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 27-MAR-2024, entry version 230. 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 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 [9] 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 [10] 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 [11] 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 [12] 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 [13] 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 [14] 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 [15] 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 [16] 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 [17] 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 [18] 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 [19] RP VARIANTS HHF1 PRO-116 AND MET-1360. 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 [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; ALA-1523 AND LEU-1523, AND CHARACTERIZATION OF VARIANTS RP PNDM3 LEU-132; SER-207; ILE-229; GLU-1184 AND LEU-1523. 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: Hyperinsulinemic hypoglycemia, familial, 1 (HHF1) CC [MIM:256450]: A form of hyperinsulinemic hypoglycemia, a clinically and CC genetically heterogeneous disorder characterized by inappropriate CC insulin secretion from the pancreatic beta-cells in the presence of low CC blood glucose levels. HHF1 is the most common cause of persistent CC hypoglycemia in infancy. Unless early and aggressive intervention is CC undertaken, brain damage from recurrent episodes of hypoglycemia may CC occur. HHF1 inheritance can be autosomal dominant or autosomal CC recessive. {ECO:0000269|PubMed:10202168, ECO:0000269|PubMed:10204114, 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 --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 EMDB; EMD-24840; -. DR EMDB; EMD-24842; -. DR EMDB; EMD-24843; -. DR EMDB; EMD-24844; -. DR EMDB; EMD-24845; -. DR EMDB; EMD-24846; -. DR EMDB; EMD-7338; -. DR EMDB; EMD-7339; -. 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.ENSP00000494321; -. 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 GlyCosmos; Q09428; 2 sites, No reported glycans. 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 ProteomicsDB; 58720; -. [Q09428-1] DR ProteomicsDB; 58721; -. [Q09428-2] DR Antibodypedia; 24846; 342 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 AGR; HGNC:59; -. 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; 3384185at2759; -. 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; 10 hits in 1157 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 126 other cell types or tissues. DR ExpressionAtlas; Q09428; baseline and differential. DR GO; GO:0008282; C:inward rectifying potassium channel; IDA:BHF-UCL. DR GO; GO:0016020; C:membrane; IBA:GO_Central. 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:0043531; F:ADP binding; IEA:Ensembl. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:InterPro. DR GO; GO:0015272; F:ATP-activated inward rectifier potassium channel activity; TAS:Reactome. DR GO; GO:0019829; F:ATPase-coupled monoatomic 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:0071310; P:cellular response to organic substance; IEA:Ensembl. DR GO; GO:0007565; P:female pregnancy; IEA:Ensembl. DR GO; GO:0061535; P:glutamate secretion, neurotransmission; IEA:Ensembl. DR GO; GO:0098662; P:inorganic cation transmembrane transport; ISS:ARUK-UCL. DR GO; GO:0001678; P:intracellular glucose homeostasis; IEA:Ensembl. 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:0050905; P:neuromuscular process; IEA:Ensembl. DR GO; GO:0035774; P:positive regulation of insulin secretion involved in cellular response to glucose stimulus; IEA:Ensembl. DR GO; GO:0043268; P:positive regulation of potassium ion transport; 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:1990573; P:potassium ion import across plasma membrane; ISS: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 CDD; cd18591; ABC_6TM_SUR1_D1_like; 1. DR CDD; cd18602; ABC_6TM_SUR1_D2_like; 1. DR DisProt; DP02881; -. DR Gene3D; 1.20.1560.10; ABC transporter type 1, transmembrane domain; 2. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 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; IPR000388; ABCC8/9. DR InterPro; IPR027417; P-loop_NTPase. DR PANTHER; PTHR24223; ATP-BINDING CASSETTE SUB-FAMILY C; 1. DR PANTHER; PTHR24223:SF187; ATP-BINDING CASSETTE SUB-FAMILY C MEMBER 8; 1. 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; SSF90123; ABC transporter transmembrane region; 2. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 2. DR PROSITE; PS50929; ABC_TM1F; 2. DR PROSITE; PS00211; ABC_TRANSPORTER_1; 2. DR PROSITE; PS50893; ABC_TRANSPORTER_2; 2. DR Genevisible; Q09428; HS. 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; likely pathogenic; FT 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; uncertain significance; FT 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; likely pathogenic; FT 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; likely pathogenic; FT 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 /evidence="ECO:0000269|PubMed:10204114" 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; pathogenic; reduces the FT sensitivity of the K(ATP) channel to inhibition by MgATP; FT increases whole-cell K(ATP) current; 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; likely pathogenic; FT 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; likely pathogenic; reduced FT 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; likely pathogenic; FT dbSNP:rs80356640)" FT /evidence="ECO:0000269|PubMed:17668386" FT /id="VAR_072934" FT VARIANT 211 FT /note="Q -> K (in PNDM3; likely pathogenic; FT 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; likely pathogenic; FT dbSNP:rs1048095)" FT /evidence="ECO:0000269|PubMed:17668386" FT /id="VAR_072936" FT VARIANT 229 FT /note="T -> I (in PNDM3; uncertain significance; affects FT channel function resulting in increased potassium currents FT at physiological MgATP concentrations; 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; uncertain significance; FT 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; uncertain significance; slightly FT reduced inhibition by 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; associated in cis with A-1523; FT uncertain significance; 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; dbSNP:rs1953962707)" FT /evidence="ECO:0000269|PubMed:10204114" 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 1523 FT /note="V -> A (in PNDM3; associated in cis with K-1326; FT uncertain significance)" FT /evidence="ECO:0000269|PubMed:17668386" FT /id="VAR_088691" FT VARIANT 1523 FT /note="V -> L (in PNDM3; uncertain significance; affects FT channel function resulting in increased potassium currents FT at physiological MgATP concentrations)" FT /evidence="ECO:0000269|PubMed:17668386" FT /id="VAR_088692" 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 //