C56D2_MOUSE
ID C56D2_MOUSE Reviewed; 222 AA.
AC Q9WUE3; Q3TRQ1;
DT 10-MAY-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 131.
DE RecName: Full=Transmembrane reductase CYB561D2 {ECO:0000305|PubMed:17938141};
DE EC=7.2.1.3 {ECO:0000269|PubMed:17938141};
DE AltName: Full=Cytochrome b561 domain-containing protein 2 {ECO:0000312|MGI:MGI:1929280};
GN Name=Cyb561d2 {ECO:0000312|MGI:MGI:1929280};
GN Synonyms=101f6 {ECO:0000303|PubMed:17938141};
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 STRAIN=C57BL/6J;
RA Duh F.-M., Minna J.D., Lerman M.I.;
RT "Mouse ortholog of the human 101F6 gene.";
RL Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, COFACTOR,
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND MUTAGENESIS OF
RP 111-LEU--PRO-222 AND 139-MET--PRO-222.
RX PubMed=17938141; DOI=10.1093/jb/mvm185;
RA Mizutani A., Sanuki R., Kakimoto K., Kojo S., Taketani S.;
RT "Involvement of 101F6, a homologue of cytochrome b561, in the reduction of
RT ferric ions.";
RL J. Biochem. 142:699-705(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Cerebellum, and Testis;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
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 [5]
RP FUNCTION, COFACTOR, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=19943161; DOI=10.1007/s00249-009-0564-4;
RA Berczi A., Desmet F., Van Doorslaer S., Asard H.;
RT "Spectral characterization of the recombinant mouse tumor suppressor 101F6
RT protein.";
RL Eur. Biophys. J. 39:1129-1142(2010).
CC -!- FUNCTION: Transmembrane reductase that may use ascorbate as an electron
CC donor in the cytoplasm and transfer electrons across endoplasmic
CC reticulum membranes to reduce monodehydro-L-ascorbate radical and iron
CC cations Fe(3+) in the lumen of that compartment.
CC {ECO:0000269|PubMed:17938141, ECO:0000269|PubMed:19943161}.
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:O14569};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66525;
CC Evidence={ECO:0000250|UniProtKB:O14569};
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:0000269|PubMed:17938141};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:30404;
CC Evidence={ECO:0000305|PubMed:17938141};
CC -!- COFACTOR:
CC Name=heme b; Xref=ChEBI:CHEBI:60344;
CC Evidence={ECO:0000269|PubMed:17938141, ECO:0000269|PubMed:19943161};
CC Note=Binds 2 heme b groups non-covalently.
CC {ECO:0000269|PubMed:19943161};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Redox potential:
CC E(0) is +141 +/-9 mV for the high potential heme and +43 +/-9 mV for
CC the low potential heme. {ECO:0000269|PubMed:19943161};
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:17938141}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q53TN4}. Cytoplasmic vesicle membrane
CC {ECO:0000269|PubMed:17938141}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q53TN4}.
CC -!- TISSUE SPECIFICITY: Highly expressed in the brain, lung, liver, and
CC kidney (PubMed:17938141). Moderately expressed in the heart, placenta,
CC skeletal muscle, and pancreas (PubMed:17938141).
CC {ECO:0000269|PubMed:17938141}.
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DR EMBL; AF131206; AAD33473.1; -; mRNA.
DR EMBL; AK030225; BAC26855.1; -; mRNA.
DR EMBL; AK162586; BAE36976.1; -; mRNA.
DR EMBL; BC027212; AAH27212.1; -; mRNA.
DR CCDS; CCDS23491.1; -.
DR RefSeq; NP_062694.1; NM_019720.4.
DR RefSeq; XP_006511838.1; XM_006511775.3.
DR RefSeq; XP_006511839.1; XM_006511776.3.
DR AlphaFoldDB; Q9WUE3; -.
DR SMR; Q9WUE3; -.
DR STRING; 10090.ENSMUSP00000044093; -.
DR TCDB; 5.B.2.1.2; the eukaryotic cytochrome b561 (cytb561) family.
DR iPTMnet; Q9WUE3; -.
DR PhosphoSitePlus; Q9WUE3; -.
DR EPD; Q9WUE3; -.
DR jPOST; Q9WUE3; -.
DR MaxQB; Q9WUE3; -.
DR PaxDb; Q9WUE3; -.
DR PRIDE; Q9WUE3; -.
DR ProteomicsDB; 281719; -.
DR Antibodypedia; 30954; 144 antibodies from 28 providers.
DR DNASU; 56368; -.
DR Ensembl; ENSMUST00000041459; ENSMUSP00000044093; ENSMUSG00000037190.
DR Ensembl; ENSMUST00000195235; ENSMUSP00000141723; ENSMUSG00000037190.
DR GeneID; 56368; -.
DR KEGG; mmu:56368; -.
DR UCSC; uc009rll.1; mouse.
DR CTD; 11068; -.
DR MGI; MGI:1929280; Cyb561d2.
DR VEuPathDB; HostDB:ENSMUSG00000037190; -.
DR eggNOG; ENOG502QRPJ; Eukaryota.
DR GeneTree; ENSGT00440000038072; -.
DR HOGENOM; CLU_072399_3_0_1; -.
DR InParanoid; Q9WUE3; -.
DR OMA; ATWHGWA; -.
DR OrthoDB; 1586923at2759; -.
DR PhylomeDB; Q9WUE3; -.
DR TreeFam; TF323584; -.
DR BRENDA; 7.2.1.3; 3474.
DR BioGRID-ORCS; 56368; 1 hit in 72 CRISPR screens.
DR PRO; PR:Q9WUE3; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q9WUE3; protein.
DR Bgee; ENSMUSG00000037190; Expressed in Meckel's cartilage and 247 other tissues.
DR ExpressionAtlas; Q9WUE3; baseline and differential.
DR Genevisible; Q9WUE3; MM.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0031982; C:vesicle; IDA:UniProtKB.
DR GO; GO:0020037; F:heme binding; IDA: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; IMP:UniProtKB.
DR GO; GO:0140575; F:transmembrane monodehydroascorbate reductase activity; ISS:UniProtKB.
DR GO; GO:0140576; P:ascorbate homeostasis; ISS:UniProtKB.
DR InterPro; IPR045150; CYB561D1/2.
DR InterPro; IPR006593; Cyt_b561/ferric_Rdtase_TM.
DR PANTHER; PTHR15422; PTHR15422; 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 Cytoplasmic vesicle; Electron transport; Endoplasmic reticulum; Heme; Iron;
KW Membrane; Metal-binding; Reference proteome; Translocase; Transmembrane;
KW Transmembrane helix; Transport.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:O14569"
FT CHAIN 2..222
FT /note="Transmembrane reductase CYB561D2"
FT /id="PRO_0000151037"
FT TOPO_DOM 2..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..46
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT TRANSMEM 47..67
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 68..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..122
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT TRANSMEM 123..143
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 144..162
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT TRANSMEM 163..183
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 184..186
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT TRANSMEM 187..207
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 208..222
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT DOMAIN 14..217
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 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 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 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 MUTAGEN 111..222
FT /note="Missing: Loss of heme binding."
FT /evidence="ECO:0000269|PubMed:17938141"
FT MUTAGEN 139..222
FT /note="Missing: Loss of heme binding."
FT /evidence="ECO:0000269|PubMed:17938141"
SQ SEQUENCE 222 AA; 24187 MW; 149EC4899F051BF2 CRC64;
MALSVETESH IYRALRTASG AAAHLVALGF TIFVAVLARP GSSLFSWHPV LMSLAFSFLM
TEALLMFSPE SSLLRSLSRK VRARCHWVLQ LLALLCALLG LGLVILHKEQ LGKAHLTTRH
GQAGLLAVLW AGLQCSGGMG LLYPKLLPRW PLAKLKLYHA TSGLVGYLLG SASLLLGMFS
LWFTATVTGG AWYLAVLCPI LTSLVIMNQV SNAYLYRKRI QP
