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 14-OCT-2015, entry version 96. 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; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND RP VARIANT 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 RT ubiquitously 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 RT for 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 RP 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 RT project: 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 RP VARIANT 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., RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., RA Ottenwaelder B., Poustka A., 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 CC desaturation and elongation of fatty acids, cholesterol CC biosynthesis, drug metabolism, and, in erythrocyte, methemoglobin CC reduction (By similarity). Responsible for NADH-dependent CC lucigenin chemiluminescence in spermatozoa by reducing both CC lucigenin and 2-[4-iodophenyl]-3-[4-nitrophenyl]-5-[2,4- CC disulfophenyl]-2H tetrazolium monosodium salt (WST-1). CC {ECO:0000250, ECO:0000269|PubMed:15858218}. CC -!- CATALYTIC ACTIVITY: NADH + 2 ferricytochrome b5 = NAD(+) + H(+) + CC 2 ferrocytochrome b5. CC -!- COFACTOR: CC Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000250}; CC -!- INTERACTION: CC Q9UJX2:CDC23; NbExp=3; IntAct=EBI-744761, EBI-396137; CC Q08379:GOLGA2; NbExp=3; IntAct=EBI-744761, EBI-618309; CC P62333:PSMC6; NbExp=3; IntAct=EBI-744761, EBI-357669; CC Q13077:TRAF1; NbExp=3; IntAct=EBI-744761, EBI-359224; CC Q12933:TRAF2; NbExp=3; IntAct=EBI-744761, EBI-355744; CC Q15645:TRIP13; NbExp=4; IntAct=EBI-744761, EBI-358993; 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 Note=No experimental confirmation available.; CC -!- TISSUE SPECIFICITY: Restricted expression. CC {ECO:0000269|PubMed:10611283}. CC -!- SIMILARITY: Belongs to the flavoprotein pyridine nucleotide CC cytochrome reductase family. {ECO:0000305}. CC -!- SIMILARITY: Contains 1 FAD-binding FR-type domain. CC {ECO:0000255|PROSITE-ProRule:PRU00716}. 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_005252975.3. [Q6BCY4-1] DR RefSeq; XP_006718314.1; XM_006718251.2. [Q6BCY4-1] DR RefSeq; XP_006718315.1; XM_006718252.2. [Q6BCY4-1] DR UniGene; Hs.414362; -. DR ProteinModelPortal; Q6BCY4; -. DR SMR; Q6BCY4; 9-276. DR BioGrid; 119684; 8. DR IntAct; Q6BCY4; 8. DR MINT; MINT-1447606; -. DR STRING; 9606.ENSP00000299498; -. DR PhosphoSite; Q6BCY4; -. DR BioMuta; CYB5R2; -. DR DMDM; 74709211; -. DR REPRODUCTION-2DPAGE; IPI00332396; -. DR MaxQB; Q6BCY4; -. DR PaxDb; Q6BCY4; -. DR PRIDE; Q6BCY4; -. 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.3; human. [Q6BCY4-1] DR CTD; 51700; -. DR GeneCards; CYB5R2; -. DR HGNC; HGNC:24376; CYB5R2. DR HPA; HPA038962; -. DR MIM; 608342; gene. DR neXtProt; NX_Q6BCY4; -. DR PharmGKB; PA142672060; -. DR eggNOG; COG0543; -. DR GeneTree; ENSGT00390000008881; -. DR HOGENOM; HOG000175005; -. DR HOVERGEN; HBG052580; -. DR InParanoid; Q6BCY4; -. DR KO; K00326; -. DR OMA; YAPEMQF; -. DR OrthoDB; EOG7CZK69; -. DR PhylomeDB; Q6BCY4; -. DR TreeFam; TF314333; -. DR BRENDA; 1.6.2.2; 2681. DR GeneWiki; CYB5R2; -. DR GenomeRNAi; 51700; -. DR NextBio; 55720; -. DR PRO; PR:Q6BCY4; -. DR Proteomes; UP000005640; Chromosome 11. DR Bgee; Q6BCY4; -. DR CleanEx; HS_CYB5R2; -. DR ExpressionAtlas; Q6BCY4; baseline and differential. DR Genevisible; Q6BCY4; HS. DR GO; GO:0016020; C:membrane; IDA:UniProtKB. DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0004128; F:cytochrome-b5 reductase activity, acting on NAD(P)H; IDA:UniProtKB. DR GO; GO:0055114; P:oxidation-reduction process; IDA:UniProtKB. DR GO; GO:0016126; P:sterol biosynthetic process; IEA:UniProtKB-KW. DR InterPro; IPR017927; Fd_Rdtase_FAD-bd. DR InterPro; IPR001709; Flavoprot_Pyr_Nucl_cyt_Rdtase. DR InterPro; IPR001834; NADH-Cyt_B5_reductase. DR InterPro; IPR008333; OxRdtase_FAD-bd_dom. 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; SSF63380; SSF63380; 1. DR PROSITE; PS51384; FAD_FR; 1. PE 1: Evidence at protein level; KW Alternative splicing; Complete proteome; FAD; Flavoprotein; KW Lipid biosynthesis; Lipid metabolism; NAD; Oxidoreductase; KW Polymorphism; Reference proteome; Steroid biosynthesis; KW Steroid metabolism; Sterol biosynthesis; Sterol metabolism. FT CHAIN 1 276 NADH-cytochrome b5 reductase 2. FT /FTId=PRO_0000287548. FT DOMAIN 15 127 FAD-binding FR-type. FT {ECO:0000255|PROSITE-ProRule:PRU00716}. FT NP_BIND 107 137 FAD. {ECO:0000250}. FT NP_BIND 146 181 FAD. {ECO:0000250}. FT VAR_SEQ 221 276 WKYSSGFVTADMIKEHLPPPAKSTLILVCGPPPLIQTAAHP FT NLEKLGYTQDMIFTY -> PWSAEGATLLSNSAQFH (in FT isoform 2). FT {ECO:0000303|PubMed:15489334}. FT /FTId=VSP_025559. FT VARIANT 15 15 E -> A (in dbSNP:rs11041525). FT /FTId=VAR_032321. FT VARIANT 209 209 N -> D (in dbSNP:rs12801394). FT {ECO:0000269|PubMed:10611283, FT ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:17974005}. FT /FTId=VAR_032322. FT CONFLICT 130 130 G -> R (in Ref. 1; AAF04811). FT {ECO:0000305}. FT CONFLICT 253 253 P -> T (in Ref. 1; AAF04811). FT {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 //