ABCC8_HUMAN
ID ABCC8_HUMAN Reviewed; 1581 AA.
AC Q09428; A6NMX8; E3UYX6; O75948; Q16583;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 02-NOV-2010, sequence version 6.
DT 03-AUG-2022, entry version 221.
DE RecName: Full=ATP-binding cassette sub-family C member 8;
DE AltName: Full=Sulfonylurea receptor 1;
GN Name=ABCC8; Synonyms=HRINS, SUR, SUR1;
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 3).
RC TISSUE=Heart;
RX PubMed=21671119; DOI=10.1007/s00018-011-0739-x;
RA Schmid D., Stolzlechner M., Sorgner A., Bentele C., Assinger A., Chiba P.,
RA Moeslinger T.;
RT "An abundant, truncated human sulfonylurea receptor 1 splice variant has
RT prodiabetic properties and impairs sulfonylurea action.";
RL Cell. Mol. Life Sci. 69:129-148(2012).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], ALTERNATIVE SPLICING, AND VARIANT
RP SER-1369.
RC TISSUE=Pancreatic islet;
RA Gonzalez G., Aguilar-Bryan L., Bryan J.;
RT "Human beta cell sulfonylurea receptor, SUR1, expression.";
RL Submitted (JUN-1996) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), VARIANT SER-1369, AND
RP VARIANT PNDM3 PRO-225.
RC TISSUE=Brain, and Foreskin;
RA Thomas P.T., Wohllk N., Huang E., Gagel R.F., Cote G.J.;
RL Submitted (JUL-1996) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT SER-1369.
RC TISSUE=Pancreas;
RA Nishimura M., Miki T., Aizawa T., Seino S.;
RL Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1187-1581, AND VARIANT SER-1369.
RC TISSUE=Pancreatic islet;
RX PubMed=7716548; DOI=10.1126/science.7716548;
RA Thomas P.M., Cote G.J., Wohllk N., Haddad B., Mathew P.M., Rabl W.,
RA Aguilar-Bryan L., Gagel R.F., Bryan J.;
RT "Mutations in the sulfonylurea receptor gene in familial persistent
RT hyperinsulinemic hypoglycemia of infancy.";
RL Science 268:426-429(1995).
RN [7]
RP TOPOLOGY.
RX PubMed=10506167; DOI=10.1074/jbc.274.41.29122;
RA Raab-Graham K.F., Cirilo L.J., Boettcher A.A., Radeke C.M.,
RA Vandenberg C.A.;
RT "Membrane topology of the amino-terminal region of the sulfonylurea
RT receptor.";
RL J. Biol. Chem. 274:29122-29129(1999).
RN [8]
RP REVIEW.
RX PubMed=10204114; DOI=10.1210/edrv.20.2.0361;
RA Aguilar-Bryan L., Bryan J.;
RT "Molecular biology of adenosine triphosphate-sensitive potassium
RT channels.";
RL Endocr. Rev. 20:101-135(1999).
RN [9]
RP REVIEW ON VARIANTS.
RX PubMed=10338089;
RX DOI=10.1002/(sici)1098-1004(1999)13:5<351::aid-humu3>3.0.co;2-r;
RA Meissner T., Beinbrech B., Mayatepek E.;
RT "Congenital hyperinsulinism: molecular basis of a heterogeneous disease.";
RL Hum. Mutat. 13:351-361(1999).
RN [10]
RP VARIANT HHF1 VAL-716.
RX PubMed=8751851;
RA Thomas P.M., Wohllk N., Huang E., Kuhnle U., Rabl W., Gagel R.F.,
RA Cote G.J.;
RT "Inactivation of the first nucleotide-binding fold of the sulfonylurea
RT receptor, and familial persistent hyperinsulinemic hypoglycemia of
RT infancy.";
RL Am. J. Hum. Genet. 59:510-518(1996).
RN [11]
RP VARIANT SER-1369.
RX PubMed=8635661; DOI=10.2337/diab.45.6.825;
RA Inoue H., Ferrer J., Welling C.M., Elbein S.C., Hoffman M., Mayorga R.,
RA Warren-Perry M., Zhang Y., Millns H., Turner R., Province M., Bryan J.,
RA Permutt M.A., Aguilar-Bryan L.;
RT "Sequence variants in the sulfonylurea receptor (SUR) gene are associated
RT with NIDDM in Caucasians.";
RL Diabetes 45:825-831(1996).
RN [12]
RP VARIANT HHF1 PHE-1387 DEL, AND VARIANTS GLY-1360; SER-1369 AND ILE-1572.
RX PubMed=8923011; DOI=10.1093/hmg/5.11.1813;
RA Nestorowicz A., Wilson B.A., Schoor K.P., Inoue H., Glaser B., Landau H.,
RA Stanley C.A., Thornton P.S., Clement J.P. IV, Bryan J., Aguilar-Bryan L.,
RA Permutt M.A.;
RT "Mutations in the sulfonylurea receptor gene are associated with familial
RT hyperinsulinism in Ashkenazi Jews.";
RL Hum. Mol. Genet. 5:1813-1822(1996).
RN [13]
RP CHARACTERIZATION OF VARIANT HHF1 ARG-1478.
RX PubMed=8650576; DOI=10.1126/science.272.5269.1785;
RA Nichols C.G., Shyng S.-L., Nestorowicz A., Glaser B., Clement J.P. IV,
RA Gonzalez G., Aguilar-Bryan L., Permutt M.A., Bryan J.;
RT "Adenosine diphosphate as an intracellular regulator of insulin
RT secretion.";
RL Science 272:1785-1787(1996).
RN [14]
RP VARIANTS GLN-275; MET-560; ASN-810; CYS-834 AND SER-1369.
RX PubMed=9519757; DOI=10.2337/diabetes.47.3.476;
RA Ohta Y., Tanizawa Y., Inoue H., Hosaka T., Ueda K., Matsutani A.,
RA Repunte V.P., Yamada M., Kurachi Y., Bryan J., Aguilar-Bryan L.,
RA Permutt M.A., Oka Y.;
RT "Identification and functional analysis of sulfonylurea receptor 1 variants
RT in Japanese patients with NIDDM.";
RL Diabetes 47:476-481(1998).
RN [15]
RP VARIANTS ASN-673 AND SER-1369.
RX PubMed=9568693; DOI=10.2337/diabetes.47.4.598;
RA Hansen T., Echwald S.M., Hansen L., Moeller A.M., Almind K., Clausen J.O.,
RA Urhammer S.A., Inoue H., Ferrer J., Bryan J., Aguilar-Bryan L.,
RA Permutt M.A., Pedersen O.;
RT "Decreased tolbutamide-stimulated insulin secretion in healthy subjects
RT with sequence variants in the high-affinity sulfonylurea receptor gene.";
RL Diabetes 47:598-605(1998).
RN [16]
RP CHARACTERIZATION OF VARIANTS HHF1 GLN-125; SER-188; LEU-591; MET-1138;
RP GLN-1214; SER-1381; PHE-1387 DEL AND HIS-1393.
RX PubMed=9648840; DOI=10.2337/diabetes.47.7.1145;
RA Shyng S.-L., Ferrigni T., Shepard J.B., Nestorowicz A., Glaser B.,
RA Permutt M.A., Nichols C.G.;
RT "Functional analyses of novel mutations in the sulfonylurea receptor 1
RT associated with persistent hyperinsulinemic hypoglycemia of infancy.";
RL Diabetes 47:1145-1151(1998).
RN [17]
RP VARIANTS HHF1 GLN-74; GLN-125; SER-188; ASP-406; LEU-591; MET-1138;
RP GLN-1214; ARG-1378; SER-1381; PHE-1387 DEL AND HIS-1393.
RX PubMed=9618169; DOI=10.1093/hmg/7.7.1119;
RA Nestorowicz A., Glaser B., Wilson B.A., Shyng S.-L., Nichols C.G.,
RA Stanley C.A., Thornton P.S., Permutt M.A.;
RT "Genetic heterogeneity in familial hyperinsulinism.";
RL Hum. Mol. Genet. 7:1119-1128(1998).
RN [18]
RP VARIANTS HHF1 PRO-1352; CYS-1420 AND TRP-1493.
RX PubMed=9769320; DOI=10.1172/jci4495;
RA Verkarre V., Fournet J.-C., de Lonlay P., Gross-Morand M.-S., Devillers M.,
RA Rahier J., Brunelle F., Robert J.-J., Nihoul-Fekete C., Saudubray J.-M.,
RA Junien C.;
RT "Paternal mutation of the sulfonylurea receptor (SUR1) gene and maternal
RT loss of 11p15 imprinted genes lead to persistent hyperinsulinism in focal
RT adenomatous hyperplasia.";
RL J. Clin. Invest. 102:1286-1291(1998).
RN [19]
RP VARIANT HHF1 ASP-187.
RX PubMed=10334322; DOI=10.2337/diabetes.48.2.408;
RA Otonkoski T., Aemmaelae C., Huopio H., Cote G.J., Chapman J., Cosgrove K.,
RA Ashfield R., Huang E., Komulainen J., Ashcroft F.M., Dunne M.J., Kere J.,
RA Thomas P.M.;
RT "A point mutation inactivating the sulfonylurea receptor causes the severe
RT form of persistent hyperinsulinemic hypoglycemia of infancy in Finland.";
RL Diabetes 48:408-415(1999).
RN [20]
RP VARIANTS SER-1369 AND ILE-1572.
RX PubMed=10447255;
RX DOI=10.1002/(sici)1098-1004(1999)14:1<23::aid-humu3>3.0.co;2-#;
RA Glaser B., Furth J., Stanley C.A., Baker L., Thornton P.S., Landau H.,
RA Permutt M.A.;
RT "Intragenic single nucleotide polymorphism haplotype analysis of SUR1
RT mutations in familial hyperinsulinism.";
RL Hum. Mutat. 14:23-29(1999).
RN [21]
RP VARIANTS HHF1 GLY-841; CYS-1420 AND TRP-1493.
RX PubMed=10202168; DOI=10.1056/nejm199904153401505;
RA de Lonlay-Debeney P., Poggi-Travert F., Fournet J.-C., Sempoux C.,
RA Vici C.D., Brunelle F., Touati G., Rahier J., Junien C., Nihoul-Fekete C.,
RA Robert J.-J., Saudubray J.-M.;
RT "Clinical features of 52 neonates with hyperinsulinism.";
RL N. Engl. J. Med. 340:1169-1175(1999).
RN [22]
RP CHARACTERIZATION OF VARIANTS HHF1 CYS-1420 AND GLN-1436, AND VARIANT
RP SER-1369.
RX PubMed=10615958; DOI=10.2337/diabetes.49.1.114;
RA Tanizawa Y., Matsuda K., Matsuo M., Ohta Y., Ochi N., Adachi M., Koga M.,
RA Mizuno S., Kajita M., Tanaka Y., Tachibana K., Inoue H., Furukawa S.,
RA Amachi T., Ueda K., Oka Y.;
RT "Genetic analysis of Japanese patients with persistent hyperinsulinemic
RT hypoglycemia of infancy: nucleotide-binding fold-2 mutation impairs
RT cooperative binding of adenine nucleotides to sulfonylurea receptor 1.";
RL Diabetes 49:114-120(2000).
RN [23]
RP CHARACTERIZATION OF VARIANT HHF1 LYS-1506.
RX PubMed=11018078; DOI=10.1172/jci9804;
RA Huopio H., Reimann F., Ashfield R., Komulainen J., Lenko H.-L., Rahier J.,
RA Vauhkonen I., Kere J., Laakso M., Ashcroft F., Otonkoski T.;
RT "Dominantly inherited hyperinsulinism caused by a mutation in the
RT sulfonylurea receptor type 1.";
RL J. Clin. Invest. 106:897-906(2000).
RN [24]
RP CHARACTERIZATION OF VARIANT HHF1 PHE-1387 DEL.
RX PubMed=11226335; DOI=10.1073/pnas.051499698;
RA Cartier E.A., Conti L.R., Vandenberg C.A., Shyng S.-L.;
RT "Defective trafficking and function of KATP channels caused by a
RT sulfonylurea receptor 1 mutation associated with persistent
RT hyperinsulinemic hypoglycemia of infancy.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:2882-2887(2001).
RN [25]
RP CHARACTERIZATION OF VARIANT HHF1 PRO-1543.
RX PubMed=11867634; DOI=10.1074/jbc.m200363200;
RA Taschenberger G., Mougey A., Shen S., Lester L.B., LaFranchi S.,
RA Shyng S.-L.;
RT "Identification of a familial hyperinsulinism-causing mutation in the
RT sulfonylurea receptor 1 that prevents normal trafficking and function of
RT KATP channels.";
RL J. Biol. Chem. 277:17139-17146(2002).
RN [26]
RP VARIANTS HHF1 ASP-187; THR-1457; LYS-1506; ASP-1550 AND VAL-1551.
RX PubMed=12364426; DOI=10.1210/jc.2002-020378;
RA Huopio H., Jaeaeskelaeinen J., Komulainen J., Miettinen R.,
RA Kaerkkaeinen P., Laakso M., Tapanainen P., Voutilainen R., Otonkoski T.;
RT "Acute insulin response tests for the differential diagnosis of congenital
RT hyperinsulinism.";
RL J. Clin. Endocrinol. Metab. 87:4502-4507(2002).
RN [27]
RP VARIANT HHF1 SER-1385 DEL, AND CHARACTERIZATION OF VARIANT HHF1 SER-1385
RP DEL.
RX PubMed=12941782; DOI=10.2337/diabetes.52.9.2403;
RA Thornton P.S., MacMullen C., Ganguly A., Ruchelli E., Steinkrauss L.,
RA Crane A., Aguilar-Bryan L., Stanley C.A.;
RT "Clinical and molecular characterization of a dominant form of congenital
RT hyperinsulinism caused by a mutation in the high-affinity sulfonylurea
RT receptor.";
RL Diabetes 52:2403-2410(2003).
RN [28]
RP VARIANT LIH HIS-1352, AND CHARACTERIZATION OF VARIANT LIH HIS-1352.
RX PubMed=15356046; DOI=10.1210/jc.2004-0441;
RA Magge S.N., Shyng S.-L., MacMullen C., Steinkrauss L., Ganguly A.,
RA Katz L.E.L., Stanley C.A.;
RT "Familial leucine-sensitive hypoglycemia of infancy due to a dominant
RT mutation of the beta-cell sulfonylurea receptor.";
RL J. Clin. Endocrinol. Metab. 89:4450-4456(2004).
RN [29]
RP VARIANTS HHF1 GLU-70; ARG-111; GLU-1342; HIS-1418 AND TRP-1493, AND
RP CHARACTERIZATION OF VARIANTS HHF1 GLU-70; ARG-111; GLU-1342; HIS-1418 AND
RP TRP-1493.
RX PubMed=15579781; DOI=10.1210/jc.2004-1233;
RA Tornovsky S., Crane A., Cosgrove K.E., Hussain K., Lavie J., Heyman M.,
RA Nesher Y., Kuchinski N., Ben-Shushan E., Shatz O., Nahari E., Potikha T.,
RA Zangen D., Tenenbaum-Rakover Y., de Vries L., Argente J., Gracia R.,
RA Landau H., Eliakim A., Lindley K., Dunne M.J., Aguilar-Bryan L., Glaser B.;
RT "Hyperinsulinism of infancy: novel ABCC8 and KCNJ11 mutations and evidence
RT for additional locus heterogeneity.";
RL J. Clin. Endocrinol. Metab. 89:6224-6234(2004).
RN [30]
RP VARIANTS HHF1 GLN-1384 AND LYS-1486, AND VARIANT SER-1369.
RX PubMed=15807877; DOI=10.1111/j.1365-2265.2005.02242.x;
RA Ohkubo K., Nagashima M., Naito Y., Taguchi T., Suita S., Okamoto N.,
RA Fujinaga H., Tsumura K., Kikuchi K., Ono J.;
RT "Genotypes of the pancreatic beta-cell K-ATP channel and clinical
RT phenotypes of Japanese patients with persistent hyperinsulinaemic
RT hypoglycaemia of infancy.";
RL Clin. Endocrinol. (Oxf.) 62:458-465(2005).
RN [31]
RP VARIANTS HHF1 SER-27; TRP-74; SER-188; GLN-495; LYS-501; SER-686; TRP-1214;
RP GLN-1214; ASN-1336; PHE-1387 DEL; HIS-1471 AND ASN-1471.
RX PubMed=15562009; DOI=10.1210/jc.2004-1604;
RA Henwood M.J., Kelly A., MacMullen C., Bhatia P., Ganguly A., Thornton P.S.,
RA Stanley C.A.;
RT "Genotype-phenotype correlations in children with congenital
RT hyperinsulinism due to recessive mutations of the adenosine triphosphate-
RT sensitive potassium channel genes.";
RL J. Clin. Endocrinol. Metab. 90:789-794(2005).
RN [32]
RP VARIANT PNDM3 LEU-132, AND CHARACTERIZATION OF VARIANT PNDM3 LEU-132.
RX PubMed=16613899; DOI=10.1093/hmg/ddl101;
RA Proks P., Arnold A.L., Bruining J., Girard C., Flanagan S.E., Larkin B.,
RA Colclough K., Hattersley A.T., Ashcroft F.M., Ellard S.;
RT "A heterozygous activating mutation in the sulphonylurea receptor SUR1
RT (ABCC8) causes neonatal diabetes.";
RL Hum. Mol. Genet. 15:1793-1800(2006).
RN [33]
RP VARIANTS HHF1 TRP-74; ARG-111; SER-188; ARG-233; ASN-310; ARG-551; THR-719;
RP PRO-1130; ARG-1147; LYS-1295 AND PRO-1450, AND VARIANTS SER-1369 AND
RP ILE-1572.
RX PubMed=16429405; DOI=10.1002/humu.9401;
RA Fernandez-Marmiesse A., Salas A., Vega A., Fernandez-Lorenzo J.R.,
RA Barreiro J., Carracedo A.;
RT "Mutation spectra of ABCC8 gene in Spanish patients with Hyperinsulinism of
RT Infancy (HI).";
RL Hum. Mutat. 27:214-214(2006).
RN [34]
RP VARIANTS HHF1 ARG-7; ASP-21; SER-27; TRP-74; LYS-501; PRO-503; SER-686;
RP TRP-1214; TRP-1214; GLN-1349; ARG-1378; PHE-1387 DEL; ARG-1400 AND
RP GLN-1493.
RX PubMed=16357843; DOI=10.1038/modpathol.3800497;
RA Suchi M., MacMullen C.M., Thornton P.S., Adzick N.S., Ganguly A.,
RA Ruchelli E.D., Stanley C.A.;
RT "Molecular and immunohistochemical analyses of the focal form of congenital
RT hyperinsulinism.";
RL Mod. Pathol. 19:122-129(2006).
RN [35]
RP VARIANTS PNDM3 ARG-213 AND VAL-1424, VARIANTS TNDM2 ARG-435; VAL-582;
RP TYR-1023; GLN-1182 AND CYS-1379, CHARACTERIZATION OF VARIANT PNDM3
RP VAL-1424, AND CHARACTERIZATION OF VARIANT TNDM2 TYR-1023.
RX PubMed=16885549; DOI=10.1056/nejmoa055068;
RA Babenko A.P., Polak M., Cave H., Busiah K., Czernichow P., Scharfmann R.,
RA Bryan J., Aguilar-Bryan L., Vaxillaire M., Froguel P.;
RT "Activating mutations in the ABCC8 gene in neonatal diabetes mellitus.";
RL N. Engl. J. Med. 355:456-466(2006).
RN [36]
RP VARIANTS PNDM3 LEU-45; SER-72; ALA-86; GLY-86; LEU-132; VAL-132; SER-207;
RP LYS-208; GLU-209; LYS-211; PRO-225; ILE-229; ASP-263; LYS-382; GLU-1184;
RP LYS-1326; ARG-1400 AND LEU-1522, AND CHARACTERIZATION OF VARIANTS PNDM3
RP LEU-132; SER-207; ILE-229; GLU-1184 AND LEU-1522.
RX PubMed=17668386; DOI=10.1086/519174;
RA Ellard S., Flanagan S.E., Girard C.A., Patch A.M., Harries L.W.,
RA Parrish A., Edghill E.L., Mackay D.J., Proks P., Shimomura K.,
RA Haberland H., Carson D.J., Shield J.P., Hattersley A.T., Ashcroft F.M.;
RT "Permanent neonatal diabetes caused by dominant, recessive, or compound
RT heterozygous SUR1 mutations with opposite functional effects.";
RL Am. J. Hum. Genet. 81:375-382(2007).
RN [37]
RP VARIANT PNDM3 ALA-86.
RX PubMed=17213273; DOI=10.1210/jc.2006-2490;
RA Stanik J., Gasperikova D., Paskova M., Barak L., Javorkova J., Jancova E.,
RA Ciljakova M., Hlava P., Michalek J., Flanagan S.E., Pearson E.,
RA Hattersley A.T., Ellard S., Klimes I.;
RT "Prevalence of permanent neonatal diabetes in Slovakia and successful
RT replacement of insulin with sulfonylurea therapy in KCNJ11 and ABCC8
RT mutation carriers.";
RL J. Clin. Endocrinol. Metab. 92:1276-1282(2007).
RN [38]
RP VARIANTS HHF1 MET-511; ASP-716; LYS-824; THR-889; PRO-890; PRO-1352;
RP SER-1378; PHE-1386; TYR-1388; PRO-1389; VAL-1457; ILE-1480; GLU-1505 AND
RP SER-1511, CHARACTERIZATION OF VARIANTS HHF1 MET-511; LYS-824; THR-889;
RP PRO-890; SER-1378; VAL-1457; ILE-1480; GLU-1505 AND SER-1511, FUNCTION, AND
RP SUBCELLULAR LOCATION.
RX PubMed=24814349; DOI=10.1111/cge.12428;
RA Saint-Martin C., Zhou Q., Martin G.M., Vaury C., Leroy G., Arnoux J.B.,
RA de Lonlay P., Shyng S.L., Bellanne-Chantelot C.;
RT "Monoallelic ABCC8 mutations are a common cause of diazoxide-unresponsive
RT diffuse form of congenital hyperinsulinism.";
RL Clin. Genet. 87:448-454(2015).
RN [39]
RP VARIANT HHF1 HIS-1418, CHARACTERIZATION OF VARIANT HHF1 HIS-1418, AND
RP FUNCTION.
RX PubMed=25720052; DOI=10.1515/jpem-2014-0265;
RA Harel S., Cohen A.S., Hussain K., Flanagan S.E., Schlade-Bartusiak K.,
RA Patel M., Courtade J., Li J.B., Van Karnebeek C., Kurata H., Ellard S.,
RA Chanoine J.P., Gibson W.T.;
RT "Alternating hypoglycemia and hyperglycemia in a toddler with a homozygous
RT p.R1419H ABCC8 mutation: an unusual clinical picture.";
RL J. Pediatr. Endocrinol. Metab. 28:345-351(2015).
CC -!- FUNCTION: Subunit of the beta-cell ATP-sensitive potassium channel
CC (KATP). Regulator of ATP-sensitive K(+) channels and insulin release.
CC {ECO:0000269|PubMed:24814349, ECO:0000269|PubMed:25720052}.
CC -!- SUBUNIT: Interacts with KCNJ11.
CC -!- INTERACTION:
CC Q09428-1; Q14654: KCNJ11; NbExp=2; IntAct=EBI-15807650, EBI-2866553;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:24814349};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q09428-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q09428-2; Sequence=VSP_000055;
CC Name=3; Synonyms=SUR1Delta2;
CC IsoId=Q09428-3; Sequence=VSP_044090;
CC -!- DISEASE: Leucine-induced hypoglycemia (LIH) [MIM:240800]: Rare cause of
CC hypoglycemia and is described as a condition in which symptomatic
CC hypoglycemia is provoked by high protein feedings. Hypoglycemia is also
CC elicited by administration of oral or intravenous infusions of a single
CC amino acid, leucine. {ECO:0000269|PubMed:15356046}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- DISEASE: Familial hyperinsulinemic hypoglycemia 1 (HHF1) [MIM:256450]:
CC Most common cause of persistent hypoglycemia in infancy. Unless early
CC and aggressive intervention is undertaken, brain damage from recurrent
CC episodes of hypoglycemia may occur. {ECO:0000269|PubMed:10202168,
CC ECO:0000269|PubMed:10334322, ECO:0000269|PubMed:10615958,
CC ECO:0000269|PubMed:11018078, ECO:0000269|PubMed:11226335,
CC ECO:0000269|PubMed:11867634, ECO:0000269|PubMed:12364426,
CC ECO:0000269|PubMed:12941782, ECO:0000269|PubMed:15562009,
CC ECO:0000269|PubMed:15579781, ECO:0000269|PubMed:15807877,
CC ECO:0000269|PubMed:16357843, ECO:0000269|PubMed:16429405,
CC ECO:0000269|PubMed:24814349, ECO:0000269|PubMed:25720052,
CC ECO:0000269|PubMed:8650576, ECO:0000269|PubMed:8751851,
CC ECO:0000269|PubMed:8923011, ECO:0000269|PubMed:9618169,
CC ECO:0000269|PubMed:9648840, ECO:0000269|PubMed:9769320}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Diabetes mellitus, permanent neonatal, 3 (PNDM3) [MIM:618857]:
CC A form of permanent neonatal diabetes mellitus, a type of diabetes
CC characterized by onset of persistent hyperglycemia within the first six
CC months of life. Initial clinical manifestations include intrauterine
CC growth retardation, hyperglycemia, glycosuria, osmotic polyuria, severe
CC dehydration, and failure to thrive. Some PNDM3 patients may also have
CC developmental delay, muscle weakness, and epilepsy. PNDM3 transmission
CC pattern is consistent with autosomal dominant or autosomal recessive
CC inheritance. {ECO:0000269|PubMed:16613899, ECO:0000269|PubMed:16885549,
CC ECO:0000269|PubMed:17213273, ECO:0000269|PubMed:17668386}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Transient neonatal diabetes mellitus 2 (TNDM2) [MIM:610374]:
CC Neonatal diabetes is a form of diabetes mellitus defined by the onset
CC of mild-to-severe hyperglycemia within the first months of life.
CC Transient neonatal diabetes remits early, with a possible relapse
CC during adolescence. {ECO:0000269|PubMed:16885549}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: [Isoform 3]: Abundant isoform with prodiabetic
CC properties, predominant in heart. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the ABC transporter superfamily. ABCC family.
CC Conjugate transporter (TC 3.A.1.208) subfamily. {ECO:0000305}.
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; HM635782; ADM67556.1; -; mRNA.
DR EMBL; L78207; AAB02278.1; -; mRNA.
DR EMBL; L78243; AAB02417.1; -; Genomic_DNA.
DR EMBL; L78208; AAB02417.1; JOINED; Genomic_DNA.
DR EMBL; L78209; AAB02417.1; JOINED; Genomic_DNA.
DR EMBL; L78210; AAB02417.1; JOINED; Genomic_DNA.
DR EMBL; L78211; AAB02417.1; JOINED; Genomic_DNA.
DR EMBL; L78212; AAB02417.1; JOINED; Genomic_DNA.
DR EMBL; L78255; AAB02417.1; JOINED; Genomic_DNA.
DR EMBL; L78213; AAB02417.1; JOINED; Genomic_DNA.
DR EMBL; L78214; AAB02417.1; JOINED; Genomic_DNA.
DR EMBL; L78215; AAB02417.1; JOINED; Genomic_DNA.
DR EMBL; L78216; AAB02417.1; JOINED; Genomic_DNA.
DR EMBL; L78217; AAB02417.1; JOINED; Genomic_DNA.
DR EMBL; L78218; AAB02417.1; JOINED; Genomic_DNA.
DR EMBL; L78219; AAB02417.1; JOINED; Genomic_DNA.
DR EMBL; L78220; AAB02417.1; JOINED; Genomic_DNA.
DR EMBL; L78221; AAB02417.1; JOINED; Genomic_DNA.
DR EMBL; L78222; AAB02417.1; JOINED; Genomic_DNA.
DR EMBL; L78223; AAB02417.1; JOINED; Genomic_DNA.
DR EMBL; L78225; AAB02417.1; JOINED; Genomic_DNA.
DR EMBL; L78254; AAB02417.1; JOINED; Genomic_DNA.
DR EMBL; L78226; AAB02417.1; JOINED; Genomic_DNA.
DR EMBL; L78227; AAB02417.1; JOINED; Genomic_DNA.
DR EMBL; L78228; AAB02417.1; JOINED; Genomic_DNA.
DR EMBL; L78229; AAB02417.1; JOINED; Genomic_DNA.
DR EMBL; L78230; AAB02417.1; JOINED; Genomic_DNA.
DR EMBL; L78231; AAB02417.1; JOINED; Genomic_DNA.
DR EMBL; L78232; AAB02417.1; JOINED; Genomic_DNA.
DR EMBL; L78233; AAB02417.1; JOINED; Genomic_DNA.
DR EMBL; L78234; AAB02417.1; JOINED; Genomic_DNA.
DR EMBL; L78235; AAB02417.1; JOINED; Genomic_DNA.
DR EMBL; L78236; AAB02417.1; JOINED; Genomic_DNA.
DR EMBL; L78237; AAB02417.1; JOINED; Genomic_DNA.
DR EMBL; L78238; AAB02417.1; JOINED; Genomic_DNA.
DR EMBL; L78239; AAB02417.1; JOINED; Genomic_DNA.
DR EMBL; L78240; AAB02417.1; JOINED; Genomic_DNA.
DR EMBL; L78241; AAB02417.1; JOINED; Genomic_DNA.
DR EMBL; L78242; AAB02417.1; JOINED; Genomic_DNA.
DR EMBL; L78243; AAB02418.1; -; Genomic_DNA.
DR EMBL; L78208; AAB02418.1; JOINED; Genomic_DNA.
DR EMBL; L78209; AAB02418.1; JOINED; Genomic_DNA.
DR EMBL; L78210; AAB02418.1; JOINED; Genomic_DNA.
DR EMBL; L78211; AAB02418.1; JOINED; Genomic_DNA.
DR EMBL; L78212; AAB02418.1; JOINED; Genomic_DNA.
DR EMBL; L78255; AAB02418.1; JOINED; Genomic_DNA.
DR EMBL; L78213; AAB02418.1; JOINED; Genomic_DNA.
DR EMBL; L78214; AAB02418.1; JOINED; Genomic_DNA.
DR EMBL; L78215; AAB02418.1; JOINED; Genomic_DNA.
DR EMBL; L78216; AAB02418.1; JOINED; Genomic_DNA.
DR EMBL; L78217; AAB02418.1; JOINED; Genomic_DNA.
DR EMBL; L78218; AAB02418.1; JOINED; Genomic_DNA.
DR EMBL; L78219; AAB02418.1; JOINED; Genomic_DNA.
DR EMBL; L78220; AAB02418.1; JOINED; Genomic_DNA.
DR EMBL; L78221; AAB02418.1; JOINED; Genomic_DNA.
DR EMBL; L78222; AAB02418.1; JOINED; Genomic_DNA.
DR EMBL; L78224; AAB02418.1; JOINED; Genomic_DNA.
DR EMBL; L78225; AAB02418.1; JOINED; Genomic_DNA.
DR EMBL; L78254; AAB02418.1; JOINED; Genomic_DNA.
DR EMBL; L78226; AAB02418.1; JOINED; Genomic_DNA.
DR EMBL; L78227; AAB02418.1; JOINED; Genomic_DNA.
DR EMBL; L78228; AAB02418.1; JOINED; Genomic_DNA.
DR EMBL; L78229; AAB02418.1; JOINED; Genomic_DNA.
DR EMBL; L78230; AAB02418.1; JOINED; Genomic_DNA.
DR EMBL; L78231; AAB02418.1; JOINED; Genomic_DNA.
DR EMBL; L78232; AAB02418.1; JOINED; Genomic_DNA.
DR EMBL; L78233; AAB02418.1; JOINED; Genomic_DNA.
DR EMBL; L78234; AAB02418.1; JOINED; Genomic_DNA.
DR EMBL; L78235; AAB02418.1; JOINED; Genomic_DNA.
DR EMBL; L78236; AAB02418.1; JOINED; Genomic_DNA.
DR EMBL; L78237; AAB02418.1; JOINED; Genomic_DNA.
DR EMBL; L78238; AAB02418.1; JOINED; Genomic_DNA.
DR EMBL; L78239; AAB02418.1; JOINED; Genomic_DNA.
DR EMBL; L78240; AAB02418.1; JOINED; Genomic_DNA.
DR EMBL; L78241; AAB02418.1; JOINED; Genomic_DNA.
DR EMBL; L78242; AAB02418.1; JOINED; Genomic_DNA.
DR EMBL; U63421; AAB36699.1; -; mRNA.
DR EMBL; U63455; AAB36700.1; -; Genomic_DNA.
DR EMBL; U63422; AAB36700.1; JOINED; Genomic_DNA.
DR EMBL; U63423; AAB36700.1; JOINED; Genomic_DNA.
DR EMBL; U63424; AAB36700.1; JOINED; Genomic_DNA.
DR EMBL; U63425; AAB36700.1; JOINED; Genomic_DNA.
DR EMBL; U63426; AAB36700.1; JOINED; Genomic_DNA.
DR EMBL; U63427; AAB36700.1; JOINED; Genomic_DNA.
DR EMBL; U63428; AAB36700.1; JOINED; Genomic_DNA.
DR EMBL; U63429; AAB36700.1; JOINED; Genomic_DNA.
DR EMBL; U63430; AAB36700.1; JOINED; Genomic_DNA.
DR EMBL; U63431; AAB36700.1; JOINED; Genomic_DNA.
DR EMBL; U63432; AAB36700.1; JOINED; Genomic_DNA.
DR EMBL; U63433; AAB36700.1; JOINED; Genomic_DNA.
DR EMBL; U63434; AAB36700.1; JOINED; Genomic_DNA.
DR EMBL; U63435; AAB36700.1; JOINED; Genomic_DNA.
DR EMBL; U63436; AAB36700.1; JOINED; Genomic_DNA.
DR EMBL; U63437; AAB36700.1; JOINED; Genomic_DNA.
DR EMBL; U63438; AAB36700.1; JOINED; Genomic_DNA.
DR EMBL; U63439; AAB36700.1; JOINED; Genomic_DNA.
DR EMBL; U63441; AAB36700.1; JOINED; Genomic_DNA.
DR EMBL; U63442; AAB36700.1; JOINED; Genomic_DNA.
DR EMBL; U63443; AAB36700.1; JOINED; Genomic_DNA.
DR EMBL; U63444; AAB36700.1; JOINED; Genomic_DNA.
DR EMBL; U63445; AAB36700.1; JOINED; Genomic_DNA.
DR EMBL; U63446; AAB36700.1; JOINED; Genomic_DNA.
DR EMBL; U63447; AAB36700.1; JOINED; Genomic_DNA.
DR EMBL; U63448; AAB36700.1; JOINED; Genomic_DNA.
DR EMBL; U63449; AAB36700.1; JOINED; Genomic_DNA.
DR EMBL; U63450; AAB36700.1; JOINED; Genomic_DNA.
DR EMBL; U63451; AAB36700.1; JOINED; Genomic_DNA.
DR EMBL; U63452; AAB36700.1; JOINED; Genomic_DNA.
DR EMBL; U63453; AAB36700.1; JOINED; Genomic_DNA.
DR EMBL; U63454; AAB36700.1; JOINED; Genomic_DNA.
DR EMBL; AF087138; AAC36724.1; -; mRNA.
DR EMBL; AC124798; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; L40625; AAA99227.1; -; mRNA.
DR CCDS; CCDS31437.1; -. [Q09428-1]
DR CCDS; CCDS73264.1; -. [Q09428-2]
DR RefSeq; NP_000343.2; NM_000352.4. [Q09428-1]
DR RefSeq; NP_001274103.1; NM_001287174.1. [Q09428-2]
DR PDB; 6C3O; EM; 3.90 A; E/F/G/H=1-1581.
DR PDB; 6C3P; EM; 5.60 A; E/F/G/H=1-1581.
DR PDB; 7S5V; EM; 3.30 A; E=2-1581.
DR PDB; 7S5X; EM; 3.70 A; E=2-1581.
DR PDB; 7S5Y; EM; 3.90 A; E=2-1581.
DR PDB; 7S5Z; EM; 3.90 A; E=2-1581.
DR PDB; 7S60; EM; 3.70 A; E=2-1581.
DR PDB; 7S61; EM; 4.00 A; E=2-1581.
DR PDBsum; 6C3O; -.
DR PDBsum; 6C3P; -.
DR PDBsum; 7S5V; -.
DR PDBsum; 7S5X; -.
DR PDBsum; 7S5Y; -.
DR PDBsum; 7S5Z; -.
DR PDBsum; 7S60; -.
DR PDBsum; 7S61; -.
DR AlphaFoldDB; Q09428; -.
DR SMR; Q09428; -.
DR BioGRID; 112700; 10.
DR ComplexPortal; CPX-195; Inward rectifying potassium channel complex, Kir6.2-SUR1.
DR DIP; DIP-58642N; -.
DR ELM; Q09428; -.
DR IntAct; Q09428; 4.
DR MINT; Q09428; -.
DR STRING; 9606.ENSP00000303960; -.
DR BindingDB; Q09428; -.
DR ChEMBL; CHEMBL2071; -.
DR DrugBank; DB00171; ATP.
DR DrugBank; DB00672; Chlorpropamide.
DR DrugBank; DB01120; Gliclazide.
DR DrugBank; DB00222; Glimepiride.
DR DrugBank; DB01067; Glipizide.
DR DrugBank; DB01251; Gliquidone.
DR DrugBank; DB01016; Glyburide.
DR DrugBank; DB01382; Glymidine.
DR DrugBank; DB01252; Mitiglinide.
DR DrugBank; DB00731; Nateglinide.
DR DrugBank; DB00912; Repaglinide.
DR DrugBank; DB00839; Tolazamide.
DR DrugBank; DB01124; Tolbutamide.
DR DrugCentral; Q09428; -.
DR GuidetoPHARMACOLOGY; 2594; -.
DR TCDB; 3.A.1.208.4; the atp-binding cassette (abc) superfamily.
DR GlyGen; Q09428; 2 sites.
DR iPTMnet; Q09428; -.
DR PhosphoSitePlus; Q09428; -.
DR BioMuta; ABCC8; -.
DR DMDM; 311033501; -.
DR jPOST; Q09428; -.
DR MassIVE; Q09428; -.
DR PaxDb; Q09428; -.
DR PeptideAtlas; Q09428; -.
DR PRIDE; Q09428; -.
DR ProteomicsDB; 58720; -. [Q09428-1]
DR ProteomicsDB; 58721; -. [Q09428-2]
DR Antibodypedia; 24846; 320 antibodies from 37 providers.
DR DNASU; 6833; -.
DR Ensembl; ENST00000302539.9; ENSP00000303960.4; ENSG00000006071.16. [Q09428-2]
DR Ensembl; ENST00000389817.8; ENSP00000374467.4; ENSG00000006071.16. [Q09428-1]
DR Ensembl; ENST00000644542.1; ENSP00000495532.1; ENSG00000006071.16. [Q09428-3]
DR Ensembl; ENST00000684593.1; ENSP00000507005.1; ENSG00000006071.16. [Q09428-3]
DR GeneID; 6833; -.
DR KEGG; hsa:6833; -.
DR MANE-Select; ENST00000389817.8; ENSP00000374467.4; NM_000352.6; NP_000343.2.
DR UCSC; uc001mnc.4; human. [Q09428-1]
DR CTD; 6833; -.
DR DisGeNET; 6833; -.
DR GeneCards; ABCC8; -.
DR GeneReviews; ABCC8; -.
DR HGNC; HGNC:59; ABCC8.
DR HPA; ENSG00000006071; Group enriched (pancreas, pituitary gland).
DR MalaCards; ABCC8; -.
DR MIM; 240800; phenotype.
DR MIM; 256450; phenotype.
DR MIM; 600509; gene.
DR MIM; 602485; phenotype.
DR MIM; 610374; phenotype.
DR MIM; 618857; phenotype.
DR neXtProt; NX_Q09428; -.
DR OpenTargets; ENSG00000006071; -.
DR Orphanet; 276575; Autosomal dominant hyperinsulinism due to SUR1 deficiency.
DR Orphanet; 79643; Autosomal recessive hyperinsulinism due to SUR1 deficiency.
DR Orphanet; 79134; DEND syndrome.
DR Orphanet; 276598; Diazoxide-resistant focal hyperinsulinism due to SUR1 deficiency.
DR Orphanet; 99885; Isolated permanent neonatal diabetes mellitus.
DR Orphanet; 552; MODY.
DR Orphanet; 99886; Transient neonatal diabetes mellitus.
DR PharmGKB; PA24395; -.
DR VEuPathDB; HostDB:ENSG00000006071; -.
DR eggNOG; KOG0054; Eukaryota.
DR GeneTree; ENSGT00940000156626; -.
DR HOGENOM; CLU_000604_27_6_1; -.
DR InParanoid; Q09428; -.
DR OMA; ANTVVLW; -.
DR OrthoDB; 1287094at2759; -.
DR PhylomeDB; Q09428; -.
DR TreeFam; TF105201; -.
DR PathwayCommons; Q09428; -.
DR Reactome; R-HSA-1296025; ATP sensitive Potassium channels.
DR Reactome; R-HSA-422356; Regulation of insulin secretion.
DR Reactome; R-HSA-5683177; Defective ABCC8 can cause hypo- and hyper-glycemias.
DR SignaLink; Q09428; -.
DR SIGNOR; Q09428; -.
DR BioGRID-ORCS; 6833; 8 hits in 1071 CRISPR screens.
DR ChiTaRS; ABCC8; human.
DR GeneWiki; ABCC8; -.
DR GenomeRNAi; 6833; -.
DR Pharos; Q09428; Tclin.
DR PRO; PR:Q09428; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q09428; protein.
DR Bgee; ENSG00000006071; Expressed in islet of Langerhans and 124 other tissues.
DR ExpressionAtlas; Q09428; baseline and differential.
DR Genevisible; Q09428; HS.
DR GO; GO:0008282; C:inward rectifying potassium channel; IDA:BHF-UCL.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0031004; C:potassium ion-transporting ATPase complex; ISS:ARUK-UCL.
DR GO; GO:0042383; C:sarcolemma; IEA:Ensembl.
DR GO; GO:0030672; C:synaptic vesicle membrane; IEA:Ensembl.
DR GO; GO:0140359; F:ABC-type transporter activity; IEA:InterPro.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0015272; F:ATP-activated inward rectifier potassium channel activity; TAS:Reactome.
DR GO; GO:0019829; F:ATPase-coupled cation transmembrane transporter activity; IDA:ARUK-UCL.
DR GO; GO:0042626; F:ATPase-coupled transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0005267; F:potassium channel activity; IMP:UniProtKB.
DR GO; GO:0008281; F:sulfonylurea receptor activity; IEA:InterPro.
DR GO; GO:0044325; F:transmembrane transporter binding; IPI:BHF-UCL.
DR GO; GO:0001678; P:cellular glucose homeostasis; IEA:Ensembl.
DR GO; GO:0071310; P:cellular response to organic substance; IEA:Ensembl.
DR GO; GO:0007565; P:female pregnancy; IEA:Ensembl.
DR GO; GO:0098662; P:inorganic cation transmembrane transport; ISS:ARUK-UCL.
DR GO; GO:0007613; P:memory; IEA:Ensembl.
DR GO; GO:0016525; P:negative regulation of angiogenesis; IEA:Ensembl.
DR GO; GO:1905604; P:negative regulation of blood-brain barrier permeability; IEA:Ensembl.
DR GO; GO:0060253; P:negative regulation of glial cell proliferation; IEA:Ensembl.
DR GO; GO:0046676; P:negative regulation of insulin secretion; IEA:Ensembl.
DR GO; GO:0010989; P:negative regulation of low-density lipoprotein particle clearance; IEA:Ensembl.
DR GO; GO:0061855; P:negative regulation of neuroblast migration; IEA:Ensembl.
DR GO; GO:0061045; P:negative regulation of wound healing; IEA:Ensembl.
DR GO; GO:1905075; P:positive regulation of tight junction disassembly; IEA:Ensembl.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IEA:Ensembl.
DR GO; GO:1900721; P:positive regulation of uterine smooth muscle relaxation; IEA:Ensembl.
DR GO; GO:1903818; P:positive regulation of voltage-gated potassium channel activity; IEA:Ensembl.
DR GO; GO:1990573; P:potassium ion import across plasma membrane; IC:ComplexPortal.
DR GO; GO:0071805; P:potassium ion transmembrane transport; NAS:ARUK-UCL.
DR GO; GO:0006813; P:potassium ion transport; TAS:ProtInc.
DR GO; GO:0032868; P:response to insulin; IEA:Ensembl.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEA:Ensembl.
DR GO; GO:0009268; P:response to pH; IEA:Ensembl.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0010043; P:response to zinc ion; IEA:Ensembl.
DR GO; GO:0055085; P:transmembrane transport; IBA:GO_Central.
DR GO; GO:0008542; P:visual learning; IEA:Ensembl.
DR DisProt; DP02881; -.
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; IPR000844; ABCC8.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR000388; Sulphorea_rcpt.
DR Pfam; PF00664; ABC_membrane; 2.
DR Pfam; PF00005; ABC_tran; 2.
DR PRINTS; PR01093; SULFNYLUR1.
DR PRINTS; PR01092; SULFNYLUREAR.
DR SMART; SM00382; AAA; 2.
DR SUPFAM; SSF52540; SSF52540; 2.
DR SUPFAM; SSF90123; SSF90123; 2.
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 Diabetes mellitus; Disease variant; Glycoprotein; Membrane;
KW Nucleotide-binding; Receptor; Reference proteome; Repeat; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..1581
FT /note="ATP-binding cassette sub-family C member 8"
FT /id="PRO_0000093400"
FT TOPO_DOM 1..34
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 35..55
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 56..75
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 76..96
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 97..101
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 102..122
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 123..134
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 135..154
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 155..167
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 168..194
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 195..311
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 312..331
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 332..355
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 356..376
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 377..434
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 435..455
FT /note="Helical; Name=8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 456..458
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 459..479
FT /note="Helical; Name=9"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 480..541
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 542..562
FT /note="Helical; Name=10"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 563..584
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 585..605
FT /note="Helical; Name=11"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 606..1004
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 1005..1025
FT /note="Helical; Name=12"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 1026..1072
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 1073..1093
FT /note="Helical; Name=13"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 1094..1137
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 1138..1158
FT /note="Helical; Name=14"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 1159
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 1160..1180
FT /note="Helical; Name=15"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 1181..1251
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 1252..1272
FT /note="Helical; Name=16"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 1273..1276
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 1277..1297
FT /note="Helical; Name=17"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 1298..1581
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT DOMAIN 299..602
FT /note="ABC transmembrane type-1 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT DOMAIN 679..929
FT /note="ABC transporter 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT DOMAIN 1012..1306
FT /note="ABC transmembrane type-1 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT DOMAIN 1344..1578
FT /note="ABC transporter 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT REGION 935..987
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 966..982
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 713..720
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT BINDING 1378..1385
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT CARBOHYD 10
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250"
FT CARBOHYD 1049
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250"
FT VAR_SEQ 51..1581
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:21671119"
FT /id="VSP_044090"
FT VAR_SEQ 740
FT /note="S -> SS (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_000055"
FT VARIANT 7
FT /note="G -> R (in HHF1; dbSNP:rs781059815)"
FT /evidence="ECO:0000269|PubMed:16357843"
FT /id="VAR_031349"
FT VARIANT 21
FT /note="V -> D (in HHF1; dbSNP:rs200670692)"
FT /evidence="ECO:0000269|PubMed:16357843"
FT /id="VAR_031350"
FT VARIANT 27
FT /note="F -> S (in HHF1)"
FT /evidence="ECO:0000269|PubMed:15562009,
FT ECO:0000269|PubMed:16357843"
FT /id="VAR_031351"
FT VARIANT 45
FT /note="P -> L (in PNDM3; dbSNP:rs267606623)"
FT /evidence="ECO:0000269|PubMed:17668386"
FT /id="VAR_072928"
FT VARIANT 70
FT /note="G -> E (in HHF1; altered intracellular trafficking)"
FT /evidence="ECO:0000269|PubMed:15579781"
FT /id="VAR_031352"
FT VARIANT 72
FT /note="N -> S (in PNDM3; mosaic; dbSNP:rs80356634)"
FT /evidence="ECO:0000269|PubMed:17668386"
FT /id="VAR_072929"
FT VARIANT 74
FT /note="R -> Q (in HHF1; dbSNP:rs72559734)"
FT /evidence="ECO:0000269|PubMed:9618169"
FT /id="VAR_008639"
FT VARIANT 74
FT /note="R -> W (in HHF1; dbSNP:rs201682634)"
FT /evidence="ECO:0000269|PubMed:15562009,
FT ECO:0000269|PubMed:16357843, ECO:0000269|PubMed:16429405"
FT /id="VAR_031353"
FT VARIANT 86
FT /note="V -> A (in PNDM3; dbSNP:rs193929360)"
FT /evidence="ECO:0000269|PubMed:17213273,
FT ECO:0000269|PubMed:17668386"
FT /id="VAR_031354"
FT VARIANT 86
FT /note="V -> G (in PNDM3; dbSNP:rs193929360)"
FT /evidence="ECO:0000269|PubMed:17668386"
FT /id="VAR_072930"
FT VARIANT 104
FT /note="L -> V (in dbSNP:rs10400391)"
FT /id="VAR_029777"
FT VARIANT 111
FT /note="G -> R (in HHF1; altered intracellular trafficking;
FT dbSNP:rs761749884)"
FT /evidence="ECO:0000269|PubMed:15579781,
FT ECO:0000269|PubMed:16429405"
FT /id="VAR_031355"
FT VARIANT 116
FT /note="A -> P (in HHF1; dbSNP:rs72559731)"
FT /id="VAR_031356"
FT VARIANT 125
FT /note="H -> Q (in HHF1; mild; dbSNP:rs60637558)"
FT /evidence="ECO:0000269|PubMed:9618169,
FT ECO:0000269|PubMed:9648840"
FT /id="VAR_008640"
FT VARIANT 132
FT /note="F -> L (in PNDM3; with neurologic features; reduces
FT the sensitivity of the K(ATP) channel to inhibition by
FT MgATP; increases whole-cell K(ATP) current;
FT dbSNP:rs80356637)"
FT /evidence="ECO:0000269|PubMed:16613899,
FT ECO:0000269|PubMed:17668386"
FT /id="VAR_029778"
FT VARIANT 132
FT /note="F -> V (in PNDM3; dbSNP:rs80356637)"
FT /evidence="ECO:0000269|PubMed:17668386"
FT /id="VAR_072931"
FT VARIANT 187
FT /note="V -> D (in HHF1; severe; high prevalence in Finland;
FT loss of channel activity; dbSNP:rs137852672)"
FT /evidence="ECO:0000269|PubMed:10334322,
FT ECO:0000269|PubMed:12364426"
FT /id="VAR_008641"
FT VARIANT 188
FT /note="N -> S (in HHF1; severe; dbSNP:rs797045213)"
FT /evidence="ECO:0000269|PubMed:15562009,
FT ECO:0000269|PubMed:16429405, ECO:0000269|PubMed:9618169,
FT ECO:0000269|PubMed:9648840"
FT /id="VAR_008642"
FT VARIANT 207
FT /note="P -> S (in PNDM3; reduced inhibition by ATP)"
FT /evidence="ECO:0000269|PubMed:17668386"
FT /id="VAR_072932"
FT VARIANT 208
FT /note="E -> K (in PNDM3)"
FT /evidence="ECO:0000269|PubMed:17668386"
FT /id="VAR_072933"
FT VARIANT 209
FT /note="D -> E (in PNDM3; dbSNP:rs80356640)"
FT /evidence="ECO:0000269|PubMed:17668386"
FT /id="VAR_072934"
FT VARIANT 211
FT /note="Q -> K (in PNDM3; dbSNP:rs193929366)"
FT /evidence="ECO:0000269|PubMed:17668386"
FT /id="VAR_072935"
FT VARIANT 213
FT /note="L -> R (in PNDM3; dbSNP:rs80356642)"
FT /evidence="ECO:0000269|PubMed:16885549"
FT /id="VAR_029779"
FT VARIANT 225
FT /note="L -> P (in PNDM3; dbSNP:rs1048095)"
FT /evidence="ECO:0000269|PubMed:17668386"
FT /id="VAR_072936"
FT VARIANT 229
FT /note="T -> I (in PNDM3; highly reduced inhibition by ATP
FT when associated with L-1523; dbSNP:rs768017509)"
FT /evidence="ECO:0000269|PubMed:17668386"
FT /id="VAR_072937"
FT VARIANT 233
FT /note="M -> R (in HHF1)"
FT /evidence="ECO:0000269|PubMed:16429405"
FT /id="VAR_031357"
FT VARIANT 263
FT /note="Y -> D (in PNDM3; dbSNP:rs778892038)"
FT /evidence="ECO:0000269|PubMed:17668386"
FT /id="VAR_072938"
FT VARIANT 275
FT /note="R -> Q (in dbSNP:rs185040406)"
FT /evidence="ECO:0000269|PubMed:9519757"
FT /id="VAR_008643"
FT VARIANT 310
FT /note="D -> N (in HHF1; dbSNP:rs769569410)"
FT /evidence="ECO:0000269|PubMed:16429405"
FT /id="VAR_031358"
FT VARIANT 382
FT /note="E -> K (in PNDM3; dbSNP:rs80356651)"
FT /evidence="ECO:0000269|PubMed:17668386"
FT /id="VAR_072939"
FT VARIANT 406
FT /note="N -> D (in HHF1; dbSNP:rs72559728)"
FT /evidence="ECO:0000269|PubMed:9618169"
FT /id="VAR_008644"
FT VARIANT 418
FT /note="C -> R (in HHF1; dbSNP:rs67254669)"
FT /id="VAR_031359"
FT VARIANT 435
FT /note="C -> R (in TNDM2)"
FT /evidence="ECO:0000269|PubMed:16885549"
FT /id="VAR_029780"
FT VARIANT 495
FT /note="R -> Q (in HHF1; dbSNP:rs1420601296)"
FT /evidence="ECO:0000269|PubMed:15562009"
FT /id="VAR_031360"
FT VARIANT 501
FT /note="E -> K (in HHF1; dbSNP:rs372307320)"
FT /evidence="ECO:0000269|PubMed:15562009,
FT ECO:0000269|PubMed:16357843"
FT /id="VAR_031361"
FT VARIANT 503
FT /note="L -> P (in HHF1; dbSNP:rs1554933168)"
FT /evidence="ECO:0000269|PubMed:16357843"
FT /id="VAR_031362"
FT VARIANT 508
FT /note="L -> P (in HHF1; dbSNP:rs72559727)"
FT /id="VAR_031363"
FT VARIANT 511
FT /note="L -> M (in HHF1; no effect on cell membrane
FT expression; no effect on traffic efficiency; dramatically
FT reduced potassium channel response to activators such as
FT MgADP or to diazoxide)"
FT /evidence="ECO:0000269|PubMed:24814349"
FT /id="VAR_072940"
FT VARIANT 551
FT /note="P -> R (in HHF1)"
FT /evidence="ECO:0000269|PubMed:16429405"
FT /id="VAR_031364"
FT VARIANT 560
FT /note="V -> M (in dbSNP:rs4148619)"
FT /evidence="ECO:0000269|PubMed:9519757"
FT /id="VAR_008645"
FT VARIANT 582
FT /note="L -> V (in TNDM2; dbSNP:rs137852674)"
FT /evidence="ECO:0000269|PubMed:16885549"
FT /id="VAR_029781"
FT VARIANT 591
FT /note="F -> L (in HHF1; dbSNP:rs72559726)"
FT /evidence="ECO:0000269|PubMed:9618169,
FT ECO:0000269|PubMed:9648840"
FT /id="VAR_008646"
FT VARIANT 620
FT /note="R -> C (in HHF1; dbSNP:rs58241708)"
FT /id="VAR_031365"
FT VARIANT 673
FT /note="D -> N (in dbSNP:rs777986828)"
FT /evidence="ECO:0000269|PubMed:9568693"
FT /id="VAR_015006"
FT VARIANT 686
FT /note="F -> S (in HHF1)"
FT /evidence="ECO:0000269|PubMed:15562009,
FT ECO:0000269|PubMed:16357843"
FT /id="VAR_031366"
FT VARIANT 716
FT /note="G -> D (in HHF1; dbSNP:rs72559723)"
FT /evidence="ECO:0000269|PubMed:24814349"
FT /id="VAR_072941"
FT VARIANT 716
FT /note="G -> V (in HHF1; dbSNP:rs72559723)"
FT /evidence="ECO:0000269|PubMed:8751851"
FT /id="VAR_000100"
FT VARIANT 719
FT /note="K -> T (in HHF1)"
FT /evidence="ECO:0000269|PubMed:16429405"
FT /id="VAR_031367"
FT VARIANT 810
FT /note="D -> N (in dbSNP:rs767572066)"
FT /evidence="ECO:0000269|PubMed:9519757"
FT /id="VAR_008647"
FT VARIANT 824
FT /note="E -> K (in HHF1; no effect on cell membrane
FT expression; no effect on traffic efficiency; dramatically
FT reduced potassium channel response to activators such as
FT MgADP or to diazoxide)"
FT /evidence="ECO:0000269|PubMed:24814349"
FT /id="VAR_072942"
FT VARIANT 834
FT /note="R -> C (in dbSNP:rs140068774)"
FT /evidence="ECO:0000269|PubMed:9519757"
FT /id="VAR_008648"
FT VARIANT 841
FT /note="R -> G (in HHF1)"
FT /evidence="ECO:0000269|PubMed:10202168"
FT /id="VAR_031368"
FT VARIANT 889
FT /note="K -> T (in HHF1; no effect on cell membrane
FT expression; no effect on traffic efficiency; reduced
FT potassium channel response to activators such as MgADP or
FT to diazoxide; dbSNP:rs761862121)"
FT /evidence="ECO:0000269|PubMed:24814349"
FT /id="VAR_031369"
FT VARIANT 890
FT /note="L -> P (in HHF1; no effect on cell membrane
FT expression; no effect on traffic efficiency; dramatically
FT reduced potassium channel response to activators such as
FT MgADP or to diazoxide)"
FT /evidence="ECO:0000269|PubMed:24814349"
FT /id="VAR_072943"
FT VARIANT 956
FT /note="S -> F (in HHF1; dbSNP:rs72559721)"
FT /id="VAR_031370"
FT VARIANT 1023
FT /note="H -> Y (in TNDM2; overactive channel)"
FT /evidence="ECO:0000269|PubMed:16885549"
FT /id="VAR_029782"
FT VARIANT 1130
FT /note="T -> P (in HHF1)"
FT /evidence="ECO:0000269|PubMed:16429405"
FT /id="VAR_031371"
FT VARIANT 1138
FT /note="T -> M (in HHF1; dbSNP:rs201351976)"
FT /evidence="ECO:0000269|PubMed:9618169,
FT ECO:0000269|PubMed:9648840"
FT /id="VAR_008649"
FT VARIANT 1147
FT /note="L -> R (in HHF1; dbSNP:rs1262517518)"
FT /evidence="ECO:0000269|PubMed:16429405"
FT /id="VAR_031372"
FT VARIANT 1182
FT /note="R -> Q (in TNDM2; dbSNP:rs193922400)"
FT /evidence="ECO:0000269|PubMed:16885549"
FT /id="VAR_029783"
FT VARIANT 1184
FT /note="A -> E (in PNDM3; slightly reduced inhibition by
FT ATP; dbSNP:rs137852675)"
FT /evidence="ECO:0000269|PubMed:17668386"
FT /id="VAR_072944"
FT VARIANT 1214
FT /note="R -> Q (in HHF1; severe; dbSNP:rs367850779)"
FT /evidence="ECO:0000269|PubMed:15562009,
FT ECO:0000269|PubMed:9618169, ECO:0000269|PubMed:9648840"
FT /id="VAR_008650"
FT VARIANT 1214
FT /note="R -> W (in HHF1; dbSNP:rs139964066)"
FT /evidence="ECO:0000269|PubMed:15562009,
FT ECO:0000269|PubMed:16357843"
FT /id="VAR_031373"
FT VARIANT 1295
FT /note="N -> K (in HHF1; dbSNP:rs542157938)"
FT /evidence="ECO:0000269|PubMed:16429405"
FT /id="VAR_031374"
FT VARIANT 1326
FT /note="E -> K (in PNDM3; dbSNP:rs200563930)"
FT /evidence="ECO:0000269|PubMed:17668386"
FT /id="VAR_072945"
FT VARIANT 1336
FT /note="K -> N (in HHF1; dbSNP:rs67767715)"
FT /evidence="ECO:0000269|PubMed:15562009"
FT /id="VAR_031375"
FT VARIANT 1342
FT /note="G -> E (in HHF1; altered intracellular trafficking)"
FT /evidence="ECO:0000269|PubMed:15579781"
FT /id="VAR_031376"
FT VARIANT 1349
FT /note="L -> Q (in HHF1)"
FT /evidence="ECO:0000269|PubMed:16357843"
FT /id="VAR_031377"
FT VARIANT 1352
FT /note="R -> H (in LIH; partially impairs ATP-dependent
FT potassium channel function; dbSNP:rs28936370)"
FT /evidence="ECO:0000269|PubMed:15356046"
FT /id="VAR_029784"
FT VARIANT 1352
FT /note="R -> P (in HHF1; dbSNP:rs28936370)"
FT /evidence="ECO:0000269|PubMed:24814349,
FT ECO:0000269|PubMed:9769320"
FT /id="VAR_008537"
FT VARIANT 1360
FT /note="V -> G"
FT /evidence="ECO:0000269|PubMed:8923011"
FT /id="VAR_008651"
FT VARIANT 1360
FT /note="V -> M (in HHF1)"
FT /id="VAR_015007"
FT VARIANT 1369
FT /note="A -> S (in dbSNP:rs757110)"
FT /evidence="ECO:0000269|PubMed:10447255,
FT ECO:0000269|PubMed:10615958, ECO:0000269|PubMed:15807877,
FT ECO:0000269|PubMed:16429405, ECO:0000269|PubMed:7716548,
FT ECO:0000269|PubMed:8635661, ECO:0000269|PubMed:8923011,
FT ECO:0000269|PubMed:9519757, ECO:0000269|PubMed:9568693,
FT ECO:0000269|Ref.2, ECO:0000269|Ref.3, ECO:0000269|Ref.4"
FT /id="VAR_008652"
FT VARIANT 1378
FT /note="G -> R (in HHF1; dbSNP:rs925231098)"
FT /evidence="ECO:0000269|PubMed:16357843,
FT ECO:0000269|PubMed:9618169"
FT /id="VAR_008653"
FT VARIANT 1378
FT /note="G -> S (in HHF1; highly decreases cell membrane
FT expression; highly reduced traffic efficiency; dramatically
FT reduced potassium channel response to activators such as
FT MgADP or to diazoxide; dbSNP:rs925231098)"
FT /evidence="ECO:0000269|PubMed:24814349"
FT /id="VAR_072946"
FT VARIANT 1379
FT /note="R -> C (in TNDM2; dbSNP:rs137852673)"
FT /evidence="ECO:0000269|PubMed:16885549"
FT /id="VAR_029785"
FT VARIANT 1381
FT /note="G -> S (in HHF1; dbSNP:rs773448052)"
FT /evidence="ECO:0000269|PubMed:9618169,
FT ECO:0000269|PubMed:9648840"
FT /id="VAR_008654"
FT VARIANT 1384
FT /note="K -> Q (in HHF1)"
FT /evidence="ECO:0000269|PubMed:15807877"
FT /id="VAR_031378"
FT VARIANT 1385
FT /note="Missing (in HHF1; does not alter surface expression
FT but channels are not functional; dbSNP:rs387906408)"
FT /evidence="ECO:0000269|PubMed:12941782"
FT /id="VAR_029786"
FT VARIANT 1386
FT /note="S -> F (in HHF1; dbSNP:rs72559718)"
FT /evidence="ECO:0000269|PubMed:24814349"
FT /id="VAR_031379"
FT VARIANT 1387
FT /note="Missing (in HHF1; severe; high frequency in
FT Ashkenazi Jewish patients; defective trafficking and lack
FT of surface expression)"
FT /evidence="ECO:0000269|PubMed:11226335,
FT ECO:0000269|PubMed:15562009, ECO:0000269|PubMed:16357843,
FT ECO:0000269|PubMed:8923011, ECO:0000269|PubMed:9618169,
FT ECO:0000269|PubMed:9648840"
FT /id="VAR_008538"
FT VARIANT 1388
FT /note="S -> Y (in HHF1)"
FT /evidence="ECO:0000269|PubMed:24814349"
FT /id="VAR_072947"
FT VARIANT 1389
FT /note="L -> P (in HHF1)"
FT /evidence="ECO:0000269|PubMed:24814349"
FT /id="VAR_072948"
FT VARIANT 1393
FT /note="R -> H (in HHF1; severe; loss of channel activity;
FT dbSNP:rs769279368)"
FT /evidence="ECO:0000269|PubMed:9618169,
FT ECO:0000269|PubMed:9648840"
FT /id="VAR_008655"
FT VARIANT 1400
FT /note="G -> R (in HHF1 and PNDM3; dbSNP:rs137852676)"
FT /evidence="ECO:0000269|PubMed:16357843,
FT ECO:0000269|PubMed:17668386"
FT /id="VAR_031380"
FT VARIANT 1418
FT /note="R -> H (in HHF1; altered intracellular trafficking;
FT dbSNP:rs1446306735)"
FT /evidence="ECO:0000269|PubMed:15579781,
FT ECO:0000269|PubMed:25720052"
FT /id="VAR_031381"
FT VARIANT 1420
FT /note="R -> C (in HHF1; modest impairment of channel
FT function; dbSNP:rs28938469)"
FT /evidence="ECO:0000269|PubMed:10202168,
FT ECO:0000269|PubMed:10615958, ECO:0000269|PubMed:9769320"
FT /id="VAR_008539"
FT VARIANT 1424
FT /note="I -> V (in PNDM3; overactive channel;
FT dbSNP:rs80356653)"
FT /evidence="ECO:0000269|PubMed:16885549"
FT /id="VAR_029787"
FT VARIANT 1436
FT /note="R -> Q (in HHF1; cannot form a functional channel,
FT due to protein instability or defective transport to the
FT membrane; dbSNP:rs387906407)"
FT /evidence="ECO:0000269|PubMed:10615958"
FT /id="VAR_015008"
FT VARIANT 1450
FT /note="L -> P (in HHF1; dbSNP:rs1554904565)"
FT /evidence="ECO:0000269|PubMed:16429405"
FT /id="VAR_031382"
FT VARIANT 1457
FT /note="A -> T (in HHF1; dbSNP:rs72559717)"
FT /evidence="ECO:0000269|PubMed:12364426"
FT /id="VAR_031383"
FT VARIANT 1457
FT /note="A -> V (in HHF1)"
FT /evidence="ECO:0000269|PubMed:24814349"
FT /id="VAR_072949"
FT VARIANT 1471
FT /note="D -> H (in HHF1)"
FT /evidence="ECO:0000269|PubMed:15562009"
FT /id="VAR_031384"
FT VARIANT 1471
FT /note="D -> N (in HHF1; dbSNP:rs72559716)"
FT /evidence="ECO:0000269|PubMed:15562009"
FT /id="VAR_031385"
FT VARIANT 1478
FT /note="G -> R (in HHF1; channels insensitive to metabolic
FT inhibition and to activation by ADP; dbSNP:rs72559715)"
FT /evidence="ECO:0000269|PubMed:8650576"
FT /id="VAR_008656"
FT VARIANT 1480
FT /note="N -> I (in HHF1; no effect on cell membrane
FT expression; no effect on traffic efficiency; dramatically
FT reduced potassium channel response to activators such as
FT MgADP or to diazoxide)"
FT /evidence="ECO:0000269|PubMed:24814349"
FT /id="VAR_072950"
FT VARIANT 1486
FT /note="R -> K (in HHF1)"
FT /evidence="ECO:0000269|PubMed:15807877"
FT /id="VAR_031386"
FT VARIANT 1493
FT /note="R -> Q (in HHF1; dbSNP:rs746480424)"
FT /evidence="ECO:0000269|PubMed:16357843"
FT /id="VAR_031387"
FT VARIANT 1493
FT /note="R -> W (in HHF1; altered intracellular trafficking;
FT dbSNP:rs28936371)"
FT /evidence="ECO:0000269|PubMed:10202168,
FT ECO:0000269|PubMed:15579781, ECO:0000269|PubMed:9769320"
FT /id="VAR_008540"
FT VARIANT 1505
FT /note="D -> E (in HHF1; no effect on cell membrane
FT expression; no effect on traffic efficiency; dramatically
FT reduced potassium channel response to activators such as
FT MgADP or to diazoxide)"
FT /evidence="ECO:0000269|PubMed:24814349"
FT /id="VAR_072951"
FT VARIANT 1506
FT /note="E -> K (in HHF1; mild; dominantly inherited;
FT channels insensitive to metabolic inhibition and to
FT activation by ADP; dbSNP:rs137852671)"
FT /evidence="ECO:0000269|PubMed:11018078,
FT ECO:0000269|PubMed:12364426"
FT /id="VAR_015009"
FT VARIANT 1507
FT /note="A -> AAS (in HHF1)"
FT /id="VAR_008657"
FT VARIANT 1511
FT /note="I -> S (in HHF1; no effect on cell membrane
FT expression; no effect on traffic efficiency; dramatically
FT reduced potassium channel response to activators such as
FT MgADP or to diazoxide)"
FT /evidence="ECO:0000269|PubMed:24814349"
FT /id="VAR_072952"
FT VARIANT 1522
FT /note="V -> L (in PNDM3; highly reduced inhibition by ATP
FT when associated with I-229)"
FT /evidence="ECO:0000269|PubMed:17668386"
FT /id="VAR_072953"
FT VARIANT 1543
FT /note="L -> P (in HHF1; reduced channels surface expression
FT and response to ADP; dbSNP:rs72559713)"
FT /evidence="ECO:0000269|PubMed:11867634"
FT /id="VAR_015010"
FT VARIANT 1550
FT /note="V -> D (in HHF1; dbSNP:rs1221760584)"
FT /evidence="ECO:0000269|PubMed:12364426"
FT /id="VAR_031388"
FT VARIANT 1551
FT /note="L -> V (in HHF1; dbSNP:rs1320740169)"
FT /evidence="ECO:0000269|PubMed:12364426"
FT /id="VAR_031389"
FT VARIANT 1572
FT /note="V -> I (in dbSNP:rs8192690)"
FT /evidence="ECO:0000269|PubMed:10447255,
FT ECO:0000269|PubMed:16429405, ECO:0000269|PubMed:8923011"
FT /id="VAR_008658"
FT CONFLICT 30
FT /note="A -> V (in Ref. 2; AAB02278/AAB02417/AAB02418)"
FT /evidence="ECO:0000305"
FT CONFLICT 157
FT /note="F -> L (in Ref. 3; AAB36699/AAB36700)"
FT /evidence="ECO:0000305"
FT CONFLICT 163
FT /note="G -> A (in Ref. 2; AAB02278/AAB02417/AAB02418)"
FT /evidence="ECO:0000305"
FT CONFLICT 167
FT /note="L -> V (in Ref. 2; AAB02278/AAB02417/AAB02418)"
FT /evidence="ECO:0000305"
FT CONFLICT 256
FT /note="A -> V (in Ref. 3; AAB36699/AAB36700)"
FT /evidence="ECO:0000305"
FT CONFLICT 487
FT /note="S -> T (in Ref. 2; AAB02278/AAB02417/AAB02418)"
FT /evidence="ECO:0000305"
FT CONFLICT 1069..1070
FT /note="VL -> AV (in Ref. 2; AAB02278/AAB02417/AAB02418)"
FT /evidence="ECO:0000305"
FT CONFLICT 1172
FT /note="I -> V (in Ref. 3; AAB36699/AAB36700)"
FT /evidence="ECO:0000305"
FT CONFLICT 1410
FT /note="A -> R (in Ref. 3; AAB36699/AAB36700)"
FT /evidence="ECO:0000305"
FT CONFLICT 1418
FT /note="R -> P (in Ref. 3; AAB36699/AAB36700)"
FT /evidence="ECO:0000305"
FT STRAND 12..15
FT /evidence="ECO:0007829|PDB:7S5V"
FT STRAND 21..23
FT /evidence="ECO:0007829|PDB:7S5V"
FT STRAND 25..28
FT /evidence="ECO:0007829|PDB:7S5V"
FT TURN 29..31
FT /evidence="ECO:0007829|PDB:7S5V"
FT HELIX 34..49
FT /evidence="ECO:0007829|PDB:7S5V"
FT HELIX 71..98
FT /evidence="ECO:0007829|PDB:7S5V"
FT STRAND 99..101
FT /evidence="ECO:0007829|PDB:7S5V"
FT TURN 104..107
FT /evidence="ECO:0007829|PDB:7S5V"
FT HELIX 108..128
FT /evidence="ECO:0007829|PDB:7S5V"
FT TURN 129..131
FT /evidence="ECO:0007829|PDB:7S5V"
FT HELIX 133..136
FT /evidence="ECO:0007829|PDB:7S5V"
FT HELIX 137..155
FT /evidence="ECO:0007829|PDB:7S5V"
FT STRAND 164..166
FT /evidence="ECO:0007829|PDB:7S5V"
FT HELIX 167..190
FT /evidence="ECO:0007829|PDB:7S5V"
FT TURN 208..214
FT /evidence="ECO:0007829|PDB:7S5V"
FT HELIX 224..228
FT /evidence="ECO:0007829|PDB:7S5V"
FT HELIX 231..233
FT /evidence="ECO:0007829|PDB:7S5V"
FT HELIX 234..238
FT /evidence="ECO:0007829|PDB:7S5V"
FT TURN 239..242
FT /evidence="ECO:0007829|PDB:7S5V"
FT TURN 247..249
FT /evidence="ECO:0007829|PDB:7S5V"
FT STRAND 250..252
FT /evidence="ECO:0007829|PDB:7S5V"
FT HELIX 259..271
FT /evidence="ECO:0007829|PDB:7S5V"
FT HELIX 285..294
FT /evidence="ECO:0007829|PDB:7S5V"
FT HELIX 296..313
FT /evidence="ECO:0007829|PDB:7S5V"
FT HELIX 316..327
FT /evidence="ECO:0007829|PDB:7S5V"
FT TURN 349..353
FT /evidence="ECO:0007829|PDB:7S5V"
FT HELIX 356..399
FT /evidence="ECO:0007829|PDB:7S5V"
FT TURN 404..407
FT /evidence="ECO:0007829|PDB:7S5V"
FT STRAND 408..411
FT /evidence="ECO:0007829|PDB:7S5V"
FT HELIX 414..422
FT /evidence="ECO:0007829|PDB:7S5V"
FT HELIX 424..431
FT /evidence="ECO:0007829|PDB:7S5V"
FT TURN 432..434
FT /evidence="ECO:0007829|PDB:7S5V"
FT HELIX 435..455
FT /evidence="ECO:0007829|PDB:7S5V"
FT HELIX 459..462
FT /evidence="ECO:0007829|PDB:7S5V"
FT HELIX 465..503
FT /evidence="ECO:0007829|PDB:7S5V"
FT HELIX 506..509
FT /evidence="ECO:0007829|PDB:7S5V"
FT TURN 510..513
FT /evidence="ECO:0007829|PDB:7S5V"
FT HELIX 515..563
FT /evidence="ECO:0007829|PDB:7S5V"
FT HELIX 573..585
FT /evidence="ECO:0007829|PDB:7S5V"
FT STRAND 587..589
FT /evidence="ECO:0007829|PDB:7S5V"
FT HELIX 590..599
FT /evidence="ECO:0007829|PDB:7S5V"
FT TURN 600..604
FT /evidence="ECO:0007829|PDB:7S5V"
FT HELIX 605..614
FT /evidence="ECO:0007829|PDB:7S5V"
FT STRAND 677..679
FT /evidence="ECO:0007829|PDB:7S5V"
FT STRAND 682..692
FT /evidence="ECO:0007829|PDB:7S5V"
FT STRAND 695..699
FT /evidence="ECO:0007829|PDB:7S5V"
FT STRAND 707..712
FT /evidence="ECO:0007829|PDB:7S5V"
FT HELIX 719..726
FT /evidence="ECO:0007829|PDB:7S5V"
FT STRAND 730..732
FT /evidence="ECO:0007829|PDB:7S5V"
FT STRAND 734..736
FT /evidence="ECO:0007829|PDB:7S5V"
FT STRAND 770..772
FT /evidence="ECO:0007829|PDB:7S5V"
FT HELIX 785..788
FT /evidence="ECO:0007829|PDB:7S5V"
FT HELIX 795..804
FT /evidence="ECO:0007829|PDB:7S5V"
FT HELIX 808..813
FT /evidence="ECO:0007829|PDB:7S5V"
FT STRAND 814..816
FT /evidence="ECO:0007829|PDB:7S5V"
FT HELIX 817..819
FT /evidence="ECO:0007829|PDB:7S5V"
FT STRAND 822..827
FT /evidence="ECO:0007829|PDB:7S5V"
FT HELIX 831..842
FT /evidence="ECO:0007829|PDB:7S5V"
FT STRAND 848..852
FT /evidence="ECO:0007829|PDB:7S5V"
FT STRAND 856..858
FT /evidence="ECO:0007829|PDB:7S5V"
FT HELIX 861..869
FT /evidence="ECO:0007829|PDB:7S5V"
FT TURN 870..880
FT /evidence="ECO:0007829|PDB:7S5V"
FT STRAND 882..886
FT /evidence="ECO:0007829|PDB:7S5V"
FT HELIX 890..895
FT /evidence="ECO:0007829|PDB:7S5V"
FT STRAND 897..903
FT /evidence="ECO:0007829|PDB:7S5V"
FT STRAND 906..911
FT /evidence="ECO:0007829|PDB:7S5V"
FT HELIX 913..918
FT /evidence="ECO:0007829|PDB:7S5V"
FT HELIX 923..928
FT /evidence="ECO:0007829|PDB:7S5V"
FT TURN 929..932
FT /evidence="ECO:0007829|PDB:7S5V"
FT HELIX 998..1005
FT /evidence="ECO:0007829|PDB:7S5V"
FT HELIX 1009..1016
FT /evidence="ECO:0007829|PDB:7S5V"
FT TURN 1017..1019
FT /evidence="ECO:0007829|PDB:7S5V"
FT HELIX 1020..1031
FT /evidence="ECO:0007829|PDB:7S5V"
FT TURN 1032..1036
FT /evidence="ECO:0007829|PDB:7S5V"
FT HELIX 1037..1040
FT /evidence="ECO:0007829|PDB:7S5V"
FT TURN 1062..1067
FT /evidence="ECO:0007829|PDB:7S5V"
FT HELIX 1068..1071
FT /evidence="ECO:0007829|PDB:7S5V"
FT HELIX 1072..1074
FT /evidence="ECO:0007829|PDB:7S5V"
FT HELIX 1076..1105
FT /evidence="ECO:0007829|PDB:7S5V"
FT HELIX 1109..1114
FT /evidence="ECO:0007829|PDB:7S5V"
FT HELIX 1117..1125
FT /evidence="ECO:0007829|PDB:7S5V"
FT HELIX 1127..1133
FT /evidence="ECO:0007829|PDB:7S5V"
FT HELIX 1135..1153
FT /evidence="ECO:0007829|PDB:7S5V"
FT TURN 1154..1158
FT /evidence="ECO:0007829|PDB:7S5V"
FT HELIX 1162..1165
FT /evidence="ECO:0007829|PDB:7S5V"
FT HELIX 1168..1189
FT /evidence="ECO:0007829|PDB:7S5V"
FT TURN 1190..1195
FT /evidence="ECO:0007829|PDB:7S5V"
FT HELIX 1196..1208
FT /evidence="ECO:0007829|PDB:7S5V"
FT HELIX 1210..1215
FT /evidence="ECO:0007829|PDB:7S5V"
FT HELIX 1219..1271
FT /evidence="ECO:0007829|PDB:7S5V"
FT HELIX 1278..1293
FT /evidence="ECO:0007829|PDB:7S5V"
FT HELIX 1295..1318
FT /evidence="ECO:0007829|PDB:7S5V"
FT TURN 1331..1333
FT /evidence="ECO:0007829|PDB:7S5V"
FT STRAND 1345..1350
FT /evidence="ECO:0007829|PDB:7S5V"
FT STRAND 1363..1367
FT /evidence="ECO:0007829|PDB:7S5V"
FT STRAND 1375..1378
FT /evidence="ECO:0007829|PDB:7S5V"
FT HELIX 1384..1389
FT /evidence="ECO:0007829|PDB:7S5V"
FT TURN 1390..1393
FT /evidence="ECO:0007829|PDB:7S5V"
FT STRAND 1399..1404
FT /evidence="ECO:0007829|PDB:7S5V"
FT STRAND 1407..1412
FT /evidence="ECO:0007829|PDB:7S5V"
FT HELIX 1414..1417
FT /evidence="ECO:0007829|PDB:7S5V"
FT HELIX 1418..1420
FT /evidence="ECO:0007829|PDB:7S5V"
FT STRAND 1421..1424
FT /evidence="ECO:0007829|PDB:7S5V"
FT STRAND 1432..1434
FT /evidence="ECO:0007829|PDB:7S5V"
FT HELIX 1435..1439
FT /evidence="ECO:0007829|PDB:7S5V"
FT HELIX 1449..1455
FT /evidence="ECO:0007829|PDB:7S5V"
FT TURN 1456..1458
FT /evidence="ECO:0007829|PDB:7S5V"
FT HELIX 1460..1463
FT /evidence="ECO:0007829|PDB:7S5V"
FT STRAND 1466..1471
FT /evidence="ECO:0007829|PDB:7S5V"
FT HELIX 1476..1478
FT /evidence="ECO:0007829|PDB:7S5V"
FT HELIX 1484..1495
FT /evidence="ECO:0007829|PDB:7S5V"
FT STRAND 1500..1506
FT /evidence="ECO:0007829|PDB:7S5V"
FT HELIX 1507..1509
FT /evidence="ECO:0007829|PDB:7S5V"
FT HELIX 1513..1526
FT /evidence="ECO:0007829|PDB:7S5V"
FT STRAND 1528..1535
FT /evidence="ECO:0007829|PDB:7S5V"
FT STRAND 1545..1560
FT /evidence="ECO:0007829|PDB:7S5V"
FT HELIX 1562..1566
FT /evidence="ECO:0007829|PDB:7S5V"
FT STRAND 1568..1571
FT /evidence="ECO:0007829|PDB:7S5V"
FT HELIX 1572..1576
FT /evidence="ECO:0007829|PDB:7S5V"
FT TURN 1577..1580
FT /evidence="ECO:0007829|PDB:7S5V"
SQ SEQUENCE 1581 AA; 176992 MW; 09CF2EC97899D1CE CRC64;
MPLAFCGSEN HSAAYRVDQG VLNNGCFVDA LNVVPHVFLL FITFPILFIG WGSQSSKVHI
HHSTWLHFPG HNLRWILTFM LLFVLVCEIA EGILSDGVTE SHHLHLYMPA GMAFMAAVTS
VVYYHNIETS NFPKLLIALL VYWTLAFITK TIKFVKFLDH AIGFSQLRFC LTGLLVILYG
MLLLVEVNVI RVRRYIFFKT PREVKPPEDL QDLGVRFLQP FVNLLSKGTY WWMNAFIKTA
HKKPIDLRAI GKLPIAMRAL TNYQRLCEAF DAQVRKDIQG TQGARAIWQA LSHAFGRRLV
LSSTFRILAD LLGFAGPLCI FGIVDHLGKE NDVFQPKTQF LGVYFVSSQE FLANAYVLAV
LLFLALLLQR TFLQASYYVA IETGINLRGA IQTKIYNKIM HLSTSNLSMG EMTAGQICNL
VAIDTNQLMW FFFLCPNLWA MPVQIIVGVI LLYYILGVSA LIGAAVIILL APVQYFVATK
LSQAQRSTLE YSNERLKQTN EMLRGIKLLK LYAWENIFRT RVETTRRKEM TSLRAFAIYT
SISIFMNTAI PIAAVLITFV GHVSFFKEAD FSPSVAFASL SLFHILVTPL FLLSSVVRST
VKALVSVQKL SEFLSSAEIR EEQCAPHEPT PQGPASKYQA VPLRVVNRKR PAREDCRGLT
GPLQSLVPSA DGDADNCCVQ IMGGYFTWTP DGIPTLSNIT IRIPRGQLTM IVGQVGCGKS
SLLLAALGEM QKVSGAVFWS SLPDSEIGED PSPERETATD LDIRKRGPVA YASQKPWLLN
ATVEENIIFE SPFNKQRYKM VIEACSLQPD IDILPHGDQT QIGERGINLS GGQRQRISVA
RALYQHANVV FLDDPFSALD IHLSDHLMQA GILELLRDDK RTVVLVTHKL QYLPHADWII
AMKDGTIQRE GTLKDFQRSE CQLFEHWKTL MNRQDQELEK ETVTERKATE PPQGLSRAMS
SRDGLLQDEE EEEEEAAESE EDDNLSSMLH QRAEIPWRAC AKYLSSAGIL LLSLLVFSQL
LKHMVLVAID YWLAKWTDSA LTLTPAARNC SLSQECTLDQ TVYAMVFTVL CSLGIVLCLV
TSVTVEWTGL KVAKRLHRSL LNRIILAPMR FFETTPLGSI LNRFSSDCNT IDQHIPSTLE
CLSRSTLLCV SALAVISYVT PVFLVALLPL AIVCYFIQKY FRVASRDLQQ LDDTTQLPLL
SHFAETVEGL TTIRAFRYEA RFQQKLLEYT DSNNIASLFL TAANRWLEVR MEYIGACVVL
IAAVTSISNS LHRELSAGLV GLGLTYALMV SNYLNWMVRN LADMELQLGA VKRIHGLLKT
EAESYEGLLA PSLIPKNWPD QGKIQIQNLS VRYDSSLKPV LKHVNALIAP GQKIGICGRT
GSGKSSFSLA FFRMVDTFEG HIIIDGIDIA KLPLHTLRSR LSIILQDPVL FSGTIRFNLD
PERKCSDSTL WEALEIAQLK LVVKALPGGL DAIITEGGEN FSQGQRQLFC LARAFVRKTS
IFIMDEATAS IDMATENILQ KVVMTAFADR TVVTIAHRVH TILSADLVIV LKRGAILEFD
KPEKLLSRKD SVFASFVRAD K
