O75844 (FACE1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	475 AA.
Sequence status	Complete.
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	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.10 Ref.12 Ref.13 Ref.14 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.11
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 Transmembrane helix
Ligand	Metal-binding Zinc
Molecular function	Hydrolase Metalloprotease Protease
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	CAAX-box protein processing Inferred from electronic annotation. Source: InterPro nuclear envelope organization Inferred from electronic annotation. Source: Compara prenylated protein catabolic process Inferred from electronic annotation. Source: Compara proteolysis Traceable author statement Ref.3. 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	metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW metalloendopeptidase activity Inferred from electronic annotation. Source: Compara metalloexopeptidase activity Traceable author statement Ref.3. Source: ProtInc
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

Helical; Potential

Transmembrane

82 – 102

21

Helical; Potential

Transmembrane

124 – 144

21

Helical; Potential

Transmembrane

171 – 191

21

Helical; Potential

Transmembrane

196 – 216

21

Helical; Potential

Transmembrane

348 – 368

21

Helical; Potential

Transmembrane

383 – 405

23

Helical; 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

Natural variations

Natural variant

137

1

T → A. Ref.7
Corresponds to variant rs17853725 [ dbSNP | Ensembl ].

VAR_034711

Natural variant

248

1

P → L in MADB; found in compound heterozygotes carrying a null allele; does not affect enzyme activity. Ref.13 Ref.14

VAR_064501

Natural variant

265

1

N → S in MADB. Ref.12

VAR_064502

Natural variant

340

1

W → R in MADB. Ref.10

VAR_019308

Experimental info

Sequence conflict

16

1

E → K in BAA33727. Ref.1

Secondary structure

1

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475

Helix Strand Turn

Details...

Beta strand

11 – 13

3

Helix

16 – 47

32

Helix

54 – 56

3

Helix

61 – 95

35

Helix

97 – 104

8

Helix

117 – 147

31

Helix

149 – 152

4

Helix

160 – 191

32

Helix

196 – 215

20

Turn

216 – 219

4

Helix

220 – 223

4

Beta strand

226 – 228

3

Helix

233 – 244

12

Beta strand

249 – 255

7

Helix

257 – 259

3

Beta strand

266 – 273

8

Beta strand

275 – 280

6

Helix

281 – 284

4

Helix

326 – 341

16

Helix

344 – 366

23

Helix

371 – 375

5

Helix

384 – 393

10

Helix

397 – 424

28

Turn

425 – 427

3

Helix

428 – 441

14

Helix

450 – 455

6

Helix

462 – 471

10

Sequences

	Sequence		Length	Mass (Da)
	O75844 [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] [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. , 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. , 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. , 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]	"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.
[11]	"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.
[12]	"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.
[13]	"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.
[14]	"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

GeneReviews

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.

IPI

IPI00027180.

RefSeq

NP_005848.2. NM_005857.4.

UniGene

Hs.132642.
Hs.721062.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2YPT	X-ray	3.80	A/B/D/E	1-475	[»]
4AW6	X-ray	3.40	A/B/D/E	1-475	[»]

ProteinModelPortal

O75844.

ModBase

Search...

Protein-protein interaction databases

IntAct

O75844. 2 interactions.

STRING

9606.ENSP00000361845.

Protein family/group databases

MEROPS

M48.003.

PTM databases

PhosphoSite

O75844.

Proteomic databases

PaxDb

O75844.

PeptideAtlas

O75844.

PRIDE

O75844.

Protocols and materials databases

DNASU

10269.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000372759; ENSP00000361845; ENSG00000084073.

GeneID

10269.

KEGG

hsa:10269.

UCSC

uc001cfg.3. human.

Organism-specific databases

CTD

10269.

GeneCards

GC01P040723.

HGNC

HGNC:12877. ZMPSTE24.

HPA

HPA006988.

MIM

275210. phenotype.
606480. gene.
608612. phenotype.

neXtProt

NX_O75844.

Orphanet

740. Hutchinson-Gilford progeria syndrome.
1662. Lethal restrictive dermopathy.
90154. Mandibuloacral dysplasia with type B lipodystrophy.

PharmGKB

PA37466.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0501.

HOGENOM

HOG000257874.

HOVERGEN

HBG051541.

InParanoid

O75844.

KO

K06013.

OMA

MDGSKRS.

OrthoDB

EOG469QTR.

PhylomeDB

O75844.

Enzyme and pathway databases

BRENDA

3.4.24.84. 2681.

Gene expression databases

ArrayExpress

O75844.

Bgee

O75844.

CleanEx

HS_ZMPSTE24.

Genevestigator

O75844.

GermOnline

ENSG00000084073. Homo sapiens.

Family and domain databases

InterPro

IPR027057. CAXX_Prtase_1.
IPR001915. Peptidase_M48.
[Graphical view]

PANTHER

PTHR10120:SF17. PTHR10120:SF17. 1 hit.

Pfam

PF01435. Peptidase_M48. 1 hit.
[Graphical view]

PROSITE

PS00142. ZINC_PROTEASE. False negative.
[Graphical view]

ProtoNet

Search...

Other

GenomeRNAi

10269.

NextBio

38906.

SOURCE

Search...

Entry information

Entry name

FACE1_HUMAN

Accession

Primary (citable) accession number: O75844
Secondary accession number(s): B3KQI7 , D3DPU7, Q8NDZ8, Q9UBQ2

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	April 27, 2001
Last modified:	May 1, 2013
This is version 125 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.