ZIC3

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 key	Position(s)	DescriptionActions	Length
Zinc fingerⁱ	251 – 286	C2H2-type 1; atypicalPROSITE-ProRule annotationAdd BLAST	36
Zinc fingerⁱ	295 – 322	C2H2-type 2; atypicalPROSITE-ProRule annotationAdd BLAST	28
Zinc fingerⁱ	328 – 352	C2H2-type 3PROSITE-ProRule annotationAdd BLAST	25
Zinc fingerⁱ	358 – 382	C2H2-type 4PROSITE-ProRule annotationAdd BLAST	25
Zinc fingerⁱ	388 – 410	C2H2-type 5PROSITE-ProRule annotationAdd BLAST	23

GO - Molecular functionⁱ

DNA-binding transcription activator activity, RNA polymerase II-specific
Source: NTNU_SB
Inferred from direct assayⁱ
- Ref.5
  "Characterization of the interactions of human ZIC3 mutants with GLI3."
  Zhu L., Zhou G., Poole S., Belmont J.W.
  Hum. Mutat. 29:99-105(2008) [PubMed] [Europe PMC] [Abstract]
  Cited for: FUNCTION, INTERACTION WITH GLI3, DNA-BINDING, CHARACTERIZATION OF VARIANTS HTX1 SER-253; ARG-286; MET-323 AND GLU-405, CHARACTERIZATION OF VARIANT CHTD1 ALA-217.
DNA-binding transcription factor activity
Source: UniProtKB
Inferred from direct assayⁱ
- Ref.5
  "Characterization of the interactions of human ZIC3 mutants with GLI3."
  Zhu L., Zhou G., Poole S., Belmont J.W.
  Hum. Mutat. 29:99-105(2008) [PubMed] [Europe PMC] [Abstract]
  Cited for: FUNCTION, INTERACTION WITH GLI3, DNA-BINDING, CHARACTERIZATION OF VARIANTS HTX1 SER-253; ARG-286; MET-323 AND GLU-405, CHARACTERIZATION OF VARIANT CHTD1 ALA-217.
DNA-binding transcription factor activity, RNA polymerase II-specific
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
  Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
  Brief Bioinform 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]
metal ion binding Source: UniProtKB-KW
RNA polymerase II cis-regulatory region sequence-specific DNA binding
Source: NTNU_SB
Inferred from direct assayⁱ
- Ref.5
  "Characterization of the interactions of human ZIC3 mutants with GLI3."
  Zhu L., Zhou G., Poole S., Belmont J.W.
  Hum. Mutat. 29:99-105(2008) [PubMed] [Europe PMC] [Abstract]
  Cited for: FUNCTION, INTERACTION WITH GLI3, DNA-BINDING, CHARACTERIZATION OF VARIANTS HTX1 SER-253; ARG-286; MET-323 AND GLU-405, CHARACTERIZATION OF VARIANT CHTD1 ALA-217.
sequence-specific DNA binding
Source: UniProtKB
Inferred from direct assayⁱ
- Ref.5
  "Characterization of the interactions of human ZIC3 mutants with GLI3."
  Zhu L., Zhou G., Poole S., Belmont J.W.
  Hum. Mutat. 29:99-105(2008) [PubMed] [Europe PMC] [Abstract]
  Cited for: FUNCTION, INTERACTION WITH GLI3, DNA-BINDING, CHARACTERIZATION OF VARIANTS HTX1 SER-253; ARG-286; MET-323 AND GLU-405, CHARACTERIZATION OF VARIANT CHTD1 ALA-217.
sequence-specific double-stranded DNA binding
Source: ARUK-UCL
Inferred from direct assayⁱ
- "Impact of cytosine methylation on DNA binding specificities of human transcription factors."
  Yin Y., Morgunova E., Jolma A., Kaasinen E., Sahu B., Khund-Sayeed S., Das P.K., Kivioja T., Dave K., Zhong F., Nitta K.R., Taipale M., Popov A., Ginno P.A., Domcke S., Yan J., Schubeler D., Vinson C., Taipale J.
  Science 356:0-0(2017) [PubMed] [Europe PMC] [Abstract]

Complete GO annotation on QuickGO ...

GO - Biological processⁱ

Complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Activator, Developmental protein, DNA-binding
Biological process	Differentiation, Neurogenesis, Transcription, Transcription regulation
Ligand	Metal-binding, Zinc

Enzyme and pathway databases

PathwayCommonsⁱ	O60481
Reactomeⁱ	R-HSA-2892247, POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation R-HSA-452723, Transcriptional regulation of pluripotent stem cells
SignaLinkⁱ	O60481
SIGNORⁱ	O60481

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
Organismⁱ	Homo sapiens (Human)
Taxonomic identifierⁱ	9606 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo
Proteomesⁱ	UP000005640 Componentⁱ: Chromosome X

Organism-specific databases

Human Gene Nomenclature Database More...HGNCⁱ	HGNC:12874, ZIC3
MIMⁱ	300265, gene
neXtProtⁱ	NX_O60481
VEuPathDBⁱ	HostDB:ENSG00000156925

Keywords - Cellular componentⁱ

Cytoplasm, Nucleus

Pathology & Biotechⁱ

Involvement in diseaseⁱ

Heterotaxy, visceral, 1, X-linked (HTX1)6 Publications

The disease is caused by variants 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 be associated with a variety of congenital defects including cardiac malformations.

Related information in OMIM

Feature key	Position(s)	DescriptionActions	Length
Natural variantⁱVAR_025632	217	P → 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_025633	253	C → 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_042416	255	W → G in HTX1; decreases protein expression and transcriptional activity and increases its cytoplasmic localization. 2 PublicationsCorresponds to variant dbSNP:rs122463168EnsemblClinVar.	1
Natural variantⁱVAR_025634	286	H → R in HTX1; inreases weakly its cytoplasmic localization; lacks DNA-binding; does not inhibit transcriptional activation and interaction with GLI3. 3 Publications	1
Natural variantⁱVAR_007753	323	T → M in HTX1; lacks DNA-binding; does not inhibit transcriptional activation and interaction with GLI3. 2 PublicationsCorresponds to variant dbSNP:rs122462165EnsemblClinVar.	1
Natural variantⁱVAR_025635	405	K → 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 variants 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.

Related information in OMIM

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Natural variantⁱVAR_066626	46	A → AAA in VACTERLX. 1 Publication		1
Natural variantⁱVAR_071333	318	H → N in VACTERLX; decrease in transcriptional activator activity; significant decrease in nuclear localization. 1 Publication		1

Congenital heart defects, multiple types, 1, X-linked (CHTD1)3 Publications

The disease is caused by variants 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.

Related information in OMIM

Feature key	Position(s)	DescriptionActions	Length
Natural variantⁱVAR_071332	109	S → C in CHTD1; does not affect its transcriptional activator activity; decrease in nuclear localization. 1 PublicationCorresponds to variant dbSNP:rs373628598EnsemblClinVar.	1
Natural variantⁱVAR_025632	217	P → 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_071334	447	A → G in CHTD1; Increase in transcriptional activator activity; decrease in nuclear localization. 1 Publication	1

Mutagenesis

Feature key	Position(s)	DescriptionActions	Length
Mutagenesisⁱ	268	C → S: Increases weakly its cytoplasmic localization. 1 Publication	1
Mutagenesisⁱ	281	H → R: Increases its cytoplasmic localization. 1 Publication	1
Mutagenesisⁱ	304	R → M: Increases its cytoplasmic localization. 1 Publication	1
Mutagenesisⁱ	307	K → M: Increases its cytoplasmic localization. 1 Publication	1
Mutagenesisⁱ	310	K → M: Increases its cytoplasmic localization. 1 Publication	1
Mutagenesisⁱ	312	K → M: Increases its cytoplasmic localization. 1 Publication	1
Mutagenesisⁱ	314	K → M: Does not increase its cytoplasmic localization. 1 Publication	1
Mutagenesisⁱ	320	R → 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 Publication	1
Mutagenesisⁱ	326	K → M: Does not increase its cytoplasmic localization. 1 Publication	1
Mutagenesisⁱ	337	K → 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 Publication	1
Mutagenesisⁱ	341	R → 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 Publication	1
Mutagenesisⁱ	346	K → 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 Publication	1
Mutagenesisⁱ	349	K → 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 Publication	1
Mutagenesisⁱ	350	R → 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 Publication	1
Mutagenesisⁱ	356	K → A: Does not increase its cytoplasmic localization. 1 Publication	1

Keywords - Diseaseⁱ

Disease variant, Heterotaxy

Organism-specific databases

DisGeNET More...DisGeNETⁱ	7547
MalaCards human disease database More...MalaCardsⁱ	ZIC3
MIMⁱ	306955, phenotype 314390, phenotype
Open Targets More...OpenTargetsⁱ	ENSG00000156925
Orphanetⁱ	216718, Isolated congenitally uncorrected transposition of the great arteries 157769, Situs ambiguus
PharmGKBⁱ	PA37463

Miscellaneous databases

Pharosⁱ	O60481, Tbio

Pharosⁱ

O60481, Tbio

Genetic variation databases

BioMutaⁱ	ZIC3

BioMutaⁱ

ZIC3

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
ChainⁱPRO_0000047250	1 – 467	Zinc finger protein ZIC 3Add BLAST		467

Amino acid modifications

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Cross-linkⁱ	248	Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources

Keywords - PTMⁱ

Isopeptide bond, Ubl conjugation

Proteomic databases

jPOSTⁱ	O60481
MassIVEⁱ	O60481
MaxQB - The MaxQuant DataBase More...MaxQBⁱ	O60481
PaxDbⁱ	O60481
PeptideAtlas More...PeptideAtlasⁱ	O60481
PRIDEⁱ	O60481
ProteomicsDBⁱ	49422 [O60481-1] 49423 [O60481-2]

PTM databases

iPTMnetⁱ	O60481
PhosphoSitePlusⁱ	O60481

Expressionⁱ

Gene expression databases

Bgeeⁱ	ENSG00000156925, Expressed in embryo and 71 other tissues
Genevisibleⁱ	O60481, HS

Organism-specific databases

Human Protein Atlas More...HPAⁱ	ENSG00000156925, Tissue enhanced (brain, choroid plexus, retina)

HPAⁱ

ENSG00000156925, Tissue enhanced (brain, choroid plexus, retina)

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

BioGRIDⁱ	113379, 8 interactors
IntActⁱ	O60481, 3 interactors
STRINGⁱ	9606.ENSP00000287538

Miscellaneous databases

RNActⁱ	O60481, protein

RNActⁱ

O60481, protein

Structureⁱ

Secondary structure

Legend: HelixTurnBeta strandPDB Structure known for this area

Feature key	Position(s)	DescriptionActions	Length
Beta strandⁱ	261 – 264	Combined sources	4
Beta strandⁱ	272 – 274	Combined sources	3
Helixⁱ	275 – 284	Combined sources	10
Turnⁱ	285 – 287	Combined sources	3
Helixⁱ	312 – 323	Combined sources	12
Beta strandⁱ	327 – 329	Combined sources	3
Turnⁱ	333 – 335	Combined sources	3
Beta strandⁱ	338 – 340	Combined sources	3
Helixⁱ	342 – 349	Combined sources	8
Turnⁱ	350 – 352	Combined sources	3
Beta strandⁱ	369 – 371	Combined sources	3
Helixⁱ	372 – 377	Combined sources	6
Turnⁱ	380 – 383	Combined sources	4

Show more details

3D structure databases

SMRⁱ	O60481
ModBaseⁱ	Search...
PDBe-KBⁱ	Search...

Miscellaneous databases

EvolutionaryTraceⁱ	O60481

EvolutionaryTraceⁱ

O60481

Family & Domainsⁱ

Region

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Regionⁱ	66 – 107	DisorderedSequence analysisAdd BLAST		42
Regionⁱ	404 – 467	DisorderedSequence analysisAdd BLAST		64

Motif

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Motifⁱ	297 – 322	Nuclear localization signalAdd BLAST		26
Motifⁱ	330 – 352	Nuclear localization signalAdd BLAST		23

Compositional bias

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Compositional biasⁱ	85 – 99	Basic residuesSequence analysisAdd BLAST		15
Compositional biasⁱ	413 – 459	Polar residuesSequence analysisAdd BLAST		47

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 key	Position(s)	DescriptionActions	Length
Zinc fingerⁱ	251 – 286	C2H2-type 1; atypicalPROSITE-ProRule annotationAdd BLAST	36
Zinc fingerⁱ	295 – 322	C2H2-type 2; atypicalPROSITE-ProRule annotationAdd BLAST	28
Zinc fingerⁱ	328 – 352	C2H2-type 3PROSITE-ProRule annotationAdd BLAST	25
Zinc fingerⁱ	358 – 382	C2H2-type 4PROSITE-ProRule annotationAdd BLAST	25
Zinc fingerⁱ	388 – 410	C2H2-type 5PROSITE-ProRule annotationAdd BLAST	23

Keywords - Domainⁱ

Repeat, Zinc-finger

Phylogenomic databases

eggNOGⁱ	KOG1721, Eukaryota
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00940000160788
HOGENOMⁱ	CLU_002678_37_1_1
InParanoidⁱ	O60481
OMAⁱ	PRHHDIG
Database of Orthologous Groups More...OrthoDBⁱ	768287at2759
PhylomeDBⁱ	O60481
TreeFamⁱ	TF351425

Family and domain databases

InterProⁱ	View protein in InterPro IPR036236, Znf_C2H2_sf IPR013087, Znf_C2H2_type IPR041643, Znf_ZIC
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF00096, zf-C2H2, 4 hits PF18366, zf_ZIC, 1 hit
SMARTⁱ	View protein in SMART SM00355, ZnF_C2H2, 5 hits
SUPFAMⁱ	SSF57667, SSF57667, 2 hits
PROSITEⁱ	View 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. Align Add to basket

Isoform 1 (identifier: O60481-1) [UniParc]FASTA Add to basket

Also known as: ZIC3-A

This isoform has been chosen as the canonicalⁱ 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]FASTA Add 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

« 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
SSLRKHMKCC PAWYPGQSLI PDEELDTDVG MQQPALHNTT YPKCRVNAEP 

TVQEMIY

Show »

Length:457

Mass (Da):50,045

Checksum:ⁱ28FFD09D87CC2AF5

GO

Natural variant

Feature key	Position(s)	DescriptionActions	Length
Natural variantⁱVAR_071330	17	G → C Unknown pathological significance; no effect on its transcriptional activator activity or subcellular localization. 1 PublicationCorresponds to variant dbSNP:rs147232392EnsemblClinVar.	1
Natural variantⁱVAR_066626	46	A → AAA in VACTERLX. 1 Publication	1
Natural variantⁱVAR_071331	53	A → AA Unknown pathological significance; no effect on its transcriptional activator activity or subcellular localization. 1 Publication	1
Natural variantⁱVAR_071332	109	S → C in CHTD1; does not affect its transcriptional activator activity; decrease in nuclear localization. 1 PublicationCorresponds to variant dbSNP:rs373628598EnsemblClinVar.	1
Natural variantⁱVAR_025632	217	P → 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_025633	253	C → 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_042416	255	W → G in HTX1; decreases protein expression and transcriptional activity and increases its cytoplasmic localization. 2 PublicationsCorresponds to variant dbSNP:rs122463168EnsemblClinVar.	1
Natural variantⁱVAR_025634	286	H → R in HTX1; inreases weakly its cytoplasmic localization; lacks DNA-binding; does not inhibit transcriptional activation and interaction with GLI3. 3 Publications	1
Natural variantⁱVAR_071333	318	H → N in VACTERLX; decrease in transcriptional activator activity; significant decrease in nuclear localization. 1 Publication	1
Natural variantⁱVAR_007753	323	T → M in HTX1; lacks DNA-binding; does not inhibit transcriptional activation and interaction with GLI3. 2 PublicationsCorresponds to variant dbSNP:rs122462165EnsemblClinVar.	1
Natural variantⁱVAR_025635	405	K → E in HTX1; lacks DNA-binding; does not inhibit transcriptional activation and interaction with GLI3. 2 PublicationsCorresponds to variant dbSNP:rs104894962EnsemblClinVar.	1
Natural variantⁱVAR_071334	447	A → G in CHTD1; Increase in transcriptional activator activity; decrease in nuclear localization. 1 Publication	1

Alternative sequence

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Alternative sequenceⁱVSP_044010	409 – 467	VHESQ…NEWYV → CCPAWYPGQSLIPDEELDTD VGMQQPALHNTTYPKCRVNA EPTVQEMIY in isoform 2. CuratedAdd BLAST		59

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
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS14663.1 [O60481-1] CCDS83494.1 [O60481-2]
NCBI Reference Sequences More...RefSeqⁱ	NP_001317590.1, NM_001330661.1 [O60481-2] NP_003404.1, NM_003413.3 [O60481-1]

Genome annotation databases

Ensemblⁱ	ENST00000287538; ENSP00000287538; ENSG00000156925 ENST00000370606; ENSP00000359638; ENSG00000156925 [O60481-2]
GeneIDⁱ	7547
KEGGⁱ	hsa:7547
MANE-Selectⁱ	ENST00000287538.10; ENSP00000287538.5; NM_003413.4; NP_003404.1
UCSC genome browser More...UCSCⁱ	uc004fak.4, human [O60481-1]

Keywords - Coding sequence diversityⁱ

Alternative splicing, Triplet repeat expansion

Similar proteinsⁱ

90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length	Source
O60481	Zic family member 3		pale spear-nosed bat		469	UniRef90_O60481
Zic family member 3		PIPKU		468
Zic family member 3		AOTNA		467
Zic family member 3		SAIBB		467
Zic family member 3		RABIT		467
+36
O60481-2	zinc finger protein ZIC 3 isoform X2		ZALCA		548	UniRef90_O60481-2
zinc finger protein ZIC 3 isoform X2		CALUR		457
Zinc finger protein ZIC 3		CAMDR		520
zinc finger protein ZIC 3 isoform X2		VICPA		454
Zic family member 3		pale spear-nosed bat		460
+110

Protein	Similar proteins		Species	Score	Length	Source
O60481	Zinc finger protein ZIC 3		XENTR		441	UniRef50_O60481
Zinc finger protein ZIC 3		XENLA		441
Zic family member 3		pale spear-nosed bat		469
Zic family member 3		PIPKU		468
Zic family member 3		CEBIM		467
+239
O60481-2	zinc finger protein ZIC 3 isoform X2		ZALCA		548	UniRef50_O60481-2
zinc finger protein ZIC 3 isoform X2		CALUR		457
Zinc finger protein ZIC 3		CAMDR		520
zinc finger protein ZIC 3 isoform X2		VICPA		454
Zic family member 3		pale spear-nosed bat		460
+153

Cross-referencesⁱ

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
CCDSⁱ	CCDS14663.1 [O60481-1] CCDS83494.1 [O60481-2]
RefSeqⁱ	NP_001317590.1, NM_001330661.1 [O60481-2] NP_003404.1, NM_003413.3 [O60481-1]

3D structure databases

Select the link destinations: Protein Data Bank Europe More...PDBeⁱ Protein Data Bank RCSB More...RCSB PDBⁱ Protein Data Bank Japan More...PDBjⁱ Links Updated	PDB entry	Method	Resolution (Å)	Chain	Positions	PDBsum
	2EJ4	NMR	-	A	245-326	[»]
	2RPC	NMR	-	A	245-386	[»]
SMRⁱ	O60481
ModBaseⁱ	Search...
PDBe-KBⁱ	Search...

Protein-protein interaction databases

BioGRIDⁱ	113379, 8 interactors
IntActⁱ	O60481, 3 interactors
STRINGⁱ	9606.ENSP00000287538

PTM databases

iPTMnetⁱ	O60481
PhosphoSitePlusⁱ	O60481

Genetic variation databases

BioMutaⁱ	ZIC3

BioMutaⁱ

ZIC3

Proteomic databases

jPOSTⁱ	O60481
MassIVEⁱ	O60481
MaxQBⁱ	O60481
PaxDbⁱ	O60481
PeptideAtlasⁱ	O60481
PRIDEⁱ	O60481
ProteomicsDBⁱ	49422 [O60481-1] 49423 [O60481-2]

Protocols and materials databases

Antibodypediaⁱ	30470, 277 antibodies from 32 providers
The DNASU plasmid repository More...DNASUⁱ	7547

Genome annotation databases

Ensemblⁱ	ENST00000287538; ENSP00000287538; ENSG00000156925 ENST00000370606; ENSP00000359638; ENSG00000156925 [O60481-2]
GeneIDⁱ	7547
KEGGⁱ	hsa:7547
MANE-Selectⁱ	ENST00000287538.10; ENSP00000287538.5; NM_003413.4; NP_003404.1
UCSCⁱ	uc004fak.4, human [O60481-1]

Organism-specific databases

CTDⁱ	7547
DisGeNETⁱ	7547
GeneCardsⁱ	ZIC3
HGNCⁱ	HGNC:12874, ZIC3
HPAⁱ	ENSG00000156925, Tissue enhanced (brain, choroid plexus, retina)
MalaCardsⁱ	ZIC3
MIMⁱ	300265, gene 306955, phenotype 314390, phenotype
neXtProtⁱ	NX_O60481
OpenTargetsⁱ	ENSG00000156925
Orphanetⁱ	216718, Isolated congenitally uncorrected transposition of the great arteries 157769, Situs ambiguus
PharmGKBⁱ	PA37463
VEuPathDBⁱ	HostDB:ENSG00000156925
GenAtlas: human gene database More...GenAtlasⁱ	Search...

Phylogenomic databases

eggNOGⁱ	KOG1721, Eukaryota
GeneTreeⁱ	ENSGT00940000160788
HOGENOMⁱ	CLU_002678_37_1_1
InParanoidⁱ	O60481
OMAⁱ	PRHHDIG
OrthoDBⁱ	768287at2759
PhylomeDBⁱ	O60481
TreeFamⁱ	TF351425

Enzyme and pathway databases

PathwayCommonsⁱ	O60481
Reactomeⁱ	R-HSA-2892247, POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation R-HSA-452723, Transcriptional regulation of pluripotent stem cells
SignaLinkⁱ	O60481
SIGNORⁱ	O60481

Miscellaneous databases

BioGRID-ORCSⁱ	7547, 4 hits in 682 CRISPR screens
EvolutionaryTraceⁱ	O60481
GeneWikiⁱ	ZIC3
GenomeRNAiⁱ	7547
Pharosⁱ	O60481, Tbio
Protein Ontology More...PROⁱ	PR:O60481
RNActⁱ	O60481, protein
SOURCEⁱ	Search...

Gene expression databases

Bgeeⁱ	ENSG00000156925, Expressed in embryo and 71 other tissues
Genevisibleⁱ	O60481, HS

Family and domain databases

InterProⁱ	View protein in InterPro IPR036236, Znf_C2H2_sf IPR013087, Znf_C2H2_type IPR041643, Znf_ZIC
Pfamⁱ	View protein in Pfam PF00096, zf-C2H2, 4 hits PF18366, zf_ZIC, 1 hit
SMARTⁱ	View protein in SMART SM00355, ZnF_C2H2, 5 hits
SUPFAMⁱ	SSF57667, SSF57667, 2 hits
PROSITEⁱ	View protein in PROSITE PS00028, ZINC_FINGER_C2H2_1, 3 hits PS50157, ZINC_FINGER_C2H2_2, 4 hits
MobiDBⁱ	Search...

Entry informationⁱ

Entry nameⁱ	ZIC3_HUMAN
Accessionⁱ	O60481Primary (citable) accession number: O60481 Secondary accession number(s): B2CNW4, Q14DE5, Q5JY75
Entry historyⁱ	Integrated into UniProtKB/Swiss-Prot:	December 15, 1998
	Last sequence update:	August 1, 1998
	Last modified:	February 23, 2022
	This is version 197 of the entry and version 1 of the sequence. See complete history.
Entry statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Chordata Protein Annotation Program
Disclaimer	Any 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, Reference proteome

Documents

Human chromosome X
Human chromosome X: entries, gene names and cross-references to MIM
Human entries with genetic variants
List of human entries with genetic variants
Human variants curated from literature reports
Index of human variants curated from literature reports
MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
PDB cross-references
Index of Protein Data Bank (PDB) cross-references
SIMILARITY comments
Index of protein domains and families

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UniProtKB - O60481 (ZIC3_HUMAN)

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Zinc finger protein ZIC 3

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<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Regions

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GO - Biological processi

Enzyme and pathway databases

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<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

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Keywords - Cellular componenti

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<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

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Keywords - PTMi

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

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<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

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<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

3D structure databases

Miscellaneous databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

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<p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Zinc finger

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Keywords - Coding sequence diversityi

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Sequence databases

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PTM databases

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Protocols and materials databases

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Miscellaneous databases

Gene expression databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

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Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

Keywords - Diseaseⁱ

PTM / Processingⁱ

Keywords - PTMⁱ

Expressionⁱ

Interactionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Keywords - Domainⁱ

Keywords - Coding sequence diversityⁱ

Cross-referencesⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ