ABCA2 (ATP binding cassette subfamily A member 2)

Gene

• Entrez ID: 20
• Gene name: ATP binding cassette subfamily A member 2
• Gene symbol: ABCA2
• Synonyms: ABC2, IDPOGSA
• Chromosome: 9
• Chromosome location: 9q34.3
• Summary: The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intracellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the ABC1 subfamily. Members of the ABC1 subfamily comprise the only major ABC subfamily found exclusively in multicellular eukaryotes. This protein is highly expressed in brain tissue and may play a role in macrophage lipid metabolism and neural development. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs1588511352	C>-	Pathogenic, uncertain-significance	Coding sequence variant, frameshift variant, non coding transcript variant
rs1588512383	TACTCGCGGCG>C	Pathogenic	Coding sequence variant, frameshift variant, non coding transcript variant
rs1588524458	G>A	Pathogenic	Coding sequence variant, stop gained, non coding transcript variant
rs1588525874	->A	Pathogenic	Coding sequence variant, frameshift variant, non coding transcript variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT437529	hsa-miR-19b-3p	Immunoprecipitaion	22382630
MIRT441311	hsa-miR-485-5p	HITS-CLIP	24374217
MIRT682977	hsa-miR-4644	HITS-CLIP	23706177
MIRT682978	hsa-miR-218-1-3p	HITS-CLIP	23706177
MIRT682979	hsa-miR-6721-5p	HITS-CLIP	23706177
MIRT682980	hsa-miR-4722-5p	HITS-CLIP	23706177
MIRT682981	hsa-miR-6089	HITS-CLIP	23706177
MIRT682982	hsa-miR-7112-5p	HITS-CLIP	23706177
MIRT682983	hsa-miR-4768-3p	HITS-CLIP	23706177
MIRT682984	hsa-miR-320e	HITS-CLIP	23706177
MIRT682985	hsa-miR-4429	HITS-CLIP	23706177
MIRT682986	hsa-miR-320d	HITS-CLIP	23706177
MIRT682987	hsa-miR-320c	HITS-CLIP	23706177
MIRT682988	hsa-miR-320b	HITS-CLIP	23706177
MIRT682989	hsa-miR-320a	HITS-CLIP	23706177

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000166	Function	Nucleotide binding	NAS	12363033
GO:0001573	Process	Ganglioside metabolic process	ISS
GO:0005319	Function	Lipid transporter activity	IBA	21873635
GO:0005524	Function	ATP binding	IDA	15999530
GO:0005524	Function	ATP binding	ISS
GO:0005764	Component	Lysosome	IDA	11309290
GO:0005765	Component	Lysosomal membrane	ISS
GO:0005765	Component	Lysosomal membrane	NAS	11309290
GO:0005768	Component	Endosome	IDA	11309290
GO:0005815	Component	Microtubule organizing center	ISS
GO:0005886	Component	Plasma membrane	IDA	23137377, 24201375
GO:0006357	Process	Regulation of transcription by RNA polymerase II	IDA	15238223
GO:0006629	Process	Lipid metabolic process	NAS	11178988
GO:0006684	Process	Sphingomyelin metabolic process	ISS
GO:0006687	Process	Glycosphingolipid metabolic process	ISS
GO:0006869	Process	Lipid transport	IBA	21873635
GO:0007626	Process	Locomotory behavior	ISS
GO:0010008	Component	Endosome membrane	IEA
GO:0010872	Process	Regulation of cholesterol esterification	IDA	24201375
GO:0010872	Process	Regulation of cholesterol esterification	IMP	15238223
GO:0016020	Component	Membrane	HDA	19946888
GO:0016021	Component	Integral component of membrane	IDA	15999530
GO:0016021	Component	Integral component of membrane	NAS	11309290, 12363033
GO:0016887	Function	ATPase activity	IDA	15999530
GO:0031410	Component	Cytoplasmic vesicle	ISS
GO:0032289	Process	Central nervous system myelin formation	ISS
GO:0032383	Process	Regulation of intracellular cholesterol transport	IMP	15238223
GO:0032383	Process	Regulation of intracellular cholesterol transport	ISS
GO:0032384	Process	Negative regulation of intracellular cholesterol transport	IDA	21810484
GO:0032805	Process	Positive regulation of low-density lipoprotein particle receptor catabolic process	IDA	21810484
GO:0042493	Process	Response to drug	TAS	12363033
GO:0042626	Function	ATPase-coupled transmembrane transporter activity	IBA	21873635
GO:0042626	Function	ATPase-coupled transmembrane transporter activity	NAS	7766993
GO:0042632	Process	Cholesterol homeostasis	IEP	15238223
GO:0042986	Process	Positive regulation of amyloid precursor protein biosynthetic process	IDA	20704561
GO:0043190	Component	ATP-binding cassette (ABC) transporter complex	NAS	11178988
GO:0043231	Component	Intracellular membrane-bounded organelle	IBA	21873635
GO:0045540	Process	Regulation of cholesterol biosynthetic process	IDA	21810484
GO:0046512	Process	Sphingosine biosynthetic process	IDA	26510981
GO:0048545	Process	Response to steroid hormone	IEP	15238223
GO:0052548	Process	Regulation of endopeptidase activity	IEA
GO:0055085	Process	Transmembrane transport	NAS	7766993
GO:0060049	Process	Regulation of protein glycosylation	ISS	22086926
GO:0061135	Function	Endopeptidase regulator activity	IMP	22086926
GO:0070723	Process	Response to cholesterol	IEP	11178988
GO:0071072	Process	Negative regulation of phospholipid biosynthetic process	IDA	24201375
GO:0090155	Process	Negative regulation of sphingolipid biosynthetic process	IDA	24201375
GO:0090156	Process	Cellular sphingolipid homeostasis	IDA	26510981
GO:0090370	Process	Negative regulation of cholesterol efflux	IDA	21810484
GO:0099038	Function	Ceramide floppase activity	IDA	24201375
GO:0099040	Process	Ceramide translocation	IDA	24201375
GO:0150104	Process	Transport across blood-brain barrier	NAS	26590417, 30280653
GO:0150110	Process	Negative regulation of cholesterol esterification	IDA	21810484
GO:0150110	Process	Negative regulation of cholesterol esterification	ISS	24201375
GO:1901873	Process	Regulation of post-translational protein modification	IMP	22086926
GO:1902004	Process	Positive regulation of amyloid-beta formation	IMP	22086926
GO:1902004	Process	Positive regulation of amyloid-beta formation	ISS	22086926
GO:1902993	Process	Positive regulation of amyloid precursor protein catabolic process	IGI	20704561
GO:1902993	Process	Positive regulation of amyloid precursor protein catabolic process	IMP	22086926
GO:1904375	Process	Regulation of protein localization to cell periphery	ISS	22086926
GO:1905598	Process	Negative regulation of low-density lipoprotein receptor activity	IDA	21810484
GO:1905601	Process	Negative regulation of receptor-mediated endocytosis involved in cholesterol transport	IDA	21810484
GO:2000008	Process	Regulation of protein localization to cell surface	ISS	22086926

Other IDs

• MIM: 600047
• HGNC: 32
• e!Ensembl: ENSG00000107331

Protein

• UniProt ID: Q9BZC7
• Protein name: ATP-binding cassette sub-family A member 2 (EC 7.6.2.-) (ATP-binding cassette transporter 2) (ATP-binding cassette 2)
• Protein function: Probable lipid tranporter that modulates cholesterol sequestration in the late endosome/lysosome by regulating the intracellular sphingolipid metabolism, in turn participates in cholesterol homeostasis (PubMed:15238223, PubMed:21810484, PubMed:24201375) (Probable). May alter the transbilayer distribution of ceramide in the intraluminal membrane lipid bilayer, favoring its retention in the outer leaflet that results in increased acid ceramidase activity in the late endosome/lysosome, facilitating ceramide deacylation to sphingosine leading to the sequestration of free cholesterol in lysosomes (PubMed:24201375). In addition regulates amyloid-beta production either by activating a signaling pathway that regulates amyloid precursor protein transcription through the modulation of sphingolipid metabolism or through its role in gamma-secretase processing of APP (PubMed:22086926, PubMed:26510981). May play a role in myelin formation (By similarity).
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF12698	ABC2_membrane_3	684 → 912		Family
  PF00005	ABC_tran	1007 → 1151	ABC transporter	Domain
  PF12698	ABC2_membrane_3	1692 → 2008		Family
  PF00005	ABC_tran	2070 → 2214	ABC transporter	Domain

• Sequence:

  MGFLHQLQLLLWKNVTLKRRSPWVLAFEIFIPLVLFFILLGLRQKKPTISVKEAFYTAAP
  LTSAGILPVMQSLCPDGQRDEFGFLQYANSTVTQLLERLDRVVEEGNLFDPARPSLGSEL
  EALRQHLEALSAGPGTSGSHLDRSTVSSFSLDSVARNPQELWRFLTQNLSLPNSTAQALL
  AARVDPPEVYHLLFGPSSALDSQSGLHKGQEPWSRLGGNPLFRMEELLLAPALLEQLTCT
  PGSGELGRILTVPESQKGALQGYRDAVCSGQAAARARRFSGLSAELRNQLDVAKVSQQLG
  LDAPNGSDSSPQAPPPRRLQALLGDLLDAQKVLQDVDVLSALALLLPQGACTGRTPGPPA
  SGAGGAANGTGAGAVMGPNATAEEGAPSAAALATPDTLQGQCSAFVQLWAGLQPILCGNN
  RTIEPEALRRGNMSSLGFTSKEQRNLGLLVHLMTSNPKILYAPAGSEVDRVILKANETFA
  FVGNVTHYAQVWLNISAEIRSFLEQGRLQQHLRWLQQYVAELRLHPEALNLSLDELPPAL
  RQDNFSLPSGMALLQQLDTIDNAACGWIQFMSKVSVDIFKGFPDEESIVNYTLNQAYQDN
  VTVFASVIFQTRKDGSLPPHVHYKIRQNSSFTEKTNEIRRAYWRPGPNTGGRFYFLYGFV
  WIQDMMERAIIDTFVGHDVVEPGSYVQMFPYPCYTRDDFLFVIEHMMPLCMVISWVYSVA
  MTIQHIVAEKEHRLKEVMKTMGLNNAVHWVAWFITGFVQLSISVTALTAILKYGQVLMHS
  HVVIIWLFLAVYAVATIMFCFLVSVLYSKAKLASACGGIIYFLSYVPYMYVAIREEVAHD
  KITAFEKCIASLMSTTAFGLGSKYFALYEVAGVGIQWHTFSQSPVEGDDFNLLLAVTMLM
  VDAVVYGILTWYIEAVHPGMYGLPRPWYFPLQKSYWLGSGRTEAWEWSWPWARTPRLSVM
  EEDQACAMESRRFEETRGMEEEPTHLPLVVCVDKLTKVYKDDKKLALNKLSLNLYENQVV
  SFLGHNGAGKTTTMSILTGLFPPTSGSATIYGHDIRTEMDEIRKNLGMCPQHNVLFDRLT
  VEEHLWFYSRLKSMAQEEIRREMDKMIEDLELSNKRHSLVQTLSGGMKRKLSVAIAFVGG
  SRAIILDEPTAGVDPYARRAIWDLILKYKPGRTILLSTHHMDEADLLGDRIAIISHGKLK
  CCGSPLFLKGTYGDGYRLTLVKRPAEPGGPQEPGLASSPPGRAPLSSCSELQVSQFIRKH
  VASCLLVSDTSTELSYILPSEAAKKGAFERLFQHLERSLDALHLSSFGLMDTTLEEVFLK
  VSEEDQSLENSEADVKESRKDVLPGAEGPASGEGHAGNLARCSELTQSQASLQSASSVGS
  ARGDEGAGYTDVYGDYRPLFDNPQDPDNVSLQEVEAEALSRVGQGSRKLDGGWLKVRQFH
  GLLVKRFHCARRNSKALFSQILLPAFFVCVAMTVALSVPEIGDLPPLVLSPSQYHNYTQP
  RGNFIPYANEERREYRLRLSPDASPQQLVSTFRLPSGVGATCVLKSPANGSLGPTLNLSS
  GESRLLAARFFDSMCLESFTQGLPLSNFVPPPPSPAPSDSPASPDEDLQAWNVSLPPTAG
  PEMWTSAPSLPRLVREPVRCTCSAQGTGFSCPSSVGGHPPQMRVVTGDILTDITGHNVSE
  YLLFTSDRFRLHRYGAITFGNVLKSIPASFGTRAPPMVRKIAVRRAAQVFYNNKGYHSMP
  TYLNSLNNAILRANLPKSKGNPAAYGITVTNHPMNKTSASLSLDYLLQGTDVVIAIFIIV
  AMSFVPASFVVFLVAEKSTKAKHLQFVSGCNPIIYWLANYVWDMLNYLVPATCCVIILFV
  FDLPAYTSPTNFPAVLSLFLLYGWSITPIMYPASFWFEVPSSAYVFLIVINLFIGITATV
  ATFLLQLFEHDKDLKVVNSYLKSCFLIFPNYNLGHGLMEMAYNEYINEYYAKIGQFDKMK
  SPFEWDIVTRGLVAMAVEGVVGFLLTIMCQYNFLRRPQRMPVSTKPVEDDVDVASERQRV
  LRGDADNDMVKIENLTKVYKSRKIGRILAVDRLCLGVRPGECFGLLGVNGAGKTSTFKML
  TGDESTTGGEAFVNGHSVLKELLQVQQSLGYCPQCDALFDELTAREHLQLYTRLRGISWK
  DEARVVKWALEKLELTKYADKPAGTYSGGNKRKLSTAIALIGYPAFIFLDEPTTGMDPKA
  RRFLWNLILDLIKTGRSVVLTSHSMEECEALCTRLAIMVNGRLRCLGSIQHLKNRFGDGY
  MITVRTKSSQSVKDVVRFFNRNFPEAMLKERHHTKVQYQLKSEHISLAQVFSKMEQVSGV
  LGIEDYSVSQTTLDNVFVNFAKKQSDNLEQQETEPPSALQSPLGCLLSLLRPRSAPTELR
  ALVADEPEDLDTEDEGLISFEEERAQLSFNTDTLC

• Sequence length: 2435