3.A.3.8.11
Phospholipid (e.g., cardiolipin) transporter, Atp8b1 or ATP881 which functions with CDC50A (see TC# 8.A.27.1.5). The structural basis of a broad lipid specificity of ATP8B1 has been determined (Dieudonné et al. 2023). Phosphatidylinositol and cardiolipin are transport substrates. A critical role of the sn-2 ester bond of glycerophospholipids is important (Dieudonné et al. 2023). A mutant version is associated with severe pneumonia in humans and mice. It binds and internalizes cardiolipin and other phospholipids from extracellular fluid via a basic residue-enriched motif. Administration of a peptide encompassing the cardiolipin binding motif of the Atp8b1 gene product in mice lessens bacterium-induced lung injury and improves survival (Ray et al., 2010). Mutations have been identified that give rise to progressive familial intrahepatic cholestasis (Stone et al. 2012). This lipid flippase forms a heterodimer with CDC50A/Transmembrane protein 30A (TC# 8.A.27.1.5) and is essential for surface expressioin of the apical Na+-bile acid transporter, Slc10A2/ASBT (TC#2.A.28.1.2) (van der Mark et al. 2014; Schlosser et al. 2023).
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| Accession Number: | O43520 |
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| Protein Name: | Probable phospholipid-transporting ATPase IC |
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| Length: | 1251 |
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| Molecular Weight: | 143695.00 |
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| Species: | Homo sapiens (Human) [9606] |
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| Number of TMSs: | 7 |
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| Location1 / Topology2 / Orientation3: |
Cell membrane1 / Multi-pass membrane protein2 |
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| Substrate |
phospholipid, cardiolipin |
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1: MSTERDSETT FDEDSQPNDE VVPYSDDETE DELDDQGSAV EPEQNRVNRE AEENREPFRK
61: ECTWQVKAND RKYHEQPHFM NTKFLCIKES KYANNAIKTY KYNAFTFIPM NLFEQFKRAA
121: NLYFLALLIL QAVPQISTLA WYTTLVPLLV VLGVTAIKDL VDDVARHKMD KEINNRTCEV
181: IKDGRFKVAK WKEIQVGDVI RLKKNDFVPA DILLLSSSEP NSLCYVETAE LDGETNLKFK
241: MSLEITDQYL QREDTLATFD GFIECEEPNN RLDKFTGTLF WRNTSFPLDA DKILLRGCVI
301: RNTDFCHGLV IFAGADTKIM KNSGKTRFKR TKIDYLMNYM VYTIFVVLIL LSAGLAIGHA
361: YWEAQVGNSS WYLYDGEDDT PSYRGFLIFW GYIIVLNTMV PISLYVSVEV IRLGQSHFIN
421: WDLQMYYAEK DTPAKARTTT LNEQLGQIHY IFSDKTGTLT QNIMTFKKCC INGQIYGDHR
481: DASQHNHNKI EQVDFSWNTY ADGKLAFYDH YLIEQIQSGK EPEVRQFFFL LAVCHTVMVD
541: RTDGQLNYQA ASPDEGALVN AARNFGFAFL ARTQNTITIS ELGTERTYNV LAILDFNSDR
601: KRMSIIVRTP EGNIKLYCKG ADTVIYERLH RMNPTKQETQ DALDIFANET LRTLCLCYKE
661: IEEKEFTEWN KKFMAASVAS TNRDEALDKV YEEIEKDLIL LGATAIEDKL QDGVPETISK
721: LAKADIKIWV LTGDKKETAE NIGFACELLT EDTTICYGED INSLLHARME NQRNRGGVYA
781: KFAPPVQESF FPPGGNRALI ITGSWLNEIL LEKKTKRNKI LKLKFPRTEE ERRMRTQSKR
841: RLEAKKEQRQ KNFVDLACEC SAVICCRVTP KQKAMVVDLV KRYKKAITLA IGDGANDVNM
901: IKTAHIGVGI SGQEGMQAVM SSDYSFAQFR YLQRLLLVHG RWSYIRMCKF LRYFFYKNFA
961: FTLVHFWYSF FNGYSAQTAY EDWFITLYNV LYTSLPVLLM GLLDQDVSDK LSLRFPGLYI
1021: VGQRDLLFNY KRFFVSLLHG VLTSMILFFI PLGAYLQTVG QDGEAPSDYQ SFAVTIASAL
1081: VITVNFQIGL DTSYWTFVNA FSIFGSIALY FGIMFDFHSA GIHVLFPSAF QFTGTASNAL
1141: RQPYIWLTII LAVAVCLLPV VAIRFLSMTI WPSESDKIQK HRKRLKAEEQ WQRRQQVFRR
1201: GVSTRRSAYA FSHQRGYADL ISSGRSIRKK RSPLDAIVAD GTAEYRRTGD S