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 27-MAR-2024, entry version 195. 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. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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.ENSP00000464215; -. DR TCDB; 5.B.2.1.4; the eukaryotic cytochrome b561 (cytb561) family. DR iPTMnet; P49447; -. DR PhosphoSitePlus; P49447; -. DR SwissPalm; P49447; -. DR BioMuta; CYB561; -. DR DMDM; 25453426; -. DR EPD; P49447; -. DR jPOST; P49447; -. DR MassIVE; P49447; -. DR MaxQB; P49447; -. DR PaxDb; 9606-ENSP00000376702; -. DR PeptideAtlas; P49447; -. DR ProteomicsDB; 56011; -. [P49447-1] DR Pumba; P49447; -. DR Antibodypedia; 18653; 90 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 AGR; HGNC:2571; -. 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; EFHYHPT; -. DR OrthoDB; 2877457at2759; -. DR PhylomeDB; P49447; -. DR TreeFam; TF314222; -. DR BRENDA; 7.2.1.3; 2681. DR PathwayCommons; P49447; -. DR SignaLink; P49447; -. DR BioGRID-ORCS; 1534; 21 hits in 1153 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 186 other cell types or tissues. DR ExpressionAtlas; P49447; baseline and differential. DR GO; GO:0042584; C:chromaffin granule membrane; ISS:UniProtKB. DR GO; GO:0005765; C:lysosomal membrane; IBA:GO_Central. DR GO; GO:0016020; C:membrane; NAS: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:0140575; F:transmembrane monodehydroascorbate reductase activity; ISS:UniProtKB. DR GO; GO:0140576; P:ascorbate homeostasis; ISS:UniProtKB. DR GO; GO:0022900; P:electron transport chain; NAS:UniProtKB. DR GO; GO:0006879; P:intracellular iron ion homeostasis; IEA:Ensembl. DR CDD; cd08763; Cyt_b561_CYB561; 1. DR Gene3D; 1.20.120.1770; -; 1. DR InterPro; IPR043205; CYB561/CYBRD1-like. DR InterPro; IPR006593; Cyt_b561/ferric_Rdtase_TM. DR PANTHER; PTHR10106; CYTOCHROME B561-RELATED; 1. DR PANTHER; PTHR10106:SF14; TRANSMEMBRANE ASCORBATE-DEPENDENT REDUCTASE CYB561; 1. DR Pfam; PF03188; Cytochrom_B561; 1. DR SMART; SM00665; B561; 1. DR PROSITE; PS50939; CYTOCHROME_B561; 1. DR Genevisible; P49447; HS. 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 //