UniProtKB/SwissProt variant VAR

Variant information

Variant position:

286

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 Histidine (H) to Arginine (R) at position 286 (H286R, p.His286Arg).

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 (H) to large size and basic (R)

The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:

0

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; inreases weakly its cytoplasmic localization; lacks DNA-binding; does not inhibit transcriptional activation and interaction with GLI3.

Any additional useful information about the variant.

Sequence information

Variant position:

286

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:

KSCDRTFSTMHELVTHVTME H VGGPEQNNHVCYWEECPREG

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                         KSCDRTFSTMHELVTHVTMEHVGGPEQNNHVCYWEECPREG

Mouse                         KSCDRTFSTMHELVTHVTMEHVGGPEQNNHVCYWEECPREG

Xenopus laevis                KTCDRTFSSMHELVTHMTMEHVGGPEQNNHICYWEECPRGG

Xenopus tropicalis            KTCDRTFSSMHELVTHMTMEHVGGPEQTNHICYWEECPRGG

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.

Type	Positions	Description
Chain	1 – 467	Zinc finger protein ZIC 3
Zinc finger	251 – 286	C2H2-type 1; atypical
Mutagenesis	268 – 268	C -> S. Increases weakly its cytoplasmic localization.
Mutagenesis	281 – 281	H -> R. Increases its cytoplasmic localization.
Mutagenesis	304 – 304	R -> M. Increases its cytoplasmic localization.
Turn	285 – 287

Literature citations

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)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1); VARIANTS HTX1 ARG-286 AND MET-323;

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;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O60481: Variant p.His286Arg