NB5R4_RAT
ID NB5R4_RAT Reviewed; 520 AA.
AC Q68EJ0; Q6VXY2; Q6VXY3; Q9EPZ4;
DT 15-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 15-MAY-2007, sequence version 2.
DT 03-AUG-2022, entry version 129.
DE RecName: Full=Cytochrome b5 reductase 4;
DE EC=1.6.2.2;
DE AltName: Full=Flavohemoprotein b5/b5R;
DE Short=b5+b5R;
DE AltName: Full=N-terminal cytochrome b5 and cytochrome b5 oxidoreductase domain-containing protein;
DE AltName: Full=cb5/cb5R;
GN Name=Cyb5r4; Synonyms=Ncb5or;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 35-520 (ISOFORM 1), ENZYME ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, FAD-BINDING, HEME-BINDING AT HIS-89 AND
RP HIS-112, AND MUTAGENESIS OF HIS-89 AND HIS-112.
RX PubMed=11913972; DOI=10.1006/abbi.2002.2783;
RA Davis C.A., Dhawan I.K., Johnson M.K., Barber M.J.;
RT "Heterologous expression of an endogenous rat cytochrome b(5)/cytochrome
RT b(5) reductase fusion protein: identification of histidines 62 and 85 as
RT the heme axial ligands.";
RL Arch. Biochem. Biophys. 400:63-75(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 35-520 (ISOFORMS 1 AND 2), AND TISSUE
RP SPECIFICITY.
RC STRAIN=Wistar; TISSUE=Testis;
RX PubMed=14962668; DOI=10.1016/j.ygeno.2003.08.020;
RA Curry B.J., Roman S.D., Wallace C.A., Scott R., Miriami E., Aitken R.J.;
RT "Identification and characterization of a novel splice variant of mouse and
RT rat cytochrome b5/cytochrome b5 reductase.";
RL Genomics 83:425-438(2004).
CC -!- FUNCTION: NADH-cytochrome b5 reductase involved in endoplasmic
CC reticulum stress response pathway. Plays a critical role in protecting
CC pancreatic beta-cells against oxidant stress, possibly by protecting
CC the cell from excess buildup of reactive oxygen species (ROS).
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:0000269|PubMed:11913972};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000269|PubMed:11913972};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=28 uM for ferricyanide {ECO:0000269|PubMed:11913972};
CC KM=1 uM for NADPH {ECO:0000269|PubMed:11913972};
CC KM=7 uM for cytochrome c {ECO:0000269|PubMed:11913972};
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum. Note=Soluble protein.
CC {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q68EJ0-1; Sequence=Displayed;
CC Name=2; Synonyms=cb5/cb5rDelta12;
CC IsoId=Q68EJ0-2; Sequence=VSP_025563;
CC -!- TISSUE SPECIFICITY: Isoform 2 is expressed in testis, brain, skeletal
CC muscle and in the male germline. {ECO:0000269|PubMed:14962668}.
CC -!- SIMILARITY: Belongs to the flavoprotein pyridine nucleotide cytochrome
CC reductase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH80240.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; BC080240; AAH80240.1; ALT_INIT; mRNA.
DR EMBL; AF307840; AAG45053.1; -; mRNA.
DR EMBL; AY321370; AAQ83902.1; -; mRNA.
DR EMBL; AY321371; AAQ83903.1; -; mRNA.
DR RefSeq; NP_596918.3; NM_133427.3.
DR AlphaFoldDB; Q68EJ0; -.
DR SMR; Q68EJ0; -.
DR STRING; 10116.ENSRNOP00000013909; -.
DR PhosphoSitePlus; Q68EJ0; -.
DR jPOST; Q68EJ0; -.
DR PaxDb; Q68EJ0; -.
DR GeneID; 171015; -.
DR KEGG; rno:171015; -.
DR UCSC; RGD:621834; rat. [Q68EJ0-1]
DR CTD; 51167; -.
DR RGD; 621834; Cyb5r4.
DR eggNOG; KOG0534; Eukaryota.
DR eggNOG; KOG0536; Eukaryota.
DR InParanoid; Q68EJ0; -.
DR OrthoDB; 1311668at2759; -.
DR PhylomeDB; Q68EJ0; -.
DR BRENDA; 1.6.2.2; 5301.
DR Reactome; R-RNO-1237044; Erythrocytes take up carbon dioxide and release oxygen.
DR SABIO-RK; Q68EJ0; -.
DR PRO; PR:Q68EJ0; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:RGD.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:RGD.
DR GO; GO:0004128; F:cytochrome-b5 reductase activity, acting on NAD(P)H; ISO:RGD.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IDA:RGD.
DR GO; GO:0020037; F:heme binding; IDA:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0016174; F:NAD(P)H oxidase H2O2-forming activity; ISO:RGD.
DR GO; GO:0003958; F:NADPH-hemoprotein reductase activity; IDA:RGD.
DR GO; GO:0016653; F:oxidoreductase activity, acting on NAD(P)H, heme protein as acceptor; ISO:RGD.
DR GO; GO:0048468; P:cell development; ISO:RGD.
DR GO; GO:0006091; P:generation of precursor metabolites and energy; ISO:RGD.
DR GO; GO:0042593; P:glucose homeostasis; ISO:RGD.
DR GO; GO:0030073; P:insulin secretion; ISO:RGD.
DR GO; GO:0006739; P:NADP metabolic process; IDA:RGD.
DR GO; GO:0072593; P:reactive oxygen species metabolic process; ISO:RGD.
DR GO; GO:0046677; P:response to antibiotic; ISO:RGD.
DR GO; GO:0006801; P:superoxide metabolic process; ISO:RGD.
DR CDD; cd06490; p23_NCB5OR; 1.
DR Gene3D; 2.60.40.790; -; 1.
DR Gene3D; 3.10.120.10; -; 1.
DR Gene3D; 3.40.50.80; -; 1.
DR InterPro; IPR001834; CBR-like.
DR InterPro; IPR008333; Cbr1-like_FAD-bd_dom.
DR InterPro; IPR007052; CS_dom.
DR InterPro; IPR001199; Cyt_B5-like_heme/steroid-bd.
DR InterPro; IPR036400; Cyt_B5-like_heme/steroid_sf.
DR InterPro; IPR018506; Cyt_B5_heme-BS.
DR InterPro; IPR017927; FAD-bd_FR_type.
DR InterPro; IPR039261; FNR_nucleotide-bd.
DR InterPro; IPR008978; HSP20-like_chaperone.
DR InterPro; IPR001433; OxRdtase_FAD/NAD-bd.
DR InterPro; IPR037908; p23_NCB5OR.
DR InterPro; IPR017938; Riboflavin_synthase-like_b-brl.
DR PANTHER; PTHR19370; PTHR19370; 1.
DR Pfam; PF04969; CS; 1.
DR Pfam; PF00173; Cyt-b5; 1.
DR Pfam; PF00970; FAD_binding_6; 1.
DR Pfam; PF00175; NAD_binding_1; 1.
DR PRINTS; PR00363; CYTOCHROMEB5.
DR SMART; SM01117; Cyt-b5; 1.
DR SUPFAM; SSF49764; SSF49764; 1.
DR SUPFAM; SSF52343; SSF52343; 1.
DR SUPFAM; SSF55856; SSF55856; 1.
DR SUPFAM; SSF63380; SSF63380; 1.
DR PROSITE; PS51203; CS; 1.
DR PROSITE; PS00191; CYTOCHROME_B5_1; 1.
DR PROSITE; PS50255; CYTOCHROME_B5_2; 1.
DR PROSITE; PS51384; FAD_FR; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Endoplasmic reticulum; FAD;
KW Flavoprotein; Heme; Iron; Metal-binding; NAD; Oxidoreductase;
KW Reference proteome.
FT CHAIN 1..520
FT /note="Cytochrome b5 reductase 4"
FT /id="PRO_0000287558"
FT DOMAIN 54..130
FT /note="Cytochrome b5 heme-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00279"
FT DOMAIN 164..255
FT /note="CS"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00547"
FT DOMAIN 272..384
FT /note="FAD-binding FR-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00716"
FT REGION 1..27
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 89
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT BINDING 112
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT BINDING 364..379
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 391..423
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:Q7L1T6"
FT VAR_SEQ 318..368
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14962668"
FT /id="VSP_025563"
FT MUTAGEN 89
FT /note="H->A,M: Abolishes heme-binding but does not affect
FT reductase activity."
FT /evidence="ECO:0000269|PubMed:11913972"
FT MUTAGEN 112
FT /note="H->A,M: Abolishes heme-binding but does not affect
FT reductase activity."
FT /evidence="ECO:0000269|PubMed:11913972"
FT CONFLICT 38
FT /note="F -> I (in Ref. 1; AAH80240)"
FT /evidence="ECO:0000305"
FT CONFLICT 244
FT /note="Q -> L (in Ref. 2; AAG45053)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 520 AA; 58835 MW; F0C0553206F7976A CRC64;
MLNVPSQAFP APGSQQRVAS QGRSKVPLKQ GRSLMDWFRL TKSGKDFTGL KGGLIEVTEE
ELKKHNKKDD CWICIRGFVY NVSPYMEYHP GGEDELMRAA GADGTDLFNE VHRWVNYESM
LKECLVGRMA VKPAVPKDCH EGKRVLNGML PKSQVTDTLP REGPSSPSYD WFQTESSVTI
VIYTKQKNIN LDSVIVDLQD DSLRAEAVIK DHSYLIHIGL SHEVQENFSV RVIENVGKIE
IVLQKKETVS WKCLGDPLEK HDSFIPKKDT GLYYRQCQLI SKEDVTHDTR LFCLMLPPST
HLQVPVGQHV YLKLSVTGAE IVKPYTPVSE SLLSDFKEPV LSPNKYIYFL IKIYPAGLFT
PELDRLQIGD FVSVSGPEGN FKVSKLQEVE DLFLLAAGTG FTPMVTVLNH ALTHMSSLRK
VKLMFFNKTE DDIIWRCQLE KLALKDKRFH VEYVLSAPSP EWNGKQGHVS RALLSEFLQR
SLENSKVFLC ICGPTPFTDE GIRLLHDLNF SDDEIHGFTA
