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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
Corresponding disease
HGPSA Hutchinson-Gilford progeria syndrome, atypical
LPCMD partial lipodystrophic syndrome with cardiomyopathy and diabetes
MADYS2 mandibuloacral dysplasia 2
RDMP1 restrictive dermopathy, lethal 1
Location 1p34.2      Physical location : 40.723.732 - 40.759.855
Synonym name
  • farnesylated-proteins converting enzyme 1
  • prenyl protein-specific endoprotease 1
  • zinc metalloproteinase (STE24 homolog, yeast)
  • CAAX prenyl protease
  • farnesylated proteins-converting enzyme 1
    • Synonym symbol(s) FACE1, FACE-1, Ste24p, STE24, HGPS, PRO1, FLJ14968, MADB
    EC.number 3.4.24.84
    DNA
    TYPE functioning gene
    STRUCTURE 36.12 kb     10 Exon(s)
    Genomic sequence alignment details
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked   status confirmed
    Map pter - D1S478 - D1S2864 - C1QB C1QB - D1S482 - D1S2674 - FUCA1 - D1S2749 - D1S449 - D1S2639 - D1S247 - D1S513 - COL16A1 - D1S2676 - D1S2613 - D1S2783 - D1S2729 - D1S472 - POU3F1 - D1S432 - D1S4743 - D1S2645 - ZMPSTE24 - D1S193 - D1S2861 - UROD - D1S443 - D1S447 - D1S2724 - D1S197 - EPS15 - D1S231 - D1S2661 - D1S417 - cen
    Authors GeneMap (98)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    10 - 3154 - 475 - 2004 15317753
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularvesselsaorta   
    Reproductivefemale systemovary   
     male systemtestis   
     male systemprostate   
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    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