CY561_BOVIN
ID CY561_BOVIN Reviewed; 252 AA.
AC P10897; Q0P5F5;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2000, sequence version 2.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Transmembrane ascorbate-dependent reductase CYB561 {ECO:0000305|PubMed:1623014};
DE EC=7.2.1.- {ECO:0000269|PubMed:1623014, ECO:0000269|PubMed:3597367};
DE AltName: Full=Chromomembrin B {ECO:0000303|PubMed:7465055};
DE AltName: Full=Cytochrome b-561;
DE AltName: Full=Cytochrome b561 {ECO:0000303|PubMed:2460342};
GN Name=CYB561;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, TISSUE SPECIFICITY,
RP AND SUBCELLULAR LOCATION.
RC TISSUE=Adrenal chromaffin;
RX PubMed=2460342; DOI=10.1002/j.1460-2075.1988.tb03123.x;
RA Perin M.S., Fried V.A., Slaughter C.A., Suedhof T.C.;
RT "The structure of cytochrome b561, a secretory vesicle-specific electron
RT transport protein.";
RL EMBO J. 7:2697-2703(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Fetal pons;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (AUG-2006) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP PROTEIN SEQUENCE OF 2-9, AND ACETYLATION AT MET-1.
RC TISSUE=Adrenal chromaffin;
RX PubMed=12768340; DOI=10.1007/s00709-002-0062-3;
RA Nakamura M., Takeuchi F., Tsubaki M.;
RT "Cytochrome b561 is not fatty acylated but acetylated at amino terminus in
RT chromaffin vesicle membranes: an approach for the identification of
RT posttranslational modification of transmembrane proteins.";
RL Protoplasma 221:41-46(2003).
RN [4]
RP IDENTIFICATION.
RX PubMed=7465055; DOI=10.1016/0306-4522(80)90143-8;
RA Apps D.K., Pryde J.G., Phillips J.H.;
RT "Cytochrome b561 is identical with chromomembrin B, a major polypeptide of
RT chromaffin granule membranes.";
RL Neuroscience 5:2279-2287(1980).
RN [5]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=3597367; DOI=10.1016/s0021-9258(18)47545-x;
RA Kent U.M., Fleming P.J.;
RT "Purified cytochrome b561 catalyzes transmembrane electron transfer for
RT dopamine beta-hydroxylase and peptidyl glycine alpha-amidating
RT monooxygenase activities in reconstituted systems.";
RL J. Biol. Chem. 262:8174-8178(1987).
RN [6]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=1623014; DOI=10.1016/0167-4889(92)90232-z;
RA Harnadek G.J., Ries E.A., Tse D.G., Fitz J.S., Njus D.;
RT "Electron transfer in chromaffin-vesicle ghosts containing peroxidase.";
RL Biochim. Biophys. Acta 1135:280-286(1992).
RN [7]
RP COFACTOR.
RX PubMed=9287327; DOI=10.1074/jbc.272.37.23206;
RA Tsubaki M., Nakayama M., Okuyama E., Ichikawa Y., Hori H.;
RT "Existence of two heme B centers in cytochrome b561 from bovine adrenal
RT chromaffin vesicles as revealed by a new purification procedure and EPR
RT spectroscopy.";
RL J. Biol. Chem. 272:23206-23210(1997).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND MUTAGENESIS OF HIS-54; ASN-78;
RP HIS-88; HIS-92; HIS-109; HIS-110; HIS-122 AND HIS-161.
RX PubMed=18501187; DOI=10.1016/j.bbabio.2008.04.039;
RA Liu W., Rogge C.E., da Silva G.F., Shinkarev V.P., Tsai A.L., Kamensky Y.,
RA Palmer G., Kulmacz R.J.;
RT "His92 and His110 selectively affect different heme centers of adrenal
RT cytochrome b(561).";
RL Biochim. Biophys. Acta 1777:1218-1228(2008).
CC -!- FUNCTION: Transmembrane reductase that uses ascorbate as an electron
CC donor in the cytoplasm and transfers electrons across membranes to
CC reduce monodehydro-L-ascorbate radical in the lumen of secretory
CC vesicles (PubMed:3597367, PubMed:1623014, PubMed:18501187). It is
CC therefore involved the regeneration and homeostasis within secretory
CC vesicles of ascorbate which in turn provides reducing equivalents
CC needed to support the activity of intravesicular enzymes (Probable).
CC {ECO:0000269|PubMed:1623014, ECO:0000269|PubMed:18501187,
CC ECO:0000269|PubMed:3597367, ECO:0000305|PubMed:3597367}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-ascorbate(in) + monodehydro-L-ascorbate radical(out) = L-
CC ascorbate(out) + monodehydro-L-ascorbate radical(in);
CC Xref=Rhea:RHEA:66524, ChEBI:CHEBI:38290, ChEBI:CHEBI:59513;
CC Evidence={ECO:0000269|PubMed:1623014, ECO:0000269|PubMed:18501187,
CC ECO:0000269|PubMed:3597367};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66525;
CC Evidence={ECO:0000305|PubMed:1623014};
CC -!- COFACTOR:
CC Name=heme b; Xref=ChEBI:CHEBI:60344;
CC Evidence={ECO:0000269|PubMed:18501187, ECO:0000269|PubMed:9287327};
CC Note=Binds 2 heme b groups non-covalently.
CC {ECO:0000305|PubMed:18501187, ECO:0000305|PubMed:9287327};
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle,
CC chromaffin granule membrane {ECO:0000269|PubMed:2460342}; Multi-pass
CC membrane protein {ECO:0000250|UniProtKB:Q53TN4}. Note=Secretory vesicle
CC containing catecholamines and amidated peptides.
CC {ECO:0000269|PubMed:2460342}.
CC -!- TISSUE SPECIFICITY: Expressed in the adrenal medulla and all brain
CC regions, but not in visceral organs. {ECO:0000269|PubMed:2460342}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA31274.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; X12783; CAA31274.1; ALT_INIT; mRNA.
DR EMBL; BC120119; AAI20120.1; -; mRNA.
DR PIR; S01167; S01167.
DR RefSeq; NP_777262.1; NM_174837.2.
DR RefSeq; XP_005220876.1; XM_005220819.2.
DR RefSeq; XP_005220878.1; XM_005220821.3.
DR RefSeq; XP_010814617.1; XM_010816315.2.
DR AlphaFoldDB; P10897; -.
DR SMR; P10897; -.
DR STRING; 9913.ENSBTAP00000027732; -.
DR TCDB; 5.B.2.1.1; the eukaryotic cytochrome b561 (cytb561) family.
DR iPTMnet; P10897; -.
DR PaxDb; P10897; -.
DR Ensembl; ENSBTAT00000042727; ENSBTAP00000040358; ENSBTAG00000020810.
DR GeneID; 317663; -.
DR KEGG; bta:317663; -.
DR CTD; 1534; -.
DR VEuPathDB; HostDB:ENSBTAG00000020810; -.
DR VGNC; VGNC:50257; CYB561.
DR eggNOG; KOG1619; Eukaryota.
DR GeneTree; ENSGT00950000183197; -.
DR HOGENOM; CLU_069712_1_1_1; -.
DR InParanoid; P10897; -.
DR OrthoDB; 1503869at2759; -.
DR TreeFam; TF314222; -.
DR BRENDA; 7.2.1.3; 908.
DR Proteomes; UP000009136; Chromosome 19.
DR Bgee; ENSBTAG00000020810; Expressed in saliva-secreting gland and 97 other tissues.
DR ExpressionAtlas; P10897; baseline and differential.
DR GO; GO:0042584; C:chromaffin granule membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005765; C:lysosomal membrane; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0140575; F:transmembrane monodehydroascorbate reductase activity; IDA:UniProtKB.
DR GO; GO:0140576; P:ascorbate homeostasis; IDA:UniProtKB.
DR InterPro; IPR028837; CYB561.
DR InterPro; IPR043205; CYB561/CYBRD1-like.
DR InterPro; IPR006593; Cyt_b561/ferric_Rdtase_TM.
DR PANTHER; PTHR10106; PTHR10106; 1.
DR PANTHER; PTHR10106:SF14; PTHR10106:SF14; 1.
DR Pfam; PF03188; Cytochrom_B561; 1.
DR SMART; SM00665; B561; 1.
DR PROSITE; PS50939; CYTOCHROME_B561; 1.
PE 1: Evidence at protein level;
KW Acetylation; Cytoplasmic vesicle; Direct protein sequencing;
KW Electron transport; Heme; Iron; Membrane; Metal-binding; Phosphoprotein;
KW Reference proteome; Translocase; Transmembrane; Transmembrane helix;
KW Transport.
FT CHAIN 1..252
FT /note="Transmembrane ascorbate-dependent reductase CYB561"
FT /id="PRO_0000151026"
FT TOPO_DOM 1..17
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT TRANSMEM 18..38
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 39..52
FT /note="Vesicular"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT TRANSMEM 53..73
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 74..86
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT TRANSMEM 87..107
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 108..125
FT /note="Vesicular"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT TRANSMEM 126..146
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 147..159
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT TRANSMEM 160..180
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 181..199
FT /note="Vesicular"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT TRANSMEM 200..220
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 221..252
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT DOMAIN 20..221
FT /note="Cytochrome b561"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00242"
FT BINDING 54
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 74
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT BINDING 81
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /ligand_label="2"
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 85
FT /ligand="L-ascorbate"
FT /ligand_id="ChEBI:CHEBI:38290"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT BINDING 88
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 117..120
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT BINDING 122
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 154
FT /ligand="L-ascorbate"
FT /ligand_id="ChEBI:CHEBI:38290"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT BINDING 161
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 182
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT BINDING 226
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000269|PubMed:12768340"
FT MOD_RES 248
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q60720"
FT MOD_RES 250
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q60720"
FT MUTAGEN 54
FT /note="H->Q: Decreased protein expression."
FT /evidence="ECO:0000269|PubMed:18501187"
FT MUTAGEN 78
FT /note="N->K: No effect on heme b binding."
FT /evidence="ECO:0000269|PubMed:18501187"
FT MUTAGEN 88
FT /note="H->Q: Decreased protein expression. Decreased heme b
FT binding. Loss of oxidoreductase activity."
FT /evidence="ECO:0000269|PubMed:18501187"
FT MUTAGEN 88
FT /note="H->Y: Decreased heme b binding. Loss of
FT oxidoreductase activity."
FT /evidence="ECO:0000269|PubMed:18501187"
FT MUTAGEN 92
FT /note="H->Q: No effect on heme b binding. Decreased
FT oxidoreductase activity."
FT /evidence="ECO:0000269|PubMed:18501187"
FT MUTAGEN 92
FT /note="H->Y: No effect on heme b binding."
FT /evidence="ECO:0000269|PubMed:18501187"
FT MUTAGEN 109
FT /note="H->Y: No effect on heme b binding."
FT /evidence="ECO:0000269|PubMed:18501187"
FT MUTAGEN 110
FT /note="H->Q: No effect on heme b binding."
FT /evidence="ECO:0000269|PubMed:18501187"
FT MUTAGEN 110
FT /note="H->Y: No effect on heme b binding."
FT /evidence="ECO:0000269|PubMed:18501187"
FT MUTAGEN 122
FT /note="H->Q: Decreased protein expression."
FT /evidence="ECO:0000269|PubMed:18501187"
FT MUTAGEN 161
FT /note="H->Q: Decreased protein expression. Decreased heme b
FT binding. Loss of transmembrane oxidoreductase activity."
FT /evidence="ECO:0000269|PubMed:18501187"
FT MUTAGEN 161
FT /note="H->Y: Decreased heme b binding. Loss of
FT oxidoreductase activity."
FT /evidence="ECO:0000269|PubMed:18501187"
SQ SEQUENCE 252 AA; 27904 MW; B64599D5C06AF969 CRC64;
MEGPASPARA PGALPYYVAF SQLLGLIVVA MTGAWLGMYR GGIAWESALQ FNVHPLCMII
GLVFLQGDAL LVYRVFRNEA KRTTKVLHGL LHVFAFVIAL VGLVAVFEHH RKKGYADLYS
LHSWCGILVF ALFFAQWLVG FSFFLFPGAS FSLRSRYRPQ HVFFGAAIFL LSVATALLGL
KEALLFELGT KYSMFEPEGV LANVLGLLLA TFATVILYIL TRADWKRPLQ AEEQALSMDF
KTLTEGDSPS SQ
