UniProtKB/SwissProt variant VAR

Variant information

Variant position:

268

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

Type of variant:

Unclassified

The variants are classified into three categories: Disease, Polymorphism and Unclassified.

Disease: Variants implicated in disease according to literature reports.
Polymorphism: Variants not reported to be implicated in disease.
Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:

From Glycine (G) to Valine (V) at position 268 (G268V, p.Gly268Val).

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 glycine (G) to medium size and hydrophobic (V)

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

BLOSUM score:

-3

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:

Associated with resistance to anticancer indisulam; decreased interaction with the DCX(DCAF15) complex in presence of indisulam; abolished degradation by the DCX(DCAF15) complex in presence of indisulam.

Any additional useful information about the variant.

Sequence information

Variant position:

268

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

Protein sequence length:

530

The length of the canonical sequence.

Location on the sequence:

GPMRLYVGSLHFNITEDMLR G IFEPFGRIESIQLMMDSETG

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                         GPMRLYVGSLHFNITEDMLRGIFEPFGRIESIQLMMDSETG

Mouse                         GPMRLYVGSLHFNITEDMLRGIFEPFGRIESIQLMMDSETG

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 – 530	RNA-binding protein 39
Domain	250 – 328	RRM 2
Helix	263 – 270

Literature citations

Selective degradation of splicing factor CAPERalpha by anticancer sulfonamides.
Uehara T.; Minoshima Y.; Sagane K.; Sugi N.H.; Mitsuhashi K.O.; Yamamoto N.; Kamiyama H.; Takahashi K.; Kotake Y.; Uesugi M.; Yokoi A.; Inoue A.; Yoshida T.; Mabuchi M.; Tanaka A.; Owa T.;
Nat. Chem. Biol. 13:675-680(2017)
Cited for: FUNCTION; UBIQUITINATION; VARIANT VAL-268; CHARACTERIZATION OF VARIANT VAL-268;

Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15.
Han T.; Goralski M.; Gaskill N.; Capota E.; Kim J.; Ting T.C.; Xie Y.; Williams N.S.; Nijhawan D.;
Science 356:0-0(2017)
Cited for: FUNCTION; UBIQUITINATION; VARIANTS LEU-265; ARG-268; GLU-268; TRP-268; VAL-268; GLN-271; GLY-271 AND SER-272; CHARACTERIZATION OF VARIANTS LEU-265; ARG-268; TRP-268; VAL-268; GLN-271 AND SER-272;

Structural basis of indisulam-mediated RBM39 recruitment to DCAF15 E3 ligase complex.
Bussiere D.E.; Xie L.; Srinivas H.; Shu W.; Burke A.; Be C.; Zhao J.; Godbole A.; King D.; Karki R.G.; Hornak V.; Xu F.; Cobb J.; Carte N.; Frank A.O.; Frommlet A.; Graff P.; Knapp M.; Fazal A.; Okram B.; Jiang S.; Michellys P.Y.; Beckwith R.; Voshol H.; Wiesmann C.; Solomon J.M.; Paulk J.;
Nat. Chem. Biol. 0:0-0(2019)
Cited for: X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 91-171 IN COMPLEX WITH DCAF15; STRUCTURE BY ELECTRON MICROSCOPY (3.54 ANGSTROMS) IN COMPLEX WITH DCAF15; IDENTIFICATION IN THE DCX(DCAF15) COMPLEX; VARIANTS LEU-265; TRP-268 AND VAL-268; CHARACTERIZATION OF VARIANTS LEU-265; TRP-268 AND VAL-268;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q14498: Variant p.Gly268Val