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UniProtKB/Swiss-Prot Q5T4F4: Variant p.Gly191Val

Protrudin
Gene: ZFYVE27
Variant information

Variant position:  191
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 Glycine (G) to Valine (V) at position 191 (G191V, p.Gly191Val).
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 glycine (G) to medium size and hydrophobic (V)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -3
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 SPG33; no effect on its function in the regulation of ER morphology and stability, no effect on its localization to ER but according to PubMed:16826525 an aberrant subcellular localization to cell membrane seen, altered interaction with SPAST, increased susceptibility to ER stress, no effect on its interaction with REEP1, REEP5 and ATL1 and increased protein stability.
Any additional useful information about the variant.

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



Sequence information

Variant position:  191
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  411
The length of the canonical sequence.

Location on the sequence:   YRVLHWENPVVSSQFYGALL  G TVCMLYLLPLCWVLTLLNST
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                         YRVLHWENPVVSSQFYGALLGTVCMLYLLPLCWVLTLLNST

Mouse                         YRVLHWENPVVSSQFYGALLGMVCMLYLLPLCWVLALLNST

Rat                           YRVLHWENPVVSSQFYGALLGMVCMLYLLPLCWVLALLNST

Bovine                        YRVLHWENPAVSSQFYGALLGTVCMLYLLPLCWVLALLNST

Chicken                       YRVLYWENPTVSSQFYGALLGSVCILYLLPLCWVMAILNST

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 – 411 Protrudin
Intramembrane 188 – 208 Helical
Region 1 – 205 Sufficient for localization to endoplasmic reticulum tubular network and for interactions with REEP1, REEP5, ATL1, ATL2, ATL3 and SPAST


Literature citations

ZFYVE27 (SPG33), a novel spastin-binding protein, is mutated in hereditary spastic paraplegia.
Mannan A.U.; Krawen P.; Sauter S.M.; Boehm J.; Chronowska A.; Paulus W.; Neesen J.; Engel W.;
Am. J. Hum. Genet. 79:351-357(2006)
Cited for: VARIANT SPG33 VAL-191; CHARACTERIZATION OF VARIANT SPG33 VAL-191; SUBCELLULAR LOCATION; INTERACTION WITH SPAST;

The role of ZFYVE27/protrudin in hereditary spastic paraplegia.
Martignoni M.; Riano E.; Rugarli E.I.;
Am. J. Hum. Genet. 83:127-130(2008)
Cited for: CHARACTERIZATION OF VARIANT SPG33 VAL-191;

Protrudin binds atlastins and endoplasmic reticulum-shaping proteins and regulates network formation.
Chang J.; Lee S.; Blackstone C.;
Proc. Natl. Acad. Sci. U.S.A. 110:14954-14959(2013)
Cited for: CHARACTERIZATION OF VARIANT SPG33 VAL-191; FUNCTION; SUBUNIT; SUBCELLULAR LOCATION; TOPOLOGY; INTERACTION WITH REEP1; REEP5; ATL1; ATL2; ATL3 AND SPAST;

Protrudin regulates endoplasmic reticulum morphology and function associated with the pathogenesis of hereditary spastic paraplegia.
Hashimoto Y.; Shirane M.; Matsuzaki F.; Saita S.; Ohnishi T.; Nakayama K.I.;
J. Biol. Chem. 289:12946-12961(2014)
Cited for: CHARACTERIZATION OF VARIANT SPG33 VAL-191; FUNCTION; SUBCELLULAR LOCATION; INTERACTION WITH REEP1; REEP5 AND ATL1;

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.