Reviewed, UniProtKB/Swiss-Prot O60481 (ZIC3_HUMAN)

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

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	467 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Probably functions as a transcription factor in the earliest stages of the left-right (LR) body axis formation.
Subcellular location	Nucleus.
Involvement in disease	Defects in ZIC3 are the cause of X-linked visceral heterotaxy (HTX1) [MIM:306955]. HTX1 is a disease characterized by congenital heart disease and alterations of visceral situs, including asplenia or polysplenia, symmetric liver, intestinal malrotation, and abnormal lung lobation. Ref.1 Ref.6 Ref.8
Sequence similarities	Belongs to the GLI C2H2-type zinc-finger protein family. Contains 5 C2H2-type zinc fingers.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Repeat Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Technical term	3D-structure
Gene Ontology (GO)
Biological process	determination of left/right symmetry Ref.1 Traceable author statement. Source: ProtInc regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW transcription Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	DNA binding Inferred from electronic annotation. Source: UniProtKB-KW zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 467

467

Zinc finger protein ZIC 3

PRO_0000047250

Regions

Zinc finger

251 – 286

36

C2H2-type 1; atypical

Zinc finger

295 – 322

28

C2H2-type 2; atypical

Zinc finger

328 – 352

25

C2H2-type 3

Zinc finger

358 – 382

25

C2H2-type 4

Zinc finger

388 – 410

23

C2H2-type 5

Compositional bias

46 – 55

10

Poly-Ala

Compositional bias

87 – 97

11

Poly-His

Natural variations

Natural variant

217

1

P → A in heart disease; with non-congenital heterotaxy. Ref.6 Ref.7

VAR_025632

Natural variant

253

1

C → S in HTX1. Ref.6

VAR_025633

Natural variant

255

1

W → G in HTX1; decreased protein expression, decreased transcriptional activity and decreased nuclear localization. Ref.8

VAR_042416

Natural variant

286

1

H → R in HTX1. Ref.1

VAR_025634

Natural variant

323

1

T → M in HTX1. Ref.1

VAR_007753

Natural variant

405

1

K → E in HTX1. Ref.6

VAR_025635

Secondary structure

1

.

.

.

.

.

.

.

.

467

Helix Strand Turn

Details...

Beta strand

261 – 264

4

Helix

275 – 284

10

Turn

285 – 287

3

Helix

312 – 323

12

Sequences

	Sequence		Length	Mass (Da)
	O60481-1 [UniParc]. Last modified August 1, 1998. Version 1. Checksum: 3150CF13C0679568	FASTA	467	50,569
	10 20 30 40 50 60 MTMLLDGGPQ FPGLGVGSFG APRHHEMPNR EPAGMGLNPF GDSTHAAAAA AAAAAFKLSP 70 80 90 100 110 120 AAAHDLSSGQ SSAFTPQGSG YANALGHHHH HHHHHHHTSQ VPSYGGAASA AFNSTREFLF 130 140 150 160 170 180 RQRSSGLSEA ASGGGQHGLF AGSASSLHAP AGIPEPPSYL LFPGLHEQGA GHPSPTGHVD 190 200 210 220 230 240 NNQVHLGLRG ELFGRADPYR PVASPRTDPY AAGAQFPNYS PMNMNMGVNV AAHHGPGAFF 250 260 270 280 290 300 RYMRQPIKQE LSCKWIDEAQ LSRPKKSCDR TFSTMHELVT HVTMEHVGGP EQNNHVCYWE 310 320 330 340 350 360 ECPREGKSFK AKYKLVNHIR VHTGEKPFPC PFPGCGKIFA RSENLKIHKR THTGEKPFKC 370 380 390 400 410 420 EFEGCDRRFA NSSDRKKHMH VHTSDKPYIC KVCDKSYTHP SSLRKHMKVH ESQGSDSSPA 430 440 450 460 ASSGYESSTP PAIASANSKD TTKTPSAVQT STSHNPGLPP NFNEWYV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"X-linked situs abnormalities result from mutations in ZIC3." Gebbia M., Ferrero G.B., Pilia G., Bassi M.T., Aylsworth A.S., Penman-Splitt M., Bird L.M., Bamforth J.S., Burn J., Schlessiner D., Nelson D.L., Casey B. Nat. Genet. 17:305-308(1997) [PubMed: 9354794] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS HTX1 ARG-286 AND MET-323.
[2]	"The DNA sequence of the human X chromosome." Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R. Nature 434:325-337(2005) [PubMed: 15772651] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"Analysis of polyhistidine-containing proteins." Salichs E., de la Luna S. Submitted (FEB-2008) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[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]. Tissue: Brain.
[5]	"Functional and structural basis of nuclear localization signal in ZIC3 zinc finger domain: a role of conserved tryptophan residue in the zinc finger domain." RIKEN structural genomics initiative (RSGI) Submitted (FEB-2008) to the PDB data bank Cited for: STRUCTURE BY NMR OF 246-329 IN COMPLEX WITH ZINC IONS.
[6]	"Identification and functional analysis of ZIC3 mutations in heterotaxy and related congenital heart defects." Ware S.M., Peng J., Zhu L., Fernbach S., Colicos S., Casey B., Towbin J., Belmont J.W. Am. J. Hum. Genet. 74:93-105(2004) [PubMed: 14681828] [Abstract] Cited for: VARIANT HEART DISEASE ALA-217, VARIANTS HTX1 SER-253 AND GLU-405.
[7]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] ALA-217.
[8]	"Elucidation of penetrance variability of a ZIC3 mutation in a family with complex heart defects and functional analysis of ZIC3 mutations in the first zinc finger domain." Chhin B., Hatayama M., Bozon D., Ogawa M., Schoen P., Tohmonda T., Sassolas F., Aruga J., Valard A.-G., Chen S.-C., Bouvagnet P. Hum. Mutat. 28:563-570(2007) [PubMed: 17295247] [Abstract] Cited for: VARIANT HTX1 GLY-255, CHARACTERIZATION OF VARIANT HTX1 GLY-255.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBLGenBankDDBJ

AF028706 mRNA. Translation: AAC05594.1.
AL035443 Genomic DNA. Translation: CAB41648.1.
EU532020 mRNA. Translation: ACB30403.1.
BC113393 mRNA. Translation: AAI13394.1.
BC113395 mRNA. Translation: AAI13396.1.

IPI

IPI00029724.

RefSeq

NP_003404.1.

UniGene

Hs.111227

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2EJ4	NMR	-	A	245-326	[»]
2RPC	NMR	-	A	245-386	[»]

ModBase

Search...

Proteomic databases

PRIDE

O60481.

Genome annotation databases

Ensembl

ENSG00000156925. Homo sapiens. [Contig view]

GeneID

7547.

KEGG

hsa:7547.

Organism-specific databases

GeneCards

GC0XP136475.

HGNC

HGNC:12874. ZIC3.

MIM

300265. gene.
306955. phenotype.

Orphanet

450. Heterotaxia.
157769. Situs ambiguus.

PharmGKB

PA37463.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

O60481.

HOVERGEN

O60481.

OMA

O60481. YTAGAQF.

Gene expression databases

ArrayExpress

O60481.

Bgee

O60481.

CleanEx

HS_ZIC3.

GermOnline

ENSG00000156925. Homo sapiens.

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. 2 hits.

Pfam

PF00096. zf-C2H2. 4 hits.
[Graphical view]

ProDom

PD000003. Znf_C2H2. 1 hit.
[Graphical view] [Entries sharing at least one domain]

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 Resources

NextBio

29529.

SOURCE

Search...

Entry information

Entry name

ZIC3_HUMAN

Accession

Primary (citable) accession number: O60481
Secondary accession number(s): B2CNW4, Q14DE5

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 15, 1998
Last sequence update:	August 1, 1998
Last modified:	June 16, 2009
This is version 84 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)