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Q62521

- ZIC3_MOUSE

UniProt

Q62521 - ZIC3_MOUSE

Protein

Zinc finger protein ZIC 3

Gene

Zic3

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 126 (01 Oct 2014)
      Sequence version 2 (27 Jul 2011)
      Previous versions | rss
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    Functioni

    Acts as transcriptional activator. Required in the earliest stages in both axial midline development and left-right (LR) asymmetry specification. Binds to the minimal GLI-consensus sequence 5'-GGGTGGTC-3'.3 Publications

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri250 – 28536C2H2-type 1; atypicalPROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri294 – 32128C2H2-type 2; atypicalPROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri327 – 35125C2H2-type 3PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri357 – 38125C2H2-type 4PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri387 – 40923C2H2-type 5PROSITE-ProRule annotationAdd
    BLAST

    GO - Molecular functioni

    1. metal ion binding Source: UniProtKB-KW
    2. protein binding Source: UniProtKB
    3. sequence-specific DNA binding Source: UniProtKB
    4. sequence-specific DNA binding transcription factor activity Source: UniProtKB

    GO - Biological processi

    1. anterior/posterior pattern specification Source: MGI
    2. cell differentiation Source: UniProtKB-KW
    3. determination of digestive tract left/right asymmetry Source: Ensembl
    4. determination of left/right asymmetry in nervous system Source: UniProtKB
    5. determination of left/right symmetry Source: MGI
    6. determination of liver left/right asymmetry Source: Ensembl
    7. determination of pancreatic left/right asymmetry Source: Ensembl
    8. heart looping Source: MGI
    9. lung development Source: Ensembl
    10. pattern specification process Source: MGI
    11. positive regulation of transcription, DNA-templated Source: UniProtKB
    12. positive regulation of transcription from RNA polymerase II promoter Source: MGI
    13. transcription, DNA-templated Source: UniProtKB-KW

    Keywords - Molecular functioni

    Activator, Developmental protein

    Keywords - Biological processi

    Differentiation, Neurogenesis, Transcription, Transcription regulation

    Keywords - Ligandi

    DNA-binding, Metal-binding, Zinc

    Enzyme and pathway databases

    ReactomeiREACT_216222. Transcriptional regulation of pluripotent stem cells.
    REACT_220962. POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Zinc finger protein ZIC 3
    Alternative name(s):
    Zinc finger protein of the cerebellum 3
    Gene namesi
    Name:Zic3
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome X

    Organism-specific databases

    MGIiMGI:106676. Zic3.

    Subcellular locationi

    Nucleus 1 Publication. Cytoplasm 1 Publication
    Note: Translocation to the nucleus requires KPNA1 or KPNA6 By similarity. Localizes in the cytoplasm in presence of MDFIC overexpression.By similarity

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB
    2. nucleus Source: UniProtKB

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Disruption phenotypei

    Some mice exhibit embryonic and postnatal lethality. Viable mice show heart disease, disturbances of laterality, neural tube defects and vertebral and rib defects.1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 466466Zinc finger protein ZIC 3PRO_0000047251Add
    BLAST

    Proteomic databases

    PRIDEiQ62521.

    Expressioni

    Tissue specificityi

    CNS. A high level expression is seen in the cerebellum.

    Developmental stagei

    Expressed in the CNS, tailbud and somites.1 Publication

    Gene expression databases

    ArrayExpressiQ62521.
    BgeeiQ62521.
    CleanExiMM_ZIC3.
    GenevestigatoriQ62521.

    Interactioni

    Subunit structurei

    Interacts with KPNA1 and KPNA6. Interacts (via C2H2-type domains 3, 4 and 5) with GLI3; the interaction enhances its transcriptional activity By similarity. Interacts (via the C2H2-type domains 3, 4 and 5) with MDFIC (via the C2H2-type domains 3, 4 and 5); the interaction reduces its transcriptional activity.By similarity1 Publication

    Protein-protein interaction databases

    BioGridi204696. 1 interaction.
    IntActiQ62521. 2 interactions.
    MINTiMINT-190020.
    STRINGi10090.ENSMUSP00000085999.

    Structurei

    3D structure databases

    ProteinModelPortaliQ62521.
    SMRiQ62521. Positions 244-409.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni296 – 32126Nuclear localization signalBy similarityAdd
    BLAST
    Regioni329 – 35123Nuclear localization signalBy similarityAdd
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi46 – 5510Poly-Ala
    Compositional biasi87 – 9610Poly-His

    Domaini

    The C2H2-type 3, 4 and 5 zinc finger domains are necessary for transcription activation.

    Sequence similaritiesi

    Contains 5 C2H2-type zinc fingers.PROSITE-ProRule annotation

    Zinc finger

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri250 – 28536C2H2-type 1; atypicalPROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri294 – 32128C2H2-type 2; atypicalPROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri327 – 35125C2H2-type 3PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri357 – 38125C2H2-type 4PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri387 – 40923C2H2-type 5PROSITE-ProRule annotationAdd
    BLAST

    Keywords - Domaini

    Repeat, Zinc-finger

    Phylogenomic databases

    eggNOGiCOG5048.
    GeneTreeiENSGT00650000092933.
    HOGENOMiHOG000232057.
    HOVERGENiHBG007135.
    InParanoidiQ3UYV1.
    KOiK09224.
    OMAiKKTCDRT.
    TreeFamiTF351425.

    Family and domain databases

    Gene3Di3.30.160.60. 4 hits.
    InterProiIPR007087. Znf_C2H2.
    IPR015880. Znf_C2H2-like.
    IPR013087. Znf_C2H2/integrase_DNA-bd.
    [Graphical view]
    PfamiPF00096. zf-C2H2. 1 hit.
    [Graphical view]
    SMARTiSM00355. ZnF_C2H2. 5 hits.
    [Graphical view]
    PROSITEiPS00028. ZINC_FINGER_C2H2_1. 3 hits.
    PS50157. ZINC_FINGER_C2H2_2. 4 hits.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q62521-1) [UniParc]FASTAAdd to Basket

    Also known as: Zic3-A

    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

    MTMLLDGGPQ FPGLGVGSFG APRHHEMPNR EPAGMGLNPF GDSTHAAAAA    50
    AAAAAFKLSP ATAHDLSSGQ SSAFTPQGSG YANALGHHHH HHHHHHASQV 100
    PTYGGAASAA FNSTRDFLFR QRGSGLSEAA SGGGQHGLFA GSASSLHAPA 150
    GIPEPPSYLL FPGLHEQGAG HPSPTGHVDN NQVHLGLRGE LFGRADPYRP 200
    VASPRTDPYA ASAQFPNYSP MNMNMGVNVA AHHGPGAFFR YMRQPIKQEL 250
    SCKWIEEAQL SRPKKSCDRT FSTMHELVTH VTMEHVGGPE QNNHVCYWEE 300
    CPREGKSFKA KYKLVNHIRV HTGEKPFPCP FPGCGKIFAR SENLKIHKRT 350
    HTGEKPFKCE FEGCDRRFAN SSDRKKHMHV HTSDKPYICK VCDKSYTHPS 400
    SLRKHMKVHE SQGSDSSPAA SSGYESSTPP AIASANSKDT TKTPSAVQTS 450
    TSHNPGLPPN FNEWYV 466
    Length:466
    Mass (Da):50,446
    Last modified:July 27, 2011 - v2
    Checksum:iC92C06EC06DF601A
    GO
    Isoform 2 (identifier: Q62521-2) [UniParc]FASTAAdd to Basket

    Also known as: Zic3-B

    The sequence of this isoform differs from the canonical sequence as follows:
         408-466: VHESQGSDSS...LPPNFNEWYV → CCPAWYLGQS...AEPTVQEMIY

    Show »
    Length:456
    Mass (Da):49,952
    Checksum:iBD0ECE4D3780FBAA
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti104 – 1063GGA → ARR in BAA11116. (PubMed:8557628)Curated
    Isoform 2 (identifier: Q62521-2)
    Sequence conflicti419 – 4191I → V in BAC28831. (PubMed:16141072)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei408 – 46659VHESQ…NEWYV → CCPAWYLGQSLIPDEELDTD VGMQQPVLHNTSYPKCRVNA EPTVQEMIY in isoform 2. 1 PublicationVSP_044011Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    D70849 mRNA. Translation: BAA11116.1.
    AK134355 mRNA. Translation: BAE22110.1.
    AK034780 mRNA. Translation: BAC28831.1.
    AL954389 Genomic DNA. Translation: CAM20753.1.
    AL954389, AL671920 Genomic DNA. Translation: CAM20751.1.
    AL671920, AL954389 Genomic DNA. Translation: CAM24569.1.
    CH466583 Genomic DNA. Translation: EDL42177.1.
    CH466583 Genomic DNA. Translation: EDL42178.1.
    CCDSiCCDS30155.1. [Q62521-1]
    RefSeqiNP_033601.2. NM_009575.2. [Q62521-1]
    UniGeneiMm.255890.

    Genome annotation databases

    EnsembliENSMUST00000088627; ENSMUSP00000085999; ENSMUSG00000067860. [Q62521-1]
    ENSMUST00000088629; ENSMUSP00000086001; ENSMUSG00000067860. [Q62521-2]
    GeneIDi22773.
    KEGGimmu:22773.
    UCSCiuc009tho.1. mouse. [Q62521-1]
    uc009thp.1. mouse.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    D70849 mRNA. Translation: BAA11116.1 .
    AK134355 mRNA. Translation: BAE22110.1 .
    AK034780 mRNA. Translation: BAC28831.1 .
    AL954389 Genomic DNA. Translation: CAM20753.1 .
    AL954389 , AL671920 Genomic DNA. Translation: CAM20751.1 .
    AL671920 , AL954389 Genomic DNA. Translation: CAM24569.1 .
    CH466583 Genomic DNA. Translation: EDL42177.1 .
    CH466583 Genomic DNA. Translation: EDL42178.1 .
    CCDSi CCDS30155.1. [Q62521-1 ]
    RefSeqi NP_033601.2. NM_009575.2. [Q62521-1 ]
    UniGenei Mm.255890.

    3D structure databases

    ProteinModelPortali Q62521.
    SMRi Q62521. Positions 244-409.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 204696. 1 interaction.
    IntActi Q62521. 2 interactions.
    MINTi MINT-190020.
    STRINGi 10090.ENSMUSP00000085999.

    Proteomic databases

    PRIDEi Q62521.

    Protocols and materials databases

    DNASUi 22773.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000088627 ; ENSMUSP00000085999 ; ENSMUSG00000067860 . [Q62521-1 ]
    ENSMUST00000088629 ; ENSMUSP00000086001 ; ENSMUSG00000067860 . [Q62521-2 ]
    GeneIDi 22773.
    KEGGi mmu:22773.
    UCSCi uc009tho.1. mouse. [Q62521-1 ]
    uc009thp.1. mouse.

    Organism-specific databases

    CTDi 7547.
    MGIi MGI:106676. Zic3.

    Phylogenomic databases

    eggNOGi COG5048.
    GeneTreei ENSGT00650000092933.
    HOGENOMi HOG000232057.
    HOVERGENi HBG007135.
    InParanoidi Q3UYV1.
    KOi K09224.
    OMAi KKTCDRT.
    TreeFami TF351425.

    Enzyme and pathway databases

    Reactomei REACT_216222. Transcriptional regulation of pluripotent stem cells.
    REACT_220962. POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation.

    Miscellaneous databases

    ChiTaRSi ZIC3. mouse.
    NextBioi 303317.
    PROi Q62521.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q62521.
    Bgeei Q62521.
    CleanExi MM_ZIC3.
    Genevestigatori Q62521.

    Family and domain databases

    Gene3Di 3.30.160.60. 4 hits.
    InterProi IPR007087. Znf_C2H2.
    IPR015880. Znf_C2H2-like.
    IPR013087. Znf_C2H2/integrase_DNA-bd.
    [Graphical view ]
    Pfami PF00096. zf-C2H2. 1 hit.
    [Graphical view ]
    SMARTi SM00355. ZnF_C2H2. 5 hits.
    [Graphical view ]
    PROSITEi PS00028. ZINC_FINGER_C2H2_1. 3 hits.
    PS50157. ZINC_FINGER_C2H2_2. 4 hits.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "The mouse zic gene family. Homologues of the Drosophila pair-rule gene odd-paired."
      Aruga J., Nagai T., Tokuyama T., Hayashizaki Y., Okazaki Y., Chapman V.M., Mikoshiba K.
      J. Biol. Chem. 271:1043-1047(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
      Tissue: Cerebellum.
    2. "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] (ISOFORMS 1 AND 2).
      Strain: C57BL/6J.
      Tissue: Embryo and Testis.
    3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: C57BL/6J.
    4. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
      Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    5. "Molecular properties of Zic proteins as transcriptional regulators and their relationship to GLI proteins."
      Mizugishi K., Aruga J., Nakata K., Mikoshiba K.
      J. Biol. Chem. 276:2180-2188(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, DNA-BINDING.
    6. "Physical and functional interactions between Zic and Gli proteins."
      Koyabu Y., Nakata K., Mizugishi K., Aruga J., Mikoshiba K.
      J. Biol. Chem. 276:6889-6892(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION.
    7. "A complex syndrome of left-right axis, central nervous system and axial skeleton defects in Zic3 mutant mice."
      Purandare S.M., Ware S.M., Kwan K.M., Gebbia M., Bassi M.T., Deng J.M., Vogel H., Behringer R.R., Belmont J.W., Casey B.
      Development 129:2293-2302(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, DISRUPTION PHENOTYPE, DEVELOPMENTAL STAGE.
    8. "Myogenic repressor I-mfa interferes with the function of Zic family proteins."
      Mizugishi K., Hatayama M., Tohmonda T., Ogawa M., Inoue T., Mikoshiba K., Aruga J.
      Biochem. Biophys. Res. Commun. 320:233-240(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH MDFIC.
    9. "Identification of a novel ZIC3 isoform and mutation screening in patients with heterotaxy and congenital heart disease."
      Bedard J.E., Haaning A.M., Ware S.M.
      PLoS ONE 6:E23755-E23755(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: ALTERNATIVE SPLICING.

    Entry informationi

    Entry nameiZIC3_MOUSE
    AccessioniPrimary (citable) accession number: Q62521
    Secondary accession number(s): A2AWK3, Q3UYV1, Q8BSB3
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 15, 1998
    Last sequence update: July 27, 2011
    Last modified: October 1, 2014
    This is version 126 of the entry and version 2 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