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 07-APR-2021, entry version 136. DE RecName: Full=NADH-cytochrome b5 reductase 2; DE Short=b5R.2; DE EC=1.6.2.2; GN Name=CYB5R2; 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), IDENTIFICATION BY MASS RP SPECTROMETRY, AND FUNCTION. 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 -!- 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 SMR; Q6BCY4; -. DR BioGRID; 119684; 20. 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; 128 antibodies. DR Ensembl; ENST00000299498; ENSP00000299498; ENSG00000166394. [Q6BCY4-1] DR Ensembl; ENST00000524790; ENSP00000435916; ENSG00000166394. [Q6BCY4-2] DR Ensembl; ENST00000533558; ENSP00000437041; ENSG00000166394. [Q6BCY4-1] DR GeneID; 51700; -. DR KEGG; hsa:51700; -. 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 (testis). DR MIM; 608342; gene. DR neXtProt; NX_Q6BCY4; -. DR OpenTargets; ENSG00000166394; -. DR PharmGKB; PA142672060; -. DR VEuPathDB; HostDB:ENSG00000166394.14; -. DR eggNOG; KOG0534; Eukaryota. DR GeneTree; ENSGT00940000153962; -. DR HOGENOM; CLU_003827_9_2_1; -. DR InParanoid; Q6BCY4; -. DR OMA; LDMKGPF; -. 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 BioGRID-ORCS; 51700; 7 hits in 996 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 tibial nerve and 205 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 Pfam; PF00970; FAD_binding_6; 1. DR Pfam; PF00175; NAD_binding_1; 1. DR PRINTS; PR00406; CYTB5RDTASE. 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 NP_BIND 107..137 FT /note="FAD" FT /evidence="ECO:0000250" FT NP_BIND 146..181 FT /note="FAD" 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 //