Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P01034 (
cystatin C
)
3,397
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
An artificial mutant Ala25Ser precursor
cystatin C
was created to help elucidate the cause of intracellular mis-localisation of the biochemically related variant B (Ala25Thr) precursor
cystatin C
to the mitochondria. Homozygotes of variant B precursor
cystatin C
were reported to carry an increased susceptibility to developing the exudative form of
AMD
. Ala25Ser precursor
cystatin C
shows a dual distribution to the Golgi apparatus and to the mitochondria. This localisation is thus intermediary between that of wild-type
cystatin C
(targeted to ER/Golgi compartment) and that of variant B precursor
cystatin C
. Furthermore, the level of secretion of Ala25Ser
cystatin C
by RPE cells is intermediary between wild type and variant B
cystatin C
. Ala25Ser precursor
cystatin C
thus represents a biochemical intermediate between the wild type and the
AMD
-associated
cystatin C
and as such, is a novel tool for the investigation of the mechanism of intracellular mis-localisation of variant B
cystatin C
. Our findings further support the hypothesis that substitution of the alanine residue in the penultimate position of precursor
cystatin C
signal sequence with a less hydrophobic amino acid residue, such as threonine (as in variant B
cystatin C
) or serine is sufficient to impair the intracellular trafficking and processing of the protein.
...
PMID:A dual Golgi- and mitochondria-localised Ala25Ser precursor cystatin C: an additional tool for characterising intracellular mis-localisation leading to increased AMD susceptibility. 1663 87
