Lamin A processing pathway (Homo sapiens)
From WikiPathways
Description
All lamins, except lamin C, contain a CaaX tail. This tail is comprised of respectively cysteine, two aliphatic amino acids and any amino acid with a COOH-terminal (variable). Aliphatic amino acids are nonpolar and hydrophobic and include glycine, alanine, valine, leucine and isoleucine. This structure acts as recognition point for a sequence of modifications. First the terminal cysteine is farnesylated by farnesyl transferase, where a isoprenyl group is added to the cysteine residue -also called isoprenylation. This is followed by proteolytic cleavage of the aaX part by Zmpste24 and methylation (CH3) of cysteine. Isoprenylation and methylation are both necessary for the localization of lamin A and B-type lamins in to the INM. Until this point processing of lamin A and type-B lamins is similar. While in type-B lamins the isoprenyl group remains attached to the cysteine, lamin A has a second cleavage site to cleave off an additional 15 amino acids upstream of the cysteine. This cleavage is also done by Zmpste24 and takes place at INM. When these 15 amino acids, 18 in total including aaX, are cleaved off mature lamin A is produced (1,2). Lamin processing is involved in progeria.
Quality Tags
Ontology Terms
Bibliography
- Cox LS, Faragher RG; ''From old organisms to new molecules: integrative biology and therapeutic targets in accelerated human ageing.''; Cell Mol Life Sci, 2007 PubMed Europe PMC Scholia
- Broers JL, Ramaekers FC, Bonne G, Yaou RB, Hutchison CJ; ''Nuclear lamins: laminopathies and their role in premature ageing.''; Physiol Rev, 2006 PubMed Europe PMC Scholia
History
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External references
DataNodes
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Name | Type | Database reference | Comment |
---|---|---|---|
15 amino acids | Metabolite | CHEBI:33709 (ChEBI) ![]() | |
CAAX prenyl protease 1 homolog | Protein | O75844 (Uniprot-TrEMBL) ![]() | |
C | Metabolite | CHEBI:15356 (ChEBI) ![]() | |
Farnesyl transferase | Protein | ||
LMNA | GeneProduct | ENSG00000160789 (Ensembl) ![]() | |
Mature lamin A | Protein | 72 kDa | |
Pre-lamin A | GeneProduct | P02545 (Uniprot-TrEMBL) ![]() | |
Progeria syndrome | Pathway | WP4320 (WikiPathways) ![]() | |
Protein-S-isoprenylcysteine O-methyltransferase | Protein | O60725 (Uniprot-TrEMBL) ![]() | |
ZMPSTE24 | GeneProduct | ENSG00000084073 (Ensembl) ![]() | |
aaX | Protein |
Annotated Interactions
No annotated interactions