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3.A.1.211.1
The cholesterol/phospholipid/leutein flippase, ABC1 (called ABCA1 in humans; Tangier disease proteins; 2261 aas and 14 TMSs in a 1 + 6 + 1 + 6 TMS arrangement; UniProt: O95477). An amphipathic helical region of the N-terminal barrel of the phospholipid transfer protein (PLTP) is critical for ABCA1-dependent cholesterol efflux (Oram et al., 2008). PLTP helix 144-163 removes lipid domains formed by ABCA1, stabilizing ABCA1, interacting with phospholipids, and promoting phospholipid transfer by direct interactions with ABCA1. May transport sphingosine-1-phosphate (Kobayashi et al., 2009). May protect from cardiovascular disease and diabetes (Tang and Oram, 2009). Mediates efflux of cellular cholesterol and phospholipids to apoA-I (Voloshyna and Reiss, 2011).  Hyperglycemia accelerates ABCA1 degradation (Chang et al. 2013).  Human ABCA1 is down regulated upon infection with Chlamydia pneumoniae which inhibits bacterial growth (Korhonen et al. 2013).  Curcumin induces expression of ABCA1 (Tian et al. 2013). May also export retinol and retinyl palmitate (Reboul 2013). The role of ABCA1 in human diseases has been reviewed (Jacobo-Albavera et al. 2021). Production of high density lipoprotein (HDL) requires ABCA1 to drive phospholipid (PL) from the plasma membrane into extracellular apolipoprotein A-I. Segrest et al. 2022 showed that domains of ABCA1 within the plasma membrane remove PL from the membrane's outer leaflet. After the lipid diffuses into the interior of ABCA1's outward-open cavity, PL extracted by the gateway passes through a ring-shaped domain, the annulus orifice, which forms the base of an elongated hydrophobic tunnel in the transporter's extracellular domain. Engineered mutations in the gateway and annulus inhibit lipid export by ABCA1 without affecting cell-surface expression levels. These finding that ABCA1 extracts lipid from the outer face of the plasma membrane and forces it through its gateway and annulus into an elongated hydrophobic tunnel contrasts with the alternating access model, which proposes that ABCA1 flops PL substrate from the inner leaflet to the outer leaflet of the membrane. Thus, ABCA1 lacks the charged amino acid residues in the transmembrane domain found in the floppase members of the ABC transporter family (Segrest et al. 2022).  Regulation of lipid metabolism by APOE4 in intrahepatic cholangiocarcinoma via the enhancement of ABCA1 membrane expression (Qian et al. 2024).  Tumour metastasis in colorectal cancer occurs via the RAC1/ABCA1 axis (Chen et al. 2024).

Accession Number:P41233
Protein Name:ABC1 aka ABCA1
Length:2261
Molecular Weight:253974.00
Species:Mus musculus (Mouse) [10090]
Number of TMSs:15
Location1 / Topology2 / Orientation3: Membrane1 / Multi-pass membrane protein2
Substrate phospholipid, all-trans-retinal, all-trans-retinol, cholesterol, lutein, sphingosine 1-phosphate

Cross database links:

Pfam: PF00005   

Gene Ontology

GO:0005794 C:Golgi apparatus
GO:0005887 C:integral to plasma membrane
GO:0008509 F:anion transmembrane transporter activity
GO:0005524 F:ATP binding
GO:0016887 F:ATPase activity
GO:0017127 F:cholesterol transporter activity
GO:0005548 F:phospholipid transporter activity
GO:0033344 P:cholesterol efflux
GO:0008203 P:cholesterol metabolic process
GO:0002790 P:peptide secretion
GO:0006911 P:phagocytosis, engulfment
GO:0033700 P:phospholipid efflux
GO:0045332 P:phospholipid translocation
GO:0010875 P:positive regulation of cholesterol efflux
GO:0006497 P:protein amino acid lipidation
GO:0043691 P:reverse cholesterol transport

References (7)

[1] “Cloning of two novel ABC transporters mapping on human chromosome 9.”  Luciani M.-F.et.al.   8088782
[2] “Human and mouse ABCA1 comparative sequencing and transgenesis studies revealing novel regulatory sequences.”  Qiu Y.et.al.   11352567
[3] “Bacterial lipopolysaccharide induces expression of ABCA1 but not ABCG1 via an LXR-independent pathway.”  Kaplan R.et.al.   12032171
[4] “Endotoxin down-regulates ABCG5 and ABCG8 in mouse liver and ABCA1 and ABCG1 in J774 murine macrophages: differential role of LXR.”  Khovidhunkit W.et.al.   12777468
[5] “Cooperation between engulfment receptors: the case of ABCA1 and MEGF10.”  Hamon Y.et.al.   17205124
[6] “Large-scale phosphorylation analysis of mouse liver.”  Villen J.et.al.   17242355
[7] “Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins.”  Wollscheid B.et.al.   19349973

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence 
1:	MACWPQLRLL LWKNLTFRRR QTCQLLLEVA WPLFIFLILI SVRLSYPPYE QHECHFPNKA 
61:	MPSAGTLPWV QGIICNANNP CFRYPTPGEA PGVVGNFNKS IVSRLFSDAQ RLLLYSQRDT 
121:	SIKDMHKVLR MLRQIKHPNS NLKLQDFLVD NETFSGFLQH NLSLPRSTVD SLLQANVGLQ 
181:	KVFLQGYQLH LASLCNGSKL EEIIQLGDAE VSALCGLPRK KLDAAERVLR YNMDILKPVV 
241:	TKLNSTSHLP TQHLAEATTV LLDSLGGLAQ ELFSTKSWSD MRQEVMFLTN VNSSSSSTQI 
301:	YQAVSRIVCG HPEGGGLKIK SLNWYEDNNY KALFGGNNTE EDVDTFYDNS TTPYCNDLMK 
361:	NLESSPLSRI IWKALKPLLV GKILYTPDTP ATRQVMAEVN KTFQELAVFH DLEGMWEELS 
421:	PQIWTFMENS QEMDLVRTLL DSRGNDQFWE QKLDGLDWTA QDIMAFLAKN PEDVQSPNGS 
481:	VYTWREAFNE TNQAIQTISR FMECVNLNKL EPIPTEVRLI NKSMELLDER KFWAGIVFTG 
541:	ITPDSVELPH HVKYKIRMDI DNVERTNKIK DGYWDPGPRA DPFEDMRYVW GGFAYLQDVV 
601:	EQAIIRVLTG SEKKTGVYVQ QMPYPCYVDD IFLRVMSRSM PLFMTLAWIY SVAVIIKSIV 
661:	YEKEARLKET MRIMGLDNGI LWFSWFVSSL IPLLVSAGLL VVILKLGNLL PYSDPSVVFV 
721:	FLSVFAMVTI LQCFLISTLF SRANLAAACG GIIYFTLYLP YVLCVAWQDY VGFSIKIFAS 
781:	LLSPVAFGFG CEYFALFEEQ GIGVQWDNLF ESPVEEDGFN LTTAVSMMLF DTFLYGVMTW 
841:	YIEAVFPGQY GIPRPWYFPC TKSYWFGEEI DEKSHPGSSQ KGVSEICMEE EPTHLRLGVS 
901:	IQNLVKVYRD GMKVAVDGLA LNFYEGQITS FLGHNGAGKT TTMSILTGLF PPTSGTAYIL 
961:	GKDIRSEMSS IRQNLGVCPQ HNVLFDMLTV EEHIWFYARL KGLSEKHVKA EMEQMALDVG 
1021:	LPPSKLKSKT SQLSGGMQRK LSVALAFVGG SKVVILDEPT AGVDPYSRRG IWELLLKYRQ 
1081:	GRTIILSTHH MDEADILGDR IAIISHGKLC CVGSSLFLKN QLGTGYYLTL VKKDVESSLS 
1141:	SCRNSSSTVS CLKKEDSVSQ SSSDAGLGSD HESDTLTIDV SAISNLIRKH VSEARLVEDI 
1201:	GHELTYVLPY EAAKEGAFVE LFHEIDDRLS DLGISSYGIS ETTLEEIFLK VAEESGVDAE 
1261:	TSDGTLPARR NRRAFGDKQS CLHPFTEDDA VDPNDSDIDP ESRETDLLSG MDGKGSYQLK 
1321:	GWKLTQQQFV ALLWKRLLIA RRSRKGFFAQ IVLPAVFVCI ALVFSLIVPP FGKYPSLELQ 
1381:	PWMYNEQYTF VSNDAPEDMG TQELLNALTK DPGFGTRCME GNPIPDTPCL AGEEDWTISP 
1441:	VPQSIVDLFQ NGNWTMKNPS PACQCSSDKI KKMLPVCPPG AGGLPPPQRK QKTADILQNL 
1501:	TGRNISDYLV KTYVQIIAKS LKNKIWVNEF RYGGFSLGVS NSQALPPSHE VNDAIKQMKK 
1561:	LLKLTKDTSA DRFLSSLGRF MAGLDTKNNV KVWFNNKGWH AISSFLNVIN NAILRANLQK 
1621:	GENPSQYGIT AFNHPLNLTK QQLSEVALMT TSVDVLVSIC VIFAMSFVPA SFVVFLIQER 
1681:	VSKAKHLQFI SGVKPVIYWL SNFVWDMCNY VVPATLVIII FICFQQKSYV SSTNLPVLAL 
1741:	LLLLYGWSIT PLMYPASFVF KIPSTAYVVL TSVNLFIGIN GSVATFVLEL FTNNKLNDIN 
1801:	DILKSVFLIF PHFCLGRGLI DMVKNQAMAD ALERFGENRF VSPLSWDLVG RNLFAMAVEG 
1861:	VVFFLITVLI QYRFFIRPRP VKAKLPPLND EDEDVRRERQ RILDGGGQND ILEIKELTKI 
1921:	YRRKRKPAVD RICIGIPPGE CFGLLGVNGA GKSTTFKMLT GDTPVTRGDA FLNKNSILSN 
1981:	IHEVHQNMGY CPQFDAITEL LTGREHVEFF ALLRGVPEKE VGKFGEWAIR KLGLVKYGEK 
2041:	YASNYSGGNK RKLSTAMALI GGPPVVFLDE PTTGMDPKAR RFLWNCALSI VKEGRSVVLT 
2101:	SHSMEECEAL CTRMAIMVNG RFRCLGSVQH LKNRFGDGYT IVVRIAGSNP DLKPVQEFFG 
2161:	LAFPGSVLKE KHRNMLQYQL PSSLSSLARI FSILSQSKKR LHIEDYSVSQ TTLDQVFVNF 
2221:	AKDQSDDDHL KDLSLHKNQT VVDVAVLTSF LQDEKVKESY V