YMEL1_DROME
ID YMEL1_DROME Reviewed; 740 AA.
AC F3YDF1; Q8MMD4; Q9W1Y0;
DT 16-OCT-2019, integrated into UniProtKB/Swiss-Prot.
DT 28-JUN-2011, sequence version 1.
DT 03-AUG-2022, entry version 87.
DE RecName: Full=ATP-dependent zinc metalloprotease YME1L {ECO:0000305};
DE EC=3.4.24.- {ECO:0000312|EMBL:AFH08226.1};
DE AltName: Full=YME1-like ATPase {ECO:0000312|FlyBase:FBgn0034792};
GN Name=YME1L {ECO:0000312|FlyBase:FBgn0034792};
GN ORFNames=CG3499 {ECO:0000312|FlyBase:FBgn0034792};
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227 {ECO:0000312|Proteomes:UP000000803};
RN [1] {ECO:0000312|Proteomes:UP000000803}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [2] {ECO:0000312|Proteomes:UP000000803}
RP GENOME REANNOTATION.
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [3] {ECO:0000312|EMBL:AAK92904.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B).
RC STRAIN=Berkeley {ECO:0000312|EMBL:AAK92904.1};
RC TISSUE=Head {ECO:0000312|EMBL:AAK92904.1};
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [4] {ECO:0000312|EMBL:AEB39673.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM C).
RC STRAIN=Berkeley {ECO:0000312|EMBL:AEB39673.1};
RA Carlson J., Booth B., Frise E., Sandler J., Wan K., Yu C., Celniker S.;
RL Submitted (APR-2011) to the EMBL/GenBank/DDBJ databases.
RN [5] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=26160069; DOI=10.1038/cdd.2015.94;
RA Qi Y., Liu H., Daniels M.P., Zhang G., Xu H.;
RT "Loss of Drosophila i-AAA protease, dYME1L, causes abnormal mitochondria
RT and apoptotic degeneration.";
RL Cell Death Differ. 23:291-302(2016).
RN [6] {ECO:0000305}
RP FUNCTION.
RX PubMed=31125351; DOI=10.1371/journal.pgen.1008184;
RA Yoon W., Hwang S.H., Lee S.H., Chung J.;
RT "Drosophila ADCK1 is critical for maintaining mitochondrial structures and
RT functions in the muscle.";
RL PLoS Genet. 15:E1008184-E1008184(2019).
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:26160069). Plays an
CC important role in regulating mitochondrial morphology and function by
CC cleaving Opa1, giving rise to a form of Opa1 that promotes maintenance
CC of normal mitochondrial structure and mitochondrial protein metabolism
CC (PubMed:31125351). 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:26160069, PubMed:31125351). Required
CC to control the accumulation of nonassembled respiratory chain subunits
CC such as ND-30 (PubMed:26160069). {ECO:0000269|PubMed:26160069,
CC ECO:0000269|PubMed:31125351}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:Q96TA2};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:Q96TA2};
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:26160069}; Single-pass membrane protein
CC {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=C {ECO:0000312|FlyBase:FBgn0034792};
CC IsoId=F3YDF1-1; Sequence=Displayed;
CC Name=B {ECO:0000312|FlyBase:FBgn0034792};
CC IsoId=F3YDF1-2; Sequence=VSP_060331, VSP_060332;
CC -!- DISRUPTION PHENOTYPE: Viable but lifespan is reduced and males are
CC sterile. Mitochondrial proteostasis is disrupted leading to crista
CC disorganization, mitochondrial unfolded protein stress and impaired
CC complex I activity which increases levels of reactive oxygen species
CC (ROS). These defects all likely contribute to the increase in Dronc-
CC mediated apoptosis in neuromuscular tissue. The severity of the
CC mitochondrial abnormalities and their resulting phenotypes increase
CC with age, resulting in the progressive degeneration of photoreceptor
CC neurons and locomotor activity and increased sensitivity to genetic and
CC environmental stresses. {ECO:0000269|PubMed:26160069}.
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; AE013599; AAM71132.2; -; Genomic_DNA.
DR EMBL; AE013599; AFH08226.1; -; Genomic_DNA.
DR EMBL; AY051480; AAK92904.1; -; mRNA.
DR EMBL; BT126312; AEB39673.1; -; mRNA.
DR RefSeq; NP_001246473.1; NM_001259544.2. [F3YDF1-1]
DR RefSeq; NP_726263.1; NM_166568.3. [F3YDF1-2]
DR AlphaFoldDB; F3YDF1; -.
DR SMR; F3YDF1; -.
DR IntAct; F3YDF1; 7.
DR STRING; 7227.FBpp0293463; -.
DR MEROPS; M41.A11; -.
DR PaxDb; F3YDF1; -.
DR PRIDE; F3YDF1; -.
DR DNASU; 37636; -.
DR EnsemblMetazoa; FBtr0071906; FBpp0071817; FBgn0034792. [F3YDF1-2]
DR EnsemblMetazoa; FBtr0304924; FBpp0293463; FBgn0034792. [F3YDF1-1]
DR GeneID; 37636; -.
DR KEGG; dme:Dmel_CG3499; -.
DR UCSC; CG3499-RB; d. melanogaster.
DR CTD; 37636; -.
DR FlyBase; FBgn0034792; YME1L.
DR VEuPathDB; VectorBase:FBgn0034792; -.
DR eggNOG; KOG0734; Eukaryota.
DR GeneTree; ENSGT00550000074836; -.
DR HOGENOM; CLU_000688_19_1_1; -.
DR OMA; FQQNEGV; -.
DR PhylomeDB; F3YDF1; -.
DR Reactome; R-DME-8949664; Processing of SMDT1.
DR BioGRID-ORCS; 37636; 1 hit in 1 CRISPR screen.
DR GenomeRNAi; 37636; -.
DR PRO; PR:F3YDF1; -.
DR Proteomes; UP000000803; Chromosome 2R.
DR Bgee; FBgn0034792; Expressed in testis and 33 other tissues.
DR ExpressionAtlas; F3YDF1; baseline and differential.
DR GO; GO:0005745; C:m-AAA complex; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; IDA:FlyBase.
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; IEA:InterPro.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004222; F:metalloendopeptidase activity; IEA:InterPro.
DR GO; GO:0034982; P:mitochondrial protein processing; IBA:GO_Central.
DR GO; GO:0065003; P:protein-containing complex assembly; 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 2: Evidence at transcript level;
KW Alternative splicing; ATP-binding; Hydrolase; Membrane; Metal-binding;
KW Metalloprotease; Mitochondrion; Mitochondrion inner membrane;
KW Nucleotide-binding; Protease; Reference proteome; Transmembrane;
KW Transmembrane helix; Zinc.
FT CHAIN 1..740
FT /note="ATP-dependent zinc metalloprotease YME1L"
FT /id="PRO_0000448069"
FT TOPO_DOM 1..256
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000305"
FT TRANSMEM 257..277
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 278..740
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000305"
FT ACT_SITE 564
FT /evidence="ECO:0000250|UniProtKB:Q9WZ49"
FT BINDING 347..351
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9WZ49"
FT BINDING 563
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q9WZ49"
FT BINDING 567
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q9WZ49"
FT BINDING 641
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q9WZ49"
FT VAR_SEQ 257..259
FT /note="Missing (in isoform B)"
FT /id="VSP_060331"
FT VAR_SEQ 285
FT /note="Missing (in isoform B)"
FT /id="VSP_060332"
SQ SEQUENCE 740 AA; 81081 MW; AECFDEA5B316795D CRC64;
MFSTTTHSVP YLYLGNFSRK PHYYSVNRTK LHGSAGAARL SKSTSTSSRS HDLVLDLRNL
LSRSSASIQG MVERAARLNG ILDRRLVDDV LAKVTSMLPS MRDVRVTLEE SATQIGRVQL
QNYQFEVSLT GAAGSVPTGA NVKVIPTITP GLLRPLFSQQ QLNQIRGFKT DRSIEAEQKR
NPTMTSRLKN ALANSPQRLD GDTPLQAEKL RRLLAKSEEH GFNKAESLKI AFAEGYLAAA
NSEDSPKSGK TMKYLKTLQT IVVIVVFLGI FLSFFTTSNG SVFRSIQLGN QVEVDPEEIN
VTFEDVKGCD EAKQELKEVV EFLKSPEKFS NLGGKLPKGV LLVGPPGTGK TLLARAVAGE
AKVPFFHAAG PEFDEVLVGQ GARRVRDLFK AAKARAPCVI FIDEIDSVGA KRTNSVLHPY
ANQTINQLLS EMDGFHQNAG VIVLGATNRR DDLDQALLRP GRFDVEVMVS TPDFTGRKEI
LSLYLTKILH DEIDLDMLAR GTSGFTGADL ENMINQAALR AAIDGAETVS MKHLETARDK
VLMGPERKAR LPDEEANTIT AYHEGGHAIV AFYTKESHPL HKVTIMPRGP SLGHTAYIPE
KERYHVTKAQ LLAMMDTMMG GRAAEELVFG TDKITSGASS DLKQATSIAT HMVRDWGMSD
KVGLRTIEAS KGLGTGDTLG PNTIEAVDAE IKRILSDSYE RAKAILRKHT REHKALAEAL
LKYETLDADD IKAILNESQT
