ZMPSTE24

Protein identityUniProt · HPA

UniProt accession

O75844

Gene

ZMPSTE24

Ensembl

ENSG00000084073

Chromosome

1

Canonical length

475 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Potential drug targets, Predicted membrane proteins, Transporters

OverviewNCBI Gene

This gene encodes a member of the peptidase M48A family. The encoded protein is a zinc metalloproteinase involved in the two step post-translational proteolytic cleavage of carboxy terminal residues of farnesylated prelamin A to form mature lamin A. Mutations in this gene have been associated with mandibuloacral dysplasia and restrictive dermopathy. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

475 residues, UniProt reviewed canonical sequence.

>O75844|ZMPSTE24
     1  MGMWASLDAL WEMPAEKRIF GAVLLFSWTV YLWETFLAQR QRRIYKTTTH VPPELGQIMD
    61  SETFEKSRLY QLDKSTFSFW SGLYSETEGT LILLFGGIPY LWRLSGRFCG YAGFGPEYEI
   121  TQSLVFLLLA TLFSALTGLP WSLYNTFVIE EKHGFNQQTL GFFMKDAIKK FVVTQCILLP
   181  VSSLLLYIIK IGGDYFFIYA WLFTLVVSLV LVTIYADYIA PLFDKFTPLP EGKLKEEIEV
   241  MAKSIDFPLT KVYVVEGSKR SSHSNAYFYG FFKNKRIVLF DTLLEEYSVL NKDIQEDSGM
   301  EPRNEEEGNS EEIKAKVKNK KQGCKNEEVL AVLGHELGHW KLGHTVKNII ISQMNSFLCF
   361  FLFAVLIGRK ELFAAFGFYD SQPTLIGLLI IFQFIFSPYN EVLSFCLTVL SRRFEFQADA
   421  FAKKLGKAKD LYSALIKLNK DNLGFPVSDW LFSMWHYSHP PLLERLQALK TMKQH

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ZMPSTE24 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Other membrane

Secreted

No

Transmembrane segments

7

Mean surface accessibility (rSASA)

0.3

Highest tissue expression

50 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ZMPSTE24.

Disease | AllUniProt

Conditions ZMPSTE24 is implicated in, by any mechanism.

• Mandibuloacral dysplasia with type B lipodystrophy (MADB) MIM:608612
• Restrictive dermopathy 1 (RSDM1) MIM:275210

Disease | GeneticClinVar

38 pathogenic / likely-pathogenic of 259 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Mandibuloacral dysplasia with type B lipodystrophy
• Lethal tight skin contracture syndrome
• Restrictive dermopathy 1
• ZMPSTE24-related disorder
• Autosomal recessive ZMPSTE24-related disorders

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.33

gnomAD pLI

0

gnomAD missense Z

0.37

DepMap mean gene effect

-0.01

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 7% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• adult walking behavior
• bone mineralization
• CAAX-box protein processing
• calcium ion import into sarcoplasmic reticulum
• CAMKK-AMPK signaling cascade
• cardiac conduction
• cardiac muscle cell development
• cardiac ventricle development
• cellular response to gamma radiation
• determination of adult lifespan
• DNA repair
• growth plate cartilage development
• hair follicle development
• heart morphogenesis
• inflammatory cell apoptotic process
• kidney morphogenesis
• lipid metabolic process
• liver development
• maintenance of rDNA
• multicellular organism growth
• negative regulation of miRNA processing
• neuromuscular process
• nuclear envelope organization
• positive regulation of gene expression via chromosomal CpG island demethylation
• prenylated protein catabolic process
• protein maturation
• proteolysis
• regulation of autophagy
• regulation of bone mineralization
• regulation of cell shape
• regulation of cellular senescence
• regulation of defense response to virus
• regulation of DNA damage response, signal transduction by p53 class mediator
• regulation of fibroblast proliferation
• regulation of glucose metabolic process
• regulation of hormone metabolic process
• regulation of lipid metabolic process
• regulation of multicellular organism growth
• regulation of TOR signaling
• regulation of ventricular cardiac muscle cell membrane repolarization
• response to DNA damage checkpoint signaling
• thymus development
• ventricular cardiac muscle tissue development
• regulation of mitotic cell cycle DNA replication
• regulation of stress-activated protein kinase signaling cascade
• regulation of termination of RNA polymerase I transcription

Molecular functions

• double-stranded DNA binding
• endopeptidase activity
• metal ion binding
• metalloendopeptidase activity
• metalloexopeptidase activity

Cellular components

• early endosome membrane
• endoplasmic reticulum membrane
• extracellular exosome
• late endosome membrane
• membrane
• nuclear inner membrane
• protein-containing complex

Protein domainsUniProt · Pfam · InterPro

• Peptidase M48
• Peptidase family M48
• CAAX prenyl protease 1
• CAAX prenyl protease 1, N-terminal
• CAAX prenyl protease N-terminal, five membrane helices

KeywordsUniProt

• Antiviral protein
• Endoplasmic reticulum
• Endosome
• Hydrolase
• Membrane
• Metal-binding
• Metalloprotease
• Nucleus
• Protease
• Transmembrane
• Transmembrane helix
• Zinc

InteractionsUniProt · HPA

Protein binding partners of ZMPSTE24 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• STX8