ID ZIC2_HUMAN Reviewed; 532 AA. AC O95409; Q5VYA9; Q9H309; DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot. DT 16-APR-2002, sequence version 2. DT 03-NOV-2009, entry version 90. DE RecName: Full=Zinc finger protein ZIC 2; DE AltName: Full=Zinc finger protein of the cerebellum 2; GN Name=ZIC2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT HPE5 POLY-ALA INSERTION. RX MEDLINE=98442655; PubMed=9771712; DOI=10.1038/2484; RA Brown S.A., Warburton D., Brown L.Y., Yu C.Y., Roeder E.R., RA Stengel-Rutkowski S., Hennekam R.C.M., Muenke M.; RT "Holoprosencephaly due to mutations in ZIC2, a homologue of Drosophila RT odd-paired."; RL Nat. Genet. 20:180-183(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Brain; RX PubMed=10984499; DOI=10.1074/jbc.M007906200; RA Yang Y., Hwang C.K., Junn E., Lee G., Mouradian M.M.; RT "ZIC2 and Sp3 repress Sp1-induced activation of the human D1A dopamine RT receptor gene."; RL J. Biol. Chem. 275:38863-38869(2000). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15057823; DOI=10.1038/nature02379; RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., RA Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E., RA Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T., RA Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R., RA Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S., RA Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., RA Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J., RA Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E., RA Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L., RA Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J., RA Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S., RA Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J., RA Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M., RA King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A., RA Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S., RA Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., RA Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S., RA Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A., RA Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B., RA Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., RA Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M., RA Hubbard T., Sulston J.E., Beck S., Bentley D.R., Rogers J., Ross M.T.; RT "The DNA sequence and analysis of human chromosome 13."; RL Nature 428:522-528(2004). RN [4] RP VARIANTS HPE5 POLY-ALA INSERTION AND PHE-152, AND POLYMORPHISM OF RP POLY-HIS REGION. RX MEDLINE=21181702; PubMed=11285244; DOI=10.1093/hmg/10.8.791; RA Brown L.Y., Odent S., David V., Blayau M., Dubourg C., Apacik C., RA Delgado M.A., Hall B.D., Reynolds J.F., Sommer A., Wieczorek D., RA Brown S.A., Muenke M.; RT "Holoprosencephaly due to mutations in ZIC2: alanine tract expansion RT mutations may be caused by parental somatic recombination."; RL Hum. Mol. Genet. 10:791-796(2001). RN [5] RP VARIANTS HPE5 PRO-36 AND PHE-152, AND VARIANTS HIS-239 INS AND HIS-239 RP DEL. RX PubMed=15221788; DOI=10.1002/humu.20056; RA Dubourg C., Lazaro L., Pasquier L., Bendavid C., Blayau M., RA Le Duff F., Durou M.-R., Odent S., David V.; RT "Molecular screening of SHH, ZIC2, SIX3, and TGIF genes in patients RT with features of holoprosencephaly spectrum: mutation review and RT genotype-phenotype correlations."; RL Hum. Mutat. 24:43-51(2004). RN [6] RP CHARACTERIZATION OF VARIANTS HPE5 PRO-36; PHE-152 AND POLY-ALA INS. RX PubMed=15590697; DOI=10.1093/hmg/ddi037; RA Brown L., Paraso M., Arkell R., Brown S.; RT "In vitro analysis of partial loss-of-function ZIC2 mutations in RT holoprosencephaly: alanine tract expansion modulates DNA binding and RT transactivation."; RL Hum. Mol. Genet. 14:411-420(2005). RN [7] RP VARIANTS HPE5 ASN-37; ASN-128; ASN-272; LEU-286; GLN-286; TYR-286; RP TYR-291; ARG-304; CYS-314; SER-325; LEU-325; TYR-327; PHE-335; RP PRO-373; ASN-402; LYS-403; ARG-404; TRP-409 AND GLN-415. RX PubMed=19177455; DOI=10.1002/humu.20982; RA Roessler E., Lacbawan F., Dubourg C., Paulussen A., Herbergs J., RA Hehr U., Bendavid C., Zhou N., Ouspenskaia M., Bale S., Odent S., RA David V., Muenke M.; RT "The full spectrum of holoprosencephaly-associated mutations within RT the ZIC2 gene in humans predicts loss-of-function as the predominant RT disease mechanism."; RL Hum. Mutat. 30:E541-E554(2009). CC -!- FUNCTION: Involved in cerebellar development (By similarity). CC -!- SUBCELLULAR LOCATION: Nucleus. CC -!- POLYMORPHISM: The poly-His region between amino acids 231-239 of CC ZIC2 is polymorphic and the number of His can vary from 8 to 12. CC -!- DISEASE: Defects in ZIC2 are a cause of holoprosencephaly type 5 CC (HPE5) [MIM:609637]. A structural anomaly of the brain, in which CC the developing forebrain fails to correctly separate into right CC and left hemispheres. Holoprosencephaly is genetically CC heterogeneous and associated with several distinct facies and CC phenotypic variability. Although severe facial anomalies are CC common in HPE, patients with ZINC2 mutations have relatively CC normal faces. CC -!- SIMILARITY: Belongs to the GLI C2H2-type zinc-finger protein CC family. CC -!- SIMILARITY: Contains 5 C2H2-type zinc fingers. CC -!- WEB RESOURCE: Name=GeneReviews; CC URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/ZIC2"; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; AF104902; AAC96325.1; -; mRNA. DR EMBL; AF193855; AAG28409.1; -; mRNA. DR EMBL; AL355338; CAH70367.1; -; Genomic_DNA. DR IPI; IPI00030652; -. DR RefSeq; NP_009060.2; -. DR UniGene; Hs.653700; -. DR HSSP; P08047; 1SP2. DR STRING; O95409; -. DR PhosphoSite; O95409; -. DR PeptideAtlas; O95409; -. DR PRIDE; O95409; -. DR Ensembl; ENST00000376335; ENSP00000365514; ENSG00000043355; Homo sapiens. DR Ensembl; ENST00000397444; ENSP00000380586; ENSG00000043355; Homo sapiens. DR Ensembl; ENST00000425702; ENSP00000403352; ENSG00000043355; Homo sapiens. DR GeneID; 7546; -. DR KEGG; hsa:7546; -. DR UCSC; uc001von.1; human. DR CTD; 7546; -. DR GeneCards; GC13P099432; -. DR HGNC; HGNC:12873; ZIC2. DR MIM; 603073; gene. DR MIM; 609637; phenotype. DR Orphanet; 2162; Holoprosencephaly. DR PharmGKB; PA37462; -. DR HOGENOM; O95409; -. DR HOVERGEN; O95409; -. DR OMA; VSSPRTD; -. DR NextBio; 29525; -. DR ArrayExpress; O95409; -. DR Bgee; O95409; -. DR CleanEx; HS_ZIC2; -. DR Genevestigator; O95409; -. DR GermOnline; ENSG00000043355; Homo sapiens. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell. DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW. DR GO; GO:0008270; F:zinc ion binding; IEA:UniProtKB-KW. DR GO; GO:0007420; P:brain development; TAS:ProtInc. DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW. DR InterPro; IPR007087; Znf_C2H2. DR InterPro; IPR015880; Znf_C2H2-like. DR InterPro; IPR013087; Znf_C2H2/integrase_DNA-bd. DR Gene3D; G3DSA:3.30.160.60; Znf_C2H2/integrase_DNA-bd; 2. DR Pfam; PF00096; zf-C2H2; 3. DR ProDom; PD000003; Znf_C2H2; 1. DR SMART; SM00355; ZnF_C2H2; 5. DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 3. DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 4. PE 1: Evidence at protein level; KW Complete proteome; Developmental protein; Differentiation; KW Disease mutation; DNA-binding; Holoprosencephaly; Metal-binding; KW Neurogenesis; Nucleus; Polymorphism; Repeat; Zinc; Zinc-finger. FT CHAIN 1 532 Zinc finger protein ZIC 2. FT /FTId=PRO_0000047247. FT ZN_FING 256 291 C2H2-type 1; atypical. FT ZN_FING 300 327 C2H2-type 2; atypical. FT ZN_FING 333 357 C2H2-type 3. FT ZN_FING 363 387 C2H2-type 4. FT ZN_FING 393 415 C2H2-type 5. FT COMPBIAS 20 23 Poly-His. FT COMPBIAS 25 33 Poly-Ala. FT COMPBIAS 89 97 Poly-Ala. FT COMPBIAS 226 230 Poly-Ala. FT COMPBIAS 231 239 Poly-His. FT COMPBIAS 456 470 Poly-Ala. FT COMPBIAS 490 508 Poly-Gly. FT VARIANT 36 36 Q -> P (in HPE5; 2-fold increase in FT luciferase activity). FT /FTId=VAR_023793. FT VARIANT 37 37 D -> N (in HPE5). FT /FTId=VAR_058592. FT VARIANT 128 128 D -> N (in HPE5). FT /FTId=VAR_058593. FT VARIANT 152 152 D -> F (in HPE5; requires 2 nucleotide FT substitutions; 50% reduction of FT luciferase activity). FT /FTId=VAR_023794. FT VARIANT 239 239 H -> HH. FT /FTId=VAR_023795. FT VARIANT 239 239 Missing. FT /FTId=VAR_023796. FT VARIANT 272 272 S -> N (in HPE5). FT /FTId=VAR_058594. FT VARIANT 286 286 H -> L (in HPE5). FT /FTId=VAR_058595. FT VARIANT 286 286 H -> Q (in HPE5). FT /FTId=VAR_058596. FT VARIANT 286 286 H -> Y (in HPE5). FT /FTId=VAR_058597. FT VARIANT 291 291 H -> Y (in HPE5). FT /FTId=VAR_058598. FT VARIANT 304 304 W -> R (in HPE5). FT /FTId=VAR_058599. FT VARIANT 314 314 F -> C (in HPE5). FT /FTId=VAR_058600. FT VARIANT 325 325 R -> L (in HPE5). FT /FTId=VAR_058601. FT VARIANT 325 325 R -> S (in HPE5). FT /FTId=VAR_058602. FT VARIANT 327 327 H -> Y (in HPE5). FT /FTId=VAR_058603. FT VARIANT 335 335 C -> F (in HPE5). FT /FTId=VAR_058604. FT VARIANT 373 373 R -> P (in HPE5). FT /FTId=VAR_058605. FT VARIANT 402 402 Y -> N (in HPE5). FT /FTId=VAR_058606. FT VARIANT 403 403 T -> K (in HPE5). FT /FTId=VAR_058607. FT VARIANT 404 404 H -> R (in HPE5). FT /FTId=VAR_058608. FT VARIANT 409 409 R -> W (in HPE5). FT /FTId=VAR_058609. FT VARIANT 415 415 H -> Q (in HPE5). FT /FTId=VAR_058610. FT VARIANT 470 470 A -> AAAAAAAAAAA (in HPE5; near-complete FT loss of luciferase activity). FT /FTId=VAR_008856. FT CONFLICT 124 128 RGFGD -> ARLPGT (in Ref. 1; AAC96325). SQ SEQUENCE 532 AA; 55006 MW; BA3E6455DAF97EAC CRC64; MLLDAGPQFP AIGVGSFARH HHHSAAAAAA AAAEMQDREL SLAAAQNGFV DSAAAHMGAF KLNPGAHELS PGQSSAFTSQ GPGAYPGSAA AAAAAAALGP HAAHVGSYSG PPFNSTRDFL FRSRGFGDSA PGGGQHGLFG PGAGGLHHAH SDAQGHLLFP GLPEQHGPHG SQNVLNGQMR LGLPGEVFGR SEQYRQVASP RTDPYSAAQL HNQYGPMNMN MGMNMAAAAA HHHHHHHHHP GAFFRYMRQQ CIKQELICKW IDPEQLSNPK KSCNKTFSTM HELVTHVSVE HVGGPEQSNH VCFWEECPRE GKPFKAKYKL VNHIRVHTGE KPFPCPFPGC GKVFARSENL KIHKRTHTGE KPFQCEFEGC DRRFANSSDR KKHMHVHTSD KPYLCKMCDK SYTHPSSLRK HMKVHESSPQ GSESSPAASS GYESSTPPGL VSPSAEPQSS SNLSPAAAAA AAAAAAAAAA VSAVHRGGGS GSGGAGGGSG GGSGSGGGGG GAGGGGGGSS GGGSGTAGGH SGLSSNFNEW YV //