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UniProtKB - O60481 (ZIC3_HUMAN)

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Protein

Zinc finger protein ZIC 3

Gene

ZIC3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Acts as transcriptional activator. Required in the earliest stages in both axial midline development and left-right (LR) asymmetry specification. Binds to the minimal GLI-consensus sequence 5'-GGGTGGTC-3'.1 Publication

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri251 – 286C2H2-type 1; atypicalPROSITE-ProRule annotationAdd BLAST36
Zinc fingeri295 – 322C2H2-type 2; atypicalPROSITE-ProRule annotationAdd BLAST28
Zinc fingeri328 – 352C2H2-type 3PROSITE-ProRule annotationAdd BLAST25
Zinc fingeri358 – 382C2H2-type 4PROSITE-ProRule annotationAdd BLAST25
Zinc fingeri388 – 410C2H2-type 5PROSITE-ProRule annotationAdd BLAST23

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

GO - Biological processi

  • anterior/posterior pattern specification Source: Ensembl
  • cell differentiation Source: UniProtKB-KW
  • determination of digestive tract left/right asymmetry Source: BHF-UCL
  • determination of left/right asymmetry in nervous system Source: Ensembl
  • determination of left/right symmetry Source: BHF-UCL
  • determination of liver left/right asymmetry Source: BHF-UCL
  • determination of pancreatic left/right asymmetry Source: BHF-UCL
  • heart looping Source: BHF-UCL
  • lung development Source: BHF-UCL
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of transcription by RNA polymerase II Source: UniProtKB
  • somatic stem cell population maintenance Source: Reactome
View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionActivator, Developmental protein, DNA-binding
Biological processDifferentiation, Neurogenesis, Transcription, Transcription regulation
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-2892247 POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation
R-HSA-452723 Transcriptional regulation of pluripotent stem cells
SignaLinkiO60481
SIGNORiO60481

Names & Taxonomyi

Protein namesi
Recommended name:
Zinc finger protein ZIC 3
Alternative name(s):
Zinc finger protein 203
Zinc finger protein of the cerebellum 3
Gene namesi
Name:ZIC3
Synonyms:ZNF203
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome X

Organism-specific databases

EuPathDBiHostDB:ENSG00000156925.11
HGNCiHGNC:12874 ZIC3
MIMi300265 gene
neXtProtiNX_O60481

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Heterotaxy, visceral, 1, X-linked (HTX1)6 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of visceral heterotaxy, a complex disorder due to disruption of the normal left-right asymmetry of the thoracoabdominal organs. Visceral heterotaxy or situs ambiguus results in randomization of the placement of visceral organs, including the heart, lungs, liver, spleen, and stomach. The organs are oriented randomly with respect to the left-right axis and with respect to one another. It can been associated with variety of congenital defects including cardiac malformations.
See also OMIM:306955
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_025633253C → S in HTX1; increases strongly its cytoplasmic localization; lacks DNA-binding; does not inhibit transcriptional activation and interaction with GLI3. 3 PublicationsCorresponds to variant dbSNP:rs104894961EnsemblClinVar.1
Natural variantiVAR_042416255W → G in HTX1; decreases protein expression and transcriptional activity and increases its cytoplasmic localization. 2 PublicationsCorresponds to variant dbSNP:rs122463168EnsemblClinVar.1
Natural variantiVAR_025634286H → R in HTX1; inreases weakly its cytoplasmic localization; lacks DNA-binding; does not inhibit transcriptional activation and interaction with GLI3. 3 Publications1
Natural variantiVAR_007753323T → M in HTX1; lacks DNA-binding; does not inhibit transcriptional activation and interaction with GLI3. 2 PublicationsCorresponds to variant dbSNP:rs122462165EnsemblClinVar.1
Natural variantiVAR_025635405K → E in HTX1; lacks DNA-binding; does not inhibit transcriptional activation and interaction with GLI3. 2 PublicationsCorresponds to variant dbSNP:rs104894962EnsemblClinVar.1
VACTERL association X-linked with or without hydrocephalus (VACTERLX)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA syndrome characterized by a non-random association of congenital defects. Affected individuals manifest vertebral anomalies (V), anal atresia (A), cardiac malformations (C), tracheoesophageal fistula (TE), renal anomalies (R) such as urethral atresia with hydronephrosis, and limb anomalies (L) such as hexadactyly, humeral hypoplasia, radial aplasia, and proximally placed thumb. Some patients may have hydrocephalus. Some cases of VACTERL-H are associated with increased chromosome breakage and rearrangement.
See also OMIM:314390
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06662646A → AAA in VACTERLX. 1 Publication1
Natural variantiVAR_071333318H → N in VACTERLX; decrease in transcriptional activator activity; significant decrease in nuclear localization. 1 Publication1
Congenital heart defects, multiple types, 1, X-linked (CHTD1)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder characterized by congenital developmental abnormalities involving structures of the heart. Common defects include transposition of the great arteries, aortic stenosis, atrial septal defect, ventricular septal defect, pulmonic stenosis, and patent ductus arteriosus. The etiology of CHTD is complex, with contributions from environmental exposure, chromosomal abnormalities, and gene defects. Some patients with CHTD also have cardiac arrhythmias, which may be due to the anatomic defect itself or to surgical interventions.
See also OMIM:306955
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_071332109S → C in CHTD1; does not affect its transcriptional activator activity; decrease in nuclear localization. 1 PublicationCorresponds to variant dbSNP:rs373628598Ensembl.1
Natural variantiVAR_071334447A → G in CHTD1; Increase in transcriptional activator activity; decrease in nuclear localization. 1 Publication1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi268C → S: Increases weakly its cytoplasmic localization. 1 Publication1
Mutagenesisi281H → R: Increases its cytoplasmic localization. 1 Publication1
Mutagenesisi304R → M: Increases its cytoplasmic localization. 1 Publication1
Mutagenesisi307K → M: Increases its cytoplasmic localization. 1 Publication1
Mutagenesisi310K → M: Increases its cytoplasmic localization. 1 Publication1
Mutagenesisi312K → M: Increases its cytoplasmic localization. 1 Publication1
Mutagenesisi314K → M: Does not increase its cytoplasmic localization. 1 Publication1
Mutagenesisi320R → A: Increases its cytoplasmic localization. Does not interact with KPNA1 and KPNA6 and increases strongly its cytoplasmic localization; when associated with A-337; A-341; A-346; A-349 and A-350. 1 Publication1
Mutagenesisi326K → M: Does not increase its cytoplasmic localization. 1 Publication1
Mutagenesisi337K → A: Increases its cytoplasmic localization. Does not interact with KPNA1 and KPNA6 and increases strongly its cytoplasmic localization; when associated with A-320; A-341; A-346; A-349 and A-350. 1 Publication1
Mutagenesisi341R → A: Increases its cytoplasmic localization. Does not interact with KPNA1 and KPNA6 and increases strongly its cytoplasmic localization; when associated with A-320; A-337; A-346; A-349 and A-350. 1 Publication1
Mutagenesisi346K → A: Increases its cytoplasmic localization. Does not interact with KPNA1 and KPNA6 and increases strongly its cytoplasmic localization; when associated with A-320; A-337; A-341; A-349 and A-350. 1 Publication1
Mutagenesisi349K → A: Increases its cytoplasmic localization. Does not interacts with KPNA1 and KPNA6 and increases strongly its cytoplasmic localization; when associated with A-320; A-337; A-341; A-346 and A-350. 1 Publication1
Mutagenesisi350R → A: Increases its cytoplasmic localization. Does not interact with KPNA1 and KPNA6 and increases strongly its cytoplasmic localization; when associated with A-320; A-337; A-341; A-346 and A-349. 1 Publication1
Mutagenesisi356K → A: Does not increase its cytoplasmic localization. 1 Publication1

Keywords - Diseasei

Disease mutation, Heterotaxy

Organism-specific databases

DisGeNETi7547
MalaCardsiZIC3
MIMi306955 phenotype
314390 phenotype
OpenTargetsiENSG00000156925
Orphaneti3426 Double outlet right ventricle
216718 Isolated congenitally uncorrected transposition of the great arteries
157769 Situs ambiguus
PharmGKBiPA37463

Polymorphism and mutation databases

BioMutaiZIC3

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000472501 – 467Zinc finger protein ZIC 3Add BLAST467

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki248Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources

Keywords - PTMi

Isopeptide bond, Ubl conjugation

Proteomic databases

EPDiO60481
MaxQBiO60481
PaxDbiO60481
PeptideAtlasiO60481
PRIDEiO60481
ProteomicsDBi49422
49423 [O60481-2]

PTM databases

iPTMnetiO60481
PhosphoSitePlusiO60481

Expressioni

Gene expression databases

BgeeiENSG00000156925
CleanExiHS_ZIC3
GenevisibleiO60481 HS

Organism-specific databases

HPAiHPA052936
HPA069523

Interactioni

Subunit structurei

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 (By similarity). Interacts with KPNA1 and KPNA6. Interacts (via C2H2-type domains 3, 4 and 5) with GLI3; the interaction enhances its transcriptional activity.By similarity2 Publications

Protein-protein interaction databases

BioGridi113379, 7 interactors
IntActiO60481, 3 interactors
STRINGi9606.ENSP00000287538

Structurei

Secondary structure

1467
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi261 – 264Combined sources4
Beta strandi272 – 274Combined sources3
Helixi275 – 284Combined sources10
Turni285 – 287Combined sources3
Helixi312 – 323Combined sources12
Beta strandi327 – 329Combined sources3
Turni333 – 335Combined sources3
Beta strandi338 – 340Combined sources3
Helixi342 – 349Combined sources8
Turni350 – 352Combined sources3
Beta strandi369 – 371Combined sources3
Helixi372 – 377Combined sources6
Turni380 – 383Combined sources4

3D structure databases

ProteinModelPortaliO60481
SMRiO60481
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO60481

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi297 – 322Nuclear localization signalAdd BLAST26
Motifi330 – 352Nuclear localization signalAdd BLAST23

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi46 – 55Poly-Ala10
Compositional biasi87 – 97Poly-HisAdd BLAST11

Domaini

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

Sequence similaritiesi

Belongs to the GLI C2H2-type zinc-finger protein family.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri251 – 286C2H2-type 1; atypicalPROSITE-ProRule annotationAdd BLAST36
Zinc fingeri295 – 322C2H2-type 2; atypicalPROSITE-ProRule annotationAdd BLAST28
Zinc fingeri328 – 352C2H2-type 3PROSITE-ProRule annotationAdd BLAST25
Zinc fingeri358 – 382C2H2-type 4PROSITE-ProRule annotationAdd BLAST25
Zinc fingeri388 – 410C2H2-type 5PROSITE-ProRule annotationAdd BLAST23

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG1721 Eukaryota
COG5048 LUCA
GeneTreeiENSGT00900000140802
HOGENOMiHOG000232057
HOVERGENiHBG007135
InParanoidiO60481
KOiK18487
OMAiKKTCDRT
OrthoDBiEOG091G0M59
PhylomeDBiO60481
TreeFamiTF351425

Family and domain databases

InterProiView protein in InterPro
IPR036236 Znf_C2H2_sf
IPR013087 Znf_C2H2_type
SMARTiView protein in SMART
SM00355 ZnF_C2H2, 5 hits
SUPFAMiSSF57667 SSF57667, 2 hits
PROSITEiView protein in PROSITE
PS00028 ZINC_FINGER_C2H2_1, 3 hits
PS50157 ZINC_FINGER_C2H2_2, 4 hits

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O60481-1) [UniParc]FASTAAdd to basket
Also known as: ZIC3-A

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MTMLLDGGPQ FPGLGVGSFG APRHHEMPNR EPAGMGLNPF GDSTHAAAAA 
        60         70         80         90        100
AAAAAFKLSP AAAHDLSSGQ SSAFTPQGSG YANALGHHHH HHHHHHHTSQ 
       110        120        130        140        150
VPSYGGAASA AFNSTREFLF RQRSSGLSEA ASGGGQHGLF AGSASSLHAP 
       160        170        180        190        200
AGIPEPPSYL LFPGLHEQGA GHPSPTGHVD NNQVHLGLRG ELFGRADPYR 
       210        220        230        240        250
PVASPRTDPY AAGAQFPNYS PMNMNMGVNV AAHHGPGAFF RYMRQPIKQE 
       260        270        280        290        300
LSCKWIDEAQ LSRPKKSCDR TFSTMHELVT HVTMEHVGGP EQNNHVCYWE 
       310        320        330        340        350
ECPREGKSFK AKYKLVNHIR VHTGEKPFPC PFPGCGKIFA RSENLKIHKR 
       360        370        380        390        400
THTGEKPFKC EFEGCDRRFA NSSDRKKHMH VHTSDKPYIC KVCDKSYTHP 
       410        420        430        440        450
SSLRKHMKVH ESQGSDSSPA ASSGYESSTP PAIASANSKD TTKTPSAVQT 
       460 
STSHNPGLPP NFNEWYV
Length:467
Mass (Da):50,569
Last modified:August 1, 1998 - v1
Checksum:i3150CF13C0679568
GO
Isoform 2 (identifier: O60481-2) [UniParc]FASTAAdd to basket
Also known as: ZIC3-B

The sequence of this isoform differs from the canonical sequence as follows:
     409-467: VHESQGSDSS...LPPNFNEWYV → CCPAWYPGQS...AEPTVQEMIY

Show »
Length:457
Mass (Da):50,045
Checksum:i28FFD09D87CC2AF5
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07133017G → C Unknown pathological significance; no effect on its transcriptional activator activity or subcellular localization. 1 PublicationCorresponds to variant dbSNP:rs147232392EnsemblClinVar.1
Natural variantiVAR_06662646A → AAA in VACTERLX. 1 Publication1
Natural variantiVAR_07133153A → AA Unknown pathological significance; no effect on its transcriptional activator activity or subcellular localization. 1 Publication1
Natural variantiVAR_071332109S → C in CHTD1; does not affect its transcriptional activator activity; decrease in nuclear localization. 1 PublicationCorresponds to variant dbSNP:rs373628598Ensembl.1
Natural variantiVAR_025632217P → A in HTX1 and CHTD1; lacks DNA-binding; does not inhibit transcriptional activation and interaction with GLI3; decrease in nuclear localization. 4 PublicationsCorresponds to variant dbSNP:rs104894963EnsemblClinVar.1
Natural variantiVAR_025633253C → S in HTX1; increases strongly its cytoplasmic localization; lacks DNA-binding; does not inhibit transcriptional activation and interaction with GLI3. 3 PublicationsCorresponds to variant dbSNP:rs104894961EnsemblClinVar.1
Natural variantiVAR_042416255W → G in HTX1; decreases protein expression and transcriptional activity and increases its cytoplasmic localization. 2 PublicationsCorresponds to variant dbSNP:rs122463168EnsemblClinVar.1
Natural variantiVAR_025634286H → R in HTX1; inreases weakly its cytoplasmic localization; lacks DNA-binding; does not inhibit transcriptional activation and interaction with GLI3. 3 Publications1
Natural variantiVAR_071333318H → N in VACTERLX; decrease in transcriptional activator activity; significant decrease in nuclear localization. 1 Publication1
Natural variantiVAR_007753323T → M in HTX1; lacks DNA-binding; does not inhibit transcriptional activation and interaction with GLI3. 2 PublicationsCorresponds to variant dbSNP:rs122462165EnsemblClinVar.1
Natural variantiVAR_025635405K → E in HTX1; lacks DNA-binding; does not inhibit transcriptional activation and interaction with GLI3. 2 PublicationsCorresponds to variant dbSNP:rs104894962EnsemblClinVar.1
Natural variantiVAR_071334447A → G in CHTD1; Increase in transcriptional activator activity; decrease in nuclear localization. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_044010409 – 467VHESQ…NEWYV → CCPAWYPGQSLIPDEELDTD VGMQQPALHNTTYPKCRVNA EPTVQEMIY in isoform 2. CuratedAdd BLAST59

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF028706 mRNA Translation: AAC05594.1
EU532020 mRNA Translation: ACB30403.1
AL035443 Genomic DNA No translation available.
BC113393 mRNA Translation: AAI13394.1
BC113395 mRNA Translation: AAI13396.1
CCDSiCCDS14663.1 [O60481-1]
CCDS83494.1 [O60481-2]
RefSeqiNP_001317590.1, NM_001330661.1 [O60481-2]
NP_003404.1, NM_003413.3 [O60481-1]
UniGeneiHs.111227

Genome annotation databases

EnsembliENST00000287538; ENSP00000287538; ENSG00000156925 [O60481-1]
ENST00000370606; ENSP00000359638; ENSG00000156925 [O60481-2]
GeneIDi7547
KEGGihsa:7547
UCSCiuc004fak.4 human [O60481-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism, Triplet repeat expansion

Similar proteinsi

Entry informationi

Entry nameiZIC3_HUMAN
AccessioniPrimary (citable) accession number: O60481
Secondary accession number(s): B2CNW4, Q14DE5, Q5JY75
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: August 1, 1998
Last modified: July 18, 2018
This is version 174 of the entry and version 1 of the sequence. See 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome X
    Human chromosome X: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

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