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Protein

Cytochrome b5 reductase 4

Gene

Cyb5r4

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -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)DescriptionActionsGraphical viewLength
    Metal bindingi89Iron (heme axial ligand)1
    Metal bindingi112Iron (heme axial ligand)1

    Regions

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Nucleotide bindingi364 – 379FADBy similarityAdd BLAST16
    Nucleotide bindingi391 – 423FADBy similarityAdd BLAST33

    GO - Molecular functioni

    GO - Biological processi

    • generation of precursor metabolites and energy Source: GO_Central
    • NADP metabolic process Source: RGD
    • superoxide metabolic process Source: GO_Central

    Keywordsi

    Molecular functionOxidoreductase
    LigandFAD, Flavoprotein, Heme, Iron, Metal-binding, NAD

    Enzyme and pathway databases

    BRENDAi1.6.2.2 5301
    SABIO-RKiQ68EJ0

    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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
    Proteomesi
    • UP000002494 Componenti: Unplaced

    Organism-specific databases

    RGDi621834 Cyb5r4

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    Keywords - Cellular componenti

    Endoplasmic reticulum

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi89H → A or M: Abolishes heme-binding but does not affect reductase activity. 1 Publication1
    Mutagenesisi112H → A or M: Abolishes heme-binding but does not affect reductase activity. 1 Publication1

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00002875581 – 520Cytochrome b5 reductase 4Add BLAST520

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei1N-acetylmethionineBy similarity1

    Keywords - PTMi

    Acetylation

    Proteomic databases

    PaxDbiQ68EJ0
    PRIDEiQ68EJ0

    PTM databases

    PhosphoSitePlusiQ68EJ0

    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
    SMRiQ68EJ0
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Domaini54 – 130Cytochrome b5 heme-bindingPROSITE-ProRule annotationAdd BLAST77
    Domaini164 – 255CSPROSITE-ProRule annotationAdd BLAST92
    Domaini272 – 384FAD-binding FR-typePROSITE-ProRule annotationAdd BLAST113

    Sequence similaritiesi

    Phylogenomic databases

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

    Family and domain databases

    CDDicd06490 p23_NCB5OR, 1 hit
    Gene3Di2.60.40.790, 1 hit
    3.10.120.10, 1 hit
    3.40.50.80, 1 hit
    InterProiView protein in InterPro
    IPR008333 Cbr1-like_FAD-bd_dom
    IPR007052 CS_dom
    IPR001199 Cyt_B5-like_heme/steroid-bd
    IPR036400 Cyt_B5-like_heme/steroid_sf
    IPR018506 Cyt_B5_heme-BS
    IPR017927 FAD-bd_FR_type
    IPR039261 FNR_nucleotide-bd
    IPR008978 HSP20-like_chaperone
    IPR001834 NADH-Cyt_B5_reductase
    IPR001433 OxRdtase_FAD/NAD-bd
    IPR037908 p23_NCB5OR
    IPR017938 Riboflavin_synthase-like_b-brl
    PfamiView protein in Pfam
    PF04969 CS, 1 hit
    PF00173 Cyt-b5, 1 hit
    PF00970 FAD_binding_6, 1 hit
    PF00175 NAD_binding_1, 1 hit
    PRINTSiPR00406 CYTB5RDTASE
    PR00363 CYTOCHROMEB5
    SMARTiView protein in SMART
    SM01117 Cyt-b5, 1 hit
    SUPFAMiSSF49764 SSF49764, 1 hit
    SSF52343 SSF52343, 1 hit
    SSF55856 SSF55856, 1 hit
    SSF63380 SSF63380, 1 hit
    PROSITEiView protein in PROSITE
    PS51203 CS, 1 hit
    PS00191 CYTOCHROME_B5_1, 1 hit
    PS50255 CYTOCHROME_B5_2, 1 hit
    PS51384 FAD_FR, 1 hit

    Sequences (2+)i

    Sequence statusi: Complete.

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

    This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

    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

    Computationally mapped potential isoform sequencesi

    There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
    EntryEntry nameProtein names
    Gene namesLengthAnnotation
    A0A0G2JSK2A0A0G2JSK2_RAT
    Cytochrome b5 reductase 4
    Cyb5r4 rCG_25399
    520Annotation score:

    Sequence cautioni

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

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti38F → I in AAH80240 (PubMed:15489334).Curated1
    Sequence conflicti244Q → L in AAG45053 (PubMed:11913972).Curated1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_025563318 – 368Missing in isoform 2. 1 PublicationAdd BLAST51

    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
    UniGeneiRn.3334

    Genome annotation databases

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

    Keywords - Coding sequence diversityi

    Alternative splicing

    Similar proteinsi

    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
    UniGeneiRn.3334

    3D structure databases

    ProteinModelPortaliQ68EJ0
    SMRiQ68EJ0
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    STRINGi10116.ENSRNOP00000013909

    PTM databases

    PhosphoSitePlusiQ68EJ0

    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
    PhylomeDBiQ68EJ0

    Enzyme and pathway databases

    BRENDAi1.6.2.2 5301
    SABIO-RKiQ68EJ0

    Miscellaneous databases

    PROiPR:Q68EJ0

    Family and domain databases

    CDDicd06490 p23_NCB5OR, 1 hit
    Gene3Di2.60.40.790, 1 hit
    3.10.120.10, 1 hit
    3.40.50.80, 1 hit
    InterProiView protein in InterPro
    IPR008333 Cbr1-like_FAD-bd_dom
    IPR007052 CS_dom
    IPR001199 Cyt_B5-like_heme/steroid-bd
    IPR036400 Cyt_B5-like_heme/steroid_sf
    IPR018506 Cyt_B5_heme-BS
    IPR017927 FAD-bd_FR_type
    IPR039261 FNR_nucleotide-bd
    IPR008978 HSP20-like_chaperone
    IPR001834 NADH-Cyt_B5_reductase
    IPR001433 OxRdtase_FAD/NAD-bd
    IPR037908 p23_NCB5OR
    IPR017938 Riboflavin_synthase-like_b-brl
    PfamiView protein in Pfam
    PF04969 CS, 1 hit
    PF00173 Cyt-b5, 1 hit
    PF00970 FAD_binding_6, 1 hit
    PF00175 NAD_binding_1, 1 hit
    PRINTSiPR00406 CYTB5RDTASE
    PR00363 CYTOCHROMEB5
    SMARTiView protein in SMART
    SM01117 Cyt-b5, 1 hit
    SUPFAMiSSF49764 SSF49764, 1 hit
    SSF52343 SSF52343, 1 hit
    SSF55856 SSF55856, 1 hit
    SSF63380 SSF63380, 1 hit
    PROSITEiView protein in PROSITE
    PS51203 CS, 1 hit
    PS00191 CYTOCHROME_B5_1, 1 hit
    PS50255 CYTOCHROME_B5_2, 1 hit
    PS51384 FAD_FR, 1 hit
    ProtoNetiSearch...

    Entry informationi

    Entry nameiNB5R4_RAT
    AccessioniPrimary (citable) accession number: Q68EJ0
    Secondary accession number(s): Q6VXY2, Q6VXY3, Q9EPZ4
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 15, 2007
    Last sequence update: May 15, 2007
    Last modified: November 7, 2018
    This is version 111 of the entry and version 2 of the sequence. See 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
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