ABCB6_MESAU
ID ABCB6_MESAU Reviewed; 842 AA.
AC A0A125QXJ1;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 13-APR-2016, sequence version 1.
DT 03-AUG-2022, entry version 19.
DE RecName: Full=ATP-binding cassette sub-family B member 6 {ECO:0000250|UniProtKB:Q9NP58};
DE AltName: Full=ABC-type heme transporter ABCB6 {ECO:0000250|UniProtKB:Q9NP58};
DE EC=7.6.2.5 {ECO:0000250|UniProtKB:Q9NP58};
DE AltName: Full=Mitochondrial ABC transporter 3 {ECO:0000250|UniProtKB:Q9NP58};
DE Short=Mt-ABC transporter 3 {ECO:0000250|UniProtKB:Q9NP58};
DE AltName: Full=P-glycoprotein-related protein;
DE AltName: Full=Ubiquitously-expressed mammalian ABC half transporter;
GN Name=ABCB6 {ECO:0000250|UniProtKB:Q9NP58};
OS Mesocricetus auratus (Golden hamster).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC Cricetidae; Cricetinae; Mesocricetus.
OX NCBI_TaxID=10036;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=30878759; DOI=10.1016/j.cbpa.2019.03.006;
RA Mares L., Vilchis F., Chavez B., Ramos L.;
RT "Isolation and sex steroid effects on the expression of the ATP-binding
RT cassette transporter ABCB6 in Harderian glands of hamster (Mesocricetus
RT auratus).";
RL Comp. Biochem. Physiol. 232A:40-46(2019).
CC -!- FUNCTION: ATP-dependent transporter that catalyzes the transport of a
CC broad-spectrum of porphyrins from the cytoplasm to the extracellular
CC space through the plasma membrane or into the vesicle lumen. May also
CC function as an ATP-dependent importer of porphyrins from the cytoplasm
CC into the mitochondria, in turn may participate in the de novo heme
CC biosynthesis regulation and in the coordination of heme and iron
CC homeostasis during phenylhydrazine stress. May also play a key role in
CC the early steps of melanogenesis producing PMEL amyloid fibrils. In
CC vitro, it confers to cells a resistance to toxic metal such as arsenic
CC and cadmium and against chemotherapeutics agent such as 5-fluorouracil,
CC SN-38 and vincristin (By similarity). In addition may play a role in
CC the transition metal homeostasis (By similarity).
CC {ECO:0000250|UniProtKB:O70595, ECO:0000250|UniProtKB:Q9NP58}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + heme b(in) = ADP + H(+) + heme b(out) + phosphate;
CC Xref=Rhea:RHEA:19261, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:60344,
CC ChEBI:CHEBI:456216; EC=7.6.2.5;
CC Evidence={ECO:0000250|UniProtKB:Q9NP58};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19262;
CC Evidence={ECO:0000250|UniProtKB:Q9NP58};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + coproporphyrin III(in) + H2O = ADP + coproporphyrin
CC III(out) + H(+) + phosphate; Xref=Rhea:RHEA:66664, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:131725, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000250|UniProtKB:Q9NP58};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66665;
CC Evidence={ECO:0000250|UniProtKB:Q9NP58};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + pheophorbide a(in) = ADP + H(+) + pheophorbide
CC a(out) + phosphate; Xref=Rhea:RHEA:61360, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:58687, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000250|UniProtKB:Q9NP58};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61361;
CC Evidence={ECO:0000250|UniProtKB:Q9NP58};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + coproporphyrinogen III(in) + H2O = ADP +
CC coproporphyrinogen III(out) + H(+) + phosphate; Xref=Rhea:RHEA:66680,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:57309, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000250|UniProtKB:Q9DC29};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66681;
CC Evidence={ECO:0000250|UniProtKB:Q9DC29};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + protoporphyrin IX(in) = ADP + H(+) + phosphate +
CC protoporphyrin IX(out); Xref=Rhea:RHEA:61336, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:57306, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000250|UniProtKB:Q9NP58};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61337;
CC Evidence={ECO:0000250|UniProtKB:Q9NP58};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + coproporphyrin I(in) + H2O = ADP + coproporphyrin I(out)
CC + H(+) + phosphate; Xref=Rhea:RHEA:66768, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:167478, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000250|UniProtKB:Q9DC29};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66769;
CC Evidence={ECO:0000250|UniProtKB:Q9DC29};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + uroporphyrin I(in) = ADP + H(+) + phosphate +
CC uroporphyrin I(out); Xref=Rhea:RHEA:66772, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:167480, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000250|UniProtKB:Q9DC29};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66773;
CC Evidence={ECO:0000250|UniProtKB:Q9DC29};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + uroporphyrin III(in) = ADP + H(+) + phosphate +
CC uroporphyrin III(out); Xref=Rhea:RHEA:66776, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:167479, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000250|UniProtKB:Q9DC29};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66777;
CC Evidence={ECO:0000250|UniProtKB:Q9DC29};
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q9NP58}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q9NP58};
CC Multi-pass membrane protein {ECO:0000255}. Mitochondrion outer membrane
CC {ECO:0000250|UniProtKB:Q9NP58}; Multi-pass membrane protein
CC {ECO:0000255}. Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q9NP58}; Multi-pass membrane protein
CC {ECO:0000255}. Golgi apparatus membrane {ECO:0000250|UniProtKB:Q9NP58};
CC Multi-pass membrane protein {ECO:0000255}. Endosome membrane
CC {ECO:0000250|UniProtKB:Q9NP58}; Multi-pass membrane protein
CC {ECO:0000255}. Lysosome membrane {ECO:0000250|UniProtKB:Q9NP58}. Late
CC endosome membrane {ECO:0000250|UniProtKB:O70595}. Early endosome
CC membrane {ECO:0000250|UniProtKB:O70595}. Secreted, extracellular
CC exosome {ECO:0000250|UniProtKB:Q9NP58}. Mitochondrion
CC {ECO:0000250|UniProtKB:Q9NP58}. Endosome, multivesicular body membrane
CC {ECO:0000250|UniProtKB:Q9NP58}. Melanosome membrane
CC {ECO:0000250|UniProtKB:Q9NP58}. Note=Present in the membrane of mature
CC erythrocytes and in exosomes released from reticulocytes during the
CC final steps of erythroid maturation. Traffics from endoplasmic
CC reticulum to Golgi during its glycans's maturation, therefrom is first
CC targeted to the plasma membrane, and is rapidly internalized through
CC endocytosis to be distributed to the limiting membrane of
CC multivesicular bodies and lysosomes. Localized on the limiting membrane
CC of early melanosomes of pigment cells (By similarity). Targeted to the
CC endolysosomal compartment (By similarity).
CC {ECO:0000250|UniProtKB:O70595, ECO:0000250|UniProtKB:Q9NP58}.
CC -!- TISSUE SPECIFICITY: Highly expressed in the liver, adrenal glands, and
CC testis. {ECO:0000269|PubMed:30878759}.
CC -!- DOMAIN: Contains two independently folding units, the N-terminal
CC transmembrane domain (residues 1-205) and the ABC-core domain (206-842)
CC are respectively responsible for the lysosomal targeting and the ATPase
CC activity. {ECO:0000250|UniProtKB:Q9NP58}.
CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:Q9NP58}.
CC -!- SIMILARITY: Belongs to the ABC transporter superfamily. ABCB family.
CC Heavy Metal importer (TC 3.A.1.210) subfamily. {ECO:0000305}.
CC -!- CAUTION: To date, the intracellular localization of ABCB6 is a matter
CC of debate, with conflicting reports suggesting mitochondrial or
CC endolysosomal localization, therefore questioning the requirement of
CC ABCB6 in the mitochondrial import of porphyrins.
CC {ECO:0000250|UniProtKB:Q9NP58}.
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DR EMBL; KU244541; AMA11216.1; -; mRNA.
DR AlphaFoldDB; A0A125QXJ1; -.
DR SMR; A0A125QXJ1; -.
DR Proteomes; UP000189706; Unplaced.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0036020; C:endolysosome membrane; ISS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005765; C:lysosomal membrane; ISS:UniProtKB.
DR GO; GO:0033162; C:melanosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005741; C:mitochondrial outer membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0032585; C:multivesicular body membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0015439; F:ABC-type heme transporter activity; IEA:UniProtKB-EC.
DR GO; GO:0140359; F:ABC-type transporter activity; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; ISS:UniProtKB.
DR GO; GO:0016887; F:ATP hydrolysis activity; ISS:UniProtKB.
DR GO; GO:0098849; P:cellular detoxification of cadmium ion; ISS:UniProtKB.
DR GO; GO:0042168; P:heme metabolic process; ISS:UniProtKB.
DR GO; GO:0035351; P:heme transmembrane transport; ISS:UniProtKB.
DR GO; GO:0006778; P:porphyrin-containing compound metabolic process; ISS:UniProtKB.
DR Gene3D; 1.20.1560.10; -; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR003593; AAA+_ATPase.
DR InterPro; IPR011527; ABC1_TM_dom.
DR InterPro; IPR036640; ABC1_TM_sf.
DR InterPro; IPR003439; ABC_transporter-like_ATP-bd.
DR InterPro; IPR017871; ABC_transporter-like_CS.
DR InterPro; IPR032410; MTABC_N.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR039421; Type_1_exporter.
DR PANTHER; PTHR24221; PTHR24221; 1.
DR Pfam; PF00664; ABC_membrane; 1.
DR Pfam; PF00005; ABC_tran; 1.
DR Pfam; PF16185; MTABC_N; 1.
DR SMART; SM00382; AAA; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR SUPFAM; SSF90123; SSF90123; 1.
DR PROSITE; PS50929; ABC_TM1F; 1.
DR PROSITE; PS00211; ABC_TRANSPORTER_1; 1.
DR PROSITE; PS50893; ABC_TRANSPORTER_2; 1.
PE 2: Evidence at transcript level;
KW ATP-binding; Cell membrane; Disulfide bond; Endoplasmic reticulum;
KW Endosome; Glycoprotein; Golgi apparatus; Lysosome; Membrane; Mitochondrion;
KW Mitochondrion outer membrane; Nucleotide-binding; Reference proteome;
KW Secreted; Translocase; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..842
FT /note="ATP-binding cassette sub-family B member 6"
FT /id="PRO_0000452718"
FT TOPO_DOM 1..26
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:Q9NP58"
FT TRANSMEM 27..47
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 48..72
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 73..93
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 94..106
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:Q9NP58"
FT TRANSMEM 107..127
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 128..147
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 148..168
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 169..185
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:Q9NP58"
FT TRANSMEM 186..206
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 207..263
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 264..284
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT TOPO_DOM 285..305
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:Q9NP58"
FT TRANSMEM 306..326
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT TOPO_DOM 327..375
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 376..396
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT TOPO_DOM 397
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:Q9NP58"
FT TRANSMEM 398..418
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT TOPO_DOM 419..499
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 500..520
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT TOPO_DOM 521..529
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:Q9NP58"
FT TRANSMEM 530..550
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT TOPO_DOM 551..842
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT DOMAIN 265..556
FT /note="ABC transmembrane type-1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT DOMAIN 590..824
FT /note="ABC transporter"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT REGION 1..236
FT /note="Required for ATPase activity"
FT /evidence="ECO:0000250|UniProtKB:Q9NP58"
FT REGION 1..205
FT /note="Required for the lysosomal targeting"
FT /evidence="ECO:0000250|UniProtKB:Q9NP58"
FT BINDING 623..630
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT DISULFID 8..26
FT /evidence="ECO:0000250|UniProtKB:Q9NP58"
SQ SEQUENCE 842 AA; 93746 MW; 564BCFC9DDB40334 CRC64;
MVTVGNYCEA EGPLGPAWAQ NGLSPCFFFT LVPSTLMALG ALALVLVLPC RRRDVPSGTE
ELFWAADSRV APYALQLFLA TLQVALPLAG LAGRVGTARG VRLPGYLLLA SMLGSLASAC
GLWLLVAERR QARQSLAMGV WMKFRHSSGL LLLWTVAFAA ENLALVSWNS PQWWWARADL
GQQVQFGLWV LRYVISGGLF ILGLWAPGLR PQSYTLRVHE ADQDVERNQA QSTDRTSTWR
DLGRKLRLLS SYLWPRGSPA LQFIVLICLG LMGLDRALNV LVPIFYRDIV NLLTSKAPWS
SLAWTVTTYV FLKFLQGGGT GSTGFVSNLR TFLWIRVQQF TSRGVELRLF SHLHELSLRW
HLGRRTGEVL RVVDRGTSSV TGLLSYLVFN IIPTLADIII GIIYFSMFFN AWFGLIVFLC
MSLYLFLTIV VTEWRAKFRR AMNTQENITR ARAVDSLLNF ETVKYYNAEG YEVERYREAI
IKYQGLEWKS SASLVVLNQT QNLVIGLGLL AGSLLCAYFV SEQKLQVGDF VLFGTYITQL
YMPLNWFGTY YRMIQTNFID MENMFDLLKE ETEVKDVPGA GPLRFHKGQI EFENVHFSYA
DGRETLQDVS FTVMPGQTVA LVGPSGAGKS TILRLLFRFY DISSGCIRID GQDISQVTQI
SLRSHIGVVP QDTVLFNDTI ANNIRYGRIA AGDSEVEAAA QAAGIHDAIL SFPEGYETQV
GERGLKLSGG EKQRVAIART ILKAPDIILL DEATSALDTS NERAIQASLA KVCTNRTTIV
VAHRLSTVVS ADQILVIKDG CIIERGRHEA LLSQGGVYAE MWQLQQKGQE TVSEDSKPQD
IA
