UniProtKB/Swiss-Prot Q92560: Variant p.Phe81Val

• Variant information
• Sequence information
• Literature citations
• All

Variant information

Variant position: 81 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 Phenylalanine (F) to Valine (V) at position 81 (F81V, p.Phe81Val). 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 large size and aromatic (F) to medium size and hydrophobic (V) 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: Found in a malignant pleural mesothelioma sample; somatic mutation; 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: 81 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: KVSTLVDDTSVIDDDIVNNM F FAHQLIPNSCATHALLSVLL 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
Domain	4 – 235	UCH catalytic
Active site	91 – 91	Nucleophile
Site	85 – 85	Transition state stabilizer
Mutagenesis	91 – 91	C -> A. Abolishes deubiquitinase activity. Has no effect on interaction with HCFC1.

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; 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;