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O75844 (FACE1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 133. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
CAAX prenyl protease 1 homolog

EC=3.4.24.84
Alternative name(s):
Farnesylated proteins-converting enzyme 1
Short name=FACE-1
Prenyl protein-specific endoprotease 1
Zinc metalloproteinase Ste24 homolog
Gene names
Name:ZMPSTE24
Synonyms:FACE1, STE24
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length475 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Proteolytically removes the C-terminal three residues of farnesylated proteins. Acts on lamin A/C.

Catalytic activity

The peptide bond hydrolyzed can be designated -C-|-A-A-X in which C is an S-isoprenylated cysteine residue, A is usually aliphatic and X is the C-terminal residue of the substrate protein, and may be any of several amino acids.

Cofactor

Binds 1 zinc ion per subunit. Ref.10

Subcellular location

Endoplasmic reticulum membrane; Multi-pass membrane protein. Nucleus inner membrane; Multi-pass membrane protein Ref.10.

Tissue specificity

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

Domain

The metalloprotease domain is constituted by the two C-terminal nuclear regions. Ref.10

Involvement in disease

Mandibuloacral dysplasia with type B lipodystrophy (MADB) [MIM:608612]: A disorder 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.11 Ref.13 Ref.14 Ref.15

Lethal tight skin contracture syndrome (LTSCS) [MIM:275210]: Rare disorder mainly characterized by intrauterine growth retardation, tight and rigid skin with erosions, prominent superficial vasculature and epidermal hyperkeratosis, facial features (small mouth, small pinched nose and micrognathia), 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. The overall prevalence of consanguineous cases suggested an autosomal recessive inheritance.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.12

Sequence similarities

Belongs to the peptidase M48A family.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 475475CAAX prenyl protease 1 homolog
PRO_0000138844

Regions

Topological domain1 – 1818Lumenal Potential
Transmembrane19 – 3921Helical; Potential
Topological domain40 – 8142Nuclear Potential
Transmembrane82 – 10221Helical; Potential
Topological domain103 – 12321Lumenal Potential
Transmembrane124 – 14421Helical; Potential
Topological domain145 – 17026Nuclear Potential
Transmembrane171 – 19121Helical; Potential
Topological domain192 – 1954Lumenal Potential
Transmembrane196 – 21621Helical; Potential
Topological domain217 – 347131Nuclear Potential
Transmembrane348 – 36821Helical; Potential
Topological domain369 – 38214Lumenal Potential
Transmembrane383 – 40523Helical; Potential
Topological domain406 – 47570Nuclear Potential

Sites

Active site3361 Ref.10
Active site4191Proton donor By similarity
Metal binding3351Zinc; catalytic
Metal binding3391Zinc; catalytic
Metal binding4151Zinc; catalytic

Natural variations

Natural variant1371T → A. Ref.7
Corresponds to variant rs17853725 [ dbSNP | Ensembl ].
VAR_034711
Natural variant2481P → L in MADB; found in compound heterozygotes carrying a null allele; does not affect enzyme activity. Ref.14 Ref.15
VAR_064501
Natural variant2651N → S in MADB. Ref.13
VAR_064502
Natural variant3401W → R in MADB. Ref.11
VAR_019308

Experimental info

Sequence conflict161E → K in BAA33727. Ref.1

Secondary structure

.................................................. 475
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
O75844 [UniParc].

Last modified April 27, 2001. Version 2.
Checksum: 6C49179DEB0C8F7F

FASTA47554,813
        10         20         30         40         50         60 
MGMWASLDAL WEMPAEKRIF GAVLLFSWTV YLWETFLAQR QRRIYKTTTH VPPELGQIMD 

        70         80         90        100        110        120 
SETFEKSRLY QLDKSTFSFW SGLYSETEGT LILLFGGIPY LWRLSGRFCG YAGFGPEYEI 

       130        140        150        160        170        180 
TQSLVFLLLA TLFSALTGLP WSLYNTFVIE EKHGFNQQTL GFFMKDAIKK FVVTQCILLP 

       190        200        210        220        230        240 
VSSLLLYIIK IGGDYFFIYA WLFTLVVSLV LVTIYADYIA PLFDKFTPLP EGKLKEEIEV 

       250        260        270        280        290        300 
MAKSIDFPLT KVYVVEGSKR SSHSNAYFYG FFKNKRIVLF DTLLEEYSVL NKDIQEDSGM 

       310        320        330        340        350        360 
EPRNEEEGNS EEIKAKVKNK KQGCKNEEVL AVLGHELGHW KLGHTVKNII ISQMNSFLCF 

       370        380        390        400        410        420 
FLFAVLIGRK ELFAAFGFYD SQPTLIGLLI IFQFIFSPYN EVLSFCLTVL SRRFEFQADA 

       430        440        450        460        470 
FAKKLGKAKD LYSALIKLNK DNLGFPVSDW LFSMWHYSHP PLLERLQALK TMKQH 

« Hide

References

« Hide 'large scale' references
[1]"Identification of a human cDNA encoding a novel protein structurally related to the yeast membrane-associated metalloprotease, Ste24p."
Kumagai H., Kawamura Y., Yanagisawa K., Komano H.
Biochim. Biophys. Acta 1426:468-474(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Brain.
[2]"Dual roles for Ste24p in yeast a-factor maturation: NH2-terminal proteolysis and COOH-terminal CAAX processing."
Tam A., Nouvet F.J., Fujimura-Kamada K., Slunt H., Sisodia S.S., Michaelis S.
J. Cell Biol. 142:635-649(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: B-cell and Fetal brain.
[3]"Identification and chromosomal location of two human genes encoding enzymes potentially involved in proteolytic maturation of farnesylated proteins."
Freije J.M.P., Blay P., Pendas A.M., Cadinanos J., Crespo P., Lopez-Otin C.
Genomics 58:270-280(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Ovary.
[4]"Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries."
Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J., Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S., Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y. expand/collapse author list , Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S., Isogai T.
DNA Res. 12:117-126(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ALA-137.
Tissue: Testis.
[8]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[9]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]"The structural basis of ZMPSTE24-dependent laminopathies."
Quigley A., Dong Y.Y., Pike A.C., Dong L., Shrestha L., Berridge G., Stansfeld P.J., Sansom M.S., Edwards A.M., Bountra C., von Delft F., Bullock A.N., Burgess-Brown N.A., Carpenter E.P.
Science 339:1604-1607(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.4 ANGSTROMS) IN COMPLEX WITH TETRAPEPTIDE, ACTIVE SITE, COFACTOR, METALLOPROTEASE DOMAIN, TOPOLOGY, ZINC-BINDING SITES, SUBCELLULAR LOCATION.
[11]"Zinc metalloproteinase, ZMPSTE24, is mutated in mandibuloacral dysplasia."
Agarwal A.K., Fryns J.-P., Auchus R.J., Garg A.
Hum. Mol. Genet. 12:1995-2001(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MADB ARG-340.
[12]"Lamin A and ZMPSTE24 (FACE-1) defects cause nuclear disorganization and identify restrictive dermopathy as a lethal neonatal laminopathy."
Navarro C.L., De Sandre-Giovannoli A., Bernard R., Boccaccio I., Boyer A., Genevieve D., Hadj-Rabia S., Gaudy-Marqueste C., Smitt H.S., Vabres P., Faivre L., Verloes A., Van Essen T., Flori E., Hennekam R., Beemer F.A., Laurent N., Le Merrer M., Cau P., Levy N.
Hum. Mol. Genet. 13:2493-2503(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN LTSCS.
[13]"Focal segmental glomerulosclerosis in patients with mandibuloacral dysplasia owing to ZMPSTE24 deficiency."
Agarwal A.K., Zhou X.J., Hall R.K., Nicholls K., Bankier A., Van Esch H., Fryns J.P., Garg A.
J. Invest. Med. 54:208-213(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MADB SER-265.
[14]"Severe mandibuloacral dysplasia caused by novel compound heterozygous ZMPSTE24 mutations in two Japanese siblings."
Miyoshi Y., Akagi M., Agarwal A.K., Namba N., Kato-Nishimura K., Mohri I., Yamagata M., Nakajima S., Mushiake S., Shima M., Auchus R.J., Taniike M., Garg A., Ozono K.
Clin. Genet. 73:535-544(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MADB LEU-248, CHARACTERIZATION OF VARIANT MADB.
[15]"Early onset mandibuloacral dysplasia due to compound heterozygous mutations in ZMPSTE24."
Ahmad Z., Zackai E., Medne L., Garg A.
Am. J. Med. Genet. A 152:2703-2710(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MADB LEU-248.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB016068 mRNA. Translation: BAA33727.1.
AF064867 mRNA. Translation: AAC68866.1.
Y13834 mRNA. Translation: CAB46277.1.
AK075007 mRNA. Translation: BAG52049.1.
AL050341 Genomic DNA. Translation: CAB81610.1.
CH471059 Genomic DNA. Translation: EAX07233.1.
CH471059 Genomic DNA. Translation: EAX07234.1.
BC037283 mRNA. Translation: AAH37283.1.
RefSeqNP_005848.2. NM_005857.4.
UniGeneHs.132642.
Hs.721062.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2YPTX-ray3.80A/B/D/E1-475[»]
4AW6X-ray3.40A/B/D/E1-475[»]
ProteinModelPortalO75844.
SMRO75844. Positions 2-472.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid115560. 23 interactions.
IntActO75844. 2 interactions.
STRING9606.ENSP00000361845.

Protein family/group databases

MEROPSM48.003.
TCDB9.B.1.1.1. the integral membrane caax protease (caax protease) family.

PTM databases

PhosphoSiteO75844.

Proteomic databases

PaxDbO75844.
PeptideAtlasO75844.
PRIDEO75844.

Protocols and materials databases

DNASU10269.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000372759; ENSP00000361845; ENSG00000084073.
GeneID10269.
KEGGhsa:10269.
UCSCuc001cfg.4. human.

Organism-specific databases

CTD10269.
GeneCardsGC01P040723.
HGNCHGNC:12877. ZMPSTE24.
HPAHPA006988.
MIM275210. phenotype.
606480. gene.
608612. phenotype.
neXtProtNX_O75844.
Orphanet740. Hutchinson-Gilford progeria syndrome.
1662. Lethal restrictive dermopathy.
90154. Mandibuloacral dysplasia with type B lipodystrophy.
PharmGKBPA37466.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0501.
HOGENOMHOG000257874.
HOVERGENHBG051541.
InParanoidO75844.
KOK06013.
OMARFGFNKM.
OrthoDBEOG7RRF70.
PhylomeDBO75844.
TreeFamTF105972.

Enzyme and pathway databases

BRENDA3.4.24.84. 2681.

Gene expression databases

ArrayExpressO75844.
BgeeO75844.
CleanExHS_ZMPSTE24.
GenevestigatorO75844.

Family and domain databases

InterProIPR027057. CAXX_Prtase_1.
IPR001915. Peptidase_M48.
[Graphical view]
PANTHERPTHR10120:SF17. PTHR10120:SF17. 1 hit.
PfamPF01435. Peptidase_M48. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi10269.
NextBio38906.
PROO75844.
SOURCESearch...

Entry information

Entry nameFACE1_HUMAN
AccessionPrimary (citable) accession number: O75844
Secondary accession number(s): B3KQI7 expand/collapse secondary AC list , D3DPU7, Q8NDZ8, Q9UBQ2
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: April 27, 2001
Last modified: March 19, 2014
This is version 133 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM