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UniProtKB/Swiss-Prot P40818: Variant p.Ser718Pro

Ubiquitin carboxyl-terminal hydrolase 8
Gene: USP8
Variant information

Variant position:  718
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 Serine (S) to Proline (P) at position 718 (S718P, p.Ser718Pro).
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 polar (S) to medium size and hydrophobic (P)
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

Involvement in disease:  Pituitary adenoma 4, ACTH-secreting (PITA4) [MIM:219090]: A form of pituitary adenoma, a neoplasm of the pituitary gland and one of the most common neuroendocrine tumors. Pituitary adenomas are clinically classified as functional and non-functional tumors, and manifest with a variety of features, including local invasion of surrounding structures and excessive hormone secretion. Functional pituitary adenomas are further classified by the type of hormone they secrete. PITA4 results in excessive production of adrenocorticotropic hormone. This leads to hypersecretion of cortisol by the adrenal glands and ACTH-dependent Cushing syndrome. Clinical manifestations of Cushing syndrome include facial and truncal obesity, abdominal striae, muscular weakness, osteoporosis, arterial hypertension, diabetes. {ECO:0000269|PubMed:28505279}. Note=The disease is caused by mutations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In PITA4; somatic mutation; unknown pathological significance; localizes to nucleus instead of cytoplasm.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  718
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1118
The length of the canonical sequence.

Location on the sequence:   AKPQIPAERDREPSKLKRSY  S SPDITQAIQEEEKRKPTVTP
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                         AKPQIPAERDREPSKLKRSYSSPDITQAIQEEEKRKPTVTP

Mouse                         VKPQVPAERDREPSKLKRSYSSPDITQALQEEEKRRPAVTP

Baker's yeast                 -----------------------------------------

Fission yeast                 -----------------------------------------

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.

TypePositionsDescription
Chain 1 – 1118 Ubiquitin carboxyl-terminal hydrolase 8
Modified residue 718 – 718 Phosphoserine
Modified residue 719 – 719 Phosphoserine


Literature citations

Somatic USP8 gene mutations are a common cause of pediatric Cushing disease.
Faucz F.R.; Tirosh A.; Tatsi C.; Berthon A.; Hernandez-Ramirez L.C.; Settas N.; Angelousi A.; Correa R.; Papadakis G.Z.; Chittiboina P.; Quezado M.; Pankratz N.; Lane J.; Dimopoulos A.; Mills J.L.; Lodish M.; Stratakis C.A.;
J. Clin. Endocrinol. Metab. 102:2836-2843(2017)
Cited for: VARIANTS PITA4 718-SER--THR-723 DEL; CYS-718; PRO-718; SER-718 DEL AND ARG-720; CHARACTERIZATION OF VARIANT PITA4 PRO-718; SUBCELLULAR LOCATION;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.