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E63A7D59DCE5B9ED
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FUNCTION ATP-dependent transporter that catalyzes the transport of a broad-spectrum of porphyrins from the cytoplasm to the extracellular space through the plasma membrane or into the vesicle lumen (PubMed:17661442, PubMed:23792964, PubMed:27507172, PubMed:33007128). May also function as an ATP-dependent importer of porphyrins from the cytoplasm into the mitochondria, in turn may participate in the de novo heme biosynthesis regulation and in the coordination of heme and iron homeostasis during phenylhydrazine stress (PubMed:10837493, PubMed:17006453, PubMed:23792964, PubMed:33007128). May also play a key role in the early steps of melanogenesis producing PMEL amyloid fibrils (PubMed:29940187). In vitro, it confers to cells a resistance to toxic metal such as arsenic and cadmium and against chemotherapeutics agent such as 5-fluorouracil, SN-38 and vincristin (PubMed:21266531, PubMed:25202056, PubMed:31053883). In addition may play a role in the transition metal homeostasis (By similarity).CATALYTIC ACTIVITY heme b(in) + ATP + H2O = heme b(out) + ADP + phosphate + H(+)CATALYTIC ACTIVITY coproporphyrin III(in) + ATP + H2O = coproporphyrin III(out) + ADP + phosphate + H(+)CATALYTIC ACTIVITY pheophorbide a(in) + ATP + H2O = pheophorbide a(out) + ADP + phosphate + H(+)CATALYTIC ACTIVITY coproporphyrinogen III(in) + ATP + H2O = coproporphyrinogen III(out) + ADP + phosphate + H(+)CATALYTIC ACTIVITY protoporphyrin IX(in) + ATP + H2O = protoporphyrin IX(out) + ADP + phosphate + H(+)CATALYTIC ACTIVITY coproporphyrin I(in) + ATP + H2O = coproporphyrin I(out) + ADP + phosphate + H(+)CATALYTIC ACTIVITY uroporphyrin I(in) + ATP + H2O = uroporphyrin I(out) + ADP + phosphate + H(+)CATALYTIC ACTIVITY uroporphyrin III(in) + ATP + H2O = uroporphyrin III(out) + ADP + phosphate + H(+)ACTIVITY REGULATION ATPase activity is inhibited by MgATP with an IC(50) of 1.03 mM and up-regulated by coporphyrin III> hemin > protoporphyrin IX (PubMed:23792964). ATPase activity for hemin is up-regulated by glutathione (PubMed:33007128). The ATPase activity is impaired by increasing copper concentrations (0-300 uM) (PubMed:33007128). The ATPase activity is stimulated in presence of glutathione for increasing copper concentrations (0-300 uM) (PubMed:33007128).BIOPHYSICOCHEMICAL PROPERTIES Homodimer.SUBCELLULAR LOCATION Present in the membrane of mature erythrocytes and in exosomes released from reticulocytes during the final steps of erythroid maturation (PubMed:22655043). Traffics from endoplasmic reticulum to Golgi during its glycans's maturation, therefrom is first targeted to the plasma membrane, and is rapidly internalized through endocytosis to be distributed to the limiting membrane of multivesicular bodies and lysosomes (PubMed:18279659, PubMed:21199866, PubMed:25627919). Localized on the limiting membrane of early melanosomes of pigment cells (PubMed:29940187). Targeted to the endolysosomal compartment (By similarity).ALTERNATIVE PRODUCTS Widely expressed. High expression is detected in the retinal epithelium (PubMed:10837493, PubMed:22226084). Expressed in mature erythrocytes (PubMed:22655043).DEVELOPMENTAL STAGE Highly expressed in fetal liver.INDUCTION Up-regulated by cellular porphyrins (at protein level) (PubMed:17006453, PubMed:22655043, PubMed:23180570). Up-regulated during erythroid differentiation (at protein level) (PubMed:22655043). Induced by sodium arsenite in a dose-dependent manner (PubMed:21266531).DOMAIN Contains two independently folding units, the N-terminal transmembrane domain (residues 1-205) and the ABC-core domain (206-842) are respectively responsible for the lysosomal targeting and the ATPase activity.PTM N-glycosylated.POLYMORPHISM Genetic variations in ABCB6 define the Langereis blood group system (LAN) [MIM:111600]. Individuals with Lan(-) blood group lack the Lan antigen on their red blood cells. These individuals may have anti-Lan antibodies in their serum, which can cause transfusion reactions or hemolytic disease of the fetus or newborn. The Lan(-) blood group is only clinically significant in transfusion settings or during pregnancy; otherwise Lan(-) individuals have no clinical features.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE Defects in ABCB6 may be the cause of a severe porphyria. Affected individuals show higher urinary porphyrin concentrations.SIMILARITY Belongs to the ABC transporter superfamily. ABCB family. Heavy Metal importer (TC 3.A.1.210) subfamily.CAUTION To date, the intracellular localization of ABCB6 is a matter of debate, with conflicting reports suggesting mitochondrial (PubMed:10837493, PubMed:17006453, PubMed:17661442) or endolysosomal localization (PubMed:22655043, PubMed:25627919, PubMed:29940187, PubMed:31053883), therefore questioning the requirement of ABCB6 in the mitochondrial import of porphyrins.SEQUENCE CAUTION Extended N-terminus.SEQUENCE CAUTION Extended N-terminus.SEQUENCE CAUTION Intron retention.SEQUENCE CAUTION Truncated C-terminus.SEQUENCE CAUTION Chimeric cDNA.SEQUENCE CAUTION splicing through aberrant splice sites.ONLINE INFORMATION Database for mutations in ABC proteins
databaseName
UniProt
dbId
49418
description
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recommendedName: fullName evidence="33"ATP-binding cassette sub-family B member 6 alternativeName: fullName evidence="33"ABC-type heme transporter ABCB6 ecNumber evidence="9 10"7.6.2.5 alternativeName: fullName evidence="31"Mitochondrial ABC transporter 3 shortName evidence="31"Mt-ABC transporter 3 alternativeName: P-glycoprotein-related protein alternativeName: Ubiquitously-expressed mammalian ABC half transporter
displayName
UniProt:Q9NP58 ABCB6
identifier
Q9NP58
isSequenceChanged
false
keyword
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3D-structure
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Alternative splicing
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ATP-binding
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Cell membrane
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Disease variant
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Disulfide bond
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Dyskeratosis congenita
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Endoplasmic reticulum
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Endosome
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Glycoprotein
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Golgi apparatus
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Lysosome
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Membrane
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Microphthalmia
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Mitochondrion
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Mitochondrion outer membrane
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Nucleotide-binding
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Proteomics identification
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Reference proteome
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Secreted
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Translocase
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Transmembrane
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Transmembrane helix
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Transport
moleculeType
Protein
schemaClass
ReferenceGeneProduct
secondaryIdentifier
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ABCB6_HUMAN
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O75542
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Q49A66
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Q59GQ5
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Q6ZME6
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Q96ME8
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Q9HAQ6
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Q9HAQ7
sequenceLength
842
stId
uniprot:Q9NP58