Probable phospholipid-transporting ATPase IC

Sequence

>sp|O43520|AT8B1_HUMAN Probable phospholipid-transporting ATPase IC OS=Homo sapiens GN=ATP8B1 PE=1 SV=2 MSTERDSETTFDEDSQPNDEVVPYSDDETEDELDDQGSAVEPEQNRVNREAEENREPFRK ECTWQVKANDRKYHEQPHFMNTKFLCIKESKYANNAIKTYKYNAFTFIPMNLFEQFKRAA NLYFLALLILQAVPQISTLAWYTTLVPLLVVLGVTAIKDLVDDVARHKMDKEINNRTCEV IKDGRFKVAKWKEIQVGDVIRLKKNDFVPADILLLSSSEPNSLCYVETAELDGETNLKFK MSLEITDQYLQREDTLATFDGFIECEEPNNRLDKFTGTLFWRNTSFPLDADKILLRGCVI RNTDFCHGLVIFAGADTKIMKNSGKTRFKRTKIDYLMNYMVYTIFVVLILLSAGLAIGHA YWEAQVGNSSWYLYDGEDDTPSYRGFLIFWGYIIVLNTMVPISLYVSVEVIRLGQSHFIN WDLQMYYAEKDTPAKARTTTLNEQLGQIHYIFSDKTGTLTQNIMTFKKCCINGQIYGDHR DASQHNHNKIEQVDFSWNTYADGKLAFYDHYLIEQIQSGKEPEVRQFFFLLAVCHTVMVD RTDGQLNYQAASPDEGALVNAARNFGFAFLARTQNTITISELGTERTYNVLAILDFNSDR KRMSIIVRTPEGNIKLYCKGADTVIYERLHRMNPTKQETQDALDIFANETLRTLCLCYKE IEEKEFTEWNKKFMAASVASTNRDEALDKVYEEIEKDLILLGATAIEDKLQDGVPETISK LAKADIKIWVLTGDKKETAENIGFACELLTEDTTICYGEDINSLLHARMENQRNRGGVYA KFAPPVQESFFPPGGNRALIITGSWLNEILLEKKTKRNKILKLKFPRTEEERRMRTQSKR RLEAKKEQRQKNFVDLACECSAVICCRVTPKQKAMVVDLVKRYKKAITLAIGDGANDVNM IKTAHIGVGISGQEGMQAVMSSDYSFAQFRYLQRLLLVHGRWSYIRMCKFLRYFFYKNFA FTLVHFWYSFFNGYSAQTAYEDWFITLYNVLYTSLPVLLMGLLDQDVSDKLSLRFPGLYI VGQRDLLFNYKRFFVSLLHGVLTSMILFFIPLGAYLQTVGQDGEAPSDYQSFAVTIASAL VITVNFQIGLDTSYWTFVNAFSIFGSIALYFGIMFDFHSAGIHVLFPSAFQFTGTASNAL RQPYIWLTIILTVAVCLLPVVAIRFLSMTIWPSESDKIQKHRKRLKAEEQWQRRQQVFRR GVSTRRSAYAFSHQRGYADLISSGRSIRKKRSPLDAIVADGTAEYRRTGDS

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Sequence length	1251 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

Function	May play a role in the transport of aminophospholipids from the outer to the inner leaflet of various membranes and the maintenance of asymmetric distribution of phospholipids in the canicular membrane. May have a role in transport of bile acids into the canaliculus, uptake of bile acids from intestinal contents into intestinal mucosa or both.
Catalytic activity	ATP + H(2)O + phospholipid(In) = ADP + phosphate + phospholipid(Out).
Subcellular location	Membrane; Multi-pass membrane protein.
Tissue specificity	Found in most tissues except brain and skeletal muscle. Most abundant in pancreas and small intestine.
Involvement in disease	Defects in ATP8B1 are the cause of progressive familial intrahepatic cholestasis type 1 (PFIC1) [MIM:211600]; also known as Byler disease. PFIC1 is an autosomal recessive disorder, characterized by early infancy cholestasis, that may be initially episodic but progresses to malnutrition, growth retardation and end-stage liver disease before adulthood. Ref.1 Ref.5 Ref.6 Defects in ATP8B1 are the cause of benign recurrent intrahepatic cholestasis type 1 (BRIC1) [MIM:243300]; also known as Summerskill syndrome. BRIC is characterized by intermittent episodes of cholestasis without progression to liver failure. There is initial elevation of serum bile acids, followed by cholestatic jaundice which generally spontaneously resolves after periods of weeks to months. The cholestatic attacks vary in severity and duration. Patients are asymptomatic between episodes, both clinically and biochemically. Ref.1 Ref.6 Ref.4 Defects in ATP8B1 can be associated with intrahepatic cholestasis of pregnancy (ICP) [MIM:147480]; also known as pregnancy-related cholestasis. ICP is a multifactorial liver disorder of pregnancy. It presents during the second or, more commonly, the third trimestre of pregnancy with intense pruritus which becomes more severe with advancing gestation and cholestasis. Cholestasis results from abnormal biliary transport from the liver into the small intestine. ICP causes fetal distress, spontaneous premature delivery and intrauterine death. ICP patients have spontaneous and progressive disappearance of cholestasis after delivery. Ref.7 Ref.8
Sequence similarities	Belongs to the cation transport ATPase (P-type) family. Type IV subfamily.

Keywords
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation Intrahepatic cholestasis
Domain	Transmembrane
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Hydrolase
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	bile acid and bile salt transport Non-traceable author statement. Source: UniProtKB negative regulation of transcription Inferred from mutant phenotype. Source: UniProtKB phospholipid transport Inferred from electronic annotation. Source: InterPro
Cellular component	apical plasma membrane Inferred from direct assay. Source: UniProtKB integral to plasma membrane Non-traceable author statement. Source: UniProtKB membrane fraction Inferred from direct assay. Source: UniProtKB
Molecular function	ATP binding Inferred from electronic annotation. Source: InterPro ATPase activity, coupled to transmembrane movement of ions, phosphorylative mechanism Inferred from electronic annotation. Source: InterPro magnesium ion binding Inferred from electronic annotation. Source: InterPro phospholipid-translocating ATPase activity Traceable author statement. Source: UniProtKB
Complete GO annotation...

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A gene encoding a P-type ATPase mutated in two forms of hereditary cholestasis." Bull L.N., van Eijk M.J.T., Pawlikowska L., DeYoung J.A., Juijn J.A., Liao M., Klomp L.W.J., Lomri N., Berger R., Scharschmidt B.F., Knisely A.S., Houwen R.H.J., Freimer N.B. Nat. Genet. 18:219-223(1998) [PubMed: 9500542] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS PFIC1 SER-288; VAL-308; 645-ILE--ILE 699 DEL AND ARG-892, VARIANTS BRIC1 THR-661 AND 795-GLY--ARG-797 DEL. Tissue: Intestine and Liver.
[2]	"Multiple members of a third subfamily of P-type ATPases identified by genomic sequences and ESTs." Halleck M.S., Pradhan D., Blackman C.F., Berkes C., Williamson P.L., Schlegel R.A. Genome Res. 8:354-361(1998) [PubMed: 9548971] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 388-661. Tissue: Colon tumor.
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 359-1251. Tissue: Uterus.
[4]	"Recurrent familial intrahepatic cholestasis in the Faeroe Islands. Phenotypic heterogeneity but genetic homogeneity." Tygstrup N., Steig B.A., Juijn J.A., Bull L.N., Houwen R.H.J. Hepatology 29:506-508(1999) [PubMed: 9918928] [Abstract] Cited for: VARIANT BRIC1 THR-661.
[5]	"A missense mutation in FIC1 is associated with Greenland familial cholestasis." Klomp L.W.J., Bull L.N., Knisely A.S., van Der Doelen M.A., Juijn J.A., Berger R., Forget S., Nielsen I.-M., Eiberg H., Houwen R.H.J. Hepatology 32:1337-1341(2000) [PubMed: 11093741] [Abstract] Cited for: VARIANT PFIC1 ASN-554.
[6]	"Characterization of mutations in ATP8B1 associated with hereditary cholestasis." Klomp L.W.J., Vargas J.C., van Mil S.W.C., Pawlikowska L., Strautnieks S.S.,

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