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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P04792: Variant p.Ser135Phe

Heat shock protein beta-1
Gene: HSPB1
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Variant information Variant position: help 135 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help 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: help From Serine (S) to Phenylalanine (F) at position 135 (S135F, p.Ser135Phe). 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: help Change from small size and polar (S) to large size and aromatic (F) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -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: help In CMT2F and HMND3; decreased homodimerization; increased client proteins binding; increased function in chaperone-mediated protein folding; alters CDK5-mediated phosphorylation of neurofilament proteins; alters CDK5-mediated phosphorylation of neurofilament proteins and indirectly impairs their anterograde axonal transport. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 135 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 205 The length of the canonical sequence.
Location on the sequence: help DGVVEITGKHEERQDEHGYI S RCFTRKYTLPPGVDPTQVSS 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         DGVVEITGKHEERQDEHGYISRCFTRKYTLPPGVDPTQVSS

                              DGVVEITGKHEERQDEHGYISRRLTPKYTLPPGVDPTLVSS

Mouse                         EGVVEITGKHEERQDEHGYISRCFTRKYTLPPGVDPTLVSS

Rat                           EGVVEITGKHEERQDEHGYISRCFTRKYTLPPGVDPTLVSS

Pig                           DGVVEITGKHEERQDEHGFISRCFTRKYTLPPGVDPTQVSS

Bovine                        DGVVEITGKHEERQDEHGYISRCFTRKYTLPPGVDPTLVSS

Chicken                       DNIVEITGKHEEKQDEHGFISRCFTRKYTLPPGVEATAVRS
Sequence annotation in neighborhood: help 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 – 205 Heat shock protein beta-1
Domain 76 – 184 sHSP
Region 70 – 205 Interaction with TGFB1I1
Modified residue 123 – 123 N6-acetyllysine



Literature citations
Mutant small heat-shock protein 27 causes axonal Charcot-Marie-Tooth disease and distal hereditary motor neuropathy.
Evgrafov O.V.; Mersiyanova I.; Irobi J.; Van Den Bosch L.; Dierick I.; Leung C.L.; Schagina O.; Verpoorten N.; Van Impe K.; Fedotov V.; Dadali E.; Auer-Grumbach M.; Windpassinger C.; Wagner K.; Mitrovic Z.; Hilton-Jones D.; Talbot K.; Martin J.-J.; Vasserman N.; Tverskaya S.; Polyakov A.; Liem R.K.H.; Gettemans J.; Robberecht W.; De Jonghe P.; Timmerman V.;
Nat. Genet. 36:602-606(2004)
Cited for: VARIANTS CMT2F PHE-135 AND TRP-136; VARIANTS HMND3 TRP-127; PHE-135; ILE-151 AND LEU-182; Mutations in the HSP27 (HSPB1) gene cause dominant, recessive, and sporadic distal HMN/CMT type 2.
Houlden H.; Laura M.; Wavrant-De Vrieze F.; Blake J.; Wood N.; Reilly M.M.;
Neurology 71:1660-1668(2008)
Cited for: VARIANTS HMND3 LEU-39; ARG-84; MET-99; PHE-135 AND GLY-140; Increased monomerization of mutant HSPB1 leads to protein hyperactivity in Charcot-Marie-Tooth neuropathy.
Almeida-Souza L.; Goethals S.; de Winter V.; Dierick I.; Gallardo R.; Van Durme J.; Irobi J.; Gettemans J.; Rousseau F.; Schymkowitz J.; Timmerman V.; Janssens S.;
J. Biol. Chem. 285:12778-12786(2010)
Cited for: VARIANT TYR-156; CHARACTERIZATION OF VARIANT TYR-156; CHARACTERIZATION OF VARIANTS HMND3 TRP-127; PHE-135; ILE-151 AND LEU-182; CHARACTERIZATION OF VARIANT CMT2F TRP-136; FUNCTION; SUBUNIT; Charcot-Marie-Tooth causing HSPB1 mutations increase Cdk5-mediated phosphorylation of neurofilaments.
Holmgren A.; Bouhy D.; De Winter V.; Asselbergh B.; Timmermans J.P.; Irobi J.; Timmerman V.;
Acta Neuropathol. 126:93-108(2013)
Cited for: FUNCTION; CHARACTERIZATION OF VARIANTS HMND3 TRP-127 AND LEU-182; CHARACTERIZATION OF VARIANT CMT2F PHE-135;
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.