C56D1_HUMAN
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 03-AUG-2022, entry version 140.
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; 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; 3.
DR IntAct; Q8N8Q1; 3.
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 PRIDE; 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; 114 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 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; WFQATVK; -.
DR PhylomeDB; Q8N8Q1; -.
DR TreeFam; TF323584; -.
DR PathwayCommons; Q8N8Q1; -.
DR SignaLink; Q8N8Q1; -.
DR BioGRID-ORCS; 284613; 17 hits in 1078 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 141 other tissues.
DR ExpressionAtlas; Q8N8Q1; baseline and differential.
DR Genevisible; Q8N8Q1; HS.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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 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 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
