UniProt functional annotation for Q9NP58



	UniProt functional annotation for Q9NP58

UniProt code: Q9NP58.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

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:33007128, PubMed:27507172, PubMed:17661442, PubMed:23792964). May also function as an ATP-dependent importer of porphyrins from the cytoplasm into the mitochondria, in turns may participate in the de novo heme biosynthesis regulation and in the coordination of heme and iron homeostasis during phenylhydrazine stress (PubMed:17006453, PubMed:10837493, 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:25202056, PubMed:21266531, PubMed:31053883). In addition may play a role in the transition metal homeostasis (By similarity). {ECO:0000250|UniProtKB:O70595, ECO:0000269|PubMed:10837493, ECO:0000269|PubMed:17006453, ECO:0000269|PubMed:17661442, ECO:0000269|PubMed:21266531, ECO:0000269|PubMed:23792964, ECO:0000269|PubMed:25202056, ECO:0000269|PubMed:27507172, ECO:0000269|PubMed:29940187, ECO:0000269|PubMed:31053883, ECO:0000269|PubMed:33007128}.

Catalytic activity: Reaction=ATP + H2O + heme b(in) = ADP + H(+) + heme b(out) + phosphate; Xref=Rhea:RHEA:19261, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:60344, ChEBI:CHEBI:456216; EC=7.6.2.5; Evidence={ECO:0000269|PubMed:17006453, ECO:0000269|PubMed:17661442, ECO:0000269|PubMed:23792964}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19262; Evidence={ECO:0000269|PubMed:17006453, ECO:0000305|PubMed:17661442};

Catalytic activity: Reaction=ATP + coproporphyrin III(in) + H2O = ADP + coproporphyrin III(out) + H(+) + phosphate; Xref=Rhea:RHEA:66664, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:131725, ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:23792964, ECO:0000269|PubMed:27507172, ECO:0000269|PubMed:33007128}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66665; Evidence={ECO:0000269|PubMed:23792964, ECO:0000269|PubMed:27507172};

Catalytic activity: Reaction=ATP + H2O + pheophorbide a(in) = ADP + H(+) + pheophorbide a(out) + phosphate; Xref=Rhea:RHEA:61360, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:58687, ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:17661442, ECO:0000269|PubMed:23792964}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61361; Evidence={ECO:0000305|PubMed:17661442};

Catalytic activity: Reaction=ATP + coproporphyrinogen III(in) + H2O = ADP + coproporphyrinogen III(out) + H(+) + phosphate; Xref=Rhea:RHEA:66680, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:57309, ChEBI:CHEBI:456216; Evidence={ECO:0000250|UniProtKB:Q9DC29}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66681; Evidence={ECO:0000250|UniProtKB:Q9DC29};

Catalytic activity: Reaction=ATP + H2O + protoporphyrin IX(in) = ADP + H(+) + phosphate + protoporphyrin IX(out); Xref=Rhea:RHEA:61336, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:57306, ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:23792964, ECO:0000269|PubMed:33007128}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61337; Evidence={ECO:0000269|PubMed:23792964};

Catalytic activity: Reaction=ATP + coproporphyrin I(in) + H2O = ADP + coproporphyrin I(out) + H(+) + phosphate; Xref=Rhea:RHEA:66768, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:167478, ChEBI:CHEBI:456216; Evidence={ECO:0000250|UniProtKB:Q9DC29}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66769; Evidence={ECO:0000250|UniProtKB:Q9DC29};

Catalytic activity: Reaction=ATP + H2O + uroporphyrin I(in) = ADP + H(+) + phosphate + uroporphyrin I(out); Xref=Rhea:RHEA:66772, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:167480, ChEBI:CHEBI:456216; Evidence={ECO:0000250|UniProtKB:Q9DC29}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66773; Evidence={ECO:0000250|UniProtKB:Q9DC29};

Catalytic activity: Reaction=ATP + H2O + uroporphyrin III(in) = ADP + H(+) + phosphate + uroporphyrin III(out); Xref=Rhea:RHEA:66776, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:167479, ChEBI:CHEBI:456216; Evidence={ECO:0000250|UniProtKB:Q9DC29}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66777; Evidence={ECO:0000250|UniProtKB:Q9DC29};

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 impairs by increasing copper concentrations (0-300 muM) (PubMed:33007128). The ATPase activity is stimulated in presence of glutathione for increasing copper concentrations (0-300 muM) (PubMed:33007128). {ECO:0000269|PubMed:23792964, ECO:0000269|PubMed:33007128}.

Biophysicochemical properties: Kinetic parameters: KM=0.99 mM for ATP (from purified mitochondrial ABCB6) {ECO:0000269|PubMed:23792964}; KM=0.97 mM for ATP (from liposome-reconstituted purified mitochondrial ABCB6) {ECO:0000269|PubMed:23792964}; KM=11.97 uM for coproporphyrin III (from liposome-reconstituted purified mitochondrial ABCB6) {ECO:0000269|PubMed:23792964}; KM=51 uM for glutathione (in the presence of 10 uM of hemin) {ECO:0000269|PubMed:33007128}; KM=190 nM for hemin (in the presence of 1 mM of glutathione) {ECO:0000269|PubMed:33007128}; KM=600 nM for hematin (in the presence of 1 mM of glutathione) {ECO:0000269|PubMed:33007128}; KM=148 nM for Fe-coproporphyrin III (in the presence of 1 mM of glutathione) {ECO:0000269|PubMed:33007128}; Vmax=492.3 nmol/min/mg enzyme toward ATP (from purified mitochondrial ABCB6) {ECO:0000269|PubMed:23792964}; Vmax=614 nmol/min/mg enzyme toward ATP (from liposome-reconstituted purified mitochondrial ABCB6) {ECO:0000269|PubMed:23792964}; Vmax=29.6 pmol/min/mg enzyme toward coproporphyrin III (from liposome-reconstituted purified mitochondrial ABCB6) {ECO:0000269|PubMed:23792964}; Vmax=5.13 pmol/min/mg enzyme toward verteporfin {ECO:0000269|PubMed:23792964}; Vmax=2.7 pmol/min/mg enzyme toward tomatine {ECO:0000269|PubMed:23792964};

Subunit: Homodimer. {ECO:0000269|PubMed:16791740, ECO:0000269|PubMed:17006453, ECO:0000269|PubMed:23792964, ECO:0000269|PubMed:25627919, ECO:0000269|PubMed:33007128}.

Subcellular location: Cell membrane {ECO:0000269|PubMed:17661442, ECO:0000269|PubMed:22246506, ECO:0000269|PubMed:22655043, ECO:0000269|PubMed:23180570, ECO:0000269|PubMed:27507172}; Multi-pass membrane protein {ECO:0000255}. Mitochondrion outer membrane {ECO:0000269|PubMed:17006453, ECO:0000269|PubMed:17661442}; Multi-pass membrane protein {ECO:0000255}. Endoplasmic reticulum membrane {ECO:0000269|PubMed:18279659, ECO:0000269|PubMed:21199866, ECO:0000269|PubMed:22226084}; Multi-pass membrane protein {ECO:0000255}. Golgi apparatus membrane {ECO:0000269|PubMed:18279659, ECO:0000269|PubMed:21199866, ECO:0000269|PubMed:22226084}; Multi-pass membrane protein {ECO:0000255}. Endosome membrane {ECO:0000269|PubMed:25627919}; Multi-pass membrane protein {ECO:0000255}. Lysosome membrane {ECO:0000269|PubMed:22655043, ECO:0000269|PubMed:25627919, ECO:0000269|PubMed:29940187, ECO:0000269|PubMed:31053883}. Late endosome membrane {ECO:0000250|UniProtKB:O70595}. Early endosome membrane {ECO:0000250|UniProtKB:O70595}. Secreted, extracellular exosome {ECO:0000269|PubMed:22655043}. Mitochondrion {ECO:0000269|PubMed:10837493, ECO:0000269|PubMed:23792964}. Endosome, multivesicular body membrane {ECO:0000269|PubMed:25627919}. Melanosome membrane {ECO:0000269|PubMed:29940187}. Note=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:25627919, PubMed:21199866, PubMed:18279659). Localized on the limiting membrane of early melanosomes of pigment cells (PubMed:29940187). Targeted to the endolysosomal compartment (By similarity). {ECO:0000250|UniProtKB:O70595, ECO:0000269|PubMed:18279659, ECO:0000269|PubMed:21199866, ECO:0000269|PubMed:22655043, ECO:0000269|PubMed:25627919, ECO:0000269|PubMed:29940187}.

Tissue specificity: Widely expressed. High expression is detected in the retinal epithelium (PubMed:10837493, PubMed:22226084). Expressed in mature erythrocytes (PubMed:22655043). {ECO:0000269|PubMed:10837493, ECO:0000269|PubMed:22226084, ECO:0000269|PubMed:22655043}.

Developmental stage: Highly expressed in fetal liver. {ECO:0000269|PubMed:17006453}.

Induction: Up-regulated by cellular porphyrins (at protein level) (PubMed:22655043, PubMed:17006453, PubMed:23180570). Up-regulated during erythroid differentiation (at protein level) (PubMed:22655043). Induced by sodium arsenite in a dose-dependent manner (PubMed:21266531). {ECO:0000269|PubMed:17006453, ECO:0000269|PubMed:21266531, ECO:0000269|PubMed:22655043, ECO:0000269|PubMed:23180570}.

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. {ECO:0000269|PubMed:25627919}.

Ptm: N-glycosylated. {ECO:0000269|PubMed:18279659, ECO:0000269|PubMed:21199866, ECO:0000269|PubMed:22655043, ECO:0000269|PubMed:25627919}.

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. {ECO:0000269|PubMed:22246506}.

Disease: Microphthalmia, isolated, with coloboma, 7 (MCOPCB7) [MIM:614497]: A disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues. Ocular abnormalities like opacities of the cornea and lens, scaring of the retina and choroid, and other abnormalities may also be present. Ocular colobomas are a set of malformations resulting from abnormal morphogenesis of the optic cup and stalk, and the fusion of the fetal fissure (optic fissure). {ECO:0000269|PubMed:22226084}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Dyschromatosis universalis hereditaria 3 (DUH3) [MIM:615402]: An autosomal dominant pigmentary genodermatosis characterized by a mixture of hyperpigmented and hypopigmented macules distributed randomly over the body, that appear in infancy or early childhood. The trunk and extremities are the dominant sites of abnormal pigmentation. Facial lesions can be seen in 50% of affected individuals, but involvement of palms and soles is unusual. Abnormalities of hair and nails have also been reported. Dyschromatosis universalis hereditaria may be associated with abnormalities of dermal connective tissue, nerve tissue, or other systemic complications. {ECO:0000269|PubMed:23519333, ECO:0000269|PubMed:24224009, ECO:0000269|PubMed:24498303, ECO:0000269|PubMed:25288164, ECO:0000269|PubMed:29940187}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Pseudohyperkalemia, familial, 2, due to red cell leak (PSHK2) [MIM:609153]: A dominantly inherited condition characterized by increased serum potassium levels, measured in whole-blood specimens stored at or below room temperature. This condition is not accompanied by clinical symptoms or biological signs except for borderline abnormalities of red cell shape. {ECO:0000269|PubMed:23180570, ECO:0000269|PubMed:24947683}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Note=Defects in ABCB6 may be the cause of a severe porphyria. Affected individuals show higher urinary porphyrin concentrations. {ECO:0000269|PubMed:27507172}.

Similarity: Belongs to the ABC transporter superfamily. ABCB family. Heavy Metal importer (TC 3.A.1.210) subfamily. {ECO:0000305}.

Sequence caution: Sequence=AAG33617.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=AAG33618.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=AAH43423.1; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305}; Sequence=BAD18782.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305}; Sequence=BAD92291.1; Type=Miscellaneous discrepancy; Note=Chimeric cDNA.; Evidence={ECO:0000305};

Sequence caution: [Isoform 2]: Sequence=BAB71347.1; Type=Miscellaneous discrepancy; Note=splicing through aberrant splice sites.; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



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:33007128, PubMed:27507172, PubMed:17661442, PubMed:23792964). May also function as an ATP-dependent importer of porphyrins from the cytoplasm into the mitochondria, in turns may participate in the de novo heme biosynthesis regulation and in the coordination of heme and iron homeostasis during phenylhydrazine stress (PubMed:17006453, PubMed:10837493, 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:25202056, PubMed:21266531, PubMed:31053883). In addition may play a role in the transition metal homeostasis (By similarity). {ECO:0000250\|UniProtKB:O70595, ECO:0000269\|PubMed:10837493, ECO:0000269\|PubMed:17006453, ECO:0000269\|PubMed:17661442, ECO:0000269\|PubMed:21266531, ECO:0000269\|PubMed:23792964, ECO:0000269\|PubMed:25202056, ECO:0000269\|PubMed:27507172, ECO:0000269\|PubMed:29940187, ECO:0000269\|PubMed:31053883, ECO:0000269\|PubMed:33007128}.


Catalytic activity:		Reaction=ATP + H2O + heme b(in) = ADP + H(+) + heme b(out) + phosphate; Xref=Rhea:RHEA:19261, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:60344, ChEBI:CHEBI:456216; EC=7.6.2.5; Evidence={ECO:0000269\|PubMed:17006453, ECO:0000269\|PubMed:17661442, ECO:0000269\|PubMed:23792964}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19262; Evidence={ECO:0000269\|PubMed:17006453, ECO:0000305\|PubMed:17661442};
Catalytic activity:		Reaction=ATP + coproporphyrin III(in) + H2O = ADP + coproporphyrin III(out) + H(+) + phosphate; Xref=Rhea:RHEA:66664, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:131725, ChEBI:CHEBI:456216; Evidence={ECO:0000269\|PubMed:23792964, ECO:0000269\|PubMed:27507172, ECO:0000269\|PubMed:33007128}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66665; Evidence={ECO:0000269\|PubMed:23792964, ECO:0000269\|PubMed:27507172};
Catalytic activity:		Reaction=ATP + H2O + pheophorbide a(in) = ADP + H(+) + pheophorbide a(out) + phosphate; Xref=Rhea:RHEA:61360, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:58687, ChEBI:CHEBI:456216; Evidence={ECO:0000269\|PubMed:17661442, ECO:0000269\|PubMed:23792964}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61361; Evidence={ECO:0000305\|PubMed:17661442};
Catalytic activity:		Reaction=ATP + coproporphyrinogen III(in) + H2O = ADP + coproporphyrinogen III(out) + H(+) + phosphate; Xref=Rhea:RHEA:66680, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:57309, ChEBI:CHEBI:456216; Evidence={ECO:0000250\|UniProtKB:Q9DC29}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66681; Evidence={ECO:0000250\|UniProtKB:Q9DC29};
Catalytic activity:		Reaction=ATP + H2O + protoporphyrin IX(in) = ADP + H(+) + phosphate + protoporphyrin IX(out); Xref=Rhea:RHEA:61336, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:57306, ChEBI:CHEBI:456216; Evidence={ECO:0000269\|PubMed:23792964, ECO:0000269\|PubMed:33007128}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61337; Evidence={ECO:0000269\|PubMed:23792964};
Catalytic activity:		Reaction=ATP + coproporphyrin I(in) + H2O = ADP + coproporphyrin I(out) + H(+) + phosphate; Xref=Rhea:RHEA:66768, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:167478, ChEBI:CHEBI:456216; Evidence={ECO:0000250\|UniProtKB:Q9DC29}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66769; Evidence={ECO:0000250\|UniProtKB:Q9DC29};
Catalytic activity:		Reaction=ATP + H2O + uroporphyrin I(in) = ADP + H(+) + phosphate + uroporphyrin I(out); Xref=Rhea:RHEA:66772, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:167480, ChEBI:CHEBI:456216; Evidence={ECO:0000250\|UniProtKB:Q9DC29}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66773; Evidence={ECO:0000250\|UniProtKB:Q9DC29};
Catalytic activity:		Reaction=ATP + H2O + uroporphyrin III(in) = ADP + H(+) + phosphate + uroporphyrin III(out); Xref=Rhea:RHEA:66776, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:167479, ChEBI:CHEBI:456216; Evidence={ECO:0000250\|UniProtKB:Q9DC29}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66777; Evidence={ECO:0000250\|UniProtKB:Q9DC29};
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 impairs by increasing copper concentrations (0-300 muM) (PubMed:33007128). The ATPase activity is stimulated in presence of glutathione for increasing copper concentrations (0-300 muM) (PubMed:33007128). {ECO:0000269\|PubMed:23792964, ECO:0000269\|PubMed:33007128}.
Biophysicochemical properties:		Kinetic parameters: KM=0.99 mM for ATP (from purified mitochondrial ABCB6) {ECO:0000269\|PubMed:23792964}; KM=0.97 mM for ATP (from liposome-reconstituted purified mitochondrial ABCB6) {ECO:0000269\|PubMed:23792964}; KM=11.97 uM for coproporphyrin III (from liposome-reconstituted purified mitochondrial ABCB6) {ECO:0000269\|PubMed:23792964}; KM=51 uM for glutathione (in the presence of 10 uM of hemin) {ECO:0000269\|PubMed:33007128}; KM=190 nM for hemin (in the presence of 1 mM of glutathione) {ECO:0000269\|PubMed:33007128}; KM=600 nM for hematin (in the presence of 1 mM of glutathione) {ECO:0000269\|PubMed:33007128}; KM=148 nM for Fe-coproporphyrin III (in the presence of 1 mM of glutathione) {ECO:0000269\|PubMed:33007128}; Vmax=492.3 nmol/min/mg enzyme toward ATP (from purified mitochondrial ABCB6) {ECO:0000269\|PubMed:23792964}; Vmax=614 nmol/min/mg enzyme toward ATP (from liposome-reconstituted purified mitochondrial ABCB6) {ECO:0000269\|PubMed:23792964}; Vmax=29.6 pmol/min/mg enzyme toward coproporphyrin III (from liposome-reconstituted purified mitochondrial ABCB6) {ECO:0000269\|PubMed:23792964}; Vmax=5.13 pmol/min/mg enzyme toward verteporfin {ECO:0000269\|PubMed:23792964}; Vmax=2.7 pmol/min/mg enzyme toward tomatine {ECO:0000269\|PubMed:23792964};
Subunit:		Homodimer. {ECO:0000269\|PubMed:16791740, ECO:0000269\|PubMed:17006453, ECO:0000269\|PubMed:23792964, ECO:0000269\|PubMed:25627919, ECO:0000269\|PubMed:33007128}.
Subcellular location:		Cell membrane {ECO:0000269\|PubMed:17661442, ECO:0000269\|PubMed:22246506, ECO:0000269\|PubMed:22655043, ECO:0000269\|PubMed:23180570, ECO:0000269\|PubMed:27507172}; Multi-pass membrane protein {ECO:0000255}. Mitochondrion outer membrane {ECO:0000269\|PubMed:17006453, ECO:0000269\|PubMed:17661442}; Multi-pass membrane protein {ECO:0000255}. Endoplasmic reticulum membrane {ECO:0000269\|PubMed:18279659, ECO:0000269\|PubMed:21199866, ECO:0000269\|PubMed:22226084}; Multi-pass membrane protein {ECO:0000255}. Golgi apparatus membrane {ECO:0000269\|PubMed:18279659, ECO:0000269\|PubMed:21199866, ECO:0000269\|PubMed:22226084}; Multi-pass membrane protein {ECO:0000255}. Endosome membrane {ECO:0000269\|PubMed:25627919}; Multi-pass membrane protein {ECO:0000255}. Lysosome membrane {ECO:0000269\|PubMed:22655043, ECO:0000269\|PubMed:25627919, ECO:0000269\|PubMed:29940187, ECO:0000269\|PubMed:31053883}. Late endosome membrane {ECO:0000250\|UniProtKB:O70595}. Early endosome membrane {ECO:0000250\|UniProtKB:O70595}. Secreted, extracellular exosome {ECO:0000269\|PubMed:22655043}. Mitochondrion {ECO:0000269\|PubMed:10837493, ECO:0000269\|PubMed:23792964}. Endosome, multivesicular body membrane {ECO:0000269\|PubMed:25627919}. Melanosome membrane {ECO:0000269\|PubMed:29940187}. Note=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:25627919, PubMed:21199866, PubMed:18279659). Localized on the limiting membrane of early melanosomes of pigment cells (PubMed:29940187). Targeted to the endolysosomal compartment (By similarity). {ECO:0000250\|UniProtKB:O70595, ECO:0000269\|PubMed:18279659, ECO:0000269\|PubMed:21199866, ECO:0000269\|PubMed:22655043, ECO:0000269\|PubMed:25627919, ECO:0000269\|PubMed:29940187}.
Tissue specificity:		Widely expressed. High expression is detected in the retinal epithelium (PubMed:10837493, PubMed:22226084). Expressed in mature erythrocytes (PubMed:22655043). {ECO:0000269\|PubMed:10837493, ECO:0000269\|PubMed:22226084, ECO:0000269\|PubMed:22655043}.
Developmental stage:		Highly expressed in fetal liver. {ECO:0000269\|PubMed:17006453}.
Induction:		Up-regulated by cellular porphyrins (at protein level) (PubMed:22655043, PubMed:17006453, PubMed:23180570). Up-regulated during erythroid differentiation (at protein level) (PubMed:22655043). Induced by sodium arsenite in a dose-dependent manner (PubMed:21266531). {ECO:0000269\|PubMed:17006453, ECO:0000269\|PubMed:21266531, ECO:0000269\|PubMed:22655043, ECO:0000269\|PubMed:23180570}.
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. {ECO:0000269\|PubMed:25627919}.
Ptm:		N-glycosylated. {ECO:0000269\|PubMed:18279659, ECO:0000269\|PubMed:21199866, ECO:0000269\|PubMed:22655043, ECO:0000269\|PubMed:25627919}.
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. {ECO:0000269\|PubMed:22246506}.
Disease:		Microphthalmia, isolated, with coloboma, 7 (MCOPCB7) [MIM:614497]: A disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues. Ocular abnormalities like opacities of the cornea and lens, scaring of the retina and choroid, and other abnormalities may also be present. Ocular colobomas are a set of malformations resulting from abnormal morphogenesis of the optic cup and stalk, and the fusion of the fetal fissure (optic fissure). {ECO:0000269\|PubMed:22226084}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Dyschromatosis universalis hereditaria 3 (DUH3) [MIM:615402]: An autosomal dominant pigmentary genodermatosis characterized by a mixture of hyperpigmented and hypopigmented macules distributed randomly over the body, that appear in infancy or early childhood. The trunk and extremities are the dominant sites of abnormal pigmentation. Facial lesions can be seen in 50% of affected individuals, but involvement of palms and soles is unusual. Abnormalities of hair and nails have also been reported. Dyschromatosis universalis hereditaria may be associated with abnormalities of dermal connective tissue, nerve tissue, or other systemic complications. {ECO:0000269\|PubMed:23519333, ECO:0000269\|PubMed:24224009, ECO:0000269\|PubMed:24498303, ECO:0000269\|PubMed:25288164, ECO:0000269\|PubMed:29940187}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Pseudohyperkalemia, familial, 2, due to red cell leak (PSHK2) [MIM:609153]: A dominantly inherited condition characterized by increased serum potassium levels, measured in whole-blood specimens stored at or below room temperature. This condition is not accompanied by clinical symptoms or biological signs except for borderline abnormalities of red cell shape. {ECO:0000269\|PubMed:23180570, ECO:0000269\|PubMed:24947683}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Note=Defects in ABCB6 may be the cause of a severe porphyria. Affected individuals show higher urinary porphyrin concentrations. {ECO:0000269\|PubMed:27507172}.
Similarity:		Belongs to the ABC transporter superfamily. ABCB family. Heavy Metal importer (TC 3.A.1.210) subfamily. {ECO:0000305}.
Sequence caution:		Sequence=AAG33617.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=AAG33618.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=AAH43423.1; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305}; Sequence=BAD18782.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305}; Sequence=BAD92291.1; Type=Miscellaneous discrepancy; Note=Chimeric cDNA.; Evidence={ECO:0000305};
Sequence caution:		[Isoform 2]: Sequence=BAB71347.1; Type=Miscellaneous discrepancy; Note=splicing through aberrant splice sites.; Evidence={ECO:0000305};