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Protein

Zinc finger protein ZIC 3

Gene

Zic3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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'.3 Publications

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri250 – 28536C2H2-type 1; atypicalPROSITE-ProRule annotationAdd
BLAST
Zinc fingeri294 – 32128C2H2-type 2; atypicalPROSITE-ProRule annotationAdd
BLAST
Zinc fingeri327 – 35125C2H2-type 3PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri357 – 38125C2H2-type 4PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri387 – 40923C2H2-type 5PROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  1. metal ion binding Source: UniProtKB-KW
  2. RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: NTNU_SB
  3. RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription Source: NTNU_SB
  4. sequence-specific DNA binding Source: UniProtKB
  5. sequence-specific DNA binding transcription factor activity Source: UniProtKB

GO - Biological processi

  1. anterior/posterior pattern specification Source: MGI
  2. cell differentiation Source: UniProtKB-KW
  3. determination of digestive tract left/right asymmetry Source: MGI
  4. determination of left/right asymmetry in nervous system Source: UniProtKB
  5. determination of left/right symmetry Source: MGI
  6. determination of liver left/right asymmetry Source: MGI
  7. determination of pancreatic left/right asymmetry Source: MGI
  8. heart looping Source: MGI
  9. lung development Source: MGI
  10. pattern specification process Source: MGI
  11. positive regulation of transcription, DNA-templated Source: UniProtKB
  12. positive regulation of transcription from RNA polymerase II promoter Source: NTNU_SB
Complete GO annotation...

Keywords - Molecular functioni

Activator, Developmental protein

Keywords - Biological processi

Differentiation, Neurogenesis, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
Zinc finger protein ZIC 3
Alternative name(s):
Zinc finger protein of the cerebellum 3
Gene namesi
Name:Zic3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome X

Organism-specific databases

MGIiMGI:106676. Zic3.

Subcellular locationi

Nucleus 1 Publication. Cytoplasm 1 Publication
Note: Translocation to the nucleus requires KPNA1 or KPNA6 (By similarity). Localizes in the cytoplasm in presence of MDFIC overexpression.By similarity

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Disruption phenotypei

Some mice exhibit embryonic and postnatal lethality. Viable mice show heart disease, disturbances of laterality, neural tube defects and vertebral and rib defects.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 466466Zinc finger protein ZIC 3PRO_0000047251Add
BLAST

Proteomic databases

PRIDEiQ62521.

Expressioni

Tissue specificityi

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

Developmental stagei

Expressed in the CNS, tailbud and somites.1 Publication

Gene expression databases

BgeeiQ62521.
CleanExiMM_ZIC3.
ExpressionAtlasiQ62521. baseline and differential.
GenevestigatoriQ62521.

Interactioni

Subunit structurei

Interacts with KPNA1 and KPNA6. Interacts (via C2H2-type domains 3, 4 and 5) with GLI3; the interaction enhances its transcriptional activity (By similarity). 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 similarity1 Publication

Protein-protein interaction databases

BioGridi204696. 1 interaction.
IntActiQ62521. 2 interactions.
MINTiMINT-190020.
STRINGi10090.ENSMUSP00000085999.

Structurei

3D structure databases

ProteinModelPortaliQ62521.
SMRiQ62521. Positions 244-424.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi296 – 32126Nuclear localization signalBy similarityAdd
BLAST
Motifi329 – 35123Nuclear localization signalBy similarityAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi46 – 5510Poly-Ala
Compositional biasi87 – 9610Poly-His

Domaini

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

Sequence similaritiesi

Contains 5 C2H2-type zinc fingers.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri250 – 28536C2H2-type 1; atypicalPROSITE-ProRule annotationAdd
BLAST
Zinc fingeri294 – 32128C2H2-type 2; atypicalPROSITE-ProRule annotationAdd
BLAST
Zinc fingeri327 – 35125C2H2-type 3PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri357 – 38125C2H2-type 4PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri387 – 40923C2H2-type 5PROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiCOG5048.
GeneTreeiENSGT00760000118771.
HOGENOMiHOG000232057.
HOVERGENiHBG007135.
InParanoidiQ62521.
KOiK18487.
OMAiKKTCDRT.
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. 1 hit.
[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]

Sequences (2)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: Q62521-1) [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 ATAHDLSSGQ SSAFTPQGSG YANALGHHHH HHHHHHASQV
110 120 130 140 150
PTYGGAASAA FNSTRDFLFR QRGSGLSEAA SGGGQHGLFA GSASSLHAPA
160 170 180 190 200
GIPEPPSYLL FPGLHEQGAG HPSPTGHVDN NQVHLGLRGE LFGRADPYRP
210 220 230 240 250
VASPRTDPYA ASAQFPNYSP MNMNMGVNVA AHHGPGAFFR YMRQPIKQEL
260 270 280 290 300
SCKWIEEAQL SRPKKSCDRT FSTMHELVTH VTMEHVGGPE QNNHVCYWEE
310 320 330 340 350
CPREGKSFKA KYKLVNHIRV HTGEKPFPCP FPGCGKIFAR SENLKIHKRT
360 370 380 390 400
HTGEKPFKCE FEGCDRRFAN SSDRKKHMHV HTSDKPYICK VCDKSYTHPS
410 420 430 440 450
SLRKHMKVHE SQGSDSSPAA SSGYESSTPP AIASANSKDT TKTPSAVQTS
460
TSHNPGLPPN FNEWYV
Length:466
Mass (Da):50,446
Last modified:July 27, 2011 - v2
Checksum:iC92C06EC06DF601A
GO
Isoform 2 (identifier: Q62521-2) [UniParc]FASTAAdd to basket

Also known as: Zic3-B

The sequence of this isoform differs from the canonical sequence as follows:
     408-466: VHESQGSDSS...LPPNFNEWYV → CCPAWYLGQS...AEPTVQEMIY

Show »
Length:456
Mass (Da):49,952
Checksum:iBD0ECE4D3780FBAA
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti104 – 1063GGA → ARR in BAA11116 (PubMed:8557628).Curated
Isoform 2 (identifier: Q62521-2)
Sequence conflicti419 – 4191I → V in BAC28831 (PubMed:16141072).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei408 – 46659VHESQ…NEWYV → CCPAWYLGQSLIPDEELDTD VGMQQPVLHNTSYPKCRVNA EPTVQEMIY in isoform 2. 1 PublicationVSP_044011Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D70849 mRNA. Translation: BAA11116.1.
AK134355 mRNA. Translation: BAE22110.1.
AK034780 mRNA. Translation: BAC28831.1.
AL954389 Genomic DNA. Translation: CAM20753.1.
AL954389, AL671920 Genomic DNA. Translation: CAM20751.1.
AL671920, AL954389 Genomic DNA. Translation: CAM24569.1.
CH466583 Genomic DNA. Translation: EDL42177.1.
CH466583 Genomic DNA. Translation: EDL42178.1.
CCDSiCCDS30155.1. [Q62521-1]
RefSeqiNP_033601.2. NM_009575.2. [Q62521-1]
UniGeneiMm.255890.

Genome annotation databases

EnsembliENSMUST00000088627; ENSMUSP00000085999; ENSMUSG00000067860. [Q62521-1]
ENSMUST00000088629; ENSMUSP00000086001; ENSMUSG00000067860. [Q62521-2]
GeneIDi22773.
KEGGimmu:22773.
UCSCiuc009tho.1. mouse. [Q62521-1]
uc009thp.1. mouse.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D70849 mRNA. Translation: BAA11116.1.
AK134355 mRNA. Translation: BAE22110.1.
AK034780 mRNA. Translation: BAC28831.1.
AL954389 Genomic DNA. Translation: CAM20753.1.
AL954389, AL671920 Genomic DNA. Translation: CAM20751.1.
AL671920, AL954389 Genomic DNA. Translation: CAM24569.1.
CH466583 Genomic DNA. Translation: EDL42177.1.
CH466583 Genomic DNA. Translation: EDL42178.1.
CCDSiCCDS30155.1. [Q62521-1]
RefSeqiNP_033601.2. NM_009575.2. [Q62521-1]
UniGeneiMm.255890.

3D structure databases

ProteinModelPortaliQ62521.
SMRiQ62521. Positions 244-424.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi204696. 1 interaction.
IntActiQ62521. 2 interactions.
MINTiMINT-190020.
STRINGi10090.ENSMUSP00000085999.

Proteomic databases

PRIDEiQ62521.

Protocols and materials databases

DNASUi22773.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000088627; ENSMUSP00000085999; ENSMUSG00000067860. [Q62521-1]
ENSMUST00000088629; ENSMUSP00000086001; ENSMUSG00000067860. [Q62521-2]
GeneIDi22773.
KEGGimmu:22773.
UCSCiuc009tho.1. mouse. [Q62521-1]
uc009thp.1. mouse.

Organism-specific databases

CTDi7547.
MGIiMGI:106676. Zic3.

Phylogenomic databases

eggNOGiCOG5048.
GeneTreeiENSGT00760000118771.
HOGENOMiHOG000232057.
HOVERGENiHBG007135.
InParanoidiQ62521.
KOiK18487.
OMAiKKTCDRT.
TreeFamiTF351425.

Miscellaneous databases

ChiTaRSiZic3. mouse.
NextBioi303317.
PROiQ62521.
SOURCEiSearch...

Gene expression databases

BgeeiQ62521.
CleanExiMM_ZIC3.
ExpressionAtlasiQ62521. baseline and differential.
GenevestigatoriQ62521.

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. 1 hit.
[Graphical view]
SMARTiSM00355. ZnF_C2H2. 5 hits.
[Graphical view]
PROSITEiPS00028. ZINC_FINGER_C2H2_1. 3 hits.
PS50157. ZINC_FINGER_C2H2_2. 4 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "The mouse zic gene family. Homologues of the Drosophila pair-rule gene odd-paired."
    Aruga J., Nagai T., Tokuyama T., Hayashizaki Y., Okazaki Y., Chapman V.M., Mikoshiba K.
    J. Biol. Chem. 271:1043-1047(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Tissue: Cerebellum.
  2. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
    Strain: C57BL/6J.
    Tissue: Embryo and Testis.
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  4. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
    Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. "Molecular properties of Zic proteins as transcriptional regulators and their relationship to GLI proteins."
    Mizugishi K., Aruga J., Nakata K., Mikoshiba K.
    J. Biol. Chem. 276:2180-2188(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DNA-BINDING.
  6. "Physical and functional interactions between Zic and Gli proteins."
    Koyabu Y., Nakata K., Mizugishi K., Aruga J., Mikoshiba K.
    J. Biol. Chem. 276:6889-6892(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.
  7. "A complex syndrome of left-right axis, central nervous system and axial skeleton defects in Zic3 mutant mice."
    Purandare S.M., Ware S.M., Kwan K.M., Gebbia M., Bassi M.T., Deng J.M., Vogel H., Behringer R.R., Belmont J.W., Casey B.
    Development 129:2293-2302(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE, DEVELOPMENTAL STAGE.
  8. "Myogenic repressor I-mfa interferes with the function of Zic family proteins."
    Mizugishi K., Hatayama M., Tohmonda T., Ogawa M., Inoue T., Mikoshiba K., Aruga J.
    Biochem. Biophys. Res. Commun. 320:233-240(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH MDFIC.
  9. "Identification of a novel ZIC3 isoform and mutation screening in patients with heterotaxy and congenital heart disease."
    Bedard J.E., Haaning A.M., Ware S.M.
    PLoS ONE 6:E23755-E23755(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: ALTERNATIVE SPLICING.

Entry informationi

Entry nameiZIC3_MOUSE
AccessioniPrimary (citable) accession number: Q62521
Secondary accession number(s): A2AWK3, Q3UYV1, Q8BSB3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: July 27, 2011
Last modified: April 1, 2015
This is version 131 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.