CY561_HUMAN
ID CY561_HUMAN Reviewed; 251 AA.
AC P49447; B2RE96; B7Z775; D3DU11; Q5BJG9; Q9BU05; Q9BWR9;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 25-NOV-2002, sequence version 2.
DT 03-AUG-2022, entry version 186.
DE RecName: Full=Transmembrane ascorbate-dependent reductase CYB561 {ECO:0000305};
DE EC=7.2.1.- {ECO:0000250|UniProtKB:P10897};
DE AltName: Full=Cytochrome b-561;
DE AltName: Full=Cytochrome b561;
GN Name=CYB561 {ECO:0000312|HGNC:HGNC:2571};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Peripheral blood;
RX PubMed=7559396; DOI=10.1074/jbc.270.39.22714;
RA Srivastava M.;
RT "Genomic structure and expression of the human gene encoding cytochrome
RT b561, an integral protein of the chromaffin granule membrane.";
RL J. Biol. Chem. 270:22714-22720(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Mammary gland, and Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain, Lung, and PNS;
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 [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 6-251.
RC TISSUE=Caudate nucleus;
RX PubMed=7980462; DOI=10.1042/bj3030915;
RA Srivastava M., Gibson K.R., Pollard H.B., Fleming P.J.;
RT "Human cytochrome b561: a revised hypothesis for conformation in membranes
RT which reconciles sequence and functional information.";
RL Biochem. J. 303:915-921(1994).
RN [8]
RP INVOLVEMENT IN ORTHYP2, VARIANTS ORTHYP2 44-TRP--GLN-251 DEL AND ARG-88,
RP AND TISSUE SPECIFICITY.
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. It is therefore involved the regeneration and homeostasis
CC within secretory vesicles of ascorbate which in turn provides reducing
CC equivalents needed to support the activity of intravesicular enzymes.
CC {ECO:0000250|UniProtKB:P10897}.
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:0000250|UniProtKB:P10897};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66525;
CC Evidence={ECO:0000250|UniProtKB:P10897};
CC -!- COFACTOR:
CC Name=heme b; Xref=ChEBI:CHEBI:60344;
CC Evidence={ECO:0000250|UniProtKB:P10897};
CC Note=Binds 2 heme b groups non-covalently.
CC {ECO:0000250|UniProtKB:P10897};
CC -!- INTERACTION:
CC P49447; Q86W74-2: ANKRD46; NbExp=3; IntAct=EBI-8646596, EBI-12109402;
CC P49447; Q13520: AQP6; NbExp=3; IntAct=EBI-8646596, EBI-13059134;
CC P49447; Q8NFU1: BEST2; NbExp=3; IntAct=EBI-8646596, EBI-19947314;
CC P49447; O15155: BET1; NbExp=3; IntAct=EBI-8646596, EBI-749204;
CC P49447; Q13323: BIK; NbExp=3; IntAct=EBI-8646596, EBI-700794;
CC P49447; Q12981: BNIP1; NbExp=3; IntAct=EBI-8646596, EBI-4402847;
CC P49447; P11912: CD79A; NbExp=3; IntAct=EBI-8646596, EBI-7797864;
CC P49447; O14735: CDIPT; NbExp=3; IntAct=EBI-8646596, EBI-358858;
CC P49447; O95484: CLDN9; NbExp=3; IntAct=EBI-8646596, EBI-18341636;
CC P49447; Q8TAZ6: CMTM2; NbExp=3; IntAct=EBI-8646596, EBI-2339374;
CC P49447; Q6PI48: DARS2; NbExp=3; IntAct=EBI-8646596, EBI-3917045;
CC P49447; Q15125: EBP; NbExp=3; IntAct=EBI-8646596, EBI-3915253;
CC P49447; Q92838: EDA; NbExp=6; IntAct=EBI-8646596, EBI-529425;
CC P49447; P52803: EFNA5; NbExp=3; IntAct=EBI-8646596, EBI-1753674;
CC P49447; Q08426: EHHADH; NbExp=3; IntAct=EBI-8646596, EBI-2339219;
CC P49447; Q9UKR5: ERG28; NbExp=3; IntAct=EBI-8646596, EBI-711490;
CC P49447; Q9Y282: ERGIC3; NbExp=3; IntAct=EBI-8646596, EBI-781551;
CC P49447; Q14318: FKBP8; NbExp=3; IntAct=EBI-8646596, EBI-724839;
CC P49447; Q9UJ14: GGT7; NbExp=3; IntAct=EBI-8646596, EBI-1058791;
CC P49447; Q96F15: GIMAP5; NbExp=3; IntAct=EBI-8646596, EBI-6166686;
CC P49447; O14653: GOSR2; NbExp=3; IntAct=EBI-8646596, EBI-4401517;
CC P49447; Q8TDT2: GPR152; NbExp=3; IntAct=EBI-8646596, EBI-13345167;
CC P49447; Q8TED1: GPX8; NbExp=3; IntAct=EBI-8646596, EBI-11721746;
CC P49447; P09601: HMOX1; NbExp=3; IntAct=EBI-8646596, EBI-2806151;
CC P49447; Q8TAF8: LHFPL5; NbExp=3; IntAct=EBI-8646596, EBI-2820517;
CC P49447; Q9UBY5: LPAR3; NbExp=3; IntAct=EBI-8646596, EBI-12033434;
CC P49447; P35372-10: OPRM1; NbExp=3; IntAct=EBI-8646596, EBI-12807478;
CC P49447; Q53FV1: ORMDL2; NbExp=3; IntAct=EBI-8646596, EBI-11075081;
CC P49447; Q04941: PLP2; NbExp=3; IntAct=EBI-8646596, EBI-608347;
CC P49447; Q96HR9-2: REEP6; NbExp=3; IntAct=EBI-8646596, EBI-14065960;
CC P49447; Q99942: RNF5; NbExp=3; IntAct=EBI-8646596, EBI-348482;
CC P49447; O00767: SCD; NbExp=3; IntAct=EBI-8646596, EBI-2684237;
CC P49447; Q96IW7: SEC22A; NbExp=3; IntAct=EBI-8646596, EBI-8652744;
CC P49447; Q8N6R1: SERP2; NbExp=3; IntAct=EBI-8646596, EBI-749270;
CC P49447; Q9BZV2: SLC19A3; NbExp=3; IntAct=EBI-8646596, EBI-3923779;
CC P49447; Q9NQQ7-3: SLC35C2; NbExp=3; IntAct=EBI-8646596, EBI-17295964;
CC P49447; Q9NVC3: SLC38A7; NbExp=3; IntAct=EBI-8646596, EBI-10314552;
CC P49447; Q9NY26: SLC39A1; NbExp=3; IntAct=EBI-8646596, EBI-726491;
CC P49447; Q9NP94: SLC39A2; NbExp=3; IntAct=EBI-8646596, EBI-12898013;
CC P49447; B2RUZ4: SMIM1; NbExp=3; IntAct=EBI-8646596, EBI-12188413;
CC P49447; Q8WWF3: SSMEM1; NbExp=3; IntAct=EBI-8646596, EBI-17280858;
CC P49447; Q13277: STX3; NbExp=3; IntAct=EBI-8646596, EBI-1394295;
CC P49447; P57105: SYNJ2BP; NbExp=3; IntAct=EBI-8646596, EBI-1049004;
CC P49447; Q96CE8: TM4SF18; NbExp=3; IntAct=EBI-8646596, EBI-13351685;
CC P49447; P17152: TMEM11; NbExp=3; IntAct=EBI-8646596, EBI-723946;
CC P49447; Q5BJH2-2: TMEM128; NbExp=3; IntAct=EBI-8646596, EBI-10694905;
CC P49447; Q9NUH8: TMEM14B; NbExp=3; IntAct=EBI-8646596, EBI-8638294;
CC P49447; Q7Z7N9: TMEM179B; NbExp=3; IntAct=EBI-8646596, EBI-11724423;
CC P49447; Q9NWH2: TMEM242; NbExp=3; IntAct=EBI-8646596, EBI-10315004;
CC P49447; Q6PI78: TMEM65; NbExp=3; IntAct=EBI-8646596, EBI-6656213;
CC P49447; Q6ZT21: TMPPE; NbExp=3; IntAct=EBI-8646596, EBI-11724433;
CC P49447; Q9NSU2-1: TREX1; NbExp=3; IntAct=EBI-8646596, EBI-16746122;
CC P49447; A0AVG3: TSNARE1; NbExp=3; IntAct=EBI-8646596, EBI-12003468;
CC P49447; Q9Y385: UBE2J1; NbExp=3; IntAct=EBI-8646596, EBI-988826;
CC P49447; Q9P0L0: VAPA; NbExp=3; IntAct=EBI-8646596, EBI-1059156;
CC P49447; O95292: VAPB; NbExp=3; IntAct=EBI-8646596, EBI-1188298;
CC P49447; Q9NXF8-2: ZDHHC7; NbExp=3; IntAct=EBI-8646596, EBI-12948063;
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle,
CC chromaffin granule membrane {ECO:0000250|UniProtKB:P10897}; Multi-pass
CC membrane protein {ECO:0000250|UniProtKB:Q53TN4}. Note=Secretory vesicle
CC containing catecholamines and amidated peptides.
CC {ECO:0000250|UniProtKB:P10897}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P49447-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P49447-2; Sequence=VSP_056950;
CC -!- TISSUE SPECIFICITY: Expressed in many tissues, in particular the brain
CC especially in the cortex and hippocampus.
CC {ECO:0000269|PubMed:29343526}.
CC -!- DISEASE: Orthostatic hypotension 2 (ORTHYP2) [MIM:618182]: An autosomal
CC recessive disorder characterized by severe orthostatic hypotension
CC apparent from infancy or early childhood, low plasma and urinary levels
CC of norepinephrine and epinephrine, and episodic hypoglycemia. Some
CC patients may also have renal dysfunction and reduced life expectancy.
CC Orthostatic hypotension, also known as postural hypotension, is a
CC finding defined as a 20-mm Hg decrease in systolic pressure or a 10-mm
CC Hg decrease in diastolic pressure occurring 3 minutes after a person
CC has risen from supine to standing. Symptoms include dizziness, blurred
CC vision, and sometimes syncope. {ECO:0000269|PubMed:29343526}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
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DR EMBL; U29462; AAC50212.1; -; Genomic_DNA.
DR EMBL; U29460; AAC50212.1; JOINED; Genomic_DNA.
DR EMBL; U29461; AAC50212.1; JOINED; Genomic_DNA.
DR EMBL; U29464; AAC50212.1; JOINED; Genomic_DNA.
DR EMBL; U29469; AAC50212.1; JOINED; Genomic_DNA.
DR EMBL; BT007096; AAP35760.1; -; mRNA.
DR EMBL; AK301541; BAH13511.1; -; mRNA.
DR EMBL; AK316606; BAG38193.1; -; mRNA.
DR EMBL; AC005828; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471109; EAW94322.1; -; Genomic_DNA.
DR EMBL; CH471109; EAW94323.1; -; Genomic_DNA.
DR EMBL; CH471109; EAW94326.1; -; Genomic_DNA.
DR EMBL; BC000021; AAH00021.1; -; mRNA.
DR EMBL; BC002976; AAH02976.1; -; mRNA.
DR EMBL; BC091485; AAH91485.1; -; mRNA.
DR EMBL; U06715; AAA50952.1; -; mRNA.
DR CCDS; CCDS11636.1; -. [P49447-1]
DR PIR; S53321; S53321.
DR RefSeq; NP_001017916.1; NM_001017916.1. [P49447-1]
DR RefSeq; NP_001017917.1; NM_001017917.1. [P49447-1]
DR RefSeq; NP_001317350.1; NM_001330421.1.
DR RefSeq; NP_001906.3; NM_001915.3. [P49447-1]
DR RefSeq; XP_005257148.1; XM_005257091.1.
DR AlphaFoldDB; P49447; -.
DR SMR; P49447; -.
DR BioGRID; 107914; 63.
DR IntAct; P49447; 59.
DR MINT; P49447; -.
DR STRING; 9606.ENSP00000376702; -.
DR TCDB; 5.B.2.1.4; the eukaryotic cytochrome b561 (cytb561) family.
DR iPTMnet; P49447; -.
DR PhosphoSitePlus; P49447; -.
DR BioMuta; CYB561; -.
DR DMDM; 25453426; -.
DR EPD; P49447; -.
DR jPOST; P49447; -.
DR MassIVE; P49447; -.
DR MaxQB; P49447; -.
DR PaxDb; P49447; -.
DR PeptideAtlas; P49447; -.
DR PRIDE; P49447; -.
DR ProteomicsDB; 56011; -. [P49447-1]
DR Antibodypedia; 18653; 87 antibodies from 17 providers.
DR DNASU; 1534; -.
DR Ensembl; ENST00000360793.8; ENSP00000354028.3; ENSG00000008283.16. [P49447-1]
DR Ensembl; ENST00000392975.6; ENSP00000376701.2; ENSG00000008283.16. [P49447-1]
DR Ensembl; ENST00000392976.5; ENSP00000376702.1; ENSG00000008283.16. [P49447-1]
DR Ensembl; ENST00000448884.6; ENSP00000400350.2; ENSG00000008283.16. [P49447-2]
DR Ensembl; ENST00000581573.5; ENSP00000462325.1; ENSG00000008283.16. [P49447-1]
DR Ensembl; ENST00000584291.5; ENSP00000462543.1; ENSG00000008283.16. [P49447-1]
DR GeneID; 1534; -.
DR KEGG; hsa:1534; -.
DR MANE-Select; ENST00000360793.8; ENSP00000354028.3; NM_001915.4; NP_001906.3.
DR UCSC; uc002jap.4; human. [P49447-1]
DR CTD; 1534; -.
DR DisGeNET; 1534; -.
DR GeneCards; CYB561; -.
DR HGNC; HGNC:2571; CYB561.
DR HPA; ENSG00000008283; Low tissue specificity.
DR MalaCards; CYB561; -.
DR MIM; 600019; gene.
DR MIM; 618182; phenotype.
DR neXtProt; NX_P49447; -.
DR OpenTargets; ENSG00000008283; -.
DR PharmGKB; PA27069; -.
DR VEuPathDB; HostDB:ENSG00000008283; -.
DR eggNOG; KOG1619; Eukaryota.
DR GeneTree; ENSGT00950000183197; -.
DR HOGENOM; CLU_069712_3_2_1; -.
DR InParanoid; P49447; -.
DR OMA; SYLPIHV; -.
DR PhylomeDB; P49447; -.
DR TreeFam; TF314222; -.
DR BRENDA; 7.2.1.3; 2681.
DR PathwayCommons; P49447; -.
DR SignaLink; P49447; -.
DR BioGRID-ORCS; 1534; 19 hits in 1077 CRISPR screens.
DR ChiTaRS; CYB561; human.
DR GeneWiki; CYB561; -.
DR GenomeRNAi; 1534; -.
DR Pharos; P49447; Tbio.
DR PRO; PR:P49447; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; P49447; protein.
DR Bgee; ENSG00000008283; Expressed in right uterine tube and 184 other tissues.
DR ExpressionAtlas; P49447; baseline and differential.
DR Genevisible; P49447; HS.
DR GO; GO:0042584; C:chromaffin granule membrane; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; NAS:UniProtKB.
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; ISS:UniProtKB.
DR GO; GO:0140576; P:ascorbate homeostasis; ISS:UniProtKB.
DR GO; GO:0006879; P:cellular iron ion homeostasis; IEA:Ensembl.
DR GO; GO:0022900; P:electron transport chain; NAS: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; Alternative splicing; Cytoplasmic vesicle; Disease variant;
KW Electron transport; Heme; Iron; Membrane; Metal-binding; Phosphoprotein;
KW Reference proteome; Translocase; Transmembrane; Transmembrane helix;
KW Transport.
FT CHAIN 1..251
FT /note="Transmembrane ascorbate-dependent reductase CYB561"
FT /id="PRO_0000151027"
FT TOPO_DOM 1..16
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT TRANSMEM 17..37
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 38..51
FT /note="Vesicular"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT TRANSMEM 52..72
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 73..85
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT TRANSMEM 86..106
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 107..124
FT /note="Vesicular"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT TRANSMEM 125..145
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 146..158
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT TRANSMEM 159..179
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 180..198
FT /note="Vesicular"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT TRANSMEM 199..219
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 220..251
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT DOMAIN 19..220
FT /note="Cytochrome b561"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00242"
FT BINDING 53
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 73
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT BINDING 80
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT BINDING 80
FT /ligand="L-ascorbate"
FT /ligand_id="ChEBI:CHEBI:38290"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT BINDING 84
FT /ligand="L-ascorbate"
FT /ligand_id="ChEBI:CHEBI:38290"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT BINDING 87
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 116..119
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT BINDING 121
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 153
FT /ligand="L-ascorbate"
FT /ligand_id="ChEBI:CHEBI:38290"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT BINDING 160
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 181
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT BINDING 225
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 247
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q60720"
FT VAR_SEQ 136..251
FT /note="WLVGFSFFLFPGASFSLRSRYRPQHIFFGATIFLLSVGTALLGLKEALLFNL
FT GGKYSAFEPEGVLANVLGLLLACFGGAVLYILTRADWKRPSQAEEQALSMDFKTLTEGD
FT SPGSQ -> GQV (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056950"
FT VARIANT 44..251
FT /note="Missing (in ORTHYP2)"
FT /evidence="ECO:0000269|PubMed:29343526"
FT /id="VAR_081730"
FT VARIANT 88
FT /note="G -> R (in ORTHYP2; dbSNP:rs772361572)"
FT /evidence="ECO:0000269|PubMed:29343526"
FT /id="VAR_081731"
FT CONFLICT 6
FT /note="A -> S (in Ref. 6; AAH02976)"
FT /evidence="ECO:0000305"
FT CONFLICT 171
FT /note="S -> P (in Ref. 1; AAC50212 and 7; AAA50952)"
FT /evidence="ECO:0000305"
FT CONFLICT 243..244
FT /note="TE -> RQ (in Ref. 1; AAC50212 and 7; AAA50952)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 251 AA; 27559 MW; 8EE53AE4D2569B77 CRC64;
MEGGAAAATP TALPYYVAFS QLLGLTLVAM TGAWLGLYRG GIAWESDLQF NAHPLCMVIG
LIFLQGNALL VYRVFRNEAK RTTKVLHGLL HIFALVIALV GLVAVFDYHR KKGYADLYSL
HSWCGILVFV LYFVQWLVGF SFFLFPGASF SLRSRYRPQH IFFGATIFLL SVGTALLGLK
EALLFNLGGK YSAFEPEGVL ANVLGLLLAC FGGAVLYILT RADWKRPSQA EEQALSMDFK
TLTEGDSPGS Q
