CYAC3_DANRE
ID CYAC3_DANRE Reviewed; 247 AA.
AC A3KPR5; A8E5P6; Q566W0;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 03-APR-2007, sequence version 1.
DT 03-AUG-2022, entry version 91.
DE RecName: Full=Lysosomal membrane ascorbate-dependent ferrireductase CYB561A3 {ECO:0000305};
DE EC=7.2.1.3 {ECO:0000250|UniProtKB:Q6P1H1};
DE AltName: Full=Cytochrome b ascorbate-dependent protein 3;
DE AltName: Full=Cytochrome b561 family member A3;
DE AltName: Full=Lysosomal cytochrome b {ECO:0000250|UniProtKB:Q6P1H1};
DE Short=LCytb {ECO:0000250|UniProtKB:Q6P1H1};
GN Name=cyb561a3a; Synonyms=cybasc3; ORFNames=si:dkeyp-38h2.4;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Embryo, and Olfactory epithelium;
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (SEP-2007) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Transmembrane reductase that uses ascorbate as an electron
CC donor in the cytoplasm and transfers electrons across membranes to
CC reduce iron cations Fe(3+) into Fe(2+) in the lumen of the late
CC endosome and lysosome. Reduced iron can then be extruded from the late
CC endosome and lysosome to the cytoplasm by divalent metal-specific
CC transporters. It is therefore most probably involved in endosomal and
CC lysosomal cellular iron homeostasis. {ECO:0000250|UniProtKB:Q6P1H1}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Fe(3+)(out) + L-ascorbate(in) = Fe(2+)(out) + H(+) +
CC monodehydro-L-ascorbate radical(in); Xref=Rhea:RHEA:30403,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29033, ChEBI:CHEBI:29034,
CC ChEBI:CHEBI:38290, ChEBI:CHEBI:59513; EC=7.2.1.3;
CC Evidence={ECO:0000250|UniProtKB:Q6P1H1};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:30404;
CC Evidence={ECO:0000250|UniProtKB:Q6P1H1};
CC -!- COFACTOR:
CC Name=heme b; Xref=ChEBI:CHEBI:60344;
CC Evidence={ECO:0000250|UniProtKB:Q53TN4};
CC Note=Binds 2 heme b groups non-covalently.
CC {ECO:0000250|UniProtKB:Q53TN4};
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q53TN4}.
CC -!- SUBCELLULAR LOCATION: Late endosome membrane
CC {ECO:0000250|UniProtKB:Q6P1H1}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q53TN4}. Lysosome membrane
CC {ECO:0000250|UniProtKB:Q6P1H1}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q53TN4}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH93310.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAH93310.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; BX323062; CAM47032.1; -; Genomic_DNA.
DR EMBL; BC093310; AAH93310.1; ALT_SEQ; mRNA.
DR EMBL; BC153668; AAI53669.1; -; mRNA.
DR RefSeq; NP_001099054.1; NM_001105584.1.
DR AlphaFoldDB; A3KPR5; -.
DR SMR; A3KPR5; -.
DR STRING; 7955.ENSDARP00000120020; -.
DR PaxDb; A3KPR5; -.
DR Ensembl; ENSDART00000098590; ENSDARP00000089361; ENSDARG00000056281.
DR Ensembl; ENSDART00000146285; ENSDARP00000120020; ENSDARG00000056281.
DR GeneID; 100002371; -.
DR KEGG; dre:100002371; -.
DR CTD; 100002371; -.
DR ZFIN; ZDB-GENE-060526-374; cyb561a3a.
DR eggNOG; KOG1619; Eukaryota.
DR GeneTree; ENSGT00950000183197; -.
DR HOGENOM; CLU_069712_1_3_1; -.
DR InParanoid; A3KPR5; -.
DR OMA; FAWDGSI; -.
DR OrthoDB; 1503869at2759; -.
DR PhylomeDB; A3KPR5; -.
DR TreeFam; TF314222; -.
DR PRO; PR:A3KPR5; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 5.
DR Bgee; ENSDARG00000056281; Expressed in mature ovarian follicle and 19 other tissues.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0031902; C:late endosome membrane; ISS:UniProtKB.
DR GO; GO:0005765; C:lysosomal membrane; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0140571; F:transmembrane ascorbate ferrireductase activity; ISS:UniProtKB.
DR GO; GO:0006879; P:cellular iron ion homeostasis; ISS:UniProtKB.
DR InterPro; IPR043205; CYB561/CYBRD1-like.
DR InterPro; IPR006593; Cyt_b561/ferric_Rdtase_TM.
DR PANTHER; PTHR10106; PTHR10106; 1.
DR Pfam; PF03188; Cytochrom_B561; 1.
DR SMART; SM00665; B561; 1.
DR PROSITE; PS50939; CYTOCHROME_B561; 1.
PE 2: Evidence at transcript level;
KW Electron transport; Endosome; Glycoprotein; Heme; Iron; Lysosome; Membrane;
KW Metal-binding; Oxidoreductase; Reference proteome; Translocase;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..247
FT /note="Lysosomal membrane ascorbate-dependent
FT ferrireductase CYB561A3"
FT /id="PRO_0000314841"
FT TOPO_DOM 1..3
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 4..24
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 25..46
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 47..67
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 68..82
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 83..103
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 104..120
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 121..141
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 142..155
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 156..176
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 177..201
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 202..222
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 223..247
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT DOMAIN 13..223
FT /note="Cytochrome b561"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00242"
FT BINDING 48
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /ligand_label="1"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT BINDING 68
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT BINDING 77
FT /ligand="L-ascorbate"
FT /ligand_id="ChEBI:CHEBI:38290"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT BINDING 81
FT /ligand="L-ascorbate"
FT /ligand_id="ChEBI:CHEBI:38290"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT BINDING 84
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /ligand_label="2"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT BINDING 113..116
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT BINDING 118
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /ligand_label="1"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT BINDING 150
FT /ligand="L-ascorbate"
FT /ligand_id="ChEBI:CHEBI:38290"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT BINDING 157
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /ligand_label="2"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT BINDING 178
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT BINDING 228
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT CARBOHYD 189
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 64
FT /note="A -> V (in Ref. 2; AAI53669)"
FT /evidence="ECO:0000305"
FT CONFLICT 114
FT /note="L -> I (in Ref. 2; AAH93310)"
FT /evidence="ECO:0000305"
FT CONFLICT 126
FT /note="A -> T (in Ref. 2; AAH93310)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 247 AA; 27426 MW; 1B94668209456FDF CRC64;
MRGIVGFYIT YLLCLILGIA CVVLVVHWNF MYRDGFAWDG SSKNFNWHPV LMVTGMLVLY
GNAAVVYRIP LTWGHNKLPW KLLHAGLLLL SFIFSVIGLC AVFNFHNVHH TANLYSLHSW
VGICTAALFT AQWVMGFTSF LLPCTPMAVR AFVKPTHVWM GAMILVLSIV SCISGINEKL
FFVLKETTNG TKPYSALPPE AVAANSLGVI IVAFGLVVLK ILSNQMWQRP EPGDDEGVYR
PLAYDGS
