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O43520

- AT8B1_HUMAN

UniProt

O43520 - AT8B1_HUMAN

Protein

Phospholipid-transporting ATPase IC

Gene

ATP8B1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 149 (01 Oct 2014)
      Sequence version 3 (05 May 2009)
      Previous versions | rss
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    Functioni

    Catalytic component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of aminophospholipids from the outer to the inner leaflet of various membranes and ensures the maintenance of asymmetric distribution of phospholipids. Phospholipid translocation seems also to be implicated in vesicle formation and in uptake of lipid signaling molecules. May play a role in 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. In cooperation with ABCB4 may be involved in establishing integrity of the canalicular membrane thus protecting hepatocytes from bile salts. Together with TMEM30A is involved in uptake of the synthetic drug alkylphospholipid perifosine. Involved in the microvillus formation in polarized epithelial cells; the function seems to be independent from its flippase activity. Required for the preservation of cochlear hair cells in the inner ear. May act as cardiolipin transporter during inflammatory injury.3 Publications

    Catalytic activityi

    ATP + H2O + phospholipid(Side 1) = ADP + phosphate + phospholipid(Side 2).

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei454 – 45414-aspartylphosphate intermediateBy similarity
    Metal bindingi893 – 8931MagnesiumBy similarity
    Metal bindingi897 – 8971MagnesiumBy similarity

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. cation-transporting ATPase activity Source: InterPro
    3. magnesium ion binding Source: InterPro
    4. phospholipid-translocating ATPase activity Source: UniProtKB
    5. protein binding Source: UniProtKB

    GO - Biological processi

    1. bile acid and bile salt transport Source: UniProtKB
    2. bile acid metabolic process Source: Ensembl
    3. drug transmembrane transport Source: UniProtKB
    4. ion transmembrane transport Source: Reactome
    5. negative regulation of transcription, DNA-templated Source: UniProtKB
    6. phospholipid translocation Source: UniProtKB
    7. regulation of microvillus assembly Source: UniProtKB
    8. sensory perception of sound Source: UniProtKB-KW
    9. transmembrane transport Source: Reactome

    Keywords - Molecular functioni

    Hydrolase

    Keywords - Biological processi

    Hearing, Lipid transport, Transport

    Keywords - Ligandi

    ATP-binding, Magnesium, Metal-binding, Nucleotide-binding

    Enzyme and pathway databases

    ReactomeiREACT_25149. Ion transport by P-type ATPases.

    Protein family/group databases

    TCDBi3.A.3.8.11. the p-type atpase (p-atpase) superfamily.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Phospholipid-transporting ATPase IC (EC:3.6.3.1)
    Alternative name(s):
    ATPase class I type 8B member 1
    Familial intrahepatic cholestasis type 1
    P4-ATPase flippase complex alpha subunit ATP8B1
    Gene namesi
    Name:ATP8B1
    Synonyms:ATPIC, FIC1, PFIC
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 18

    Organism-specific databases

    HGNCiHGNC:3706. ATP8B1.

    Subcellular locationi

    Cell membrane; Multi-pass membrane protein. Apical cell membrane. Cell projectionstereocilium By similarity. Endoplasmic reticulum. Golgi apparatus
    Note: Exit from the endoplasmic reticulum requires the presence of TMEM30A or TMEM30B. Localizes to apical membranes in epithelial cells.

    GO - Cellular componenti

    1. apical plasma membrane Source: UniProtKB
    2. brush border membrane Source: Ensembl
    3. endoplasmic reticulum Source: UniProtKB
    4. Golgi apparatus Source: UniProtKB
    5. integral component of plasma membrane Source: UniProtKB
    6. plasma membrane Source: UniProtKB
    7. stereocilium Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cell membrane, Cell projection, Endoplasmic reticulum, Golgi apparatus, Membrane

    Pathology & Biotechi

    Involvement in diseasei

    Cholestasis, progressive familial intrahepatic, 1 (PFIC1) [MIM:211600]: A disorder characterized by early onset of cholestasis that progresses to hepatic fibrosis, cirrhosis, and end-stage liver disease before adulthood.5 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti127 – 1271L → P in PFIC1. 1 Publication
    VAR_043046
    Natural varianti209 – 2091P → T in PFIC1. 1 Publication
    VAR_071045
    Natural varianti288 – 2881L → S in PFIC1. 1 Publication
    VAR_008809
    Natural varianti308 – 3081G → V in PFIC1; greatly reduced expression due to proteosomal degradation; abolishes interaction with TMEM30A. 1 Publication
    Corresponds to variant rs28939685 [ dbSNP | Ensembl ].
    VAR_008810
    Natural varianti403 – 4031S → Y in PFIC1. 1 Publication
    VAR_043053
    Natural varianti412 – 4121R → P in PFIC1. 1 Publication
    VAR_043054
    Natural varianti456 – 4561T → M in PFIC1. 1 Publication
    VAR_043058
    Natural varianti500 – 5001Y → H in PFIC1. 1 Publication
    VAR_043059
    Natural varianti529 – 5291Missing in PFIC1. 1 Publication
    VAR_043060
    Natural varianti535 – 5351H → L in PFIC1. 1 Publication
    VAR_043061
    Natural varianti554 – 5541D → N in PFIC1; greatly reduced expression due to proteosomal degradation; abolishes interaction with TMEM30A. 2 Publications
    VAR_015423
    Natural varianti645 – 69955Missing in PFIC1.
    VAR_008811Add
    BLAST
    Natural varianti661 – 6611I → T in BRIC1 and PFIC1; common mutation; reduces interaction with TMEM30A. 3 Publications
    Corresponds to variant rs28939686 [ dbSNP | Ensembl ].
    VAR_008812
    Natural varianti688 – 6881D → G in PFIC1. 1 Publication
    VAR_043067
    Natural varianti733 – 7331G → R in PFIC1. 1 Publication
    VAR_043069
    Natural varianti853 – 8531F → S in PFIC1. 1 Publication
    VAR_043071
    Natural varianti892 – 8921G → R in PFIC1 and BRIC1. 2 Publications
    VAR_008813
    Natural varianti1012 – 10121S → I in PFIC1. 1 Publication
    VAR_071046
    Natural varianti1040 – 10401G → R in PFIC1; greatly reduces interaction with TMEM30A. 1 Publication
    VAR_043073
    Cholestasis, benign recurrent intrahepatic, 1 (BRIC1) [MIM:243300]: A disorder 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.3 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti70 – 701D → N in BRIC1; compound heterozygote with Q-600; uncertain pathological significance; may be associated with ICP; reduces interaction with TMEM30A. 2 Publications
    Corresponds to variant rs34719006 [ dbSNP | Ensembl ].
    VAR_043045
    Natural varianti308 – 3081G → D in BRIC1. 1 Publication
    Corresponds to variant rs28939685 [ dbSNP | Ensembl ].
    VAR_043049
    Natural varianti344 – 3441I → F in BRIC1. 1 Publication
    VAR_043050
    Natural varianti453 – 4531S → Y in BRIC1. 1 Publication
    VAR_043056
    Natural varianti454 – 4541D → G in BRIC1. 1 Publication
    VAR_043057
    Natural varianti600 – 6001R → Q in BRIC1; compound heterozygote with N-70. 1 Publication
    VAR_043063
    Natural varianti600 – 6001R → W in BRIC1. 1 Publication
    VAR_043064
    Natural varianti628 – 6281R → W in BRIC1. 1 Publication
    VAR_043065
    Natural varianti661 – 6611I → T in BRIC1 and PFIC1; common mutation; reduces interaction with TMEM30A. 3 Publications
    Corresponds to variant rs28939686 [ dbSNP | Ensembl ].
    VAR_008812
    Natural varianti694 – 6941I → T in BRIC1. 1 Publication
    VAR_043068
    Natural varianti795 – 7973Missing in BRIC1.
    VAR_008814
    Natural varianti892 – 8921G → R in PFIC1 and BRIC1. 2 Publications
    VAR_008813
    Cholestasis of pregnancy, intrahepatic 1 (ICP1) [MIM:147480]: A liver disorder of pregnancy. It presents during the second or, more commonly, the third trimester 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. ICP1 causes fetal distress, spontaneous premature delivery and intrauterine death. ICP1 patients have spontaneous and progressive disappearance of cholestasis after delivery.2 Publications
    Note: The disease may be caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti45 – 451N → T in ICP1. 1 Publication
    Corresponds to variant rs146599962 [ dbSNP | Ensembl ].
    VAR_043044
    Natural varianti203 – 2031K → E in ICP1. 1 Publication
    Corresponds to variant rs56355310 [ dbSNP | Ensembl ].
    VAR_043047
    Natural varianti867 – 8671R → C in ICP1; reduces interaction with TMEM30A. 1 Publication
    VAR_043072

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi454 – 4541D → A: Greatly reduced expression due to proteosomal degradation; abolishes interaction with TMEM30A. 1 Publication

    Keywords - Diseasei

    Disease mutation, Intrahepatic cholestasis

    Organism-specific databases

    MIMi147480. phenotype.
    211600. phenotype.
    243300. phenotype.
    Orphaneti99960. Benign recurrent intrahepatic cholestasis type 1.
    69665. Intrahepatic cholestasis of pregnancy.
    79306. Progressive familial intrahepatic cholestasis type 1.
    PharmGKBiPA265.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 12511251Phospholipid-transporting ATPase ICPRO_0000046364Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei1223 – 12231PhosphoserineBy similarity

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiO43520.
    PaxDbiO43520.
    PRIDEiO43520.

    PTM databases

    PhosphoSiteiO43520.

    Expressioni

    Tissue specificityi

    Found in most tissues except brain and skeletal muscle. Most abundant in pancreas and small intestine.

    Gene expression databases

    ArrayExpressiO43520.
    BgeeiO43520.
    CleanExiHS_ATP8B1.
    GenevestigatoriO43520.

    Organism-specific databases

    HPAiHPA018673.
    HPA018674.

    Interactioni

    Subunit structurei

    Component of a P4-ATPase flippase complex which consists of a catalytic alpha subunit and an accessory beta subunit Probable. The probable flippase ATP8B1:TMEM30A complex can form an intermediate phosphoenzyme in vitro. Also interacts with beta subunit TMEM30B.4 PublicationsCurated

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    TMEM30AQ9NV963EBI-9524729,EBI-2836942

    Protein-protein interaction databases

    BioGridi111227. 2 interactions.
    IntActiO43520. 2 interactions.
    STRINGi9606.ENSP00000283684.

    Structurei

    3D structure databases

    ProteinModelPortaliO43520.
    SMRiO43520. Positions 434-784, 867-927.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 108108CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini131 – 1366Exoplasmic loopSequence Analysis
    Topological domaini157 – 340184CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini363 – 38927Exoplasmic loopSequence AnalysisAdd
    BLAST
    Topological domaini412 – 949538CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini971 – 98212Exoplasmic loopSequence AnalysisAdd
    BLAST
    Topological domaini1003 – 103230CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini1055 – 106814Exoplasmic loopSequence AnalysisAdd
    BLAST
    Topological domaini1092 – 10976CytoplasmicSequence Analysis
    Topological domaini1119 – 113820Exoplasmic loopSequence AnalysisAdd
    BLAST
    Topological domaini1164 – 125188CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei109 – 13022HelicalSequence AnalysisAdd
    BLAST
    Transmembranei137 – 15620HelicalSequence AnalysisAdd
    BLAST
    Transmembranei341 – 36222HelicalSequence AnalysisAdd
    BLAST
    Transmembranei390 – 41122HelicalSequence AnalysisAdd
    BLAST
    Transmembranei950 – 97021HelicalSequence AnalysisAdd
    BLAST
    Transmembranei983 – 100220HelicalSequence AnalysisAdd
    BLAST
    Transmembranei1033 – 105422HelicalSequence AnalysisAdd
    BLAST
    Transmembranei1069 – 109123HelicalSequence AnalysisAdd
    BLAST
    Transmembranei1098 – 111821HelicalSequence AnalysisAdd
    BLAST
    Transmembranei1139 – 116325HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Sequence similaritiesi

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiCOG0474.
    HOGENOMiHOG000202528.
    HOVERGENiHBG050601.
    InParanoidiO43520.
    KOiK01530.
    OMAiHSKIEPV.
    OrthoDBiEOG7RRF68.
    PhylomeDBiO43520.
    TreeFamiTF300654.

    Family and domain databases

    Gene3Di2.70.150.10. 2 hits.
    3.40.1110.10. 2 hits.
    3.40.50.1000. 2 hits.
    InterProiIPR023299. ATPase_P-typ_cyto_domN.
    IPR018303. ATPase_P-typ_P_site.
    IPR006539. ATPase_P-typ_Plipid-transp.
    IPR008250. ATPase_P-typ_transduc_dom_A.
    IPR001757. Cation_transp_P_typ_ATPase.
    IPR023214. HAD-like_dom.
    [Graphical view]
    PANTHERiPTHR24092. PTHR24092. 1 hit.
    PfamiPF00122. E1-E2_ATPase. 1 hit.
    [Graphical view]
    PRINTSiPR00119. CATATPASE.
    SUPFAMiSSF56784. SSF56784. 3 hits.
    SSF81660. SSF81660. 2 hits.
    TIGRFAMsiTIGR01652. ATPase-Plipid. 1 hit.
    TIGR01494. ATPase_P-type. 1 hit.
    PROSITEiPS00154. ATPASE_E1_E2. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    O43520-1 [UniParc]FASTAAdd to Basket

    « Hide

    MSTERDSETT FDEDSQPNDE VVPYSDDETE DELDDQGSAV EPEQNRVNRE     50
    AEENREPFRK ECTWQVKAND RKYHEQPHFM NTKFLCIKES KYANNAIKTY 100
    KYNAFTFIPM NLFEQFKRAA NLYFLALLIL QAVPQISTLA WYTTLVPLLV 150
    VLGVTAIKDL VDDVARHKMD KEINNRTCEV IKDGRFKVAK WKEIQVGDVI 200
    RLKKNDFVPA DILLLSSSEP NSLCYVETAE LDGETNLKFK MSLEITDQYL 250
    QREDTLATFD GFIECEEPNN RLDKFTGTLF WRNTSFPLDA DKILLRGCVI 300
    RNTDFCHGLV IFAGADTKIM KNSGKTRFKR TKIDYLMNYM VYTIFVVLIL 350
    LSAGLAIGHA YWEAQVGNSS WYLYDGEDDT PSYRGFLIFW GYIIVLNTMV 400
    PISLYVSVEV IRLGQSHFIN WDLQMYYAEK DTPAKARTTT LNEQLGQIHY 450
    IFSDKTGTLT QNIMTFKKCC INGQIYGDHR DASQHNHNKI EQVDFSWNTY 500
    ADGKLAFYDH YLIEQIQSGK EPEVRQFFFL LAVCHTVMVD RTDGQLNYQA 550
    ASPDEGALVN AARNFGFAFL ARTQNTITIS ELGTERTYNV LAILDFNSDR 600
    KRMSIIVRTP EGNIKLYCKG ADTVIYERLH RMNPTKQETQ DALDIFANET 650
    LRTLCLCYKE IEEKEFTEWN KKFMAASVAS TNRDEALDKV YEEIEKDLIL 700
    LGATAIEDKL QDGVPETISK LAKADIKIWV LTGDKKETAE NIGFACELLT 750
    EDTTICYGED INSLLHARME NQRNRGGVYA KFAPPVQESF FPPGGNRALI 800
    ITGSWLNEIL LEKKTKRNKI LKLKFPRTEE ERRMRTQSKR RLEAKKEQRQ 850
    KNFVDLACEC SAVICCRVTP KQKAMVVDLV KRYKKAITLA IGDGANDVNM 900
    IKTAHIGVGI SGQEGMQAVM SSDYSFAQFR YLQRLLLVHG RWSYIRMCKF 950
    LRYFFYKNFA FTLVHFWYSF FNGYSAQTAY EDWFITLYNV LYTSLPVLLM 1000
    GLLDQDVSDK LSLRFPGLYI VGQRDLLFNY KRFFVSLLHG VLTSMILFFI 1050
    PLGAYLQTVG QDGEAPSDYQ SFAVTIASAL VITVNFQIGL DTSYWTFVNA 1100
    FSIFGSIALY FGIMFDFHSA GIHVLFPSAF QFTGTASNAL RQPYIWLTII 1150
    LAVAVCLLPV VAIRFLSMTI WPSESDKIQK HRKRLKAEEQ WQRRQQVFRR 1200
    GVSTRRSAYA FSHQRGYADL ISSGRSIRKK RSPLDAIVAD GTAEYRRTGD 1250
    S 1251
    Length:1,251
    Mass (Da):143,695
    Last modified:May 5, 2009 - v3
    Checksum:i770FEF3946CB579F
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti1016 – 10161P → L in AAH03534. (PubMed:15489334)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti45 – 451N → T in ICP1. 1 Publication
    Corresponds to variant rs146599962 [ dbSNP | Ensembl ].
    VAR_043044
    Natural varianti70 – 701D → N in BRIC1; compound heterozygote with Q-600; uncertain pathological significance; may be associated with ICP; reduces interaction with TMEM30A. 2 Publications
    Corresponds to variant rs34719006 [ dbSNP | Ensembl ].
    VAR_043045
    Natural varianti78 – 781H → Q.
    Corresponds to variant rs3745079 [ dbSNP | Ensembl ].
    VAR_029271
    Natural varianti127 – 1271L → P in PFIC1. 1 Publication
    VAR_043046
    Natural varianti203 – 2031K → E in ICP1. 1 Publication
    Corresponds to variant rs56355310 [ dbSNP | Ensembl ].
    VAR_043047
    Natural varianti209 – 2091P → T in PFIC1. 1 Publication
    VAR_071045
    Natural varianti288 – 2881L → S in PFIC1. 1 Publication
    VAR_008809
    Natural varianti305 – 3051F → I.1 Publication
    Corresponds to variant rs150860808 [ dbSNP | Ensembl ].
    VAR_043048
    Natural varianti308 – 3081G → D in BRIC1. 1 Publication
    Corresponds to variant rs28939685 [ dbSNP | Ensembl ].
    VAR_043049
    Natural varianti308 – 3081G → V in PFIC1; greatly reduced expression due to proteosomal degradation; abolishes interaction with TMEM30A. 1 Publication
    Corresponds to variant rs28939685 [ dbSNP | Ensembl ].
    VAR_008810
    Natural varianti344 – 3441I → F in BRIC1. 1 Publication
    VAR_043050
    Natural varianti384 – 3841R → H.
    Corresponds to variant rs2271260 [ dbSNP | Ensembl ].
    VAR_043051
    Natural varianti393 – 3931I → V.
    Corresponds to variant rs34315917 [ dbSNP | Ensembl ].
    VAR_043052
    Natural varianti403 – 4031S → Y in PFIC1. 1 Publication
    VAR_043053
    Natural varianti412 – 4121R → P in PFIC1. 1 Publication
    VAR_043054
    Natural varianti429 – 4291E → A.1 Publication
    Corresponds to variant rs34018205 [ dbSNP | Ensembl ].
    VAR_043055
    Natural varianti453 – 4531S → Y in BRIC1. 1 Publication
    VAR_043056
    Natural varianti454 – 4541D → G in BRIC1. 1 Publication
    VAR_043057
    Natural varianti456 – 4561T → M in PFIC1. 1 Publication
    VAR_043058
    Natural varianti500 – 5001Y → H in PFIC1. 1 Publication
    VAR_043059
    Natural varianti529 – 5291Missing in PFIC1. 1 Publication
    VAR_043060
    Natural varianti535 – 5351H → L in PFIC1. 1 Publication
    VAR_043061
    Natural varianti554 – 5541D → N in PFIC1; greatly reduced expression due to proteosomal degradation; abolishes interaction with TMEM30A. 2 Publications
    VAR_015423
    Natural varianti577 – 5771I → V.
    Corresponds to variant rs3745078 [ dbSNP | Ensembl ].
    VAR_029272
    Natural varianti580 – 5801S → N.
    Corresponds to variant rs33963153 [ dbSNP | Ensembl ].
    VAR_043062
    Natural varianti600 – 6001R → Q in BRIC1; compound heterozygote with N-70. 1 Publication
    VAR_043063
    Natural varianti600 – 6001R → W in BRIC1. 1 Publication
    VAR_043064
    Natural varianti628 – 6281R → W in BRIC1. 1 Publication
    VAR_043065
    Natural varianti645 – 69955Missing in PFIC1.
    VAR_008811Add
    BLAST
    Natural varianti661 – 6611I → T in BRIC1 and PFIC1; common mutation; reduces interaction with TMEM30A. 3 Publications
    Corresponds to variant rs28939686 [ dbSNP | Ensembl ].
    VAR_008812
    Natural varianti674 – 6741M → T.
    Corresponds to variant rs35470719 [ dbSNP | Ensembl ].
    VAR_043066
    Natural varianti688 – 6881D → G in PFIC1. 1 Publication
    VAR_043067
    Natural varianti694 – 6941I → T in BRIC1. 1 Publication
    VAR_043068
    Natural varianti733 – 7331G → R in PFIC1. 1 Publication
    VAR_043069
    Natural varianti795 – 7973Missing in BRIC1.
    VAR_008814
    Natural varianti814 – 8141K → N.
    Corresponds to variant rs34018300 [ dbSNP | Ensembl ].
    VAR_043070
    Natural varianti853 – 8531F → S in PFIC1. 1 Publication
    VAR_043071
    Natural varianti867 – 8671R → C in ICP1; reduces interaction with TMEM30A. 1 Publication
    VAR_043072
    Natural varianti886 – 8861A → V in a breast cancer sample; somatic mutation. 1 Publication
    VAR_036499
    Natural varianti892 – 8921G → R in PFIC1 and BRIC1. 2 Publications
    VAR_008813
    Natural varianti952 – 9521R → Q.2 Publications
    Corresponds to variant rs12968116 [ dbSNP | Ensembl ].
    VAR_029273
    Natural varianti1012 – 10121S → I in PFIC1. 1 Publication
    VAR_071046
    Natural varianti1040 – 10401G → R in PFIC1; greatly reduces interaction with TMEM30A. 1 Publication
    VAR_043073
    Natural varianti1152 – 11521A → T.2 Publications
    Corresponds to variant rs222581 [ dbSNP | Ensembl ].
    VAR_055045
    Natural varianti1178 – 11781I → M in a breast cancer sample; somatic mutation. 1 Publication
    VAR_036500

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF038007 mRNA. Translation: AAC63461.1.
    AC027097 Genomic DNA. No translation available.
    AF032442 mRNA. Translation: AAC04328.1.
    BC003534 mRNA. Translation: AAH03534.1.
    CCDSiCCDS11965.1.
    RefSeqiNP_005594.1. NM_005603.4.
    XP_006722544.1. XM_006722481.1.
    UniGeneiHs.216623.

    Genome annotation databases

    EnsembliENST00000283684; ENSP00000283684; ENSG00000081923.
    ENST00000536015; ENSP00000445359; ENSG00000081923.
    GeneIDi5205.
    KEGGihsa:5205.
    UCSCiuc002lgw.3. human.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF038007 mRNA. Translation: AAC63461.1 .
    AC027097 Genomic DNA. No translation available.
    AF032442 mRNA. Translation: AAC04328.1 .
    BC003534 mRNA. Translation: AAH03534.1 .
    CCDSi CCDS11965.1.
    RefSeqi NP_005594.1. NM_005603.4.
    XP_006722544.1. XM_006722481.1.
    UniGenei Hs.216623.

    3D structure databases

    ProteinModelPortali O43520.
    SMRi O43520. Positions 434-784, 867-927.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 111227. 2 interactions.
    IntActi O43520. 2 interactions.
    STRINGi 9606.ENSP00000283684.

    Protein family/group databases

    TCDBi 3.A.3.8.11. the p-type atpase (p-atpase) superfamily.

    PTM databases

    PhosphoSitei O43520.

    Proteomic databases

    MaxQBi O43520.
    PaxDbi O43520.
    PRIDEi O43520.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000283684 ; ENSP00000283684 ; ENSG00000081923 .
    ENST00000536015 ; ENSP00000445359 ; ENSG00000081923 .
    GeneIDi 5205.
    KEGGi hsa:5205.
    UCSCi uc002lgw.3. human.

    Organism-specific databases

    CTDi 5205.
    GeneCardsi GC18M055290.
    GeneReviewsi ATP8B1.
    HGNCi HGNC:3706. ATP8B1.
    HPAi HPA018673.
    HPA018674.
    MIMi 147480. phenotype.
    211600. phenotype.
    243300. phenotype.
    602397. gene.
    neXtProti NX_O43520.
    Orphaneti 99960. Benign recurrent intrahepatic cholestasis type 1.
    69665. Intrahepatic cholestasis of pregnancy.
    79306. Progressive familial intrahepatic cholestasis type 1.
    PharmGKBi PA265.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0474.
    HOGENOMi HOG000202528.
    HOVERGENi HBG050601.
    InParanoidi O43520.
    KOi K01530.
    OMAi HSKIEPV.
    OrthoDBi EOG7RRF68.
    PhylomeDBi O43520.
    TreeFami TF300654.

    Enzyme and pathway databases

    Reactomei REACT_25149. Ion transport by P-type ATPases.

    Miscellaneous databases

    GeneWikii ATP8B1.
    GenomeRNAii 5205.
    NextBioi 20132.
    PROi O43520.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O43520.
    Bgeei O43520.
    CleanExi HS_ATP8B1.
    Genevestigatori O43520.

    Family and domain databases

    Gene3Di 2.70.150.10. 2 hits.
    3.40.1110.10. 2 hits.
    3.40.50.1000. 2 hits.
    InterProi IPR023299. ATPase_P-typ_cyto_domN.
    IPR018303. ATPase_P-typ_P_site.
    IPR006539. ATPase_P-typ_Plipid-transp.
    IPR008250. ATPase_P-typ_transduc_dom_A.
    IPR001757. Cation_transp_P_typ_ATPase.
    IPR023214. HAD-like_dom.
    [Graphical view ]
    PANTHERi PTHR24092. PTHR24092. 1 hit.
    Pfami PF00122. E1-E2_ATPase. 1 hit.
    [Graphical view ]
    PRINTSi PR00119. CATATPASE.
    SUPFAMi SSF56784. SSF56784. 3 hits.
    SSF81660. SSF81660. 2 hits.
    TIGRFAMsi TIGR01652. ATPase-Plipid. 1 hit.
    TIGR01494. ATPase_P-type. 1 hit.
    PROSITEi PS00154. ATPASE_E1_E2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. 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. 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] [Europe PMC] [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] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 359-1251, VARIANT THR-1152.
      Tissue: Uterus.
    5. "ATP8B1 requires an accessory protein for endoplasmic reticulum exit and plasma membrane lipid flippase activity."
      Paulusma C.C., Folmer D.E., Ho-Mok K.S., de Waart D.R., Hilarius P.M., Verhoeven A.J., Oude Elferink R.P.
      Hepatology 47:268-278(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBUNIT, SUBCELLULAR LOCATION.
    6. "CDC50A plays a key role in the uptake of the anticancer drug perifosine in human carcinoma cells."
      Munoz-Martinez F., Torres C., Castanys S., Gamarro F.
      Biochem. Pharmacol. 80:793-800(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    7. "A flippase-independent function of ATP8B1, the protein affected in familial intrahepatic cholestasis type 1, is required for apical protein expression and microvillus formation in polarized epithelial cells."
      Verhulst P.M., van der Velden L.M., Oorschot V., van Faassen E.E., Klumperman J., Houwen R.H., Pomorski T.G., Holthuis J.C., Klomp L.W.
      Hepatology 51:2049-2060(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION.
    8. "Heteromeric interactions required for abundance and subcellular localization of human CDC50 proteins and class 1 P4-ATPases."
      van der Velden L.M., Wichers C.G., van Breevoort A.E., Coleman J.A., Molday R.S., Berger R., Klomp L.W., van de Graaf S.F.
      J. Biol. Chem. 285:40088-40096(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH TMEM30A AND TMEM30B, SUBCELLULAR LOCATION.
    9. "CDC50 proteins are critical components of the human class-1 P4-ATPase transport machinery."
      Bryde S., Hennrich H., Verhulst P.M., Devaux P.F., Lenoir G., Holthuis J.C.
      J. Biol. Chem. 285:40562-40572(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH TMEM30A AND TMEM30B, SUBCELLULAR LOCATION.
    10. "ATP9B, a P4-ATPase (a putative aminophospholipid translocase), localizes to the trans-Golgi network in a CDC50 protein-independent manner."
      Takatsu H., Baba K., Shima T., Umino H., Kato U., Umeda M., Nakayama K., Shin H.W.
      J. Biol. Chem. 286:38159-38167(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH TMEM30A AND TMEM30B, SUBCELLULAR LOCATION.
    11. "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] [Europe PMC] [Abstract]
      Cited for: VARIANT BRIC1 THR-661.
    12. Cited for: VARIANT PFIC1 ASN-554.
    13. 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.
    14. "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] [Europe PMC] [Abstract]
      Cited for: VARIANTS ICP1 THR-45 AND GLU-203, VARIANT GLN-952.
    15. "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] [Europe PMC] [Abstract]
      Cited for: VARIANT ICP1 CYS-867, VARIANTS ASN-70; ILE-305 AND GLN-952.
    16. Cited for: VARIANTS [LARGE SCALE ANALYSIS] VAL-886 AND MET-1178.
    17. "Differential effects of progressive familial intrahepatic cholestasis type 1 and benign recurrent intrahepatic cholestasis type 1 mutations on canalicular localization of ATP8B1."
      Folmer D.E., van der Mark V.A., Ho-Mok K.S., Oude Elferink R.P., Paulusma C.C.
      Hepatology 50:1597-1605(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: CHARACTERIZATION OF VARIANTS PFIC1 VAL-308; ASN-554; THR-661 AND ARG-1040, CHARACTERIZATION OF VARIANTS BRIC1 ASN-70 AND THR-661, CHARACTERIZATION OF VARIANT ICP1 CYS-867, MUTAGENESIS OF ASP-454.
    18. "Characterization of ATP8B1 gene mutations and a hot-linked mutation found in Chinese children with progressive intrahepatic cholestasis and low GGT."
      Liu L.Y., Wang X.H., Wang Z.L., Zhu Q.R., Wang J.S.
      J. Pediatr. Gastroenterol. Nutr. 50:179-183(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT PFIC1 THR-209.
    19. "Novel ATP8B1 mutation in an adult male with progressive familial intrahepatic cholestasis."
      Deng B.C., Lv S., Cui W., Zhao R., Lu X., Wu J., Liu P.
      World J. Gastroenterol. 18:6504-6509(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT PFIC1 ILE-1012.

    Entry informationi

    Entry nameiAT8B1_HUMAN
    AccessioniPrimary (citable) accession number: O43520
    Secondary accession number(s): Q9BTP8
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 30, 2000
    Last sequence update: May 5, 2009
    Last modified: October 1, 2014
    This is version 149 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 18
      Human chromosome 18: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3