Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTJW1GN)

• DTT Name: ATP-binding cassette transporter A1 (ABCA1)
• Synonyms: Cholesterol mobilizing transporter ABCA1; Cholesterol efflux regulatory protein; CERP; ATP-binding cassette transporter (ABCA1) transmembrane protein; ATP-binding cassette sub-family A member 1; ATP-binding cassette 1; ABC1; ABC-1
• Gene Name: ABCA1
• DTT Type: Successful target; [1]
• BioChemical Class: ABC transporter
• UniProt ID: ABCA1_HUMAN
• TTD ID: T00494
• EC Number: EC 7.6.2.1
• Sequence:
  MACWPQLRLLLWKNLTFRRRQTCQLLLEVAWPLFIFLILISVRLSYPPYEQHECHFPNKA
  MPSAGTLPWVQGIICNANNPCFRYPTPGEAPGVVGNFNKSIVARLFSDARRLLLYSQKDT
  SMKDMRKVLRTLQQIKKSSSNLKLQDFLVDNETFSGFLYHNLSLPKSTVDKMLRADVILH
  KVFLQGYQLHLTSLCNGSKSEEMIQLGDQEVSELCGLPREKLAAAERVLRSNMDILKPIL
  RTLNSTSPFPSKELAEATKTLLHSLGTLAQELFSMRSWSDMRQEVMFLTNVNSSSSSTQI
  YQAVSRIVCGHPEGGGLKIKSLNWYEDNNYKALFGGNGTEEDAETFYDNSTTPYCNDLMK
  NLESSPLSRIIWKALKPLLVGKILYTPDTPATRQVMAEVNKTFQELAVFHDLEGMWEELS
  PKIWTFMENSQEMDLVRMLLDSRDNDHFWEQQLDGLDWTAQDIVAFLAKHPEDVQSSNGS
  VYTWREAFNETNQAIRTISRFMECVNLNKLEPIATEVWLINKSMELLDERKFWAGIVFTG
  ITPGSIELPHHVKYKIRMDIDNVERTNKIKDGYWDPGPRADPFEDMRYVWGGFAYLQDVV
  EQAIIRVLTGTEKKTGVYMQQMPYPCYVDDIFLRVMSRSMPLFMTLAWIYSVAVIIKGIV
  YEKEARLKETMRIMGLDNSILWFSWFISSLIPLLVSAGLLVVILKLGNLLPYSDPSVVFV
  FLSVFAVVTILQCFLISTLFSRANLAAACGGIIYFTLYLPYVLCVAWQDYVGFTLKIFAS
  LLSPVAFGFGCEYFALFEEQGIGVQWDNLFESPVEEDGFNLTTSVSMMLFDTFLYGVMTW
  YIEAVFPGQYGIPRPWYFPCTKSYWFGEESDEKSHPGSNQKRISEICMEEEPTHLKLGVS
  IQNLVKVYRDGMKVAVDGLALNFYEGQITSFLGHNGAGKTTTMSILTGLFPPTSGTAYIL
  GKDIRSEMSTIRQNLGVCPQHNVLFDMLTVEEHIWFYARLKGLSEKHVKAEMEQMALDVG
  LPSSKLKSKTSQLSGGMQRKLSVALAFVGGSKVVILDEPTAGVDPYSRRGIWELLLKYRQ
  GRTIILSTHHMDEADVLGDRIAIISHGKLCCVGSSLFLKNQLGTGYYLTLVKKDVESSLS
  SCRNSSSTVSYLKKEDSVSQSSSDAGLGSDHESDTLTIDVSAISNLIRKHVSEARLVEDI
  GHELTYVLPYEAAKEGAFVELFHEIDDRLSDLGISSYGISETTLEEIFLKVAEESGVDAE
  TSDGTLPARRNRRAFGDKQSCLRPFTEDDAADPNDSDIDPESRETDLLSGMDGKGSYQVK
  GWKLTQQQFVALLWKRLLIARRSRKGFFAQIVLPAVFVCIALVFSLIVPPFGKYPSLELQ
  PWMYNEQYTFVSNDAPEDTGTLELLNALTKDPGFGTRCMEGNPIPDTPCQAGEEEWTTAP
  VPQTIMDLFQNGNWTMQNPSPACQCSSDKIKKMLPVCPPGAGGLPPPQRKQNTADILQDL
  TGRNISDYLVKTYVQIIAKSLKNKIWVNEFRYGGFSLGVSNTQALPPSQEVNDAIKQMKK
  HLKLAKDSSADRFLNSLGRFMTGLDTKNNVKVWFNNKGWHAISSFLNVINNAILRANLQK
  GENPSHYGITAFNHPLNLTKQQLSEVALMTTSVDVLVSICVIFAMSFVPASFVVFLIQER
  VSKAKHLQFISGVKPVIYWLSNFVWDMCNYVVPATLVIIIFICFQQKSYVSSTNLPVLAL
  LLLLYGWSITPLMYPASFVFKIPSTAYVVLTSVNLFIGINGSVATFVLELFTDNKLNNIN
  DILKSVFLIFPHFCLGRGLIDMVKNQAMADALERFGENRFVSPLSWDLVGRNLFAMAVEG
  VVFFLITVLIQYRFFIRPRPVNAKLSPLNDEDEDVRRERQRILDGGGQNDILEIKELTKI
  YRRKRKPAVDRICVGIPPGECFGLLGVNGAGKSSTFKMLTGDTTVTRGDAFLNKNSILSN
  IHEVHQNMGYCPQFDAITELLTGREHVEFFALLRGVPEKEVGKVGEWAIRKLGLVKYGEK
  YAGNYSGGNKRKLSTAMALIGGPPVVFLDEPTTGMDPKARRFLWNCALSVVKEGRSVVLT
  SHSMEECEALCTRMAIMVNGRFRCLGSVQHLKNRFGDGYTIVVRIAGSNPDLKPVQDFFG
  LAFPGSVLKEKHRNMLQYQLPSSLSSLARIFSILSQSKKRLHIEDYSVSQTTLDQVFVNF
  AKDQSDDDHLKDLSLHKNQTVVDVAVLTSFLQDEKVKESYV
• Function: Involved in the efflux of intracellular cholesterol and phospholipids and their transfer to apoliproteins to form nascent high density lipoproteins/HDLs. cAMP-dependent and sulfonylurea-sensitive anion transporter.
• KEGG Pathway:
  ABC transporters (hsa02010)
  Fat digestion and absorption (hsa04975)
• Reactome Pathway:
  PPARA activates gene expression (R-HSA-1989781)
  HDL-mediated lipid transport (R-HSA-194223)

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Probucol	DMVZQ2M	Coronary artery disease	BA80	Approved	[1]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
RG-7273	DMXMQAT	Lipid metabolism disorder	5C52.Z	Discontinued in Phase 1	[2]

1 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
RG7232	DMSTL12	Dyslipidemia	5C80-5C81	Investigative	[3]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Coronary artery disease	BA80-BA8Z	Peripheral blood	4.88E-01	-0.1	-0.33

The Drug Transporter (DTP) Role of This DTT

• DTT DTP Name: ATP-binding cassette sub-family A member 1 (ABCA1) DTP Info
• Gene Name: ABCA1

1 Approved Drug(s) Transported by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
FENOFIBRIC ACID	DMGO2MC	Cardiovascular disease	BA00-BE2Z	Approved	[4]

1 Investigative Drug(s) Transported by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cholesterol	DMR3J6S	Discovery agent	N.A.	Investigative	[5]

References

• [1] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [2] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 756).
• [3] Analysis of "On/Off" Kinetics of a CETP Inhibitor Using a Mechanistic Model of Lipoprotein Metabolism and Kinetics. CPT Pharmacometrics Syst Pharmacol. 2015 Aug;4(8):465-73.
• [4] Fenofibric acid, an active form of fenofibrate, increases apolipoprotein A-I-mediated high-density lipoprotein biogenesis by enhancing transcription of ATP-binding cassette transporter A1 gene in a liver X receptor-dependent manner. Arterioscler Thromb Vasc Biol. 2005 Jun;25(6):1193-7.
• [5] ABCA1 redistributes membrane cholesterol independent of apolipoprotein interactions. J Lipid Res. 2003 Jul;44(7):1373-80.