NB5R1_HUMAN
ID NB5R1_HUMAN Reviewed; 305 AA.
AC Q9UHQ9; A0PK21; B2R8E0; O95329; Q53F73; Q8NCL5; Q9UHJ1;
DT 15-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=NADH-cytochrome b5 reductase 1;
DE Short=b5R.1;
DE EC=1.6.2.2;
DE AltName: Full=Humb5R2;
DE AltName: Full=NAD(P)H:quinone oxidoreductase type 3 polypeptide A2;
GN Name=CYB5R1; Synonyms=NQO3A2; ORFNames=UNQ3049/PRO9865;
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 [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=10611283; DOI=10.1073/pnas.96.26.14742;
RA Zhu H., Qiu H., Yoon H.-W., Huang S., Bunn H.F.;
RT "Identification of a cytochrome b-type NAD(P)H oxidoreductase ubiquitously
RT expressed in human cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:14742-14747(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Xu Z.G., Yu L., Yue P., Tu Q., Zheng L.H., Zhao S.Y.;
RT "Cloning of a new human cDNA homology to human NADH-cytochrome-b5 reductase
RT mRNA.";
RL Submitted (SEP-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=16303743; DOI=10.1093/dnares/12.2.117;
RA Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J.,
RA Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S.,
RA Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y.,
RA Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S.,
RA Isogai T.;
RT "Signal sequence and keyword trap in silico for selection of full-length
RT human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA
RT libraries.";
RL DNA Res. 12:117-126(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Adrenal gland;
RA Peng Y., Gu Y., Li Y., Fu S., Gu J., Zhang L., Jiang C., Yu Y., Fu G.,
RA Wang Y., Chen Z., Han Z.;
RT "A novel gene expressed in human adrenal gland.";
RL Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
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 [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 172-305.
RA Barrow I.K.-P., Boguski M.S., Touchman J., Spencer F.;
RT "Full-insert sequence of mapped XREF EST.";
RL Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP PROTEIN SEQUENCE OF 66-81 AND 140-158, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC TISSUE=Platelet;
RA Bienvenut W.V., Claeys D.;
RL Submitted (NOV-2005) to UniProtKB.
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
CC -!- FUNCTION: NADH-cytochrome b5 reductases are involved in desaturation
CC and elongation of fatty acids, cholesterol biosynthesis, drug
CC metabolism, and, in erythrocyte, methemoglobin reduction.
CC {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 Fe(III)-[cytochrome b5] + NADH = 2 Fe(II)-[cytochrome b5] +
CC H(+) + NAD(+); Xref=Rhea:RHEA:46680, Rhea:RHEA-COMP:10438, Rhea:RHEA-
CC COMP:10439, ChEBI:CHEBI:15378, ChEBI:CHEBI:29033, ChEBI:CHEBI:29034,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.6.2.2;
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000250};
CC -!- INTERACTION:
CC Q9UHQ9; A8MV81: HIGD1C; NbExp=3; IntAct=EBI-953870, EBI-12809676;
CC Q9UHQ9; O43765: SGTA; NbExp=3; IntAct=EBI-953870, EBI-347996;
CC Q9UHQ9; Q96EQ0: SGTB; NbExp=3; IntAct=EBI-953870, EBI-744081;
CC Q9UHQ9; Q86UW2: SLC51B; NbExp=3; IntAct=EBI-953870, EBI-12266756;
CC Q9UHQ9; Q99614: TTC1; NbExp=3; IntAct=EBI-953870, EBI-742074;
CC Q9UHQ9; Q9UMX0: UBQLN1; NbExp=3; IntAct=EBI-953870, EBI-741480;
CC Q9UHQ9; Q9UMX0-2: UBQLN1; NbExp=3; IntAct=EBI-953870, EBI-10173939;
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass membrane
CC protein {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:10611283}.
CC -!- SIMILARITY: Belongs to the flavoprotein pyridine nucleotide cytochrome
CC reductase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC72953.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=AAI27946.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF169481; AAF06147.1; -; mRNA.
DR EMBL; AF087912; AAP97209.1; -; mRNA.
DR EMBL; AF093822; AAP97218.1; -; mRNA.
DR EMBL; AY359026; AAQ89385.1; -; mRNA.
DR EMBL; AK074654; BAC11115.1; -; mRNA.
DR EMBL; AF125533; AAF17227.1; -; mRNA.
DR EMBL; AK223416; BAD97136.1; -; mRNA.
DR EMBL; AK313333; BAG36137.1; -; mRNA.
DR EMBL; CH471067; EAW91452.1; -; Genomic_DNA.
DR EMBL; BC018732; AAH18732.1; -; mRNA.
DR EMBL; BC127945; AAI27946.1; ALT_INIT; mRNA.
DR EMBL; AF091084; AAC72953.1; ALT_INIT; mRNA.
DR CCDS; CCDS1431.1; -.
DR RefSeq; NP_057327.2; NM_016243.2.
DR AlphaFoldDB; Q9UHQ9; -.
DR SMR; Q9UHQ9; -.
DR BioGRID; 119690; 120.
DR IntAct; Q9UHQ9; 27.
DR MINT; Q9UHQ9; -.
DR STRING; 9606.ENSP00000356218; -.
DR DrugBank; DB03147; Flavin adenine dinucleotide.
DR CarbonylDB; Q9UHQ9; -.
DR iPTMnet; Q9UHQ9; -.
DR PhosphoSitePlus; Q9UHQ9; -.
DR BioMuta; CYB5R1; -.
DR DMDM; 74761957; -.
DR EPD; Q9UHQ9; -.
DR jPOST; Q9UHQ9; -.
DR MassIVE; Q9UHQ9; -.
DR MaxQB; Q9UHQ9; -.
DR PaxDb; Q9UHQ9; -.
DR PeptideAtlas; Q9UHQ9; -.
DR PRIDE; Q9UHQ9; -.
DR ProteomicsDB; 84401; -.
DR Antibodypedia; 2536; 271 antibodies from 28 providers.
DR DNASU; 51706; -.
DR Ensembl; ENST00000367249.9; ENSP00000356218.4; ENSG00000159348.13.
DR GeneID; 51706; -.
DR KEGG; hsa:51706; -.
DR MANE-Select; ENST00000367249.9; ENSP00000356218.4; NM_016243.3; NP_057327.2.
DR UCSC; uc001gyt.3; human.
DR CTD; 51706; -.
DR DisGeNET; 51706; -.
DR GeneCards; CYB5R1; -.
DR HGNC; HGNC:13397; CYB5R1.
DR HPA; ENSG00000159348; Tissue enhanced (skeletal).
DR MIM; 608341; gene.
DR neXtProt; NX_Q9UHQ9; -.
DR OpenTargets; ENSG00000159348; -.
DR PharmGKB; PA134979668; -.
DR VEuPathDB; HostDB:ENSG00000159348; -.
DR eggNOG; KOG0534; Eukaryota.
DR GeneTree; ENSGT00940000160784; -.
DR HOGENOM; CLU_003827_9_2_1; -.
DR InParanoid; Q9UHQ9; -.
DR OMA; QAQHPNR; -.
DR OrthoDB; 1311668at2759; -.
DR PhylomeDB; Q9UHQ9; -.
DR TreeFam; TF314333; -.
DR PathwayCommons; Q9UHQ9; -.
DR Reactome; R-HSA-114608; Platelet degranulation.
DR Reactome; R-HSA-1237044; Erythrocytes take up carbon dioxide and release oxygen.
DR SignaLink; Q9UHQ9; -.
DR BioGRID-ORCS; 51706; 11 hits in 1081 CRISPR screens.
DR ChiTaRS; CYB5R1; human.
DR GeneWiki; CYB5R1; -.
DR GenomeRNAi; 51706; -.
DR Pharos; Q9UHQ9; Tbio.
DR PRO; PR:Q9UHQ9; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9UHQ9; protein.
DR Bgee; ENSG00000159348; Expressed in skeletal muscle tissue of biceps brachii and 201 other tissues.
DR ExpressionAtlas; Q9UHQ9; baseline and differential.
DR Genevisible; Q9UHQ9; HS.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; HDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0031092; C:platelet alpha granule membrane; TAS:Reactome.
DR GO; GO:0004128; F:cytochrome-b5 reductase activity, acting on NAD(P)H; TAS:Reactome.
DR GO; GO:0071949; F:FAD binding; IBA:GO_Central.
DR GO; GO:0015701; P:bicarbonate transport; TAS:Reactome.
DR GO; GO:0016126; P:sterol biosynthetic process; IEA:UniProtKB-KW.
DR Gene3D; 3.40.50.80; -; 1.
DR InterPro; IPR001834; CBR-like.
DR InterPro; IPR008333; Cbr1-like_FAD-bd_dom.
DR InterPro; IPR017927; FAD-bd_FR_type.
DR InterPro; IPR001709; Flavoprot_Pyr_Nucl_cyt_Rdtase.
DR InterPro; IPR039261; FNR_nucleotide-bd.
DR InterPro; IPR001433; OxRdtase_FAD/NAD-bd.
DR InterPro; IPR017938; Riboflavin_synthase-like_b-brl.
DR PANTHER; PTHR19370; PTHR19370; 1.
DR Pfam; PF00970; FAD_binding_6; 1.
DR Pfam; PF00175; NAD_binding_1; 1.
DR PRINTS; PR00371; FPNCR.
DR SUPFAM; SSF52343; SSF52343; 1.
DR SUPFAM; SSF63380; SSF63380; 1.
DR PROSITE; PS51384; FAD_FR; 1.
PE 1: Evidence at protein level;
KW Direct protein sequencing; FAD; Flavoprotein; Lipid biosynthesis;
KW Lipid metabolism; Membrane; NAD; Oxidoreductase; Reference proteome;
KW Steroid biosynthesis; Steroid metabolism; Sterol biosynthesis;
KW Sterol metabolism; Transmembrane; Transmembrane helix.
FT CHAIN 1..305
FT /note="NADH-cytochrome b5 reductase 1"
FT /id="PRO_0000287545"
FT TRANSMEM 8..28
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 44..156
FT /note="FAD-binding FR-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00716"
FT BINDING 136..166
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 175..210
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT VARIANT 44
FT /note="N -> S (in dbSNP:rs2232842)"
FT /id="VAR_032320"
FT CONFLICT 82
FT /note="H -> R (in Ref. 7; BAD97136)"
FT /evidence="ECO:0000305"
FT CONFLICT 92
FT /note="S -> N (in Ref. 1; AAF06147)"
FT /evidence="ECO:0000305"
FT CONFLICT 142
FT /note="D -> H (in Ref. 1; AAF06147)"
FT /evidence="ECO:0000305"
FT CONFLICT 212
FT /note="F -> S (in Ref. 5; BAC11115)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 305 AA; 34095 MW; DC9DAFEC619F9317 CRC64;
MGIQTSPVLL ASLGVGLVTL LGLAVGSYLV RRSRRPQVTL LDPNEKYLLR LLDKTTVSHN
TKRFRFALPT AHHTLGLPVG KHIYLSTRID GSLVIRPYTP VTSDEDQGYV DLVIKVYLKG
VHPKFPEGGK MSQYLDSLKV GDVVEFRGPS GLLTYTGKGH FNIQPNKKSP PEPRVAKKLG
MIAGGTGITP MLQLIRAILK VPEDPTQCFL LFANQTEKDI ILREDLEELQ ARYPNRFKLW
FTLDHPPKDW AYSKGFVTAD MIREHLPAPG DDVLVLLCGP PPMVQLACHP NLDKLGYSQK
MRFTY
