O75844 · FACE1_HUMAN
- ProteinCAAX prenyl protease 1 homolog
- GeneZMPSTE24
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids475 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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).
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
Cofactor
Note: Binds 1 zinc ion per subunit.
Features
Showing features for binding site, active site.
GO annotations
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameCAAX prenyl protease 1 homolog
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionO75844
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
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.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-18 | Lumenal | ||||
Sequence: MGMWASLDALWEMPAEKR | ||||||
Transmembrane | 19-39 | Helical | ||||
Sequence: IFGAVLLFSWTVYLWETFLAQ | ||||||
Topological domain | 40-81 | Nuclear | ||||
Sequence: RQRRIYKTTTHVPPELGQIMDSETFEKSRLYQLDKSTFSFWS | ||||||
Transmembrane | 82-102 | Helical | ||||
Sequence: GLYSETEGTLILLFGGIPYLW | ||||||
Topological domain | 103-123 | Lumenal | ||||
Sequence: RLSGRFCGYAGFGPEYEITQS | ||||||
Transmembrane | 124-144 | Helical | ||||
Sequence: LVFLLLATLFSALTGLPWSLY | ||||||
Topological domain | 145-170 | Nuclear | ||||
Sequence: NTFVIEEKHGFNQQTLGFFMKDAIKK | ||||||
Transmembrane | 171-191 | Helical | ||||
Sequence: FVVTQCILLPVSSLLLYIIKI | ||||||
Topological domain | 192-195 | Lumenal | ||||
Sequence: GGDY | ||||||
Transmembrane | 196-216 | Helical | ||||
Sequence: FFIYAWLFTLVVSLVLVTIYA | ||||||
Topological domain | 217-347 | Nuclear | ||||
Sequence: DYIAPLFDKFTPLPEGKLKEEIEVMAKSIDFPLTKVYVVEGSKRSSHSNAYFYGFFKNKRIVLFDTLLEEYSVLNKDIQEDSGMEPRNEEEGNSEEIKAKVKNKKQGCKNEEVLAVLGHELGHWKLGHTVK | ||||||
Transmembrane | 348-368 | Helical | ||||
Sequence: NIIISQMNSFLCFFLFAVLIG | ||||||
Topological domain | 369-382 | Lumenal | ||||
Sequence: RKELFAAFGFYDSQ | ||||||
Transmembrane | 383-405 | Helical | ||||
Sequence: PTLIGLLIIFQFIFSPYNEVLSF | ||||||
Topological domain | 406-475 | Nuclear | ||||
Sequence: CLTVLSRRFEFQADAFAKKLGKAKDLYSALIKLNKDNLGFPVSDWLFSMWHYSHPPLLERLQALKTMKQH |
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Mandibuloacral dysplasia with type B lipodystrophy (MADB)
- Note
- DescriptionA 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 alsoMIM:608612
Natural variants in MADB
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_064501 | 248 | P>L | in MADB; does not affect enzyme activity; dbSNP:rs121908095 | |
VAR_064502 | 265 | N>S | in MADB; dbSNP:rs281875371 | |
VAR_019308 | 340 | W>R | in MADB; dbSNP:rs121908093 |
Restrictive dermopathy 1 (RSDM1)
- Note
- DescriptionAn 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 alsoMIM:275210
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_034711 | 137 | in dbSNP:rs17853725 | |||
Sequence: T → A | ||||||
Natural variant | VAR_064501 | 248 | in MADB; does not affect enzyme activity; dbSNP:rs121908095 | |||
Sequence: P → L | ||||||
Natural variant | VAR_064502 | 265 | in MADB; dbSNP:rs281875371 | |||
Sequence: N → S | ||||||
Mutagenesis | 335 | Loss of catalytic activity but not viral restriction. | ||||
Sequence: H → A | ||||||
Mutagenesis | 336 | Loss of catalytic activity but not viral restriction. | ||||
Sequence: E → A | ||||||
Natural variant | VAR_019308 | 340 | in MADB; dbSNP:rs121908093 | |||
Sequence: W → R |
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.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000138844 | 1-475 | UniProt | CAAX prenyl protease 1 homolog | |||
Sequence: MGMWASLDALWEMPAEKRIFGAVLLFSWTVYLWETFLAQRQRRIYKTTTHVPPELGQIMDSETFEKSRLYQLDKSTFSFWSGLYSETEGTLILLFGGIPYLWRLSGRFCGYAGFGPEYEITQSLVFLLLATLFSALTGLPWSLYNTFVIEEKHGFNQQTLGFFMKDAIKKFVVTQCILLPVSSLLLYIIKIGGDYFFIYAWLFTLVVSLVLVTIYADYIAPLFDKFTPLPEGKLKEEIEVMAKSIDFPLTKVYVVEGSKRSSHSNAYFYGFFKNKRIVLFDTLLEEYSVLNKDIQEDSGMEPRNEEEGNSEEIKAKVKNKKQGCKNEEVLAVLGHELGHWKLGHTVKNIIISQMNSFLCFFLFAVLIGRKELFAAFGFYDSQPTLIGLLIIFQFIFSPYNEVLSFCLTVLSRRFEFQADAFAKKLGKAKDLYSALIKLNKDNLGFPVSDWLFSMWHYSHPPLLERLQALKTMKQH | |||||||
Modified residue (large scale data) | 298 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 310 | PRIDE | Phosphoserine | ||||
Sequence: S |
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
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | O75844 | DEFB4B O15263 | 2 | EBI-1056377, EBI-21800352 | |
BINARY | O75844 | LMNA P02545-1 | 2 | EBI-1056377, EBI-351949 | |
XENO | O75844 | M P06821 | 2 | EBI-1056377, EBI-2547404 | |
XENO | O75844 | M2 C5E519 | 2 | EBI-1056377, EBI-12562139 | |
XENO | O75844 | M2 Q20MH8 | 2 | EBI-1056377, EBI-12576433 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Sequence
- Sequence statusComplete
- Length475
- Mass (Da)54,813
- Last updated2001-04-27 v2
- Checksum6C49179DEB0C8F7F
Computationally mapped potential isoform sequences
There are 3 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A6Q8PH40 | A0A6Q8PH40_HUMAN | ZMPSTE24 | 124 | ||
A0A6Q8PF67 | A0A6Q8PF67_HUMAN | ZMPSTE24 | 102 | ||
A0A6Q8PHG9 | A0A6Q8PHG9_HUMAN | ZMPSTE24 | 315 |
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 16 | in Ref. 1; BAA33727 | ||||
Sequence: E → K |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
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 |