MRP6_HUMAN
ID MRP6_HUMAN Reviewed; 1503 AA.
AC O95255; A2RRN8; A8KIG6; A8Y988; E7ESW8; P78420; Q8TCY8; Q9UMZ7;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 24-NOV-2009, sequence version 2.
DT 03-AUG-2022, entry version 221.
DE RecName: Full=ATP-binding cassette sub-family C member 6;
DE EC=7.6.2.- {ECO:0000250|UniProtKB:O88269};
DE EC=7.6.2.3 {ECO:0000269|PubMed:11880368, ECO:0000269|PubMed:12414644};
DE AltName: Full=Anthracycline resistance-associated protein;
DE AltName: Full=Multi-specific organic anion transporter E;
DE Short=MOAT-E;
DE AltName: Full=Multidrug resistance-associated protein 6;
GN Name=ABCC6; Synonyms=ARA, MRP6;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT VAL-848.
RX PubMed=10424734; DOI=10.1038/sj.bjc.6690527;
RA Belinsky M.G., Kruh G.D.;
RT "MOAT-E (ARA) is a full-length MRP/cMOAT subfamily transporter expressed in
RT kidney and liver.";
RL Br. J. Cancer 80:1342-1349(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS TRP-64 AND VAL-848.
RX PubMed=9892204;
RA Kool M., van der Linden M., de Haas M., Baas F., Borst P.;
RT "Expression of human MRP6, a homologue of the multidrug resistance protein
RT gene MRP1, in tissues and cancer cells.";
RL Cancer Res. 59:175-182(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RX PubMed=11431746; DOI=10.1053/jhep.2001.25545;
RA Lian Z., Liu J., Pan J., Tufan N.L.S., Zhu M., Arbuthnot P., Kew M.,
RA Clayton M.M., Feitelson M.A.;
RT "A cellular gene up-regulated by hepatitis B virus-encoded X antigen
RT promotes hepatocellular growth and survival.";
RL Hepatology 34:146-157(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3), VARIANTS VAL-319 AND
RP VAL-848, AND ALTERNATIVE SPLICING.
RC TISSUE=Liver;
RX PubMed=21318057; DOI=10.1155/2008/912478;
RA Armentano M.F., Ostuni A., Infantino V., Iacobazzi V.,
RA Castiglione Morelli M.A., Bisaccia F.;
RT "Identification of a new splice variant of the human ABCC6 transporter.";
RL Biochem. Res. Int. 2008:912478-912478(2008).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANTS TRP-64 AND
RP VAL-848.
RX PubMed=10493829; DOI=10.1006/geno.1999.5927;
RA Loftus B.J., Kim U.-J., Sneddon V.P., Kalush F., Brandon R., Fuhrmann J.,
RA Mason T., Crosby M.L., Barnstead M., Cronin L., Mays A.D., Cao Y., Xu R.X.,
RA Kang H.-L., Mitchell S., Eichler E.E., Harris P.C., Venter J.C.,
RA Adams M.D.;
RT "Genome duplications and other features in 12 Mb of DNA sequence from human
RT chromosome 16p and 16q.";
RL Genomics 60:295-308(1999).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANTS
RP ALA-614; GLN-632 AND VAL-848.
RC TISSUE=Retinoblastoma;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP CATALYTIC ACTIVITY, FUNCTION, AND COFACTOR.
RX PubMed=12414644;
RA Belinsky M.G., Chen Z.S., Shchaveleva I., Zeng H., Kruh G.D.;
RT "Characterization of the drug resistance and transport properties of
RT multidrug resistance protein 6 (MRP6, ABCC6).";
RL Cancer Res. 62:6172-6177(2002).
RN [9]
RP FUNCTION, CHARACTERIZATION OF VARIANTS PXE PHE-1298; ARG-1302 AND SER-1321,
RP CATALYTIC ACTIVITY, COFACTOR, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=11880368; DOI=10.1074/jbc.m110918200;
RA Ilias A., Urban Z., Seidl T.L., Le Saux O., Sinko E., Boyd C.D.,
RA Sarkadi B., Varadi A.;
RT "Loss of ATP-dependent transport activity in pseudoxanthoma elasticum-
RT associated mutants of human ABCC6 (MRP6).";
RL J. Biol. Chem. 277:16860-16867(2002).
RN [10]
RP REVIEW, AND VARIANT PXE PRO-455.
RX PubMed=11427982; DOI=10.1016/s1471-4914(00)01869-4;
RA Uitto J., Pulkkinen L., Ringpfeil F.;
RT "Molecular genetics of pseudoxanthoma elasticum: a metabolic disorder at
RT the environment-genome interface?";
RL Trends Mol. Med. 7:13-17(2001).
RN [11]
RP SUBCELLULAR LOCATION, TOPOLOGY, AND GLYCOSYLATION AT ASN-15.
RX PubMed=12901863; DOI=10.1016/s0006-291x(03)01349-4;
RA Sinko E., Ilias A., Ujhelly O., Homolya L., Scheffer G.L., Bergen A.A.,
RA Sarkadi B., Varadi A.;
RT "Subcellular localization and N-glycosylation of human ABCC6, expressed in
RT MDCKII cells.";
RL Biochem. Biophys. Res. Commun. 308:263-269(2003).
RN [12]
RP SUBCELLULAR LOCATION.
RX PubMed=23625951; DOI=10.1161/circresaha.111.300194;
RA Pomozi V., Le Saux O., Brampton C., Apana A., Ilias A., Szeri F.,
RA Martin L., Monostory K., Paku S., Sarkadi B., Szakacs G., Varadi A.;
RT "ABCC6 is a basolateral plasma membrane protein.";
RL Circ. Res. 112:E148-E151(2013).
RN [13]
RP FUNCTION (ISOFORM 2), INDUCTION (ISOFORM 2), AND SUBCELLULAR LOCATION
RP (ISOFORM 2).
RX PubMed=23912081; DOI=10.1016/j.febslet.2013.07.042;
RA Ostuni A., Lara P., Armentano M.F., Miglionico R., Salvia A.M., Monnich M.,
RA Carmosino M., Lasorsa F.M., Monne M., Nilsson I., Bisaccia F.;
RT "The hepatitis B x antigen anti-apoptotic effector URG7 is localized to the
RT endoplasmic reticulum membrane.";
RL FEBS Lett. 587:3058-3062(2013).
RN [14]
RP FUNCTION, AND CHARACTERIZATION OF VARIANT PXE PHE-1298.
RX PubMed=24277820; DOI=10.1073/pnas.1319582110;
RA Jansen R.S., Kuecuekosmanoglu A., de Haas M., Sapthu S., Otero J.A.,
RA Hegman I.E., Bergen A.A., Gorgels T.G., Borst P., van de Wetering K.;
RT "ABCC6 prevents ectopic mineralization seen in pseudoxanthoma elasticum by
RT inducing cellular nucleotide release.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:20206-20211(2013).
RN [15]
RP FUNCTION.
RX PubMed=24969777; DOI=10.1161/atvbaha.114.304017;
RA Jansen R.S., Duijst S., Mahakena S., Sommer D., Szeri F., Varadi A.,
RA Plomp A., Bergen A.A., Oude Elferink R.P., Borst P., van de Wetering K.;
RT "ABCC6-mediated ATP secretion by the liver is the main source of the
RT mineralization inhibitor inorganic pyrophosphate in the systemic
RT circulation-brief report.";
RL Arterioscler. Thromb. Vasc. Biol. 34:1985-1989(2014).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1286, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [17]
RP VARIANT GLN-1268.
RX PubMed=10913334; DOI=10.1006/bbrc.2000.3101;
RA Germain D.P., Perdu J., Remones V., Jeunemaitre X.;
RT "Homozygosity for the R1268Q mutation in MRP6, the pseudoxanthoma elasticum
RT gene, is not disease-causing.";
RL Biochem. Biophys. Res. Commun. 274:297-301(2000).
RN [18]
RP VARIANT TRP-64.
RX PubMed=11058917;
RX DOI=10.1002/1098-1004(200011)16:5<449::aid-humu24>3.0.co;2-o;
RA Germain D.P., Perdu J., Remones V., Manzoni K., Jeunemaitre X.;
RT "Identification of two polymorphisms (c189G>C; c190T>C) in exon 2 of the
RT human MRP6 gene (ABCC6) by screening of Pseudoxanthoma elasticum patients:
RT possible sequence correction?";
RL Hum. Mutat. 16:449-449(2000).
RN [19]
RP VARIANT PXE CYS-1339, AND VARIANT GLN-632.
RX PubMed=10954200; DOI=10.1007/s001090000114;
RA Struk B., Cai L., Zaech S., Ji W., Chung J., Lumsden A., Stumm M.,
RA Huber M., Schaen L., Kim C.-A., Goldsmith L.A., Viljoen D., Figuera L.E.,
RA Fuchs W., Munier F., Ramesar R., Hohl D., Richards R., Neldner K.H.,
RA Lindpaintner K.;
RT "Mutations of the gene encoding the transmembrane transporter protein ABC-
RT C6 cause pseudoxanthoma elasticum.";
RL J. Mol. Med. 78:282-286(2000).
RN [20]
RP VARIANTS PXE PRO-1114; GLN-1138 AND TRP-1314, AND VARIANT ALA-614.
RX PubMed=10835642; DOI=10.1038/76102;
RA Le Saux O., Urban Z., Tschuch C., Csiszar K., Bacchelli B., Quaglino D.,
RA Pasquali-Ronchetti I., Pope F.M., Richards A., Terry S., Bercovitch L.,
RA de Paepe A., Boyd C.D.;
RT "Mutations in a gene encoding an ABC transporter cause pseudoxanthoma
RT elasticum.";
RL Nat. Genet. 25:223-227(2000).
RN [21]
RP VARIANT PXE TRP-1138, AND VARIANT GLN-1268.
RX PubMed=10811882; DOI=10.1073/pnas.100041297;
RA Ringpfeil F., Lebwohl M.G., Christiano A.M., Uitto J.;
RT "Pseudoxanthoma elasticum: mutations in the MRP6 gene encoding a
RT transmembrane ATP-binding cassette (ABC) transporter.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:6001-6006(2000).
RN [22]
RP VARIANTS PXE LYS-411; GLN-518; SER-568; PRO-673; GLN-765; PRO-1114;
RP TRP-1121; PRO-1138; GLN-1138; ASP-1203; PHE-1298; ILE-1301; ARG-1302;
RP PRO-1303; GLN-1314; TRP-1314; SER-1321; CYS-1339; HIS-1347; ASN-1361 AND
RP THR-1424, AND VARIANTS ASP-61; ARG-207; GLY-265; GLU-281; VAL-319; LYS-497;
RP ALA-614; GLN-632; HIS-953; CYS-1241 AND GLN-1268.
RX PubMed=11536079; DOI=10.1086/323704;
RA Le Saux O., Beck K., Sachsinger C., Silvestri C., Treiber C.,
RA Goering H.H.H., Johnson E.W., De Paepe A., Pope F.M.,
RA Pasquali-Ronchetti I., Bercovitch L., Terry S., Boyd C.D.;
RT "A spectrum of ABCC6 mutations is responsible for pseudoxanthoma
RT elasticum.";
RL Am. J. Hum. Genet. 69:749-764(2001).
RN [23]
RP VARIANTS PXE 60-ARG--TYR-62 DEL; ARG-364 AND ARG-1354, AND VARIANT GLY-265.
RX PubMed=11702217; DOI=10.1007/s004390100582;
RA Pulkkinen L., Nakano A., Ringpfeil F., Uitto J.;
RT "Identification of ABCC6 pseudogenes on human chromosome 16p: implications
RT for mutation detection in pseudoxanthoma elasticum.";
RL Hum. Genet. 109:356-365(2001).
RN [24]
RP VARIANTS ALA-614; GLN-632 AND GLN-1268.
RX PubMed=11776382; DOI=10.1007/s100380170003;
RA Wang J., Near S., Young K., Connelly P.W., Hegele R.A.;
RT "ABCC6 gene polymorphism associated with variation in plasma
RT lipoproteins.";
RL J. Hum. Genet. 46:699-705(2001).
RN [25]
RP VARIANT PXE CYS-1459.
RX PubMed=15098239; DOI=10.1002/ajmg.a.20632;
RA Plomp A.S., Hu X., de Jong P.T., Bergen A.A.;
RT "Does autosomal dominant pseudoxanthoma elasticum exist?";
RL Am. J. Med. Genet. A 126:403-412(2004).
RN [26]
RP VARIANTS PXE ARG-364; LYS-411; GLY-440; GLN-518; CYS-600; MET-810; PRO-820;
RP CYS-1114; MET-1130; GLN-1138; CYS-1339; SER-1346 AND LYS-1400.
RX PubMed=15459974; DOI=10.1002/humu.9284;
RA Gheduzzi D., Guidetti R., Anzivino C., Tarugi P., Di Leo E., Quaglino D.,
RA Ronchetti I.P.;
RT "ABCC6 mutations in Italian families affected by pseudoxanthoma elasticum
RT (PXE).";
RL Hum. Mutat. 24:438-439(2004).
RN [27]
RP VARIANTS PXE VAL-74 DEL; 363-GLN--ARG-373 DEL; GLY-391; GLN-518; ASP-766;
RP MET-1130; GLN-1138 HIS-1238; PRO-1335 AND LYS-1400.
RX PubMed=15086542; DOI=10.1111/j.0022-202x.2004.22312.x;
RA Chassaing N., Martin L., Mazereeuw J., Barrie L., Nizard S., Bonafe J.L.,
RA Calvas P., Hovnanian A.;
RT "Novel ABCC6 mutations in pseudoxanthoma elasticum.";
RL J. Invest. Dermatol. 122:608-613(2004).
RN [28]
RP VARIANTS PXE 60-ARG--TYR-62 DEL; GLU-129; ARG-317; ARG-355; ARG-364;
RP ASP-370; GLY-391; GLY-398; HIS-495; GLN-518; SER-551; VAL-594; PRO-677;
RP TRP-760; GLN-765; GLN-807; TRP-807; GLU-1056; PHE-1036 DEL; PHE-1048 DEL;
RP CYS-1114; LEU-1121; GLN-1138; TRP-1138; GLN-1164; CYS-1221; TRP-1235;
RP ARG-1302; PRO-1303; GLN-1314; CYS-1339; LEU-1339 AND TRP-1357, AND VARIANTS
RP THR-78; LYS-125; VAL-158; GLY-265; GLU-281; VAL-319; ILE-514; ALA-614;
RP GLN-632; LYS-724; VAL-742; ILE-946; TRP-1064 AND GLN-1268.
RX PubMed=16086317; DOI=10.1002/humu.20206;
RA Miksch S., Lumsden A., Guenther U.P., Foernzler D., Christen-Zach S.,
RA Daugherty C., Ramesar R.K., Lebwohl M., Hohl D., Neldner K.H.,
RA Lindpaintner K., Richards R.I., Struk B.;
RT "Molecular genetics of pseudoxanthoma elasticum: type and frequency of
RT mutations in ABCC6.";
RL Hum. Mutat. 26:235-248(2005).
RN [29]
RP VARIANTS PXE 60-ARG--TYR-62 DEL; ARG-317; ARG-364; TRP-382; GLY-391;
RP ASN-392; HIS-463 HIS-495; GLN-518; PRO-535; SER-568; CYS-600; CYS-663;
RP PRO-698; ASP-699; PRO-726; LYS-751; ARG-755; TRP-760; GLN-765; ASN-777;
RP MET-811; SER-881; ILE-944; THR-950; ARG-992; CYS-1114; MET-1130; ALA-1133;
RP GLN-1138; TRP-1138; THR-1139; GLN-1164; CYS-1221; HIS-1221; ILE-1226;
RP PHE-1298; ARG-1302; PRO-1303; GLN-1314; TRP-1314; GLN-1335; CYS-1339;
RP HIS-1339 AND THR-1342.
RX PubMed=17617515; DOI=10.1136/jmg.2007.051094;
RA Pfendner E.G., Vanakker O.M., Terry S.F., Vourthis S., McAndrew P.E.,
RA McClain M.R., Fratta S., Marais A.S., Hariri S., Coucke P.J., Ramsay M.,
RA Viljoen D., Terry P.F., De Paepe A., Uitto J., Bercovitch L.G.;
RT "Mutation detection in the ABCC6 gene and genotype-phenotype analysis in a
RT large international case series affected by pseudoxanthoma elasticum.";
RL J. Med. Genet. 44:621-628(2007).
RN [30]
RP VARIANT [LARGE SCALE ANALYSIS] GLN-1268.
RX PubMed=18987736; DOI=10.1038/nature07485;
RA Ley T.J., Mardis E.R., Ding L., Fulton B., McLellan M.D., Chen K.,
RA Dooling D., Dunford-Shore B.H., McGrath S., Hickenbotham M., Cook L.,
RA Abbott R., Larson D.E., Koboldt D.C., Pohl C., Smith S., Hawkins A.,
RA Abbott S., Locke D., Hillier L.W., Miner T., Fulton L., Magrini V.,
RA Wylie T., Glasscock J., Conyers J., Sander N., Shi X., Osborne J.R.,
RA Minx P., Gordon D., Chinwalla A., Zhao Y., Ries R.E., Payton J.E.,
RA Westervelt P., Tomasson M.H., Watson M., Baty J., Ivanovich J., Heath S.,
RA Shannon W.D., Nagarajan R., Walter M.J., Link D.C., Graubert T.A.,
RA DiPersio J.F., Wilson R.K.;
RT "DNA sequencing of a cytogenetically normal acute myeloid leukaemia
RT genome.";
RL Nature 456:66-72(2008).
RN [31]
RP VARIANTS PXE GLN-518; PRO-726; GLN-1138; ARG-1302; PRO-1335 AND CYS-1339,
RP AND VARIANTS THR-78; GLY-265; MET-417; ALA-614; GLN-632; LEU-724; VAL-742;
RP VAL-848 AND ILE-946.
RX PubMed=19339160; DOI=10.1016/j.jdermsci.2009.02.008;
RA Ramsay M., Greenberg T., Lombard Z., Labrum R., Lubbe S., Aron S.,
RA Marais A.S., Terry S., Bercovitch L., Viljoen D.;
RT "Spectrum of genetic variation at the ABCC6 locus in South Africans:
RT Pseudoxanthoma elasticum patients and healthy individuals.";
RL J. Dermatol. Sci. 54:198-204(2009).
RN [32]
RP VARIANTS PXE GLN-765 AND LYS-1406.
RX PubMed=20034067; DOI=10.1002/ajmg.a.33162;
RA Le Boulanger G., Labreze C., Croue A., Schurgers L.J., Chassaing N.,
RA Wittkampf T., Rutsch F., Martin L.;
RT "An unusual severe vascular case of pseudoxanthoma elasticum presenting as
RT generalized arterial calcification of infancy.";
RL Am. J. Med. Genet. A 152:118-123(2010).
RN [33]
RP VARIANTS GACI2 ARG-355; GLY-391; PHE-590; PHE-1036 DEL; CYS-1114; HIS-1221
RP AND TRP-1314.
RX PubMed=22209248; DOI=10.1016/j.ajhg.2011.11.020;
RA Nitschke Y., Baujat G., Botschen U., Wittkampf T., du Moulin M., Stella J.,
RA Le Merrer M., Guest G., Lambot K., Tazarourte-Pinturier M.F., Chassaing N.,
RA Roche O., Feenstra I., Loechner K., Deshpande C., Garber S.J.,
RA Chikarmane R., Steinmann B., Shahinyan T., Martorell L., Davies J.,
RA Smith W.E., Kahler S.G., McCulloch M., Wraige E., Loidi L., Hohne W.,
RA Martin L., Hadj-Rabia S., Terkeltaub R., Rutsch F.;
RT "Generalized arterial calcification of infancy and pseudoxanthoma elasticum
RT can be caused by mutations in either ENPP1 or ABCC6.";
RL Am. J. Hum. Genet. 90:25-39(2012).
RN [34]
RP VARIANTS PXE THR-78 AND LYS-125, VARIANTS HIS-4; GLU-9; SER-21; GLN-64;
RP THR-90; GLN-419; PRO-605; GLY-709; THR-834; PRO-948 AND THR-1442,
RP CHARACTERIZATION OF VARIANTS HIS-4; GLU-9; SER-21; GLN-64; THR-90; GLN-419;
RP PRO-605; GLY-709; THR-834; PRO-948 AND THR-1442, AND CHARACTERIZATION OF
RP VARIANTS PXE THR-78 AND LYS-125.
RX PubMed=25615550; DOI=10.1038/jid.2015.10;
RA Jin L., Jiang Q., Wu Z., Shao C., Zhou Y., Yang L., Uitto J., Wang G.;
RT "Genetic heterogeneity of pseudoxanthoma elasticum: the chinese signature
RT profile of ABCC6 and ENPP1 mutations.";
RL J. Invest. Dermatol. 135:1294-1302(2015).
RN [35] {ECO:0007744|PDB:6BZS}
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 622-859, CHARACTERIZATION OF
RP VARIANTS PXE CYS-663; PRO-673; PRO-677; PRO-698; ASP-699; PRO-726; ARG-755;
RP TRP-760; GLN-765; ASP-766; ASN-777; MET-811 AND PRO-820, AND GLYCOSYLATION.
RX PubMed=30154241; DOI=10.1074/jbc.ra118.004806;
RA Ran Y., Zheng A., Thibodeau P.H.;
RT "Structural analysis reveals pathomechanisms associated with pseudoxanthoma
RT elasticum-causing mutations in the ABCC6 transporter.";
RL J. Biol. Chem. 293:15855-15866(2018).
RN [36] {ECO:0007744|PDB:6BZR, ECO:0007744|PDB:6NLO, ECO:0007744|PDB:6P7F}
RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 1254-1503.
RA Zheng A., Thibodeau P.H.;
RT "Structures of human ABCC6 NBD1 and NBD2.";
RL Submitted (JUN-2019) to the PDB data bank.
CC -!- FUNCTION: [Isoform 1]: ATP-dependent transporter of the ATP-binding
CC cassette (ABC) family that actively extrudes physiological compounds,
CC and xenobiotics from cells. Mediates ATP-dependent transport of
CC glutathione conjugates such as leukotriene-c4 (LTC4) and N-
CC ethylmaleimide S-glutathione (NEM-GS) (in vitro), and an anionic
CC cyclopentapeptide endothelin antagonist, BQ-123 (PubMed:11880368,
CC PubMed:12414644). Does not appear to actively transport drugs outside
CC the cell. Confers low levels of cellular resistance to etoposide,
CC teniposide, anthracyclines and cisplatin (PubMed:12414644).
CC {ECO:0000269|PubMed:11880368, ECO:0000269|PubMed:12414644}.
CC -!- FUNCTION: [Isoform 1]: Mediates the release of nucleoside
CC triphosphates, predominantly ATP, into the circulation, where it is
CC rapidly converted into AMP and the mineralization inhibitor inorganic
CC pyrophosphate (PPi) by the ecto-enzyme ectonucleotide pyrophosphatase
CC phosphodiesterase 1 (ENPP1), therefore playing a role in PPi
CC homeostasis. {ECO:0000269|PubMed:24277820,
CC ECO:0000269|PubMed:24969777}.
CC -!- FUNCTION: [Isoform 2]: Inhibits TNF-alpha-mediated apoptosis through
CC blocking one or more caspases. {ECO:0000269|PubMed:23912081}.
CC -!- CATALYTIC ACTIVITY: [Isoform 1]:
CC Reaction=an S-substituted glutathione(in) + ATP + H2O = ADP + an S-
CC substituted glutathione(out) + H(+) + phosphate;
CC Xref=Rhea:RHEA:19121, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:90779,
CC ChEBI:CHEBI:456216; EC=7.6.2.3;
CC Evidence={ECO:0000269|PubMed:11880368, ECO:0000269|PubMed:12414644};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19122;
CC Evidence={ECO:0000305|PubMed:11880368, ECO:0000305|PubMed:12414644};
CC -!- CATALYTIC ACTIVITY: [Isoform 1]:
CC Reaction=ATP + H2O + leukotriene C4(in) = ADP + H(+) + leukotriene
CC C4(out) + phosphate; Xref=Rhea:RHEA:38963, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:57973, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:11880368, ECO:0000269|PubMed:12414644};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38964;
CC Evidence={ECO:0000305|PubMed:11880368, ECO:0000305|PubMed:12414644};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:11880368, ECO:0000269|PubMed:12414644};
CC -!- ACTIVITY REGULATION: LTC4 transport is completely inhibited by 1 mM
CC orthovanadate. {ECO:0000269|PubMed:11880368}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=600 nM for LTC4 {ECO:0000269|PubMed:11880368};
CC KM=282 uM for N-ethylmaleimide S-glutathione
CC {ECO:0000269|PubMed:11880368};
CC Vmax=106 pmol/min/mg enzyme for N-ethylmaleimide S-glutathione
CC transport {ECO:0000269|PubMed:11880368};
CC Vmax=50 pmol/min/mg enzyme for LTC4 transport
CC {ECO:0000269|PubMed:11880368};
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Basolateral cell membrane
CC {ECO:0000269|PubMed:12901863, ECO:0000269|PubMed:23625951}; Multi-pass
CC membrane protein {ECO:0000255}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:23912081}; Single-pass membrane protein
CC {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=O95255-1; Sequence=Displayed;
CC Name=2; Synonyms=URG7 {ECO:0000303|PubMed:23912081};
CC IsoId=O95255-2; Sequence=VSP_047315, VSP_047316;
CC Name=3; Synonyms=Delta19Delta24;
CC IsoId=O95255-3; Sequence=VSP_057077, VSP_057078;
CC -!- TISSUE SPECIFICITY: Expressed in kidney and liver. Very low expression
CC in other tissues.
CC -!- INDUCTION: [Isoform 2]: Induced by HBV x antigen upon hepatitis B viral
CC infection. {ECO:0000269|PubMed:23912081}.
CC -!- PTM: Glycosylated. {ECO:0000269|PubMed:30154241}.
CC -!- DISEASE: Pseudoxanthoma elasticum (PXE) [MIM:264800]: A multisystem
CC disorder characterized by accumulation of mineralized and fragmented
CC elastic fibers in the skin, vascular walls, and Burch membrane in the
CC eye. Clinically, patients exhibit characteristic lesions of the
CC posterior segment of the eye including peau d'orange, angioid streaks,
CC and choroidal neovascularizations, of the skin including soft, ivory
CC colored papules in a reticular pattern that predominantly affect the
CC neck and large flexor surfaces, and of the cardiovascular system with
CC peripheral and coronary arterial occlusive disease as well as
CC gastrointestinal bleedings. {ECO:0000269|PubMed:10811882,
CC ECO:0000269|PubMed:10835642, ECO:0000269|PubMed:10954200,
CC ECO:0000269|PubMed:11427982, ECO:0000269|PubMed:11536079,
CC ECO:0000269|PubMed:11702217, ECO:0000269|PubMed:11880368,
CC ECO:0000269|PubMed:15086542, ECO:0000269|PubMed:15098239,
CC ECO:0000269|PubMed:15459974, ECO:0000269|PubMed:16086317,
CC ECO:0000269|PubMed:17617515, ECO:0000269|PubMed:19339160,
CC ECO:0000269|PubMed:20034067, ECO:0000269|PubMed:24277820,
CC ECO:0000269|PubMed:25615550, ECO:0000269|PubMed:30154241}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry. Homozygous or compound heterozygous ABCC6 mutations have been
CC found in the overwhelming majority of cases. Individuals carrying
CC heterozygous mutations express limited manifestations of the
CC pseudoxanthoma elasticum phenotype.
CC -!- DISEASE: Arterial calcification of infancy, generalized, 2 (GACI2)
CC [MIM:614473]: A severe autosomal recessive disorder characterized by
CC calcification of the internal elastic lamina of muscular arteries and
CC stenosis due to myointimal proliferation. The disorder is often fatal
CC within the first 6 months of life because of myocardial ischemia
CC resulting in refractory heart failure. {ECO:0000269|PubMed:22209248}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- MISCELLANEOUS: [Isoform 3]: May function as a half transporter.
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the ABC transporter superfamily. ABCC family.
CC Conjugate transporter (TC 3.A.1.208) subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC15785.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Mutations of the ABCC6 gene; Note=Retina
CC International's Scientific Newsletter;
CC URL="https://www.retina-international.org/files/sci-news/abcc6mut.htm";
CC -!- WEB RESOURCE: Name=ABCMdb; Note=Database for mutations in ABC proteins;
CC URL="http://abcm2.hegelab.org/search";
CC ---------------------------------------------------------------------------
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DR EMBL; AF168791; AAD51293.1; -; mRNA.
DR EMBL; AF076622; AAC79696.1; -; mRNA.
DR EMBL; AY078405; AAL83711.1; -; mRNA.
DR EMBL; AM711638; CAN84639.1; -; mRNA.
DR EMBL; AM774324; CAO81806.1; -; mRNA.
DR EMBL; U91318; AAC15785.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AC136624; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC050733; AAH50733.1; -; mRNA.
DR EMBL; BC131732; AAI31733.1; -; mRNA.
DR CCDS; CCDS10568.1; -. [O95255-1]
DR CCDS; CCDS58430.1; -. [O95255-2]
DR RefSeq; NP_001072996.1; NM_001079528.3. [O95255-2]
DR RefSeq; NP_001162.4; NM_001171.5. [O95255-1]
DR PDB; 6BZR; X-ray; 2.80 A; A/B=1254-1503.
DR PDB; 6BZS; X-ray; 2.30 A; A=622-859.
DR PDB; 6NLO; X-ray; 2.85 A; A=622-859.
DR PDB; 6P7F; X-ray; 2.85 A; A=1254-1503.
DR PDBsum; 6BZR; -.
DR PDBsum; 6BZS; -.
DR PDBsum; 6NLO; -.
DR PDBsum; 6P7F; -.
DR AlphaFoldDB; O95255; -.
DR SMR; O95255; -.
DR BioGRID; 106863; 53.
DR IntAct; O95255; 10.
DR STRING; 9606.ENSP00000205557; -.
DR ChEMBL; CHEMBL2073661; -.
DR DrugBank; DB00171; ATP.
DR DrugBank; DB00515; Cisplatin.
DR DrugBank; DB00970; Dactinomycin.
DR DrugBank; DB00694; Daunorubicin.
DR DrugBank; DB00997; Doxorubicin.
DR DrugBank; DB00773; Etoposide.
DR DrugBank; DB00328; Indomethacin.
DR DrugBank; DB01032; Probenecid.
DR DrugBank; DB01138; Sulfinpyrazone.
DR DrugBank; DB00444; Teniposide.
DR DrugBank; DB00570; Vinblastine.
DR DrugCentral; O95255; -.
DR TCDB; 3.A.1.208.10; the atp-binding cassette (abc) superfamily.
DR GlyGen; O95255; 1 site.
DR iPTMnet; O95255; -.
DR PhosphoSitePlus; O95255; -.
DR BioMuta; ABCC6; -.
DR MassIVE; O95255; -.
DR MaxQB; O95255; -.
DR PaxDb; O95255; -.
DR PeptideAtlas; O95255; -.
DR PRIDE; O95255; -.
DR ProteomicsDB; 18076; -.
DR ProteomicsDB; 50749; -. [O95255-1]
DR Antibodypedia; 11866; 166 antibodies from 32 providers.
DR DNASU; 368; -.
DR Ensembl; ENST00000205557.12; ENSP00000205557.7; ENSG00000091262.17. [O95255-1]
DR Ensembl; ENST00000456970.6; ENSP00000405002.2; ENSG00000091262.17. [O95255-3]
DR Ensembl; ENST00000575728.1; ENSP00000461686.1; ENSG00000091262.17. [O95255-2]
DR Ensembl; ENST00000600761.3; ENSP00000481979.2; ENSG00000275331.5. [O95255-2]
DR GeneID; 368; -.
DR KEGG; hsa:368; -.
DR MANE-Select; ENST00000205557.12; ENSP00000205557.7; NM_001171.6; NP_001162.5.
DR UCSC; uc002den.5; human. [O95255-1]
DR CTD; 368; -.
DR DisGeNET; 368; -.
DR GeneCards; ABCC6; -.
DR GeneReviews; ABCC6; -.
DR HGNC; HGNC:57; ABCC6.
DR HPA; ENSG00000091262; Tissue enriched (liver).
DR MalaCards; ABCC6; -.
DR MIM; 264800; phenotype.
DR MIM; 603234; gene.
DR MIM; 614473; phenotype.
DR neXtProt; NX_O95255; -.
DR OpenTargets; ENSG00000091262; -.
DR Orphanet; 51608; Generalized arterial calcification of infancy.
DR Orphanet; 758; Pseudoxanthoma elasticum.
DR PharmGKB; PA58; -.
DR VEuPathDB; HostDB:ENSG00000091262; -.
DR eggNOG; KOG0054; Eukaryota.
DR GeneTree; ENSGT00940000157145; -.
DR HOGENOM; CLU_000604_27_3_1; -.
DR InParanoid; O95255; -.
DR OMA; AAMYLTY; -.
DR OrthoDB; 1529167at2759; -.
DR PhylomeDB; O95255; -.
DR TreeFam; TF105199; -.
DR BRENDA; 7.6.2.3; 2681.
DR PathwayCommons; O95255; -.
DR Reactome; R-HSA-382556; ABC-family proteins mediated transport.
DR Reactome; R-HSA-5690338; Defective ABCC6 causes PXE.
DR SignaLink; O95255; -.
DR SIGNOR; O95255; -.
DR BioGRID-ORCS; 368; 13 hits in 1065 CRISPR screens.
DR ChiTaRS; ABCC6; human.
DR GeneWiki; ABCC6; -.
DR GenomeRNAi; 368; -.
DR Pharos; O95255; Tbio.
DR PRO; PR:O95255; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; O95255; protein.
DR Bgee; ENSG00000091262; Expressed in right lobe of liver and 97 other tissues.
DR ExpressionAtlas; O95255; baseline and differential.
DR Genevisible; O95255; HS.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005576; C:extracellular region; IDA:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0015431; F:ABC-type glutathione S-conjugate transporter activity; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0043225; F:ATPase-coupled inorganic anion transmembrane transporter activity; TAS:Reactome.
DR GO; GO:0042626; F:ATPase-coupled transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0046034; P:ATP metabolic process; IDA:MGI.
DR GO; GO:0015867; P:ATP transport; IDA:UniProtKB.
DR GO; GO:0110148; P:biomineralization; IEA:Ensembl.
DR GO; GO:0055074; P:calcium ion homeostasis; IDA:MGI.
DR GO; GO:0030643; P:cellular phosphate ion homeostasis; IEA:Ensembl.
DR GO; GO:0010467; P:gene expression; IDA:MGI.
DR GO; GO:0030505; P:inorganic diphosphate transport; IEA:Ensembl.
DR GO; GO:0071716; P:leukotriene transport; IDA:UniProtKB.
DR GO; GO:0055062; P:phosphate ion homeostasis; IDA:MGI.
DR GO; GO:0032026; P:response to magnesium ion; IEA:Ensembl.
DR GO; GO:1904383; P:response to sodium phosphate; IEA:Ensembl.
DR GO; GO:0009410; P:response to xenobiotic stimulus; TAS:ProtInc.
DR GO; GO:0055085; P:transmembrane transport; IBA:GO_Central.
DR GO; GO:0007601; P:visual perception; IEA:UniProtKB-KW.
DR Gene3D; 1.20.1560.10; -; 2.
DR Gene3D; 3.40.50.300; -; 2.
DR InterPro; IPR003593; AAA+_ATPase.
DR InterPro; IPR011527; ABC1_TM_dom.
DR InterPro; IPR036640; ABC1_TM_sf.
DR InterPro; IPR003439; ABC_transporter-like_ATP-bd.
DR InterPro; IPR017871; ABC_transporter-like_CS.
DR InterPro; IPR030239; ABCC6.
DR InterPro; IPR005292; Multidrug-R_assoc.
DR InterPro; IPR027417; P-loop_NTPase.
DR PANTHER; PTHR24223:SF339; PTHR24223:SF339; 1.
DR Pfam; PF00664; ABC_membrane; 2.
DR Pfam; PF00005; ABC_tran; 2.
DR SMART; SM00382; AAA; 2.
DR SUPFAM; SSF52540; SSF52540; 2.
DR SUPFAM; SSF90123; SSF90123; 2.
DR TIGRFAMs; TIGR00957; MRP_assoc_pro; 1.
DR PROSITE; PS50929; ABC_TM1F; 2.
DR PROSITE; PS00211; ABC_TRANSPORTER_1; 2.
DR PROSITE; PS50893; ABC_TRANSPORTER_2; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Cell membrane;
KW Disease variant; Endoplasmic reticulum; Glycoprotein; Membrane;
KW Nucleotide-binding; Phosphoprotein; Reference proteome; Repeat;
KW Sensory transduction; Translocase; Transmembrane; Transmembrane helix;
KW Transport; Vision.
FT CHAIN 1..1503
FT /note="ATP-binding cassette sub-family C member 6"
FT /id="PRO_0000093366"
FT TOPO_DOM 1..31
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 32..52
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 53..72
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 73..93
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 94..98
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 99..119
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 120..131
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 132..149
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 150..167
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 168..188
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 189..302
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 303..323
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 324..349
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 350..370
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 371..426
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 427..447
FT /note="Helical; Name=8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 448..450
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 451..471
FT /note="Helical; Name=9"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 472..533
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 534..554
FT /note="Helical; Name=10"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 555..575
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 576..596
FT /note="Helical; Name=11"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 597..939
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 940..960
FT /note="Helical; Name=12"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 961..997
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 998..1018
FT /note="Helical; Name=13"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 1019..1061
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 1062..1082
FT /note="Helical; Name=14"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 1083
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 1084..1104
FT /note="Helical; Name=15"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 1105..1175
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 1176..1196
FT /note="Helical; Name=16"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 1197..1198
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 1199..1219
FT /note="Helical; Name=17"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 1220..1503
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT DOMAIN 311..593
FT /note="ABC transmembrane type-1 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT DOMAIN 629..853
FT /note="ABC transporter 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT DOMAIN 947..1228
FT /note="ABC transmembrane type-1 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT DOMAIN 1265..1499
FT /note="ABC transporter 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT REGION 854..919
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 877..910
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 663..670
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT BINDING 1299..1306
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT MOD_RES 1286
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT CARBOHYD 15
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000305|PubMed:12901863"
FT VAR_SEQ 75..99
FT /note="LGFALIVLCTSSVAVALWKIQQGTP -> AAIPGSLEPGNVRGRQGTGWNLV
FT KS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11431746,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_047315"
FT VAR_SEQ 100..1503
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11431746,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_047316"
FT VAR_SEQ 806..871
FT /note="TRILVTHALHILPQADWIIVLANGAIAEMGSYQELLQRKGALMCLLDQARQP
FT GDRGEGETEPGTST -> KQNLGPAPRTPEAPLQAGGPSLDARGPSSQSLRRTVPLQKP
FT RQRFLWMTLTGQDGQQERTASNTAG (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:21318057"
FT /id="VSP_057077"
FT VAR_SEQ 872..1503
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:21318057"
FT /id="VSP_057078"
FT VARIANT 4
FT /note="P -> H (found in patient with putative diagnosis of
FT PXE; uncertain pathological significance; loss-of-function
FT mutation; localization comparable to wild-type;
FT dbSNP:rs1555523872)"
FT /evidence="ECO:0000269|PubMed:25615550"
FT /id="VAR_072803"
FT VARIANT 9
FT /note="A -> E (found in patient with putative diagnosis of
FT PXE; uncertain pathological significance; loss-of-function
FT mutation; localization comparable to wild-type;
FT dbSNP:rs1555523855)"
FT /evidence="ECO:0000269|PubMed:25615550"
FT /id="VAR_072804"
FT VARIANT 21
FT /note="P -> S (found in patient with putative diagnosis of
FT PXE; uncertain pathological significance; loss-of-function
FT mutation; localization comparable to wild-type;
FT dbSNP:rs1235912910)"
FT /evidence="ECO:0000269|PubMed:25615550"
FT /id="VAR_072805"
FT VARIANT 60..62
FT /note="Missing (in PXE; autosomal recessive)"
FT /evidence="ECO:0000269|PubMed:11702217,
FT ECO:0000269|PubMed:16086317, ECO:0000269|PubMed:17617515"
FT /id="VAR_013363"
FT VARIANT 61
FT /note="G -> D (in dbSNP:rs72657696)"
FT /evidence="ECO:0000269|PubMed:11536079"
FT /id="VAR_013364"
FT VARIANT 64
FT /note="R -> Q (found in patient with putative diagnosis of
FT PXE; uncertain pathological significance; localization
FT comparable to wild-type; dbSNP:rs777566074)"
FT /evidence="ECO:0000269|PubMed:25615550"
FT /id="VAR_072806"
FT VARIANT 64
FT /note="R -> W (in dbSNP:rs557180313)"
FT /evidence="ECO:0000269|PubMed:10493829,
FT ECO:0000269|PubMed:11058917, ECO:0000269|PubMed:9892204"
FT /id="VAR_013365"
FT VARIANT 74
FT /note="Missing (in PXE; dbSNP:rs72664225)"
FT /evidence="ECO:0000269|PubMed:15086542"
FT /id="VAR_067840"
FT VARIANT 78
FT /note="A -> T (in PXE; dbSNP:rs2856597)"
FT /evidence="ECO:0000269|PubMed:16086317,
FT ECO:0000269|PubMed:19339160, ECO:0000269|PubMed:25615550"
FT /id="VAR_067841"
FT VARIANT 90
FT /note="A -> T (found in patient with putative diagnosis of
FT PXE; uncertain pathological significance;
FT dbSNP:rs957828732)"
FT /evidence="ECO:0000269|PubMed:25615550"
FT /id="VAR_072807"
FT VARIANT 125
FT /note="E -> K (in PXE; loss-of-function mutation;
FT localization comparable to wild-type; dbSNP:rs3853814)"
FT /evidence="ECO:0000269|PubMed:16086317,
FT ECO:0000269|PubMed:25615550"
FT /id="VAR_067842"
FT VARIANT 129
FT /note="G -> E (in PXE; autosomal recessive;
FT dbSNP:rs72653753)"
FT /evidence="ECO:0000269|PubMed:16086317"
FT /id="VAR_067843"
FT VARIANT 158
FT /note="A -> V (in dbSNP:rs2606921)"
FT /evidence="ECO:0000269|PubMed:16086317"
FT /id="VAR_067844"
FT VARIANT 207
FT /note="G -> R (in dbSNP:rs72657697)"
FT /evidence="ECO:0000269|PubMed:11536079"
FT /id="VAR_013366"
FT VARIANT 265
FT /note="R -> G (in dbSNP:rs72657698)"
FT /evidence="ECO:0000269|PubMed:11536079,
FT ECO:0000269|PubMed:11702217, ECO:0000269|PubMed:16086317,
FT ECO:0000269|PubMed:19339160"
FT /id="VAR_013367"
FT VARIANT 281
FT /note="K -> E (in dbSNP:rs4780606)"
FT /evidence="ECO:0000269|PubMed:11536079,
FT ECO:0000269|PubMed:16086317"
FT /id="VAR_013368"
FT VARIANT 317
FT /note="S -> R (in PXE; autosomal recessive;
FT dbSNP:rs78678589)"
FT /evidence="ECO:0000269|PubMed:16086317,
FT ECO:0000269|PubMed:17617515"
FT /id="VAR_067845"
FT VARIANT 319
FT /note="I -> V (in dbSNP:rs72657699)"
FT /evidence="ECO:0000269|PubMed:11536079,
FT ECO:0000269|PubMed:16086317, ECO:0000269|PubMed:21318057"
FT /id="VAR_013369"
FT VARIANT 355
FT /note="L -> R (in GACI2 and PXE; autosomal recessive;
FT dbSNP:rs72653758)"
FT /evidence="ECO:0000269|PubMed:16086317,
FT ECO:0000269|PubMed:22209248"
FT /id="VAR_067846"
FT VARIANT 363..373
FT /note="Missing (in PXE)"
FT /evidence="ECO:0000269|PubMed:15086542"
FT /id="VAR_067847"
FT VARIANT 364
FT /note="T -> R (in PXE; autosomal recessive;
FT dbSNP:rs72653759)"
FT /evidence="ECO:0000269|PubMed:11702217,
FT ECO:0000269|PubMed:15459974, ECO:0000269|PubMed:16086317,
FT ECO:0000269|PubMed:17617515"
FT /id="VAR_013370"
FT VARIANT 370
FT /note="N -> D (in PXE; autosomal recessive;
FT dbSNP:rs72653760)"
FT /evidence="ECO:0000269|PubMed:16086317"
FT /id="VAR_067848"
FT VARIANT 382
FT /note="R -> W (in PXE; dbSNP:rs72653761)"
FT /evidence="ECO:0000269|PubMed:17617515"
FT /id="VAR_067849"
FT VARIANT 391
FT /note="R -> G (in GACI2 and PXE; autosomal recessive;
FT dbSNP:rs72653762)"
FT /evidence="ECO:0000269|PubMed:15086542,
FT ECO:0000269|PubMed:16086317, ECO:0000269|PubMed:17617515,
FT ECO:0000269|PubMed:22209248"
FT /id="VAR_067850"
FT VARIANT 392
FT /note="K -> N (in PXE; dbSNP:rs72653763)"
FT /evidence="ECO:0000269|PubMed:17617515"
FT /id="VAR_067851"
FT VARIANT 398
FT /note="S -> G (in PXE; autosomal recessive;
FT dbSNP:rs72653764)"
FT /evidence="ECO:0000269|PubMed:16086317"
FT /id="VAR_067852"
FT VARIANT 411
FT /note="N -> K (in PXE; autosomal dominant;
FT dbSNP:rs9930886)"
FT /evidence="ECO:0000269|PubMed:11536079,
FT ECO:0000269|PubMed:15459974"
FT /id="VAR_013371"
FT VARIANT 417
FT /note="V -> M (in dbSNP:rs768869262)"
FT /evidence="ECO:0000269|PubMed:19339160"
FT /id="VAR_067853"
FT VARIANT 419
FT /note="R -> Q (found in patient with putative diagnosis of
FT PXE; uncertain pathological significance; loss-of-function
FT mutation; localization comparable to wild-type;
FT dbSNP:rs772434460)"
FT /evidence="ECO:0000269|PubMed:25615550"
FT /id="VAR_072808"
FT VARIANT 440
FT /note="C -> G (in PXE; autosomal recessive;
FT dbSNP:rs72653766)"
FT /evidence="ECO:0000269|PubMed:15459974"
FT /id="VAR_067854"
FT VARIANT 455
FT /note="A -> P (in PXE; autosomal dominant;
FT dbSNP:rs67996819)"
FT /evidence="ECO:0000269|PubMed:11427982"
FT /id="VAR_013372"
FT VARIANT 463
FT /note="L -> H (in PXE; dbSNP:rs72653767)"
FT /id="VAR_067855"
FT VARIANT 495
FT /note="L -> H (in PXE; autosomal recessive;
FT dbSNP:rs72653769)"
FT /evidence="ECO:0000269|PubMed:16086317,
FT ECO:0000269|PubMed:17617515"
FT /id="VAR_067856"
FT VARIANT 497
FT /note="N -> K (in dbSNP:rs72653770)"
FT /evidence="ECO:0000269|PubMed:11536079"
FT /id="VAR_013373"
FT VARIANT 514
FT /note="V -> I (in dbSNP:rs59157279)"
FT /evidence="ECO:0000269|PubMed:16086317"
FT /id="VAR_067857"
FT VARIANT 518
FT /note="R -> Q (in PXE; autosomal recessive;
FT dbSNP:rs72653772)"
FT /evidence="ECO:0000269|PubMed:11536079,
FT ECO:0000269|PubMed:15086542, ECO:0000269|PubMed:15459974,
FT ECO:0000269|PubMed:16086317, ECO:0000269|PubMed:17617515,
FT ECO:0000269|PubMed:19339160"
FT /id="VAR_013374"
FT VARIANT 535
FT /note="S -> P (in PXE; dbSNP:rs72653773)"
FT /evidence="ECO:0000269|PubMed:17617515"
FT /id="VAR_067858"
FT VARIANT 551
FT /note="F -> S (in PXE; autosomal recessive;
FT dbSNP:rs72653774)"
FT /evidence="ECO:0000269|PubMed:16086317"
FT /id="VAR_067859"
FT VARIANT 568
FT /note="F -> S (in PXE; autosomal dominant;
FT dbSNP:rs66864704)"
FT /evidence="ECO:0000269|PubMed:11536079,
FT ECO:0000269|PubMed:17617515"
FT /id="VAR_013375"
FT VARIANT 590
FT /note="S -> F (in GACI2; dbSNP:rs537233133)"
FT /evidence="ECO:0000269|PubMed:22209248"
FT /id="VAR_067860"
FT VARIANT 594
FT /note="A -> V (in PXE; autosomal recessive;
FT dbSNP:rs72653776)"
FT /evidence="ECO:0000269|PubMed:16086317"
FT /id="VAR_067861"
FT VARIANT 600
FT /note="R -> C (in PXE; autosomal recessive;
FT dbSNP:rs72653777)"
FT /evidence="ECO:0000269|PubMed:15459974,
FT ECO:0000269|PubMed:17617515"
FT /id="VAR_067862"
FT VARIANT 605
FT /note="L -> P (found in patient with putative diagnosis of
FT PEX; uncertain pathological significance; mutant protein is
FT retained in the cytoplasm; dbSNP:rs768271196)"
FT /evidence="ECO:0000269|PubMed:25615550"
FT /id="VAR_072809"
FT VARIANT 614
FT /note="V -> A (in dbSNP:rs12931472)"
FT /evidence="ECO:0000269|PubMed:10835642,
FT ECO:0000269|PubMed:11536079, ECO:0000269|PubMed:11776382,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:16086317,
FT ECO:0000269|PubMed:19339160"
FT /id="VAR_011490"
FT VARIANT 632
FT /note="H -> Q (in dbSNP:rs8058694)"
FT /evidence="ECO:0000269|PubMed:10954200,
FT ECO:0000269|PubMed:11536079, ECO:0000269|PubMed:11776382,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:16086317,
FT ECO:0000269|PubMed:19339160"
FT /id="VAR_013376"
FT VARIANT 663
FT /note="G -> C (in PXE; affects protein expression and
FT trafficking; expression is reduced to less than 10%, when
FT compared with the WT protein; dbSNP:rs72653780)"
FT /evidence="ECO:0000269|PubMed:17617515,
FT ECO:0000269|PubMed:30154241"
FT /id="VAR_067863"
FT VARIANT 665
FT /note="V -> A (in dbSNP:rs4341770)"
FT /id="VAR_055477"
FT VARIANT 673
FT /note="L -> P (in PXE; autosomal dominant; affects protein
FT expression and trafficking; expression is reduced to less
FT than 10%, when compared with the WT protein;
FT dbSNP:rs67470842)"
FT /evidence="ECO:0000269|PubMed:11536079,
FT ECO:0000269|PubMed:30154241"
FT /id="VAR_013377"
FT VARIANT 677
FT /note="L -> P (in PXE; autosomal recessive;
FT dbSNP:rs72653782)"
FT /evidence="ECO:0000269|PubMed:16086317,
FT ECO:0000269|PubMed:30154241"
FT /id="VAR_067864"
FT VARIANT 698
FT /note="Q -> P (in PXE; does not change protein biosynthesis
FT and folding; dbSNP:rs72653783)"
FT /evidence="ECO:0000269|PubMed:17617515,
FT ECO:0000269|PubMed:30154241"
FT /id="VAR_067865"
FT VARIANT 699
FT /note="E -> D (in PXE; does not change protein biosynthesis
FT and folding; dbSNP:rs72653784)"
FT /evidence="ECO:0000269|PubMed:17617515,
FT ECO:0000269|PubMed:30154241"
FT /id="VAR_067866"
FT VARIANT 709
FT /note="E -> G (found in patient with putative diagnosis of
FT PEX; uncertain pathological significance; loss-of-function
FT mutation; localization comparable to wild-type;
FT dbSNP:rs1555513103)"
FT /evidence="ECO:0000269|PubMed:25615550"
FT /id="VAR_072810"
FT VARIANT 724
FT /note="R -> K (in dbSNP:rs58073789)"
FT /evidence="ECO:0000269|PubMed:16086317"
FT /id="VAR_067867"
FT VARIANT 724
FT /note="R -> L"
FT /evidence="ECO:0000269|PubMed:19339160"
FT /id="VAR_067868"
FT VARIANT 726
FT /note="L -> P (in PXE; affects protein expression and
FT trafficking; expression is reduced to less than 10%, when
FT compared with the WT protein; dbSNP:rs72653785)"
FT /evidence="ECO:0000269|PubMed:17617515,
FT ECO:0000269|PubMed:19339160, ECO:0000269|PubMed:30154241"
FT /id="VAR_067869"
FT VARIANT 742
FT /note="I -> V (in dbSNP:rs59593133)"
FT /evidence="ECO:0000269|PubMed:16086317,
FT ECO:0000269|PubMed:19339160"
FT /id="VAR_067870"
FT VARIANT 751
FT /note="M -> K (in PXE; dbSNP:rs72653786)"
FT /evidence="ECO:0000269|PubMed:17617515"
FT /id="VAR_067871"
FT VARIANT 755
FT /note="G -> R (in PXE; does not change protein biosynthesis
FT and folding; dbSNP:rs72653787)"
FT /evidence="ECO:0000269|PubMed:17617515,
FT ECO:0000269|PubMed:30154241"
FT /id="VAR_067872"
FT VARIANT 760
FT /note="R -> W (in PXE; autosomal recessive; protein level
FT is 15-20% that of the WT proteins; maturation of glycan
FT chains is not affected indicating normal trafficking from
FT the endoplasmic reticulum to the cell membrane;
FT dbSNP:rs72653788)"
FT /evidence="ECO:0000269|PubMed:16086317,
FT ECO:0000269|PubMed:17617515, ECO:0000269|PubMed:30154241"
FT /id="VAR_067873"
FT VARIANT 765
FT /note="R -> Q (in PXE; autosomal dominant and autosomal
FT recessive; affects protein expression and trafficking;
FT expression is reduced to less than 10%, when compared with
FT the WT protein; dbSNP:rs67561842)"
FT /evidence="ECO:0000269|PubMed:11536079,
FT ECO:0000269|PubMed:16086317, ECO:0000269|PubMed:17617515,
FT ECO:0000269|PubMed:20034067, ECO:0000269|PubMed:30154241"
FT /id="VAR_013378"
FT VARIANT 766
FT /note="A -> D (in PXE; autosomal recessive; affects protein
FT expression and trafficking; expression is reduced to less
FT than 10%, when compared with the WT protein;
FT dbSNP:rs72653789)"
FT /evidence="ECO:0000269|PubMed:15086542,
FT ECO:0000269|PubMed:30154241"
FT /id="VAR_067874"
FT VARIANT 777
FT /note="D -> N (in PXE; affects protein expression and
FT trafficking; affects protein expression and trafficking;
FT expression is reduced to less than 10%, when compared with
FT the WT protein; dbSNP:rs72653790)"
FT /evidence="ECO:0000269|PubMed:17617515,
FT ECO:0000269|PubMed:30154241"
FT /id="VAR_067875"
FT VARIANT 807
FT /note="R -> Q (in PXE; autosomal recessive;
FT dbSNP:rs72653794)"
FT /evidence="ECO:0000269|PubMed:16086317"
FT /id="VAR_067876"
FT VARIANT 807
FT /note="R -> W (in PXE; autosomal recessive;
FT dbSNP:rs72653793)"
FT /evidence="ECO:0000269|PubMed:16086317"
FT /id="VAR_067877"
FT VARIANT 810
FT /note="V -> M (in PXE; autosomal recessive; protein level
FT is 15-20% that of the WT proteins; maturation of glycan
FT chains is not affected indicating normal trafficking from
FT the endoplasmic reticulum to the cell membrane;
FT dbSNP:rs72653795)"
FT /evidence="ECO:0000269|PubMed:15459974,
FT ECO:0000269|PubMed:30154241"
FT /id="VAR_067878"
FT VARIANT 811
FT /note="T -> M (in PXE; protein level is 15-20% that of the
FT WT proteins; maturation of glycan chains is not affected
FT indicating normal trafficking from the endoplasmic
FT reticulum to the cell membrane; dbSNP:rs72653796)"
FT /evidence="ECO:0000269|PubMed:17617515,
FT ECO:0000269|PubMed:30154241"
FT /id="VAR_067879"
FT VARIANT 820
FT /note="A -> P (in PXE; autosomal recessive; affects protein
FT expression and trafficking; dbSNP:rs72653797)"
FT /evidence="ECO:0000269|PubMed:15459974,
FT ECO:0000269|PubMed:30154241"
FT /id="VAR_067880"
FT VARIANT 834
FT /note="M -> T (found in patient with putative diagnosis of
FT PEX; uncertain pathological significance; loss-of-function
FT mutation; localization comparable to wild-type;
FT dbSNP:rs1355752953)"
FT /evidence="ECO:0000269|PubMed:25615550"
FT /id="VAR_072811"
FT VARIANT 848
FT /note="M -> V (in dbSNP:rs6416668)"
FT /evidence="ECO:0000269|PubMed:10424734,
FT ECO:0000269|PubMed:10493829, ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:19339160, ECO:0000269|PubMed:21318057,
FT ECO:0000269|PubMed:9892204"
FT /id="VAR_059108"
FT VARIANT 881
FT /note="R -> S (in PXE; dbSNP:rs72653800)"
FT /evidence="ECO:0000269|PubMed:17617515"
FT /id="VAR_067881"
FT VARIANT 944
FT /note="T -> I (in PXE; dbSNP:rs72653801)"
FT /evidence="ECO:0000269|PubMed:17617515"
FT /id="VAR_067882"
FT VARIANT 946
FT /note="L -> I (in dbSNP:rs61340537)"
FT /evidence="ECO:0000269|PubMed:16086317,
FT ECO:0000269|PubMed:19339160"
FT /id="VAR_067883"
FT VARIANT 948
FT /note="L -> P (found in patient with putative diagnosis of
FT PEX; uncertain pathological significance; loss-of-function
FT mutation; localization comparable to wild-type;
FT dbSNP:rs1555510407)"
FT /evidence="ECO:0000269|PubMed:25615550"
FT /id="VAR_072812"
FT VARIANT 950
FT /note="A -> T (in PXE; dbSNP:rs72657689)"
FT /evidence="ECO:0000269|PubMed:17617515"
FT /id="VAR_067884"
FT VARIANT 953
FT /note="L -> H (in dbSNP:rs72657700)"
FT /evidence="ECO:0000269|PubMed:11536079"
FT /id="VAR_013379"
FT VARIANT 992
FT /note="G -> R (in PXE; dbSNP:rs72657692)"
FT /evidence="ECO:0000269|PubMed:17617515"
FT /id="VAR_067885"
FT VARIANT 1036
FT /note="Missing (in GACI2 and PXE; autosomal recessive;
FT dbSNP:rs72664230)"
FT /evidence="ECO:0000269|PubMed:16086317,
FT ECO:0000269|PubMed:22209248"
FT /id="VAR_067886"
FT VARIANT 1048
FT /note="Missing (in PXE; autosomal recessive)"
FT /evidence="ECO:0000269|PubMed:16086317"
FT /id="VAR_067887"
FT VARIANT 1056
FT /note="D -> E (in PXE; dbSNP:rs72657694)"
FT /evidence="ECO:0000269|PubMed:16086317"
FT /id="VAR_067888"
FT VARIANT 1064
FT /note="R -> W (in dbSNP:rs41278174)"
FT /evidence="ECO:0000269|PubMed:16086317"
FT /id="VAR_067889"
FT VARIANT 1097
FT /note="L -> I (in dbSNP:rs60707953)"
FT /id="VAR_060988"
FT VARIANT 1114
FT /note="R -> C (in GACI2 and PXE; autosomal recessive;
FT dbSNP:rs63749794)"
FT /evidence="ECO:0000269|PubMed:15459974,
FT ECO:0000269|PubMed:16086317, ECO:0000269|PubMed:17617515,
FT ECO:0000269|PubMed:22209248"
FT /id="VAR_067890"
FT VARIANT 1114
FT /note="R -> P (in PXE; autosomal recessive;
FT dbSNP:rs63750427)"
FT /evidence="ECO:0000269|PubMed:10835642,
FT ECO:0000269|PubMed:11536079"
FT /id="VAR_011491"
FT VARIANT 1121
FT /note="S -> L (in PXE; dbSNP:rs63750987)"
FT /evidence="ECO:0000269|PubMed:16086317"
FT /id="VAR_067891"
FT VARIANT 1121
FT /note="S -> W (in PXE; autosomal dominant;
FT dbSNP:rs63750987)"
FT /evidence="ECO:0000269|PubMed:11536079"
FT /id="VAR_013380"
FT VARIANT 1130
FT /note="T -> M (in PXE; autosomal recessive;
FT dbSNP:rs63750459)"
FT /evidence="ECO:0000269|PubMed:15086542,
FT ECO:0000269|PubMed:15459974, ECO:0000269|PubMed:17617515"
FT /id="VAR_067892"
FT VARIANT 1133
FT /note="G -> A (in PXE; dbSNP:rs63750473)"
FT /evidence="ECO:0000269|PubMed:17617515"
FT /id="VAR_067893"
FT VARIANT 1138
FT /note="R -> P (in PXE; autosomal dominant;
FT dbSNP:rs60791294)"
FT /evidence="ECO:0000269|PubMed:11536079"
FT /id="VAR_013381"
FT VARIANT 1138
FT /note="R -> Q (in PXE; autosomal recessive;
FT dbSNP:rs60791294)"
FT /evidence="ECO:0000269|PubMed:10835642,
FT ECO:0000269|PubMed:11536079, ECO:0000269|PubMed:15459974,
FT ECO:0000269|PubMed:16086317, ECO:0000269|PubMed:17617515,
FT ECO:0000269|PubMed:19339160"
FT /id="VAR_011492"
FT VARIANT 1138
FT /note="R -> W (in PXE; autosomal recessive;
FT dbSNP:rs28939701)"
FT /evidence="ECO:0000269|PubMed:10811882,
FT ECO:0000269|PubMed:16086317, ECO:0000269|PubMed:17617515"
FT /id="VAR_011493"
FT VARIANT 1139
FT /note="A -> T (in PXE; dbSNP:rs63750146)"
FT /evidence="ECO:0000269|PubMed:17617515"
FT /id="VAR_067894"
FT VARIANT 1164
FT /note="R -> Q (in PXE; autosomal recessive;
FT dbSNP:rs63750457)"
FT /evidence="ECO:0000269|PubMed:16086317,
FT ECO:0000269|PubMed:17617515"
FT /id="VAR_067895"
FT VARIANT 1203
FT /note="G -> D (in PXE; autosomal dominant;
FT dbSNP:rs63750607)"
FT /evidence="ECO:0000269|PubMed:11536079"
FT /id="VAR_013382"
FT VARIANT 1221
FT /note="R -> C (in PXE; autosomal recessive;
FT dbSNP:rs63751215)"
FT /evidence="ECO:0000269|PubMed:16086317,
FT ECO:0000269|PubMed:17617515"
FT /id="VAR_067896"
FT VARIANT 1221
FT /note="R -> H (in GACI2; dbSNP:rs63751001)"
FT /evidence="ECO:0000269|PubMed:17617515,
FT ECO:0000269|PubMed:22209248"
FT /id="VAR_067897"
FT VARIANT 1226
FT /note="L -> I (in PXE; dbSNP:rs63750125)"
FT /evidence="ECO:0000269|PubMed:17617515"
FT /id="VAR_067898"
FT VARIANT 1235
FT /note="R -> W (in PXE; autosomal recessive;
FT dbSNP:rs63750402)"
FT /evidence="ECO:0000269|PubMed:16086317"
FT /id="VAR_067899"
FT VARIANT 1238
FT /note="D -> H (in PXE; pseudodominant; dbSNP:rs63749796)"
FT /evidence="ECO:0000269|PubMed:15086542"
FT /id="VAR_067900"
FT VARIANT 1241
FT /note="W -> C (in dbSNP:rs72657701)"
FT /evidence="ECO:0000269|PubMed:11536079"
FT /id="VAR_013383"
FT VARIANT 1268
FT /note="R -> Q (associated with lower plasma triglycerides
FT and higher plasma HDL cholesterol; dbSNP:rs2238472)"
FT /evidence="ECO:0000269|PubMed:10811882,
FT ECO:0000269|PubMed:10913334, ECO:0000269|PubMed:11536079,
FT ECO:0000269|PubMed:11776382, ECO:0000269|PubMed:16086317,
FT ECO:0000269|PubMed:18987736"
FT /id="VAR_011494"
FT VARIANT 1298
FT /note="V -> F (in PXE; autosomal dominant; abolishes LTC4
FT and NEM-GS transport; does not affect plasma membrane
FT localization; does not increase extracellular pyrophosphate
FT levels; dbSNP:rs63751325)"
FT /evidence="ECO:0000269|PubMed:11536079,
FT ECO:0000269|PubMed:11880368, ECO:0000269|PubMed:17617515,
FT ECO:0000269|PubMed:24277820"
FT /id="VAR_013384"
FT VARIANT 1301
FT /note="T -> I (in PXE; autosomal dominant;
FT dbSNP:rs63750494)"
FT /evidence="ECO:0000269|PubMed:11536079"
FT /id="VAR_013385"
FT VARIANT 1302
FT /note="G -> R (in PXE; autosomal dominant and autosomal
FT recessive; abolishes LTC4 and NEM-GS transport;
FT dbSNP:rs63749856)"
FT /evidence="ECO:0000269|PubMed:11536079,
FT ECO:0000269|PubMed:11880368, ECO:0000269|PubMed:16086317,
FT ECO:0000269|PubMed:17617515, ECO:0000269|PubMed:19339160"
FT /id="VAR_013386"
FT VARIANT 1303
FT /note="A -> P (in PXE; autosomal dominant and autosomal
FT recessive; dbSNP:rs63750410)"
FT /evidence="ECO:0000269|PubMed:11536079,
FT ECO:0000269|PubMed:16086317, ECO:0000269|PubMed:17617515"
FT /id="VAR_013387"
FT VARIANT 1314
FT /note="R -> Q (in PXE; autosomal dominant and autosomal
FT recessive; dbSNP:rs63751086)"
FT /evidence="ECO:0000269|PubMed:11536079,
FT ECO:0000269|PubMed:16086317, ECO:0000269|PubMed:17617515"
FT /id="VAR_013388"
FT VARIANT 1314
FT /note="R -> W (in GACI2 and PXE; autosomal recessive;
FT dbSNP:rs63750759)"
FT /evidence="ECO:0000269|PubMed:10835642,
FT ECO:0000269|PubMed:11536079, ECO:0000269|PubMed:17617515,
FT ECO:0000269|PubMed:22209248"
FT /id="VAR_011495"
FT VARIANT 1321
FT /note="G -> S (in PXE; autosomal dominant; abolishes LTC4
FT and NEM-GS transport; dbSNP:rs63749823)"
FT /evidence="ECO:0000269|PubMed:11536079,
FT ECO:0000269|PubMed:11880368"
FT /id="VAR_013389"
FT VARIANT 1335
FT /note="L -> P (in PXE; autosomal recessive;
FT dbSNP:rs63750414)"
FT /evidence="ECO:0000269|PubMed:15086542,
FT ECO:0000269|PubMed:19339160"
FT /id="VAR_067901"
FT VARIANT 1335
FT /note="L -> Q (in PXE; dbSNP:rs63750414)"
FT /evidence="ECO:0000269|PubMed:17617515"
FT /id="VAR_067902"
FT VARIANT 1339
FT /note="R -> C (in PXE; autosomal recessive;
FT dbSNP:rs28939702)"
FT /evidence="ECO:0000269|PubMed:10954200,
FT ECO:0000269|PubMed:11536079, ECO:0000269|PubMed:15459974,
FT ECO:0000269|PubMed:16086317, ECO:0000269|PubMed:17617515,
FT ECO:0000269|PubMed:19339160"
FT /id="VAR_013390"
FT VARIANT 1339
FT /note="R -> H (in PXE; autosomal recessive;
FT dbSNP:rs63750622)"
FT /evidence="ECO:0000269|PubMed:17617515"
FT /id="VAR_067904"
FT VARIANT 1339
FT /note="R -> L (in PXE; autosomal recessive;
FT dbSNP:rs63750622)"
FT /evidence="ECO:0000269|PubMed:16086317"
FT /id="VAR_067903"
FT VARIANT 1346
FT /note="P -> S (in PXE; autosomal recessive;
FT dbSNP:rs63751112)"
FT /evidence="ECO:0000269|PubMed:15459974"
FT /id="VAR_067905"
FT VARIANT 1347
FT /note="Q -> H (in PXE; autosomal dominant;
FT dbSNP:rs63751111)"
FT /evidence="ECO:0000269|PubMed:11536079"
FT /id="VAR_013391"
FT VARIANT 1354
FT /note="G -> R (in PXE; autosomal recessive;
FT dbSNP:rs63750018)"
FT /evidence="ECO:0000269|PubMed:11702217"
FT /id="VAR_013392"
FT VARIANT 1357
FT /note="R -> W (in PXE; autosomal recessive;
FT dbSNP:rs63750428)"
FT /evidence="ECO:0000269|PubMed:16086317"
FT /id="VAR_067906"
FT VARIANT 1361
FT /note="D -> N (in PXE; autosomal dominant;
FT dbSNP:rs58695352)"
FT /evidence="ECO:0000269|PubMed:11536079"
FT /id="VAR_013393"
FT VARIANT 1400
FT /note="E -> K (in PXE; autosomal recessive;
FT dbSNP:rs63751241)"
FT /evidence="ECO:0000269|PubMed:15086542,
FT ECO:0000269|PubMed:15459974"
FT /id="VAR_067907"
FT VARIANT 1406
FT /note="Q -> K (in PXE; autosomal recessive;
FT dbSNP:rs387906859)"
FT /evidence="ECO:0000269|PubMed:20034067"
FT /id="VAR_067908"
FT VARIANT 1424
FT /note="I -> T (in PXE; autosomal dominant;
FT dbSNP:rs63750295)"
FT /evidence="ECO:0000269|PubMed:11536079"
FT /id="VAR_013394"
FT VARIANT 1442
FT /note="A -> T (found in patient with putative diagnosis of
FT PEX; uncertain pathological significance;
FT dbSNP:rs1462269230)"
FT /evidence="ECO:0000269|PubMed:25615550"
FT /id="VAR_072813"
FT VARIANT 1459
FT /note="R -> C (in PXE; putative autosomal dominant;
FT dbSNP:rs72547524)"
FT /evidence="ECO:0000269|PubMed:15098239"
FT /id="VAR_067909"
FT CONFLICT 6
FT /note="E -> Q (in Ref. 4; CAO81806)"
FT /evidence="ECO:0000305"
FT CONFLICT 377
FT /note="L -> P (in Ref. 1; AAD51293)"
FT /evidence="ECO:0000305"
FT CONFLICT 401
FT /note="R -> K (in Ref. 4; CAO81806)"
FT /evidence="ECO:0000305"
FT CONFLICT 986
FT /note="L -> P (in Ref. 4; CAO81806)"
FT /evidence="ECO:0000305"
FT CONFLICT 1274
FT /note="Y -> C (in Ref. 1; AAD51293)"
FT /evidence="ECO:0000305"
FT CONFLICT 1455
FT /note="L -> P (in Ref. 1; AAD51293)"
FT /evidence="ECO:0000305"
FT STRAND 627..639
FT /evidence="ECO:0007829|PDB:6BZS"
FT STRAND 645..654
FT /evidence="ECO:0007829|PDB:6BZS"
FT STRAND 658..662
FT /evidence="ECO:0007829|PDB:6BZS"
FT HELIX 669..676
FT /evidence="ECO:0007829|PDB:6BZS"
FT STRAND 680..689
FT /evidence="ECO:0007829|PDB:6BZS"
FT STRAND 693..696
FT /evidence="ECO:0007829|PDB:6BZS"
FT STRAND 704..706
FT /evidence="ECO:0007829|PDB:6BZS"
FT HELIX 707..712
FT /evidence="ECO:0007829|PDB:6BZS"
FT HELIX 719..728
FT /evidence="ECO:0007829|PDB:6BZS"
FT HELIX 732..737
FT /evidence="ECO:0007829|PDB:6BZS"
FT STRAND 738..740
FT /evidence="ECO:0007829|PDB:6NLO"
FT HELIX 741..743
FT /evidence="ECO:0007829|PDB:6BZS"
FT STRAND 745..751
FT /evidence="ECO:0007829|PDB:6BZS"
FT HELIX 755..768
FT /evidence="ECO:0007829|PDB:6BZS"
FT STRAND 772..778
FT /evidence="ECO:0007829|PDB:6BZS"
FT STRAND 781..783
FT /evidence="ECO:0007829|PDB:6BZS"
FT HELIX 785..795
FT /evidence="ECO:0007829|PDB:6BZS"
FT TURN 801..804
FT /evidence="ECO:0007829|PDB:6BZS"
FT STRAND 805..810
FT /evidence="ECO:0007829|PDB:6BZS"
FT HELIX 817..819
FT /evidence="ECO:0007829|PDB:6BZS"
FT STRAND 820..827
FT /evidence="ECO:0007829|PDB:6BZS"
FT STRAND 830..835
FT /evidence="ECO:0007829|PDB:6BZS"
FT HELIX 837..842
FT /evidence="ECO:0007829|PDB:6BZS"
FT HELIX 846..852
FT /evidence="ECO:0007829|PDB:6BZS"
FT STRAND 1265..1272
FT /evidence="ECO:0007829|PDB:6BZR"
FT STRAND 1274..1278
FT /evidence="ECO:0007829|PDB:6P7F"
FT STRAND 1281..1289
FT /evidence="ECO:0007829|PDB:6BZR"
FT STRAND 1294..1298
FT /evidence="ECO:0007829|PDB:6BZR"
FT HELIX 1305..1312
FT /evidence="ECO:0007829|PDB:6BZR"
FT STRAND 1319..1325
FT /evidence="ECO:0007829|PDB:6BZR"
FT HELIX 1330..1332
FT /evidence="ECO:0007829|PDB:6BZR"
FT HELIX 1335..1340
FT /evidence="ECO:0007829|PDB:6BZR"
FT STRAND 1342..1345
FT /evidence="ECO:0007829|PDB:6BZR"
FT STRAND 1353..1355
FT /evidence="ECO:0007829|PDB:6BZR"
FT HELIX 1356..1360
FT /evidence="ECO:0007829|PDB:6BZR"
FT HELIX 1368..1377
FT /evidence="ECO:0007829|PDB:6BZR"
FT HELIX 1381..1386
FT /evidence="ECO:0007829|PDB:6BZR"
FT STRAND 1387..1389
FT /evidence="ECO:0007829|PDB:6BZR"
FT HELIX 1390..1392
FT /evidence="ECO:0007829|PDB:6BZR"
FT HELIX 1404..1417
FT /evidence="ECO:0007829|PDB:6BZR"
FT STRAND 1421..1426
FT /evidence="ECO:0007829|PDB:6BZR"
FT STRAND 1430..1432
FT /evidence="ECO:0007829|PDB:6P7F"
FT HELIX 1434..1444
FT /evidence="ECO:0007829|PDB:6BZR"
FT TURN 1445..1450
FT /evidence="ECO:0007829|PDB:6BZR"
FT STRAND 1451..1459
FT /evidence="ECO:0007829|PDB:6BZR"
FT HELIX 1460..1463
FT /evidence="ECO:0007829|PDB:6BZR"
FT STRAND 1464..1473
FT /evidence="ECO:0007829|PDB:6BZR"
FT STRAND 1476..1481
FT /evidence="ECO:0007829|PDB:6BZR"
FT HELIX 1483..1488
FT /evidence="ECO:0007829|PDB:6BZR"
FT HELIX 1492..1499
FT /evidence="ECO:0007829|PDB:6BZR"
SQ 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
