P46684 (ZIC1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Zinc finger protein ZIC 1

Alternative name(s):
Zinc finger protein of the cerebellum 1

Gene names

Name:	Zic1
Synonyms:	Zic

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	447 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Acts as a transcriptional activator. Involved in neurogenesis. Plays important roles in the early stage of organogenesis of the CNS, as well as during dorsal spinal cord development and maturation of the cerebellum. Involved in the spatial distribution of mossy fiber (MF) neurons within the pontine gray nucleus (PGN). Plays a role in the regulation of MF axon pathway choice. Promotes MF migration towards ipsilaterally-located cerebellar territories. May have a role in shear flow mechanotransduction in osteocytes. Retains nuclear GLI1 and GLI3 in the cytoplasm. Binds to the minimal GLI-consensus sequence 5'-TGGGTGGTC-3'. Ref.1 Ref.5 Ref.6 Ref.7 Ref.8 Ref.9 Ref.10
Subunit structure	Interacts (via the C2H2-type domains 3, 4 and 5) with MDFIC (via the C2H2-type domains 3, 4 and 5). Interacts with GLI1; the interaction enhances transcription activation. Interacts with GLI2. Interacts with GLI3; the interaction enhances transcription activation. Ref.6 Ref.8
Subcellular location	Nucleus. Cytoplasm. Note: Localizes in the cytoplasm in presence of MDFIC overexpression. Ref.6 Ref.8 Ref.10
Tissue specificity	Expressed in osteoblasts (at protein level). Expressed in the CNS. A high level expression is seen in the cerebellum, while a low level expression is seen in the olfactory bulb, diencephalon, and brainstem. Expressed in lumbar spine and iliac crest. Ref.1 Ref.9 Ref.10
Developmental stage	Expressed in progenitor cells in the dorsal third of the ventricular zone at 12.5 dpc. Expressed in newly emerging pontine gray nucleus (PGN) precursor cells of the extramural migratory stream (ems) between 12.5 and 14.5 dpc. Expressed in precerebellar mossy fiber (MF) neurons of the PGN (located either rostromedially or caudolaterally) persisted through at least P8 after birth (at protein level). In the early embryonic stage, it is expressed in the dorsal half of the neural tube and adjacent mesenchyme, and in the developing cerebellum it is expressed persistently in the granule cell lineage throughout the prenatal and postnatal periods. Ref.1 Ref.7
Domain	The C2H2-type 3, 4 and 5 zinc finger domains are necessary for transcription activation.
Disruption phenotype	Mice show a cell mass decrease of the spinal dorsal horn, hypoplasia and abnormal foliation patterns in the cerebelum. 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
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	behavior Inferred from mutant phenotype. Source: MGI brain development Inferred from direct assay Ref.1. Source: UniProtKB cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW inner ear morphogenesis Inferred from sequence or structural similarity. Source: UniProtKB pattern specification process Inferred from direct assay. Source: UniProtKB positive regulation of protein import into nucleus Inferred from direct assay Ref.6. Source: UniProtKB positive regulation of transcription, DNA-dependent Inferred from direct assay Ref.5Ref.6. Source: UniProtKB regulation of smoothened signaling pathway Inferred from physical interaction Ref.6. Source: UniProtKB skeletal system development Non-traceable author statement Ref.6. Source: UniProtKB spinal cord development Inferred from mutant phenotype Ref.7. Source: UniProtKB 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	DNA binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction Ref.6Ref.8. 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...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
GLI1	P08151	2	EBI-308006,EBI-308084	From a different organism.
Gli2	Q8K0K3	2	EBI-308006,EBI-308039
GLI3	P10071	2	EBI-308006,EBI-308055	From a different organism.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 447	447	Zinc finger protein ZIC 1		PRO_0000047245
Regions
	Zinc finger	225 – 260	36	C2H2-type 1; atypical
	Zinc finger	269 – 296	28	C2H2-type 2; atypical
	Zinc finger	302 – 326	25	C2H2-type 3
	Zinc finger	332 – 356	25	C2H2-type 4
	Zinc finger	362 – 384	23	C2H2-type 5
	Compositional bias	73 – 76	4	Poly-Ala
	Compositional bias	79 – 82	4	Poly-His
	Compositional bias	110 – 116	7	Poly-Ala
	Compositional bias	386 – 440	55	Ser-rich
Experimental info
	Sequence conflict	72	1	A → R in BAA06878. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P46684 [UniParc]. Last modified July 27, 2011. Version 2. Checksum: D41F412F44C2AD3D	FASTA	447	48,331
	10 20 30 40 50 60 MLLDAGPQYP AIGVTTFGAS RHHSAGDVAE RDVGLGINPF ADGMGAFKLN PSSHELASAG 70 80 90 100 110 120 QTAFTSQAPG YAAAAALGHH HHPGHVGSYS SAAFNSTRDF LFRNRGFGDA AAAASAQHSL 130 140 150 160 170 180 FAASAGGFGG PHGHTDAAGH LLFSGLHEQA AGHASPNVVN GQMRLGFSGD MYPRPEQYGQ 190 200 210 220 230 240 VTSPRSEHYA APQLHGYGPM NVNMAAHHGA GAFFRYMRQP IKQELICKWI EPEQLANPKK 250 260 270 280 290 300 SCNKTFSTMH ELVTHVTVEH VGGPEQSNHI CFWEECPREG KPFKAKYKLV NHIRVHTGEK 310 320 330 340 350 360 PFPCPFPGCG KVFARSENLK IHKRTHTGEK PFKCEFEGCD RRFANSSDRK KHMHVHTSDK 370 380 390 400 410 420 PYLCKMCDKS YTHPSSLRKH MKVHESSSQG SQPSPAASSG YESSTPPTIV SPTTDNPTTS 430 440 SMSPSSSAVH HTAGHSALSS NFNEWYV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A novel zinc finger protein, zic, is involved in neurogenesis, especially in the cell lineage of cerebellar granule cells." Aruga J., Yokota N., Hashimoto M., Furuichi T., Fukuda M., Mikoshiba K. J. Neurochem. 63:1880-1890(1994) [PubMed: 7931345] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE. Strain: ICR. 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: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Embryo.
[3]	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].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6. Tissue: Brain.
[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: 11053430] [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: 11238441] [Abstract] Cited for: FUNCTION, INTERACTION WITH GLI1; GLI2 AND GLI3, SUBCELLULAR LOCATION.
[7]	"Zic1 promotes the expansion of dorsal neural progenitors in spinal cord by inhibiting neuronal differentiation." Aruga J., Tohmonda T., Homma S., Mikoshiba K. Dev. Biol. 244:329-341(2002) [PubMed: 11944941] [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: 15207726] [Abstract] Cited for: FUNCTION, INTERACTION WITH MDFIC, SUBCELLULAR LOCATION.
[9]	"Zic1 levels regulate mossy fiber neuron position and axon laterality choice in the ventral brain stem." Dipietrantonio H.J., Dymecki S.M. Neuroscience 162:560-573(2009) [PubMed: 19303920] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY.
[10]	"Zic1 transcription factor in bone: neural developmental protein regulates mechanotransduction in osteocytes." Kalogeropoulos M., Varanasi S.S., Olstad O.K., Sanderson P., Gautvik V.T., Reppe S., Francis R.M., Gautvik K.M., Birch M.A., Datta H.K. FASEB J. 24:2893-2903(2010) [PubMed: 20354137] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	D32167 mRNA. Translation: BAA06878.1. AK136977 mRNA. Translation: BAE23194.1. CH466560 Genomic DNA. Translation: EDL20910.1. BC050889 mRNA. Translation: AAH50889.2. BC060247 mRNA. Translation: AAH60247.1. BC063247 mRNA. Translation: AAH63247.1.
IPI	IPI00136023.
PIR	I56511.
RefSeq	NP_033599.2. NM_009573.3.
UniGene	Mm.335350. Mm.477226.
3D structure databases
ProteinModelPortal	P46684.
SMR	P46684. Positions 179-386.
ModBase	Search...
Protein-protein interaction databases
IntAct	P46684. 3 interactions.
MINT	MINT-189851.
STRING	P46684.
Proteomic databases
PRIDE	P46684.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000034927; ENSMUSP00000034927; ENSMUSG00000032368. ENSMUST00000065360; ENSMUSP00000068858; ENSMUSG00000032368.
GeneID	22771.
KEGG	mmu:22771.
Organism-specific databases
CTD	7545.
MGI	MGI:106683. Zic1.
Phylogenomic databases
eggNOG	roNOG12630.
GeneTree	ENSGT00600000084058.
HOGENOM	HBG506538.
HOVERGEN	HBG007135.
InParanoid	P46684.
OrthoDB	EOG4S4PG5.
Gene expression databases
ArrayExpress	P46684.
Bgee	P46684.
CleanEx	MM_ZIC1.
Genevestigator	P46684.
GermOnline	ENSMUSG00000032368. Mus musculus.
Family and domain databases
InterPro	IPR007087. Znf_C2H2. IPR015880. Znf_C2H2-like. IPR013087. Znf_C2H2/integrase_DNA-bd. [Graphical view]
Gene3D	G3DSA:3.30.160.60. Znf_C2H2/integrase_DNA-bd. 4 hits.
KO	K09224.
Pfam	PF00096. zf-C2H2. 4 hits. [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
SOURCE	Search...

Entry information

Entry name

ZIC1_MOUSE

Accession

Primary (citable) accession number: P46684
Secondary accession number(s): Q6PAK5, Q80Y18

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	July 27, 2011
Last modified:	December 14, 2011
This is version 98 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program