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UniProtKB/Swiss-Prot O60481: Variant p.Cys253Ser

Zinc finger protein ZIC 3
Gene: ZIC3
Variant information

Variant position:  253
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  LP/P [Disclaimer]
The variants are classified into three categories: LP/P, LB/B and US.
  • LP/P: likely pathogenic or pathogenic.
  • LB/B: likely benign or benign.
  • US: uncertain significance

Residue change:  From Cysteine (C) to Serine (S) at position 253 (C253S, p.Cys253Ser).
Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.

Physico-chemical properties:  Change from medium size and polar (C) to small size and polar (S)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -1
The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:
  • Lowest score: -4 (low probability of substitution).
  • Highest score: 11 (high probability of substitution).
More information can be found on the following page

Variant description:  In HTX1; increases strongly its cytoplasmic localization; lacks DNA-binding; does not inhibit transcriptional activation and interaction with GLI3.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  253
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  467
The length of the canonical sequence.

Location on the sequence:   HHGPGAFFRYMRQPIKQELS  C KWIDEAQLSRPKKSCDRTFS
The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.

Residue conservation: 
The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         HHGPGAFFRYMRQPIKQELSCKWIDEAQLSRPKKSCDRTFS

Mouse                         HHGPGAFFRYMRQPIKQELSCKWIEEAQLSRPKKSCDRTFS

Xenopus laevis                HHGQGAFFRYMRQPIKQELSCKWLEESTMNHPQKTCDRTFS

Xenopus tropicalis            HHGPGAFFRYMRQPIKQELSCKWLEESPMNRPQKTCDRTFS

Sequence annotation in neighborhood:  
The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:
  • Type: the type of sequence feature.
  • Positions: endpoints of the sequence feature.
  • Description: contains additional information about the feature.

TypePositionsDescription
Chain 1 – 467 Zinc finger protein ZIC 3
Zinc finger 251 – 286 C2H2-type 1; atypical
Cross 248 – 248 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)
Mutagenesis 268 – 268 C -> S. Increases weakly its cytoplasmic localization.


Literature citations

Characterization of the interactions of human ZIC3 mutants with GLI3.
Zhu L.; Zhou G.; Poole S.; Belmont J.W.;
Hum. Mutat. 29:99-105(2008)
Cited for: FUNCTION; INTERACTION WITH GLI3; DNA-BINDING; CHARACTERIZATION OF VARIANTS HTX1 SER-253; ARG-286; MET-323 AND GLU-405; CHARACTERIZATION OF VARIANT CHTD1 ALA-217;

Functional and structural basis of the nuclear localization signal in the ZIC3 zinc finger domain.
Hatayama M.; Tomizawa T.; Sakai-Kato K.; Bouvagnet P.; Kose S.; Imamoto N.; Yokoyama S.; Utsunomiya-Tate N.; Mikoshiba K.; Kigawa T.; Aruga J.;
Hum. Mol. Genet. 17:3459-3473(2008)
Cited for: STRUCTURE BY NMR OF 246-329 IN COMPLEX WITH ZINC IONS; INTERACTION WITH KPNA1 AND KPNA6; CHARACTERIZATION OF VARIANTS HTX1 SER-253; GLY-255 AND ARG-286; MUTAGENESIS OF CYS-268; HIS-281; ARG-304; LYS-307; LYS-310; LYS-312; LYS-314; ARG-320; LYS-326; LYS-337; ARG-341; LYS-346; LYS-349; ARG-350 AND LYS-356;

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)
Cited for: VARIANT CHTD1 ALA-217; VARIANTS HTX1 SER-253 AND GLU-405;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.