Phospholipid-transporting ATPase IC explained

Probable phospholipid-transporting ATPase IC is an enzyme that in humans is encoded by the ATP8B1 gene.^{[1] [2] [3]} This protein is associated with progressive familial intrahepatic cholestasis type 1 as well as benign recurrent intrahepatic cholestasis.^[4]

Function

This gene encodes a member of the P-type cation transport ATPase family and specifically belongs to the subfamily of aminophospholipid-transporting ATPases. This protein is highly expressed in the small intestine, stomach, pancreas, and prostate and is also found in cholangiocytes and the canalicular membranes of hepatocytes in the liver.^{[5] [6]} The aminophospholipid translocases transport phosphatidylserine and phosphatidylethanolamine from one side of a bilayer to another. Mutations in this gene may result in progressive familial intrahepatic cholestasis type 1 and in benign recurrent intrahepatic cholestasis.^[3] Exactly how mutations result in these diseases is not currently understood.

Further reading

• Knisely AS . Progressive familial intrahepatic cholestasis: a personal perspective . Pediatr. Dev. Pathol. . 3 . 2 . 113–25 . 2000 . 10679031 . 10.1007/s100240050016 . 2024-04-12 .
• Harris MJ, Le Couteur DG, Arias IM . Progressive familial intrahepatic cholestasis: genetic disorders of biliary transporters . J. Gastroenterol. Hepatol. . 20 . 6 . 807–17 . 2006 . 15946126 . 10.1111/j.1440-1746.2005.03743.x . 21480442 .
• Clayton RJ, Iber FL, Ruebner BH, McKusick VA . Byler disease. Fatal familial intrahepatic cholestasis in an Amish kindred . Am. J. Dis. Child. . 117 . 1 . 112–24 . 1969 . 5762004 . 10.1001/archpedi.1969.02100030114014.
• Houwen RH . Genome screening by searching for shared segments: mapping a gene for benign recurrent intrahepatic cholestasis . Nat. Genet. . 8 . 4 . 380–6 . 1995 . 7894490 . 10.1038/ng1294-380 . Baharloo S . Blankenship K . Raeymaekers . Peter . Juyn . Jenneke . Sandkuijl . Lodewijk A . Freimer . Nelson B . 1765/55192 . 8131209 . free.
• Halleck MS . Multiple members of a third subfamily of P-type ATPases identified by genomic sequences and ESTs . Genome Res. . 8 . 4 . 354–61 . 1998 . 9548971 . 10.1101/gr.8.4.354. Pradhan D . Blackman C . Berkes . C . Williamson . P . Schlegel . RA . free.
• Tygstrup N . Recurrent familial intrahepatic cholestasis in the Faeroe Islands. Phenotypic heterogeneity but genetic homogeneity . Hepatology . 29 . 2 . 506–8 . 1999 . 9918928 . 10.1002/hep.510290214 . Steig BA . Juijn JA . Bull . Laura N . Houwen . Roderick H . 37536841 . free .
• Halleck MS . Differential expression of putative transbilayer amphipath transporters . Physiol. Genomics . 1 . 3 . 139–50 . 2001 . 11015572 . 10.1152/physiolgenomics.1999.1.3.139. Lawler JF JR . Blackshaw S . Gao . L . Nagarajan . P . Hacker . C . Pyle . S . Newman . JT . Nakanishi . Y . 762447 .
• Klomp LW . A missense mutation in FIC1 is associated with greenland familial cholestasis . Hepatology . 32 . 6 . 1337–41 . 2001 . 11093741 . 10.1053/jhep.2000.20520 . Bull LN . Knisely AS . Vanderdoelen . M . Juijn . J . Berger . R . Forget . S . Nielsen . I . Eiberg . H . 31234172 . free .
• Strausberg RL . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . Feingold EA . Grouse LH . Derge . JG . Klausner . RD . Collins . FS . Wagner . L . Shenmen . CM . Schuler . GD . 2002PNAS...9916899M . free .
• Harris MJ, Arias IM . FIC1, a P-type ATPase linked to cholestatic liver disease, has homologues (ATP8B2 and ATP8B3) expressed throughout the body . Biochim. Biophys. Acta . 1633 . 2 . 127–31 . 2003 . 12880872 . 10.1016/S1388-1981(03)00107-0.
• Chen F . Progressive familial intrahepatic cholestasis, type 1, is associated with decreased farnesoid X receptor activity . Gastroenterology . 126 . 3 . 756–64 . 2004 . 14988830 . 10.1053/j.gastro.2003.12.013 . Ananthanarayanan M . Emre S . Neimark . Ezequiel . Bull . Laura N. . Knisely . A.S. . Strautnieks . Sandra S. . Thompson . Richard J. . Magid . Margret S. . free .
• Gerhard DS . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC) . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 . Wagner L . Feingold EA . Shenmen . CM . Grouse . LH . Schuler . G . Klein . SL . Old . S . Rasooly . R .
• Demeilliers C . Altered hepatobiliary gene expressions in PFIC1: ATP8B1 gene defect is associated with CFTR downregulation . Hepatology . 43 . 5 . 1125–34 . 2006 . 16628629 . 10.1002/hep.21160 . Jacquemin E . Barbu V . Mergey . Martine . Paye . François . Fouassier . Laura . Chignard . Nicolas . Housset . Chantal . Lomri . Nour-Eddine . 19185288 . free .

Notes and References

1. Bull LN, van Eijk MJ, Pawlikowska L, DeYoung JA, Juijn JA, Liao M, Klomp LW, Lomri N, Berger R, Scharschmidt BF, Knisely AS, Houwen RH, Freimer NB . A gene encoding a P-type ATPase mutated in two forms of hereditary cholestasis . Nat Genet . 18 . 3 . 219–24 . Mar 1998 . 9500542 . 10.1038/ng0398-219 . 9897047 .
2. Carlton VE, Knisely AS, Freimer NB . Mapping of a locus for progressive familial intrahepatic cholestasis (Byler disease) to 18q21-q22, the benign recurrent intrahepatic cholestasis region . Hum Mol Genet . 4 . 6 . 1049–53 . Oct 1995 . 7655458 . 10.1093/hmg/4.6.1049 .
3. Web site: Entrez Gene: ATP8B1 ATPase, Class I, type 8B, member 1.
4. Klomp L.W. . Characterization of mutations in ATP8B1 associated with hereditary cholestasis . Hepatology . 40 . 1 . 27–38 . July 2004 . 15239083 . 10.1002/hep.20285 . Vargas J.C. . van Mil S.W. . Pawlikowska . Ludmila . Strautnieks . Sandra S. . Van Eijk . Michiel J. T. . Juijn . Jenneke A. . Pabón-Peña . Carlos . Smith . Lauren B.. 45979358 . free .
5. Jansen PL, Müller M . The molecular genetics of familial intrahepatic cholestasis . Gut . 47 . 1 . 1–5 . July 2000 . 10861251 . 10.1136/gut.47.1.1. 1727973.
6. Eppens EF . FIC1, the protein affected in two forms of hereditary cholestasis, is localized in the cholangiocyte and the canalicular membrane of the hepatocyte . J. Hepatol. . 35 . 4 . 436–43 . October 2001 . 11682026 . 10.1016/S0168-8278(01)00158-1. van Mil SW . de Vree JM . Mok . KS . Juijn . JA . Oude Elferink . RP . Berger . R . Houwen . RH . Klomp . LW.