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UniProtKB/Swiss-Prot P04792: Variant p.Pro7Ser

Heat shock protein beta-1
Gene: HSPB1
Chromosomal location: 7q11.2-q22
Variant information

Variant position:  7
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
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 Proline (P) to Serine (S) at position 7 (P7S, p.Pro7Ser).
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 hydrophobic (P) to small size and polar (S)
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:  Neuronopathy, distal hereditary motor, 2B (HMN2B) [MIM:608634]: A neuromuscular disorder. Distal hereditary motor neuronopathies constitute a heterogeneous group of neuromuscular disorders caused by selective degeneration of motor neurons in the anterior horn of the spinal cord, without sensory deficit in the posterior horn. The overall clinical picture consists of a classical distal muscular atrophy syndrome in the legs without clinical sensory loss. The disease starts with weakness and wasting of distal muscles of the anterior tibial and peroneal compartments of the legs. Later on, weakness and atrophy may expand to the proximal muscles of the lower limbs and/or to the distal upper limbs. {ECO:0000269|PubMed:15122254, ECO:0000269|PubMed:18832141, ECO:0000269|PubMed:18952241, ECO:0000269|PubMed:20178975, ECO:0000269|PubMed:20870250, ECO:0000269|PubMed:22176143, ECO:0000269|PubMed:23643870, ECO:0000269|PubMed:23728742, ECO:0000269|PubMed:23948568, ECO:0000269|PubMed:25965061, ECO:0000269|PubMed:28144995}. 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 HMN2B; induces hyperphosphorylation of neurofilaments; no effect on cytoplasmic location; no effect on dimerization.
Any additional useful information about the variant.



Sequence information

Variant position:  7
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  205
The length of the canonical sequence.

Location on the sequence:   MTERRV  P FSLLRGPSWDPFRDWYPHSR
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                         MTERRVPFSLLRGPSWDPFRDWYP-HSR

                              MTERRVPFSLLRSPSWDPFRDWYPAHS

Mouse                         MTERRVPFSLLRSPSWEPFRDWYPAHS

Rat                           MTERRVPFSLLRSPSWEPFRDWYPAHS

Pig                           MTERRVPFSLLRSPSWDPFRDWYPAHS

Bovine                        MAERRVPFSLLRGPSWDPFRDWYPAHS

Chicken                       MAERRVPFTFLTSPSWEPFRDWYH-GS

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 – 205 Heat shock protein beta-1
Modified residue 12 – 12 Omega-N-methylarginine
Modified residue 15 – 15 Phosphoserine; by MAPKAPK2 and MAPKAPK3
Modified residue 26 – 26 Phosphoserine
Mutagenesis 15 – 15 S -> D. Mimicks phosphorylation state, leading to dreased ability to act as molecular chaperones; when associated with D-78 and D-82.


Literature citations

Human HSP27 is phosphorylated at serines 78 and 82 by heat shock and mitogen-activated kinases that recognize the same amino acid motif as S6 kinase II.
Landry J.; Lambert H.; Zhou M.; Lavoie J.N.; Hickey E.; Weber L.A.; Anderson C.W.;
J. Biol. Chem. 267:794-803(1992)
Cited for: PROTEIN SEQUENCE OF 76-89; PHOSPHORYLATION AT SER-78 AND SER-82;

Identification of MAPKAP kinase 2 as a major enzyme responsible for the phosphorylation of the small mammalian heat shock proteins.
Stokoe D.; Engel K.; Campbell D.G.; Cohen P.; Gaestel M.;
FEBS Lett. 313:307-313(1992)
Cited for: PHOSPHORYLATION AT SER-15; SER-78 AND SER-82 BY MAPKAPK2;

A comparison of the substrate specificity of MAPKAP kinase-2 and MAPKAP kinase-3 and their activation by cytokines and cellular stress.
Clifton A.D.; Young P.R.; Cohen P.;
FEBS Lett. 392:209-214(1996)
Cited for: PHOSPHORYLATION AT SER-15; SER-78 AND SER-82;

Regulation of Hsp27 oligomerization, chaperone function, and protective activity against oxidative stress/tumor necrosis factor alpha by phosphorylation.
Rogalla T.; Ehrnsperger M.; Preville X.; Kotlyarov A.; Lutsch G.; Ducasse C.; Paul C.; Wieske M.; Arrigo A.P.; Buchner J.; Gaestel M.;
J. Biol. Chem. 274:18947-18956(1999)
Cited for: FUNCTION; SUBUNIT; PHOSPHORYLATION AT SER-15; SER-78 AND SER-82; MUTAGENESIS OF SER-15; SER-78 AND SER-82;

Heat shock protein 27 is associated with freedom from graft vasculopathy after human cardiac transplantation.
De Souza A.I.; Wait R.; Mitchell A.G.; Banner N.R.; Dunn M.J.; Rose M.L.;
Circ. Res. 97:192-198(2005)
Cited for: PHOSPHORYLATION AT SER-78 AND SER-82; IDENTIFICATION BY MASS SPECTROMETRY;

PKA-induced F-actin rearrangement requires phosphorylation of Hsp27 by the MAPKAP kinase MK5.
Kostenko S.; Johannessen M.; Moens U.;
Cell. Signal. 21:712-718(2009)
Cited for: FUNCTION; PHOSPHORYLATION AT SER-78 AND SER-82;

Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.
Olsen J.V.; Vermeulen M.; Santamaria A.; Kumar C.; Miller M.L.; Jensen L.J.; Gnad F.; Cox J.; Jensen T.S.; Nigg E.A.; Brunak S.; Mann M.;
Sci. Signal. 3:RA3-RA3(2010)
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-15; SER-65; SER-78; SER-82 AND SER-199; IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS];

Toward a comprehensive characterization of a human cancer cell phosphoproteome.
Zhou H.; Di Palma S.; Preisinger C.; Peng M.; Polat A.N.; Heck A.J.; Mohammed S.;
J. Proteome Res. 12:260-271(2013)
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-15; SER-78; SER-82; SER-86; THR-174; SER-176 AND SER-199; IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS];

An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.
Bian Y.; Song C.; Cheng K.; Dong M.; Wang F.; Huang J.; Sun D.; Wang L.; Ye M.; Zou H.;
J. Proteomics 96:253-262(2014)
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-15; SER-78; SER-82; SER-86; SER-98 AND SER-199; IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS];

Axonal Neuropathies due to Mutations in Small Heat Shock Proteins: Clinical, Genetic, and Functional Insights into Novel Mutations.
Echaniz-Laguna A.; Geuens T.; Petiot P.; Pereon Y.; Adriaenssens E.; Haidar M.; Capponi S.; Maisonobe T.; Fournier E.; Dubourg O.; Degos B.; Salachas F.; Lenglet T.; Eymard B.; Delmont E.; Pouget J.; Juntas Morales R.; Goizet C.; Latour P.; Timmerman V.; Stojkovic T.;
Hum. Mutat. 38:556-568(2017)
Cited for: VARIANTS HMN2B SER-7; LEU-39; ASP-53; TRP-127; ARG-128; ILE-151; 175-GLN--LYS-205 DEL; ILE-180 AND LEU-187; SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANTS HMN2B SER-7; ASP-53; ARG-128 AND LEU-187;

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.