Lamin A processing pathway (Homo sapiens)

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CCaaX group1, 2CaaX groupCH3Farnesyl groupProgeria syndrome15 amino acidsZMPSTE24Farnesyl transferaseLMNAaaXCAAX prenyl protease 1 homologMature lamin AProtein-S-isoprenylcysteine O-methyltransferasePre-lamin ACPre-lamin APre-lamin ACAAX prenyl protease 1 homologZMPSTE24CPre-lamin A


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).

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Ontology Terms

 

Bibliography

  1. 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
  2. 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

View all...
CompareRevisionActionTimeUserComment
128824view23:55, 22 February 2024EweitzModified title
126536view09:46, 29 May 2023EgonwTyped a datanode and added a ChEBI identifier
120397view08:59, 30 November 2021Fehrhartboxed pathway node
110694view13:52, 28 May 2020LaurentAdded missing DataNode type
108074view11:42, 28 November 2019FehrhartModified description
108073view11:41, 28 November 2019FehrhartOntology Term : 'progeria' added !
108072view11:41, 28 November 2019FehrhartOntology Term : 'disease pathway' added !
108071view11:41, 28 November 2019FehrhartOntology Term : 'Disease' added !
98006view12:48, 2 July 2018DeSlConnected line
98005view12:48, 2 July 2018DeSlAdded PW link to progeria syndrome PW.
97976view13:48, 28 June 2018FehrhartOntology Term : 'signaling pathway' added !
97954view12:36, 26 June 2018LorasimonsC annotated as cysteine
97951view11:35, 26 June 2018LorasimonsModified description
97950view11:27, 26 June 2018LorasimonsAdded literature
97949view11:25, 26 June 2018LorasimonsModified description
97948view11:25, 26 June 2018LorasimonsModified description
97947view11:24, 26 June 2018LorasimonsModified description
97946view11:23, 26 June 2018LorasimonsChanged layout
97911view15:39, 23 June 2018EgonwAnd now really to the protein.
97910view15:14, 23 June 2018EgonwHave the arrow go from protein to protein here too.
97749view13:08, 7 June 2018DeSlAdded weight for mature lamin A (no ID)
97733view12:57, 7 June 2018DeSlChanged C-labels to Metabolites, added ChEBI ID.
97635view13:17, 31 May 2018LorasimonsStraightening lines
97634view13:10, 31 May 2018LorasimonsNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
15 amino acids
CAAX prenyl protease 1 homologProteinO75844 (Uniprot-TrEMBL)
CMetaboliteCHEBI:15356 (ChEBI)
Farnesyl transferaseProtein
LMNAGeneProductENSG00000160789 (Ensembl)
Mature lamin AProtein72 kDa
Pre-lamin AGeneProductP02545 (Uniprot-TrEMBL)
Progeria syndromePathwayWP4320 (WikiPathways)
Protein-S-isoprenylcysteine O-methyltransferaseProteinO60725 (Uniprot-TrEMBL)
ZMPSTE24GeneProductENSG00000084073 (Ensembl)
aaX

Annotated Interactions

No annotated interactions

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