ID FACE1_HUMAN Reviewed; 475 AA. AC O75844; B3KQI7; D3DPU7; Q8NDZ8; Q9UBQ2; DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot. DT 27-APR-2001, sequence version 2. DT 27-MAR-2024, entry version 207. DE RecName: Full=CAAX prenyl protease 1 homolog; DE EC=3.4.24.84 {ECO:0000269|PubMed:33293369, ECO:0000269|PubMed:33315887}; DE AltName: Full=Farnesylated proteins-converting enzyme 1 {ECO:0000303|PubMed:10373325}; DE Short=FACE-1 {ECO:0000303|PubMed:10373325}; DE AltName: Full=Prenyl protein-specific endoprotease 1; DE AltName: Full=Zinc metalloproteinase Ste24 homolog {ECO:0000303|PubMed:10076063}; GN Name=ZMPSTE24 {ECO:0000303|PubMed:28246125, GN ECO:0000312|HGNC:HGNC:12877}; GN Synonyms=FACE1 {ECO:0000303|PubMed:10373325}, STE24 GN {ECO:0000303|PubMed:10076063}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY. RC TISSUE=Brain; RX PubMed=10076063; DOI=10.1016/s0304-4165(98)00170-6; RA Kumagai H., Kawamura Y., Yanagisawa K., Komano H.; RT "Identification of a human cDNA encoding a novel protein structurally RT related to the yeast membrane-associated metalloprotease, Ste24p."; RL Biochim. Biophys. Acta 1426:468-474(1999). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=B-cell, and Fetal brain; RX PubMed=9700155; DOI=10.1083/jcb.142.3.635; RA Tam A., Nouvet F.J., Fujimura-Kamada K., Slunt H., Sisodia S.S., RA Michaelis S.; RT "Dual roles for Ste24p in yeast a-factor maturation: NH2-terminal RT proteolysis and COOH-terminal CAAX processing."; RL J. Cell Biol. 142:635-649(1998). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Ovary; RX PubMed=10373325; DOI=10.1006/geno.1999.5834; RA Freije J.M.P., Blay P., Pendas A.M., Cadinanos J., Crespo P., RA Lopez-Otin C.; RT "Identification and chromosomal location of two human genes encoding RT enzymes potentially involved in proteolytic maturation of farnesylated RT proteins."; RL Genomics 58:270-280(1999). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=16303743; DOI=10.1093/dnares/12.2.117; RA Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J., RA Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S., RA Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y., RA Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S., RA Isogai T.; RT "Signal sequence and keyword trap in silico for selection of full-length RT human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA RT libraries."; RL DNA Res. 12:117-126(2005). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ALA-137. RC TISSUE=Testis; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [9] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [10] RP FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF HIS-335 AND GLU-336, AND RP INDUCTION BY TYPE I INTERFERON. RX PubMed=28246125; DOI=10.1084/jem.20161270; RA Fu B., Wang L., Li S., Dorf M.E.; RT "ZMPSTE24 defends against influenza and other pathogenic viruses."; RL J. Exp. Med. 214:919-929(2017). RN [11] RP FUNCTION. RX PubMed=28169297; DOI=10.1038/ncomms13876; RA Wang L., Fu B., Li W., Patil G., Liu L., Dorf M.E., Li S.; RT "Comparative influenza protein interactomes identify the role of RT plakophilin 2 in virus restriction."; RL Nat. Commun. 8:13876-13876(2017). RN [12] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=33315887; DOI=10.1371/journal.pone.0239269; RA Wood K.M., Spear E.D., Mossberg O.W., Odinammadu K.O., Xu W., Michaelis S.; RT "Defining substrate requirements for cleavage of farnesylated prelamin A by RT the integral membrane zinc metalloprotease ZMPSTE24."; RL PLoS ONE 15:e0239269-e0239269(2020). RN [13] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=33293369; DOI=10.1074/jbc.ra120.015792; RA Babatz T.D., Spear E.D., Xu W., Sun O.L., Nie L., Carpenter E.P., RA Michaelis S.; RT "Site specificity determinants for prelamin A cleavage by the zinc RT metalloprotease ZMPSTE24."; RL J. Biol. Chem. 296:100165-100165(2021). RN [14] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH IFITM3. RX PubMed=35283811; DOI=10.3389/fmicb.2022.840885; RA Stott-Marshall R.J., Foster T.L.; RT "Inhibition of Arenavirus Entry and Replication by the Cell-Intrinsic RT Restriction Factor ZMPSTE24 Is Enhanced by IFITM Antiviral Activity."; RL Front. Microbiol. 13:840885-840885(2022). RN [15] RP X-RAY CRYSTALLOGRAPHY (3.4 ANGSTROMS) IN COMPLEX WITH TETRAPEPTIDE, ACTIVE RP SITE, COFACTOR, METALLOPROTEASE DOMAIN, TOPOLOGY, ZINC-BINDING SITES, AND RP SUBCELLULAR LOCATION. RX PubMed=23539603; DOI=10.1126/science.1231513; RA Quigley A., Dong Y.Y., Pike A.C., Dong L., Shrestha L., Berridge G., RA Stansfeld P.J., Sansom M.S., Edwards A.M., Bountra C., von Delft F., RA Bullock A.N., Burgess-Brown N.A., Carpenter E.P.; RT "The structural basis of ZMPSTE24-dependent laminopathies."; RL Science 339:1604-1607(2013). RN [16] RP VARIANT MADB ARG-340. RX PubMed=12913070; DOI=10.1093/hmg/ddg213; RA Agarwal A.K., Fryns J.-P., Auchus R.J., Garg A.; RT "Zinc metalloproteinase, ZMPSTE24, is mutated in mandibuloacral RT dysplasia."; RL Hum. Mol. Genet. 12:1995-2001(2003). RN [17] RP INVOLVEMENT IN RSDM1. RX PubMed=15317753; DOI=10.1093/hmg/ddh265; RA Navarro C.L., De Sandre-Giovannoli A., Bernard R., Boccaccio I., Boyer A., RA Genevieve D., Hadj-Rabia S., Gaudy-Marqueste C., Smitt H.S., Vabres P., RA Faivre L., Verloes A., Van Essen T., Flori E., Hennekam R., Beemer F.A., RA Laurent N., Le Merrer M., Cau P., Levy N.; RT "Lamin A and ZMPSTE24 (FACE-1) defects cause nuclear disorganization and RT identify restrictive dermopathy as a lethal neonatal laminopathy."; RL Hum. Mol. Genet. 13:2493-2503(2004). RN [18] RP VARIANT MADB SER-265. RX PubMed=17152860; DOI=10.2310/6650.2006.05068; RA Agarwal A.K., Zhou X.J., Hall R.K., Nicholls K., Bankier A., Van Esch H., RA Fryns J.P., Garg A.; RT "Focal segmental glomerulosclerosis in patients with mandibuloacral RT dysplasia owing to ZMPSTE24 deficiency."; RL J. Invest. Med. 54:208-213(2006). RN [19] RP VARIANT MADB LEU-248, AND CHARACTERIZATION OF VARIANT MADB. RX PubMed=18435794; DOI=10.1111/j.1399-0004.2008.00992.x; RA Miyoshi Y., Akagi M., Agarwal A.K., Namba N., Kato-Nishimura K., Mohri I., RA Yamagata M., Nakajima S., Mushiake S., Shima M., Auchus R.J., Taniike M., RA Garg A., Ozono K.; RT "Severe mandibuloacral dysplasia caused by novel compound heterozygous RT ZMPSTE24 mutations in two Japanese siblings."; RL Clin. Genet. 73:535-544(2008). RN [20] RP VARIANT MADB LEU-248. RX PubMed=20814950; DOI=10.1002/ajmg.a.33664; RA Ahmad Z., Zackai E., Medne L., Garg A.; RT "Early onset mandibuloacral dysplasia due to compound heterozygous RT mutations in ZMPSTE24."; RL Am. J. Med. Genet. A 152:2703-2710(2010). CC -!- FUNCTION: Transmembrane metalloprotease whose catalytic activity is CC critical for processing lamin A/LMNA on the inner nuclear membrane and CC clearing clogged translocons on the endoplasmic reticulum CC (PubMed:33315887, PubMed:33293369). Proteolytically removes the C- CC terminal three residues of farnesylated proteins (PubMed:33315887, CC PubMed:33293369). Plays also an antiviral role independently of its CC protease activity by restricting enveloped RNA and DNA viruses, CC including influenza A, Zika, Ebola, Sindbis, vesicular stomatitis, CC cowpox, and vaccinia (PubMed:28246125, PubMed:28169297). CC Mechanistically, controls IFITM antiviral pathway to hinder viruses CC from breaching the endosomal barrier by modulating membrane fluidity CC (PubMed:35283811). {ECO:0000269|PubMed:28169297, CC ECO:0000269|PubMed:28246125, ECO:0000269|PubMed:33293369, CC ECO:0000269|PubMed:33315887, ECO:0000269|PubMed:35283811}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Hydrolyzes the peptide bond -P2-(S-farnesyl or CC geranylgeranyl)C-P1'-P2'-P3'-COOH where P1' and P2' are amino acids CC with aliphatic side chains and P3' is any C-terminal residue.; CC EC=3.4.24.84; Evidence={ECO:0000269|PubMed:33293369, CC ECO:0000269|PubMed:33315887}; CC -!- COFACTOR: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; CC Evidence={ECO:0000269|PubMed:23539603}; CC Note=Binds 1 zinc ion per subunit. {ECO:0000269|PubMed:23539603}; CC -!- INTERACTION: CC O75844; P02545-1: LMNA; NbExp=2; IntAct=EBI-1056377, EBI-351949; CC O75844; P06821: M; Xeno; NbExp=2; IntAct=EBI-1056377, EBI-2547404; CC O75844; C5E519: M2; Xeno; NbExp=2; IntAct=EBI-1056377, EBI-12562139; CC O75844; Q20MH8: M2; Xeno; NbExp=2; IntAct=EBI-1056377, EBI-12576433; CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane CC {ECO:0000269|PubMed:23539603}; Multi-pass membrane protein CC {ECO:0000255}. Nucleus inner membrane {ECO:0000269|PubMed:23539603}; CC Multi-pass membrane protein {ECO:0000255}. Early endosome membrane CC {ECO:0000269|PubMed:35283811}; Multi-pass membrane protein CC {ECO:0000255}. Late endosome membrane {ECO:0000269|PubMed:35283811}; CC Multi-pass membrane protein {ECO:0000255}. CC -!- TISSUE SPECIFICITY: Widely expressed. High levels in kidney, prostate, CC testis and ovary. {ECO:0000269|PubMed:10076063}. CC -!- INDUCTION: By type I interferon. {ECO:0000269|PubMed:33315887}. CC -!- DOMAIN: The metalloprotease domain is constituted by the two C-terminal CC nuclear regions. {ECO:0000269|PubMed:23539603}. CC -!- DISEASE: Mandibuloacral dysplasia with type B lipodystrophy (MADB) CC [MIM:608612]: A form of mandibuloacral dysplasia, a rare progeroid CC disorder with clinical and genetic heterogeneity, characterized by CC growth retardation, craniofacial dysmorphic features due to distal bone CC resorption, musculoskeletal and skin abnormalities associated with CC lipodystrophy. MADB is a disease characterized by mandibular and CC clavicular hypoplasia, acroosteolysis, delayed closure of the cranial CC suture, joint contractures, and generalized lipodystrophy with loss of CC subcutaneous fat from the extremities, face, neck and trunk. CC {ECO:0000269|PubMed:12913070, ECO:0000269|PubMed:17152860, CC ECO:0000269|PubMed:18435794, ECO:0000269|PubMed:20814950}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Restrictive dermopathy 1 (RSDM1) [MIM:275210]: An autosomal CC recessive form of restrictive dermopathy, a genodermatosis mainly CC characterized by intrauterine growth retardation, tight and rigid skin CC with erosions, prominent superficial vasculature and epidermal CC hyperkeratosis, facial dysmorphism, sparse/absent eyelashes and CC eyebrows, mineralization defects of the skull, thin dysplastic CC clavicles, pulmonary hypoplasia, multiple joint contractures and an CC early neonatal lethal course. Liveborn children usually die within the CC first week of life. {ECO:0000269|PubMed:15317753}. Note=The disease is CC caused by variants affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the peptidase M48A family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AB016068; BAA33727.1; -; mRNA. DR EMBL; AF064867; AAC68866.1; -; mRNA. DR EMBL; Y13834; CAB46277.1; -; mRNA. DR EMBL; AK075007; BAG52049.1; -; mRNA. DR EMBL; AL050341; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471059; EAX07233.1; -; Genomic_DNA. DR EMBL; CH471059; EAX07234.1; -; Genomic_DNA. DR EMBL; BC037283; AAH37283.1; -; mRNA. DR CCDS; CCDS449.1; -. DR RefSeq; NP_005848.2; NM_005857.4. DR PDB; 2YPT; X-ray; 3.80 A; A/B/D/E=1-475. DR PDB; 4AW6; X-ray; 3.40 A; A/B/D/E=1-475. DR PDB; 5SYT; X-ray; 2.00 A; A=1-474. DR PDB; 6BH8; X-ray; 3.85 A; A/B=1-475. DR PDBsum; 2YPT; -. DR PDBsum; 4AW6; -. DR PDBsum; 5SYT; -. DR PDBsum; 6BH8; -. DR AlphaFoldDB; O75844; -. DR SMR; O75844; -. DR BioGRID; 115560; 175. DR DIP; DIP-39641N; -. DR IntAct; O75844; 35. DR STRING; 9606.ENSP00000361845; -. DR ChEMBL; CHEMBL3739253; -. DR MEROPS; M48.003; -. DR TCDB; 9.B.1.1.1; the integral membrane caax protease (caax protease) family. DR GlyGen; O75844; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; O75844; -. DR MetOSite; O75844; -. DR PhosphoSitePlus; O75844; -. DR SwissPalm; O75844; -. DR BioMuta; ZMPSTE24; -. DR EPD; O75844; -. DR jPOST; O75844; -. DR MassIVE; O75844; -. DR MaxQB; O75844; -. DR PaxDb; 9606-ENSP00000361845; -. DR PeptideAtlas; O75844; -. DR ProteomicsDB; 50226; -. DR Pumba; O75844; -. DR Antibodypedia; 1711; 458 antibodies from 32 providers. DR DNASU; 10269; -. DR Ensembl; ENST00000372759.4; ENSP00000361845.3; ENSG00000084073.10. DR GeneID; 10269; -. DR KEGG; hsa:10269; -. DR MANE-Select; ENST00000372759.4; ENSP00000361845.3; NM_005857.5; NP_005848.2. DR UCSC; uc001cfg.5; human. DR AGR; HGNC:12877; -. DR CTD; 10269; -. DR DisGeNET; 10269; -. DR GeneCards; ZMPSTE24; -. DR HGNC; HGNC:12877; ZMPSTE24. DR HPA; ENSG00000084073; Low tissue specificity. DR MalaCards; ZMPSTE24; -. DR MIM; 275210; phenotype. DR MIM; 606480; gene. DR MIM; 608612; phenotype. DR neXtProt; NX_O75844; -. DR OpenTargets; ENSG00000084073; -. DR Orphanet; 740; Hutchinson-Gilford progeria syndrome. DR Orphanet; 90154; Mandibuloacral dysplasia with type B lipodystrophy. DR Orphanet; 1662; Restrictive dermopathy. DR PharmGKB; PA37466; -. DR VEuPathDB; HostDB:ENSG00000084073; -. DR eggNOG; KOG2719; Eukaryota. DR GeneTree; ENSGT00390000002053; -. DR HOGENOM; CLU_025947_3_0_1; -. DR InParanoid; O75844; -. DR OMA; FVIEEKF; -. DR OrthoDB; 3080668at2759; -. DR PhylomeDB; O75844; -. DR TreeFam; TF105972; -. DR BRENDA; 3.4.24.84; 2681. DR PathwayCommons; O75844; -. DR SignaLink; O75844; -. DR BioGRID-ORCS; 10269; 26 hits in 1158 CRISPR screens. DR ChiTaRS; ZMPSTE24; human. DR GenomeRNAi; 10269; -. DR Pharos; O75844; Tbio. DR PRO; PR:O75844; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; O75844; Protein. DR Bgee; ENSG00000084073; Expressed in hair follicle and 212 other cell types or tissues. DR ExpressionAtlas; O75844; baseline and differential. DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0031902; C:late endosome membrane; IEA:UniProtKB-SubCell. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0005637; C:nuclear inner membrane; IEA:UniProtKB-SubCell. DR GO; GO:0032991; C:protein-containing complex; IDA:MGI. DR GO; GO:0003690; F:double-stranded DNA binding; IEA:Ensembl. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0004222; F:metalloendopeptidase activity; IBA:GO_Central. DR GO; GO:0008235; F:metalloexopeptidase activity; TAS:ProtInc. DR GO; GO:0007628; P:adult walking behavior; IEA:Ensembl. DR GO; GO:0030282; P:bone mineralization; IEA:Ensembl. DR GO; GO:0071586; P:CAAX-box protein processing; IBA:GO_Central. DR GO; GO:1990036; P:calcium ion import into sarcoplasmic reticulum; IEA:Ensembl. DR GO; GO:0061762; P:CAMKK-AMPK signaling cascade; IEA:Ensembl. DR GO; GO:0061337; P:cardiac conduction; IEA:Ensembl. DR GO; GO:0055013; P:cardiac muscle cell development; IEA:Ensembl. DR GO; GO:0003231; P:cardiac ventricle development; IEA:Ensembl. DR GO; GO:0044255; P:cellular lipid metabolic process; IEA:Ensembl. DR GO; GO:0071480; P:cellular response to gamma radiation; IEA:Ensembl. DR GO; GO:0008340; P:determination of adult lifespan; IEA:Ensembl. DR GO; GO:0006281; P:DNA repair; IEA:Ensembl. DR GO; GO:0003417; P:growth plate cartilage development; IEA:Ensembl. DR GO; GO:0001942; P:hair follicle development; IEA:Ensembl. DR GO; GO:0003007; P:heart morphogenesis; IEA:Ensembl. DR GO; GO:0006925; P:inflammatory cell apoptotic process; IEA:Ensembl. DR GO; GO:0060993; P:kidney morphogenesis; IEA:Ensembl. DR GO; GO:0001889; P:liver development; IEA:Ensembl. DR GO; GO:0043007; P:maintenance of rDNA; IEA:Ensembl. DR GO; GO:0035264; P:multicellular organism growth; IEA:Ensembl. DR GO; GO:1903799; P:negative regulation of miRNA processing; IEA:Ensembl. DR GO; GO:0050905; P:neuromuscular process; IEA:Ensembl. DR GO; GO:0006998; P:nuclear envelope organization; IEA:Ensembl. DR GO; GO:0044029; P:positive regulation of gene expression via CpG island demethylation; IEA:Ensembl. DR GO; GO:0030327; P:prenylated protein catabolic process; IEA:Ensembl. DR GO; GO:0006508; P:proteolysis; TAS:ProtInc. DR GO; GO:0010506; P:regulation of autophagy; IEA:Ensembl. DR GO; GO:0030500; P:regulation of bone mineralization; IEA:Ensembl. DR GO; GO:0008360; P:regulation of cell shape; IEA:Ensembl. DR GO; GO:2000772; P:regulation of cellular senescence; IEA:Ensembl. DR GO; GO:0050688; P:regulation of defense response to virus; IDA:MGI. DR GO; GO:0043516; P:regulation of DNA damage response, signal transduction by p53 class mediator; IEA:Ensembl. DR GO; GO:0044030; P:regulation of DNA methylation; IEA:Ensembl. DR GO; GO:0048145; P:regulation of fibroblast proliferation; IEA:Ensembl. DR GO; GO:0010906; P:regulation of glucose metabolic process; IEA:Ensembl. DR GO; GO:0032350; P:regulation of hormone metabolic process; IEA:Ensembl. DR GO; GO:0019216; P:regulation of lipid metabolic process; IEA:Ensembl. DR GO; GO:1903463; P:regulation of mitotic cell cycle DNA replication; IEA:Ensembl. DR GO; GO:0040014; P:regulation of multicellular organism growth; IEA:Ensembl. DR GO; GO:0070302; P:regulation of stress-activated protein kinase signaling cascade; IEA:Ensembl. DR GO; GO:2000730; P:regulation of termination of RNA polymerase I transcription; IEA:Ensembl. DR GO; GO:0032006; P:regulation of TOR signaling; IEA:Ensembl. DR GO; GO:0060307; P:regulation of ventricular cardiac muscle cell membrane repolarization; IEA:Ensembl. DR GO; GO:0072423; P:response to DNA damage checkpoint signaling; IEA:Ensembl. DR GO; GO:0048538; P:thymus development; IEA:Ensembl. DR GO; GO:0003229; P:ventricular cardiac muscle tissue development; IEA:Ensembl. DR CDD; cd07343; M48A_Zmpste24p_like; 1. DR Gene3D; 3.30.2010.10; Metalloproteases ('zincins'), catalytic domain; 1. DR InterPro; IPR027057; CAXX_Prtase_1. DR InterPro; IPR001915; Peptidase_M48. DR InterPro; IPR032456; Peptidase_M48_N. DR PANTHER; PTHR10120; CAAX PRENYL PROTEASE 1; 1. DR PANTHER; PTHR10120:SF24; CAAX PRENYL PROTEASE 1 HOMOLOG; 1. DR Pfam; PF01435; Peptidase_M48; 1. DR Pfam; PF16491; Peptidase_M48_N; 1. DR Genevisible; O75844; HS. PE 1: Evidence at protein level; KW 3D-structure; Antiviral protein; Disease variant; Endoplasmic reticulum; KW Endosome; Hydrolase; Membrane; Metal-binding; Metalloprotease; Nucleus; KW Protease; Reference proteome; Transmembrane; Transmembrane helix; Zinc. FT CHAIN 1..475 FT /note="CAAX prenyl protease 1 homolog" FT /id="PRO_0000138844" FT TOPO_DOM 1..18 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 19..39 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 40..81 FT /note="Nuclear" FT /evidence="ECO:0000255" FT TRANSMEM 82..102 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 103..123 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 124..144 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 145..170 FT /note="Nuclear" FT /evidence="ECO:0000255" FT TRANSMEM 171..191 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 192..195 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 196..216 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 217..347 FT /note="Nuclear" FT /evidence="ECO:0000255" FT TRANSMEM 348..368 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 369..382 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 383..405 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 406..475 FT /note="Nuclear" FT /evidence="ECO:0000255" FT ACT_SITE 336 FT /evidence="ECO:0000269|PubMed:23539603" FT BINDING 335 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:23539603" FT BINDING 339 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:23539603" FT BINDING 415 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:23539603" FT VARIANT 137 FT /note="T -> A (in dbSNP:rs17853725)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_034711" FT VARIANT 248 FT /note="P -> L (in MADB; does not affect enzyme activity; FT dbSNP:rs121908095)" FT /evidence="ECO:0000269|PubMed:18435794, FT ECO:0000269|PubMed:20814950" FT /id="VAR_064501" FT VARIANT 265 FT /note="N -> S (in MADB; dbSNP:rs281875371)" FT /evidence="ECO:0000269|PubMed:17152860" FT /id="VAR_064502" FT VARIANT 340 FT /note="W -> R (in MADB; dbSNP:rs121908093)" FT /evidence="ECO:0000269|PubMed:12913070" FT /id="VAR_019308" FT MUTAGEN 335 FT /note="H->A: Loss of catalytic activity but not viral FT restriction." FT /evidence="ECO:0000269|PubMed:28246125" FT MUTAGEN 336 FT /note="E->A: Loss of catalytic activity but not viral FT restriction." FT /evidence="ECO:0000269|PubMed:28246125" FT CONFLICT 16 FT /note="E -> K (in Ref. 1; BAA33727)" FT /evidence="ECO:0000305" FT STRAND 11..13 FT /evidence="ECO:0007829|PDB:4AW6" FT HELIX 15..47 FT /evidence="ECO:0007829|PDB:5SYT" FT HELIX 53..55 FT /evidence="ECO:0007829|PDB:5SYT" FT TURN 56..58 FT /evidence="ECO:0007829|PDB:5SYT" FT HELIX 61..94 FT /evidence="ECO:0007829|PDB:5SYT" FT HELIX 97..111 FT /evidence="ECO:0007829|PDB:5SYT" FT HELIX 119..147 FT /evidence="ECO:0007829|PDB:5SYT" FT HELIX 149..152 FT /evidence="ECO:0007829|PDB:5SYT" FT HELIX 160..191 FT /evidence="ECO:0007829|PDB:5SYT" FT HELIX 196..218 FT /evidence="ECO:0007829|PDB:5SYT" FT HELIX 220..223 FT /evidence="ECO:0007829|PDB:5SYT" FT STRAND 226..228 FT /evidence="ECO:0007829|PDB:5SYT" FT HELIX 233..244 FT /evidence="ECO:0007829|PDB:5SYT" FT STRAND 252..255 FT /evidence="ECO:0007829|PDB:5SYT" FT HELIX 257..259 FT /evidence="ECO:0007829|PDB:5SYT" FT STRAND 266..273 FT /evidence="ECO:0007829|PDB:4AW6" FT STRAND 277..280 FT /evidence="ECO:0007829|PDB:5SYT" FT HELIX 281..283 FT /evidence="ECO:0007829|PDB:5SYT" FT TURN 285..287 FT /evidence="ECO:0007829|PDB:5SYT" FT TURN 289..291 FT /evidence="ECO:0007829|PDB:5SYT" FT HELIX 317..319 FT /evidence="ECO:0007829|PDB:5SYT" FT STRAND 322..324 FT /evidence="ECO:0007829|PDB:5SYT" FT HELIX 326..341 FT /evidence="ECO:0007829|PDB:5SYT" FT HELIX 344..366 FT /evidence="ECO:0007829|PDB:5SYT" FT HELIX 370..374 FT /evidence="ECO:0007829|PDB:5SYT" FT TURN 375..377 FT /evidence="ECO:0007829|PDB:5SYT" FT HELIX 384..393 FT /evidence="ECO:0007829|PDB:5SYT" FT TURN 394..396 FT /evidence="ECO:0007829|PDB:5SYT" FT HELIX 397..424 FT /evidence="ECO:0007829|PDB:5SYT" FT TURN 425..427 FT /evidence="ECO:0007829|PDB:4AW6" FT HELIX 428..441 FT /evidence="ECO:0007829|PDB:5SYT" FT HELIX 450..456 FT /evidence="ECO:0007829|PDB:5SYT" FT HELIX 462..470 FT /evidence="ECO:0007829|PDB:5SYT" SQ SEQUENCE 475 AA; 54813 MW; 6C49179DEB0C8F7F CRC64; MGMWASLDAL WEMPAEKRIF GAVLLFSWTV YLWETFLAQR QRRIYKTTTH VPPELGQIMD SETFEKSRLY QLDKSTFSFW SGLYSETEGT LILLFGGIPY LWRLSGRFCG YAGFGPEYEI TQSLVFLLLA TLFSALTGLP WSLYNTFVIE EKHGFNQQTL GFFMKDAIKK FVVTQCILLP VSSLLLYIIK IGGDYFFIYA WLFTLVVSLV LVTIYADYIA PLFDKFTPLP EGKLKEEIEV MAKSIDFPLT KVYVVEGSKR SSHSNAYFYG FFKNKRIVLF DTLLEEYSVL NKDIQEDSGM EPRNEEEGNS EEIKAKVKNK KQGCKNEEVL AVLGHELGHW KLGHTVKNII ISQMNSFLCF FLFAVLIGRK ELFAAFGFYD SQPTLIGLLI IFQFIFSPYN EVLSFCLTVL SRRFEFQADA FAKKLGKAKD LYSALIKLNK DNLGFPVSDW LFSMWHYSHP PLLERLQALK TMKQH //