Q62521 (ZIC3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Zinc finger protein ZIC 3

Alternative name(s):
Zinc finger protein of the cerebellum 3

Gene names

Name:

Zic3

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	466 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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'. Ref.5 Ref.7 Ref.8
Subunit structure	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. Ref.8
Subcellular location	Nucleus. Cytoplasm. Note: Translocation to the nucleus requires KPNA1 or KPNA6 By similarity. Localizes in the cytoplasm in presence of MDFIC overexpression. Ref.6
Tissue specificity	CNS. A high level expression is seen in the cerebellum.
Developmental stage	Expressed in the CNS, tailbud and somites. Ref.7
Domain	The C2H2-type 3, 4 and 5 zinc finger domains are necessary for transcription activation.
Disruption phenotype	Some mice exhibit embryonic and postnatal lethality. Viable mice show heart disease, disturbances of laterality, neural tube defects and vertebral and rib defects. Ref.7
Sequence similarities	Belongs to the GLI C2H2-type zinc-finger protein family. Contains 5 C2H2-type zinc fingers.

Ontologies

Keywords
Biological process	Differentiation Neurogenesis Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Domain	Repeat Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Activator Developmental protein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	anterior/posterior pattern specification Inferred from genetic interaction PubMed 16496285. Source: MGI cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW determination of left/right asymmetry in nervous system Inferred from mutant phenotype Ref.7. Source: UniProtKB heart looping Inferred from mutant phenotype PubMed 16496285. Source: MGI positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 16496285. Source: MGI transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytoplasm Inferred from direct assay Ref.8. Source: UniProtKB nucleus Inferred from direct assay Ref.6Ref.8. Source: UniProtKB
Molecular_function	sequence-specific DNA binding Inferred from sequence or structural similarity. Source: UniProtKB sequence-specific DNA binding transcription factor activity Inferred from direct assay Ref.5. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q62521-1)

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.

Isoform 2 (identifier: Q62521-2)

Also known as: Zic3-B;

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

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 466	466	Zinc finger protein ZIC 3		PRO_0000047251
Regions
	Zinc finger	250 – 285	36	C2H2-type 1; atypical
	Zinc finger	294 – 321	28	C2H2-type 2; atypical
	Zinc finger	327 – 351	25	C2H2-type 3
	Zinc finger	357 – 381	25	C2H2-type 4
	Zinc finger	387 – 409	23	C2H2-type 5
	Region	296 – 321	26	Nuclear localization signal By similarity
	Region	329 – 351	23	Nuclear localization signal By similarity
	Compositional bias	46 – 55	10	Poly-Ala
	Compositional bias	87 – 96	10	Poly-His
Natural variations
	Alternative sequence	408 – 466	59	VHESQ…NEWYV → CCPAWYLGQSLIPDEELDTD VGMQQPVLHNTSYPKCRVNA EPTVQEMIY in isoform 2.		VSP_044011
Experimental info
	Sequence conflict	104 – 106	3	GGA → ARR in BAA11116. Ref.1
Isoform 2:
	Sequence conflict	419	1	I → V in BAC28831. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Zic3-A) [UniParc]. Last modified July 27, 2011. Version 2. Checksum: C92C06EC06DF601A	FASTA	466	50,446
	10 20 30 40 50 60 MTMLLDGGPQ FPGLGVGSFG APRHHEMPNR EPAGMGLNPF GDSTHAAAAA AAAAAFKLSP 70 80 90 100 110 120 ATAHDLSSGQ SSAFTPQGSG YANALGHHHH HHHHHHASQV PTYGGAASAA FNSTRDFLFR 130 140 150 160 170 180 QRGSGLSEAA SGGGQHGLFA GSASSLHAPA GIPEPPSYLL FPGLHEQGAG HPSPTGHVDN 190 200 210 220 230 240 NQVHLGLRGE LFGRADPYRP VASPRTDPYA ASAQFPNYSP MNMNMGVNVA AHHGPGAFFR 250 260 270 280 290 300 YMRQPIKQEL SCKWIEEAQL SRPKKSCDRT FSTMHELVTH VTMEHVGGPE QNNHVCYWEE 310 320 330 340 350 360 CPREGKSFKA KYKLVNHIRV HTGEKPFPCP FPGCGKIFAR SENLKIHKRT HTGEKPFKCE 370 380 390 400 410 420 FEGCDRRFAN SSDRKKHMHV HTSDKPYICK VCDKSYTHPS SLRKHMKVHE SQGSDSSPAA 430 440 450 460 SSGYESSTPP AIASANSKDT TKTPSAVQTS TSHNPGLPPN FNEWYV
	Isoform 2 (Zic3-B) [UniParc]. Checksum: BD0ECE4D3780FBAA	FASTA	456	49,952
	10 20 30 40 50 60 MTMLLDGGPQ FPGLGVGSFG APRHHEMPNR EPAGMGLNPF GDSTHAAAAA AAAAAFKLSP 70 80 90 100 110 120 ATAHDLSSGQ SSAFTPQGSG YANALGHHHH HHHHHHASQV PTYGGAASAA FNSTRDFLFR 130 140 150 160 170 180 QRGSGLSEAA SGGGQHGLFA GSASSLHAPA GIPEPPSYLL FPGLHEQGAG HPSPTGHVDN 190 200 210 220 230 240 NQVHLGLRGE LFGRADPYRP VASPRTDPYA ASAQFPNYSP MNMNMGVNVA AHHGPGAFFR 250 260 270 280 290 300 YMRQPIKQEL SCKWIEEAQL SRPKKSCDRT FSTMHELVTH VTMEHVGGPE QNNHVCYWEE 310 320 330 340 350 360 CPREGKSFKA KYKLVNHIRV HTGEKPFPCP FPGCGKIFAR SENLKIHKRT HTGEKPFKCE 370 380 390 400 410 420 FEGCDRRFAN SSDRKKHMHV HTSDKPYICK VCDKSYTHPS SLRKHMKCCP AWYLGQSLIP 430 440 450 DEELDTDVGM QQPVLHNTSY PKCRVNAEPT VQEMIY

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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(1996) [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(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Strain: C57BL/6J. Tissue: Embryo and Testis.
[3]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract] 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 (JUL-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(2001) [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(2001) [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(2002) [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(2004) [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(2011) [PubMed] [Europe PMC] [Abstract] Cited for: ALTERNATIVE SPLICING.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	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.
IPI	IPI00127146. IPI00404620.
RefSeq	NP_033601.2. NM_009575.2.
UniGene	Mm.255890.
3D structure databases
ProteinModelPortal	Q62521.
SMR	Q62521. Positions 244-409.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q62521. 1 interaction.
MINT	MINT-190020.
STRING	10090.ENSMUSP00000085999.
Proteomic databases
PRIDE	Q62521.
Protocols and materials databases
DNASU	22773.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000088627; ENSMUSP00000085999; ENSMUSG00000067860. ENSMUST00000088629; ENSMUSP00000086001; ENSMUSG00000067860.
GeneID	22773.
KEGG	mmu:22773.
Organism-specific databases
CTD	7547.
MGI	MGI:106676. Zic3.
Phylogenomic databases
eggNOG	COG5048.
GeneTree	ENSGT00650000092933.
HOGENOM	HOG000232057.
HOVERGEN	HBG007135.
InParanoid	Q3UYV1.
KO	K09224.
OrthoDB	EOG4FFD3K.
Gene expression databases
ArrayExpress	Q62521.
Bgee	Q62521.
CleanEx	MM_ZIC3.
Genevestigator	Q62521.
GermOnline	ENSMUSG00000067860. Mus musculus.
Family and domain databases
Gene3D	3.30.160.60. 4 hits.
InterPro	IPR007087. Znf_C2H2. IPR015880. Znf_C2H2-like. IPR013087. Znf_C2H2/integrase_DNA-bd. [Graphical view]
Pfam	PF00096. zf-C2H2. 1 hit. [Graphical view]
SMART	SM00355. ZnF_C2H2. 5 hits. [Graphical view]
PROSITE	PS00028. ZINC_FINGER_C2H2_1. 3 hits. PS50157. ZINC_FINGER_C2H2_2. 4 hits. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	ZIC3. mouse.
NextBio	303317.
SOURCE	Search...

Entry information

Entry name

ZIC3_MOUSE

Accession

Primary (citable) accession number: Q62521
Secondary accession number(s): A2AWK3, Q3UYV1, Q8BSB3

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	July 27, 2011
Last modified:	May 1, 2013
This is version 112 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program