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Q8N4T8

- CBR4_HUMAN

UniProt

Q8N4T8 - CBR4_HUMAN

Protein

Carbonyl reductase family member 4

Gene

CBR4

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 97 (01 Oct 2014)
      Sequence version 3 (24 Nov 2009)
      Previous versions | rss
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    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.

    Pathwayi

    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

    1. NAD(P)H dehydrogenase (quinone) activity Source: UniProtKB
    2. NADPH binding Source: UniProtKB
    3. NADPH dehydrogenase (quinone) activity Source: UniProtKB
    4. protein binding Source: UniProtKB
    5. quinone binding Source: UniProtKB

    GO - Biological processi

    1. daunorubicin metabolic process Source: UniProtKB
    2. doxorubicin metabolic process Source: UniProtKB
    3. fatty acid biosynthetic process Source: UniProtKB-UniPathway
    4. protein homotetramerization Source: UniProtKB

    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
    Gene namesi
    Name:CBR4
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 4

    Organism-specific databases

    HGNCiHGNC:25891. CBR4.

    Subcellular locationi

    Mitochondrion matrix 2 Publications

    GO - Cellular componenti

    1. mitochondrial matrix Source: UniProtKB

    Keywords - Cellular componenti

    Mitochondrion

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA144596471.

    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

    ArrayExpressiQ8N4T8.
    BgeeiQ8N4T8.
    CleanExiHS_CBR4.
    GenevestigatoriQ8N4T8.

    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

    3D structure databases

    ProteinModelPortaliQ8N4T8.
    SMRiQ8N4T8. Positions 3-233.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Phylogenomic databases

    eggNOGiCOG1028.
    HOVERGENiHBG002145.
    InParanoidiQ8N4T8.
    KOiK11539.
    OMAiPKVIAYS.
    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. Align

    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

    MDKVCAVFGG SRGIGRAVAQ LMARKGYRLA VIARNLEGAK AAAGDLGGDH    50
    LAFSCDVAKE HDVQNTFEEL EKHLGRVNFL VNAAGINRDG LLVRTKTEDM 100
    VSQLHTNLLG SMLTCKAAMR TMIQQQGGSI VNVGSIVGLK GNSGQSVYSA 150
    SKGGLVGFSR ALAKEVARKK IRVNVVAPGF VHTDMTKDLK EEHLKKNIPL 200
    GRFGETIEVA HAVVFLLESP YITGHVLVVD GGLQLIL 237
    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:
    EMBL
    GenBank
    DDBJ
    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.3. human. [Q8N4T8-1]

    Polymorphism databases

    DMDMi269849708.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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 .
    CCDSi CCDS3812.1. [Q8N4T8-1 ]
    RefSeqi NP_116172.2. NM_032783.4. [Q8N4T8-1 ]
    UniGenei Hs.659311.

    3D structure databases

    ProteinModelPortali Q8N4T8.
    SMRi Q8N4T8. Positions 3-233.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 124314. 3 interactions.
    STRINGi 9606.ENSP00000303525.

    PTM databases

    PhosphoSitei Q8N4T8.

    Polymorphism databases

    DMDMi 269849708.

    Proteomic databases

    MaxQBi Q8N4T8.
    PaxDbi Q8N4T8.
    PRIDEi Q8N4T8.

    Protocols and materials databases

    DNASUi 84869.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000306193 ; ENSP00000303525 ; ENSG00000145439 . [Q8N4T8-1 ]
    ENST00000504480 ; ENSP00000427615 ; ENSG00000145439 . [Q8N4T8-2 ]
    GeneIDi 84869.
    KEGGi hsa:84869.
    UCSCi uc003iry.3. human. [Q8N4T8-1 ]

    Organism-specific databases

    CTDi 84869.
    GeneCardsi GC04M169815.
    H-InvDB HIX0004629.
    HGNCi HGNC:25891. CBR4.
    HPAi HPA037499.
    neXtProti NX_Q8N4T8.
    PharmGKBi PA144596471.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG1028.
    HOVERGENi HBG002145.
    InParanoidi Q8N4T8.
    KOi K11539.
    OMAi PKVIAYS.
    PhylomeDBi Q8N4T8.
    TreeFami TF354265.

    Enzyme and pathway databases

    UniPathwayi UPA00094 .
    SABIO-RK Q8N4T8.

    Miscellaneous databases

    ChiTaRSi CBR4. human.
    GenomeRNAii 84869.
    NextBioi 75151.
    PROi Q8N4T8.

    Gene expression databases

    ArrayExpressi Q8N4T8.
    Bgeei Q8N4T8.
    CleanExi HS_CBR4.
    Genevestigatori Q8N4T8.

    Family and domain databases

    Gene3Di 3.40.50.720. 1 hit.
    InterProi IPR002198. DH_sc/Rdtase_SDR.
    IPR002347. Glc/ribitol_DH.
    IPR016040. NAD(P)-bd_dom.
    IPR020904. Sc_DH/Rdtase_CS.
    [Graphical view ]
    Pfami PF00106. adh_short. 1 hit.
    [Graphical view ]
    PRINTSi PR00081. GDHRDH.
    PR00080. SDRFAMILY.
    PROSITEi PS00061. ADH_SHORT. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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. 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: October 1, 2014
    This is version 97 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

    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. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3