ZIC3_HUMAN
ID ZIC3_HUMAN Reviewed; 467 AA.
AC O60481; B2CNW4; Q14DE5; Q5JY75;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1998, sequence version 1.
DT 03-AUG-2022, entry version 199.
DE RecName: Full=Zinc finger protein ZIC 3;
DE AltName: Full=Zinc finger protein 203;
DE AltName: Full=Zinc finger protein of the cerebellum 3;
GN Name=ZIC3; Synonyms=ZNF203;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS HTX1 ARG-286 AND
RP MET-323.
RX PubMed=9354794; DOI=10.1038/ng1197-305;
RA Gebbia M., Ferrero G.B., Pilia G., Bassi M.T., Aylsworth A.S.,
RA Penman-Splitt M., Bird L.M., Bamforth J.S., Burn J., Schlessiner D.,
RA Nelson D.L., Casey B.;
RT "X-linked situs abnormalities result from mutations in ZIC3.";
RL Nat. Genet. 17:305-308(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=19266028; DOI=10.1371/journal.pgen.1000397;
RA Salichs E., Ledda A., Mularoni L., Alba M.M., de la Luna S.;
RT "Genome-wide analysis of histidine repeats reveals their role in the
RT localization of human proteins to the nuclear speckles compartment.";
RL PLoS Genet. 5:E1000397-E1000397(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP FUNCTION, INTERACTION WITH GLI3, DNA-BINDING, CHARACTERIZATION OF VARIANTS
RP HTX1 SER-253; ARG-286; MET-323 AND GLU-405, AND CHARACTERIZATION OF VARIANT
RP CHTD1 ALA-217.
RX PubMed=17764085; DOI=10.1002/humu.20606;
RA Zhu L., Zhou G., Poole S., Belmont J.W.;
RT "Characterization of the interactions of human ZIC3 mutants with GLI3.";
RL Hum. Mutat. 29:99-105(2008).
RN [6]
RP ALTERNATIVE SPLICING (ISOFORM 2).
RX PubMed=21858219; DOI=10.1371/journal.pone.0023755;
RA Bedard J.E., Haaning A.M., Ware S.M.;
RT "Identification of a novel ZIC3 isoform and mutation screening in patients
RT with heterotaxy and congenital heart disease.";
RL PLoS ONE 6:E23755-E23755(2011).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [8]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-248, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [9]
RP STRUCTURE BY NMR OF 246-329 IN COMPLEX WITH ZINC IONS, INTERACTION WITH
RP KPNA1 AND KPNA6, CHARACTERIZATION OF VARIANTS HTX1 SER-253; GLY-255 AND
RP ARG-286, AND MUTAGENESIS OF CYS-268; HIS-281; ARG-304; LYS-307; LYS-310;
RP LYS-312; LYS-314; ARG-320; LYS-326; LYS-337; ARG-341; LYS-346; LYS-349;
RP ARG-350 AND LYS-356.
RX PubMed=18716025; DOI=10.1093/hmg/ddn239;
RA Hatayama M., Tomizawa T., Sakai-Kato K., Bouvagnet P., Kose S., Imamoto N.,
RA Yokoyama S., Utsunomiya-Tate N., Mikoshiba K., Kigawa T., Aruga J.;
RT "Functional and structural basis of the nuclear localization signal in the
RT ZIC3 zinc finger domain.";
RL Hum. Mol. Genet. 17:3459-3473(2008).
RN [10]
RP VARIANT CHTD1 ALA-217, AND VARIANTS HTX1 SER-253 AND GLU-405.
RX PubMed=14681828; DOI=10.1086/380998;
RA Ware S.M., Peng J., Zhu L., Fernbach S., Colicos S., Casey B., Towbin J.,
RA Belmont J.W.;
RT "Identification and functional analysis of ZIC3 mutations in heterotaxy and
RT related congenital heart defects.";
RL Am. J. Hum. Genet. 74:93-105(2004).
RN [11]
RP VARIANT [LARGE SCALE ANALYSIS] ALA-217.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [12]
RP VARIANT HTX1 GLY-255, AND CHARACTERIZATION OF VARIANT HTX1 GLY-255.
RX PubMed=17295247; DOI=10.1002/humu.20480;
RA Chhin B., Hatayama M., Bozon D., Ogawa M., Schoen P., Tohmonda T.,
RA Sassolas F., Aruga J., Valard A.-G., Chen S.-C., Bouvagnet P.;
RT "Elucidation of penetrance variability of a ZIC3 mutation in a family with
RT complex heart defects and functional analysis of ZIC3 mutations in the
RT first zinc finger domain.";
RL Hum. Mutat. 28:563-570(2007).
RN [13]
RP VARIANT VACTERLX ALA-ALA-46 INS.
RX PubMed=20452998; DOI=10.1136/jmg.2008.060913;
RA Wessels M.W., Kuchinka B., Heydanus R., Smit B.J., Dooijes D.,
RA de Krijger R.R., Lequin M.H., de Jong E.M., Husen M., Willems P.J.,
RA Casey B.;
RT "Polyalanine expansion in the ZIC3 gene leading to X-linked heterotaxy with
RT VACTERL association: a new polyalanine disorder?";
RL J. Med. Genet. 47:351-355(2010).
RN [14]
RP VARIANTS CYS-17 AND ALA-53 INS, VARIANTS CHTD1 CYS-109; ALA-217 AND
RP GLY-447, VARIANT HTX1 ALA-217, VARIANT VACTERLX ASN-318, CHARACTERIZATION
RP OF VARIANTS CYS-17 AND ALA-53 INS, CHARACTERIZATION OF VARIANTS CHTD1
RP CYS-109 AND GLY-447, CHARACTERIZATION OF VARIANT CHTD1 ALA-217,
RP CHARACTERIZATION OF VARIANT HTX1 ALA-217, AND CHARACTERIZATION OF VARIANT
RP VACTERLX ASN-318.
RX PubMed=24123890; DOI=10.1002/humu.22457;
RA Cowan J., Tariq M., Ware S.M.;
RT "Genetic and functional analyses of ZIC3 variants in congenital heart
RT disease.";
RL Hum. Mutat. 35:66-75(2014).
CC -!- FUNCTION: Acts as transcriptional activator. Required in the earliest
CC stages in both axial midline development and left-right (LR) asymmetry
CC specification. Binds to the minimal GLI-consensus sequence 5'-GGGTGGTC-
CC 3'. {ECO:0000269|PubMed:17764085}.
CC -!- SUBUNIT: Interacts (via the C2H2-type domains 3, 4 and 5) with MDFIC
CC (via the C2H2-type domains 3, 4 and 5); the interaction reduces its
CC transcriptional activity (By similarity). Interacts with KPNA1 and
CC KPNA6. Interacts (via C2H2-type domains 3, 4 and 5) with GLI3; the
CC interaction enhances its transcriptional activity. {ECO:0000250,
CC ECO:0000269|PubMed:17764085, ECO:0000269|PubMed:18716025}.
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm {ECO:0000250}. Note=Localizes
CC in the cytoplasm in presence of MDFIC overexpression (By similarity).
CC Translocation to the nucleus requires KPNA1 or KPNA6. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=ZIC3-A;
CC IsoId=O60481-1; Sequence=Displayed;
CC Name=2; Synonyms=ZIC3-B;
CC IsoId=O60481-2; Sequence=VSP_044010;
CC -!- DOMAIN: The C2H2-type 3, 4 and 5 zinc finger domains are necessary for
CC transcription activation. {ECO:0000250}.
CC -!- DISEASE: Heterotaxy, visceral, 1, X-linked (HTX1) [MIM:306955]: A form
CC of visceral heterotaxy, a complex disorder due to disruption of the
CC normal left-right asymmetry of the thoracoabdominal organs. Visceral
CC heterotaxy or situs ambiguus results in randomization of the placement
CC of visceral organs, including the heart, lungs, liver, spleen, and
CC stomach. The organs are oriented randomly with respect to the left-
CC right axis and with respect to one another. It can be associated with a
CC variety of congenital defects including cardiac malformations.
CC {ECO:0000269|PubMed:14681828, ECO:0000269|PubMed:17295247,
CC ECO:0000269|PubMed:17764085, ECO:0000269|PubMed:18716025,
CC ECO:0000269|PubMed:24123890, ECO:0000269|PubMed:9354794}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: VACTERL association X-linked with or without hydrocephalus
CC (VACTERLX) [MIM:314390]: A syndrome characterized by a non-random
CC association of congenital defects. Affected individuals manifest
CC vertebral anomalies (V), anal atresia (A), cardiac malformations (C),
CC tracheoesophageal fistula (TE), renal anomalies (R) such as urethral
CC atresia with hydronephrosis, and limb anomalies (L) such as
CC hexadactyly, humeral hypoplasia, radial aplasia, and proximally placed
CC thumb. Some patients may have hydrocephalus. Some cases of VACTERL-H
CC are associated with increased chromosome breakage and rearrangement.
CC {ECO:0000269|PubMed:20452998, ECO:0000269|PubMed:24123890}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Congenital heart defects, multiple types, 1, X-linked (CHTD1)
CC [MIM:306955]: A disorder characterized by congenital developmental
CC abnormalities involving structures of the heart. Common defects include
CC transposition of the great arteries, aortic stenosis, atrial septal
CC defect, ventricular septal defect, pulmonic stenosis, and patent ductus
CC arteriosus. The etiology of CHTD is complex, with contributions from
CC environmental exposure, chromosomal abnormalities, and gene defects.
CC Some patients with CHTD also have cardiac arrhythmias, which may be due
CC to the anatomic defect itself or to surgical interventions.
CC {ECO:0000269|PubMed:14681828, ECO:0000269|PubMed:17764085,
CC ECO:0000269|PubMed:24123890}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the GLI C2H2-type zinc-finger protein family.
CC {ECO:0000305}.
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DR EMBL; AF028706; AAC05594.1; -; mRNA.
DR EMBL; EU532020; ACB30403.1; -; mRNA.
DR EMBL; AL035443; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC113393; AAI13394.1; -; mRNA.
DR EMBL; BC113395; AAI13396.1; -; mRNA.
DR CCDS; CCDS14663.1; -. [O60481-1]
DR CCDS; CCDS83494.1; -. [O60481-2]
DR RefSeq; NP_001317590.1; NM_001330661.1. [O60481-2]
DR RefSeq; NP_003404.1; NM_003413.3. [O60481-1]
DR PDB; 2EJ4; NMR; -; A=245-326.
DR PDB; 2RPC; NMR; -; A=245-386.
DR PDBsum; 2EJ4; -.
DR PDBsum; 2RPC; -.
DR AlphaFoldDB; O60481; -.
DR SMR; O60481; -.
DR BioGRID; 113379; 51.
DR IntAct; O60481; 18.
DR STRING; 9606.ENSP00000287538; -.
DR iPTMnet; O60481; -.
DR PhosphoSitePlus; O60481; -.
DR BioMuta; ZIC3; -.
DR EPD; O60481; -.
DR jPOST; O60481; -.
DR MassIVE; O60481; -.
DR MaxQB; O60481; -.
DR PaxDb; O60481; -.
DR PeptideAtlas; O60481; -.
DR PRIDE; O60481; -.
DR ProteomicsDB; 49422; -. [O60481-1]
DR ProteomicsDB; 49423; -. [O60481-2]
DR Antibodypedia; 30470; 282 antibodies from 32 providers.
DR DNASU; 7547; -.
DR Ensembl; ENST00000287538.10; ENSP00000287538.5; ENSG00000156925.12. [O60481-1]
DR Ensembl; ENST00000370606.3; ENSP00000359638.3; ENSG00000156925.12. [O60481-2]
DR GeneID; 7547; -.
DR KEGG; hsa:7547; -.
DR MANE-Select; ENST00000287538.10; ENSP00000287538.5; NM_003413.4; NP_003404.1.
DR UCSC; uc004fak.4; human. [O60481-1]
DR CTD; 7547; -.
DR DisGeNET; 7547; -.
DR GeneCards; ZIC3; -.
DR HGNC; HGNC:12874; ZIC3.
DR HPA; ENSG00000156925; Tissue enhanced (brain, choroid plexus, retina).
DR MalaCards; ZIC3; -.
DR MIM; 300265; gene.
DR MIM; 306955; phenotype.
DR MIM; 314390; phenotype.
DR neXtProt; NX_O60481; -.
DR OpenTargets; ENSG00000156925; -.
DR Orphanet; 216718; Isolated congenitally uncorrected transposition of the great arteries.
DR Orphanet; 157769; Situs ambiguus.
DR PharmGKB; PA37463; -.
DR VEuPathDB; HostDB:ENSG00000156925; -.
DR eggNOG; KOG1721; Eukaryota.
DR GeneTree; ENSGT00940000160788; -.
DR HOGENOM; CLU_002678_37_1_1; -.
DR InParanoid; O60481; -.
DR OMA; PRHHDIG; -.
DR OrthoDB; 768287at2759; -.
DR PhylomeDB; O60481; -.
DR TreeFam; TF351425; -.
DR PathwayCommons; O60481; -.
DR Reactome; R-HSA-2892247; POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation.
DR Reactome; R-HSA-452723; Transcriptional regulation of pluripotent stem cells.
DR SignaLink; O60481; -.
DR SIGNOR; O60481; -.
DR BioGRID-ORCS; 7547; 7 hits in 715 CRISPR screens.
DR EvolutionaryTrace; O60481; -.
DR GeneWiki; ZIC3; -.
DR GenomeRNAi; 7547; -.
DR Pharos; O60481; Tbio.
DR PRO; PR:O60481; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; O60481; protein.
DR Bgee; ENSG00000156925; Expressed in right hemisphere of cerebellum and 54 other tissues.
DR Genevisible; O60481; HS.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; ISS: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:0043565; F:sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0003713; F:transcription coactivator activity; IEA:Ensembl.
DR GO; GO:0003228; P:atrial cardiac muscle tissue development; IEA:Ensembl.
DR GO; GO:0048318; P:axial mesoderm development; IEA:Ensembl.
DR GO; GO:0007417; P:central nervous system development; IBA:GO_Central.
DR GO; GO:0035283; P:central nervous system segmentation; IEA:Ensembl.
DR GO; GO:1904888; P:cranial skeletal system development; IEA:Ensembl.
DR GO; GO:0071907; P:determination of digestive tract left/right asymmetry; IMP:BHF-UCL.
DR GO; GO:0035545; P:determination of left/right asymmetry in nervous system; IEA:Ensembl.
DR GO; GO:0007368; P:determination of left/right symmetry; IMP:BHF-UCL.
DR GO; GO:0071910; P:determination of liver left/right asymmetry; IMP:BHF-UCL.
DR GO; GO:0035469; P:determination of pancreatic left/right asymmetry; IMP:BHF-UCL.
DR GO; GO:0009880; P:embryonic pattern specification; IEA:Ensembl.
DR GO; GO:0060324; P:face development; IEA:Ensembl.
DR GO; GO:0030718; P:germ-line stem cell population maintenance; IEA:Ensembl.
DR GO; GO:0001947; P:heart looping; IMP:BHF-UCL.
DR GO; GO:0021766; P:hippocampus development; IEA:Ensembl.
DR GO; GO:0070986; P:left/right axis specification; IEA:Ensembl.
DR GO; GO:0035108; P:limb morphogenesis; IEA:Ensembl.
DR GO; GO:0030324; P:lung development; IMP:BHF-UCL.
DR GO; GO:0042789; P:mRNA transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0001840; P:neural plate development; IEA:Ensembl.
DR GO; GO:0030182; P:neuron differentiation; IEA:Ensembl.
DR GO; GO:0021772; P:olfactory bulb development; IEA:Ensembl.
DR GO; GO:0042473; P:outer ear morphogenesis; IEA:Ensembl.
DR GO; GO:0048339; P:paraxial mesoderm development; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0090009; P:primitive streak formation; IEA:Ensembl.
DR GO; GO:0051090; P:regulation of DNA-binding transcription factor activity; IEA:Ensembl.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0001501; P:skeletal system development; IEA:Ensembl.
DR GO; GO:0007224; P:smoothened signaling pathway; IEA:Ensembl.
DR GO; GO:0048863; P:stem cell differentiation; IEA:Ensembl.
DR InterPro; IPR036236; Znf_C2H2_sf.
DR InterPro; IPR013087; Znf_C2H2_type.
DR InterPro; IPR041643; Znf_ZIC.
DR Pfam; PF00096; zf-C2H2; 4.
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 3D-structure; Activator; Alternative splicing; Cytoplasm;
KW Developmental protein; Differentiation; Disease variant; DNA-binding;
KW Heterotaxy; Isopeptide bond; Metal-binding; Neurogenesis; Nucleus;
KW Reference proteome; Repeat; Transcription; Transcription regulation;
KW Triplet repeat expansion; Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..467
FT /note="Zinc finger protein ZIC 3"
FT /id="PRO_0000047250"
FT ZN_FING 251..286
FT /note="C2H2-type 1; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 295..322
FT /note="C2H2-type 2; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 328..352
FT /note="C2H2-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 358..382
FT /note="C2H2-type 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 388..410
FT /note="C2H2-type 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT REGION 66..107
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 404..467
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 297..322
FT /note="Nuclear localization signal"
FT MOTIF 330..352
FT /note="Nuclear localization signal"
FT COMPBIAS 85..99
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 413..459
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CROSSLNK 248
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 409..467
FT /note="VHESQGSDSSPAASSGYESSTPPAIASANSKDTTKTPSAVQTSTSHNPGLPP
FT NFNEWYV -> CCPAWYPGQSLIPDEELDTDVGMQQPALHNTTYPKCRVNAEPTVQEMI
FT Y (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_044010"
FT VARIANT 17
FT /note="G -> C (unknown pathological significance; no effect
FT on its transcriptional activator activity or subcellular
FT localization; dbSNP:rs147232392)"
FT /evidence="ECO:0000269|PubMed:24123890"
FT /id="VAR_071330"
FT VARIANT 46
FT /note="A -> AAA (in VACTERLX)"
FT /evidence="ECO:0000269|PubMed:20452998"
FT /id="VAR_066626"
FT VARIANT 53
FT /note="A -> AA (unknown pathological significance; no
FT effect on its transcriptional activator activity or
FT subcellular localization)"
FT /evidence="ECO:0000269|PubMed:24123890"
FT /id="VAR_071331"
FT VARIANT 109
FT /note="S -> C (in CHTD1; does not affect its
FT transcriptional activator activity; decrease in nuclear
FT localization; dbSNP:rs373628598)"
FT /evidence="ECO:0000269|PubMed:24123890"
FT /id="VAR_071332"
FT VARIANT 217
FT /note="P -> A (in HTX1 and CHTD1; lacks DNA-binding; does
FT not inhibit transcriptional activation and interaction with
FT GLI3; decrease in nuclear localization; dbSNP:rs104894963)"
FT /evidence="ECO:0000269|PubMed:14681828,
FT ECO:0000269|PubMed:16959974, ECO:0000269|PubMed:17764085,
FT ECO:0000269|PubMed:24123890"
FT /id="VAR_025632"
FT VARIANT 253
FT /note="C -> S (in HTX1; increases strongly its cytoplasmic
FT localization; lacks DNA-binding; does not inhibit
FT transcriptional activation and interaction with GLI3;
FT dbSNP:rs104894961)"
FT /evidence="ECO:0000269|PubMed:14681828,
FT ECO:0000269|PubMed:17764085, ECO:0000269|PubMed:18716025"
FT /id="VAR_025633"
FT VARIANT 255
FT /note="W -> G (in HTX1; decreases protein expression and
FT transcriptional activity and increases its cytoplasmic
FT localization; dbSNP:rs122463168)"
FT /evidence="ECO:0000269|PubMed:17295247,
FT ECO:0000269|PubMed:18716025"
FT /id="VAR_042416"
FT VARIANT 286
FT /note="H -> R (in HTX1; inreases weakly its cytoplasmic
FT localization; lacks DNA-binding; does not inhibit
FT transcriptional activation and interaction with GLI3)"
FT /evidence="ECO:0000269|PubMed:17764085,
FT ECO:0000269|PubMed:18716025, ECO:0000269|PubMed:9354794"
FT /id="VAR_025634"
FT VARIANT 318
FT /note="H -> N (in VACTERLX; decrease in transcriptional
FT activator activity; significant decrease in nuclear
FT localization)"
FT /evidence="ECO:0000269|PubMed:24123890"
FT /id="VAR_071333"
FT VARIANT 323
FT /note="T -> M (in HTX1; lacks DNA-binding; does not inhibit
FT transcriptional activation and interaction with GLI3;
FT dbSNP:rs122462165)"
FT /evidence="ECO:0000269|PubMed:17764085,
FT ECO:0000269|PubMed:9354794"
FT /id="VAR_007753"
FT VARIANT 405
FT /note="K -> E (in HTX1; lacks DNA-binding; does not inhibit
FT transcriptional activation and interaction with GLI3;
FT dbSNP:rs104894962)"
FT /evidence="ECO:0000269|PubMed:14681828,
FT ECO:0000269|PubMed:17764085"
FT /id="VAR_025635"
FT VARIANT 447
FT /note="A -> G (in CHTD1; Increase in transcriptional
FT activator activity; decrease in nuclear localization)"
FT /evidence="ECO:0000269|PubMed:24123890"
FT /id="VAR_071334"
FT MUTAGEN 268
FT /note="C->S: Increases weakly its cytoplasmic
FT localization."
FT /evidence="ECO:0000269|PubMed:18716025"
FT MUTAGEN 281
FT /note="H->R: Increases its cytoplasmic localization."
FT /evidence="ECO:0000269|PubMed:18716025"
FT MUTAGEN 304
FT /note="R->M: Increases its cytoplasmic localization."
FT /evidence="ECO:0000269|PubMed:18716025"
FT MUTAGEN 307
FT /note="K->M: Increases its cytoplasmic localization."
FT /evidence="ECO:0000269|PubMed:18716025"
FT MUTAGEN 310
FT /note="K->M: Increases its cytoplasmic localization."
FT /evidence="ECO:0000269|PubMed:18716025"
FT MUTAGEN 312
FT /note="K->M: Increases its cytoplasmic localization."
FT /evidence="ECO:0000269|PubMed:18716025"
FT MUTAGEN 314
FT /note="K->M: Does not increase its cytoplasmic
FT localization."
FT /evidence="ECO:0000269|PubMed:18716025"
FT MUTAGEN 320
FT /note="R->A: Increases its cytoplasmic localization. Does
FT not interact with KPNA1 and KPNA6 and increases strongly
FT its cytoplasmic localization; when associated with A-337;
FT A-341; A-346; A-349 and A-350."
FT /evidence="ECO:0000269|PubMed:18716025"
FT MUTAGEN 326
FT /note="K->M: Does not increase its cytoplasmic
FT localization."
FT /evidence="ECO:0000269|PubMed:18716025"
FT MUTAGEN 337
FT /note="K->A: Increases its cytoplasmic localization. Does
FT not interact with KPNA1 and KPNA6 and increases strongly
FT its cytoplasmic localization; when associated with A-320;
FT A-341; A-346; A-349 and A-350."
FT /evidence="ECO:0000269|PubMed:18716025"
FT MUTAGEN 341
FT /note="R->A: Increases its cytoplasmic localization. Does
FT not interact with KPNA1 and KPNA6 and increases strongly
FT its cytoplasmic localization; when associated with A-320;
FT A-337; A-346; A-349 and A-350."
FT /evidence="ECO:0000269|PubMed:18716025"
FT MUTAGEN 346
FT /note="K->A: Increases its cytoplasmic localization. Does
FT not interact with KPNA1 and KPNA6 and increases strongly
FT its cytoplasmic localization; when associated with A-320;
FT A-337; A-341; A-349 and A-350."
FT /evidence="ECO:0000269|PubMed:18716025"
FT MUTAGEN 349
FT /note="K->A: Increases its cytoplasmic localization. Does
FT not interacts with KPNA1 and KPNA6 and increases strongly
FT its cytoplasmic localization; when associated with A-320;
FT A-337; A-341; A-346 and A-350."
FT /evidence="ECO:0000269|PubMed:18716025"
FT MUTAGEN 350
FT /note="R->A: Increases its cytoplasmic localization. Does
FT not interact with KPNA1 and KPNA6 and increases strongly
FT its cytoplasmic localization; when associated with A-320;
FT A-337; A-341; A-346 and A-349."
FT /evidence="ECO:0000269|PubMed:18716025"
FT MUTAGEN 356
FT /note="K->A: Does not increase its cytoplasmic
FT localization."
FT /evidence="ECO:0000269|PubMed:18716025"
FT STRAND 261..264
FT /evidence="ECO:0007829|PDB:2EJ4"
FT STRAND 272..274
FT /evidence="ECO:0007829|PDB:2RPC"
FT HELIX 275..284
FT /evidence="ECO:0007829|PDB:2EJ4"
FT TURN 285..287
FT /evidence="ECO:0007829|PDB:2EJ4"
FT HELIX 312..323
FT /evidence="ECO:0007829|PDB:2EJ4"
FT STRAND 327..329
FT /evidence="ECO:0007829|PDB:2RPC"
FT TURN 333..335
FT /evidence="ECO:0007829|PDB:2RPC"
FT STRAND 338..340
FT /evidence="ECO:0007829|PDB:2RPC"
FT HELIX 342..349
FT /evidence="ECO:0007829|PDB:2RPC"
FT TURN 350..352
FT /evidence="ECO:0007829|PDB:2RPC"
FT STRAND 369..371
FT /evidence="ECO:0007829|PDB:2RPC"
FT HELIX 372..377
FT /evidence="ECO:0007829|PDB:2RPC"
FT TURN 380..383
FT /evidence="ECO:0007829|PDB:2RPC"
SQ SEQUENCE 467 AA; 50569 MW; 3150CF13C0679568 CRC64;
MTMLLDGGPQ FPGLGVGSFG APRHHEMPNR EPAGMGLNPF GDSTHAAAAA AAAAAFKLSP
AAAHDLSSGQ SSAFTPQGSG YANALGHHHH HHHHHHHTSQ VPSYGGAASA AFNSTREFLF
RQRSSGLSEA ASGGGQHGLF AGSASSLHAP AGIPEPPSYL LFPGLHEQGA GHPSPTGHVD
NNQVHLGLRG ELFGRADPYR PVASPRTDPY AAGAQFPNYS PMNMNMGVNV AAHHGPGAFF
RYMRQPIKQE LSCKWIDEAQ LSRPKKSCDR TFSTMHELVT HVTMEHVGGP EQNNHVCYWE
ECPREGKSFK AKYKLVNHIR VHTGEKPFPC PFPGCGKIFA RSENLKIHKR THTGEKPFKC
EFEGCDRRFA NSSDRKKHMH VHTSDKPYIC KVCDKSYTHP SSLRKHMKVH ESQGSDSSPA
ASSGYESSTP PAIASANSKD TTKTPSAVQT STSHNPGLPP NFNEWYV
