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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

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_005857 10 - 3154 NP_005848 - 475 - 2004 15317753

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular vessels aorta       Reproductive female system ovary         male system testis         male system prostate

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