ID YMEL1_HUMAN Reviewed; 773 AA. AC Q96TA2; B4DNM1; D3DRV8; D3DRV9; Q5T8D9; Q9H1Q0; Q9UMR9; DT 13-APR-2004, integrated into UniProtKB/Swiss-Prot. DT 13-APR-2004, sequence version 2. DT 27-MAR-2024, entry version 197. DE RecName: Full=ATP-dependent zinc metalloprotease YME1L1; DE EC=3.4.24.- {ECO:0000269|PubMed:26923599, ECO:0000269|PubMed:27495975, ECO:0000269|PubMed:27786171}; DE AltName: Full=ATP-dependent metalloprotease FtsH1; DE AltName: Full=Meg-4; DE AltName: Full=Presenilin-associated metalloprotease; DE Short=PAMP; DE AltName: Full=YME1-like protein 1; GN Name=YME1L1; Synonyms=FTSH1, YME1L; ORFNames=UNQ1868/PRO4304; 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] (ISOFORM 1). RA Miyata T., Inagi R., Yasuda Y., Kurokawa K.; RT "Human ATP-dependent metalloprotease (FtsH1) homolog mRNA."; RL Submitted (MAY-1999) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND SUBCELLULAR LOCATION. RC TISSUE=Fetal brain; RX PubMed=10843804; DOI=10.1006/geno.2000.6136; RA Coppola M., Pizzigoni A., Banfi S., Bassi M.T., Casari G., Incerti B.; RT "Identification and characterization of YME1L1, a novel paraplegin-related RT gene."; RL Genomics 66:48-54(2000). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RX PubMed=12975309; DOI=10.1101/gr.1293003; RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A., RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.; RT "The secreted protein discovery initiative (SPDI), a large-scale effort to RT identify novel human secreted and transmembrane proteins: a bioinformatics RT assessment."; RL Genome Res. 13:2265-2270(2003). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164054; DOI=10.1038/nature02462; RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P., RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 10."; RL Nature 429:375-381(2004). 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] (ISOFORM 2). RC TISSUE=Muscle, and Placenta; 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 FUNCTION IN PROCESSING OF OPA1. RX PubMed=18076378; DOI=10.1042/bc20070110; RA Guillery O., Malka F., Landes T., Guillou E., Blackstone C., Lombes A., RA Belenguer P., Arnoult D., Rojo M.; RT "Metalloprotease-mediated OPA1 processing is modulated by the mitochondrial RT membrane potential."; RL Biol. Cell 100:315-325(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 SUBCELLULAR LOCATION, TISSUE SPECIFICITY, FUNCTION, SUBUNIT, AND RP MUTAGENESIS (ISOFORM 2). RX PubMed=22262461; DOI=10.1091/mbc.e11-08-0674; RA Stiburek L., Cesnekova J., Kostkova O., Fornuskova D., Vinsova K., RA Wenchich L., Houstek J., Zeman J.; RT "YME1L controls the accumulation of respiratory chain subunits and is RT required for apoptotic resistance, cristae morphogenesis and cell RT proliferation."; RL Mol. Biol. Cell 23:1010-1023(2012). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [13] RP INTERACTION WITH AFG1L. RX PubMed=26759378; DOI=10.1042/bj20151029; RA Cesnekova J., Rodinova M., Hansikova H., Houstek J., Zeman J., Stiburek L.; RT "The mammalian homologue of yeast Afg1 ATPase (lactation elevated 1) RT mediates degradation of nuclear-encoded complex IV subunits."; RL Biochem. J. 473:797-804(2016). RN [14] RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, SUBCELLULAR LOCATION, AND RP MUTAGENESIS OF GLU-439 AND GLU-600. RX PubMed=26923599; DOI=10.1016/j.celrep.2016.02.011; RA Rainbolt T.K., Lebeau J., Puchades C., Wiseman R.L.; RT "Reciprocal Degradation of YME1L and OMA1 Adapts Mitochondrial Proteolytic RT Activity during Stress."; RL Cell Rep. 14:2041-2049(2016). RN [15] RP FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, TOPOLOGY, BIOPHYSICOCHEMICAL RP PROPERTIES, AND MUTAGENESIS OF GLU-439. RX PubMed=27786171; DOI=10.1038/ncomms13301; RA Shi H., Rampello A.J., Glynn S.E.; RT "Engineered AAA+ proteases reveal principles of proteolysis at the RT mitochondrial inner membrane."; RL Nat. Commun. 7:13301-13301(2016). RN [16] RP INVOLVEMENT IN OPA11, FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, RP SUBUNIT, POST-TRANSLATIONAL PROCESSING, INVOLVEMENT IN MITOCHONDRIAL RP DISORDER, VARIANT OPA11 TRP-206, CHARACTERIZATION OF VARIANT OPA11 TRP-206, RP AND MUTAGENESIS OF GLU-439. RX PubMed=27495975; DOI=10.7554/elife.16078; RA Hartmann B., Wai T., Hu H., MacVicar T., Musante L., Fischer-Zirnsak B., RA Stenzel W., Graef R., van den Heuvel L., Ropers H.H., Wienker T.F., RA Huebner C., Langer T., Kaindl A.M.; RT "Homozygous YME1L1 mutation causes mitochondriopathy with optic atrophy and RT mitochondrial network fragmentation."; RL Elife 5:0-0(2016). CC -!- FUNCTION: ATP-dependent metalloprotease that catalyzes the degradation CC of folded and unfolded proteins with a suitable degron sequence in the CC mitochondrial intermembrane region (PubMed:26923599, PubMed:27786171). CC Plays an important role in regulating mitochondrial morphology and CC function by cleaving OPA1 at position S2, giving rise to a form of OPA1 CC that promotes maintenance of normal mitochondrial structure and CC mitochondrial protein metabolism (PubMed:18076378, PubMed:26923599, CC PubMed:27495975). Ensures cell proliferation, maintains normal cristae CC morphology and complex I respiration activity, promotes antiapoptotic CC activity and protects mitochondria from the accumulation of oxidatively CC damaged membrane proteins (PubMed:22262461). Required for normal, CC constitutive degradation of PRELID1 (PubMed:27495975). Catalyzes the CC degradation of OMA1 in response to membrane depolarization CC (PubMed:26923599). Required to control the accumulation of nonassembled CC respiratory chain subunits (NDUFB6, OX4 and ND1) (PubMed:22262461). CC {ECO:0000269|PubMed:18076378, ECO:0000269|PubMed:22262461, CC ECO:0000269|PubMed:26923599, ECO:0000269|PubMed:27495975, CC ECO:0000269|PubMed:27786171}. CC -!- COFACTOR: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; CC Evidence={ECO:0000305|PubMed:26923599}; CC Note=Binds 1 zinc ion per subunit. {ECO:0000305|PubMed:26923599}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=1.4 mM for ATP {ECO:0000269|PubMed:27786171}; CC -!- SUBUNIT: Homohexamer; may also form heterohexamers (PubMed:27786171). CC Exists in several complexes of 600-1100 kDa (PubMed:22262461, CC PubMed:27495975). Interacts with AFG1L (PubMed:26759378). CC {ECO:0000269|PubMed:22262461, ECO:0000269|PubMed:26759378, CC ECO:0000269|PubMed:27495975, ECO:0000269|PubMed:27786171}. CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane CC {ECO:0000269|PubMed:10843804, ECO:0000269|PubMed:22262461}. CC Mitochondrion {ECO:0000269|PubMed:26923599, CC ECO:0000269|PubMed:27495975}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q96TA2-1; Sequence=Displayed; CC Name=2; CC IsoId=Q96TA2-2; Sequence=VSP_010017; CC Name=3; CC IsoId=Q96TA2-3; Sequence=VSP_010017, VSP_045336; CC -!- TISSUE SPECIFICITY: High expression in cardiac and skeletal muscle CC mitochondria. {ECO:0000269|PubMed:22262461}. CC -!- PTM: Proteolytically processed by mitochondrial processing peptidase CC (MPP) to generate the mature form. {ECO:0000269|PubMed:27495975}. CC -!- DISEASE: Optic atrophy 11 (OPA11) [MIM:617302]: An autosomal recessive CC disease characterized by progressive visual loss in association with CC optic atrophy. Atrophy of the optic disk indicates a deficiency in the CC number of nerve fibers which arise in the retina and converge to form CC the optic disk, optic nerve, optic chiasm and optic tracts. OPA11 CC patients also manifest delayed psychomotor development, intellectual CC disability, ataxia, and leukoencephalopathy on brain imaging. CC {ECO:0000269|PubMed:27495975}. Note=The disease may be caused by CC variants affecting the gene represented in this entry. CC -!- MISCELLANEOUS: [Isoform 2]: Mutagenesis of Glu-543 to Gln does not CC complement excessive accumulation of subunits (NDUFB6, COX4,ND1) due to CC YME1 deletion mutant. Probably has no ATPase activity. {ECO:0000305}. CC -!- SIMILARITY: In the N-terminal section; belongs to the AAA ATPase CC family. {ECO:0000305}. CC -!- SIMILARITY: In the C-terminal section; belongs to the peptidase M41 CC 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; AF151782; AAK57555.1; -; mRNA. DR EMBL; AJ132637; CAB51858.1; -; mRNA. DR EMBL; AY358484; AAQ88848.1; -; mRNA. DR EMBL; AK297973; BAG60283.1; -; mRNA. DR EMBL; AL162272; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL160291; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471072; EAW86068.1; -; Genomic_DNA. DR EMBL; CH471072; EAW86069.1; -; Genomic_DNA. DR EMBL; CH471072; EAW86070.1; -; Genomic_DNA. DR EMBL; CH471072; EAW86071.1; -; Genomic_DNA. DR EMBL; CH471072; EAW86072.1; -; Genomic_DNA. DR EMBL; BC023507; AAH23507.1; -; mRNA. DR EMBL; BC024032; AAH24032.1; -; mRNA. DR CCDS; CCDS58072.1; -. [Q96TA2-3] DR CCDS; CCDS7151.1; -. [Q96TA2-2] DR CCDS; CCDS7152.1; -. [Q96TA2-1] DR RefSeq; NP_001240795.1; NM_001253866.1. [Q96TA2-3] DR RefSeq; NP_055078.1; NM_014263.3. [Q96TA2-2] DR RefSeq; NP_647473.1; NM_139312.2. [Q96TA2-1] DR AlphaFoldDB; Q96TA2; -. DR SMR; Q96TA2; -. DR BioGRID; 115954; 208. DR IntAct; Q96TA2; 123. DR MINT; Q96TA2; -. DR STRING; 9606.ENSP00000318480; -. DR MEROPS; M41.026; -. DR GlyGen; Q96TA2; 9 sites, 1 O-linked glycan (8 sites). DR iPTMnet; Q96TA2; -. DR MetOSite; Q96TA2; -. DR PhosphoSitePlus; Q96TA2; -. DR SwissPalm; Q96TA2; -. DR BioMuta; YME1L1; -. DR DMDM; 46397258; -. DR EPD; Q96TA2; -. DR jPOST; Q96TA2; -. DR MassIVE; Q96TA2; -. DR MaxQB; Q96TA2; -. DR PaxDb; 9606-ENSP00000318480; -. DR PeptideAtlas; Q96TA2; -. DR ProteomicsDB; 4708; -. DR ProteomicsDB; 78222; -. [Q96TA2-1] DR ProteomicsDB; 78223; -. [Q96TA2-2] DR Pumba; Q96TA2; -. DR Antibodypedia; 44412; 184 antibodies from 25 providers. DR DNASU; 10730; -. DR Ensembl; ENST00000326799.7; ENSP00000318480.3; ENSG00000136758.20. [Q96TA2-1] DR Ensembl; ENST00000376016.8; ENSP00000365184.3; ENSG00000136758.20. [Q96TA2-2] DR Ensembl; ENST00000613434.4; ENSP00000481724.1; ENSG00000136758.20. [Q96TA2-3] DR GeneID; 10730; -. DR KEGG; hsa:10730; -. DR MANE-Select; ENST00000376016.8; ENSP00000365184.3; NM_014263.4; NP_055078.1. [Q96TA2-2] DR UCSC; uc001iti.4; human. [Q96TA2-1] DR AGR; HGNC:12843; -. DR DisGeNET; 10730; -. DR GeneCards; YME1L1; -. DR HGNC; HGNC:12843; YME1L1. DR HPA; ENSG00000136758; Low tissue specificity. DR MalaCards; YME1L1; -. DR MIM; 607472; gene. DR MIM; 617302; phenotype. DR neXtProt; NX_Q96TA2; -. DR OpenTargets; ENSG00000136758; -. DR Orphanet; 98676; Autosomal recessive isolated optic atrophy. DR PharmGKB; PA37434; -. DR VEuPathDB; HostDB:ENSG00000136758; -. DR eggNOG; KOG0734; Eukaryota. DR GeneTree; ENSGT00550000074836; -. DR HOGENOM; CLU_000688_19_2_1; -. DR InParanoid; Q96TA2; -. DR OMA; RCWPVYV; -. DR OrthoDB; 9585at2759; -. DR PhylomeDB; Q96TA2; -. DR TreeFam; TF105005; -. DR BRENDA; 3.4.24.B18; 2681. DR PathwayCommons; Q96TA2; -. DR Reactome; R-HSA-8949664; Processing of SMDT1. DR SignaLink; Q96TA2; -. DR BioGRID-ORCS; 10730; 174 hits in 1173 CRISPR screens. DR ChiTaRS; YME1L1; human. DR GeneWiki; YME1L1; -. DR GenomeRNAi; 10730; -. DR Pharos; Q96TA2; Tbio. DR PRO; PR:Q96TA2; -. DR Proteomes; UP000005640; Chromosome 10. DR RNAct; Q96TA2; Protein. DR Bgee; ENSG00000136758; Expressed in germinal epithelium of ovary and 216 other cell types or tissues. DR ExpressionAtlas; Q96TA2; baseline and differential. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:UniProtKB. DR GO; GO:0005739; C:mitochondrion; IDA:HPA. DR GO; GO:0016604; C:nuclear body; IDA:HPA. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:InterPro. DR GO; GO:0004176; F:ATP-dependent peptidase activity; IDA:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0004222; F:metalloendopeptidase activity; IEA:InterPro. DR GO; GO:0008283; P:cell population proliferation; IMP:UniProtKB. DR GO; GO:0035694; P:mitochondrial protein catabolic process; IMP:UniProtKB. DR GO; GO:0034982; P:mitochondrial protein processing; IMP:UniProtKB. DR GO; GO:0007005; P:mitochondrion organization; IMP:UniProtKB. DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB. DR GO; GO:0034214; P:protein hexamerization; IDA:UniProtKB. DR GO; GO:0006515; P:protein quality control for misfolded or incompletely synthesized proteins; IMP:UniProtKB. DR CDD; cd19501; RecA-like_FtsH; 1. DR Gene3D; 1.10.8.60; -; 1. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1. DR Gene3D; 1.20.58.760; Peptidase M41; 1. DR HAMAP; MF_01458; FtsH; 1. DR InterPro; IPR003593; AAA+_ATPase. DR InterPro; IPR041569; AAA_lid_3. DR InterPro; IPR003959; ATPase_AAA_core. DR InterPro; IPR003960; ATPase_AAA_CS. DR InterPro; IPR005936; FtsH. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR000642; Peptidase_M41. DR InterPro; IPR037219; Peptidase_M41-like. DR NCBIfam; TIGR01241; FtsH_fam; 1. DR PANTHER; PTHR23076:SF37; ATP-DEPENDENT ZINC METALLOPROTEASE YME1L1; 1. DR PANTHER; PTHR23076; METALLOPROTEASE M41 FTSH; 1. DR Pfam; PF00004; AAA; 1. DR Pfam; PF17862; AAA_lid_3; 1. DR Pfam; PF01434; Peptidase_M41; 1. DR SMART; SM00382; AAA; 1. DR SUPFAM; SSF140990; FtsH protease domain-like; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1. DR PROSITE; PS00674; AAA; 1. DR Genevisible; Q96TA2; HS. PE 1: Evidence at protein level; KW Alternative splicing; ATP-binding; Disease variant; Hydrolase; Membrane; KW Metal-binding; Metalloprotease; Mitochondrion; KW Mitochondrion inner membrane; Nucleotide-binding; Protease; KW Reference proteome; Transmembrane; Transmembrane helix; Zinc. FT CHAIN 1..773 FT /note="ATP-dependent zinc metalloprotease YME1L1" FT /id="PRO_0000084667" FT TOPO_DOM 1..295 FT /note="Mitochondrial matrix" FT /evidence="ECO:0000255" FT TRANSMEM 296..316 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 317..773 FT /note="Mitochondrial intermembrane" FT /evidence="ECO:0000305|PubMed:27786171" FT ACT_SITE 600 FT /evidence="ECO:0000250|UniProtKB:P0AAI3" FT BINDING 379..386 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255" FT BINDING 599 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000250|UniProtKB:P0AAI3" FT BINDING 603 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000250|UniProtKB:P0AAI3" FT BINDING 677 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000250|UniProtKB:P0AAI3" FT VAR_SEQ 57..113 FT /note="Missing (in isoform 2 and isoform 3)" FT /evidence="ECO:0000303|PubMed:10843804, FT ECO:0000303|PubMed:12975309, ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334" FT /id="VSP_010017" FT VAR_SEQ 168..200 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_045336" FT VARIANT 206 FT /note="R -> W (in OPA11; does not affect localization to FT mitochondria; abolishes processing to mature form by MPP; FT results in decreased mitochondrial protein catabolism; has FT very low protease activity; results in mitochondrial FT fragmentation; dbSNP:rs1057519312)" FT /evidence="ECO:0000269|PubMed:27495975" FT /id="VAR_076869" FT MUTAGEN 439 FT /note="E->Q: Loss of ATPase and protease activity. Loss of FT PRELID1 degradation. Cannot restore OMA1 degradation in FT YME1L-depleted cells." FT /evidence="ECO:0000269|PubMed:26923599, FT ECO:0000269|PubMed:27495975, ECO:0000269|PubMed:27786171" FT MUTAGEN 600 FT /note="E->Q: Loss of protease activity. Cannot restore OMA1 FT degradation in YME1L-depleted cells." FT /evidence="ECO:0000269|PubMed:26923599" FT CONFLICT 12 FT /note="V -> F (in Ref. 1; AAK57555)" FT /evidence="ECO:0000305" SQ SEQUENCE 773 AA; 86455 MW; FB77990F4D7B3A58 CRC64; MFSLSSTVQP QVTVPLSHLI NAFHTPKNTS VSLSGVSVSQ NQHRDVVPEH EAPSSECMFS DFLTKLNIVS IGKGKIFEGY RSMFMEPAKR MKKSLDTTDN WHIRPEPFSL SIPPSLNLRD LGLSELKIGQ IDQLVENLLP GFCKGKNISS HWHTSHVSAQ SFFENKYGNL DIFSTLRSSC LYRHHSRALQ SICSDLQYWP VFIQSRGFKT LKSRTRRLQS TSERLAETQN IAPSFVKGFL LRDRGSDVES LDKLMKTKNI PEAHQDAFKT GFAEGFLKAQ ALTQKTNDSL RRTRLILFVL LLFGIYGLLK NPFLSVRFRT TTGLDSAVDP VQMKNVTFEH VKGVEEAKQE LQEVVEFLKN PQKFTILGGK LPKGILLVGP PGTGKTLLAR AVAGEADVPF YYASGSEFDE MFVGVGASRI RNLFREAKAN APCVIFIDEL DSVGGKRIES PMHPYSRQTI NQLLAEMDGF KPNEGVIIIG ATNFPEALDN ALIRPGRFDM QVTVPRPDVK GRTEILKWYL NKIKFDQSVD PEIIARGTVG FSGAELENLV NQAALKAAVD GKEMVTMKEL EFSKDKILMG PERRSVEIDN KNKTITAYHE SGHAIIAYYT KDAMPINKAT IMPRGPTLGH VSLLPENDRW NETRAQLLAQ MDVSMGGRVA EELIFGTDHI TTGASSDFDN ATKIAKRMVT KFGMSEKLGV MTYSDTGKLS PETQSAIEQE IRILLRDSYE RAKHILKTHA KEHKNLAEAL LTYETLDAKE IQIVLEGKKL EVR //