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ZIC3_XENLA
ID   ZIC3_XENLA              Reviewed;         441 AA.
AC   O57311; Q640K7; Q6PF77; Q7ZZN6; Q7ZZN7; Q9DG65;
DT   02-FEB-2004, integrated into UniProtKB/Swiss-Prot.
DT   10-FEB-2009, sequence version 3.
DT   03-AUG-2022, entry version 115.
DE   RecName: Full=Zinc finger protein ZIC 3;
DE            Short=XZic3;
DE            Short=XlZic3;
DE   AltName: Full=Zinc finger protein Zic3-A;
DE   AltName: Full=Zinc finger protein of the cerebellum 3;
GN   Name=zic3; Synonyms=zic3-a;
OS   Xenopus laevis (African clawed frog).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC   Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX   NCBI_TaxID=8355;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL
RP   STAGE, AND INDUCTION.
RC   TISSUE=Neurula;
RX   PubMed=9342348; DOI=10.1073/pnas.94.22.11980;
RA   Nakata K., Nagai T., Aruga J., Mikoshiba K.;
RT   "Xenopus Zic3, a primary regulator both in neural and neural crest
RT   development.";
RL   Proc. Natl. Acad. Sci. U.S.A. 94:11980-11985(1997).
RN   [2]
RP   SEQUENCE REVISION TO 17.
RA   Nakata K., Nagai T., Aruga J., Mikoshiba K.;
RL   Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Gastrula;
RG   NIH - Xenopus Gene Collection (XGC) project;
RL   Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-33, AND INDUCTION.
RX   PubMed=15557819; DOI=10.1038/emm.2004.59;
RA   Lee S.Y., Lee H.-S., Moon J.-S., Kim J.-I., Park J.-B., Lee J.-Y.,
RA   Park M.J., Kim J.;
RT   "Transcriptional regulation of Zic3 by heterodimeric AP-1(c-Jun/c-Fos)
RT   during Xenopus development.";
RL   Exp. Mol. Med. 36:468-475(2004).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 319-331 AND 374-386.
RX   PubMed=12963115; DOI=10.1016/s0925-4773(03)00082-0;
RA   Weber J.R., Sokol S.Y.;
RT   "Identification of a phylogenetically conserved activin-responsive enhancer
RT   in the Zic3 gene.";
RL   Mech. Dev. 120:955-964(2003).
RN   [6]
RP   DEVELOPMENTAL STAGE.
RX   PubMed=9739105; DOI=10.1016/s0925-4773(98)00073-2;
RA   Nakata K., Nagai T., Aruga J., Mikoshiba K.;
RT   "Xenopus Zic family and its role in neural and neural crest development.";
RL   Mech. Dev. 75:43-51(1998).
RN   [7]
RP   FUNCTION, TISSUE SPECIFICITY, DOMAIN, AND INDUCTION.
RX   PubMed=11044394; DOI=10.1242/dev.127.22.4787;
RA   Kitaguchi T., Nagai T., Nakata K., Aruga J., Mikoshiba K.;
RT   "Zic3 is involved in the left-right specification of the Xenopus embryo.";
RL   Development 127:4787-4795(2000).
RN   [8]
RP   INDUCTION.
RX   PubMed=11091076; DOI=10.1016/s0925-4773(00)00480-9;
RA   Nakata K., Koyabu Y., Aruga J., Mikoshiba K.;
RT   "A novel member of the Xenopus Zic family, Zic5, mediates neural crest
RT   development.";
RL   Mech. Dev. 99:83-91(2000).
RN   [9]
RP   FUNCTION, AND INDUCTION.
RX   PubMed=11869292; DOI=10.1046/j.1440-169x.2002.00624.x;
RA   Kitaguchi T., Mizugishi K., Hatayama M., Aruga J., Mikoshiba K.;
RT   "Xenopus Brachyury regulates mesodermal expression of Zic3, a gene
RT   controlling left-right asymmetry.";
RL   Dev. Growth Differ. 44:55-61(2002).
RN   [10]
RP   INDUCTION.
RX   PubMed=14499648; DOI=10.1016/s0012-1606(03)00298-7;
RA   Leclerc C., Lee M., Webb S.E., Moreau M., Miller A.L.;
RT   "Calcium transients triggered by planar signals induce the expression of
RT   ZIC3 gene during neural induction in Xenopus.";
RL   Dev. Biol. 261:381-390(2003).
RN   [11]
RP   INDUCTION.
RX   PubMed=16631621; DOI=10.1016/j.bbrc.2006.03.235;
RA   Kelly L.E., Carrel T.L., Herman G.E., El-Hodiri H.M.;
RT   "Pbx1 and Meis1 regulate activity of the Xenopus laevis Zic3 promoter
RT   through a highly conserved region.";
RL   Biochem. Biophys. Res. Commun. 344:1031-1037(2006).
RN   [12]
RP   TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX   PubMed=16871625; DOI=10.1002/dvdy.20906;
RA   Fujimi T.J., Mikoshiba K., Aruga J.;
RT   "Xenopus Zic4: conservation and diversification of expression profiles and
RT   protein function among the Xenopus Zic family.";
RL   Dev. Dyn. 235:3379-3386(2006).
CC   -!- FUNCTION: Probably acts as a transcriptional activator. May bind to the
CC       minimal GLI-consensus sequence 5'-GGGTGGTC-3'. Can determine the
CC       ectodermal cell fate and promote the earliest step of neural and neural
CC       crest development. Involved in establishing left-right asymmetry in the
CC       embryo. {ECO:0000269|PubMed:11044394, ECO:0000269|PubMed:11869292,
CC       ECO:0000269|PubMed:9342348}.
CC   -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm {ECO:0000250}.
CC   -!- TISSUE SPECIFICITY: First detected at early gastrula (stage 10.25) in
CC       the dorsal lip and prospective neural plate. Also expressed in the
CC       mesoderm at early gastrulation, with expression strongest on the dorsal
CC       side. Mesodermal expression continues at stage 12 but is hardly
CC       detectable after stage 14. As gastrulation proceeds, expression
CC       decreases in the dorsal lip and increases in the prospective neural
CC       plate. At the neural plate stage (stage 14), expressed strongly in the
CC       prospective mesencephalon and anterior rhombencephalon, after which
CC       expression becomes stronger in the anterior neural folds. At early
CC       tailbud stage (stage 20), expression becomes restricted to the dorsal
CC       region of forebrain, midbrain and hindbrain, and weakly to the dorsal
CC       trunk. After mid-tailbud stage, expression decreases in the
CC       diencephalon, appears in the lateral mesoderm of the tailbud region and
CC       becomes restricted in the dorsal part of the neural tube.
CC       {ECO:0000269|PubMed:11044394, ECO:0000269|PubMed:16871625,
CC       ECO:0000269|PubMed:9342348}.
CC   -!- DEVELOPMENTAL STAGE: Expressed zygotically. First expressed from the
CC       late blastula. {ECO:0000269|PubMed:16871625,
CC       ECO:0000269|PubMed:9342348, ECO:0000269|PubMed:9739105}.
CC   -!- INDUCTION: By dvr1/vg1, activin and t/bra in the mesoderm. By
CC       heteromeric AP-1 (fos/jun) during activin signaling. By increases in
CC       Ca(2+) in the dorsal ectoderm, triggered by planar signals from the
CC       mesoderm. Suppressed by bmp-signaling. By pbx1 and meis1. By zic1, zic2
CC       and zic3 but not zic5. {ECO:0000269|PubMed:11044394,
CC       ECO:0000269|PubMed:11091076, ECO:0000269|PubMed:11869292,
CC       ECO:0000269|PubMed:14499648, ECO:0000269|PubMed:15557819,
CC       ECO:0000269|PubMed:16631621, ECO:0000269|PubMed:9342348}.
CC   -!- DOMAIN: The C2H2-type 3, 4 and 5 zinc finger domains are necessary for
CC       transcription activation (By similarity). The zinc fingers and the N-
CC       terminus are independently important for establishing the L/R axis.
CC       {ECO:0000250, ECO:0000269|PubMed:11044394}.
CC   -!- SIMILARITY: Belongs to the GLI C2H2-type zinc-finger protein family.
CC       {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAH57699.2; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR   EMBL; AB005292; BAA23874.2; -; mRNA.
DR   EMBL; BC057699; AAH57699.2; ALT_INIT; mRNA.
DR   EMBL; BC082617; AAH82617.1; -; mRNA.
DR   EMBL; AF179297; AAG09377.1; -; Genomic_DNA.
DR   EMBL; AF506277; AAP20808.1; -; Genomic_DNA.
DR   EMBL; AF506278; AAP20809.1; -; Genomic_DNA.
DR   RefSeq; NP_001081088.1; NM_001087619.1.
DR   AlphaFoldDB; O57311; -.
DR   SMR; O57311; -.
DR   PRIDE; O57311; -.
DR   DNASU; 394375; -.
DR   GeneID; 394375; -.
DR   KEGG; xla:394375; -.
DR   CTD; 394375; -.
DR   Xenbase; XB-GENE-865376; zic3.S.
DR   OMA; HESQCSE; -.
DR   OrthoDB; 768287at2759; -.
DR   Proteomes; UP000186698; Chromosome 8S.
DR   Bgee; 394375; Expressed in gastrula and 4 other tissues.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR   GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR   GO; GO:0003700; F:DNA-binding transcription factor activity; ISS:UniProtKB.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0043565; F:sequence-specific DNA binding; ISS:UniProtKB.
DR   GO; GO:0007368; P:determination of left/right symmetry; IMP:UniProtKB.
DR   GO; GO:0000578; P:embryonic axis specification; IMP:UniProtKB.
DR   GO; GO:0007399; P:nervous system development; IEA:UniProtKB-KW.
DR   GO; GO:0014034; P:neural crest cell fate commitment; IMP:UniProtKB.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR   GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR   InterPro; IPR036236; Znf_C2H2_sf.
DR   InterPro; IPR013087; Znf_C2H2_type.
DR   InterPro; IPR041643; Znf_ZIC.
DR   Pfam; PF00096; zf-C2H2; 3.
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   2: Evidence at transcript level;
KW   Activator; Cytoplasm; Developmental protein; Differentiation; DNA-binding;
KW   Metal-binding; Neurogenesis; Nucleus; Reference proteome; Repeat;
KW   Transcription; Transcription regulation; Zinc; Zinc-finger.
FT   CHAIN           1..441
FT                   /note="Zinc finger protein ZIC 3"
FT                   /id="PRO_0000047252"
FT   ZN_FING         222..257
FT                   /note="C2H2-type 1; atypical"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT   ZN_FING         266..293
FT                   /note="C2H2-type 2; atypical"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT   ZN_FING         299..323
FT                   /note="C2H2-type 3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT   ZN_FING         329..353
FT                   /note="C2H2-type 4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT   ZN_FING         359..381
FT                   /note="C2H2-type 5"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT   REGION          375..441
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        384..433
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   CONFLICT        17
FT                   /note="G -> R (in Ref. 4; AAG09377)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        74
FT                   /note="S -> N (in Ref. 1; BAA23874)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        207
FT                   /note="Q -> P (in Ref. 1; BAA23874)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   441 AA;  48485 MW;  5D7959E98217E886 CRC64;
     MTMLLDGGPQ FPTLGVGGFG TARHHEMSNR DAGMGLNPFT EPSHAAAFKL SPASHDLSSS
     QSSAFTPQAS GYASSLGHHA GQVPSYGGAA FNSTRDFLFR NRNSGIADSS SAGSQHGLFA
     NHGPPGIGEP PGHLIFPGLH EQSSSHTSSN GHVVNGQMHL GLRGDIFGRP DPYRAVPSPR
     TDHYAAAQFH NYNHMNMSMN VAAHHGQGAF FRYMRQPIKQ ELSCKWLEES TMNHPQKTCD
     RTFSSMHELV THMTMEHVGG PEQNNHICYW EECPRGGKSF KAKYKLVNHI RVHTGEKPFP
     CPFPGCGKIF ARSENLKIHK RTHTGEKPFK CEFEGCDRRF ANSSDRKKHM HVHTSDKPYI
     CKVCDKSYTH PSSLRKHMKV HESQGSDSSP AASSGYESAT PPAMVSANSE EPSKNSSATH
     QTNNNSHNTG LLPPNFNEWY V
 
 
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