ABCA7 Membrane Protein Introduction

Introduction of ABCA7

ABCA7 encoded by ABCA7 gene is a member of the superfamily of ATP-binding cassette (ABC) transporters which transport various molecules across extra- and intracellular membranes. There are seven subfamilies in ABC superfamily named as ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White, respectively. ABCA7 protein belongs to ABC1 subfamily. It is highly expressed in peripheral leukocytes, thymus, spleen, and bone marrow.

Basic Information of ABCA7
Protein Name	ATP-binding cassette sub-family A member 7
Gene Name	ABCA7
Aliases	AD9, ABCX, ABCA-SSN
Organism	Homo sapiens (Human)
UniProt ID	Q8IZY2
Transmembrane Times	12
Length (aa)	2146
Sequence	MAFWTQLMLLLWKNFMYRRRQPVQLLVELLWPLFLFFILVAVRHSHPPLEHHECHFPNKPLPSAGTVPWLQGLICNVNNTCFPQLTPGEEPGRLSNFNDSLVSRLLADARTVLGGASAHRTLAGLGKLIATLRAARSTAQPQPTKQSPLEPPMLDVAELLTSLLRTESLGLALGQAQEPLHSLLEAAEDLAQELLALRSLVELRALLQRPRGTSGPLELLSEALCSVRGPSSTVGPSLNWYEASDLMELVGQEPESALPDSSLSPACSELIGALDSHPLSRLLWRRLKPLILGKLLFAPDTPFTRKLMAQVNRTFEELTLLRDVREVWEMLGPRIFTFMNDSSNVAMLQRLLQMQDEGRRQPRPGGRDHMEALRSFLDPGSGGYSWQDAHADVGHLVGTLGRVTECLSLDKLEAAPSEAALVSRALQLLAEHRFWAGVVFLGPEDSSDPTEHPTPDLGPGHVRIKIRMDIDVVTRTNKIRDRFWDPGPAADPLTDLRYVWGGFVYLQDLVERAAVRVLSGANPRAGLYLQQMPYPCYVDDVFLRVLSRSLPLFLTLAWIYSVTLTVKAVVREKETRLRDTMRAMGLSRAVLWLGWFLSCLGPFLLSAALLVLVLKLGDILPYSHPGVVFLFLAAFAVATVTQSFLLSAFFSRANLAAACGGLAYFSLYLPYVLCVAWRDRLPAGGRVAASLLSPVAFGFGCESLALLEEQGEGAQWHNVGTRPTADVFSLAQVSGLLLLDAALYGLATWYLEAVCPGQYGIPEPWNFPFRRSYWCGPRPPKSPAPCPTPLDPKVLVEEAPPGLSPGVSVRSLEKRFPGSPQPALRGLSLDFYQGHITAFLGHNGAGKTTTLSILSGLFPPSGGSAFILGHDVRSSMAAIRPHLGVCPQYNVLFDMLTVDEHVWFYGRLKGLSAAVVGPEQDRLLQDVGLVSKQSVQTRHLSGGMQRKLSVAIAFVGGSQVVILDEPTAGVDPASRRGIWELLLKYREGRTLILSTHHLDEAELLGDRVAVVAGGRLCCCGSPLFLRRHLGSGYYLTLVKARLPLTTNEKADTDMEGSVDTRQEKKNGSQGSRVGTPQLLALVQHWVPGARLVEELPHELVLVLPYTGAHDGSFATLFRELDTRLAELRLTGYGISDTSLEEIFLKVVEECAADTDMEDGSCGQHLCTGIAGLDVTLRLKMPPQETALENGEPAGSAPETDQGSGPDAVGRVQGWALTRQQLQALLLKRFLLARRSRRGLFAQIVLPALFVGLALVFSLIVPPFGHYPALRLSPTMYGAQVSFFSEDAPGDPGRARLLEALLQEAGLEEPPVQHSSHRFSAPEVPAEVAKVLASGNWTPESPSPACQCSRPGARRLLPDCPAAAGGPPPPQAVTGSGEVVQNLTGRNLSDFLVKTYPRLVRQGLKTKKWVNEVRYGGFSLGGRDPGLPSGQELGRSVEELWALLSPLPGGALDRVLKNLTAWAHSLDAQDSLKIWFNNKGWHSMVAFVNRASNAILRAHLPPGPARHAHSITTLNHPLNLTKEQLSEGALMASSVDVLVSICVVFAMSFVPASFTLVLIEERVTRAKHLQLMGGLSPTLYWLGNFLWDMCNYLVPACIVVLIFLAFQQRAYVAPANLPALLLLLLLYGWSITPLMYPASFFFSVPSTAYVVLTCINLFIGINGSMATFVLELFSDQKLQEVSRILKQVFLIFPHFCLGRGLIDMVRNQAMADAFERLGDRQFQSPLRWEVVGKNLLAMVIQGPLFLLFTLLLQHRSQLLPQPRVRSLPLLGEEDEDVARERERVVQGATQGDVLVLRNLTKVYRGQRMPAVDRLCLGIPPGECFGLLGVNGAGKTSTFRMVTGDTLASRGEAVLAGHSVAREPSAAHLSMGYCPQSDAIFELLTGREHLELLARLRGVPEAQVAQTAGSGLARLGLSWYADRPAGTYSGGNKRKLATALALVGDPAVVFLDEPTTGMDPSARRFLWNSLLAVVREGRSVMLTSHSMEECEALCSRLAIMVNGRFRCLGSPQHLKGRFAAGHTLTLRVPAARSQPAAAFVAAEFPGAELREAHGGRLRFQLPPGGRCALARVFGELAVHGAEHGVEDFSVSQTMLEEVFLYFSKDQGKDEDTEEQKEAGVGVDPAPGLQHPKRVSQFLDDPSTAETVL

Function of ABCA7 Membrane Protein

ABCA7 is an integrated transport protein that transports lipid molecules across extra- and intracellular membranes involved in the regulation of lipid homeostasis within defined microenvironments. In female mice, ABCA7 knockout can significantly reduce visceral fat and serum cholesterol concentrations. It has been reported that ABCA7 plays an essential role in the progression of Alzheimer’s disease (AD). The highest levels of ABCA7 are observed in the hippocampus that is one of the earliest affected regions in the brains of patients with AD, and in microglia cells responsible for cerebral inflammatory responses. Moreover, ABCA7 may be involved in the microglial amyloid-β (Aβ) clearance pathway that is a protective factor for AD. The deficiency of ABCA7 leads to the accumulation of Aβ thereby triggering the pathogenic cascade of AD. Several GWASs (Genome Wide Association Study) have revealed that variants in ABCA7 genes, especially loss-of-function variants, are associated with significant risk for AD. In addition, ABCA7 is also found in a variety of immune cells suggesting a role in immune response. However, the role of ABCA7 in the immune response is unknown.

ABCA7 Membrane Protein Introduction Fig.1 Possible pathogenic pathways mediated by ABCA7 in AD. (Aikawa, 2018)

Application of ABCA7 Membrane Protein in Literature

Ma F.C., et al. Meta-analysis of the association between variants in ABCA7 and Alzheimer's Disease. Journal of Alzheimer Disease Jad. 2018. 63(4): 1261-1267. PubMed ID: 29782324

The meta-analysis study shows that the loss-of-function variants in ABCA7 are significantly linked to the susceptibility to Alzheimer's Disease.
Almeida J., et al. Updated Meta-analysis of BIN1, CR1, MS4A6A, CLU, and ABCA7 variants in Alzheimer's Disease. Journal of Molecular Neuroscience. 2018, 64(3): 471-477. PubMed ID: 29504051

The meta-analysis study shows that ABCA7 (rs3764650), CR1 (rs6656401), and BIN1 (rs744373) are the risk factors of late-onset Alzheimer's disease (LOAD), while MS4A6A (rs610932) and CLU (rs11136000) are the protective factors.
May P., et al. Rare ABCA7 variants in 2 German families with Alzheimer Disease. Neurol Genet. 2018, 4(2): e224. PubMed ID: 29577078

The authors identify 2 rare variants in ABCA7 (rs143718918 and rs538591288) are associated with the development of Alzheimer Disease (AD) in 2 German families. These suggest ABCA7 is one of the most relevant genes of AD risk.
Aikawa T., et al. ABCA7 and pathogenic pathways of Alzheimer's Disease. Brain Sci. 2018, 8(2). PubMed ID: 29401741

The study shows that the dysfunctions of ABCA7 are associated with the AD-related of Alzheimer's disease involved in multiple pathways such as microglial Aβ clearance pathway.
Zhou G., et al. ATP binding cassette subfamily A member 7 rs3764650 polymorphism and the risk of Alzheimer's Disease. Pharmazie. 2017, 72(7): 425-427. PubMed ID: 29441941

The authors identify the association of ABCA7 rs3764650 polymorphism with the risk of Alzheimer's disease (AD) using a meta-analysis.

ABCA7 Preparation Options

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Reference

Aikawa T., et al. (2018). ABCA7 and pathogenic pathways of Alzheimer's disease. Brain Sci. 2018, 8(2):27.

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