ZIC3_MOUSE
ID ZIC3_MOUSE Reviewed; 466 AA.
AC Q62521; A2AWK3; Q3UYV1; Q8BSB3;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 176.
DE RecName: Full=Zinc finger protein ZIC 3;
DE AltName: Full=Zinc finger protein of the cerebellum 3;
GN Name=Zic3;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Cerebellum;
RX PubMed=8557628; DOI=10.1074/jbc.271.2.1043;
RA Aruga J., Nagai T., Tokuyama T., Hayashizaki Y., Okazaki Y., Chapman V.M.,
RA Mikoshiba K.;
RT "The mouse zic gene family. Homologues of the Drosophila pair-rule gene
RT odd-paired.";
RL J. Biol. Chem. 271:1043-1047(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Embryo, and Testis;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP FUNCTION, AND DNA-BINDING.
RX PubMed=11053430; DOI=10.1074/jbc.m004430200;
RA Mizugishi K., Aruga J., Nakata K., Mikoshiba K.;
RT "Molecular properties of Zic proteins as transcriptional regulators and
RT their relationship to GLI proteins.";
RL J. Biol. Chem. 276:2180-2188(2001).
RN [6]
RP SUBCELLULAR LOCATION.
RX PubMed=11238441; DOI=10.1074/jbc.c000773200;
RA Koyabu Y., Nakata K., Mizugishi K., Aruga J., Mikoshiba K.;
RT "Physical and functional interactions between Zic and Gli proteins.";
RL J. Biol. Chem. 276:6889-6892(2001).
RN [7]
RP FUNCTION, DISRUPTION PHENOTYPE, AND DEVELOPMENTAL STAGE.
RX PubMed=11959836; DOI=10.1242/dev.129.9.2293;
RA Purandare S.M., Ware S.M., Kwan K.M., Gebbia M., Bassi M.T., Deng J.M.,
RA Vogel H., Behringer R.R., Belmont J.W., Casey B.;
RT "A complex syndrome of left-right axis, central nervous system and axial
RT skeleton defects in Zic3 mutant mice.";
RL Development 129:2293-2302(2002).
RN [8]
RP FUNCTION, AND INTERACTION WITH MDFIC.
RX PubMed=15207726; DOI=10.1016/j.bbrc.2004.05.158;
RA Mizugishi K., Hatayama M., Tohmonda T., Ogawa M., Inoue T., Mikoshiba K.,
RA Aruga J.;
RT "Myogenic repressor I-mfa interferes with the function of Zic family
RT proteins.";
RL Biochem. Biophys. Res. Commun. 320:233-240(2004).
RN [9]
RP ALTERNATIVE SPLICING.
RX PubMed=21858219; DOI=10.1371/journal.pone.0023755;
RA Bedard J.E., Haaning A.M., Ware S.M.;
RT "Identification of a novel ZIC3 isoform and mutation screening in patients
RT with heterotaxy and congenital heart disease.";
RL PLoS ONE 6:E23755-E23755(2011).
CC -!- FUNCTION: Acts as transcriptional activator. Required in the earliest
CC stages in both axial midline development and left-right (LR) asymmetry
CC specification. Binds to the minimal GLI-consensus sequence 5'-GGGTGGTC-
CC 3'. {ECO:0000269|PubMed:11053430, ECO:0000269|PubMed:11959836,
CC ECO:0000269|PubMed:15207726}.
CC -!- SUBUNIT: Interacts with KPNA1 and KPNA6. Interacts (via C2H2-type
CC domains 3, 4 and 5) with GLI3; the interaction enhances its
CC transcriptional activity (By similarity). Interacts (via the C2H2-type
CC domains 3, 4 and 5) with MDFIC (via the C2H2-type domains 3, 4 and 5);
CC the interaction reduces its transcriptional activity. {ECO:0000250,
CC ECO:0000269|PubMed:15207726}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11238441}. Cytoplasm
CC {ECO:0000269|PubMed:11238441}. Note=Translocation to the nucleus
CC requires KPNA1 or KPNA6 (By similarity). Localizes in the cytoplasm in
CC presence of MDFIC overexpression. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Zic3-A;
CC IsoId=Q62521-1; Sequence=Displayed;
CC Name=2; Synonyms=Zic3-B;
CC IsoId=Q62521-2; Sequence=VSP_044011;
CC -!- TISSUE SPECIFICITY: CNS. A high level expression is seen in the
CC cerebellum.
CC -!- DEVELOPMENTAL STAGE: Expressed in the CNS, tailbud and somites.
CC {ECO:0000269|PubMed:11959836}.
CC -!- DOMAIN: The C2H2-type 3, 4 and 5 zinc finger domains are necessary for
CC transcription activation.
CC -!- DISRUPTION PHENOTYPE: Some mice exhibit embryonic and postnatal
CC lethality. Viable mice show heart disease, disturbances of laterality,
CC neural tube defects and vertebral and rib defects.
CC {ECO:0000269|PubMed:11959836}.
CC -!- SIMILARITY: Belongs to the GLI C2H2-type zinc-finger protein family.
CC {ECO:0000305}.
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DR EMBL; D70849; BAA11116.1; -; mRNA.
DR EMBL; AK134355; BAE22110.1; -; mRNA.
DR EMBL; AK034780; BAC28831.1; -; mRNA.
DR EMBL; AL671920; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL954389; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466583; EDL42177.1; -; Genomic_DNA.
DR EMBL; CH466583; EDL42178.1; -; Genomic_DNA.
DR CCDS; CCDS30155.1; -. [Q62521-1]
DR RefSeq; NP_033601.2; NM_009575.2. [Q62521-1]
DR AlphaFoldDB; Q62521; -.
DR SMR; Q62521; -.
DR BioGRID; 204696; 2.
DR IntAct; Q62521; 2.
DR MINT; Q62521; -.
DR STRING; 10090.ENSMUSP00000085999; -.
DR iPTMnet; Q62521; -.
DR PhosphoSitePlus; Q62521; -.
DR PaxDb; Q62521; -.
DR PeptideAtlas; Q62521; -.
DR PRIDE; Q62521; -.
DR ProteomicsDB; 299559; -. [Q62521-1]
DR ProteomicsDB; 299560; -. [Q62521-2]
DR Antibodypedia; 30470; 282 antibodies from 32 providers.
DR DNASU; 22773; -.
DR Ensembl; ENSMUST00000088627; ENSMUSP00000085999; ENSMUSG00000067860. [Q62521-1]
DR Ensembl; ENSMUST00000088629; ENSMUSP00000086001; ENSMUSG00000067860. [Q62521-2]
DR GeneID; 22773; -.
DR KEGG; mmu:22773; -.
DR UCSC; uc009tho.1; mouse. [Q62521-1]
DR UCSC; uc009thp.1; mouse. [Q62521-2]
DR CTD; 7547; -.
DR MGI; MGI:106676; Zic3.
DR VEuPathDB; HostDB:ENSMUSG00000067860; -.
DR eggNOG; KOG1721; Eukaryota.
DR GeneTree; ENSGT00940000160788; -.
DR HOGENOM; CLU_002678_37_1_1; -.
DR InParanoid; Q62521; -.
DR OMA; PRHHDIG; -.
DR OrthoDB; 768287at2759; -.
DR PhylomeDB; Q62521; -.
DR TreeFam; TF351425; -.
DR BioGRID-ORCS; 22773; 1 hit in 75 CRISPR screens.
DR ChiTaRS; Zic3; mouse.
DR PRO; PR:Q62521; -.
DR Proteomes; UP000000589; Chromosome X.
DR RNAct; Q62521; protein.
DR Bgee; ENSMUSG00000067860; Expressed in brain blood vessel and 141 other tissues.
DR ExpressionAtlas; Q62521; baseline and differential.
DR Genevisible; Q62521; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:NTNU_SB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IDA:MGI.
DR GO; GO:0043565; F:sequence-specific DNA binding; ISS:UniProtKB.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0003713; F:transcription coactivator activity; IMP:MGI.
DR GO; GO:0009952; P:anterior/posterior pattern specification; IGI:MGI.
DR GO; GO:0003228; P:atrial cardiac muscle tissue development; IMP:MGI.
DR GO; GO:0048318; P:axial mesoderm development; IGI:MGI.
DR GO; GO:0007417; P:central nervous system development; IBA:GO_Central.
DR GO; GO:0035283; P:central nervous system segmentation; IGI:MGI.
DR GO; GO:1904888; P:cranial skeletal system development; IMP:MGI.
DR GO; GO:0071907; P:determination of digestive tract left/right asymmetry; ISO:MGI.
DR GO; GO:0035545; P:determination of left/right asymmetry in nervous system; IMP:UniProtKB.
DR GO; GO:0007368; P:determination of left/right symmetry; IMP:MGI.
DR GO; GO:0071910; P:determination of liver left/right asymmetry; ISO:MGI.
DR GO; GO:0035469; P:determination of pancreatic left/right asymmetry; ISO:MGI.
DR GO; GO:0009880; P:embryonic pattern specification; IMP:MGI.
DR GO; GO:0060324; P:face development; IMP:MGI.
DR GO; GO:0030900; P:forebrain development; IGI:MGI.
DR GO; GO:0007369; P:gastrulation; IMP:MGI.
DR GO; GO:0010467; P:gene expression; IMP:MGI.
DR GO; GO:0030718; P:germ-line stem cell population maintenance; IMP:MGI.
DR GO; GO:0007507; P:heart development; IMP:MGI.
DR GO; GO:0001947; P:heart looping; IMP:MGI.
DR GO; GO:0021766; P:hippocampus development; IGI:MGI.
DR GO; GO:0070986; P:left/right axis specification; IMP:MGI.
DR GO; GO:0060972; P:left/right pattern formation; IMP:MGI.
DR GO; GO:0035108; P:limb morphogenesis; IGI:MGI.
DR GO; GO:0030324; P:lung development; ISO:MGI.
DR GO; GO:0098727; P:maintenance of cell number; IGI:MGI.
DR GO; GO:0007498; P:mesoderm development; IMP:MGI.
DR GO; GO:0042789; P:mRNA transcription by RNA polymerase II; IMP:MGI.
DR GO; GO:0001840; P:neural plate development; IGI:MGI.
DR GO; GO:0030182; P:neuron differentiation; IMP:MGI.
DR GO; GO:0021772; P:olfactory bulb development; IDA:MGI.
DR GO; GO:0042473; P:outer ear morphogenesis; IMP:MGI.
DR GO; GO:0048339; P:paraxial mesoderm development; IGI:MGI.
DR GO; GO:0007389; P:pattern specification process; IMP:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:NTNU_SB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0090009; P:primitive streak formation; IMP:MGI.
DR GO; GO:0051090; P:regulation of DNA-binding transcription factor activity; IMP:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0001501; P:skeletal system development; IMP:MGI.
DR GO; GO:0007224; P:smoothened signaling pathway; IGI:MGI.
DR GO; GO:0048863; P:stem cell differentiation; IDA:MGI.
DR GO; GO:0019827; P:stem cell population maintenance; IMP:MGI.
DR InterPro; IPR036236; Znf_C2H2_sf.
DR InterPro; IPR013087; Znf_C2H2_type.
DR InterPro; IPR041643; Znf_ZIC.
DR Pfam; PF00096; zf-C2H2; 4.
DR Pfam; PF18366; zf_ZIC; 1.
DR SMART; SM00355; ZnF_C2H2; 5.
DR SUPFAM; SSF57667; SSF57667; 2.
DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 3.
DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 4.
PE 1: Evidence at protein level;
KW Activator; Alternative splicing; Cytoplasm; Developmental protein;
KW Differentiation; DNA-binding; Isopeptide bond; Metal-binding; Neurogenesis;
KW Nucleus; Reference proteome; Repeat; Transcription;
KW Transcription regulation; Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..466
FT /note="Zinc finger protein ZIC 3"
FT /id="PRO_0000047251"
FT ZN_FING 250..285
FT /note="C2H2-type 1; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 294..321
FT /note="C2H2-type 2; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 327..351
FT /note="C2H2-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 357..381
FT /note="C2H2-type 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 387..409
FT /note="C2H2-type 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT REGION 65..103
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 403..466
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 296..321
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250"
FT MOTIF 329..351
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250"
FT COMPBIAS 65..79
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 412..458
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CROSSLNK 247
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:O60481"
FT VAR_SEQ 408..466
FT /note="VHESQGSDSSPAASSGYESSTPPAIASANSKDTTKTPSAVQTSTSHNPGLPP
FT NFNEWYV -> CCPAWYLGQSLIPDEELDTDVGMQQPVLHNTSYPKCRVNAEPTVQEMI
FT Y (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_044011"
FT CONFLICT 104..106
FT /note="GGA -> ARR (in Ref. 1; BAA11116)"
FT /evidence="ECO:0000305"
FT CONFLICT Q62521-2:419
FT /note="I -> V (in Ref. 2; BAC28831)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 466 AA; 50446 MW; C92C06EC06DF601A CRC64;
MTMLLDGGPQ FPGLGVGSFG APRHHEMPNR EPAGMGLNPF GDSTHAAAAA AAAAAFKLSP
ATAHDLSSGQ SSAFTPQGSG YANALGHHHH HHHHHHASQV PTYGGAASAA FNSTRDFLFR
QRGSGLSEAA SGGGQHGLFA GSASSLHAPA GIPEPPSYLL FPGLHEQGAG HPSPTGHVDN
NQVHLGLRGE LFGRADPYRP VASPRTDPYA ASAQFPNYSP MNMNMGVNVA AHHGPGAFFR
YMRQPIKQEL SCKWIEEAQL SRPKKSCDRT FSTMHELVTH VTMEHVGGPE QNNHVCYWEE
CPREGKSFKA KYKLVNHIRV HTGEKPFPCP FPGCGKIFAR SENLKIHKRT HTGEKPFKCE
FEGCDRRFAN SSDRKKHMHV HTSDKPYICK VCDKSYTHPS SLRKHMKVHE SQGSDSSPAA
SSGYESSTPP AIASANSKDT TKTPSAVQTS TSHNPGLPPN FNEWYV
