Reviewed,
UniProtKB/Swiss-Prot O95255 (MRP6_HUMAN)
Last modified
November 25, 2008.
Version 98.
History...
Clusters with 100%,
90%,
50% identity |
Documents (5) |
Third-party data |
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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 |
| ||||
| 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 transportTraceable author statement. Source: ProtInc visual perceptionInferred from electronic annotation. Source: UniProtKB-KW |
| Cellular component | integral to membrane Inferred from electronic annotation. Source: InterPro plasma membrane Ref.10Traceable author statement. Source: ProtInc |
| Molecular function | ATP binding Traceable author statement. Source: ProtInc ATPase activity, coupled to transmembrane movement of substancesTraceable 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 | ||||||

Clusters with