ID   C56D1_HUMAN             Reviewed;         229 AA.
AC   Q8N8Q1; B4DH97; E9PCM8; Q52M36; Q5T6C2; Q5T6C3;
DT   10-MAY-2005, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2002, sequence version 1.
DT   27-MAR-2024, entry version 149.
DE   RecName: Full=Probable transmembrane reductase CYB561D1 {ECO:0000305};
DE            EC=7.2.1.3 {ECO:0000305};
DE   AltName: Full=Cytochrome b561 domain-containing protein 1 {ECO:0000312|HGNC:HGNC:26804};
GN   Name=CYB561D1 {ECO:0000312|HGNC:HGNC:26804};
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 [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3).
RC   TISSUE=Brain;
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   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX   PubMed=16344560; DOI=10.1101/gr.4039406;
RA   Kimura K., Wakamatsu A., Suzuki Y., Ota T., Nishikawa T., Yamashita R.,
RA   Yamamoto J., Sekine M., Tsuritani K., Wakaguri H., Ishii S., Sugiyama T.,
RA   Saito K., Isono Y., Irie R., Kushida N., Yoneyama T., Otsuka R., Kanda K.,
RA   Yokoi T., Kondo H., Wagatsuma M., Murakawa K., Ishida S., Ishibashi T.,
RA   Takahashi-Fujii A., Tanase T., Nagai K., Kikuchi H., Nakai K., Isogai T.,
RA   Sugano S.;
RT   "Diversification of transcriptional modulation: large-scale identification
RT   and characterization of putative alternative promoters of human genes.";
RL   Genome Res. 16:55-65(2006).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16710414; DOI=10.1038/nature04727;
RA   Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA   Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA   Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA   Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA   Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA   Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA   Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA   Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA   Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA   Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA   Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA   Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA   Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA   Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA   Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA   Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA   Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA   Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA   McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA   Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA   Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA   Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA   Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA   Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA   White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA   Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA   Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA   Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT   "The DNA sequence and biological annotation of human chromosome 1.";
RL   Nature 441:315-321(2006).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Liver;
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).
CC   -!- FUNCTION: Probable transmembrane reductase that may use ascorbate as an
CC       electron donor and transfer electrons across membranes to reduce
CC       monodehydro-L-ascorbate radical and iron cations Fe(3+) in another
CC       cellular compartment. {ECO:0000305}.
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};
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:0000305};
CC   -!- COFACTOR:
CC       Name=heme b; Xref=ChEBI:CHEBI:60344;
CC         Evidence={ECO:0000250|UniProtKB:Q53TN4};
CC       Note=Binds 2 heme b groups non-covalently.
CC       {ECO:0000250|UniProtKB:Q53TN4};
CC   -!- INTERACTION:
CC       Q8N8Q1; Q13520: AQP6; NbExp=3; IntAct=EBI-12873482, EBI-13059134;
CC       Q8N8Q1; P13569: CFTR; NbExp=3; IntAct=EBI-12873482, EBI-349854;
CC       Q8N8Q1; Q05329: GAD2; NbExp=3; IntAct=EBI-12873482, EBI-9304251;
CC       Q8N8Q1; Q6PL24: TMED8; NbExp=3; IntAct=EBI-12873482, EBI-11603430;
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Multi-pass membrane
CC       protein {ECO:0000305}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=5;
CC       Name=1;
CC         IsoId=Q8N8Q1-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q8N8Q1-2; Sequence=VSP_038649, VSP_038650;
CC       Name=3;
CC         IsoId=Q8N8Q1-3; Sequence=VSP_041162;
CC       Name=4;
CC         IsoId=Q8N8Q1-4; Sequence=VSP_046986;
CC       Name=5;
CC         IsoId=Q8N8Q1-5; Sequence=VSP_046985;
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DR   EMBL; AK096354; BAC04767.1; -; mRNA.
DR   EMBL; AK294992; BAG58058.1; -; mRNA.
DR   EMBL; DA092655; -; NOT_ANNOTATED_CDS; mRNA.
DR   EMBL; AL355145; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC093683; AAH93683.1; -; mRNA.
DR   EMBL; BC111999; AAI12000.1; -; mRNA.
DR   CCDS; CCDS44188.1; -. [Q8N8Q1-3]
DR   CCDS; CCDS44189.1; -. [Q8N8Q1-5]
DR   CCDS; CCDS44190.1; -. [Q8N8Q1-2]
DR   CCDS; CCDS44191.1; -. [Q8N8Q1-4]
DR   CCDS; CCDS800.1; -. [Q8N8Q1-1]
DR   RefSeq; NP_001127872.1; NM_001134400.1. [Q8N8Q1-3]
DR   RefSeq; NP_001127874.1; NM_001134402.1. [Q8N8Q1-5]
DR   RefSeq; NP_872386.1; NM_182580.2. [Q8N8Q1-1]
DR   AlphaFoldDB; Q8N8Q1; -.
DR   SMR; Q8N8Q1; -.
DR   BioGRID; 129916; 5.
DR   IntAct; Q8N8Q1; 4.
DR   MINT; Q8N8Q1; -.
DR   STRING; 9606.ENSP00000358884; -.
DR   iPTMnet; Q8N8Q1; -.
DR   PhosphoSitePlus; Q8N8Q1; -.
DR   BioMuta; CYB561D1; -.
DR   DMDM; 67462193; -.
DR   EPD; Q8N8Q1; -.
DR   jPOST; Q8N8Q1; -.
DR   MassIVE; Q8N8Q1; -.
DR   MaxQB; Q8N8Q1; -.
DR   PeptideAtlas; Q8N8Q1; -.
DR   ProteomicsDB; 19474; -.
DR   ProteomicsDB; 64575; -.
DR   ProteomicsDB; 72442; -. [Q8N8Q1-1]
DR   ProteomicsDB; 72443; -. [Q8N8Q1-2]
DR   ProteomicsDB; 72444; -. [Q8N8Q1-3]
DR   TopDownProteomics; Q8N8Q1-1; -. [Q8N8Q1-1]
DR   Antibodypedia; 20066; 129 antibodies from 21 providers.
DR   DNASU; 284613; -.
DR   Ensembl; ENST00000310611.8; ENSP00000309324.4; ENSG00000174151.15. [Q8N8Q1-2]
DR   Ensembl; ENST00000369868.7; ENSP00000358884.3; ENSG00000174151.15. [Q8N8Q1-3]
DR   Ensembl; ENST00000393709.3; ENSP00000377312.3; ENSG00000174151.15. [Q8N8Q1-5]
DR   Ensembl; ENST00000420578.7; ENSP00000413530.2; ENSG00000174151.15. [Q8N8Q1-1]
DR   Ensembl; ENST00000430195.2; ENSP00000416898.2; ENSG00000174151.15. [Q8N8Q1-4]
DR   GeneID; 284613; -.
DR   KEGG; hsa:284613; -.
DR   MANE-Select; ENST00000420578.7; ENSP00000413530.2; NM_182580.3; NP_872386.1.
DR   UCSC; uc001dxu.4; human. [Q8N8Q1-1]
DR   AGR; HGNC:26804; -.
DR   CTD; 284613; -.
DR   DisGeNET; 284613; -.
DR   GeneCards; CYB561D1; -.
DR   HGNC; HGNC:26804; CYB561D1.
DR   HPA; ENSG00000174151; Low tissue specificity.
DR   neXtProt; NX_Q8N8Q1; -.
DR   OpenTargets; ENSG00000174151; -.
DR   PharmGKB; PA134872038; -.
DR   VEuPathDB; HostDB:ENSG00000174151; -.
DR   GeneTree; ENSGT00440000038072; -.
DR   HOGENOM; CLU_072399_3_1_1; -.
DR   InParanoid; Q8N8Q1; -.
DR   OMA; SDWFQAT; -.
DR   OrthoDB; 51140at2759; -.
DR   PhylomeDB; Q8N8Q1; -.
DR   TreeFam; TF323584; -.
DR   PathwayCommons; Q8N8Q1; -.
DR   SignaLink; Q8N8Q1; -.
DR   BioGRID-ORCS; 284613; 19 hits in 1156 CRISPR screens.
DR   ChiTaRS; CYB561D1; human.
DR   GenomeRNAi; 284613; -.
DR   Pharos; Q8N8Q1; Tdark.
DR   PRO; PR:Q8N8Q1; -.
DR   Proteomes; UP000005640; Chromosome 1.
DR   RNAct; Q8N8Q1; Protein.
DR   Bgee; ENSG00000174151; Expressed in upper arm skin and 143 other cell types or tissues.
DR   ExpressionAtlas; Q8N8Q1; baseline and differential.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0020037; F:heme binding; 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:0140571; F:transmembrane ascorbate ferrireductase activity; IEA:UniProtKB-EC.
DR   GO; GO:0140575; F:transmembrane monodehydroascorbate reductase activity; IEA:InterPro.
DR   CDD; cd08761; Cyt_b561_CYB561D2_like; 1.
DR   Gene3D; 1.20.120.1770; -; 1.
DR   InterPro; IPR045150; CYB561D1/2.
DR   InterPro; IPR006593; Cyt_b561/ferric_Rdtase_TM.
DR   PANTHER; PTHR15422; OS05G0565100 PROTEIN; 1.
DR   PANTHER; PTHR15422:SF9; TRANSMEMBRANE REDUCTASE CYB561D1-RELATED; 1.
DR   Pfam; PF03188; Cytochrom_B561; 1.
DR   SMART; SM00665; B561; 1.
DR   PROSITE; PS50939; CYTOCHROME_B561; 1.
DR   Genevisible; Q8N8Q1; HS.
PE   1: Evidence at protein level;
KW   Alternative splicing; Electron transport; Heme; Iron; Membrane;
KW   Metal-binding; Reference proteome; Translocase; Transmembrane;
KW   Transmembrane helix; Transport.
FT   CHAIN           1..229
FT                   /note="Probable transmembrane reductase CYB561D1"
FT                   /id="PRO_0000151034"
FT   TOPO_DOM        1..24
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        25..45
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        46..53
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        54..74
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        75..91
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        92..112
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        113..128
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        129..149
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        150..169
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        170..190
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        191..193
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        194..214
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        215..229
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   DOMAIN          22..224
FT                   /note="Cytochrome b561"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00242"
FT   BINDING         55
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         93
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         127
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         166
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   VAR_SEQ         6..62
FT                   /note="Missing (in isoform 5)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_046985"
FT   VAR_SEQ         50..229
FT                   /note="SLFSWHPVFMALAFCLCMAEAILLFSPEHSLFFFCSRKARIRLHWAGQTLAI
FT                   LCAALGLGFIISSRTRSELPHLVSWHSWVGALTLLATAVQALCGLCLLCPRAARVSRVA
FT                   RLKLYHLTCGLVVYLMATVTVLLGMYSVWFQAQIKGAAWYLCLALPVYPALVIMHQISR
FT                   SYLPRKKMEM -> KTGPLMEDRSEGGRARWVMPEIPALWEADAGGSLEVFSPGTLYSW
FT                   PWRMYESTSFFSGLQARHEAYWLSPMFTVLPLHG (in isoform 4)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_046986"
FT   VAR_SEQ         50..133
FT                   /note="SLFSWHPVFMALAFCLCMAEAILLFSPEHSLFFFCSRKARIRLHWAGQTLAI
FT                   LCAALGLGFIISSRTRSELPHLVSWHSWVGAL -> KTGPLMEDRSEGGRARWVMPEIP
FT                   ALWEADAGGSLEVFSPGTLYSWPWRSASAWLKPSYSSHLNTPCSSSAPEKHGSGSTGQG
FT                   RP (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_038649"
FT   VAR_SEQ         50..62
FT                   /note="SLFSWHPVFMALA -> KTGPLMEDRSEGGRARWVMPEIPALWEADAGGSLE
FT                   (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_041162"
FT   VAR_SEQ         134..229
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_038650"
SQ   SEQUENCE   229 AA;  25424 MW;  43978DAF7D8EC218 CRC64;
     MQPLEVGLVP APAGEPRLTR WLRRGSGILA HLVALGFTIF LTALSRPGTS LFSWHPVFMA
     LAFCLCMAEA ILLFSPEHSL FFFCSRKARI RLHWAGQTLA ILCAALGLGF IISSRTRSEL
     PHLVSWHSWV GALTLLATAV QALCGLCLLC PRAARVSRVA RLKLYHLTCG LVVYLMATVT
     VLLGMYSVWF QAQIKGAAWY LCLALPVYPA LVIMHQISRS YLPRKKMEM
//