UniProtKB/SwissProt variant VAR

Variant information

Variant position:

138

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 Glutamate (E) to Glycine (G) at position 138 (E138G, p.Glu138Gly).

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 acidic (E) to glycine (G)

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

BLOSUM score:

-2

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 RP2; reduces affinity for ARL3 150-fold and inhibits the GTP-hydrolysis rate of ARL3.

Any additional useful information about the variant.

Sequence information

Variant position:

138

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

Protein sequence length:

350

The length of the canonical sequence.

Location on the sequence:

RVRDCRKLEVFLCCATQPII E SSSNIKFGCFQWYYPELAFQ

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                         RVRDCRKLEVFLCCATQPIIESSSNIKFGCFQWYYPELAFQ

Mouse                         RVRDCRKLEVFLCCATQPIIESSTNIKFGCFQWYYPELAAQ

Chicken                       RTRDCRRLEVFLCCATQPIIESSTGMKFGCFQYYYPELALQ

Xenopus laevis                RTRDCRRMDVFLCCSTQPIIESSTSMKFGCFQYYYPELALQ

Zebrafish                     RTRDCKKMDVFLCCATQPIIESSTGMKFGCFQYYYPELAFH

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	2 – 350	Protein XRP2
Domain	24 – 179	C-CAP/cofactor C-like
Mutagenesis	118 – 118	R -> A. Reduces affinity and GTP-hydrolysis rate for mouse ARL3.
Mutagenesis	120 – 120	R -> H. Reduces affinity for mouse ARL3; when associated with S-121.
Mutagenesis	121 – 121	D -> S. Reduces affinity for mouse ARL3; when associated with H-120.
Beta strand	136 – 139

Literature citations

Crystal structure of the human retinitis pigmentosa 2 protein and its interaction with Arl3.
Kuehnel K.; Veltel S.; Schlichting I.; Wittinghofer A.;
Structure 14:367-378(2006)
Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS); INTERACTION WITH ARL3; CHARACTERIZATION OF VARIANTS RP2 HIS-118 AND GLY-138; CHARACTERIZATION OF VARIANT TRP-282;

The retinitis pigmentosa 2 gene product is a GTPase-activating protein for Arf-like 3.
Veltel S.; Gasper R.; Eisenacher E.; Wittinghofer A.;
Nat. Struct. Mol. Biol. 15:373-380(2008)
Cited for: X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 1-350 OF COMPLEX WITH MOUSE ARL3 AND GTP; FUNCTION; INTERACTION WITH ARL3; TISSUE SPECIFICITY; CHARACTERIZATION OF VARIANTS LEU-118 AND GLY-138; MUTAGENESIS OF SER-28; TRP-29; GLN-31; ARG-32; PHE-101; GLN-115; GLN-116; ARG-118; ARG-120 AND PHE-177;

Identification of novel RP2 mutations in a subset of X-linked retinitis pigmentosa families and prediction of new domains.
Miano M.G.; Testa F.; Filippini F.; Trujillo M.; Conte I.; Lanzara C.; Millan J.M.; De Bernardo C.; Grammatico B.; Mangino M.; Torrente I.; Carrozzo R.; Simonelli F.; Rinaldi E.; Ventruto V.; D'Urso M.; Ayuso C.; Ciccodicola A.;
Hum. Mutat. 18:109-119(2001)
Cited for: VARIANTS RP2 LEU-118 AND GLY-138; VARIANT TRP-282;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O75695: Variant p.Glu138Gly