UniProtKB/Swiss-Prot Q92560: Variant p.Ala95Asp

• Variant information
• Sequence information
• Literature citations
• All

Variant information

Variant position: 95 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: US 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 Alanine (A) to Aspartate (D) at position 95 (A95D, p.Ala95Asp). 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 small size and hydrophobic (A) to medium size and acidic (D) 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 a lung cancer sample; also found in a malignant pleural mesothelioma cell line; induces cytoplasmic accumulation; loss of deubiquitinase activity; up-regulates heat shock response; induces formation of amyloid-beta aggregates. Any additional useful information about the variant.

Sequence information

Variant position: 95 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: 729 The length of the canonical sequence.
Location on the sequence: DIVNNMFFAHQLIPNSCATH A LLSVLLNCSSVDLGPTLSRM 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.
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 – 729	Ubiquitin carboxyl-terminal hydrolase BAP1
Active site	91 – 91	Nucleophile
Mutagenesis	91 – 91	C -> A. Abolishes enzymatic activity. Has no effect on interaction with HCFC1.
Helix	91 – 101

Literature citations

The nuclear deubiquitinase BAP1 is commonly inactivated by somatic mutations and 3p21.1 losses in malignant pleural mesothelioma.
Bott M.; Brevet M.; Taylor B.S.; Shimizu S.; Ito T.; Wang L.; Creaney J.; Lake R.A.; Zakowski M.F.; Reva B.; Sander C.; Delsite R.; Powell S.; Zhou Q.; Shen R.; Olshen A.; Rusch V.; Ladanyi M.;
Nat. Genet. 43:668-672(2011)
Cited for: INVOLVEMENT IN MESOM; VARIANTS CYS-63; VAL-81; TRP-91; ASP-95; ALA-315 AND VAL-685; Defining biochemical functions for the BRCA1 tumor suppressor protein: analysis of the BRCA1 binding protein BAP1.
Jensen D.E.; Rauscher F.J. III;
Cancer Lett. 143:S13-S17(1999)
Cited for: VARIANTS ASP-95 AND VAL-178; BRCA1-associated protein-1 is a tumor suppressor that requires deubiquitinating activity and nuclear localization.
Ventii K.H.; Devi N.S.; Friedrich K.L.; Chernova T.A.; Tighiouart M.; Van Meir E.G.; Wilkinson K.D.;
Cancer Res. 68:6953-6962(2008)
Cited for: FUNCTION; SUBCELLULAR LOCATION; NUCLEAR LOCALIZATION SIGNAL; MUTAGENESIS OF CYS-91; 656-LYS--ARG-661 AND 717-ARG--ARG-722; CHARACTERIZATION OF VARIANTS ASP-95 AND VAL-178; Cancer associated missense mutations in BAP1 catalytic domain induce amyloidogenic aggregation: A new insight in enzymatic inactivation.
Bhattacharya S.; Hanpude P.; Maiti T.K.;
Sci. Rep. 5:18462-18462(2015)
Cited for: CHARACTERIZATION OF VARIANTS PHE-47; VAL-81; ASP-95 AND VAL-178;