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FLASH GENE
Symbol ZMPSTE24 contributors: mct/npt - updated : 26-10-2016
HGNC name zinc metallopeptidase (STE24 homolog, S. cerevisiae)
HGNC id 12877
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a HEXXH consensus motif characteristic of metalloproteinases , a consensus zinc metalloprotease motif, consisting of a HEXXH catalytic site, located in a loop predicted to reside in the cytosol/nucleoplasm
  • a GLU residue at position 415 which is a likely candidate to complete the metal binding site
  • a conserved Asp residue essential for full catalytic activity
  • seven transmembrane domains
    • secondary structure
  • seven transmembrane alpha-helical barrel structure, surrounding a large, water-filled, intramembrane chamber, capped by a zinc metalloprotease domain with the catalytic site facing into the chamber
    • conjugated MetalloP
    HOMOLOGY
    interspecies homolog to yeast S.cerevisiae Ste24p,CAAX prenyl protease
    Homologene
    FAMILY
  • peptidase M48A family
  • gluxinein subfamily of metalloproteinase
    • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,organelle,Golgi
    intracellular,nucleus
    intracellular,nuclear envelope,int
    text
  • integral membrane zinc metalloprotease (Barrowman (2009)
  • membrane-associated enzyme that is predicted to contain seven transmembrane segments and is localized to the ER membrane and the inner nuclear membrane
    • basic FUNCTION
  • involved in the proteolytic processing of farnesylated proteins
  • catalyzing the first step of the proteolytic processing of farnesylated proteins, including Ras, and also involved in NH2 terminal processing
  • endoprotease essential for the post-translational cleavage of the Lamin A precursor and the production of mature LMNA
  • key protease involved in human progeroid disorder (Barrowman 2009)
  • performs a critical endoproteolytic cleavage step that removes the hydrophobic farnesyl-modified tail of prelamin A (Barrowman 2009)
  • plays a critical role in nuclear lamin biology by cleaving the prenylated and carboxylmethylated 15-amino acid tail from the C-terminus of prelamin A to yield mature lamin A
  • only metalloprotease, which transforms prelamin into mature lamin A
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • protein constituent of membrane
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • prelamin A : cleavage of C terminal AAX tripeptide (AA 662 to 664) of farnesylated prelamin A, methylation of the prenylated cystein and cleavage of the last 15 AA (647 to 661) to form mature lamin A
  • only one identified mammalian substrate, the precursor of the nuclear scaffold protein lamin A (Barrowman 2009)
  • ZMPSTE24 processes prelamin A, a component of the nuclear lamina intermediate filaments, by cleaving it at two sites, and failure of this processing results in accumulation of farnesylated, membrane-associated prelamin A
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) MADYS2 , RDMP1 , LPCMD , HGPSA
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    • ANIMAL & CELL MODELS
  • Zmpste24-null progeroid mice (Zmpste24(-/-)), exhibit nuclear lamina defects and accumulate unprocessed prelamin A (Rivas 2009)
  • zmpste24&
    • 8722;/&
    8722; mouse exhibits a severe progeroid disorder that is completely alleviated in a mouse heterozygous for lamin A (zmpste24–/– lmna+/–), which reduces the load of toxic prelamin A by 50p100