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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 heteroteramer with HSD17B8 has NADH-dependent 3-ketoacyl-acyl carrier protein reductase activity. May play a role in biosynthesis of fatty acids in mitochondria. The homotetramer may act as NADPH-dependent quinone reductase. Has broad substrate specificity and reduces 9,10-phenanthrenequinone, 1,4-benzoquinone and various other o-quinones and p-quinones (in vitro).2 Publications

Kineticsi

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

    pH dependencei

    Optimum pH is 6-8.

    Pathway:ifatty acid biosynthesis

    This protein is involved in the pathway fatty acid biosynthesis, which is part of Lipid metabolism.
    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)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei135 – 1351SubstrateBy similarity
    Active sitei148 – 1481Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi7 – 3125NAD or NADPBy similarityAdd
    BLAST

    GO - Molecular functioni

    • 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-UniPathway
    • 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

    SABIO-RKQ8N4T8.
    UniPathwayiUPA00094.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Carbonyl reductase family member 4 (EC:1.-.-.-)
    Alternative name(s):
    3-oxoacyl-[acyl-carrier-protein] reductase (EC:1.1.1.-)
    Quinone reductase CBR4
    Short chain dehydrogenase/reductase family 45C member 1
    Gene namesi
    Name:CBR4
    Synonyms:SDR45C1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640 Componenti: Chromosome 4

    Organism-specific databases

    HGNCiHGNC:25891. CBR4.

    Subcellular locationi

    GO - Cellular componenti

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

    Keywords - Cellular componenti

    Mitochondrion

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA144596471.

    Polymorphism and mutation databases

    BioMutaiCBR4.
    DMDMi269849708.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 237237Carbonyl reductase family member 4PRO_0000319878Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei1 – 11N-acetylmethionine1 Publication
    Modified residuei40 – 401N6-acetyllysineBy similarity
    Modified residuei96 – 961N6-acetyllysineBy similarity
    Modified residuei195 – 1951N6-acetyllysineBy similarity

    Keywords - PTMi

    Acetylation

    Proteomic databases

    MaxQBiQ8N4T8.
    PaxDbiQ8N4T8.
    PRIDEiQ8N4T8.

    PTM databases

    PhosphoSiteiQ8N4T8.

    Expressioni

    Tissue specificityi

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

    Gene expression databases

    BgeeiQ8N4T8.
    CleanExiHS_CBR4.
    ExpressionAtlasiQ8N4T8. baseline and differential.
    GenevisibleiQ8N4T8. HS.

    Organism-specific databases

    HPAiHPA037499.

    Interactioni

    Subunit structurei

    Homotetramer. Heterotetramer with HSD17B8; contains two molecules of HSD17B8 and CBR4.1 Publication

    Protein-protein interaction databases

    BioGridi124314. 3 interactions.
    STRINGi9606.ENSP00000303525.

    Structurei

    Secondary structure

    1
    237
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi4 – 85Combined sources
    Turni9 – 113Combined sources
    Helixi14 – 2310Combined sources
    Turni24 – 263Combined sources
    Beta strandi28 – 347Combined sources
    Helixi36 – 4510Combined sources
    Beta strandi51 – 544Combined sources
    Helixi60 – 6910Combined sources
    Turni70 – 745Combined sources
    Beta strandi77 – 826Combined sources
    Turni92 – 943Combined sources
    Helixi97 – 10711Combined sources
    Helixi109 – 12416Combined sources
    Beta strandi128 – 1336Combined sources
    Helixi136 – 1383Combined sources
    Helixi146 – 16520Combined sources
    Helixi167 – 1693Combined sources
    Beta strandi171 – 1788Combined sources
    Helixi190 – 1934Combined sources
    Helixi206 – 21813Combined sources
    Beta strandi226 – 2327Combined sources
    Helixi233 – 2353Combined sources

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    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. Positions 1-237.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Phylogenomic databases

    eggNOGiCOG1028.
    GeneTreeiENSGT00760000118868.
    HOVERGENiHBG002145.
    InParanoidiQ8N4T8.
    KOiK11539.
    OMAiIWEMSED.
    PhylomeDBiQ8N4T8.
    TreeFamiTF354265.

    Family and domain databases

    Gene3Di3.40.50.720. 1 hit.
    InterProiIPR002198. DH_sc/Rdtase_SDR.
    IPR002347. Glc/ribitol_DH.
    IPR016040. NAD(P)-bd_dom.
    IPR020904. Sc_DH/Rdtase_CS.
    [Graphical view]
    PfamiPF00106. adh_short. 1 hit.
    [Graphical view]
    PRINTSiPR00081. GDHRDH.
    PR00080. SDRFAMILY.
    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)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti70 – 701L → M.4 Publications
    Corresponds to variant rs2877380 [ dbSNP | Ensembl ].
    VAR_039049

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei180 – 23758Missing in isoform 2. 1 PublicationVSP_031527Add
    BLAST

    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.
    ENST00000504480; ENSP00000427615; ENSG00000145439. [Q8N4T8-2]
    GeneIDi84869.
    KEGGihsa:84869.
    UCSCiuc003iry.3. 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
    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. Positions 1-237.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi124314. 3 interactions.
    STRINGi9606.ENSP00000303525.

    PTM databases

    PhosphoSiteiQ8N4T8.

    Polymorphism and mutation databases

    BioMutaiCBR4.
    DMDMi269849708.

    Proteomic databases

    MaxQBiQ8N4T8.
    PaxDbiQ8N4T8.
    PRIDEiQ8N4T8.

    Protocols and materials databases

    DNASUi84869.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000306193; ENSP00000303525; ENSG00000145439.
    ENST00000504480; ENSP00000427615; ENSG00000145439. [Q8N4T8-2]
    GeneIDi84869.
    KEGGihsa:84869.
    UCSCiuc003iry.3. human. [Q8N4T8-1]

    Organism-specific databases

    CTDi84869.
    GeneCardsiGC04M169815.
    H-InvDBHIX0004629.
    HGNCiHGNC:25891. CBR4.
    HPAiHPA037499.
    neXtProtiNX_Q8N4T8.
    PharmGKBiPA144596471.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiCOG1028.
    GeneTreeiENSGT00760000118868.
    HOVERGENiHBG002145.
    InParanoidiQ8N4T8.
    KOiK11539.
    OMAiIWEMSED.
    PhylomeDBiQ8N4T8.
    TreeFamiTF354265.

    Enzyme and pathway databases

    UniPathwayiUPA00094.
    SABIO-RKQ8N4T8.

    Miscellaneous databases

    ChiTaRSiCBR4. human.
    GenomeRNAii84869.
    NextBioi75151.
    PROiQ8N4T8.

    Gene expression databases

    BgeeiQ8N4T8.
    CleanExiHS_CBR4.
    ExpressionAtlasiQ8N4T8. baseline and differential.
    GenevisibleiQ8N4T8. HS.

    Family and domain databases

    Gene3Di3.40.50.720. 1 hit.
    InterProiIPR002198. DH_sc/Rdtase_SDR.
    IPR002347. Glc/ribitol_DH.
    IPR016040. NAD(P)-bd_dom.
    IPR020904. Sc_DH/Rdtase_CS.
    [Graphical view]
    PfamiPF00106. adh_short. 1 hit.
    [Graphical view]
    PRINTSiPR00081. GDHRDH.
    PR00080. SDRFAMILY.
    PROSITEiPS00061. ADH_SHORT. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), VARIANT MET-70.
      Tissue: Embryo and Placenta.
    2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT MET-70.
      Tissue: Melanoma.
    3. "Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
      Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H.
      , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
      Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    5. "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), VARIANT MET-70.
      Tissue: Duodenum and Uterus.
    6. "Human carbonyl reductase 4 is a mitochondrial NADPH-dependent quinone reductase."
      Endo S., Matsunaga T., Kitade Y., Ohno S., Tajima K., El-Kabbani O., Hara A.
      Biochem. Biophys. Res. Commun. 377:1326-1330(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, IDENTIFICATION BY MASS SPECTROMETRY, TISSUE SPECIFICITY.
    7. "17beta-Hydroxysteroid dehydrogenase type 8 and carbonyl reductase type 4 assemble as a ketoacyl reductase of human mitochondrial FAS."
      Chen Z., Kastaniotis A.J., Miinalainen I.J., Rajaram V., Wierenga R.K., Hiltunen J.K.
      FASEB J. 23:3682-3691(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH HSD17B8.
    8. Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    9. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
      Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
      J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Liver.
    10. Cited for: VARIANT [LARGE SCALE ANALYSIS] MET-70, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

    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: July 22, 2015
    This is version 105 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

    External Data

    Dasty 3

    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 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.