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Protein

Zinc finger protein ZIC 2

Gene

Zic2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Acts as a transcriptional activator or repressor. Plays important roles in the early stage of organogenesis of the CNS. Activates the transcription of the serotonin transporter SERT in uncrossed ipsilateral retinal ganglion cells (iRGCs) to refine eye-specific projections in primary visual targets. Its transcriptional activity is repressed by MDFIC. Involved in the formation of the ipsilateral retinal projection at the optic chiasm midline. Drives the expression of EPHB1 on ipsilaterally projecting growth cones. Binds to the minimal GLI-consensus sequence 5'-TGGGTGGTC-3'. Associates to the basal SERT promoter region from ventrotemporal retinal segments of retinal embryos.9 Publications

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri256 – 29136C2H2-type 1; atypicalPROSITE-ProRule annotationAdd
BLAST
Zinc fingeri300 – 32728C2H2-type 2; atypicalPROSITE-ProRule annotationAdd
BLAST
Zinc fingeri333 – 35725C2H2-type 3PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri363 – 38725C2H2-type 4PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri393 – 41523C2H2-type 5PROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  • chromatin DNA binding Source: UniProtKB
  • DNA binding Source: UniProtKB
  • metal ion binding Source: UniProtKB-KW
  • RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: NTNU_SB
  • RNA polymerase II regulatory region sequence-specific DNA binding Source: MGI
  • transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding Source: NTNU_SB
  • transcription factor activity, sequence-specific DNA binding Source: UniProtKB

GO - Biological processi

  • cell differentiation Source: MGI
  • central nervous system development Source: MGI
  • cilium organization Source: MGI
  • developmental pigmentation Source: MGI
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • nervous system development Source: MGI
  • neural tube closure Source: MGI
  • positive regulation of nodal signaling pathway involved in determination of lateral mesoderm left/right asymmetry Source: MGI
  • positive regulation of sequence-specific DNA binding transcription factor activity Source: UniProtKB
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: NTNU_SB
  • retinal ganglion cell axon guidance Source: UniProtKB
  • transcription from RNA polymerase II promoter Source: GOC
  • visual perception Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Activator, Developmental protein, Repressor

Keywords - Biological processi

Differentiation, Neurogenesis, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
Zinc finger protein ZIC 2
Alternative name(s):
Zinc finger protein of the cerebellum 2
Gene namesi
Name:Zic2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:106679. Zic2.

Subcellular locationi

  • Nucleus
  • Cytoplasm

  • Note: Localizes in the cytoplasm in presence of MDFIC overexpression. Both phosphorylated and unphosphorylated forms are localized in the nucleus.

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Disruption phenotypei

Mice show impaired dorsal forebrain development and insufficient closure of the posterior neuropore. Mice survive with holoprosencephaly (HPE) and spina bifida.1 Publication

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi192 – 1921S → A: Still phosphorylated. 1 Publication
Mutagenesisi200 – 2001S → A: Absence of phosphorylation. Inhibits interaction with DHX9. Does not affect DNA-binding affinity or subcellular localization. Inhibits strongly transcriptional activation. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 530530Zinc finger protein ZIC 2PRO_0000047248Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei192 – 1921Phosphoserine1 Publication
Modified residuei200 – 2001Phosphoserine1 Publication

Post-translational modificationi

Phosphorylated.1 Publication
Ubiquitinated by RNF180, leading to its degradation.By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiQ62520.
PaxDbiQ62520.
PRIDEiQ62520.

PTM databases

iPTMnetiQ62520.
PhosphoSiteiQ62520.

Expressioni

Tissue specificityi

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

Developmental stagei

Expressed in the ipsilateral retinal ganglion cells (iRGCs) of the peripheral ventrotemporal (VT) neural retina, during the outgrowth of the uncrossed retinal projection between 16.5 and 18.5 dpc (at protein level). Expression is down-regulated as RGCs extend toward chiasmatic midline at the optic chiasm.2 Publications

Gene expression databases

BgeeiQ62520.
CleanExiMM_ZIC2.

Interactioni

Subunit structurei

Interacts with RNF180 (PubMed:18363970). 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 (PubMed:15207726, PubMed:15465018). Interacts with DHX9 (PubMed:18068128). Interacts with GLI1 and GLI2 (PubMed:11238441).5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
GLI3P100712EBI-308076,EBI-308055From a different organism.

Protein-protein interaction databases

IntActiQ62520. 4 interactions.
MINTiMINT-189917.
STRINGi10090.ENSMUSP00000075283.

Structurei

3D structure databases

ProteinModelPortaliQ62520.
SMRiQ62520. Positions 250-417.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni100 – 255156Necessary for interaction with MDFIC and transcriptional activation or repressionAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi20 – 234Poly-His
Compositional biasi25 – 339Poly-Ala
Compositional biasi89 – 979Poly-Ala
Compositional biasi227 – 2315Poly-Ala
Compositional biasi232 – 2398Poly-His
Compositional biasi456 – 47015Poly-AlaAdd
BLAST
Compositional biasi492 – 50615Poly-GlyAdd
BLAST

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 fingeri256 – 29136C2H2-type 1; atypicalPROSITE-ProRule annotationAdd
BLAST
Zinc fingeri300 – 32728C2H2-type 2; atypicalPROSITE-ProRule annotationAdd
BLAST
Zinc fingeri333 – 35725C2H2-type 3PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri363 – 38725C2H2-type 4PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri393 – 41523C2H2-type 5PROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG1721. Eukaryota.
COG5048. LUCA.
HOGENOMiHOG000232057.
HOVERGENiHBG007135.
InParanoidiQ62520.
PhylomeDBiQ62520.

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. 2 hits.
[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]

Sequencei

Sequence statusi: Complete.

Q62520-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLLDAGPQFP AIGVGSFARH HHHSAAAAAA AAAEMQDREL SLAAAQNGFV
60 70 80 90 100
DSAAAHMGAF KLNPGAHELS PGQSSAFTSQ GPGAYPGSAA AAAAAAALGP
110 120 130 140 150
HAAHVGSYSG PPFNSTRDFL FRSRGFGDSA PGGGQHGLFG PGAGGLHHAH
160 170 180 190 200
SDAQGHLLFP GLPPEQHGPH ASQNVLNGQM RLGLPGEVFG RSEQYRQVAS
210 220 230 240 250
PRTDPYSAAQ LHNQYGPMNM NMGMNMAAAA AHHHHHHHHP GAFFRYMRQQ
260 270 280 290 300
CIKQELICKW IDPEQLSNPK KSCNKTFSTM HELVTHVSVE HVGGPEQSNH
310 320 330 340 350
VCFWEECPRE GKPFKAKYKL VNHIRVHTGE KPFPCPFPGC GKVFARSENL
360 370 380 390 400
KIHKRTHTGE KPFQCEFEGC DRRFANSSDR KKHMHVHTSD KPYLCKMCDK
410 420 430 440 450
SYTHPSSLRK HMKVHESSPQ GSESSPAASS GYESSTPPGL VSPSAEPQSS
460 470 480 490 500
SNLSPAAAAA AAAAAAAAAA VSAVHRGAGS GSSGSGGGSA AGSGGGGGGA
510 520 530
GGGGGGSSGG GSGTTGGHSG LSSNFNEWYV
Length:530
Mass (Da):54,954
Last modified:October 24, 2003 - v2
Checksum:iBE8B476E81B1E40B
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D70848 mRNA. Translation: BAA11115.2.
UniGeneiMm.308936.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D70848 mRNA. Translation: BAA11115.2.
UniGeneiMm.308936.

3D structure databases

ProteinModelPortaliQ62520.
SMRiQ62520. Positions 250-417.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ62520. 4 interactions.
MINTiMINT-189917.
STRINGi10090.ENSMUSP00000075283.

PTM databases

iPTMnetiQ62520.
PhosphoSiteiQ62520.

Proteomic databases

MaxQBiQ62520.
PaxDbiQ62520.
PRIDEiQ62520.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Organism-specific databases

MGIiMGI:106679. Zic2.

Phylogenomic databases

eggNOGiKOG1721. Eukaryota.
COG5048. LUCA.
HOGENOMiHOG000232057.
HOVERGENiHBG007135.
InParanoidiQ62520.
PhylomeDBiQ62520.

Miscellaneous databases

PROiQ62520.
SOURCEiSearch...

Gene expression databases

BgeeiQ62520.
CleanExiMM_ZIC2.

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. 2 hits.
[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]
ProtoNetiSearch...

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].
    Tissue: Cerebellum.
  2. Aruga J.
    Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases
    Cited for: SEQUENCE REVISION TO 488-512.
  3. Cited for: FUNCTION, DISRUPTION PHENOTYPE.
  4. "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.
  5. "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, INTERACTION WITH GLI1 AND GLI2.
  6. "Zic2 controls cerebellar development in cooperation with Zic1."
    Aruga J., Inoue T., Hoshino J., Mikoshiba K.
    J. Neurosci. 22:218-225(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  7. "Zic2 patterns binocular vision by specifying the uncrossed retinal projection."
    Herrera E., Brown L., Aruga J., Rachel R.A., Dolen G., Mikoshiba K., Brown S., Mason C.A.
    Cell 114:545-557(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, 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. "Molecular properties of Zic4 and Zic5 proteins: functional diversity within Zic family."
    Ishiguro A., Inoue T., Mikoshiba K., Aruga J.
    Biochem. Biophys. Res. Commun. 324:302-307(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH MDFIC, SUBCELLULAR LOCATION, DNA-BINDING.
  10. "Zic2 promotes axonal divergence at the optic chiasm midline by EphB1-dependent and -independent mechanisms."
    Garcia-Frigola C., Carreres M.I., Vegar C., Mason C., Herrera E.
    Development 135:1833-1841(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  11. "Functional role of Zic2 phosphorylation in transcriptional regulation."
    Ishiguro A., Aruga J.
    FEBS Lett. 582:154-158(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH DHX9, PHOSPHORYLATION AT SER-192 AND SER-200, DNA-BINDING, SUBCELLULAR LOCATION, MUTAGENESIS OF SER-192 AND SER-200.
  12. "Rines/RNF180, a novel RING finger gene-encoded product, is a membrane-bound ubiquitin ligase."
    Ogawa M., Mizugishi K., Ishiguro A., Koyabu Y., Imai Y., Takahashi R., Mikoshiba K., Aruga J.
    Genes Cells 13:397-409(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH RNF180, UBIQUITINATION.
  13. "Zic2 regulates retinal ganglion cell axon avoidance of ephrinB2 through inducing expression of the guidance receptor EphB1."
    Lee R., Petros T.J., Mason C.A.
    J. Neurosci. 28:5910-5919(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  14. "Zic2 regulates the expression of Sert to modulate eye-specific refinement at the visual targets."
    Garcia-Frigola C., Herrera E.
    EMBO J. 29:3170-3183(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, ASSOCIATION WITH DNA, DEVELOPMENTAL STAGE.

Entry informationi

Entry nameiZIC2_MOUSE
AccessioniPrimary (citable) accession number: Q62520
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: October 24, 2003
Last modified: March 16, 2016
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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.