Progerin (original) (raw)
Progerin (UniProt# P02545-6) is a truncated version of the lamin A protein involved in the pathology of Hutchinson–Gilford progeria syndrome. Progerin is most often generated by a sporadic single point nucleotide polymorphism c.1824 C>T (GGC -> GGT, p.Gly608Gly) in the gene that codes for matured Lamin A. This mutation activates a cryptic splice site that induces a mutation in premature Lamin A with the deletion of a 50 amino acids group near the C-terminus. The endopeptidase ZMPSTE24 cannot cleave between the missing RSY - LLG amino acid sequence (as seen in the figure) during the maturation of Lamin A, due to the deletion of the 50 amino acids which included that sequence. This leaves the intact premature Lamin A bonded to the methylated carboxyl farnesyl group creating the defective pro
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| dbo:abstract | La progerina (UniProt# P02545-6) és una versió truncada de la proteïna lamina A implicada en la patologia de la síndrome de progèria de Hutchinson-Gilford . La progerina es pot generar per un polimorfisme esporàdic de nucleòtids d'un sol punt c.1824 C>T (GGC -> GGT, p. Gly608Gly) en el gen que codifica per a la lamina A madura. Aquesta mutació activa un lloc d'empalmament críptic que indueix una mutació en la lamina A prematura amb la supressió d'un grup de 50 aminoàcids prop de l' extrem C-terminal . L'endopeptidasa ZMPSTE24 no pot escindir entre la seqüència d'aminoàcids RSY - LLG que falta (com es veu a la figura) durant la maduració de la lamina A, a causa de la supressió dels 50 aminoàcids que incloïen aquesta seqüència. Això deixa la lamina A prematura intacta unida al grup carboxil farnesil metilat creant la proteïna defectuosa Progerina, en lloc de la proteïna madurada desitjada Lamin A. Aproximadament el 90% de tots els casos de síndrome de progèria de Hutchinson-Gilford són heterozigots per a aquest polimorfisme deleteri d'un sol nucleòtid dins de l'exó 11 del gen LMNA causant les modificacions post-traduccions per produir progerina. (ca) Progerin (UniProt# P02545-6) is a truncated version of the lamin A protein involved in the pathology of Hutchinson–Gilford progeria syndrome. Progerin is most often generated by a sporadic single point nucleotide polymorphism c.1824 C>T (GGC -> GGT, p.Gly608Gly) in the gene that codes for matured Lamin A. This mutation activates a cryptic splice site that induces a mutation in premature Lamin A with the deletion of a 50 amino acids group near the C-terminus. The endopeptidase ZMPSTE24 cannot cleave between the missing RSY - LLG amino acid sequence (as seen in the figure) during the maturation of Lamin A, due to the deletion of the 50 amino acids which included that sequence. This leaves the intact premature Lamin A bonded to the methylated carboxyl farnesyl group creating the defective protein Progerin, rather than the desired protein matured Lamin A. Approximately 90% of all Hutchinson–Gilford progeria syndrome cases are heterozygous for this deleterious single nucleotide polymorphism within exon 11 of the LMNA gene causing the post-translational modifications to produce Progerin. Lamin A constitutes a major structural component of the lamina, a scaffold of proteins found inside the nuclear membrane of a cell; progerin does not properly integrate into the lamina, which disrupts the scaffold structure and leads to significant disfigurement of the nucleus, characterized by a globular shape. Progerin activates genes that regulate stem cell differentiation via the Notch signaling pathway. Progerin increases the frequency of unrepaired double-strand breaks in DNA following exposure to ionizing radiation. Also, overexpression of progerin is correlated with an increase in non-homologous end joining relative to homologous recombination among those DNA double-strand breaks that are repaired. Furthermore, the fraction of homologous recombination events occurring by gene conversion is increased. These findings suggest that the normal untruncated nuclear lamina has an important role in the proper repair of DNA double-strand breaks. (en) |
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| dbo:wikiPageWikiLink | dbr:DNA_repair dbr:P53 dbc:Human_proteins dbr:Gene_conversion dbr:Notch_signaling_pathway dbr:Glycine dbr:Lonafarnib dbr:Stem_cell dbr:Cell_(biology) dbr:Ageing dbr:Amino_acid dbc:Aging-related_proteins dbr:Cell_membrane dbr:Cellular_differentiation dbr:Farnesyltransferase_inhibitor dbr:Protein dbr:Ionizing_radiation dbr:Hutchinson–Gilford_progeria_syndrome dbr:Homologous_recombination dbr:C-terminus dbr:DNA_damage dbr:Rapamycin dbr:ZMPSTE24 dbr:Exon dbr:Nuclear_lamina dbr:Non-homologous_end_joining dbr:Nuclear_membrane dbr:Lamin_A dbr:Cryptic_splice_site dbr:Single_nucleotide_polymorphism dbr:File:Biogenesis_of_lamin_A_in_normal_c...o_generate_mature_lamin_A_in_HGPS.jpg |
| dcterms:subject | dbc:Human_proteins dbc:Aging-related_proteins |
| gold:hypernym | dbr:Version |
| rdf:type | dbo:Work yago:Abstraction100002137 yago:Chemical114806838 yago:Compound114818238 yago:Macromolecule114944888 yago:Material114580897 yago:Matter100020827 yago:Molecule114682133 yago:OrganicCompound114727670 yago:Part113809207 yago:PhysicalEntity100001930 yago:Protein114728724 yago:Relation100031921 yago:WikicatHumanProteins yago:Substance100019613 yago:Thing100002452 yago:Unit109465459 yago:WikicatAging-relatedProteins |
| rdfs:comment | Progerin (UniProt# P02545-6) is a truncated version of the lamin A protein involved in the pathology of Hutchinson–Gilford progeria syndrome. Progerin is most often generated by a sporadic single point nucleotide polymorphism c.1824 C>T (GGC -> GGT, p.Gly608Gly) in the gene that codes for matured Lamin A. This mutation activates a cryptic splice site that induces a mutation in premature Lamin A with the deletion of a 50 amino acids group near the C-terminus. The endopeptidase ZMPSTE24 cannot cleave between the missing RSY - LLG amino acid sequence (as seen in the figure) during the maturation of Lamin A, due to the deletion of the 50 amino acids which included that sequence. This leaves the intact premature Lamin A bonded to the methylated carboxyl farnesyl group creating the defective pro (en) |
| rdfs:label | Progerina (ca) プロジェリン (ja) Progerin (en) |
| owl:sameAs | freebase:Progerin yago-res:Progerin wikidata:Progerin dbpedia-ca:Progerin dbpedia-ja:Progerin https://global.dbpedia.org/id/4tnVm |
| prov:wasDerivedFrom | wikipedia-en:Progerin?oldid=1109471681&ns=0 |
| foaf:depiction | wiki-commons:Special:FilePath/Biogenesis_of_lamin_A...o_generate_mature_lamin_A_in_HGPS.jpg |
| foaf:isPrimaryTopicOf | wikipedia-en:Progerin |
| is dbo:wikiPageWikiLink of | dbr:Progeria dbr:Pre-Lamin_A/C dbr:Lonafarnib dbr:Progeroid_syndromes dbr:Cellular_senescence |
| is foaf:primaryTopic of | wikipedia-en:Progerin |
