CY561_MOUSE
ID CY561_MOUSE Reviewed; 250 AA.
AC Q60720; Q3TEC6; Q9D6C9;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 25-NOV-2002, sequence version 2.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Transmembrane ascorbate-dependent reductase CYB561 {ECO:0000305|PubMed:16256064};
DE EC=7.2.1.- {ECO:0000305|PubMed:16256064};
DE AltName: Full=Chromaffin granule Cyt b561 {ECO:0000303|PubMed:16256064};
DE Short=CGCytb {ECO:0000303|PubMed:16256064};
DE AltName: Full=Cytochrome b-561;
DE AltName: Full=Cytochrome b561;
GN Name=Cyb561 {ECO:0000312|MGI:MGI:103253}; Synonyms=Mcyt;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=9778036; DOI=10.1089/dna.1998.17.771;
RA Srivastava M., Pollard H.B., Fleming P.J.;
RT "Mouse cytochrome b561: cDNA cloning and expression in rat brain, mouse
RT embryos, and human glioma cell lines.";
RL DNA Cell Biol. 17:771-777(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain, and Visual cortex;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, SUBCELLULAR LOCATION, AND
RP MUTAGENESIS OF HIS-52; ARG-72; LYS-83; HIS-86; HIS-108; HIS-120 AND
RP HIS-159.
RX PubMed=16256064; DOI=10.1016/j.abb.2005.09.006;
RA Berczi A., Su D., Lakshminarasimhan M., Vargas A., Asard H.;
RT "Heterologous expression and site-directed mutagenesis of an ascorbate-
RT reducible cytochrome b561.";
RL Arch. Biochem. Biophys. 443:82-92(2005).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-246 AND SER-248, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, and Brown adipose tissue;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP DISRUPTION PHENOTYPE.
RX PubMed=29343526; DOI=10.1161/circresaha.117.311949;
RA van den Berg M.P., Almomani R., Biaggioni I., van Faassen M.,
RA van der Harst P., Sillje H.H.W., Mateo Leach I., Hemmelder M.H., Navis G.,
RA Luijckx G.J., de Brouwer A.P.M., Venselaar H., Verbeek M.M.,
RA van der Zwaag P.A., Jongbloed J.D.H., van Tintelen J.P., Wevers R.A.,
RA Kema I.P.;
RT "Mutations in CYB561 causing a novel orthostatic hypotension syndrome.";
RL Circ. Res. 122:846-854(2018).
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 (Probable). It is therefore involved the regeneration and
CC homeostasis within secretory vesicles of ascorbate which in turn
CC provides reducing equivalents needed to support the activity of
CC intravesicular enzymes (By similarity). {ECO:0000250|UniProtKB:P10897,
CC ECO:0000305|PubMed:16256064}.
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:0000305|PubMed:16256064};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66525;
CC Evidence={ECO:0000305|PubMed:16256064};
CC -!- COFACTOR:
CC Name=heme b; Xref=ChEBI:CHEBI:60344;
CC Evidence={ECO:0000305|PubMed:16256064};
CC Note=Binds 2 heme b groups non-covalently.
CC {ECO:0000305|PubMed:16256064};
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle,
CC chromaffin granule membrane {ECO:0000269|PubMed:16256064}; Multi-pass
CC membrane protein {ECO:0000250|UniProtKB:Q53TN4}. Note=Secretory vesicle
CC containing catecholamines and amidated peptides.
CC {ECO:0000250|UniProtKB:P10897}.
CC -!- TISSUE SPECIFICITY: Abundantly distributed in a number of
CC neuroendocrine tissues. {ECO:0000269|PubMed:9778036}.
CC -!- DISRUPTION PHENOTYPE: Mice lacking Cyb561 have significantly decreased
CC amounts of norepinephrine and normetanephrine in the adrenal gland and
CC brain while the biosynthesis of dopamine, the norepinephrine precursor,
CC is normal pointing to a defect in the catecholamine biosynthesis
CC downstream of dopamine probably at the level of the dopamine beta
CC synthase. {ECO:0000269|PubMed:29343526}.
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DR EMBL; U16297; AAA65643.1; -; mRNA.
DR EMBL; AK014395; BAB29321.1; -; mRNA.
DR EMBL; AK158978; BAE34753.1; -; mRNA.
DR EMBL; AK169711; BAE41322.1; -; mRNA.
DR EMBL; BC006732; AAH06732.1; -; mRNA.
DR CCDS; CCDS25542.1; -.
DR RefSeq; NP_031831.2; NM_007805.4.
DR RefSeq; XP_006532193.1; XM_006532130.3.
DR RefSeq; XP_006532194.1; XM_006532131.2.
DR RefSeq; XP_006532195.1; XM_006532132.3.
DR AlphaFoldDB; Q60720; -.
DR SMR; Q60720; -.
DR STRING; 10090.ENSMUSP00000019734; -.
DR iPTMnet; Q60720; -.
DR PhosphoSitePlus; Q60720; -.
DR MaxQB; Q60720; -.
DR PaxDb; Q60720; -.
DR PRIDE; Q60720; -.
DR ProteomicsDB; 284081; -.
DR Antibodypedia; 18653; 87 antibodies from 17 providers.
DR DNASU; 13056; -.
DR Ensembl; ENSMUST00000019734; ENSMUSP00000019734; ENSMUSG00000019590.
DR GeneID; 13056; -.
DR KEGG; mmu:13056; -.
DR UCSC; uc007lxr.1; mouse.
DR CTD; 1534; -.
DR MGI; MGI:103253; Cyb561.
DR VEuPathDB; HostDB:ENSMUSG00000019590; -.
DR eggNOG; KOG1619; Eukaryota.
DR GeneTree; ENSGT00950000183197; -.
DR HOGENOM; CLU_069712_1_1_1; -.
DR InParanoid; Q60720; -.
DR OMA; SYLPIHV; -.
DR OrthoDB; 1503869at2759; -.
DR PhylomeDB; Q60720; -.
DR TreeFam; TF314222; -.
DR BioGRID-ORCS; 13056; 0 hits in 74 CRISPR screens.
DR ChiTaRS; Cyb561; mouse.
DR PRO; PR:Q60720; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q60720; protein.
DR Bgee; ENSMUSG00000019590; Expressed in choroid plexus of fourth ventricle and 237 other tissues.
DR ExpressionAtlas; Q60720; baseline and differential.
DR Genevisible; Q60720; MM.
DR GO; GO:0042584; C:chromaffin granule membrane; IDA:ARUK-UCL.
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:HGNC-UCL.
DR GO; GO:0140576; P:ascorbate homeostasis; IDA:ARUK-UCL.
DR GO; GO:0006879; P:cellular iron ion homeostasis; IDA:ARUK-UCL.
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; Electron transport; Heme; Iron; Membrane;
KW Metal-binding; Phosphoprotein; Reference proteome; Translocase;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..250
FT /note="Transmembrane ascorbate-dependent reductase CYB561"
FT /id="PRO_0000151028"
FT TOPO_DOM 1..15
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT TRANSMEM 16..36
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 37..50
FT /note="Vesicular"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT TRANSMEM 51..71
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 72..83
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT TRANSMEM 84..104
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 105..123
FT /note="Vesicular"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT TRANSMEM 124..144
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 145..157
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT TRANSMEM 158..178
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 179..197
FT /note="Vesicular"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT TRANSMEM 198..218
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 219..250
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT DOMAIN 18..219
FT /note="Cytochrome b561"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00242"
FT BINDING 52
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 72
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT BINDING 79
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT BINDING 79
FT /ligand="L-ascorbate"
FT /ligand_id="ChEBI:CHEBI:38290"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT BINDING 83
FT /ligand="L-ascorbate"
FT /ligand_id="ChEBI:CHEBI:38290"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT BINDING 86
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 115..118
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT BINDING 120
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 152
FT /ligand="L-ascorbate"
FT /ligand_id="ChEBI:CHEBI:38290"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT BINDING 159
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 180
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT BINDING 224
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:0000250|UniProtKB:P10897"
FT MOD_RES 246
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 248
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MUTAGEN 52
FT /note="H->A: Decreased protein abundance."
FT /evidence="ECO:0000269|PubMed:16256064"
FT MUTAGEN 72
FT /note="R->A: No effect on protein abundance. Decreased
FT reduction by ascorbate."
FT /evidence="ECO:0000269|PubMed:16256064"
FT MUTAGEN 83
FT /note="K->A: No effect on protein abundance."
FT /evidence="ECO:0000269|PubMed:16256064"
FT MUTAGEN 86
FT /note="H->A: No effect on protein abundance. Decreased
FT reduction by ascorbate; when associated with A-159."
FT /evidence="ECO:0000269|PubMed:16256064"
FT MUTAGEN 108
FT /note="H->A: No effect on protein abundance."
FT /evidence="ECO:0000269|PubMed:16256064"
FT MUTAGEN 120
FT /note="H->A: Decreased protein abundance."
FT /evidence="ECO:0000269|PubMed:16256064"
FT MUTAGEN 159
FT /note="H->A: No effect on protein abundance. Decreased
FT reduction by ascorbate; when associated with A-86."
FT /evidence="ECO:0000269|PubMed:16256064"
FT CONFLICT 9..21
FT /note="PAALPYYVAFSQL -> LLHCRTMWPSPSC (in Ref. 1;
FT AAA65643)"
FT /evidence="ECO:0000305"
FT CONFLICT 171..174
FT /note="VGTA -> AGHS (in Ref. 1; AAA65643)"
FT /evidence="ECO:0000305"
FT CONFLICT 199
FT /note="L -> V (in Ref. 1; AAA65643)"
FT /evidence="ECO:0000305"
FT CONFLICT 222..226
FT /note="DWKRP -> ALERG (in Ref. 1; AAA65643)"
FT /evidence="ECO:0000305"
FT CONFLICT 248..249
FT /note="SP -> TS (in Ref. 1; AAA65643)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 250 AA; 27822 MW; D0FDE6C9DE5EA09E CRC64;
MEHSSASVPA ALPYYVAFSQ LLGLTVVAVT GAWLGLYRGG IAWESSLQFN VHPLCMVIGM
IFLQGDALLV YRVFRREAKR TTKILHGLLH VFAFIIALVG LVAVFDYHKK KGYADLYSLH
SWCGILVFVL YFVQWLVGFS FFLFPGASFS LRSRYRPQHI FFGATIFLFS VGTALLGLKE
ALLFKLGSKY STFEPEGVLA NVLGLLLVCF GVVVLYILAQ ADWKRPSQAE EQALSMDFKT
LTEGDSPSPQ
