AT8B1_HUMAN
ID AT8B1_HUMAN Reviewed; 1251 AA.
AC O43520; Q9BTP8;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 05-MAY-2009, sequence version 3.
DT 03-AUG-2022, entry version 212.
DE RecName: Full=Phospholipid-transporting ATPase IC {ECO:0000305};
DE EC=7.6.2.1 {ECO:0000269|PubMed:17948906, ECO:0000269|PubMed:25315773};
DE AltName: Full=ATPase class I type 8B member 1;
DE AltName: Full=Familial intrahepatic cholestasis type 1;
DE AltName: Full=P4-ATPase flippase complex alpha subunit ATP8B1;
GN Name=ATP8B1 {ECO:0000312|HGNC:HGNC:3706}; Synonyms=ATPIC, FIC1, PFIC;
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], VARIANTS PFIC1 SER-288; VAL-308;
RP 645-ILE--ILE-699 DEL AND ARG-892, VARIANTS BRIC1 THR-661 AND
RP 795-GLY--ARG-797 DEL, AND VARIANT THR-1152.
RC TISSUE=Intestine, and Liver;
RX PubMed=9500542; DOI=10.1038/ng0398-219;
RA Bull L.N., van Eijk M.J.T., Pawlikowska L., DeYoung J.A., Juijn J.A.,
RA Liao M., Klomp L.W.J., Lomri N., Berger R., Scharschmidt B.F.,
RA Knisely A.S., Houwen R.H.J., Freimer N.B.;
RT "A gene encoding a P-type ATPase mutated in two forms of hereditary
RT cholestasis.";
RL Nat. Genet. 18:219-223(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16177791; DOI=10.1038/nature03983;
RA Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D.,
RA Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X.,
RA Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J.,
RA Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L.,
RA Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A.,
RA Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C.,
RA Noguchi H., O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K.,
RA Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R.,
RA Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 18.";
RL Nature 437:551-555(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 388-661.
RC TISSUE=Colon tumor;
RX PubMed=9548971; DOI=10.1101/gr.8.4.354;
RA Halleck M.S., Pradhan D., Blackman C.F., Berkes C., Williamson P.L.,
RA Schlegel R.A.;
RT "Multiple members of a third subfamily of P-type ATPases identified by
RT genomic sequences and ESTs.";
RL Genome Res. 8:354-361(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 359-1251, AND VARIANT THR-1152.
RC TISSUE=Uterus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, AND CATALYTIC ACTIVITY.
RX PubMed=17948906; DOI=10.1002/hep.21950;
RA Paulusma C.C., Folmer D.E., Ho-Mok K.S., de Waart D.R., Hilarius P.M.,
RA Verhoeven A.J., Oude Elferink R.P.;
RT "ATP8B1 requires an accessory protein for endoplasmic reticulum exit and
RT plasma membrane lipid flippase activity.";
RL Hepatology 47:268-278(2008).
RN [6]
RP FUNCTION.
RX PubMed=20510206; DOI=10.1016/j.bcp.2010.05.017;
RA Munoz-Martinez F., Torres C., Castanys S., Gamarro F.;
RT "CDC50A plays a key role in the uptake of the anticancer drug perifosine in
RT human carcinoma cells.";
RL Biochem. Pharmacol. 80:793-800(2010).
RN [7]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=20512993; DOI=10.1002/hep.23586;
RA Verhulst P.M., van der Velden L.M., Oorschot V., van Faassen E.E.,
RA Klumperman J., Houwen R.H., Pomorski T.G., Holthuis J.C., Klomp L.W.;
RT "A flippase-independent function of ATP8B1, the protein affected in
RT familial intrahepatic cholestasis type 1, is required for apical protein
RT expression and microvillus formation in polarized epithelial cells.";
RL Hepatology 51:2049-2060(2010).
RN [8]
RP INTERACTION WITH TMEM30A AND TMEM30B, AND SUBCELLULAR LOCATION.
RX PubMed=20947505; DOI=10.1074/jbc.m110.139006;
RA van der Velden L.M., Wichers C.G., van Breevoort A.E., Coleman J.A.,
RA Molday R.S., Berger R., Klomp L.W., van de Graaf S.F.;
RT "Heteromeric interactions required for abundance and subcellular
RT localization of human CDC50 proteins and class 1 P4-ATPases.";
RL J. Biol. Chem. 285:40088-40096(2010).
RN [9]
RP INTERACTION WITH TMEM30A AND TMEM30B, AND SUBCELLULAR LOCATION.
RX PubMed=20961850; DOI=10.1074/jbc.m110.139543;
RA Bryde S., Hennrich H., Verhulst P.M., Devaux P.F., Lenoir G.,
RA Holthuis J.C.;
RT "CDC50 proteins are critical components of the human class-1 P4-ATPase
RT transport machinery.";
RL J. Biol. Chem. 285:40562-40572(2010).
RN [10]
RP INTERACTION WITH TMEM30A AND TMEM30B, AND SUBCELLULAR LOCATION.
RX PubMed=21914794; DOI=10.1074/jbc.m111.281006;
RA Takatsu H., Baba K., Shima T., Umino H., Kato U., Umeda M., Nakayama K.,
RA Shin H.W.;
RT "ATP9B, a P4-ATPase (a putative aminophospholipid translocase), localizes
RT to the trans-Golgi network in a CDC50 protein-independent manner.";
RL J. Biol. Chem. 286:38159-38167(2011).
RN [11]
RP COMPONENT OF A P4-ATPASE FLIPPASE COMPLEX, AND FUNCTION.
RX PubMed=25239307; DOI=10.1016/j.bbadis.2014.09.003;
RA van der Mark V.A., de Waart D.R., Ho-Mok K.S., Tabbers M.M., Voogt H.W.,
RA Oude Elferink R.P., Knisely A.S., Paulusma C.C.;
RT "The lipid flippase heterodimer ATP8B1-CDC50A is essential for surface
RT expression of the apical sodium-dependent bile acid transporter
RT (SLC10A2/ASBT) in intestinal Caco-2 cells.";
RL Biochim. Biophys. Acta 1842:2378-2386(2014).
RN [12]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, MUTAGENESIS OF GLU-234,
RP VARIANTS BRIC1 ASN-70 AND PHE-344, AND VARIANT PFIC1 PRO-127.
RX PubMed=25315773; DOI=10.1074/jbc.m114.593012;
RA Takatsu H., Tanaka G., Segawa K., Suzuki J., Nagata S., Nakayama K.,
RA Shin H.W.;
RT "Phospholipid flippase activities and substrate specificities of human type
RT IV P-type ATPases localized to the plasma membrane.";
RL J. Biol. Chem. 289:33543-33556(2014).
RN [13]
RP FUNCTION.
RX PubMed=27301931; DOI=10.1016/j.bbamcr.2016.06.005;
RA van der Mark V.A., de Jonge H.R., Chang J.C., Ho-Mok K.S., Duijst S.,
RA Vidovic D., Carlon M.S., Oude Elferink R.P., Paulusma C.C.;
RT "The phospholipid flippase ATP8B1 mediates apical localization of the
RT cystic fibrosis transmembrane regulator.";
RL Biochim. Biophys. Acta 1863:2280-2288(2016).
RN [14]
RP VARIANT BRIC1 THR-661.
RX PubMed=9918928; DOI=10.1002/hep.510290214;
RA Tygstrup N., Steig B.A., Juijn J.A., Bull L.N., Houwen R.H.J.;
RT "Recurrent familial intrahepatic cholestasis in the Faeroe Islands.
RT Phenotypic heterogeneity but genetic homogeneity.";
RL Hepatology 29:506-508(1999).
RN [15]
RP VARIANT PFIC1 ASN-554.
RX PubMed=11093741; DOI=10.1053/jhep.2000.20520;
RA Klomp L.W.J., Bull L.N., Knisely A.S., van Der Doelen M.A., Juijn J.A.,
RA Berger R., Forget S., Nielsen I.-M., Eiberg H., Houwen R.H.J.;
RT "A missense mutation in FIC1 is associated with Greenland familial
RT cholestasis.";
RL Hepatology 32:1337-1341(2000).
RN [16]
RP VARIANTS PFIC1 PRO-127; TYR-403; PRO-412; MET-456; HIS-500; PHE-529 DEL;
RP LEU-535; ASN-554; THR-661; GLY-688; ARG-733; SER-853; ARG-892 AND ARG-1040,
RP VARIANTS BRIC1 ASN-70; ASP-308; PHE-344; TYR-453; GLY-454; TRP-600;
RP GLN-600; TRP-628; THR-661; THR-694 AND ARG-892, AND VARIANT ALA-429.
RX PubMed=15239083; DOI=10.1002/hep.20285;
RA Klomp L.W.J., Vargas J.C., van Mil S.W.C., Pawlikowska L.,
RA Strautnieks S.S., van Eijk M.J.T., Juijn J.A., Pabon-Pena C., Smith L.B.,
RA DeYoung J.A., Byrne J.A., Gombert J., van der Brugge G., Berger R.,
RA Jankowska I., Pawlowska J., Villa E., Knisely A.S., Thompson R.J.,
RA Freimer N.B., Houwen R.H.J., Bull L.N.;
RT "Characterization of mutations in ATP8B1 associated with hereditary
RT cholestasis.";
RL Hepatology 40:27-38(2004).
RN [17]
RP VARIANTS ICP1 THR-45 AND GLU-203, AND VARIANT GLN-952.
RX PubMed=15657619; DOI=10.1038/sj.ejhg.5201355;
RA Painter J.N., Savander M., Ropponen A., Nupponen N., Riikonen S.,
RA Ylikorkala O., Lehesjoki A.E., Aittomaki K.;
RT "Sequence variation in the ATP8B1 gene and intrahepatic cholestasis of
RT pregnancy.";
RL Eur. J. Hum. Genet. 13:435-439(2005).
RN [18]
RP VARIANT ICP1 CYS-867, AND VARIANTS ASN-70; ILE-305 AND GLN-952.
RX PubMed=15888793; DOI=10.1136/gut.2004.058115;
RA Muellenbach R., Bennett A., Tetlow N., Patel N., Hamilton G., Cheng F.,
RA Chambers J., Howard R., Taylor-Robinson S.D., Williamson C.;
RT "ATP8B1 mutations in British cases with intrahepatic cholestasis of
RT pregnancy.";
RL Gut 54:829-834(2005).
RN [19]
RP VARIANTS [LARGE SCALE ANALYSIS] VAL-886 AND MET-1178.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [20]
RP CHARACTERIZATION OF VARIANTS PFIC1 VAL-308; ASN-554; THR-661 AND ARG-1040,
RP CHARACTERIZATION OF VARIANTS BRIC1 ASN-70 AND THR-661, CHARACTERIZATION OF
RP VARIANT ICP1 CYS-867, AND MUTAGENESIS OF ASP-454.
RX PubMed=19731236; DOI=10.1002/hep.23158;
RA Folmer D.E., van der Mark V.A., Ho-Mok K.S., Oude Elferink R.P.,
RA Paulusma C.C.;
RT "Differential effects of progressive familial intrahepatic cholestasis type
RT 1 and benign recurrent intrahepatic cholestasis type 1 mutations on
RT canalicular localization of ATP8B1.";
RL Hepatology 50:1597-1605(2009).
RN [21]
RP VARIANT PFIC1 THR-209.
RX PubMed=20038848; DOI=10.1097/mpg.0b013e3181c1b368;
RA Liu L.Y., Wang X.H., Wang Z.L., Zhu Q.R., Wang J.S.;
RT "Characterization of ATP8B1 gene mutations and a hot-linked mutation found
RT in Chinese children with progressive intrahepatic cholestasis and low
RT GGT.";
RL J. Pediatr. Gastroenterol. Nutr. 50:179-183(2010).
RN [22]
RP VARIANT PFIC1 ILE-1012.
RX PubMed=23197899; DOI=10.3748/wjg.v18.i44.6504;
RA Deng B.C., Lv S., Cui W., Zhao R., Lu X., Wu J., Liu P.;
RT "Novel ATP8B1 mutation in an adult male with progressive familial
RT intrahepatic cholestasis.";
RL World J. Gastroenterol. 18:6504-6509(2012).
CC -!- FUNCTION: Catalytic component of a P4-ATPase flippase complex which
CC catalyzes the hydrolysis of ATP coupled to the transport of
CC phospholipids, in particular phosphatidylcholines (PC), from the outer
CC to the inner leaflet of the plasma membrane (PubMed:25315773,
CC PubMed:17948906). May participate in the establishment of the
CC canalicular membrane integrity by ensuring asymmetric distribution of
CC phospholipids in the canicular membrane (By similarity). Thus may have
CC a role in the regulation of bile acids transport into the canaliculus,
CC uptake of bile acids from intestinal contents into intestinal mucosa or
CC both and protect hepatocytes from bile salts (By similarity). Involved
CC in the microvillus formation in polarized epithelial cells; the
CC function seems to be independent from its flippase activity
CC (PubMed:20512993). Participates in correct apical membrane localization
CC of CDC42, CFTR and SLC10A2 (PubMed:25239307, PubMed:27301931). Enables
CC CDC42 clustering at the apical membrane during enterocyte polarization
CC through the interaction between CDC42 polybasic region and negatively
CC charged membrane lipids provided by ATP8B1 (By similarity). Together
CC with TMEM30A is involved in uptake of the synthetic drug
CC alkylphospholipid perifosine (PubMed:20510206). Required for the
CC preservation of cochlear hair cells in the inner ear (By similarity).
CC May act as cardiolipin transporter during inflammatory injury (By
CC similarity). {ECO:0000250|UniProtKB:Q148W0,
CC ECO:0000269|PubMed:17948906, ECO:0000269|PubMed:20510206,
CC ECO:0000269|PubMed:20512993, ECO:0000269|PubMed:25239307,
CC ECO:0000269|PubMed:27301931}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + phospholipidSide 1 = ADP + phosphate +
CC phospholipidSide 2.; EC=7.6.2.1;
CC Evidence={ECO:0000269|PubMed:17948906, ECO:0000269|PubMed:25315773};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phosphocholine(out) + ATP + H2O = a
CC 1,2-diacyl-sn-glycero-3-phosphocholine(in) + ADP + H(+) + phosphate;
CC Xref=Rhea:RHEA:38583, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:57643,
CC ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:25315773};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38584;
CC Evidence={ECO:0000305|PubMed:25315773};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-L-serine(out) + ATP + H2O =
CC a 1,2-diacyl-sn-glycero-3-phospho-L-serine(in) + ADP + H(+) +
CC phosphate; Xref=Rhea:RHEA:38567, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:57262, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:17948906};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38568;
CC Evidence={ECO:0000305|PubMed:17948906};
CC -!- SUBUNIT: Component of a P4-ATPase flippase complex which consists of a
CC catalytic alpha subunit ATP8B1 and an accessory beta subunit TMEM30A
CC (PubMed:17948906, PubMed:25239307). The flippase ATP8B1:TMEM30A complex
CC can form an intermediate phosphoenzyme in vitro (PubMed:20947505,
CC PubMed:20961850, PubMed:21914794). Also interacts with beta subunit
CC TMEM30B (PubMed:20947505, PubMed:20961850, PubMed:21914794).
CC {ECO:0000269|PubMed:17948906, ECO:0000269|PubMed:20947505,
CC ECO:0000269|PubMed:20961850, ECO:0000269|PubMed:21914794,
CC ECO:0000269|PubMed:25239307}.
CC -!- INTERACTION:
CC O43520; Q9NV96: TMEM30A; NbExp=9; IntAct=EBI-9524729, EBI-2836942;
CC O43520; Q3MIR4: TMEM30B; NbExp=5; IntAct=EBI-9524729, EBI-9527107;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:17948906,
CC ECO:0000269|PubMed:20947505, ECO:0000269|PubMed:20961850,
CC ECO:0000269|PubMed:21914794, ECO:0000269|PubMed:25315773}; Multi-pass
CC membrane protein. Apical cell membrane {ECO:0000269|PubMed:20512993}.
CC Cell projection, stereocilium {ECO:0000250|UniProtKB:Q148W0}.
CC Endoplasmic reticulum {ECO:0000269|PubMed:17948906,
CC ECO:0000269|PubMed:20947505, ECO:0000269|PubMed:20961850,
CC ECO:0000269|PubMed:21914794}. Golgi apparatus
CC {ECO:0000269|PubMed:20961850}. Note=Exit from the endoplasmic reticulum
CC requires the presence of TMEM30A or TMEM30B (PubMed:20947505).
CC Localizes to apical membranes in epithelial cells (PubMed:20512993).
CC {ECO:0000269|PubMed:20512993, ECO:0000269|PubMed:20947505}.
CC -!- TISSUE SPECIFICITY: Found in most tissues except brain and skeletal
CC muscle. Most abundant in pancreas and small intestine.
CC -!- DISEASE: Cholestasis, progressive familial intrahepatic, 1 (PFIC1)
CC [MIM:211600]: A disorder characterized by early onset of cholestasis
CC that progresses to hepatic fibrosis, cirrhosis, and end-stage liver
CC disease before adulthood. PFIC1 inheritance is autosomal recessive.
CC {ECO:0000269|PubMed:11093741, ECO:0000269|PubMed:15239083,
CC ECO:0000269|PubMed:19731236, ECO:0000269|PubMed:20038848,
CC ECO:0000269|PubMed:23197899, ECO:0000269|PubMed:25315773,
CC ECO:0000269|PubMed:9500542}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Cholestasis, benign recurrent intrahepatic, 1 (BRIC1)
CC [MIM:243300]: A disorder characterized by intermittent episodes of
CC cholestasis without progression to liver failure. There is initial
CC elevation of serum bile acids, followed by cholestatic jaundice which
CC generally spontaneously resolves after periods of weeks to months. The
CC cholestatic attacks vary in severity and duration. Patients are
CC asymptomatic between episodes, both clinically and biochemically.
CC {ECO:0000269|PubMed:15239083, ECO:0000269|PubMed:19731236,
CC ECO:0000269|PubMed:25315773, ECO:0000269|PubMed:9500542,
CC ECO:0000269|PubMed:9918928}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Cholestasis of pregnancy, intrahepatic 1 (ICP1) [MIM:147480]:
CC A liver disorder of pregnancy. It presents during the second or, more
CC commonly, the third trimester of pregnancy with intense pruritus which
CC becomes more severe with advancing gestation and cholestasis.
CC Cholestasis results from abnormal biliary transport from the liver into
CC the small intestine. ICP1 causes fetal distress, spontaneous premature
CC delivery and intrauterine death. ICP1 patients have spontaneous and
CC progressive disappearance of cholestasis after delivery.
CC {ECO:0000269|PubMed:15657619, ECO:0000269|PubMed:15888793,
CC ECO:0000269|PubMed:19731236}. Note=The disease may be caused by
CC variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the cation transport ATPase (P-type) (TC 3.A.3)
CC family. Type IV subfamily. {ECO:0000305}.
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DR EMBL; AF038007; AAC63461.1; -; mRNA.
DR EMBL; AC027097; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AF032442; AAC04328.1; -; mRNA.
DR EMBL; BC003534; AAH03534.1; -; mRNA.
DR CCDS; CCDS11965.1; -.
DR RefSeq; NP_005594.1; NM_005603.4.
DR RefSeq; XP_006722544.1; XM_006722481.3.
DR RefSeq; XP_011524324.1; XM_011526022.2.
DR PDB; 7VGH; EM; 3.39 A; B=1-1251.
DR PDB; 7VGI; EM; 3.36 A; B=1-1251.
DR PDB; 7VGJ; EM; 3.98 A; A=1-1251.
DR PDBsum; 7VGH; -.
DR PDBsum; 7VGI; -.
DR PDBsum; 7VGJ; -.
DR AlphaFoldDB; O43520; -.
DR SMR; O43520; -.
DR BioGRID; 111227; 7.
DR ComplexPortal; CPX-6282; ATP8B1-CDC50A P4-ATPase complex.
DR ComplexPortal; CPX-6283; ATP8B1-CDC50B P4-ATPase complex.
DR IntAct; O43520; 4.
DR STRING; 9606.ENSP00000445359; -.
DR SwissLipids; SLP:000000342; -.
DR TCDB; 3.A.3.8.11; the p-type atpase (p-atpase) superfamily.
DR iPTMnet; O43520; -.
DR PhosphoSitePlus; O43520; -.
DR BioMuta; ATP8B1; -.
DR EPD; O43520; -.
DR jPOST; O43520; -.
DR MassIVE; O43520; -.
DR MaxQB; O43520; -.
DR PaxDb; O43520; -.
DR PeptideAtlas; O43520; -.
DR PRIDE; O43520; -.
DR ProteomicsDB; 49008; -.
DR Antibodypedia; 9722; 48 antibodies from 12 providers.
DR DNASU; 5205; -.
DR Ensembl; ENST00000648908.2; ENSP00000497896.1; ENSG00000081923.15.
DR GeneID; 5205; -.
DR KEGG; hsa:5205; -.
DR MANE-Select; ENST00000648908.2; ENSP00000497896.1; NM_001374385.1; NP_001361314.1.
DR UCSC; uc002lgw.5; human.
DR CTD; 5205; -.
DR DisGeNET; 5205; -.
DR GeneCards; ATP8B1; -.
DR GeneReviews; ATP8B1; -.
DR HGNC; HGNC:3706; ATP8B1.
DR HPA; ENSG00000081923; Tissue enhanced (intestine).
DR MalaCards; ATP8B1; -.
DR MIM; 147480; phenotype.
DR MIM; 211600; phenotype.
DR MIM; 243300; phenotype.
DR MIM; 602397; gene.
DR neXtProt; NX_O43520; -.
DR OpenTargets; ENSG00000081923; -.
DR Orphanet; 99960; Benign recurrent intrahepatic cholestasis type 1.
DR Orphanet; 69665; Intrahepatic cholestasis of pregnancy.
DR Orphanet; 79306; Progressive familial intrahepatic cholestasis type 1.
DR PharmGKB; PA265; -.
DR VEuPathDB; HostDB:ENSG00000081923; -.
DR eggNOG; KOG0206; Eukaryota.
DR GeneTree; ENSGT00940000158002; -.
DR HOGENOM; CLU_000846_3_2_1; -.
DR InParanoid; O43520; -.
DR OMA; VQEPFFP; -.
DR OrthoDB; 587717at2759; -.
DR PhylomeDB; O43520; -.
DR TreeFam; TF300654; -.
DR BRENDA; 7.6.2.1; 2681.
DR PathwayCommons; O43520; -.
DR Reactome; R-HSA-936837; Ion transport by P-type ATPases.
DR SignaLink; O43520; -.
DR SIGNOR; O43520; -.
DR BioGRID-ORCS; 5205; 13 hits in 1065 CRISPR screens.
DR ChiTaRS; ATP8B1; human.
DR GeneWiki; ATP8B1; -.
DR GenomeRNAi; 5205; -.
DR Pharos; O43520; Tbio.
DR PRO; PR:O43520; -.
DR Proteomes; UP000005640; Chromosome 18.
DR RNAct; O43520; protein.
DR Bgee; ENSG00000081923; Expressed in cardia of stomach and 213 other tissues.
DR ExpressionAtlas; O43520; baseline and differential.
DR Genevisible; O43520; HS.
DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0016604; C:nuclear body; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:1990531; C:phospholipid-translocating ATPase complex; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0032420; C:stereocilium; IEA:UniProtKB-SubCell.
DR GO; GO:0005802; C:trans-Golgi network; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:InterPro.
DR GO; GO:0140326; F:ATPase-coupled intramembrane lipid transporter activity; IBA:GO_Central.
DR GO; GO:1901612; F:cardiolipin binding; IEA:Ensembl.
DR GO; GO:0000287; F:magnesium ion binding; IEA:InterPro.
DR GO; GO:0140345; F:phosphatidylcholine flippase activity; IDA:UniProtKB.
DR GO; GO:0090554; F:phosphatidylcholine floppase activity; IEA:RHEA.
DR GO; GO:0140346; F:phosphatidylserine flippase activity; ISS:UniProtKB.
DR GO; GO:0090556; F:phosphatidylserine floppase activity; IEA:RHEA.
DR GO; GO:0045176; P:apical protein localization; IMP:UniProtKB.
DR GO; GO:0015721; P:bile acid and bile salt transport; NAS:UniProtKB.
DR GO; GO:0008206; P:bile acid metabolic process; IEA:Ensembl.
DR GO; GO:0007030; P:Golgi organization; IBA:GO_Central.
DR GO; GO:0060119; P:inner ear receptor cell development; IEA:Ensembl.
DR GO; GO:0034220; P:ion transmembrane transport; TAS:Reactome.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:0045332; P:phospholipid translocation; IDA:UniProtKB.
DR GO; GO:2001225; P:regulation of chloride transport; IMP:UniProtKB.
DR GO; GO:0032534; P:regulation of microvillus assembly; IMP:UniProtKB.
DR GO; GO:1903729; P:regulation of plasma membrane organization; IEA:Ensembl.
DR GO; GO:0007605; P:sensory perception of sound; IEA:UniProtKB-KW.
DR GO; GO:0021650; P:vestibulocochlear nerve formation; IEA:Ensembl.
DR GO; GO:0006855; P:xenobiotic transmembrane transport; IDA:UniProtKB.
DR Gene3D; 3.40.1110.10; -; 1.
DR Gene3D; 3.40.50.1000; -; 1.
DR InterPro; IPR030346; ATP8B1.
DR InterPro; IPR023299; ATPase_P-typ_cyto_dom_N.
DR InterPro; IPR018303; ATPase_P-typ_P_site.
DR InterPro; IPR023298; ATPase_P-typ_TM_dom_sf.
DR InterPro; IPR008250; ATPase_P-typ_transduc_dom_A_sf.
DR InterPro; IPR036412; HAD-like_sf.
DR InterPro; IPR023214; HAD_sf.
DR InterPro; IPR006539; P-type_ATPase_IV.
DR InterPro; IPR032631; P-type_ATPase_N.
DR InterPro; IPR001757; P_typ_ATPase.
DR InterPro; IPR032630; P_typ_ATPase_c.
DR InterPro; IPR044492; P_typ_ATPase_HD_dom.
DR PANTHER; PTHR24092:SF48; PTHR24092:SF48; 1.
DR Pfam; PF16212; PhoLip_ATPase_C; 1.
DR Pfam; PF16209; PhoLip_ATPase_N; 1.
DR SFLD; SFLDF00027; p-type_atpase; 1.
DR SUPFAM; SSF56784; SSF56784; 1.
DR SUPFAM; SSF81653; SSF81653; 1.
DR SUPFAM; SSF81660; SSF81660; 1.
DR SUPFAM; SSF81665; SSF81665; 1.
DR TIGRFAMs; TIGR01652; ATPase-Plipid; 1.
DR TIGRFAMs; TIGR01494; ATPase_P-type; 1.
DR PROSITE; PS00154; ATPASE_E1_E2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Cell membrane; Cell projection; Disease variant;
KW Endoplasmic reticulum; Golgi apparatus; Hearing; Intrahepatic cholestasis;
KW Lipid transport; Magnesium; Membrane; Metal-binding; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Translocase; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..1251
FT /note="Phospholipid-transporting ATPase IC"
FT /id="PRO_0000046364"
FT TOPO_DOM 1..108
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 109..130
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 131..136
FT /note="Exoplasmic loop"
FT /evidence="ECO:0000255"
FT TRANSMEM 137..156
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 157..340
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 341..362
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 363..389
FT /note="Exoplasmic loop"
FT /evidence="ECO:0000255"
FT TRANSMEM 390..411
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 412..949
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 950..970
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 971..982
FT /note="Exoplasmic loop"
FT /evidence="ECO:0000255"
FT TRANSMEM 983..1002
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1003..1032
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1033..1054
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1055..1068
FT /note="Exoplasmic loop"
FT /evidence="ECO:0000255"
FT TRANSMEM 1069..1091
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1092..1097
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1098..1118
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1119..1138
FT /note="Exoplasmic loop"
FT /evidence="ECO:0000255"
FT TRANSMEM 1139..1163
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1164..1251
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 1..54
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 13..38
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 454
FT /note="4-aspartylphosphate intermediate"
FT /evidence="ECO:0000250|UniProtKB:Q9HD20"
FT BINDING 893
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q8NB49"
FT BINDING 897
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q8NB49"
FT MOD_RES 1223
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q148W0"
FT VARIANT 45
FT /note="N -> T (in ICP1; dbSNP:rs146599962)"
FT /evidence="ECO:0000269|PubMed:15657619"
FT /id="VAR_043044"
FT VARIANT 70
FT /note="D -> N (in BRIC1; compound heterozygote with Q-600;
FT uncertain pathological significance; may be associated with
FT ICP; reduces interaction with TMEM30A; has no effect on PC
FT flippase activity; dbSNP:rs34719006)"
FT /evidence="ECO:0000269|PubMed:15239083,
FT ECO:0000269|PubMed:15888793, ECO:0000269|PubMed:19731236,
FT ECO:0000269|PubMed:25315773"
FT /id="VAR_043045"
FT VARIANT 78
FT /note="H -> Q (in dbSNP:rs3745079)"
FT /id="VAR_029271"
FT VARIANT 127
FT /note="L -> P (in PFIC1; loss of PC flippase activity)"
FT /evidence="ECO:0000269|PubMed:15239083,
FT ECO:0000269|PubMed:25315773"
FT /id="VAR_043046"
FT VARIANT 203
FT /note="K -> E (in ICP1; unknown pathological significance;
FT dbSNP:rs56355310)"
FT /evidence="ECO:0000269|PubMed:15657619"
FT /id="VAR_043047"
FT VARIANT 209
FT /note="P -> T (in PFIC1; dbSNP:rs515726138)"
FT /evidence="ECO:0000269|PubMed:20038848"
FT /id="VAR_071045"
FT VARIANT 288
FT /note="L -> S (in PFIC1; dbSNP:rs121909099)"
FT /evidence="ECO:0000269|PubMed:9500542"
FT /id="VAR_008809"
FT VARIANT 305
FT /note="F -> I (in dbSNP:rs150860808)"
FT /evidence="ECO:0000269|PubMed:15888793"
FT /id="VAR_043048"
FT VARIANT 308
FT /note="G -> D (in BRIC1; dbSNP:rs111033609)"
FT /evidence="ECO:0000269|PubMed:15239083"
FT /id="VAR_043049"
FT VARIANT 308
FT /note="G -> V (in PFIC1; greatly reduced expression due to
FT proteosomal degradation; abolishes interaction with
FT TMEM30A; dbSNP:rs111033609)"
FT /evidence="ECO:0000269|PubMed:19731236,
FT ECO:0000269|PubMed:9500542"
FT /id="VAR_008810"
FT VARIANT 344
FT /note="I -> F (in BRIC1; loss of PC flippase activity;
FT dbSNP:rs140665115)"
FT /evidence="ECO:0000269|PubMed:15239083,
FT ECO:0000269|PubMed:25315773"
FT /id="VAR_043050"
FT VARIANT 384
FT /note="R -> H (in dbSNP:rs2271260)"
FT /id="VAR_043051"
FT VARIANT 393
FT /note="I -> V (in dbSNP:rs34315917)"
FT /id="VAR_043052"
FT VARIANT 403
FT /note="S -> Y (in PFIC1)"
FT /evidence="ECO:0000269|PubMed:15239083"
FT /id="VAR_043053"
FT VARIANT 412
FT /note="R -> P (in PFIC1)"
FT /evidence="ECO:0000269|PubMed:15239083"
FT /id="VAR_043054"
FT VARIANT 429
FT /note="E -> A (in dbSNP:rs34018205)"
FT /evidence="ECO:0000269|PubMed:15239083"
FT /id="VAR_043055"
FT VARIANT 453
FT /note="S -> Y (in BRIC1)"
FT /evidence="ECO:0000269|PubMed:15239083"
FT /id="VAR_043056"
FT VARIANT 454
FT /note="D -> G (in BRIC1)"
FT /evidence="ECO:0000269|PubMed:15239083"
FT /id="VAR_043057"
FT VARIANT 456
FT /note="T -> M (in PFIC1; dbSNP:rs121909104)"
FT /evidence="ECO:0000269|PubMed:15239083"
FT /id="VAR_043058"
FT VARIANT 500
FT /note="Y -> H (in PFIC1; dbSNP:rs147642236)"
FT /evidence="ECO:0000269|PubMed:15239083"
FT /id="VAR_043059"
FT VARIANT 529
FT /note="Missing (in PFIC1)"
FT /evidence="ECO:0000269|PubMed:15239083"
FT /id="VAR_043060"
FT VARIANT 535
FT /note="H -> L (in PFIC1)"
FT /evidence="ECO:0000269|PubMed:15239083"
FT /id="VAR_043061"
FT VARIANT 554
FT /note="D -> N (in PFIC1; greatly reduced expression due to
FT proteosomal degradation; abolishes interaction with
FT TMEM30A; dbSNP:rs121909101)"
FT /evidence="ECO:0000269|PubMed:11093741,
FT ECO:0000269|PubMed:15239083, ECO:0000269|PubMed:19731236"
FT /id="VAR_015423"
FT VARIANT 577
FT /note="I -> V (in dbSNP:rs3745078)"
FT /id="VAR_029272"
FT VARIANT 580
FT /note="S -> N (in dbSNP:rs33963153)"
FT /id="VAR_043062"
FT VARIANT 600
FT /note="R -> Q (in BRIC1; compound heterozygote with N-70;
FT dbSNP:rs1202682161)"
FT /evidence="ECO:0000269|PubMed:15239083"
FT /id="VAR_043063"
FT VARIANT 600
FT /note="R -> W (in BRIC1; dbSNP:rs780186596)"
FT /evidence="ECO:0000269|PubMed:15239083"
FT /id="VAR_043064"
FT VARIANT 628
FT /note="R -> W (in BRIC1; dbSNP:rs752045131)"
FT /evidence="ECO:0000269|PubMed:15239083"
FT /id="VAR_043065"
FT VARIANT 645..699
FT /note="Missing (in PFIC1)"
FT /evidence="ECO:0000269|PubMed:9500542"
FT /id="VAR_008811"
FT VARIANT 661
FT /note="I -> T (in BRIC1 and PFIC1; common mutation; reduces
FT interaction with TMEM30A; dbSNP:rs121909100)"
FT /evidence="ECO:0000269|PubMed:15239083,
FT ECO:0000269|PubMed:19731236, ECO:0000269|PubMed:9500542,
FT ECO:0000269|PubMed:9918928"
FT /id="VAR_008812"
FT VARIANT 674
FT /note="M -> T (in dbSNP:rs35470719)"
FT /id="VAR_043066"
FT VARIANT 688
FT /note="D -> G (in PFIC1; dbSNP:rs1337978497)"
FT /evidence="ECO:0000269|PubMed:15239083"
FT /id="VAR_043067"
FT VARIANT 694
FT /note="I -> T (in BRIC1; dbSNP:rs541474497)"
FT /evidence="ECO:0000269|PubMed:15239083"
FT /id="VAR_043068"
FT VARIANT 733
FT /note="G -> R (in PFIC1; dbSNP:rs1350369369)"
FT /evidence="ECO:0000269|PubMed:15239083"
FT /id="VAR_043069"
FT VARIANT 795..797
FT /note="Missing (in BRIC1)"
FT /evidence="ECO:0000269|PubMed:9500542"
FT /id="VAR_008814"
FT VARIANT 814
FT /note="K -> N (in dbSNP:rs34018300)"
FT /id="VAR_043070"
FT VARIANT 853
FT /note="F -> S (in PFIC1; dbSNP:rs773092889)"
FT /evidence="ECO:0000269|PubMed:15239083"
FT /id="VAR_043071"
FT VARIANT 867
FT /note="R -> C (in ICP1; reduces interaction with TMEM30A;
FT dbSNP:rs121909103)"
FT /evidence="ECO:0000269|PubMed:15888793,
FT ECO:0000269|PubMed:19731236"
FT /id="VAR_043072"
FT VARIANT 886
FT /note="A -> V (in a breast cancer sample; somatic mutation;
FT dbSNP:rs767398921)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036499"
FT VARIANT 892
FT /note="G -> R (in PFIC1 and BRIC1; dbSNP:rs121909098)"
FT /evidence="ECO:0000269|PubMed:15239083,
FT ECO:0000269|PubMed:9500542"
FT /id="VAR_008813"
FT VARIANT 952
FT /note="R -> Q (in dbSNP:rs12968116)"
FT /evidence="ECO:0000269|PubMed:15657619,
FT ECO:0000269|PubMed:15888793"
FT /id="VAR_029273"
FT VARIANT 1012
FT /note="S -> I (in PFIC1)"
FT /evidence="ECO:0000269|PubMed:23197899"
FT /id="VAR_071046"
FT VARIANT 1040
FT /note="G -> R (in PFIC1; greatly reduces interaction with
FT TMEM30A; dbSNP:rs1438249656)"
FT /evidence="ECO:0000269|PubMed:15239083,
FT ECO:0000269|PubMed:19731236"
FT /id="VAR_043073"
FT VARIANT 1152
FT /note="A -> T (in dbSNP:rs222581)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:9500542"
FT /id="VAR_055045"
FT VARIANT 1178
FT /note="I -> M (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036500"
FT MUTAGEN 234
FT /note="E->Q: Impaired PC flippase activity."
FT /evidence="ECO:0000269|PubMed:25315773"
FT MUTAGEN 454
FT /note="D->A: Greatly reduced expression due to proteosomal
FT degradation; abolishes interaction with TMEM30A."
FT /evidence="ECO:0000269|PubMed:19731236"
FT CONFLICT 1016
FT /note="P -> L (in Ref. 4; AAH03534)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1251 AA; 143695 MW; 770FEF3946CB579F CRC64;
MSTERDSETT FDEDSQPNDE VVPYSDDETE DELDDQGSAV EPEQNRVNRE AEENREPFRK
ECTWQVKAND RKYHEQPHFM NTKFLCIKES KYANNAIKTY KYNAFTFIPM NLFEQFKRAA
NLYFLALLIL QAVPQISTLA WYTTLVPLLV VLGVTAIKDL VDDVARHKMD KEINNRTCEV
IKDGRFKVAK WKEIQVGDVI RLKKNDFVPA DILLLSSSEP NSLCYVETAE LDGETNLKFK
MSLEITDQYL QREDTLATFD GFIECEEPNN RLDKFTGTLF WRNTSFPLDA DKILLRGCVI
RNTDFCHGLV IFAGADTKIM KNSGKTRFKR TKIDYLMNYM VYTIFVVLIL LSAGLAIGHA
YWEAQVGNSS WYLYDGEDDT PSYRGFLIFW GYIIVLNTMV PISLYVSVEV IRLGQSHFIN
WDLQMYYAEK DTPAKARTTT LNEQLGQIHY IFSDKTGTLT QNIMTFKKCC INGQIYGDHR
DASQHNHNKI EQVDFSWNTY ADGKLAFYDH YLIEQIQSGK EPEVRQFFFL LAVCHTVMVD
RTDGQLNYQA ASPDEGALVN AARNFGFAFL ARTQNTITIS ELGTERTYNV LAILDFNSDR
KRMSIIVRTP EGNIKLYCKG ADTVIYERLH RMNPTKQETQ DALDIFANET LRTLCLCYKE
IEEKEFTEWN KKFMAASVAS TNRDEALDKV YEEIEKDLIL LGATAIEDKL QDGVPETISK
LAKADIKIWV LTGDKKETAE NIGFACELLT EDTTICYGED INSLLHARME NQRNRGGVYA
KFAPPVQESF FPPGGNRALI ITGSWLNEIL LEKKTKRNKI LKLKFPRTEE ERRMRTQSKR
RLEAKKEQRQ KNFVDLACEC SAVICCRVTP KQKAMVVDLV KRYKKAITLA IGDGANDVNM
IKTAHIGVGI SGQEGMQAVM SSDYSFAQFR YLQRLLLVHG RWSYIRMCKF LRYFFYKNFA
FTLVHFWYSF FNGYSAQTAY EDWFITLYNV LYTSLPVLLM GLLDQDVSDK LSLRFPGLYI
VGQRDLLFNY KRFFVSLLHG VLTSMILFFI PLGAYLQTVG QDGEAPSDYQ SFAVTIASAL
VITVNFQIGL DTSYWTFVNA FSIFGSIALY FGIMFDFHSA GIHVLFPSAF QFTGTASNAL
RQPYIWLTII LAVAVCLLPV VAIRFLSMTI WPSESDKIQK HRKRLKAEEQ WQRRQQVFRR
GVSTRRSAYA FSHQRGYADL ISSGRSIRKK RSPLDAIVAD GTAEYRRTGD S
