YMEL1_HUMAN
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 03-AUG-2022, entry version 188.
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}.
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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; 181.
DR IntAct; Q96TA2; 118.
DR MINT; Q96TA2; -.
DR STRING; 9606.ENSP00000318480; -.
DR MEROPS; M41.026; -.
DR GlyGen; Q96TA2; 2 sites, 1 O-linked glycan (1 site).
DR iPTMnet; Q96TA2; -.
DR MetOSite; Q96TA2; -.
DR PhosphoSitePlus; Q96TA2; -.
DR BioMuta; YME1L1; -.
DR DMDM; 46397258; -.
DR EPD; Q96TA2; -.
DR jPOST; Q96TA2; -.
DR MassIVE; Q96TA2; -.
DR MaxQB; Q96TA2; -.
DR PaxDb; Q96TA2; -.
DR PeptideAtlas; Q96TA2; -.
DR PRIDE; Q96TA2; -.
DR ProteomicsDB; 4708; -.
DR ProteomicsDB; 78222; -. [Q96TA2-1]
DR ProteomicsDB; 78223; -. [Q96TA2-2]
DR Antibodypedia; 44412; 159 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 CTD; 10730; -.
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; WHTSYIS; -.
DR OrthoDB; 217929at2759; -.
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; 173 hits in 1085 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 214 other tissues.
DR ExpressionAtlas; Q96TA2; baseline and differential.
DR Genevisible; Q96TA2; HS.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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:UniProtKB.
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 GO; GO:0006508; P:proteolysis; IBA:GO_Central.
DR Gene3D; 1.20.58.760; -; 1.
DR Gene3D; 3.40.50.300; -; 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 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; SSF140990; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR01241; FtsH_fam; 1.
DR PROSITE; PS00674; AAA; 1.
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
