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Protein

Zinc finger protein ZIC 2

Gene

ZIC2

Organism
Homo sapiens (Human)
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.

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

GO - Biological processi

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

Enzyme and pathway databases

SignaLinkiO95409.
SIGNORiO95409.

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 13

Organism-specific databases

HGNCiHGNC:12873. ZIC2.

Subcellular locationi

  • Nucleus
  • Cytoplasm By similarity

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

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Holoprosencephaly 5 (HPE5)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA structural anomaly of the brain, in which the developing forebrain fails to correctly separate into right and left hemispheres. Holoprosencephaly is genetically heterogeneous and associated with several distinct facies and phenotypic variability.
See also OMIM:609637
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti36 – 361Q → P in HPE5; 2-fold increase in luciferase activity. 2 Publications
VAR_023793
Natural varianti37 – 371D → N in HPE5. 1 Publication
VAR_058592
Natural varianti128 – 1281D → N in HPE5. 1 Publication
VAR_058593
Natural varianti152 – 1521D → F in HPE5; requires 2 nucleotide substitutions; 50% reduction of luciferase activity. 3 Publications
VAR_023794
Natural varianti272 – 2721S → N in HPE5. 1 Publication
VAR_058594
Natural varianti286 – 2861H → L in HPE5. 1 Publication
VAR_058595
Natural varianti286 – 2861H → Q in HPE5. 1 Publication
VAR_058596
Natural varianti286 – 2861H → Y in HPE5. 1 Publication
VAR_058597
Natural varianti291 – 2911H → Y in HPE5. 1 Publication
VAR_058598
Natural varianti304 – 3041W → R in HPE5. 1 Publication
VAR_058599
Natural varianti314 – 3141F → C in HPE5. 1 Publication
VAR_058600
Natural varianti325 – 3251R → L in HPE5. 1 Publication
VAR_058601
Natural varianti325 – 3251R → S in HPE5. 1 Publication
VAR_058602
Natural varianti327 – 3271H → Y in HPE5. 1 Publication
VAR_058603
Natural varianti335 – 3351C → F in HPE5. 1 Publication
VAR_058604
Natural varianti373 – 3731R → P in HPE5. 1 Publication
VAR_058605
Natural varianti402 – 4021Y → N in HPE5. 1 Publication
VAR_058606
Natural varianti403 – 4031T → K in HPE5. 1 Publication
VAR_058607
Natural varianti404 – 4041H → R in HPE5. 1 Publication
VAR_058608
Natural varianti409 – 4091R → W in HPE5. 1 Publication
VAR_058609
Natural varianti415 – 4151H → Q in HPE5. 1 Publication
Corresponds to variant rs794729641 [ dbSNP | Ensembl ].
VAR_058610
Natural varianti470 – 4701A → AAAAAAAAAAA in HPE5; near-complete loss of luciferase activity.
VAR_008856

Keywords - Diseasei

Disease mutation, Holoprosencephaly

Organism-specific databases

MalaCardsiZIC2.
MIMi609637. phenotype.
Orphaneti93925. Alobar holoprosencephaly.
93924. Lobar holoprosencephaly.
280200. Microform holoprosencephaly.
93926. Midline interhemispheric variant of holoprosencephaly.
220386. Semilobar holoprosencephaly.
280195. Septopreoptic holoprosencephaly.
PharmGKBiPA37462.

Polymorphism and mutation databases

BioMutaiZIC2.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 532532Zinc finger protein ZIC 2PRO_0000047247Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei191 – 1911PhosphoserineBy similarity
Modified residuei199 – 1991PhosphoserineBy similarity

Post-translational modificationi

Phosphorylated.
Ubiquitinated by RNF180, leading to its degradation.

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiO95409.
MaxQBiO95409.
PaxDbiO95409.
PeptideAtlasiO95409.
PRIDEiO95409.

PTM databases

iPTMnetiO95409.
PhosphoSiteiO95409.

Expressioni

Gene expression databases

BgeeiENSG00000043355.
CleanExiHS_ZIC2.
ExpressionAtlasiO95409. baseline and differential.
GenevisibleiO95409. HS.

Organism-specific databases

HPAiHPA055031.

Interactioni

Subunit structurei

Interacts with RNF180. 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. Interacts with DHX9 (By similarity). Interacts with GLI1 and GLI2 (By similarity).By similarity

Protein-protein interaction databases

BioGridi113378. 9 interactions.
IntActiO95409. 2 interactions.
MINTiMINT-2798893.
STRINGi9606.ENSP00000365514.

Structurei

3D structure databases

ProteinModelPortaliO95409.
SMRiO95409. Positions 250-417.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

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

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi20 – 234Poly-His
Compositional biasi25 – 339Poly-Ala
Compositional biasi89 – 979Poly-Ala
Compositional biasi226 – 2305Poly-Ala
Compositional biasi231 – 2399Poly-His
Compositional biasi456 – 47015Poly-AlaAdd
BLAST
Compositional biasi490 – 50819Poly-GlyAdd
BLAST

Domaini

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

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.
GeneTreeiENSGT00760000118771.
HOGENOMiHOG000232057.
HOVERGENiHBG007135.
InParanoidiO95409.
KOiK06235.
OMAiDSAHMGA.
OrthoDBiEOG091G0M59.
PhylomeDBiO95409.
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. 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.

O95409-1 [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 GLPEQHGPHG SQNVLNGQMR LGLPGEVFGR SEQYRQVASP
210 220 230 240 250
RTDPYSAAQL HNQYGPMNMN MGMNMAAAAA HHHHHHHHHP 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 VSAVHRGGGS GSGGAGGGSG GGSGSGGGGG
510 520 530
GAGGGGGGSS GGGSGTAGGH SGLSSNFNEW YV
Length:532
Mass (Da):55,006
Last modified:April 16, 2002 - v2
Checksum:iBA3E6455DAF97EAC
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti124 – 1285RGFGD → ARLPGT in AAC96325 (PubMed:9771712).Curated

Polymorphismi

The poly-His region between amino acids 231-239 of ZIC2 is polymorphic and the number of His can vary from 8 to 12.1 Publication

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti36 – 361Q → P in HPE5; 2-fold increase in luciferase activity. 2 Publications
VAR_023793
Natural varianti37 – 371D → N in HPE5. 1 Publication
VAR_058592
Natural varianti128 – 1281D → N in HPE5. 1 Publication
VAR_058593
Natural varianti152 – 1521D → F in HPE5; requires 2 nucleotide substitutions; 50% reduction of luciferase activity. 3 Publications
VAR_023794
Natural varianti239 – 2391H → HH.1 Publication
VAR_023795
Natural varianti239 – 2391Missing .1 Publication
VAR_023796
Natural varianti272 – 2721S → N in HPE5. 1 Publication
VAR_058594
Natural varianti286 – 2861H → L in HPE5. 1 Publication
VAR_058595
Natural varianti286 – 2861H → Q in HPE5. 1 Publication
VAR_058596
Natural varianti286 – 2861H → Y in HPE5. 1 Publication
VAR_058597
Natural varianti291 – 2911H → Y in HPE5. 1 Publication
VAR_058598
Natural varianti304 – 3041W → R in HPE5. 1 Publication
VAR_058599
Natural varianti314 – 3141F → C in HPE5. 1 Publication
VAR_058600
Natural varianti325 – 3251R → L in HPE5. 1 Publication
VAR_058601
Natural varianti325 – 3251R → S in HPE5. 1 Publication
VAR_058602
Natural varianti327 – 3271H → Y in HPE5. 1 Publication
VAR_058603
Natural varianti335 – 3351C → F in HPE5. 1 Publication
VAR_058604
Natural varianti373 – 3731R → P in HPE5. 1 Publication
VAR_058605
Natural varianti402 – 4021Y → N in HPE5. 1 Publication
VAR_058606
Natural varianti403 – 4031T → K in HPE5. 1 Publication
VAR_058607
Natural varianti404 – 4041H → R in HPE5. 1 Publication
VAR_058608
Natural varianti409 – 4091R → W in HPE5. 1 Publication
VAR_058609
Natural varianti415 – 4151H → Q in HPE5. 1 Publication
Corresponds to variant rs794729641 [ dbSNP | Ensembl ].
VAR_058610
Natural varianti470 – 4701A → AAAAAAAAAAA in HPE5; near-complete loss of luciferase activity.
VAR_008856

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF104902 mRNA. Translation: AAC96325.1.
AF193855 mRNA. Translation: AAG28409.1.
AL355338 Genomic DNA. Translation: CAH70367.1.
CCDSiCCDS9495.1.
RefSeqiNP_009060.2. NM_007129.3.
UniGeneiHs.653700.

Genome annotation databases

EnsembliENST00000376335; ENSP00000365514; ENSG00000043355.
GeneIDi7546.
KEGGihsa:7546.
UCSCiuc001von.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF104902 mRNA. Translation: AAC96325.1.
AF193855 mRNA. Translation: AAG28409.1.
AL355338 Genomic DNA. Translation: CAH70367.1.
CCDSiCCDS9495.1.
RefSeqiNP_009060.2. NM_007129.3.
UniGeneiHs.653700.

3D structure databases

ProteinModelPortaliO95409.
SMRiO95409. Positions 250-417.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113378. 9 interactions.
IntActiO95409. 2 interactions.
MINTiMINT-2798893.
STRINGi9606.ENSP00000365514.

PTM databases

iPTMnetiO95409.
PhosphoSiteiO95409.

Polymorphism and mutation databases

BioMutaiZIC2.

Proteomic databases

EPDiO95409.
MaxQBiO95409.
PaxDbiO95409.
PeptideAtlasiO95409.
PRIDEiO95409.

Protocols and materials databases

DNASUi7546.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000376335; ENSP00000365514; ENSG00000043355.
GeneIDi7546.
KEGGihsa:7546.
UCSCiuc001von.4. human.

Organism-specific databases

CTDi7546.
GeneCardsiZIC2.
GeneReviewsiZIC2.
HGNCiHGNC:12873. ZIC2.
HPAiHPA055031.
MalaCardsiZIC2.
MIMi603073. gene.
609637. phenotype.
neXtProtiNX_O95409.
Orphaneti93925. Alobar holoprosencephaly.
93924. Lobar holoprosencephaly.
280200. Microform holoprosencephaly.
93926. Midline interhemispheric variant of holoprosencephaly.
220386. Semilobar holoprosencephaly.
280195. Septopreoptic holoprosencephaly.
PharmGKBiPA37462.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1721. Eukaryota.
COG5048. LUCA.
GeneTreeiENSGT00760000118771.
HOGENOMiHOG000232057.
HOVERGENiHBG007135.
InParanoidiO95409.
KOiK06235.
OMAiDSAHMGA.
OrthoDBiEOG091G0M59.
PhylomeDBiO95409.
TreeFamiTF351425.

Enzyme and pathway databases

SignaLinkiO95409.
SIGNORiO95409.

Miscellaneous databases

GeneWikiiZIC2.
GenomeRNAii7546.
PROiO95409.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000043355.
CleanExiHS_ZIC2.
ExpressionAtlasiO95409. baseline and differential.
GenevisibleiO95409. HS.

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...

Entry informationi

Entry nameiZIC2_HUMAN
AccessioniPrimary (citable) accession number: O95409
Secondary accession number(s): Q5VYA9, Q9H309
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: April 16, 2002
Last modified: September 7, 2016
This is version 153 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 13
    Human chromosome 13: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. 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.