UniProtKB/Swiss-Prot Q92793: Variant p.Tyr1175Cys

• Variant information
• Sequence information
• Literature citations
• All

Variant information

Variant position: 1175 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: LP/P [Disclaimer: Variants classification is intended for research purposes only, not for clinical and diagnostic use. The label disease variant is assigned according to literature reports on probable disease-association that can be based on theoretical reasons. This label must not be considered as a definitive proof for the pathogenic role of a variant.] 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 Tyrosine (Y) to Cysteine (C) at position 1175 (Y1175C, p.Tyr1175Cys). 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 (Y) to medium size and polar (C) 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 RSTS1; mild form; impairs binding to ASF1A and acetylated histone H3. Any additional useful information about the variant.
Other resources: Links to websites of interest for the variant.

• Variant rs28937315 [ dbSNP | Ensembl ]

Sequence information

Variant position: 1175 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: 2442 The length of the canonical sequence.
Location on the sequence: DDVWLMFNNAWLYNRKTSRV Y KFCSKLAEVFEQEIDPVMQS 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	2 – 2442	CREB-binding protein
Domain	1103 – 1175	Bromo
Region	1162 – 1180	Interaction with ASF1A
Mutagenesis	1162 – 1162	N -> ER. Abolishes interaction with ASF1A.
Mutagenesis	1165 – 1165	W -> A. Abolishes interaction with ASF1A.
Mutagenesis	1170 – 1170	K -> E. Impairs binding to acetylated histones.
Mutagenesis	1179 – 1179	S -> I. Impairs interaction with ASF1A.
Mutagenesis	1180 – 1180	K -> E. Abolishes interaction with ASF1A.
Mutagenesis	1183 – 1183	E -> R. Abolishes interaction with ASF1A.
Helix	1173 – 1195

Literature citations

Binding of the histone chaperone ASF1 to the CBP bromodomain promotes histone acetylation.
Das C.; Roy S.; Namjoshi S.; Malarkey C.S.; Jones D.N.; Kutateladze T.G.; Churchill M.E.; Tyler J.K.;
Proc. Natl. Acad. Sci. U.S.A. 111:E1072-E1081(2014)
Cited for: X-RAY CRYSTALLOGRAPHY (1.40 ANGSTROMS) OF 1082-1197; FUNCTION; INTERACTION WITH ASF1A; ASF1B; ACETYLATED HISTONES AND TP53; MUTAGENESIS OF ASP-1116; PHE-1126; ASN-1162; TRP-1165; LYS-1170; SER-1179; LYS-1180 AND GLU-1183; CHARACTERIZATION OF VARIANT RSTS1 CYS-1175; CATALYTIC ACTIVITY; AUTOACETYLATION; Molecular studies in 10 cases of Rubinstein-Taybi syndrome, including a mild variant showing a missense mutation in codon 1175 of CREBBP.
Bartsch O.; Locher K.; Meinecke P.; Kress W.; Seemanova E.; Wagner A.; Ostermann K.; Roedel G.;
J. Med. Genet. 39:496-501(2002)
Cited for: VARIANT RSTS1 CYS-1175; Insights into genotype-phenotype correlations from CREBBP point mutation screening in a cohort of 46 Rubinstein-Taybi syndrome patients.
Spena S.; Milani D.; Rusconi D.; Negri G.; Colapietro P.; Elcioglu N.; Bedeschi F.; Pilotta A.; Spaccini L.; Ficcadenti A.; Magnani C.; Scarano G.; Selicorni A.; Larizza L.; Gervasini C.;
Clin. Genet. 88:431-440(2015)
Cited for: VARIANTS HIS-503; THR-532 AND ASN-546; VARIANTS RSTS1 PHE-650; THR-789; CYS-1175; ALA-1278; PRO-1378; TYR-1406; PRO-1415; THR-1475; PHE-1503; PRO-1507 AND ASN-1543;