ABCA1

Protein identityUniProt · HPA

UniProt accession

O95477

Gene

ABCA1

Ensembl

ENSG00000165029

Chromosome

9

Canonical length

2261 aa

Protein class

Disease related genes, Enzymes, FDA approved drug targets, Human disease related genes, Metabolic proteins, Plasma proteins, Predicted intracellular proteins, Predicted membrane proteins, Transporters

Subcellular location

Golgi apparatus,Plasma membrane

OverviewNCBI Gene

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. With cholesterol as its substrate, this protein functions as a cholesteral efflux pump in the cellular lipid removal pathway. Mutations in both alleles of this gene cause Tangier disease and familial high-density lipoprotein (HDL) deficiency. [provided by RefSeq, Sep 2019]

Canonical amino-acid sequenceUniProt

2261 residues, UniProt reviewed canonical sequence.

>O95477|ABCA1
     1  MACWPQLRLL LWKNLTFRRR QTCQLLLEVA WPLFIFLILI SVRLSYPPYE QHECHFPNKA
    61  MPSAGTLPWV QGIICNANNP CFRYPTPGEA PGVVGNFNKS IVARLFSDAR RLLLYSQKDT
   121  SMKDMRKVLR TLQQIKKSSS NLKLQDFLVD NETFSGFLYH NLSLPKSTVD KMLRADVILH
   181  KVFLQGYQLH LTSLCNGSKS EEMIQLGDQE VSELCGLPRE KLAAAERVLR SNMDILKPIL
   241  RTLNSTSPFP SKELAEATKT LLHSLGTLAQ ELFSMRSWSD MRQEVMFLTN VNSSSSSTQI
   301  YQAVSRIVCG HPEGGGLKIK SLNWYEDNNY KALFGGNGTE EDAETFYDNS TTPYCNDLMK
   361  NLESSPLSRI IWKALKPLLV GKILYTPDTP ATRQVMAEVN KTFQELAVFH DLEGMWEELS
   421  PKIWTFMENS QEMDLVRMLL DSRDNDHFWE QQLDGLDWTA QDIVAFLAKH PEDVQSSNGS
   481  VYTWREAFNE TNQAIRTISR FMECVNLNKL EPIATEVWLI NKSMELLDER KFWAGIVFTG
   541  ITPGSIELPH HVKYKIRMDI DNVERTNKIK DGYWDPGPRA DPFEDMRYVW GGFAYLQDVV
   601  EQAIIRVLTG TEKKTGVYMQ QMPYPCYVDD IFLRVMSRSM PLFMTLAWIY SVAVIIKGIV
   661  YEKEARLKET MRIMGLDNSI LWFSWFISSL IPLLVSAGLL VVILKLGNLL PYSDPSVVFV
   721  FLSVFAVVTI LQCFLISTLF SRANLAAACG GIIYFTLYLP YVLCVAWQDY VGFTLKIFAS
   781  LLSPVAFGFG CEYFALFEEQ GIGVQWDNLF ESPVEEDGFN LTTSVSMMLF DTFLYGVMTW
   841  YIEAVFPGQY GIPRPWYFPC TKSYWFGEES DEKSHPGSNQ KRISEICMEE EPTHLKLGVS
   901  IQNLVKVYRD GMKVAVDGLA LNFYEGQITS FLGHNGAGKT TTMSILTGLF PPTSGTAYIL
   961  GKDIRSEMST IRQNLGVCPQ HNVLFDMLTV EEHIWFYARL KGLSEKHVKA EMEQMALDVG
  1021  LPSSKLKSKT SQLSGGMQRK LSVALAFVGG SKVVILDEPT AGVDPYSRRG IWELLLKYRQ
  1081  GRTIILSTHH MDEADVLGDR IAIISHGKLC CVGSSLFLKN QLGTGYYLTL VKKDVESSLS
  1141  SCRNSSSTVS YLKKEDSVSQ SSSDAGLGSD HESDTLTIDV SAISNLIRKH VSEARLVEDI
  1201  GHELTYVLPY EAAKEGAFVE LFHEIDDRLS DLGISSYGIS ETTLEEIFLK VAEESGVDAE
  1261  TSDGTLPARR NRRAFGDKQS CLRPFTEDDA ADPNDSDIDP ESRETDLLSG MDGKGSYQVK
  1321  GWKLTQQQFV ALLWKRLLIA RRSRKGFFAQ IVLPAVFVCI ALVFSLIVPP FGKYPSLELQ
  1381  PWMYNEQYTF VSNDAPEDTG TLELLNALTK DPGFGTRCME GNPIPDTPCQ AGEEEWTTAP
  1441  VPQTIMDLFQ NGNWTMQNPS PACQCSSDKI KKMLPVCPPG AGGLPPPQRK QNTADILQDL
  1501  TGRNISDYLV KTYVQIIAKS LKNKIWVNEF RYGGFSLGVS NTQALPPSQE VNDAIKQMKK
  1561  HLKLAKDSSA DRFLNSLGRF MTGLDTKNNV KVWFNNKGWH AISSFLNVIN NAILRANLQK
  1621  GENPSHYGIT AFNHPLNLTK QQLSEVALMT TSVDVLVSIC VIFAMSFVPA SFVVFLIQER
  1681  VSKAKHLQFI SGVKPVIYWL SNFVWDMCNY VVPATLVIII FICFQQKSYV SSTNLPVLAL
  1741  LLLLYGWSIT PLMYPASFVF KIPSTAYVVL TSVNLFIGIN GSVATFVLEL FTDNKLNNIN
  1801  DILKSVFLIF PHFCLGRGLI DMVKNQAMAD ALERFGENRF VSPLSWDLVG RNLFAMAVEG
  1861  VVFFLITVLI QYRFFIRPRP VNAKLSPLND EDEDVRRERQ RILDGGGQND ILEIKELTKI
  1921  YRRKRKPAVD RICVGIPPGE CFGLLGVNGA GKSSTFKMLT GDTTVTRGDA FLNKNSILSN
  1981  IHEVHQNMGY CPQFDAITEL LTGREHVEFF ALLRGVPEKE VGKVGEWAIR KLGLVKYGEK
  2041  YAGNYSGGNK RKLSTAMALI GGPPVVFLDE PTTGMDPKAR RFLWNCALSV VKEGRSVVLT
  2101  SHSMEECEAL CTRMAIMVNG RFRCLGSVQH LKNRFGDGYT IVVRIAGSNP DLKPVQDFFG
  2161  LAFPGSVLKE KHRNMLQYQL PSSLSSLARI FSILSQSKKR LHIEDYSVSQ TTLDQVFVNF
  2221  AKDQSDDDHL KDLSLHKNQT VVDVAVLTSF LQDEKVKESY V

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ABCA1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

15

Mean surface accessibility (rSASA)

0.28

Highest tissue expression

36 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ABCA1.

Disease | AllUniProt

Conditions ABCA1 is implicated in, by any mechanism.

• Tangier disease (TGD) MIM:205400
• Hypoalphalipoproteinemia, primary, 1 (FHA1) MIM:604091

Disease | GeneticClinVar

77 pathogenic / likely-pathogenic of 1,934 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Tangier disease
• Hypoalphalipoproteinemia, primary, 1
• Cardiovascular phenotype
• ABCA1-related disorder
• Tangier disease, variant

ReferencesPubMed · IEDB

Publications for ABCA1 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.49

gnomAD pLI

0

gnomAD missense Z

1.75

DepMap mean gene effect

0.01

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• adenylate cyclase-activating G protein-coupled receptor signaling pathway
• cellular response to cholesterol
• cellular response to cytokine stimulus
• cellular response to lipopolysaccharide
• cellular response to low-density lipoprotein particle stimulus
• cellular response to retinoic acid
• cellular response to xenobiotic stimulus
• cholesterol efflux
• cholesterol homeostasis
• cholesterol metabolic process
• endosomal transport
• export across plasma membrane
• G protein-coupled receptor signaling pathway
• high-density lipoprotein particle assembly
• intracellular cholesterol transport
• lipoprotein biosynthetic process
• lysosome organization
• negative regulation of cholesterol storage
• negative regulation of macrophage derived foam cell differentiation
• peptide secretion
• phagocytosis, engulfment
• phospholipid efflux
• phospholipid homeostasis
• phospholipid translocation
• platelet dense granule organization
• positive regulation of cholesterol efflux
• positive regulation of high-density lipoprotein particle assembly
• protein secretion
• protein transmembrane transport
• regulation of Cdc42 protein signal transduction
• regulation of high-density lipoprotein particle assembly
• response to laminar fluid shear stress
• response to vitamin B3
• reverse cholesterol transport
• signal release

Molecular functions

• ABC-type transporter activity
• apolipoprotein A-I binding
• apolipoprotein A-I receptor activity
• apolipoprotein binding
• ATP binding
• ATP hydrolysis activity
• ATPase binding
• ATPase-coupled transmembrane transporter activity
• cholesterol binding
• cholesterol transfer activity
• floppase activity
• high-density lipoprotein particle binding
• phosphatidylcholine binding
• phosphatidylcholine floppase activity
• phosphatidylserine floppase activity
• phospholipid transporter activity
• protein transmembrane transporter activity
• signaling receptor binding
• small GTPase binding
• syntaxin binding
• sphingolipid floppase activity

Cellular components

• basolateral plasma membrane
• endocytic vesicle
• endoplasmic reticulum membrane
• endosome
• external side of plasma membrane
• Golgi apparatus
• intracellular vesicle
• membrane raft
• perinuclear region of cytoplasm
• phagocytic vesicle
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• ABC transporter-like, ATP-binding domain
• AAA+ ATPase domain
• ABC-2 type transporter, transmembrane domain
• ABC transporter-like, conserved site
• ABC transporter A
• P-loop containing nucleoside triphosphate hydrolase
• ABCA1-4-like, C-terminal R2 regulatory domain
• ABC transporter
• ABC-2 family transporter protein
• ABCA1-like, C-terminal R1 regulatory domain

KeywordsUniProt

• Atherosclerosis
• ATP-binding
• Cell membrane
• Cholesterol metabolism
• Disulfide bond
• Endosome
• Glycoprotein
• Lipid metabolism
• Lipoprotein
• Membrane
• Nucleotide-binding
• Palmitate
• Phosphoprotein
• Repeat
• Steroid metabolism
• Sterol metabolism
• Translocase
• Transmembrane
• Transmembrane helix
• Transport

InteractionsUniProt · HPA

Protein binding partners of ABCA1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• ABCA12
• ABCA8
• MEGF10
• NR1H2
• APOA1
• SNTB2