NB5R2_HUMAN
ID NB5R2_HUMAN Reviewed; 276 AA.
AC Q6BCY4; Q9BVA3; Q9UF68; Q9UHJ0;
DT 15-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 13-SEP-2004, sequence version 1.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=NADH-cytochrome b5 reductase 2 {ECO:0000305};
DE Short=b5R.2;
DE EC=1.6.2.2 {ECO:0000305|PubMed:15858218};
GN Name=CYB5R2 {ECO:0000312|HGNC:HGNC:24376};
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] (ISOFORM 1), TISSUE SPECIFICITY, AND VARIANT
RP ASP-209.
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] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=15858218; DOI=10.1095/biolreprod.104.037960;
RA Baker M.A., Krutskikh A., Curry B.J., Hetherington L., Aitken R.J.;
RT "Identification of cytochrome-b5 reductase as the enzyme responsible for
RT NADH-dependent lucigenin chemiluminescence in human spermatozoa.";
RL Biol. Reprod. 73:334-342(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT ASP-209.
RC TISSUE=Placenta;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 7-276 (ISOFORM 1), AND VARIANT
RP ASP-209.
RC TISSUE=Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
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 (By
CC similarity). Responsible for NADH-dependent lucigenin chemiluminescence
CC in spermatozoa by reducing both lucigenin and 2-[4-iodophenyl]-3-[4-
CC nitrophenyl]-5-[2,4-disulfophenyl]-2H tetrazolium monosodium salt (WST-
CC 1). {ECO:0000250, ECO:0000269|PubMed:15858218}.
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 Evidence={ECO:0000305|PubMed:15858218};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000250};
CC -!- INTERACTION:
CC Q6BCY4; Q9UJX2: CDC23; NbExp=3; IntAct=EBI-744761, EBI-396137;
CC Q6BCY4; Q08379: GOLGA2; NbExp=3; IntAct=EBI-744761, EBI-618309;
CC Q6BCY4; P62333: PSMC6; NbExp=3; IntAct=EBI-744761, EBI-357669;
CC Q6BCY4; Q13077: TRAF1; NbExp=3; IntAct=EBI-744761, EBI-359224;
CC Q6BCY4; Q12933: TRAF2; NbExp=3; IntAct=EBI-744761, EBI-355744;
CC Q6BCY4; Q15645: TRIP13; NbExp=4; IntAct=EBI-744761, EBI-358993;
CC Q6BCY4-2; O95994: AGR2; NbExp=3; IntAct=EBI-12102608, EBI-712648;
CC Q6BCY4-2; Q9NW38: FANCL; NbExp=3; IntAct=EBI-12102608, EBI-2339898;
CC Q6BCY4-2; Q08379: GOLGA2; NbExp=3; IntAct=EBI-12102608, EBI-618309;
CC Q6BCY4-2; O14964: HGS; NbExp=3; IntAct=EBI-12102608, EBI-740220;
CC Q6BCY4-2; Q9H944: MED20; NbExp=3; IntAct=EBI-12102608, EBI-394644;
CC Q6BCY4-2; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-12102608, EBI-16439278;
CC Q6BCY4-2; Q8NI38: NFKBID; NbExp=3; IntAct=EBI-12102608, EBI-10271199;
CC Q6BCY4-2; Q04864-2: REL; NbExp=3; IntAct=EBI-12102608, EBI-10829018;
CC Q6BCY4-2; P51687: SUOX; NbExp=3; IntAct=EBI-12102608, EBI-3921347;
CC Q6BCY4-2; Q12933: TRAF2; NbExp=3; IntAct=EBI-12102608, EBI-355744;
CC Q6BCY4-2; Q15645: TRIP13; NbExp=3; IntAct=EBI-12102608, EBI-358993;
CC Q6BCY4-2; Q96MU6-2: ZNF778; NbExp=3; IntAct=EBI-12102608, EBI-14242669;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q6BCY4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6BCY4-2; Sequence=VSP_025559;
CC -!- TISSUE SPECIFICITY: Restricted expression.
CC {ECO:0000269|PubMed:10611283}.
CC -!- SIMILARITY: Belongs to the flavoprotein pyridine nucleotide cytochrome
CC reductase family. {ECO:0000305}.
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DR EMBL; AF169802; AAF04811.1; -; mRNA.
DR EMBL; AY665398; AAT75296.1; -; mRNA.
DR EMBL; BC001346; AAH01346.1; -; mRNA.
DR EMBL; AL133582; CAB63726.1; -; mRNA.
DR CCDS; CCDS7780.1; -. [Q6BCY4-1]
DR PIR; T43491; T43491.
DR RefSeq; NP_001289755.1; NM_001302826.1. [Q6BCY4-1]
DR RefSeq; NP_057313.2; NM_016229.4. [Q6BCY4-1]
DR RefSeq; XP_005253032.1; XM_005252975.4. [Q6BCY4-1]
DR RefSeq; XP_006718314.1; XM_006718251.2. [Q6BCY4-1]
DR AlphaFoldDB; Q6BCY4; -.
DR SMR; Q6BCY4; -.
DR BioGRID; 119684; 30.
DR IntAct; Q6BCY4; 18.
DR STRING; 9606.ENSP00000437041; -.
DR iPTMnet; Q6BCY4; -.
DR PhosphoSitePlus; Q6BCY4; -.
DR BioMuta; CYB5R2; -.
DR DMDM; 74709211; -.
DR REPRODUCTION-2DPAGE; IPI00332396; -.
DR EPD; Q6BCY4; -.
DR jPOST; Q6BCY4; -.
DR MassIVE; Q6BCY4; -.
DR MaxQB; Q6BCY4; -.
DR PaxDb; Q6BCY4; -.
DR PeptideAtlas; Q6BCY4; -.
DR PRIDE; Q6BCY4; -.
DR ProteomicsDB; 66216; -. [Q6BCY4-1]
DR ProteomicsDB; 66217; -. [Q6BCY4-2]
DR Antibodypedia; 24030; 138 antibodies from 23 providers.
DR DNASU; 51700; -.
DR Ensembl; ENST00000299498.11; ENSP00000299498.6; ENSG00000166394.15. [Q6BCY4-1]
DR Ensembl; ENST00000524790.5; ENSP00000435916.1; ENSG00000166394.15. [Q6BCY4-2]
DR Ensembl; ENST00000533558.5; ENSP00000437041.1; ENSG00000166394.15. [Q6BCY4-1]
DR GeneID; 51700; -.
DR KEGG; hsa:51700; -.
DR MANE-Select; ENST00000299498.11; ENSP00000299498.6; NM_016229.5; NP_057313.2.
DR UCSC; uc001mfm.4; human. [Q6BCY4-1]
DR CTD; 51700; -.
DR DisGeNET; 51700; -.
DR GeneCards; CYB5R2; -.
DR HGNC; HGNC:24376; CYB5R2.
DR HPA; ENSG00000166394; Tissue enhanced (retina, testis).
DR MIM; 608342; gene.
DR neXtProt; NX_Q6BCY4; -.
DR OpenTargets; ENSG00000166394; -.
DR PharmGKB; PA142672060; -.
DR VEuPathDB; HostDB:ENSG00000166394; -.
DR eggNOG; KOG0534; Eukaryota.
DR GeneTree; ENSGT00940000153962; -.
DR HOGENOM; CLU_003827_9_2_1; -.
DR InParanoid; Q6BCY4; -.
DR OMA; NKHDHIA; -.
DR OrthoDB; 1311668at2759; -.
DR PhylomeDB; Q6BCY4; -.
DR TreeFam; TF314333; -.
DR BRENDA; 1.6.2.2; 2681.
DR PathwayCommons; Q6BCY4; -.
DR Reactome; R-HSA-1237044; Erythrocytes take up carbon dioxide and release oxygen.
DR SignaLink; Q6BCY4; -.
DR BioGRID-ORCS; 51700; 9 hits in 1078 CRISPR screens.
DR GeneWiki; CYB5R2; -.
DR GenomeRNAi; 51700; -.
DR Pharos; Q6BCY4; Tbio.
DR PRO; PR:Q6BCY4; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q6BCY4; protein.
DR Bgee; ENSG00000166394; Expressed in left testis and 167 other tissues.
DR ExpressionAtlas; Q6BCY4; baseline and differential.
DR Genevisible; Q6BCY4; HS.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; HDA:UniProtKB.
DR GO; GO:0004128; F:cytochrome-b5 reductase activity, acting on NAD(P)H; IDA:UniProtKB.
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 Acetylation; Alternative splicing; FAD; Flavoprotein; Lipid biosynthesis;
KW Lipid metabolism; NAD; Oxidoreductase; Phosphoprotein; Reference proteome;
KW Steroid biosynthesis; Steroid metabolism; Sterol biosynthesis;
KW Sterol metabolism.
FT CHAIN 1..276
FT /note="NADH-cytochrome b5 reductase 2"
FT /id="PRO_0000287548"
FT DOMAIN 15..127
FT /note="FAD-binding FR-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00716"
FT BINDING 107..137
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 146..181
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT MOD_RES 17
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P00387"
FT MOD_RES 18
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P00387"
FT VAR_SEQ 221..276
FT /note="WKYSSGFVTADMIKEHLPPPAKSTLILVCGPPPLIQTAAHPNLEKLGYTQDM
FT IFTY -> PWSAEGATLLSNSAQFH (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_025559"
FT VARIANT 15
FT /note="E -> A (in dbSNP:rs11041525)"
FT /id="VAR_032321"
FT VARIANT 209
FT /note="N -> D (in dbSNP:rs12801394)"
FT /evidence="ECO:0000269|PubMed:10611283,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:17974005"
FT /id="VAR_032322"
FT CONFLICT 130
FT /note="G -> R (in Ref. 1; AAF04811)"
FT /evidence="ECO:0000305"
FT CONFLICT 253
FT /note="P -> T (in Ref. 1; AAF04811)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 276 AA; 31458 MW; A475039D1E56ABDA CRC64;
MNSRRREPIT LQDPEAKYPL PLIEKEKISH NTRRFRFGLP SPDHVLGLPV GNYVQLLAKI
DNELVVRAYT PVSSDDDRGF VDLIIKIYFK NVHPQYPEGG KMTQYLENMK IGETIFFRGP
RGRLFYHGPG NLGIRPDQTS EPKKTLADHL GMIAGGTGIT PMLQLIRHIT KDPSDRTRMS
LIFANQTEED ILVRKELEEI ARTHPDQFNL WYTLDRPPIG WKYSSGFVTA DMIKEHLPPP
AKSTLILVCG PPPLIQTAAH PNLEKLGYTQ DMIFTY
