Reviewed,
UniProtKB/Swiss-Prot O43520 (AT8B1_HUMAN)
Last modified
June 16, 2009.
Version 93.
History...
Clusters with 100%,
90%,
50% identity |
Documents (5) |
Third-party data |
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Names and origin
| Protein names | Recommended name: Probable phospholipid-transporting ATPase IC EC=3.6.3.1 Alternative name(s): Familial intrahepatic cholestasis type 1 ATPase class I type 8B member 1 | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 1251 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| 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 + H2O + phospholipid(In) = ADP + phosphate + phospholipid(Out). |
| Subcellular location | |
| 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.6 Ref.7 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.7 Ref.5 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.8 Ref.9 |
| Sequence similarities | Belongs to the cation transport ATPase (P-type) family. Type IV subfamily. |
Ontologies
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 1251 | 1251 | Probable phospholipid-transporting ATPase IC | PRO_0000046364 | |||||
Regions | |||||||||
| Topological domain | 1 – 108 | 108 | Cytoplasmic Potential | ||||||
| Transmembrane | 109 – 130 | 22 | Potential | ||||||
| Topological domain | 131 – 136 | 6 | Extracellular Potential | ||||||
| Transmembrane | 137 – 156 | 20 | Potential | ||||||
| Topological domain | 157 – 340 | 184 | Cytoplasmic Potential | ||||||
| Transmembrane | 341 – 362 | 22 | Potential | ||||||
| Topological domain | 363 – 389 | 27 | Extracellular Potential | ||||||
| Transmembrane | 390 – 411 | 22 | Potential | ||||||
| Topological domain | 412 – 949 | 538 | Cytoplasmic Potential | ||||||
| Transmembrane | 950 – 970 | 21 | Potential | ||||||
| Topological domain | 971 – 982 | 12 | Extracellular Potential | ||||||
| Transmembrane | 983 – 1002 | 20 | Potential | ||||||
| Topological domain | 1003 – 1032 | 30 | Cytoplasmic Potential | ||||||
| Transmembrane | 1033 – 1054 | 22 | Potential | ||||||
| Topological domain | 1055 – 1068 | 14 | Extracellular Potential | ||||||
| Transmembrane | 1069 – 1091 | 23 | Potential | ||||||
| Topological domain | 1092 – 1097 | 6 | Cytoplasmic Potential | ||||||
| Transmembrane | 1098 – 1118 | 21 | Potential | ||||||
| Topological domain | 1119 – 1138 | 20 | Extracellular Potential | ||||||
| Transmembrane | 1139 – 1163 | 25 | Potential | ||||||
| Topological domain | 1164 – 1251 | 88 | Cytoplasmic Potential | ||||||
Sites | |||||||||
| Active site | 454 | 1 | 4-aspartylphosphate intermediate By similarity | ||||||
| Metal binding | 893 | 1 | Magnesium By similarity | ||||||
| Metal binding | 897 | 1 | Magnesium By similarity | ||||||
Natural variations | |||||||||
| Natural variant | 45 | 1 | N → T in ICP. Ref.8 | VAR_043044 | |||||
| Natural variant | 70 | 1 | D → N in BRIC1; compound heterozygote with Q-600; uncertain pathological significance; may be associated with ICP. dbSNP rs34719006. Ref.7 | VAR_043045 | |||||
| Natural variant | 78 | 1 | H → Q: dbSNP rs3745079. | VAR_029271 | |||||
| Natural variant | 127 | 1 | L → P in PFIC1. Ref.7 | VAR_043046 | |||||
| Natural variant | 203 | 1 | K → E in ICP. Ref.8 | VAR_043047 | |||||
| Natural variant | 288 | 1 | L → S in PFIC1. Ref.1 | VAR_008809 | |||||
| Natural variant | 305 | 1 | F → I Ref.9 | VAR_043048 | |||||
| Natural variant | 308 | 1 | G → D in BRIC1. dbSNP rs28939685. Ref.7 | VAR_043049 | |||||
| Natural variant | 308 | 1 | G → V in PFIC1. Ref.1 | VAR_008810 | |||||
| Natural variant | 344 | 1 | I → F in BRIC1. Ref.7 | VAR_043050 | |||||
| Natural variant | 384 | 1 | R → H: dbSNP rs2271260. | VAR_043051 | |||||
| Natural variant | 393 | 1 | I → V: dbSNP rs34315917. | VAR_043052 | |||||
| Natural variant | 403 | 1 | S → Y in PFIC1. Ref.7 | VAR_043053 | |||||
| Natural variant | 412 | 1 | R → P in PFIC1. Ref.7 | VAR_043054 | |||||
| Natural variant | 429 | 1 | E → A: dbSNP rs34018205. Ref.7 | VAR_043055 | |||||
| Natural variant | 453 | 1 | S → Y in BRIC1. Ref.7 | VAR_043056 | |||||
| Natural variant | 454 | 1 | D → G in BRIC1. Ref.7 | VAR_043057 | |||||
| Natural variant | 456 | 1 | T → M in PFIC1. Ref.7 | VAR_043058 | |||||
| Natural variant | 500 | 1 | Y → H in PFIC1. Ref.7 | VAR_043059 | |||||
| Natural variant | 529 | 1 | Missing in PFIC1. Ref.7 | VAR_043060 | |||||
| Natural variant | 535 | 1 | H → L in PFIC1. Ref.7 | VAR_043061 | |||||
| Natural variant | 554 | 1 | D → N in PFIC1. Ref.6 Ref.7 | VAR_015423 | |||||
| Natural variant | 577 | 1 | I → V: dbSNP rs3745078. | VAR_029272 | |||||
| Natural variant | 580 | 1 | S → N: dbSNP rs33963153. | VAR_043062 | |||||
| Natural variant | 600 | 1 | R → Q in BRIC1; compound heterozygote with N-70. Ref.7 | VAR_043063 | |||||
| Natural variant | 600 | 1 | R → W in BRIC1. Ref.7 | VAR_043064 | |||||
| Natural variant | 628 | 1 | R → W in BRIC1. Ref.7 | VAR_043065 | |||||
| Natural variant | 645 – 699 | 55 | Missing in PFIC1. Ref.1 | VAR_008811 | |||||
| Natural variant | 661 | 1 | I → T in BRIC1 and PFIC1; common mutation. | VAR_008812 | |||||
| Natural variant | 674 | 1 | M → T: dbSNP rs35470719. | VAR_043066 | |||||
| Natural variant | 688 | 1 | D → G in PFIC1. Ref.7 | VAR_043067 | |||||
| Natural variant | 694 | 1 | I → T in BRIC1. Ref.7 | VAR_043068 | |||||
| Natural variant | 733 | 1 | G → R in PFIC1. Ref.7 | VAR_043069 | |||||
| Natural variant | 795 – 797 | 3 | Missing in BRIC1. Ref.1 | VAR_008814 | |||||
| Natural variant | 814 | 1 | K → N: dbSNP rs34018300. | VAR_043070 | |||||
| Natural variant | 853 | 1 | F → S in PFIC1. Ref.7 | VAR_043071 | |||||
| Natural variant | 867 | 1 | R → C in ICP. Ref.9 | VAR_043072 | |||||
| Natural variant | 886 | 1 | A → V in a breast cancer sample; somatic mutation. Ref.10 | VAR_036499 | |||||
| Natural variant | 892 | 1 | G → R in PFIC1 and BRIC1. | VAR_008813 | |||||
| Natural variant | 952 | 1 | R → Q: dbSNP rs12968116. Ref.8 Ref.9 | VAR_029273 | |||||
| Natural variant | 1040 | 1 | G → R in PFIC1. Ref.7 | VAR_043073 | |||||
| Natural variant | 1152 | 1 | A → T: dbSNP rs222581. Ref.1 Ref.4 | VAR_055045 | |||||
| Natural variant | 1178 | 1 | I → M in a breast cancer sample; somatic mutation. Ref.10 | VAR_036500 | |||||
Experimental info | |||||||||
| Sequence conflict | 1016 | 1 | P → L in AAH03534. Ref.4 | ||||||
Sequences
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References
| « Hide '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, VARIANT THR-1152. Tissue: Intestine and Liver. |
| [2] | "DNA sequence and analysis of human chromosome 18." Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J. Lander E.S.Nature 437:551-555(2005) [PubMed: 16177791] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [3] | "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. |
| [4] | "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, VARIANT THR-1152. Tissue: Uterus. |
| [5] | "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. |
| [6] | "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. |
| [7] | "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., van Eijk M.J.T., Juijn J.A., Pabon-Pena C., Smith L.B., DeYoung J.A., Byrne J.A., Gombert J., van der Brugge G., Berger R., Jankowska I., Pawlowska J., Villa E., Knisely A.S. Bull L.N.Hepatology 40:27-38(2004) [PubMed: 15239083] [Abstract] Cited for: VARIANTS PFIC1 PRO-127; TYR-403; PRO-412; MET-456; HIS-500; PHE-529 DEL; LEU-535; ASN-554; THR-661; GLY-688; ARG-733; SER-853; ARG-892 AND ARG-1040, VARIANTS BRIC1 ASN-70; ASP-308; PHE-344; TYR-453; GLY-454; TRP-600; GLN-600; TRP-628; THR-661; THR-694 AND ARG-892, VARIANT ALA-429. |
| [8] | "Sequence variation in the ATP8B1 gene and intrahepatic cholestasis of pregnancy." Painter J.N., Savander M., Ropponen A., Nupponen N., Riikonen S., Ylikorkala O., Lehesjoki A.E., Aittomaki K. Eur. J. Hum. Genet. 13:435-439(2005) [PubMed: 15657619] [Abstract] Cited for: VARIANTS ICP THR-45 AND GLU-203, VARIANT GLN-952. |
| [9] | "ATP8B1 mutations in British cases with intrahepatic cholestasis of pregnancy." Muellenbach R., Bennett A., Tetlow N., Patel N., Hamilton G., Cheng F., Chambers J., Howard R., Taylor-Robinson S.D., Williamson C. Gut 54:829-834(2005) [PubMed: 15888793] [Abstract] Cited for: VARIANT ICP CYS-867, VARIANTS ASN-70; ILE-305 AND GLN-952. |
| [10] | "The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. Velculescu V.E.Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] VAL-886 AND MET-1178. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| AF038007 mRNA. Translation: AAC63461.1. AC027097 Genomic DNA. No translation available. AF032442 mRNA. Translation: AAC04328.1. BC003534 mRNA. Translation: AAH03534.1. | |
| IPI | IPI00012851. |
| RefSeq | NP_005594.1. |
| UniGene | Hs.216623 |
3D structure databases | |
| ModBase | Search... |
PTM databases | |
| PhosphoSite | O43520. |
Proteomic databases | |
| PRIDE | O43520. |
Genome annotation databases | |
| Ensembl | ENSG00000081923. Homo sapiens. [Contig view] |
| GeneID | 5205. |
| KEGG | hsa:5205. |
Organism-specific databases | |
| GeneCards | GC18M053466. |
| HGNC | HGNC:3706. ATP8B1. |
| MIM | 147480. phenotype. 211600. phenotype. 243300. phenotype. 602397. gene. |
| Orphanet | 65682. Benign recurrent intrahepatic cholestasis. 172. Cholestasis, progressive familial intrahepatic. 79306. Cholestasis, progressive familial intrahepatic, type 1. 69665. Intrahepatic cholestasis of pregnancy. |
| PharmGKB | PA265. |
| GenAtlas | Search... |
Phylogenomic databases | |
| HOGENOM | O43520. |
| HOVERGEN | O43520. |
Enzyme and pathway databases | |
| BRENDA | 3.6.3.1. 247. |
Gene expression databases | |
| ArrayExpress | O43520. |
| Bgee | O43520. |
| CleanEx | HS_ATP8B1. |
| GermOnline | ENSG00000081923. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR008250. ATPase_P-typ_ATPase-assoc-reg. IPR001757. ATPase_P-typ_ion-transptr. IPR018303. ATPase_P-typ_phosphor_site. IPR006539. ATPase_P-typ_Plipid-transl. [Graphical view] |
| PANTHER | PTHR11939. ATPase_P. 1 hit. |
| Pfam | PF00122. E1-E2_ATPase. 1 hit. [Graphical view] |
| PRINTS | PR00119. CATATPASE. |
| TIGRFAMs | TIGR01652. ATPase-Plipid. 1 hit. TIGR01494. ATPase_P-type. 4 hits. |
| PROSITE | PS00154. ATPASE_E1_E2. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other Resources | |
| NextBio | 20132. |
| SOURCE | Search... |
Entry information
| Entry name | AT8B1_HUMAN | ||||||||
| Accession | Primary (citable) accession number: O43520 Secondary accession number(s): Q9BTP8 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| Human chromosome 18 Human chromosome 18: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with


