Reviewed, UniProtKB/Swiss-Prot O95477 (ABCA1_HUMAN)

Names and origin

Protein names

Recommended name:
    ATP-binding cassette sub-family A member 1
Alternative name(s):
    ATP-binding cassette transporter 1
      Short name=ATP-binding cassette 1
      Short name=ABC-1
    Cholesterol efflux regulatory protein

Gene names

Name:	ABCA1
Synonyms:	ABC1, CERP

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	2261 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	cAMP-dependent and sulfonylurea-sensitive anion transporter. Key gatekeeper influencing intracellular cholesterol transport.
Subunit structure	Interacts with MEGF10.
Subcellular location	Membrane; Multi-pass membrane proteinPotential.
Tissue specificity	Widely expressed, but most abundant in macrophages.
Induction	By bacterial lipopolysaccharides (LPS). LPS regulates expression through a liver X receptor (LXR) -independent mechanism. Repressed by ZNF202.
Domain	Multifunctional polypeptide with two homologous halves, each containing an hydrophobic membrane-anchoring domain and an ATP binding cassette (ABC) domain.
Post-translational modification	Phosphorylation on Ser-2054 regulates phospholipid efflux.
Involvement in disease	Defects in ABCA1 are a cause of high density lipoprotein deficiency type 1 (HDLD1) [MIM:205400]; also known as analphalipoproteinemia or Tangier disease (TGD). HDLD1 is a recessive disorder characterized by absence of high density lipoprotein (HDL) cholesterol from plasma, accumulation of cholesteryl esters, premature coronary artery disease (CAD), hepatosplenomegaly, recurrent peripheral neuropathy and progressive muscle wasting and weakness. Defects in ABCA1 are a cause of high density lipoprotein deficiency type 2 (HDLD2) [MIM:604091]; also known as familial hypoalphalipoproteinemia (FHA). HDLD2 is inherited as autosomal dominant trait. It is characterized by moderately low HDL cholesterol, predilection toward premature coronary artery disease (CAD) and a reduction in cellular cholesterol efflux.
Sequence similarities	Belongs to the ABC transporter family. ABCA subfamily. Contains 2 ABC transporter domains.

Ontologies

Keywords
Biological process	Cholesterol metabolism Lipid metabolism Steroid metabolism Transport
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Disease	Atherosclerosis Disease mutation
Domain	Repeat Transmembrane
Ligand	ATP-binding Nucleotide-binding
PTM	Glycoprotein Phosphoprotein
Gene Ontology (GO)
Biological process	Cdc42 protein signal transduction Inferred from mutant phenotype. Source: UniProtKB G-protein coupled receptor protein signaling pathway Inferred from mutant phenotype. Source: UniProtKB cholesterol efflux Ref.13 Inferred from direct assay. Source: UniProtKB cholesterol homeostasis Ref.13 Inferred from direct assay. Source: UniProtKB cholesterol metabolic process Inferred from direct assay. Source: UniProtKB endosome transport Inferred from direct assay. Source: UniProtKB interleukin-1 beta secretion Inferred from mutant phenotype. Source: UniProtKB intracellular cholesterol transport Ref.13 Inferred from mutant phenotype. Source: UniProtKB lysosome organization and biogenesis Inferred from direct assay. Source: UniProtKB phospholipid efflux Ref.13 Inferred from direct assay. Source: UniProtKB phospholipid homeostasis Inferred from mutant phenotype. Source: UniProtKB platelet dense granule organization and biogenesis Inferred from mutant phenotype. Source: UniProtKB positive regulation of cAMP biosynthetic process Inferred from mutant phenotype. Source: UniProtKB reverse cholesterol transport Ref.13 Inferred from mutant phenotype. Source: UniProtKB
Cellular component	integral to plasma membrane Inferred from direct assay. Source: UniProtKB membrane fraction Inferred from direct assay. Source: UniProtKB membrane raft Inferred from direct assay. Source: UniProtKB phagocytic vesicle Inferred from direct assay. Source: UniProtKB
Molecular function	ATP binding Inferred from direct assay. Source: UniProtKB anion transmembrane transporter activity Inferred from sequence or structural similarity. Source: UniProtKB apolipoprotein A-I receptor activity Inferred from direct assay. Source: UniProtKB cholesterol binding Inferred by curator. Source: UniProtKB cholesterol transporter activity Inferred from direct assay. Source: UniProtKB phospholipid binding Inferred by curator. Source: UniProtKB phospholipid transporter activity Inferred from direct assay. Source: UniProtKB small GTPase binding Inferred from physical interaction. Source: UniProtKB syntaxin-13 binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ARHGEF11	O15085	1	EBI-784112,EBI-311099
ARHGEF12	Q9NZN5	1	EBI-784112,EBI-821440
DLG2	Q15700	1	EBI-784112,EBI-80426
DLG3	Q92796	1	EBI-784112,EBI-80440
Lin7a	Q9Z250	1	EBI-784112,EBI-704603	From a different organism.
LIN7B	Q9HAP6	1	EBI-784112,EBI-821335
Lin7c	O88952	1	EBI-784112,EBI-821316	From a different organism.
MPDZ	O75970	1	EBI-784112,EBI-821405
SNTA1	Q13424	1	EBI-784112,EBI-717191
SNTB1	Q13884	2	EBI-784112,EBI-295843

Sequence annotation (Features)

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	Feature key	Position(s)	Length	Description	Graphical view
Molecule processing
	Chain	1 – 2261	2261	ATP-binding cassette sub-family A member 1
Regions
	Transmembrane	22 – 42	21	Potential
	Transmembrane	640 – 660	21	Potential
	Transmembrane	683 – 703	21	Potential
	Transmembrane	716 – 736	21	Potential
	Transmembrane	745 – 765	21	Potential
	Transmembrane	777 – 797	21	Potential
	Transmembrane	827 – 847	21	Potential
	Transmembrane	1041 – 1057	17	Potential
	Transmembrane	1351 – 1371	21	Potential
	Transmembrane	1657 – 1677	21	Potential
	Transmembrane	1703 – 1723	21	Potential
	Transmembrane	1735 – 1755	21	Potential
	Transmembrane	1768 – 1788	21	Potential
	Transmembrane	1802 – 1822	21	Potential
	Transmembrane	1852 – 1872	21	Potential
	Domain	899 – 1131	233	ABC transporter 1
	Domain	1912 – 2144	233	ABC transporter 2
	Nucleotide binding	933 – 940	8	ATP 1 Potential
	Nucleotide binding	1946 – 1953	8	ATP 2 Potential
Amino acid modifications
	Modified residue	1042	1	Phosphoserine; by PKA
	Modified residue	1141	1	Phosphoserine By similarity
	Modified residue	1147	1	Phosphoserine By similarity
	Modified residue	2054	1	Phosphoserine; by PKA
	Glycosylation	14	1	N-linked (GlcNAc...) Potential
	Glycosylation	98	1	N-linked (GlcNAc...) Potential
	Glycosylation	151	1	N-linked (GlcNAc...) Potential
	Glycosylation	161	1	N-linked (GlcNAc...) Potential
	Glycosylation	196	1	N-linked (GlcNAc...) Potential
	Glycosylation	244	1	N-linked (GlcNAc...) Potential
	Glycosylation	292	1	N-linked (GlcNAc...) Potential
	Glycosylation	337	1	N-linked (GlcNAc...) Potential
	Glycosylation	349	1	N-linked (GlcNAc...) Potential
	Glycosylation	400	1	N-linked (GlcNAc...) Potential
	Glycosylation	478	1	N-linked (GlcNAc...) Potential
	Glycosylation	489	1	N-linked (GlcNAc...) Potential
	Glycosylation	521	1	N-linked (GlcNAc...) Potential
	Glycosylation	820	1	N-linked (GlcNAc...) Potential
	Glycosylation	1144	1	N-linked (GlcNAc...) Potential
	Glycosylation	1294	1	N-linked (GlcNAc...) Potential
	Glycosylation	1453	1	N-linked (GlcNAc...) Potential
	Glycosylation	1504	1	N-linked (GlcNAc...) Potential
	Glycosylation	1637	1	N-linked (GlcNAc...) Potential
	Glycosylation	2044	1	N-linked (GlcNAc...) Potential
	Glycosylation	2238	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	85	1	P → L in HDLD2; Alabama.
	Natural variant	210	1	E → D in a colorectal cancer sample; somatic mutation.
	Natural variant	219	1	R → K Common polymorphism; associated with a decreased severity of CAD. dbSNP rs2230806.
	Natural variant	230	1	R → C in HDLD2. dbSNP rs9282541.
	Natural variant	255	1	A → T in HDLD1; deficient cellular cholesterol efflux.
	Natural variant	399	1	V → A: dbSNP rs9282543.
	Natural variant	587	1	R → W in HDLD1. dbSNP rs2853574.
	Natural variant	590	1	W → S in HDLD1.
	Natural variant	597	1	Q → R in HDLD1. dbSNP rs2853578.
	Natural variant	693	1	Missing in HDLD2.
	Natural variant	771	1	V → M: dbSNP rs2066718.
	Natural variant	774	1	T → P: dbSNP rs35819696.
	Natural variant	776	1	K → N
	Natural variant	825	1	V → I Common polymorphism. dbSNP rs2066715.
	Natural variant	883	1	I → M Common polymorphism. dbSNP rs4149313.
	Natural variant	917	1	D → Y in a colorectal cancer sample; somatic mutation.
	Natural variant	929	1	T → I in HDLD1.
	Natural variant	935	1	N → H in HDLD1. dbSNP rs28937314.
	Natural variant	935	1	N → S in HDLD1. dbSNP rs28937313.
	Natural variant	937	1	A → V in HDLD1.
	Natural variant	1046	1	A → D in HDLD1.
	Natural variant	1054	1	V → I: dbSNP rs13306072.
	Natural variant	1091	1	M → T in HDLD2.
	Natural variant	1099	1	D → Y in HDLD2. dbSNP rs28933692.
	Natural variant	1172	1	E → D: dbSNP rs33918808.
	Natural variant	1181	1	S → F
	Natural variant	1289	1	D → N in HDLD1.
	Natural variant	1407	1	A → T in a colorectal cancer sample; somatic mutation.
	Natural variant	1477	1	C → R in HDLD1.
	Natural variant	1506	1	S → L in HDLD1.
	Natural variant	1517	1	I → R in HDLD1.
	Natural variant	1555	1	T → I: dbSNP rs1997618.
	Natural variant	1587	1	R → K Common polymorphism. dbSNP rs2230808.
	Natural variant	1611	1	N → D Associated with atherosclerosis; deficient cellular cholesterol efflux.