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Protein

Carbonyl reductase family member 4

Gene

CBR4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

The heterotetramer with HSD17B8 has NADH-dependent 3-ketoacyl-acyl carrier protein reductase activity, and thereby plays a role in mitochondrial fatty acid biosynthesis (PubMed:19571038, PubMed:25203508). Within the heterotetramer, HSD17B8 binds NADH; CBR4 binds NADPD (PubMed:25203508). The homotetramer has NADPH-dependent quinone reductase activity (PubMed:19000905). Both homotetramer and the heterotetramer have broad substrate specificity and can reduce 9,10-phenanthrenequinone, 1,4-benzoquinone and various other o-quinones and p-quinones (in vitro) (PubMed:19000905, PubMed:19571038, PubMed:25203508).3 Publications

Kineticsi

  1. KM=11 µM for NADPH (for homotetramer)1 Publication
  2. KM=1.6 µM for 9,10-phenanthrenequinone (for homotetramer)1 Publication
  3. KM=1.9 µM for 1,4-benzoquinone (for homotetramer)1 Publication

    pH dependencei

    Optimum pH is 6-8 (for homotetramer).1 Publication

    Pathwayi: fatty acid biosynthesis

    This protein is involved in the pathway fatty acid biosynthesis, which is part of Lipid metabolism.2 Publications
    View all proteins of this organism that are known to be involved in the pathway fatty acid biosynthesis and in Lipid metabolism.

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei56NADPCombined sources1 Publication1
    Binding sitei135Substrate1 Publication1
    Active sitei148Proton acceptorPROSITE-ProRule annotation1
    Binding sitei148NADPCombined sources1 Publication1
    Binding sitei152NADPCombined sources1 Publication1
    Sitei169Important for interaction with acyl carrier protein (ACP)1 Publication1

    Regions

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Nucleotide bindingi11 – 14NADPCombined sources1 Publication4
    Nucleotide bindingi34 – 35NADPCombined sources1 Publication2
    Nucleotide bindingi83 – 85NADPCombined sources1 Publication3
    Nucleotide bindingi181 – 183NADPCombined sources1 Publication3

    GO - Molecular functioni

    • 3-oxoacyl-[acyl-carrier-protein] reductase (NADH) activity Source: UniProtKB
    • NAD(P)H dehydrogenase (quinone) activity Source: UniProtKB
    • NADPH binding Source: UniProtKB
    • NADPH dehydrogenase (quinone) activity Source: UniProtKB
    • quinone binding Source: UniProtKB

    GO - Biological processi

    • daunorubicin metabolic process Source: UniProtKB
    • doxorubicin metabolic process Source: UniProtKB
    • fatty acid biosynthetic process Source: UniProtKB
    • oxidation-reduction process Source: UniProtKB
    • protein heterotetramerization Source: UniProtKB
    • protein homotetramerization Source: UniProtKB
    Complete GO annotation...

    Keywords - Molecular functioni

    Oxidoreductase

    Keywords - Biological processi

    Fatty acid biosynthesis, Fatty acid metabolism, Lipid biosynthesis, Lipid metabolism

    Keywords - Ligandi

    NAD, NADP

    Enzyme and pathway databases

    ReactomeiR-HSA-535734. Fatty acid, triacylglycerol, and ketone body metabolism.
    SABIO-RKQ8N4T8.
    UniPathwayiUPA00094.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Carbonyl reductase family member 4 (EC:1.-.-.-1 Publication)
    Alternative name(s):
    3-ketoacyl-[acyl-carrier-protein] reductase beta subunit1 Publication
    Short name:
    KAR beta subunit1 Publication
    3-oxoacyl-[acyl-carrier-protein] reductase (EC:1.1.1.-2 Publications)
    Quinone reductase CBR41 Publication
    Short chain dehydrogenase/reductase family 45C member 1
    Gene namesi
    Name:CBR4
    Synonyms:SDR45C1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 4

    Organism-specific databases

    HGNCiHGNC:25891. CBR4.

    Subcellular locationi

    GO - Cellular componenti

    • mitochondrial matrix Source: UniProtKB
    • oxidoreductase complex Source: UniProtKB
    Complete GO annotation...

    Keywords - Cellular componenti

    Mitochondrion

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi9G → S: Unable to restore growth of an OAR1-deficient yeast mutant. 1 Publication1
    Mutagenesisi12R → A: Strongly reduced ability to restore growth of an OAR1-deficient yeast mutant. 1 Publication1
    Mutagenesisi34R → A: Strongly reduced ability to restore growth of an OAR1-deficient yeast mutant. Strongly reduces NADPH-dependent reductase activity with acetoacetyl-CoA and 9,10-phenanthrene quinone. No effect on NADH-dependent reductase activitites. 1 Publication1
    Mutagenesisi135S → A: Unable to restore growth of an OAR1-deficient yeast mutant. 1 Publication1
    Mutagenesisi148Y → A: Unable to restore growth of an OAR1-deficient yeast mutant. 1 Publication1
    Mutagenesisi152K → A: Unable to restore growth of an OAR1-deficient yeast mutant. Abolishes NADPH-dependent reductase activity with acetoacetyl-CoA. Strongly reduces NADPH-dependent reductase activity with 9,10-phenanthrene quinone. No effect on NADH-dependent reductase activitites. 1 Publication1
    Mutagenesisi168R → E: Strongly reduced ability to restore growth of an OAR1-deficient yeast mutant. Increases NADPH-dependent reductase activity with acetoacetyl-CoA. Reduces NADPH-dependent reductase activity with 9,10-phenanthrene quinone. No effect on NADH-dependent reductase activitites. 1 Publication1
    Mutagenesisi169K → E: Unable to restore growth of an OAR1-deficient yeast mutant. Increases NADPH-dependent reductase activity with acetoacetyl-CoA. Reduces NADPH-dependent reductase activity with 9,10-phenanthrene quinone. No effect on NADH-dependent reductase activitites. 1 Publication1

    Organism-specific databases

    OpenTargetsiENSG00000145439.
    PharmGKBiPA144596471.

    Polymorphism and mutation databases

    BioMutaiCBR4.
    DMDMi269849708.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00003198781 – 237Carbonyl reductase family member 4Add BLAST237

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei1N-acetylmethionineCombined sources1
    Modified residuei40N6-acetyllysineBy similarity1
    Modified residuei96N6-acetyllysineBy similarity1
    Modified residuei195N6-acetyllysineBy similarity1

    Keywords - PTMi

    Acetylation

    Proteomic databases

    EPDiQ8N4T8.
    MaxQBiQ8N4T8.
    PaxDbiQ8N4T8.
    PeptideAtlasiQ8N4T8.
    PRIDEiQ8N4T8.

    PTM databases

    iPTMnetiQ8N4T8.
    PhosphoSitePlusiQ8N4T8.

    Expressioni

    Tissue specificityi

    Detected in liver and kidney (at protein level).1 Publication

    Gene expression databases

    BgeeiENSG00000145439.
    CleanExiHS_CBR4.
    ExpressionAtlasiQ8N4T8. baseline and differential.
    GenevisibleiQ8N4T8. HS.

    Organism-specific databases

    HPAiHPA037499.

    Interactioni

    Subunit structurei

    Homotetramer (in vitro) (PubMed:19000905). Heterotetramer with HSD17B8; contains two molecules each of HSD17B8 and CBR4 (PubMed:19571038, PubMed:25203508). Does not form homotetramers when HSD17B8 is coexpressed, only heterotetramers (in vitro) (PubMed:25203508).3 Publications

    Protein-protein interaction databases

    BioGridi124314. 4 interactors.
    IntActiQ8N4T8. 1 interactor.
    STRINGi9606.ENSP00000303525.

    Structurei

    Secondary structure

    1237
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Beta strandi4 – 8Combined sources5
    Turni9 – 11Combined sources3
    Helixi14 – 23Combined sources10
    Turni24 – 26Combined sources3
    Beta strandi28 – 34Combined sources7
    Helixi36 – 45Combined sources10
    Beta strandi51 – 54Combined sources4
    Helixi60 – 69Combined sources10
    Turni70 – 74Combined sources5
    Beta strandi77 – 82Combined sources6
    Turni92 – 94Combined sources3
    Helixi97 – 107Combined sources11
    Helixi109 – 124Combined sources16
    Beta strandi128 – 133Combined sources6
    Helixi136 – 138Combined sources3
    Helixi146 – 165Combined sources20
    Helixi167 – 169Combined sources3
    Beta strandi171 – 178Combined sources8
    Helixi190 – 193Combined sources4
    Helixi206 – 218Combined sources13
    Beta strandi226 – 232Combined sources7
    Helixi233 – 235Combined sources3

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    4CQLX-ray2.85B/C/F/G/J/K/N/O1-237[»]
    4CQMX-ray2.34B/C/F/G/J/K/N/O1-237[»]
    ProteinModelPortaliQ8N4T8.
    SMRiQ8N4T8.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Phylogenomic databases

    eggNOGiKOG1200. Eukaryota.
    COG1028. LUCA.
    GeneTreeiENSGT00760000118868.
    HOVERGENiHBG002145.
    InParanoidiQ8N4T8.
    KOiK11539.
    OMAiRIWEMSE.
    OrthoDBiEOG091G0N2V.
    PhylomeDBiQ8N4T8.
    TreeFamiTF354265.

    Family and domain databases

    Gene3Di3.40.50.720. 1 hit.
    InterProiIPR016040. NAD(P)-bd_dom.
    IPR020904. Sc_DH/Rdtase_CS.
    IPR002347. SDR_fam.
    [Graphical view]
    PANTHERiPTHR24322. PTHR24322. 2 hits.
    PRINTSiPR00081. GDHRDH.
    PR00080. SDRFAMILY.
    SUPFAMiSSF51735. SSF51735. 1 hit.
    PROSITEiPS00061. ADH_SHORT. 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: Q8N4T8-1) [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
    MDKVCAVFGG SRGIGRAVAQ LMARKGYRLA VIARNLEGAK AAAGDLGGDH
    60 70 80 90 100
    LAFSCDVAKE HDVQNTFEEL EKHLGRVNFL VNAAGINRDG LLVRTKTEDM
    110 120 130 140 150
    VSQLHTNLLG SMLTCKAAMR TMIQQQGGSI VNVGSIVGLK GNSGQSVYSA
    160 170 180 190 200
    SKGGLVGFSR ALAKEVARKK IRVNVVAPGF VHTDMTKDLK EEHLKKNIPL
    210 220 230
    GRFGETIEVA HAVVFLLESP YITGHVLVVD GGLQLIL
    Length:237
    Mass (Da):25,301
    Last modified:November 24, 2009 - v3
    Checksum:i376FF5FA0CB9ABF0
    GO
    Isoform 2 (identifier: Q8N4T8-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         180-237: Missing.

    Note: No experimental confirmation available.
    Show »
    Length:179
    Mass (Da):18,837
    Checksum:i6C43EAF3A2AFCEA0
    GO

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_03904970L → M.Combined sources3 PublicationsCorresponds to variant rs2877380dbSNPEnsembl.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_031527180 – 237Missing in isoform 2. 1 PublicationAdd BLAST58

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AK027337 mRNA. Translation: BAB55045.1.
    AK291756 mRNA. Translation: BAF84445.1.
    AL833393 mRNA. Translation: CAH10582.1.
    AC021151 Genomic DNA. No translation available.
    CH471056 Genomic DNA. Translation: EAX04797.1.
    BC021973 mRNA. Translation: AAH21973.1.
    BC033650 mRNA. Translation: AAH33650.1.
    CCDSiCCDS3812.1. [Q8N4T8-1]
    RefSeqiNP_116172.2. NM_032783.4. [Q8N4T8-1]
    UniGeneiHs.659311.

    Genome annotation databases

    EnsembliENST00000306193; ENSP00000303525; ENSG00000145439. [Q8N4T8-1]
    ENST00000504480; ENSP00000427615; ENSG00000145439. [Q8N4T8-2]
    GeneIDi84869.
    KEGGihsa:84869.
    UCSCiuc003iry.4. human. [Q8N4T8-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AK027337 mRNA. Translation: BAB55045.1.
    AK291756 mRNA. Translation: BAF84445.1.
    AL833393 mRNA. Translation: CAH10582.1.
    AC021151 Genomic DNA. No translation available.
    CH471056 Genomic DNA. Translation: EAX04797.1.
    BC021973 mRNA. Translation: AAH21973.1.
    BC033650 mRNA. Translation: AAH33650.1.
    CCDSiCCDS3812.1. [Q8N4T8-1]
    RefSeqiNP_116172.2. NM_032783.4. [Q8N4T8-1]
    UniGeneiHs.659311.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    4CQLX-ray2.85B/C/F/G/J/K/N/O1-237[»]
    4CQMX-ray2.34B/C/F/G/J/K/N/O1-237[»]
    ProteinModelPortaliQ8N4T8.
    SMRiQ8N4T8.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi124314. 4 interactors.
    IntActiQ8N4T8. 1 interactor.
    STRINGi9606.ENSP00000303525.

    PTM databases

    iPTMnetiQ8N4T8.
    PhosphoSitePlusiQ8N4T8.

    Polymorphism and mutation databases

    BioMutaiCBR4.
    DMDMi269849708.

    Proteomic databases

    EPDiQ8N4T8.
    MaxQBiQ8N4T8.
    PaxDbiQ8N4T8.
    PeptideAtlasiQ8N4T8.
    PRIDEiQ8N4T8.

    Protocols and materials databases

    DNASUi84869.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000306193; ENSP00000303525; ENSG00000145439. [Q8N4T8-1]
    ENST00000504480; ENSP00000427615; ENSG00000145439. [Q8N4T8-2]
    GeneIDi84869.
    KEGGihsa:84869.
    UCSCiuc003iry.4. human. [Q8N4T8-1]

    Organism-specific databases

    CTDi84869.
    GeneCardsiCBR4.
    H-InvDBHIX0004629.
    HGNCiHGNC:25891. CBR4.
    HPAiHPA037499.
    neXtProtiNX_Q8N4T8.
    OpenTargetsiENSG00000145439.
    PharmGKBiPA144596471.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG1200. Eukaryota.
    COG1028. LUCA.
    GeneTreeiENSGT00760000118868.
    HOVERGENiHBG002145.
    InParanoidiQ8N4T8.
    KOiK11539.
    OMAiRIWEMSE.
    OrthoDBiEOG091G0N2V.
    PhylomeDBiQ8N4T8.
    TreeFamiTF354265.

    Enzyme and pathway databases

    UniPathwayiUPA00094.
    ReactomeiR-HSA-535734. Fatty acid, triacylglycerol, and ketone body metabolism.
    SABIO-RKQ8N4T8.

    Miscellaneous databases

    ChiTaRSiCBR4. human.
    GenomeRNAii84869.
    PROiQ8N4T8.

    Gene expression databases

    BgeeiENSG00000145439.
    CleanExiHS_CBR4.
    ExpressionAtlasiQ8N4T8. baseline and differential.
    GenevisibleiQ8N4T8. HS.

    Family and domain databases

    Gene3Di3.40.50.720. 1 hit.
    InterProiIPR016040. NAD(P)-bd_dom.
    IPR020904. Sc_DH/Rdtase_CS.
    IPR002347. SDR_fam.
    [Graphical view]
    PANTHERiPTHR24322. PTHR24322. 2 hits.
    PRINTSiPR00081. GDHRDH.
    PR00080. SDRFAMILY.
    SUPFAMiSSF51735. SSF51735. 1 hit.
    PROSITEiPS00061. ADH_SHORT. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Entry informationi

    Entry nameiCBR4_HUMAN
    AccessioniPrimary (citable) accession number: Q8N4T8
    Secondary accession number(s): Q8WTW8, Q96K93
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 26, 2008
    Last sequence update: November 24, 2009
    Last modified: November 2, 2016
    This is version 118 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 4
      Human chromosome 4: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. 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.