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O35710

- NOCT_MOUSE

UniProt

O35710 - NOCT_MOUSE

Protein

Nocturnin

Gene

Ccrn4l

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 109 (01 Oct 2014)
      Sequence version 3 (02 Nov 2001)
      Previous versions | rss
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    Functioni

    Circadian deadenylase which plays an important role in post-transcriptional regulation of metabolic genes under circadian control. Degrades poly(A) tails of specific target mRNAs leading to their degradation and suppression of translation. Exerts a rhythmic post-transcriptional control of genes necessary for metabolic functions including nutrient absorption, glucose/insulin sensitivity, lipid metabolism, adipogenesis, inflammation and osteogenesis. Plays an important role in favoring adipogenesis over osteoblastogenesis and acts as a key regulator of the adipogenesis/osteogenesis balance. Promotes adipogenesis by activating PPARG transcriptional activity in a deadenylase-independent manner by facilitating its nuclear translocation. Regulates circadian expression of NOS2 in the liver and negatively regulates the circadian expression of IGF1 in the bone. Critical for proper development of early embryos.8 Publications

    Catalytic activityi

    Exonucleolytic cleavage of poly(A) to 5'-AMP.

    Cofactori

    Magnesium.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei193 – 1931By similarity
    Metal bindingi193 – 1931Magnesium 1By similarity
    Metal bindingi322 – 3221Magnesium 2By similarity
    Metal bindingi324 – 3241Magnesium 2By similarity
    Active sitei375 – 3751By similarity
    Active sitei412 – 4121By similarity
    Metal bindingi412 – 4121Magnesium 2By similarity

    GO - Molecular functioni

    1. metal ion binding Source: UniProtKB-KW
    2. mRNA binding Source: UniProtKB
    3. poly(A)-specific ribonuclease activity Source: UniProtKB
    4. protein binding Source: UniProtKB

    GO - Biological processi

    1. circadian regulation of gene expression Source: UniProtKB
    2. circadian rhythm Source: UniProtKB
    3. cytoplasmic mRNA processing body assembly Source: MGI
    4. deadenylation-dependent decapping of nuclear-transcribed mRNA Source: MGI
    5. mRNA processing Source: UniProtKB-KW
    6. mRNA stabilization Source: UniProtKB
    7. negative regulation of gene expression Source: UniProtKB
    8. negative regulation of osteoblast differentiation Source: UniProtKB
    9. positive regulation of fat cell differentiation Source: UniProtKB
    10. regulation of circadian rhythm Source: UniProtKB
    11. regulation of embryonic development Source: UniProtKB
    12. response to extracellular stimulus Source: UniProtKB
    13. response to lipopolysaccharide Source: UniProtKB
    14. RNA phosphodiester bond hydrolysis, exonucleolytic Source: GOC

    Keywords - Molecular functioni

    Exonuclease, Hydrolase, Nuclease

    Keywords - Biological processi

    Biological rhythms, mRNA processing

    Keywords - Ligandi

    Magnesium, Metal-binding, RNA-binding

    Enzyme and pathway databases

    BRENDAi3.1.13.4. 3474.
    ReactomeiREACT_198620. BMAL1:CLOCK,NPAS2 activates circadian gene expression.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Nocturnin (EC:3.1.13.4)
    Alternative name(s):
    Carbon catabolite repression 4-like protein
    Circadian deadenylase NOC
    Gene namesi
    Name:Ccrn4l
    Synonyms:Ccr4, Noc
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 3

    Organism-specific databases

    MGIiMGI:109382. Ccrn4l.

    Subcellular locationi

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB
    2. cytoplasmic mRNA processing body Source: MGI
    3. nucleus Source: UniProtKB
    4. perinuclear region of cytoplasm Source: UniProtKB

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Disruption phenotypei

    Mice exhibit metabolic defects including a resistance to diet-induced obesity, decreased fat storage, changes in lipid-related gene expression profiles in the liver, and altered glucose and insulin sensitivities. Exhibit a delayed early embryo development and at 12 weeks of age show enhanced skeletal mass and increased osteoblastogenesis.3 Publications

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 429429NocturninPRO_0000218569Add
    BLAST

    Proteomic databases

    PaxDbiO35710.
    PRIDEiO35710.

    PTM databases

    PhosphoSiteiO35710.

    Expressioni

    Tissue specificityi

    Highly expressed in the differentiated adipocyte (at protein level). Ubiquitous.3 Publications

    Developmental stagei

    Expression is highest in oocytes, begins to decrease after fertilization by the 4-cell stage and then slightly increases up to the blastocyst stage.1 Publication

    Inductioni

    Immediate early gene (IEG) showing acute responses to several stimuli including serum shock, phorbol ester, lipopolysaccharide (LPS) and rosiglitazone, a PPARG agonist. Exhibits a high amplitude circadian rhythm with maximal levels in early evening. In constant darkness or constant light, the amplitude of the rhythm decreases. Expression is regulated by both light and food-entrained cues and by the CLOCK-ARNTL/BMAL1 heterodimer and PPARG. Up-regulated in cells undergoing adipogenesis.4 Publications

    Gene expression databases

    ArrayExpressiO35710.
    BgeeiO35710.
    CleanExiMM_CCR4.
    GenevestigatoriO35710.

    Interactioni

    Subunit structurei

    Interacts with PPARG.1 Publication

    Protein-protein interaction databases

    DIPiDIP-60436N.

    Structurei

    3D structure databases

    ProteinModelPortaliO35710.
    SMRiO35710. Positions 120-422.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni341 – 35111Interaction with PPARGAdd
    BLAST

    Sequence similaritiesi

    Belongs to the CCR4/nocturin family.Curated

    Phylogenomic databases

    eggNOGiCOG5239.
    GeneTreeiENSGT00550000074364.
    HOGENOMiHOG000237357.
    HOVERGENiHBG006512.
    InParanoidiO35710.
    OMAiPEYLVSP.
    OrthoDBiEOG7Z95MC.
    PhylomeDBiO35710.
    TreeFamiTF323175.

    Family and domain databases

    Gene3Di3.60.10.10. 1 hit.
    InterProiIPR005135. Endo/exonuclease/phosphatase.
    [Graphical view]
    PfamiPF03372. Exo_endo_phos. 1 hit.
    [Graphical view]
    SUPFAMiSSF56219. SSF56219. 1 hit.

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: O35710-1) [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

    MYQSPRRLCS ALLLRDAPGL RRTLVPGPRR TLAPPVLGSR PKSPQLQAAA    50
    ASGAARSRPR TVSSMGNGTS RLYSALAKTV NSSAAAQHPE YLVSTDPEHL 100
    EPIDPKELLE ECRAVLHTRP PRYQRDFVDL RTDCSSSHSP IRVMQWNILA 150
    QALGEGKDNF VQCPVEALKW EERKCLILEE ILAYQPDILC LQEVDHYFDT 200
    FQPLLSRLGY QGTFFPKPWS PCLDVEHNNG PDGCALFFLQ NRFKLISSTN 250
    IRLTAMTLKT NQVAIAQTLE CKESGRQFCI AVTHLKARTG WERFRSAQGC 300
    DLLQNLQNIT QGAKIPLIVC GDFNAEPTEE VYKHFASSSL NLNSAYKLLS 350
    PDGQSEPPYT TWKIRTSGEC RHTLDYIWYS RHALSVTSAL DLLTEEQIGP 400
    NRLPSFHYPS DHLSLVCDFS FNEEPHELF 429
    Length:429
    Mass (Da):48,301
    Last modified:November 2, 2001 - v3
    Checksum:iCB9FB55D84E13942
    GO
    Isoform 2 (identifier: O35710-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-64: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:365
    Mass (Da):41,500
    Checksum:i762CA86E0F907EB8
    GO

    Sequence cautioni

    The sequence AAB62717.1 differs from that shown. Reason: Frameshift at position 125.

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 6464Missing in isoform 2. 1 PublicationVSP_016677Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U70139 mRNA. Translation: AAB62717.1. Frameshift.
    AF183960 mRNA. Translation: AAD56547.1.
    AF199491 mRNA. Translation: AAG01384.1.
    AK087790 mRNA. Translation: BAC40004.1.
    CCDSiCCDS17336.1. [O35710-1]
    RefSeqiNP_033964.1. NM_009834.2. [O35710-1]
    XP_006501020.1. XM_006500957.1. [O35710-2]
    UniGeneiMm.86541.

    Genome annotation databases

    EnsembliENSMUST00000023849; ENSMUSP00000023849; ENSMUSG00000023087. [O35710-1]
    ENSMUST00000167780; ENSMUSP00000130347; ENSMUSG00000023087. [O35710-1]
    GeneIDi12457.
    KEGGimmu:12457.
    UCSCiuc008pdm.2. mouse. [O35710-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U70139 mRNA. Translation: AAB62717.1 . Frameshift.
    AF183960 mRNA. Translation: AAD56547.1 .
    AF199491 mRNA. Translation: AAG01384.1 .
    AK087790 mRNA. Translation: BAC40004.1 .
    CCDSi CCDS17336.1. [O35710-1 ]
    RefSeqi NP_033964.1. NM_009834.2. [O35710-1 ]
    XP_006501020.1. XM_006500957.1. [O35710-2 ]
    UniGenei Mm.86541.

    3D structure databases

    ProteinModelPortali O35710.
    SMRi O35710. Positions 120-422.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    DIPi DIP-60436N.

    PTM databases

    PhosphoSitei O35710.

    Proteomic databases

    PaxDbi O35710.
    PRIDEi O35710.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000023849 ; ENSMUSP00000023849 ; ENSMUSG00000023087 . [O35710-1 ]
    ENSMUST00000167780 ; ENSMUSP00000130347 ; ENSMUSG00000023087 . [O35710-1 ]
    GeneIDi 12457.
    KEGGi mmu:12457.
    UCSCi uc008pdm.2. mouse. [O35710-1 ]

    Organism-specific databases

    CTDi 25819.
    MGIi MGI:109382. Ccrn4l.

    Phylogenomic databases

    eggNOGi COG5239.
    GeneTreei ENSGT00550000074364.
    HOGENOMi HOG000237357.
    HOVERGENi HBG006512.
    InParanoidi O35710.
    OMAi PEYLVSP.
    OrthoDBi EOG7Z95MC.
    PhylomeDBi O35710.
    TreeFami TF323175.

    Enzyme and pathway databases

    BRENDAi 3.1.13.4. 3474.
    Reactomei REACT_198620. BMAL1:CLOCK,NPAS2 activates circadian gene expression.

    Miscellaneous databases

    ChiTaRSi CCRN4L. mouse.
    NextBioi 281308.
    PROi O35710.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O35710.
    Bgeei O35710.
    CleanExi MM_CCR4.
    Genevestigatori O35710.

    Family and domain databases

    Gene3Di 3.60.10.10. 1 hit.
    InterProi IPR005135. Endo/exonuclease/phosphatase.
    [Graphical view ]
    Pfami PF03372. Exo_endo_phos. 1 hit.
    [Graphical view ]
    SUPFAMi SSF56219. SSF56219. 1 hit.
    ProtoNeti Search...

    Publicationsi

    1. "Characterization of two age-induced intracisternal A-particle-related transcripts in the mouse liver. Transcriptional read-through into an open reading frame with similarities to the yeast ccr4 transcription factor."
      Puech A., Dupressoir A., Loireau M.-P., Mattei M.-G., Heidmann T.
      J. Biol. Chem. 272:5995-6003(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
      Strain: DBA/2J.
      Tissue: Liver.
    2. "Characterization of a mammalian gene related to the yeast CCR4 general transcription factor and revealed by transposon insertion."
      Dupressoir A., Barbot W., Loireau M.-P., Heidmann T.
      J. Biol. Chem. 274:31068-31075(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
      Strain: BALB/c.
      Tissue: Brain.
    3. "Rhythmic expression of nocturnin mRNA in multiple tissues of the mouse."
      Wang Y., Osterbur D.L., Megaw P.L., Tosini G., Fukuhara C., Green C.B., Besharse J.C.
      BMC Dev. Biol. 1:9-9(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CIRCADIAN EXPRESSION, TISSUE SPECIFICITY.
      Strain: BALB/c.
      Tissue: Retina.
    4. "The transcriptional landscape of the mammalian genome."
      Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
      , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
      Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
      Strain: C57BL/6J.
      Tissue: Ovary.
    5. "Immediate early response of the circadian polyA ribonuclease nocturnin to two extracellular stimuli."
      Garbarino-Pico E., Niu S., Rollag M.D., Strayer C.A., Besharse J.C., Green C.B.
      RNA 13:745-755(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INDUCTION.
    6. Cited for: INDUCTION, TISSUE SPECIFICITY.
    7. "Nocturnin suppresses igf1 expression in bone by targeting the 3' untranslated region of igf1 mRNA."
      Kawai M., Delany A.M., Green C.B., Adamo M.L., Rosen C.J.
      Endocrinology 151:4861-4870(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INDUCTION.
    8. "A circadian-regulated gene, Nocturnin, promotes adipogenesis by stimulating PPAR-gamma nuclear translocation."
      Kawai M., Green C.B., Lecka-Czernik B., Douris N., Gilbert M.R., Kojima S., Ackert-Bicknell C., Garg N., Horowitz M.C., Adamo M.L., Clemmons D.R., Rosen C.J.
      Proc. Natl. Acad. Sci. U.S.A. 107:10508-10513(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, INTERACTION WITH PPARG.
    9. "An essential role for the circadian-regulated gene nocturnin in osteogenesis: the importance of local timekeeping in skeletal homeostasis."
      Guntur A.R., Kawai M., Le P., Bouxsein M.L., Bornstein S., Green C.B., Rosen C.J.
      Ann. N. Y. Acad. Sci. 1237:58-63(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    10. "Nocturnin regulates circadian trafficking of dietary lipid in intestinal enterocytes."
      Douris N., Kojima S., Pan X., Lerch-Gaggl A.F., Duong S.Q., Hussain M.M., Green C.B.
      Curr. Biol. 21:1347-1355(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, DISRUPTION PHENOTYPE.
    11. "The circadian deadenylase Nocturnin is necessary for stabilization of the iNOS mRNA in mice."
      Niu S., Shingle D.L., Garbarino-Pico E., Kojima S., Gilbert M., Green C.B.
      PLoS ONE 6:E26954-E26954(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INDUCTION.
    12. "The role of nocturnin in early adipogenesis and modulation of systemic insulin resistance in human."
      Hee S.W., Tsai S.H., Chang Y.C., Chang C.J., Yu I.S., Lee P.C., Lee W.J., Yun-Chia Chang E., Chuang L.M.
      Obesity 20:1558-1565(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    13. "Functional analysis of nocturnin, a circadian deadenylase, at maternal-to-zygotic transition in mice."
      Nishikawa S., Hatanaka Y., Tokoro M., Shin S.W., Shimizu N., Nishihara T., Kato R., Takemoto A., Amano T., Anzai M., Kishigami S., Hosoi Y., Matsumoto K.
      J. Reprod. Dev. 59:258-265(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE.

    Entry informationi

    Entry nameiNOCT_MOUSE
    AccessioniPrimary (citable) accession number: O35710
    Secondary accession number(s): Q9QZG9
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 15, 1999
    Last sequence update: November 2, 2001
    Last modified: October 1, 2014
    This is version 109 of the entry and version 3 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. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3