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UniProtKB/Swiss-Prot P28062: Variant p.Thr75Met

Proteasome subunit beta type-8
Gene: PSMB8
Variant information

Variant position:  75
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  LP/P [Disclaimer]
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 Threonine (T) to Methionine (M) at position 75 (T75M, p.Thr75Met).
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 medium size and polar (T) to medium size and hydrophobic (M)
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:  In PRAAS1; markedly decreased chymotrypsin-like activity consistent with a decrease in proteasomal activity and loss of function; some patients are heterozygotes for this mutation and also carry a mutation in PSMA3; patients' cells show reduction of proteasome content and endopeptidase activity of the proteasome.
Any additional useful information about the variant.

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



Sequence information

Variant position:  75
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  276
The length of the canonical sequence.

Location on the sequence:   QSLGGDGERNVQIEMAHGTT  T LAFKFQHGVIAAVDSRASAG
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                         QSLGGDGERNVQIEMAHGTTTLAFKFQHGVIAAVDSRASAG

                              QSLGENGEKNIRKEMVHGTTTLAFKFQHGVIVAVDSRATAG

Mouse                         RSFGGDQERNVQIEMAHGTTTLAFKFQHGVIVAVDSRATAG

Rat                           RSFGDDQERKVQIEMAHGTTTLAFKFQHGVIVAVDSRASAG

Bovine                        RSLGGNGESKVQIEMAHGTTTLAFKFQHGVIVAVDSRASAG

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 73 – 276 Proteasome subunit beta type-8
Active site 73 – 73 Nucleophile
Beta strand 74 – 80


Literature citations

PSMB8 encoding the beta5i proteasome subunit is mutated in joint contractures, muscle atrophy, microcytic anemia, and panniculitis-induced lipodystrophy syndrome.
Agarwal A.K.; Xing C.; DeMartino G.N.; Mizrachi D.; Hernandez M.D.; Sousa A.B.; Martinez de Villarreal L.; dos Santos H.G.; Garg A.;
Am. J. Hum. Genet. 87:866-872(2010)
Cited for: VARIANT PRAAS1 MET-75; CHARACTERIZATION OF VARIANT PRAAS1 MET-75;

Mutations in proteasome subunit beta type 8 cause chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature with evidence of genetic and phenotypic heterogeneity.
Liu Y.; Ramot Y.; Torrelo A.; Paller A.S.; Si N.; Babay S.; Kim P.W.; Sheikh A.; Lee C.C.; Chen Y.; Vera A.; Zhang X.; Goldbach-Mansky R.; Zlotogorski A.;
Arthritis Rheum. 64:895-907(2012)
Cited for: VARIANT PRAAS1 MET-75;

Additive loss-of-function proteasome subunit mutations in CANDLE/PRAAS patients promote type I IFN production.
Brehm A.; Liu Y.; Sheikh A.; Marrero B.; Omoyinmi E.; Zhou Q.; Montealegre G.; Biancotto A.; Reinhardt A.; Almeida de Jesus A.; Pelletier M.; Tsai W.L.; Remmers E.F.; Kardava L.; Hill S.; Kim H.; Lachmann H.J.; Megarbane A.; Chae J.J.; Brady J.; Castillo R.D.; Brown D.; Casano A.V.; Gao L.; Chapelle D.; Huang Y.; Stone D.; Chen Y.; Sotzny F.; Lee C.C.; Kastner D.L.; Torrelo A.; Zlotogorski A.; Moir S.; Gadina M.; McCoy P.; Wesley R.; Rother K.; Hildebrand P.W.; Brogan P.; Krueger E.; Aksentijevich I.; Goldbach-Mansky R.;
J. Clin. Invest. 125:4196-4211(2015)
Cited for: VARIANTS PRAAS1 MET-75 AND GLN-105; CHARACTERIZATION OF VARIANTS PRAAS1 MET-75;

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.