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Protein

Cytochrome b5 reductase 4

Gene

Cyb5r4

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

NADH-cytochrome b5 reductase involved in endoplasmic reticulum stress response pathway. Plays a critical role in protecting pancreatic beta-cells against oxidant stress, possibly by protecting the cell from excess buildup of reactive oxygen species (ROS).

Catalytic activityi

NADH + 2 ferricytochrome b5 = NAD+ + H+ + 2 ferrocytochrome b5.1 Publication

Cofactori

FAD1 Publication

Kineticsi

  1. KM=28 µM for ferricyanide1 Publication
  2. KM=1 µM for NADPH1 Publication
  3. KM=7 µM for cytochrome c1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi89 – 891Iron (heme axial ligand)
    Metal bindingi112 – 1121Iron (heme axial ligand)

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi364 – 37916FADBy similarityAdd
    BLAST
    Nucleotide bindingi391 – 42333FADBy similarityAdd
    BLAST

    GO - Molecular functioni

    • cytochrome-b5 reductase activity, acting on NAD(P)H Source: UniProtKB-EC
    • flavin adenine dinucleotide binding Source: RGD
    • heme binding Source: RGD
    • metal ion binding Source: UniProtKB-KW
    • NADPH-hemoprotein reductase activity Source: RGD

    GO - Biological processi

    • NADP metabolic process Source: RGD
    Complete GO annotation...

    Keywords - Molecular functioni

    Oxidoreductase

    Keywords - Ligandi

    FAD, Flavoprotein, Heme, Iron, Metal-binding, NAD

    Enzyme and pathway databases

    BRENDAi1.6.2.2. 5301.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Cytochrome b5 reductase 4 (EC:1.6.2.2)
    Alternative name(s):
    Flavohemoprotein b5/b5R
    Short name:
    b5+b5R
    N-terminal cytochrome b5 and cytochrome b5 oxidoreductase domain-containing protein
    cb5/cb5R
    Gene namesi
    Name:Cyb5r4
    Synonyms:Ncb5or
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    Proteomesi
    • UP000002494 Componenti: Unplaced

    Organism-specific databases

    RGDi621834. Cyb5r4.

    Subcellular locationi

    GO - Cellular componenti

    Complete GO annotation...

    Keywords - Cellular componenti

    Endoplasmic reticulum

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi89 – 891H → A or M: Abolishes heme-binding but does not affect reductase activity. 1 Publication
    Mutagenesisi112 – 1121H → A or M: Abolishes heme-binding but does not affect reductase activity. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 520520Cytochrome b5 reductase 4PRO_0000287558Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei1 – 11N-acetylmethionineBy similarity

    Keywords - PTMi

    Acetylation

    Proteomic databases

    PaxDbiQ68EJ0.
    PRIDEiQ68EJ0.

    PTM databases

    PhosphoSiteiQ68EJ0.

    Expressioni

    Tissue specificityi

    Isoform 2 is expressed in testis, brain, skeletal muscle and in the male germline.1 Publication

    Interactioni

    Protein-protein interaction databases

    STRINGi10116.ENSRNOP00000013909.

    Structurei

    3D structure databases

    ProteinModelPortaliQ68EJ0.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini54 – 13077Cytochrome b5 heme-bindingPROSITE-ProRule annotationAdd
    BLAST
    Domaini164 – 25592CSPROSITE-ProRule annotationAdd
    BLAST
    Domaini272 – 384113FAD-binding FR-typePROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Contains 1 CS domain.PROSITE-ProRule annotation
    Contains 1 cytochrome b5 heme-binding domain.PROSITE-ProRule annotation
    Contains 1 FAD-binding FR-type domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiKOG0534. Eukaryota.
    KOG0536. Eukaryota.
    COG0543. LUCA.
    COG5274. LUCA.
    HOGENOMiHOG000230826.
    HOVERGENiHBG108174.
    InParanoidiQ68EJ0.
    KOiK00326.
    OrthoDBiEOG718KBZ.
    PhylomeDBiQ68EJ0.

    Family and domain databases

    Gene3Di2.60.40.790. 1 hit.
    3.10.120.10. 1 hit.
    InterProiIPR007052. CS_dom.
    IPR001199. Cyt_B5-like_heme/steroid-bd.
    IPR018506. Cyt_B5_heme-BS.
    IPR017927. Fd_Rdtase_FAD-bd.
    IPR008978. HSP20-like_chaperone.
    IPR001834. NADH-Cyt_B5_reductase.
    IPR008333. OxRdtase_FAD-bd_dom.
    IPR001433. OxRdtase_FAD/NAD-bd.
    IPR017938. Riboflavin_synthase-like_b-brl.
    [Graphical view]
    PfamiPF04969. CS. 1 hit.
    PF00173. Cyt-b5. 1 hit.
    PF00970. FAD_binding_6. 1 hit.
    PF00175. NAD_binding_1. 1 hit.
    [Graphical view]
    PRINTSiPR00406. CYTB5RDTASE.
    PR00363. CYTOCHROMEB5.
    SMARTiSM01117. Cyt-b5. 1 hit.
    [Graphical view]
    SUPFAMiSSF49764. SSF49764. 1 hit.
    SSF55856. SSF55856. 1 hit.
    SSF63380. SSF63380. 1 hit.
    PROSITEiPS51203. CS. 1 hit.
    PS00191. CYTOCHROME_B5_1. 1 hit.
    PS50255. CYTOCHROME_B5_2. 1 hit.
    PS51384. FAD_FR. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform 1 (identifier: Q68EJ0-1) [UniParc]FASTAAdd to basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

            10         20         30         40         50
    MLNVPSQAFP APGSQQRVAS QGRSKVPLKQ GRSLMDWFRL TKSGKDFTGL
    60 70 80 90 100
    KGGLIEVTEE ELKKHNKKDD CWICIRGFVY NVSPYMEYHP GGEDELMRAA
    110 120 130 140 150
    GADGTDLFNE VHRWVNYESM LKECLVGRMA VKPAVPKDCH EGKRVLNGML
    160 170 180 190 200
    PKSQVTDTLP REGPSSPSYD WFQTESSVTI VIYTKQKNIN LDSVIVDLQD
    210 220 230 240 250
    DSLRAEAVIK DHSYLIHIGL SHEVQENFSV RVIENVGKIE IVLQKKETVS
    260 270 280 290 300
    WKCLGDPLEK HDSFIPKKDT GLYYRQCQLI SKEDVTHDTR LFCLMLPPST
    310 320 330 340 350
    HLQVPVGQHV YLKLSVTGAE IVKPYTPVSE SLLSDFKEPV LSPNKYIYFL
    360 370 380 390 400
    IKIYPAGLFT PELDRLQIGD FVSVSGPEGN FKVSKLQEVE DLFLLAAGTG
    410 420 430 440 450
    FTPMVTVLNH ALTHMSSLRK VKLMFFNKTE DDIIWRCQLE KLALKDKRFH
    460 470 480 490 500
    VEYVLSAPSP EWNGKQGHVS RALLSEFLQR SLENSKVFLC ICGPTPFTDE
    510 520
    GIRLLHDLNF SDDEIHGFTA
    Length:520
    Mass (Da):58,835
    Last modified:May 15, 2007 - v2
    Checksum:iF0C0553206F7976A
    GO
    Isoform 2 (identifier: Q68EJ0-2) [UniParc]FASTAAdd to basket

    Also known as: cb5/cb5rDelta12

    The sequence of this isoform differs from the canonical sequence as follows:
         318-368: Missing.

    Show »
    Length:469
    Mass (Da):53,038
    Checksum:iF51B15B52318FFE2
    GO

    Sequence cautioni

    The sequence AAH80240.1 differs from that shown. Reason: Erroneous initiation. Curated

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti38 – 381F → I in AAH80240 (PubMed:15489334).Curated
    Sequence conflicti244 – 2441Q → L in AAG45053 (PubMed:11913972).Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei318 – 36851Missing in isoform 2. 1 PublicationVSP_025563Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    BC080240 mRNA. Translation: AAH80240.1. Different initiation.
    AF307840 mRNA. Translation: AAG45053.1.
    AY321370 mRNA. Translation: AAQ83902.1.
    AY321371 mRNA. Translation: AAQ83903.1.
    RefSeqiNP_596918.3. NM_133427.3.
    XP_008764659.1. XM_008766437.1.
    UniGeneiRn.3334.

    Genome annotation databases

    GeneIDi171015.
    KEGGirno:171015.
    UCSCiRGD:621834. rat. [Q68EJ0-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    BC080240 mRNA. Translation: AAH80240.1. Different initiation.
    AF307840 mRNA. Translation: AAG45053.1.
    AY321370 mRNA. Translation: AAQ83902.1.
    AY321371 mRNA. Translation: AAQ83903.1.
    RefSeqiNP_596918.3. NM_133427.3.
    XP_008764659.1. XM_008766437.1.
    UniGeneiRn.3334.

    3D structure databases

    ProteinModelPortaliQ68EJ0.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    STRINGi10116.ENSRNOP00000013909.

    PTM databases

    PhosphoSiteiQ68EJ0.

    Proteomic databases

    PaxDbiQ68EJ0.
    PRIDEiQ68EJ0.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    GeneIDi171015.
    KEGGirno:171015.
    UCSCiRGD:621834. rat. [Q68EJ0-1]

    Organism-specific databases

    CTDi51167.
    RGDi621834. Cyb5r4.

    Phylogenomic databases

    eggNOGiKOG0534. Eukaryota.
    KOG0536. Eukaryota.
    COG0543. LUCA.
    COG5274. LUCA.
    HOGENOMiHOG000230826.
    HOVERGENiHBG108174.
    InParanoidiQ68EJ0.
    KOiK00326.
    OrthoDBiEOG718KBZ.
    PhylomeDBiQ68EJ0.

    Enzyme and pathway databases

    BRENDAi1.6.2.2. 5301.

    Miscellaneous databases

    PROiQ68EJ0.

    Family and domain databases

    Gene3Di2.60.40.790. 1 hit.
    3.10.120.10. 1 hit.
    InterProiIPR007052. CS_dom.
    IPR001199. Cyt_B5-like_heme/steroid-bd.
    IPR018506. Cyt_B5_heme-BS.
    IPR017927. Fd_Rdtase_FAD-bd.
    IPR008978. HSP20-like_chaperone.
    IPR001834. NADH-Cyt_B5_reductase.
    IPR008333. OxRdtase_FAD-bd_dom.
    IPR001433. OxRdtase_FAD/NAD-bd.
    IPR017938. Riboflavin_synthase-like_b-brl.
    [Graphical view]
    PfamiPF04969. CS. 1 hit.
    PF00173. Cyt-b5. 1 hit.
    PF00970. FAD_binding_6. 1 hit.
    PF00175. NAD_binding_1. 1 hit.
    [Graphical view]
    PRINTSiPR00406. CYTB5RDTASE.
    PR00363. CYTOCHROMEB5.
    SMARTiSM01117. Cyt-b5. 1 hit.
    [Graphical view]
    SUPFAMiSSF49764. SSF49764. 1 hit.
    SSF55856. SSF55856. 1 hit.
    SSF63380. SSF63380. 1 hit.
    PROSITEiPS51203. CS. 1 hit.
    PS00191. CYTOCHROME_B5_1. 1 hit.
    PS50255. CYTOCHROME_B5_2. 1 hit.
    PS51384. FAD_FR. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
      Tissue: Lung.
    2. "Heterologous expression of an endogenous rat cytochrome b(5)/cytochrome b(5) reductase fusion protein: identification of histidines 62 and 85 as the heme axial ligands."
      Davis C.A., Dhawan I.K., Johnson M.K., Barber M.J.
      Arch. Biochem. Biophys. 400:63-75(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 35-520 (ISOFORM 1), ENZYME ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, FAD-BINDING, HEME-BINDING AT HIS-89 AND HIS-112, MUTAGENESIS OF HIS-89 AND HIS-112.
    3. "Identification and characterization of a novel splice variant of mouse and rat cytochrome b5/cytochrome b5 reductase."
      Curry B.J., Roman S.D., Wallace C.A., Scott R., Miriami E., Aitken R.J.
      Genomics 83:425-438(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 35-520 (ISOFORMS 1 AND 2), TISSUE SPECIFICITY.
      Strain: Wistar.
      Tissue: Testis.

    Entry informationi

    Entry nameiNB5R4_RAT
    AccessioniPrimary (citable) accession number: Q68EJ0
    Secondary accession number(s): Q6VXY2, Q6VXY3, Q9EPZ4
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 15, 2007
    Last sequence update: May 15, 2007
    Last modified: June 8, 2016
    This is version 95 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.