Reviewed, UniProtKB/Swiss-Prot O95255 (MRP6_HUMAN)

Names and origin

Protein names

Recommended name:
    Multidrug resistance-associated protein 6
Alternative name(s):
    ATP-binding cassette sub-family C member 6
    Anthracycline resistance-associated protein
    Multi-specific organic anion transporter E
      Short name=MOAT-E

Gene names

Name:	ABCC6
Synonyms:	ARA, MRP6

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	1503 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	May participate directly in the active transport of drugs into subcellular organelles or influence drug distribution indirectly. Transports glutathione conjugates as Leukotriene-c4 (LTC4) and N-ethylmaleimide S-glutathione (NEM-GS).
Subcellular location	Membrane; Multi-pass membrane proteinBy similarity.
Tissue specificity	Expressed in kidney and liver. Very low expression in other tissues.
Involvement in disease	Defects in ABCC6 are the cause of pseudoxanthoma elasticum (PXE) [MIM:264800]. PXE is a disorder characterized by calcification of elastic fibers in skin, arteries and retina that results in dermal lesions with associated laxity and loss of elasticity, arterial insufficiency and retinal hemorrhages leading to macular degeneration. PXE is caused in the overwhelming majority of cases by homozygous or compound heterozygous mutations in the ABCC6 gene (autosomal recessive PXE). Individuals carrying heterozygous mutations express limited manifestations of the pseudoxanthoma elasticum phenotype (autosomal dominant PXE).
Sequence similarities	Belongs to the ABC transporter family. Conjugate transporter (TC 3.A.1.208) subfamily. [View classification] Contains 2 ABC transmembrane type-1 domains. Contains 2 ABC transporter domains.
Sequence caution	The sequence AAC15785.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Biological process	Sensory transduction Transport Vision
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Repeat Transmembrane
Ligand	ATP-binding Nucleotide-binding
PTM	Glycoprotein Phosphoprotein
Gene Ontology (GO)
Biological process	response to drug Traceable author statement. Source: ProtInc transport Traceable author statement. Source: ProtInc visual perception Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	integral to membrane Inferred from electronic annotation. Source: InterPro plasma membrane Ref.10 Traceable author statement. Source: ProtInc
Molecular function	ATP binding Traceable author statement. Source: ProtInc ATPase activity, coupled to transmembrane movement of substances Traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1503	1503	Multidrug resistance-associated protein 6		PRO_0000093366
Regions
	Topological domain	1 – 31	31	Extracellular By similarity
	Transmembrane	32 – 52	21	1 By similarity
	Topological domain	53 – 72	20	Cytoplasmic By similarity
	Transmembrane	73 – 93	21	2 By similarity
	Topological domain	94 – 98	5	Extracellular By similarity
	Transmembrane	99 – 119	21	3 By similarity
	Topological domain	120 – 131	12	Cytoplasmic By similarity
	Transmembrane	132 – 149	18	4 By similarity
	Topological domain	150 – 167	18	Extracellular By similarity
	Transmembrane	168 – 188	21	5 By similarity
	Topological domain	189 – 302	114	Cytoplasmic By similarity
	Transmembrane	303 – 323	21	6 By similarity
	Topological domain	324 – 349	26	Extracellular By similarity
	Transmembrane	350 – 370	21	7 By similarity
	Topological domain	371 – 426	56	Cytoplasmic By similarity
	Transmembrane	427 – 447	21	8 By similarity
	Topological domain	448 – 450	3	Extracellular By similarity
	Transmembrane	451 – 471	21	9 By similarity
	Topological domain	472 – 533	62	Cytoplasmic By similarity
	Transmembrane	534 – 554	21	10 By similarity
	Topological domain	555 – 575	21	Extracellular By similarity
	Transmembrane	576 – 596	21	11 By similarity
	Topological domain	597 – 939	343	Cytoplasmic By similarity
	Transmembrane	940 – 960	21	12 By similarity
	Topological domain	961 – 997	37	Extracellular By similarity
	Transmembrane	998 – 1018	21	13 By similarity
	Topological domain	1019 – 1061	43	Cytoplasmic By similarity
	Transmembrane	1062 – 1082	21	14 By similarity
	Topological domain	1083	1	Extracellular By similarity
	Transmembrane	1084 – 1104	21	15 By similarity
	Topological domain	1105 – 1175	71	Cytoplasmic By similarity
	Transmembrane	1176 – 1196	21	16 By similarity
	Topological domain	1197 – 1198	2	Extracellular By similarity
	Transmembrane	1199 – 1219	21	17 By similarity
	Topological domain	1220 – 1503	284	Cytoplasmic By similarity
	Domain	311 – 593	283	ABC transmembrane type-1 1
	Domain	629 – 853	225	ABC transporter 1
	Domain	947 – 1228	282	ABC transmembrane type-1 2
	Domain	1265 – 1499	235	ABC transporter 2
	Nucleotide binding	663 – 670	8	ATP 1 Potential
	Nucleotide binding	1299 – 1306	8	ATP 2 Potential
Amino acid modifications
	Modified residue	244	1	Phosphoserine By similarity
	Modified residue	902	1	Phosphoserine
	Glycosylation	15	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	60 – 62	3	Missing in PXE; autosomal recessive.		VAR_013363
	Natural variant	61	1	G → D		VAR_013364
	Natural variant	64	1	W → R		VAR_013365
	Natural variant	207	1	G → R		VAR_013366
	Natural variant	265	1	R → G		VAR_013367
	Natural variant	281	1	K → E: dbSNP rs4780606.		VAR_013368
	Natural variant	319	1	I → V		VAR_013369
	Natural variant	364	1	T → R in PXE; autosomal recessive.		VAR_013370
	Natural variant	411	1	N → K in PXE; autosomal dominant.		VAR_013371
	Natural variant	455	1	A → P in PXE; autosomal dominant.		VAR_013372
	Natural variant	497	1	N → K		VAR_013373
	Natural variant	518	1	R → Q in PXE.		VAR_013374
	Natural variant	568	1	F → S in PXE; autosomal dominant.		VAR_013375
	Natural variant	614	1	V → A: dbSNP rs12931472.		VAR_011490
	Natural variant	632	1	H → Q: dbSNP rs8058694.		VAR_013376
	Natural variant	673	1	L → P in PXE; autosomal dominant.		VAR_013377
	Natural variant	765	1	R → Q in PXE; autosomal dominant.		VAR_013378
	Natural variant	953	1	L → H		VAR_013379
	Natural variant	1114	1	R → P in PXE; autosomal recessive.		VAR_011491
	Natural variant	1121	1	S → W in PXE; autosomal dominant.		VAR_013380
	Natural variant	1138	1	R → P in PXE; autosomal dominant.		VAR_013381
	Natural variant	1138	1	R → Q in PXE; autosomal recessive.		VAR_011492
	Natural variant	1138	1	R → W in PXE; autosomal recessive.		VAR_011493
	Natural variant	1203	1	G → D in PXE; autosomal dominant.		VAR_013382
	Natural variant	1241	1	W → C		VAR_013383
	Natural variant	1268	1	R → Q Associated with lower plasma triglycerides and higher plasma HDL cholesterol. dbSNP rs2238472.		VAR_011494
	Natural variant	1298	1	V → F in PXE; autosomal dominant; abolishes LTC4 and NEM-GS transport.		VAR_013384
	Natural variant	1301	1	T → I in PXE; autosomal dominant.		VAR_013385
	Natural variant	1302	1	G → R in PXE; autosomal dominant; abolishes LTC4 and NEM-GS transport.		VAR_013386
	Natural variant	1303	1	A → P in PXE; autosomal dominant.		VAR_013387
	Natural variant	1314	1	R → Q in PXE; autosomal dominant.		VAR_013388
	Natural variant	1314	1	R → W in PXE; autosomal recessive.		VAR_011495
	Natural variant	1321	1	G → S in PXE; autosomal dominant; abolishes LTC4 and NEM-GS transport.		VAR_013389
	Natural variant	1339	1	R → C in PXE; autosomal recessive.		VAR_013390
	Natural variant	1347	1	Q → H in PXE; autosomal dominant.		VAR_013391
	Natural variant	1354	1	G → R in PXE; autosomal recessive.		VAR_013392
	Natural variant	1361	1	D → N in PXE; autosomal dominant.		VAR_013393
	Natural variant	1424	1	I → T in PXE; autosomal dominant.		VAR_013394
Experimental info
	Sequence conflict	74 – 115	42	Missing Ref.2
	Sequence conflict	377	1	L → P in AAD51293. Ref.3
	Sequence conflict	1274	1	Y → C in AAD51293. Ref.3
	Sequence conflict	1455	1	L → P in AAD51293. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	O95255-1 [UniParc]. Last modified May 1, 1999. Version 1. Checksum: BB71B0A9C46163CC