MNLSGGQKQR LSLARAVYRK AAVYLLDDPL
AALDAHVGQH VFNQVIGPGG LLQGTTRILV THALHILPQA DWIIVLANGA IAEMGSYQEL
LQRKGALMCL LDQARQPGDR GEGETEPGTS TKDPRGTSAG RRPELRRERS IKSVPEKDRT
TSEAQTEVPL DDPDRAGWPA GKDSIQYGRV KATVHLAYLR AVGTPLCLYA LFLFLCQQVA
SFCRGYWLSL WADDPAVGGQ QTQAALRGGI FGLLGCLQAI GLFASMAAVL LGGARASRLL
FQRLLWDVVR SPISFFERTP IGHLLNRFSK ETDTVDVDIP DKLRSLLMYA FGLLEVSLVV
AVATPLATVA ILPLFLLYAG FQSLYVVSSC QLRRLESASY SSVCSHMAET FQGSTVVRAF
RTQAPFVAQN NARVDESQRI SFPRLVADRW LAANVELLGN GLVFAAATCA VLSKAHLSAG
LVGFSVSAAL QVTQTLQWVV RNWTDLENSI VSVERMQDYA WTPKEAPWRL PTCAAQPPWP
QGGQIEFRDF GLRYRPELPL AVQGVSFKIH AGEKVGIVGR TGAGKSSLAS GLLRLQEAAE
GGIWIDGVPI AHVGLHTLRS RISIIPQDPI LFPGSLRMNL DLLQEHSDEA IWAALETVQL
KALVASLPGQ LQYKCADRGE DLSVGQKQLL CLARALLRKT QILILDEATA AVDPGTELQM
QAMLGSWFAQ CTVLLIAHRL RSVMDCARVL VMDKGQVAES GSPAQLLAQK GLFYRLAQES
GLV


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