O75844 · FACE1_HUMAN

  • Protein
    CAAX prenyl protease 1 homolog
  • Gene
    ZMPSTE24
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

Transmembrane metalloprotease whose catalytic activity is critical for processing lamin A/LMNA on the inner nuclear membrane and clearing clogged translocons on the endoplasmic reticulum (PubMed:33293369, PubMed:33315887).
Proteolytically removes the C-terminal three residues of farnesylated proteins (PubMed:33293369, PubMed:33315887).
Plays also an antiviral role independently of its protease activity by restricting enveloped RNA and DNA viruses, including influenza A, Zika, Ebola, Sindbis, vesicular stomatitis, cowpox, and vaccinia (PubMed:28169297, PubMed:28246125).
Mechanistically, controls IFITM antiviral pathway to hinder viruses from breaching the endosomal barrier by modulating membrane fluidity (PubMed:35283811).

Catalytic activity

  • Hydrolyzes the peptide bond -P2-(S-farnesyl or geranylgeranyl)C-P1'-P2'-P3'-COOH where P1' and P2' are amino acids with aliphatic side chains and P3' is any C-terminal residue.
    EC:3.4.24.84 (UniProtKB | ENZYME | Rhea)

Cofactor

Zn2+ (UniProtKB | Rhea| CHEBI:29105 )

Note: Binds 1 zinc ion per subunit.

Features

Showing features for binding site, active site.

TypeIDPosition(s)Description
Binding site335Zn2+ (UniProtKB | ChEBI); catalytic
Active site336
Binding site339Zn2+ (UniProtKB | ChEBI); catalytic
Binding site415Zn2+ (UniProtKB | ChEBI); catalytic

GO annotations

AspectTerm
Cellular Componentearly endosome membrane
Cellular Componentendoplasmic reticulum membrane
Cellular Componentextracellular exosome
Cellular Componentlate endosome membrane
Cellular Componentmembrane
Cellular Componentnuclear inner membrane
Cellular Componentprotein-containing complex
Molecular Functiondouble-stranded DNA binding
Molecular Functionendopeptidase activity
Molecular Functionmetal ion binding
Molecular Functionmetalloendopeptidase activity
Molecular Functionmetalloexopeptidase activity
Biological Processadult walking behavior
Biological Processbone mineralization
Biological ProcessCAAX-box protein processing
Biological Processcalcium ion import into sarcoplasmic reticulum
Biological ProcessCAMKK-AMPK signaling cascade
Biological Processcardiac conduction
Biological Processcardiac muscle cell development
Biological Processcardiac ventricle development
Biological Processcellular lipid metabolic process
Biological Processcellular response to gamma radiation
Biological Processdetermination of adult lifespan
Biological ProcessDNA repair
Biological Processgrowth plate cartilage development
Biological Processhair follicle development
Biological Processheart morphogenesis
Biological Processinflammatory cell apoptotic process
Biological Processkidney morphogenesis
Biological Processliver development
Biological Processmaintenance of rDNA
Biological Processmulticellular organism growth
Biological Processnegative regulation of miRNA processing
Biological Processneuromuscular process
Biological Processnuclear envelope organization
Biological Processpositive regulation of gene expression via chromosomal CpG island demethylation
Biological Processprenylated protein catabolic process
Biological Processprotein maturation
Biological Processproteolysis
Biological Processregulation of autophagy
Biological Processregulation of bone mineralization
Biological Processregulation of cell shape
Biological Processregulation of cellular senescence
Biological Processregulation of defense response to virus
Biological Processregulation of DNA damage response, signal transduction by p53 class mediator
Biological Processregulation of fibroblast proliferation
Biological Processregulation of glucose metabolic process
Biological Processregulation of hormone metabolic process
Biological Processregulation of lipid metabolic process
Biological Processregulation of mitotic cell cycle DNA replication
Biological Processregulation of multicellular organism growth
Biological Processregulation of stress-activated protein kinase signaling cascade
Biological Processregulation of termination of RNA polymerase I transcription
Biological Processregulation of TOR signaling
Biological Processregulation of ventricular cardiac muscle cell membrane repolarization
Biological Processresponse to DNA damage checkpoint signaling
Biological Processthymus development
Biological Processventricular cardiac muscle tissue development

Keywords

Enzyme and pathway databases

Protein family/group databases

Names & Taxonomy

Protein names

  • Recommended name
    CAAX prenyl protease 1 homolog
  • EC number
  • Alternative names
    • Farnesylated proteins-converting enzyme 1
      (FACE-1
      )
    • Prenyl protein-specific endoprotease 1
    • Zinc metalloproteinase Ste24 homolog

Gene names

    • Name
      ZMPSTE24
    • Synonyms
      FACE1
      , STE24

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo

Accessions

  • Primary accession
    O75844
  • Secondary accessions
    • B3KQI7
    • D3DPU7
    • Q8NDZ8
    • Q9UBQ2

Proteomes

Organism-specific databases

Subcellular Location

Endoplasmic reticulum membrane
; Multi-pass membrane protein
Nucleus inner membrane
; Multi-pass membrane protein
Early endosome membrane
; Multi-pass membrane protein
Late endosome membrane
; Multi-pass membrane protein

Features

Showing features for topological domain, transmembrane.

TypeIDPosition(s)Description
Topological domain1-18Lumenal
Transmembrane19-39Helical
Topological domain40-81Nuclear
Transmembrane82-102Helical
Topological domain103-123Lumenal
Transmembrane124-144Helical
Topological domain145-170Nuclear
Transmembrane171-191Helical
Topological domain192-195Lumenal
Transmembrane196-216Helical
Topological domain217-347Nuclear
Transmembrane348-368Helical
Topological domain369-382Lumenal
Transmembrane383-405Helical
Topological domain406-475Nuclear

Keywords

Disease & Variants

Involvement in disease

Mandibuloacral dysplasia with type B lipodystrophy (MADB)

  • Note
    • The disease is caused by variants affecting the gene represented in this entry
  • Description
    A form of mandibuloacral dysplasia, a rare progeroid disorder with clinical and genetic heterogeneity, characterized by growth retardation, craniofacial dysmorphic features due to distal bone resorption, musculoskeletal and skin abnormalities associated with lipodystrophy. MADB is a disease characterized by mandibular and clavicular hypoplasia, acroosteolysis, delayed closure of the cranial suture, joint contractures, and generalized lipodystrophy with loss of subcutaneous fat from the extremities, face, neck and trunk.
  • See also
    MIM:608612
Natural variants in MADB
Variant IDPosition(s)ChangeDescription
VAR_064501248P>Lin MADB; does not affect enzyme activity; dbSNP:rs121908095
VAR_064502265N>Sin MADB; dbSNP:rs281875371
VAR_019308340W>Rin MADB; dbSNP:rs121908093

Restrictive dermopathy 1 (RSDM1)

  • Note
    • The disease is caused by variants affecting the gene represented in this entry
  • Description
    An autosomal recessive form of restrictive dermopathy, a genodermatosis mainly characterized by intrauterine growth retardation, tight and rigid skin with erosions, prominent superficial vasculature and epidermal hyperkeratosis, facial dysmorphism, sparse/absent eyelashes and eyebrows, mineralization defects of the skull, thin dysplastic clavicles, pulmonary hypoplasia, multiple joint contractures and an early neonatal lethal course. Liveborn children usually die within the first week of life.
  • See also
    MIM:275210

Features

Showing features for natural variant, mutagenesis.

TypeIDPosition(s)Description
Natural variantVAR_034711137in dbSNP:rs17853725
Natural variantVAR_064501248in MADB; does not affect enzyme activity; dbSNP:rs121908095
Natural variantVAR_064502265in MADB; dbSNP:rs281875371
Mutagenesis335Loss of catalytic activity but not viral restriction.
Mutagenesis336Loss of catalytic activity but not viral restriction.
Natural variantVAR_019308340in MADB; dbSNP:rs121908093

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 509 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

Keywords

Organism-specific databases

Miscellaneous

Chemistry

Genetic variation databases

PTM/Processing

Features

Showing features for chain, modified residue (large scale data).

TypeIDPosition(s)SourceDescription
ChainPRO_00001388441-475UniProtCAAX prenyl protease 1 homolog
Modified residue (large scale data)298PRIDEPhosphoserine
Modified residue (large scale data)310PRIDEPhosphoserine

Proteomic databases

PTM databases

Expression

Tissue specificity

Widely expressed. High levels in kidney, prostate, testis and ovary.

Induction

By type I interferon.

Gene expression databases

Organism-specific databases

Interaction

Binary interactions

Protein-protein interaction databases

Miscellaneous

Family & Domains

Domain

The metalloprotease domain is constituted by the two C-terminal nuclear regions.

Sequence similarities

Belongs to the peptidase M48A family.

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    475
  • Mass (Da)
    54,813
  • Last updated
    2001-04-27 v2
  • Checksum
    6C49179DEB0C8F7F
MGMWASLDALWEMPAEKRIFGAVLLFSWTVYLWETFLAQRQRRIYKTTTHVPPELGQIMDSETFEKSRLYQLDKSTFSFWSGLYSETEGTLILLFGGIPYLWRLSGRFCGYAGFGPEYEITQSLVFLLLATLFSALTGLPWSLYNTFVIEEKHGFNQQTLGFFMKDAIKKFVVTQCILLPVSSLLLYIIKIGGDYFFIYAWLFTLVVSLVLVTIYADYIAPLFDKFTPLPEGKLKEEIEVMAKSIDFPLTKVYVVEGSKRSSHSNAYFYGFFKNKRIVLFDTLLEEYSVLNKDIQEDSGMEPRNEEEGNSEEIKAKVKNKKQGCKNEEVLAVLGHELGHWKLGHTVKNIIISQMNSFLCFFLFAVLIGRKELFAAFGFYDSQPTLIGLLIIFQFIFSPYNEVLSFCLTVLSRRFEFQADAFAKKLGKAKDLYSALIKLNKDNLGFPVSDWLFSMWHYSHPPLLERLQALKTMKQH

Computationally mapped potential isoform sequences

There are 3 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
A0A6Q8PH40A0A6Q8PH40_HUMANZMPSTE24124
A0A6Q8PF67A0A6Q8PF67_HUMANZMPSTE24102
A0A6Q8PHG9A0A6Q8PHG9_HUMANZMPSTE24315

Features

Showing features for sequence conflict.

TypeIDPosition(s)Description
Sequence conflict16in Ref. 1; BAA33727

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AB016068
EMBL· GenBank· DDBJ
BAA33727.1
EMBL· GenBank· DDBJ
mRNA
AF064867
EMBL· GenBank· DDBJ
AAC68866.1
EMBL· GenBank· DDBJ
mRNA
Y13834
EMBL· GenBank· DDBJ
CAB46277.1
EMBL· GenBank· DDBJ
mRNA
AK075007
EMBL· GenBank· DDBJ
BAG52049.1
EMBL· GenBank· DDBJ
mRNA
AL050341
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
CH471059
EMBL· GenBank· DDBJ
EAX07233.1
EMBL· GenBank· DDBJ
Genomic DNA
CH471059
EMBL· GenBank· DDBJ
EAX07234.1
EMBL· GenBank· DDBJ
Genomic DNA
BC037283
EMBL· GenBank· DDBJ
AAH37283.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

Disclaimer

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