Reviewed, UniProtKB/Swiss-Prot O75844 (FACE1_HUMAN)

Names and origin

Protein names

Recommended name:
    CAAX prenyl protease 1 homolog
    EC=3.4.24.84
Alternative name(s):
    Prenyl protein-specific endoprotease 1
    Farnesylated proteins-converting enzyme 1
      Short name=FACE-1
    Zinc metalloproteinase Ste24 homolog

Gene names

Name:	ZMPSTE24
Synonyms:	FACE1, STE24

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	475 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence 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 By similarity.
Subcellular location	Endoplasmic reticulum membrane; Multi-pass membrane protein. Golgi apparatus membrane; Multi-pass membrane protein Probable.
Tissue specificity	Widely expressed. High levels in kidney, prostate, testis and ovary.
Involvement in disease	Defects in ZMPSTE24 are the cause of mandibuloacral dysplasia with type B lipodystrophy (MADB) [MIM:608612]. Mandibuloacral dysplasia (MAD) is a rare autosomal recessive disorder characterized by mandibular and clavicular hypoplasia, acroosteolysis, delayed closure of the cranial suture, joint contractures, and types A or B patterns of lipodystrophy. Type B lipodystrophy observed in MADB, is characterized by generalized fat loss. Ref.8 Defects in ZMPSTE24 are a cause of lethal tight skin contracture syndrome [MIM:275210]; also called restrictive dermopathy (RD). Lethal tight skin contracture syndrome is a 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.
Sequence similarities	Belongs to the peptidase M48A family.

Ontologies

Keywords
Cellular component	Endoplasmic reticulum Golgi apparatus Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Transmembrane
Ligand	Metal-binding Zinc
Molecular function	Hydrolase Metalloprotease Protease
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	proteolysis Ref.3 Traceable author statement. Source: ProtInc
Cellular component	Golgi membrane Inferred from electronic annotation. Source: UniProtKB-SubCell endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	metalloendopeptidase activity Inferred from electronic annotation. Source: InterPro metalloexopeptidase activity Ref.3 Traceable author statement. Source: ProtInc zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 475	475	CAAX prenyl protease 1 homolog		PRO_0000138844
Regions
	Transmembrane	19 – 39	21	Potential
	Transmembrane	82 – 102	21	Potential
	Transmembrane	124 – 144	21	Potential
	Transmembrane	171 – 191	21	Potential
	Transmembrane	196 – 216	21	Potential
	Transmembrane	348 – 368	21	Potential
	Transmembrane	383 – 405	23	Potential
Sites
	Active site	336	1	By similarity
	Active site	419	1	Proton donor By similarity
	Metal binding	335	1	Zinc; catalytic By similarity
	Metal binding	339	1	Zinc; catalytic By similarity
	Metal binding	415	1	Zinc; catalytic By similarity
Amino acid modifications
	Modified residue	310	1	Phosphoserine Ref.6
Natural variations
	Natural variant	137	1	T → A: dbSNP rs17853725. Ref.5		VAR_034711
	Natural variant	340	1	W → R in MADB. Ref.8		VAR_019308
Experimental info
	Sequence conflict	16	1	E → K in BAA33727. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	O75844-1 [UniParc]. Last modified April 27, 2001. Version 2. Checksum: 6C49179DEB0C8F7F	FASTA	475	54,813
	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

References

	« Hide 'large scale' referencesShow '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: 10076063] [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: 9700155] [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: 10373325] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Ovary.
[4]	"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. , 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: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ALA-137. Tissue: Testis.
[6]	"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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-310, MASS SPECTROMETRY.
[7]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[8]	"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: 12913070] [Abstract] Cited for: VARIANT MADB ARG-340.
[9]	"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: 15317753] [Abstract] Cited for: INVOLVEMENT IN LETHAL TIGHT SKIN CONTRACTURE SYNDROME.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBLGenBankDDBJ	AB016068 mRNA. Translation: BAA33727.1. AF064867 mRNA. Translation: AAC68866.1. Y13834 mRNA. Translation: CAB46277.1. AL050341 Genomic DNA. Translation: CAB81610.1. BC037283 mRNA. Translation: AAH37283.1.
IPI	IPI00027180.
RefSeq	NP_005848.2.
UniGene	Hs.132642 Hs.591501
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	O75844. 2 interactions.
Protein family/group databases
MEROPS	M48.003.
PTM databases
PhosphoSite	O75844.
Proteomic databases
PeptideAtlas	O75844.
PRIDE	O75844.
Genome annotation databases
Ensembl	ENSG00000084073. Homo sapiens. [Contig view]
GeneID	10269.
KEGG	hsa:10269.
Organism-specific databases
GeneCards	GC01P040496.
H-InvDB	HIX0000469.
HGNC	HGNC:12877. ZMPSTE24.
HPA	HPA006988.
MIM	275210. phenotype. 606480. gene. 608612. phenotype.
Orphanet	1662. Dermopathy restrictive, lethal. 2457. Dysplasia, mandibuloacral. 90154. Dysplasia, mandibuloacral with type B lipodystrophy.
PharmGKB	PA37466.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	O75844.
HOVERGEN	O75844.
OMA	O75844. KAADYTI.
Enzyme and pathway databases
BRENDA	3.4.24.84. 247.
Gene expression databases
ArrayExpress	O75844.
Bgee	O75844.
CleanEx	HS_ZMPSTE24.
GermOnline	ENSG00000084073. Homo sapiens.
Family and domain databases
InterPro	IPR006025. Pept_M_Zn_BS. IPR001915. Peptidase_M48. [Graphical view]
Pfam	PF01435. Peptidase_M48. 1 hit. [Graphical view]
PROSITE	PS00142. ZINC_PROTEASE. False negative. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	38906.
SOURCE	Search...

Entry information

Entry name

FACE1_HUMAN

Accession

Primary (citable) accession number: O75844
Secondary accession number(s): Q8NDZ8, Q9UBQ2

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	April 27, 2001
Last modified:	June 16, 2009
This is version 87 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)