ZIC2_MOUSE
ID ZIC2_MOUSE Reviewed; 530 AA.
AC Q62520;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 24-OCT-2003, sequence version 2.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Zinc finger protein ZIC 2;
DE AltName: Full=Zinc finger protein of the cerebellum 2;
GN Name=Zic2;
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].
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 SEQUENCE REVISION TO 488-512.
RA Aruga J.;
RL Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=10677508; DOI=10.1073/pnas.97.4.1618;
RA Nagai T., Aruga J., Minowa O., Sugimoto T., Ohno Y., Noda T., Mikoshiba K.;
RT "Zic2 regulates the kinetics of neurulation.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:1618-1623(2000).
RN [4]
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 [5]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH GLI1 AND GLI2.
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 [6]
RP FUNCTION.
RX PubMed=11756505; DOI=10.1523/jneurosci.22-01-00218.2002;
RA Aruga J., Inoue T., Hoshino J., Mikoshiba K.;
RT "Zic2 controls cerebellar development in cooperation with Zic1.";
RL J. Neurosci. 22:218-225(2002).
RN [7]
RP FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=13678579; DOI=10.1016/s0092-8674(03)00684-6;
RA Herrera E., Brown L., Aruga J., Rachel R.A., Dolen G., Mikoshiba K.,
RA Brown S., Mason C.A.;
RT "Zic2 patterns binocular vision by specifying the uncrossed retinal
RT projection.";
RL Cell 114:545-557(2003).
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 FUNCTION, INTERACTION WITH MDFIC, SUBCELLULAR LOCATION, AND DNA-BINDING.
RX PubMed=15465018; DOI=10.1016/j.bbrc.2004.09.052;
RA Ishiguro A., Inoue T., Mikoshiba K., Aruga J.;
RT "Molecular properties of Zic4 and Zic5 proteins: functional diversity
RT within Zic family.";
RL Biochem. Biophys. Res. Commun. 324:302-307(2004).
RN [10]
RP FUNCTION.
RX PubMed=18417618; DOI=10.1242/dev.020693;
RA Garcia-Frigola C., Carreres M.I., Vegar C., Mason C., Herrera E.;
RT "Zic2 promotes axonal divergence at the optic chiasm midline by EphB1-
RT dependent and -independent mechanisms.";
RL Development 135:1833-1841(2008).
RN [11]
RP INTERACTION WITH DHX9, PHOSPHORYLATION AT SER-192 AND SER-200, DNA-BINDING,
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF SER-192 AND SER-200.
RX PubMed=18068128; DOI=10.1016/j.febslet.2007.11.080;
RA Ishiguro A., Aruga J.;
RT "Functional role of Zic2 phosphorylation in transcriptional regulation.";
RL FEBS Lett. 582:154-158(2008).
RN [12]
RP INTERACTION WITH RNF180, AND UBIQUITINATION.
RX PubMed=18363970; DOI=10.1111/j.1365-2443.2008.01169.x;
RA Ogawa M., Mizugishi K., Ishiguro A., Koyabu Y., Imai Y., Takahashi R.,
RA Mikoshiba K., Aruga J.;
RT "Rines/RNF180, a novel RING finger gene-encoded product, is a membrane-
RT bound ubiquitin ligase.";
RL Genes Cells 13:397-409(2008).
RN [13]
RP FUNCTION.
RX PubMed=18524895; DOI=10.1523/jneurosci.0632-08.2008;
RA Lee R., Petros T.J., Mason C.A.;
RT "Zic2 regulates retinal ganglion cell axon avoidance of ephrinB2 through
RT inducing expression of the guidance receptor EphB1.";
RL J. Neurosci. 28:5910-5919(2008).
RN [14]
RP FUNCTION, ASSOCIATION WITH DNA, AND DEVELOPMENTAL STAGE.
RX PubMed=20676059; DOI=10.1038/emboj.2010.172;
RA Garcia-Frigola C., Herrera E.;
RT "Zic2 regulates the expression of Sert to modulate eye-specific refinement
RT at the visual targets.";
RL EMBO J. 29:3170-3183(2010).
CC -!- FUNCTION: Acts as a transcriptional activator or repressor. Plays
CC important roles in the early stage of organogenesis of the CNS.
CC Activates the transcription of the serotonin transporter SERT in
CC uncrossed ipsilateral retinal ganglion cells (iRGCs) to refine eye-
CC specific projections in primary visual targets. Its transcriptional
CC activity is repressed by MDFIC. Involved in the formation of the
CC ipsilateral retinal projection at the optic chiasm midline. Drives the
CC expression of EPHB1 on ipsilaterally projecting growth cones. Binds to
CC the minimal GLI-consensus sequence 5'-TGGGTGGTC-3'. Associates to the
CC basal SERT promoter region from ventrotemporal retinal segments of
CC retinal embryos. {ECO:0000269|PubMed:10677508,
CC ECO:0000269|PubMed:11053430, ECO:0000269|PubMed:11756505,
CC ECO:0000269|PubMed:13678579, ECO:0000269|PubMed:15207726,
CC ECO:0000269|PubMed:15465018, ECO:0000269|PubMed:18417618,
CC ECO:0000269|PubMed:18524895, ECO:0000269|PubMed:20676059}.
CC -!- SUBUNIT: Interacts with RNF180 (PubMed:18363970). Interacts (via the
CC C2H2-type domains 3, 4 and 5) with MDFIC (via the C2H2-type domains 3,
CC 4 and 5); the interaction reduces its transcriptional activity
CC (PubMed:15207726, PubMed:15465018). Interacts (via C2H2-type domain 3)
CC with DHX9 (PubMed:18068128). Interacts with GLI1 and GLI2
CC (PubMed:11238441). {ECO:0000250|UniProtKB:O95409,
CC ECO:0000269|PubMed:11238441, ECO:0000269|PubMed:15207726,
CC ECO:0000269|PubMed:15465018, ECO:0000269|PubMed:18068128,
CC ECO:0000269|PubMed:18363970}.
CC -!- INTERACTION:
CC Q62520; P10071: GLI3; Xeno; NbExp=2; IntAct=EBI-308076, EBI-308055;
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=Localizes in the
CC cytoplasm in presence of MDFIC overexpression. Both phosphorylated and
CC unphosphorylated forms are localized in the nucleus.
CC -!- TISSUE SPECIFICITY: CNS. A high level expression is seen in the
CC cerebellum.
CC -!- DEVELOPMENTAL STAGE: Expressed in the ipsilateral retinal ganglion
CC cells (iRGCs) of the peripheral ventrotemporal (VT) neural retina,
CC during the outgrowth of the uncrossed retinal projection between 16.5
CC and 18.5 dpc (at protein level). Expression is down-regulated as RGCs
CC extend toward chiasmatic midline at the optic chiasm.
CC {ECO:0000269|PubMed:13678579, ECO:0000269|PubMed:20676059}.
CC -!- DOMAIN: The C2H2-type 3, 4 and 5 zinc finger domains are necessary for
CC transcription activation.
CC -!- PTM: Phosphorylated. {ECO:0000269|PubMed:18068128}.
CC -!- PTM: Ubiquitinated by RNF180, leading to its degradation.
CC {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Mice show impaired dorsal forebrain development
CC and insufficient closure of the posterior neuropore. Mice survive with
CC holoprosencephaly (HPE) and spina bifida.
CC {ECO:0000269|PubMed:10677508}.
CC -!- SIMILARITY: Belongs to the GLI C2H2-type zinc-finger protein family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; D70848; BAA11115.2; -; mRNA.
DR AlphaFoldDB; Q62520; -.
DR SMR; Q62520; -.
DR IntAct; Q62520; 5.
DR MINT; Q62520; -.
DR STRING; 10090.ENSMUSP00000075283; -.
DR iPTMnet; Q62520; -.
DR PhosphoSitePlus; Q62520; -.
DR PaxDb; Q62520; -.
DR PRIDE; Q62520; -.
DR ProteomicsDB; 274992; -.
DR MGI; MGI:106679; Zic2.
DR eggNOG; KOG1721; Eukaryota.
DR InParanoid; Q62520; -.
DR PhylomeDB; Q62520; -.
DR PRO; PR:Q62520; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q62520; protein.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0016604; C:nuclear body; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0031490; F:chromatin DNA binding; IDA:UniProtKB.
DR GO; GO:0003677; F:DNA binding; 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:0048318; P:axial mesoderm development; IGI:MGI.
DR GO; GO:0007417; P:central nervous system development; IGI:MGI.
DR GO; GO:0035283; P:central nervous system segmentation; IGI:MGI.
DR GO; GO:0044782; P:cilium organization; IMP:MGI.
DR GO; GO:0048066; P:developmental pigmentation; IMP:MGI.
DR GO; GO:0010467; P:gene expression; IMP:MGI.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0007399; P:nervous system development; IMP:MGI.
DR GO; GO:0014033; P:neural crest cell differentiation; IMP:MGI.
DR GO; GO:0001840; P:neural plate development; IGI:MGI.
DR GO; GO:0001843; P:neural tube closure; IMP:MGI.
DR GO; GO:0048339; P:paraxial mesoderm development; IGI:MGI.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IDA:UniProtKB.
DR GO; GO:1900224; P:positive regulation of nodal signaling pathway involved in determination of lateral mesoderm left/right asymmetry; 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:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0031290; P:retinal ganglion cell axon guidance; IMP:UniProtKB.
DR GO; GO:0007601; P:visual perception; IMP: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 1: Evidence at protein level;
KW Activator; Cytoplasm; Developmental protein; Differentiation; DNA-binding;
KW Isopeptide bond; Metal-binding; Neurogenesis; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Repressor; Transcription;
KW Transcription regulation; Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..530
FT /note="Zinc finger protein ZIC 2"
FT /id="PRO_0000047248"
FT ZN_FING 256..291
FT /note="C2H2-type 1; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 300..327
FT /note="C2H2-type 2; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 333..357
FT /note="C2H2-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 363..387
FT /note="C2H2-type 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 393..415
FT /note="C2H2-type 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT REGION 100..255
FT /note="Necessary for interaction with MDFIC and
FT transcriptional activation or repression"
FT REGION 406..452
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 476..530
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 418..452
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 508..530
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 192
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18068128"
FT MOD_RES 200
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18068128"
FT CROSSLNK 253
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:O95409"
FT MUTAGEN 192
FT /note="S->A: Still phosphorylated."
FT /evidence="ECO:0000269|PubMed:18068128"
FT MUTAGEN 200
FT /note="S->A: Absence of phosphorylation. Inhibits
FT interaction with DHX9. Does not affect DNA-binding affinity
FT or subcellular localization. Inhibits strongly
FT transcriptional activation."
FT /evidence="ECO:0000269|PubMed:18068128"
SQ SEQUENCE 530 AA; 54954 MW; BE8B476E81B1E40B CRC64;
MLLDAGPQFP AIGVGSFARH HHHSAAAAAA AAAEMQDREL SLAAAQNGFV DSAAAHMGAF
KLNPGAHELS PGQSSAFTSQ GPGAYPGSAA AAAAAAALGP HAAHVGSYSG PPFNSTRDFL
FRSRGFGDSA PGGGQHGLFG PGAGGLHHAH SDAQGHLLFP GLPPEQHGPH ASQNVLNGQM
RLGLPGEVFG RSEQYRQVAS PRTDPYSAAQ LHNQYGPMNM NMGMNMAAAA AHHHHHHHHP
GAFFRYMRQQ CIKQELICKW IDPEQLSNPK KSCNKTFSTM HELVTHVSVE HVGGPEQSNH
VCFWEECPRE GKPFKAKYKL VNHIRVHTGE KPFPCPFPGC GKVFARSENL KIHKRTHTGE
KPFQCEFEGC DRRFANSSDR KKHMHVHTSD KPYLCKMCDK SYTHPSSLRK HMKVHESSPQ
GSESSPAASS GYESSTPPGL VSPSAEPQSS SNLSPAAAAA AAAAAAAAAA VSAVHRGAGS
GSSGSGGGSA AGSGGGGGGA GGGGGGSSGG GSGTTGGHSG LSSNFNEWYV
