YMEL1_MOUSE
ID YMEL1_MOUSE Reviewed; 715 AA.
AC O88967; Q7TNN5;
DT 13-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 169.
DE RecName: Full=ATP-dependent zinc metalloprotease YME1L1;
DE EC=3.4.24.- {ECO:0000269|PubMed:27495975};
DE AltName: Full=ATP-dependent metalloprotease FtsH1;
DE AltName: Full=YME1-like protein 1;
GN Name=Yme1l1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Butterworth T., Taylor H.C., Zvetkova I., Poinat P., Stott D.;
RT "A member of the FtsH/YME1 family of ATP-dependent metalloproteases from
RT the mouse genome.";
RL Submitted (SEP-1998) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=ICR; TISSUE=Brain;
RA Ganesh S., Suzuki T., Yamakawa K.;
RT "Cloning and characterization of Yme1l1 homolog in mice.";
RL Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Urinary bladder;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [5]
RP FUNCTION.
RX PubMed=17709429; DOI=10.1083/jcb.200704110;
RA Song Z., Chen H., Fiket M., Alexander C., Chan D.C.;
RT "OPA1 processing controls mitochondrial fusion and is regulated by mRNA
RT splicing, membrane potential, and Yme1L.";
RL J. Cell Biol. 178:749-755(2007).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
RP FUNCTION.
RX PubMed=24616225; DOI=10.1083/jcb.201308006;
RA Anand R., Wai T., Baker M.J., Kladt N., Schauss A.C., Rugarli E.,
RA Langer T.;
RT "The i-AAA protease YME1L and OMA1 cleave OPA1 to balance mitochondrial
RT fusion and fission.";
RL J. Cell Biol. 204:919-929(2014).
RN [8]
RP FUNCTION, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=26785494; DOI=10.1126/science.aad0116;
RA Wai T., Garcia-Prieto J., Baker M.J., Merkwirth C., Benit P., Rustin P.,
RA Ruperez F.J., Barbas C., Ibanez B., Langer T.;
RT "Imbalanced OPA1 processing and mitochondrial fragmentation cause heart
RT failure in mice.";
RL Science 350:116-116(2015).
RN [9]
RP FUNCTION, AND CATALYTIC ACTIVITY.
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 (By similarity). Plays an important
CC role in regulating mitochondrial morphology and function by cleaving
CC OPA1 at position S2, giving rise to a form of OPA1 that promotes
CC maintenance of normal mitochondrial structure (PubMed:17709429,
CC PubMed:24616225, PubMed:26785494, PubMed:27495975). Ensures cell
CC proliferation, maintains normal cristae morphology and complex I
CC respiration activity, promotes antiapoptotic activity and protects
CC mitochondria from the accumulation of oxidatively damaged membrane
CC proteins (By similarity). Required for normal, constitutive degradation
CC of PRELID1 (PubMed:26785494). Catalyzes the degradation of OMA1 in
CC response to membrane depolarization. Required to control the
CC accumulation of nonassembled respiratory chain subunits (NDUFB6, OX4
CC and ND1) (By similarity). {ECO:0000250|UniProtKB:Q96TA2,
CC ECO:0000269|PubMed:17709429, ECO:0000269|PubMed:24616225,
CC ECO:0000269|PubMed:26785494, ECO:0000269|PubMed:27495975}.
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 -!- SUBUNIT: Homohexamer; may also form heterohexamers. Exists in several
CC complexes of 600-1100 kDa. Interacts with AFG1L.
CC {ECO:0000250|UniProtKB:Q96TA2}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000250|UniProtKB:Q96TA2}. Mitochondrion
CC {ECO:0000250|UniProtKB:Q96TA2}.
CC -!- TISSUE SPECIFICITY: Detected in heart and skeletal muscle (at protein
CC level). {ECO:0000269|PubMed:26785494}.
CC -!- PTM: Proteolytically processed by mitochondrial processing peptidase
CC (MPP) to generate the mature form. {ECO:0000250|UniProtKB:Q96TA2}.
CC -!- DISRUPTION PHENOTYPE: Complete embryonic lethality; embryos present a
CC clear developmental delay at 8.5 dpc, and the hearts of mutant embryos
CC fail to beat properly at 9.5 and 10.5 dpc. Cardiomyocyte-specific gene
CC disruption gives rise to animals that develop dilated cardiomyopathy
CC and myocardial fibrosis at about 20 weeks after birth; mutants have a
CC median life span of about 46 weeks, much shorter than wild-type.
CC Mitochondria from mutant cardiomyocytes are smaller than normal, but
CC have normal cristae architecture and display no significant difference
CC in the assembly of respiratory complexes. Keeping mice with a
CC cardiomyocyte-specific gene disruption on a high-fat diet leads to
CC weight gain and reduced glucose tolerance, and prevents the development
CC of cardiomyopathy. Mice with Yme1l gene disruption in cardiomyocytes
CC and skeletal muscle have a median life span of 125 weeks, similar to
CC wild-type. Their heart function is normal, in spite of the presence of
CC fragmented mitochondria due to the loss of Opa1 cleavage at position
CC S2. Skeletal muscle mitochondrial dysfunction is known to be associated
CC with impaired insulin signaling and glucose intolerance, and as
CC expected, these mice display impaired glucose homeostasis with
CC decreased fasting insulin levels in the blood serum and glucose
CC intolerance. Mice with a double, cardiomyocyte-specific gene disruption
CC of Yme1l and Oma1 have normal cardiac function and do not display
CC myocardial fibrosis. Likewise, cardiomyocyte mitochondria have normal
CC morphology. Mice with a skeletal muscle Yme1l gene disruption plus a
CC double, cardiomyocyte-specific gene disruption of Yme1l and Oma1
CC display normal glucose tolerance. {ECO:0000269|PubMed:26785494}.
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; AF090430; AAC35558.1; -; mRNA.
DR EMBL; AY136286; AAN17724.1; -; mRNA.
DR EMBL; AY136287; AAN17725.1; -; mRNA.
DR EMBL; AK079175; BAC37568.1; -; mRNA.
DR EMBL; BC007128; AAH07128.1; -; mRNA.
DR CCDS; CCDS15728.1; -.
DR RefSeq; NP_038799.1; NM_013771.5.
DR AlphaFoldDB; O88967; -.
DR SMR; O88967; -.
DR BioGRID; 205184; 7.
DR IntAct; O88967; 4.
DR MINT; O88967; -.
DR STRING; 10090.ENSMUSP00000028117; -.
DR MEROPS; M41.026; -.
DR iPTMnet; O88967; -.
DR PhosphoSitePlus; O88967; -.
DR EPD; O88967; -.
DR MaxQB; O88967; -.
DR PaxDb; O88967; -.
DR PeptideAtlas; O88967; -.
DR PRIDE; O88967; -.
DR ProteomicsDB; 275254; -.
DR Antibodypedia; 44412; 159 antibodies from 25 providers.
DR DNASU; 27377; -.
DR Ensembl; ENSMUST00000028117; ENSMUSP00000028117; ENSMUSG00000026775.
DR GeneID; 27377; -.
DR KEGG; mmu:27377; -.
DR UCSC; uc008ioe.2; mouse.
DR CTD; 10730; -.
DR MGI; MGI:1351651; Yme1l1.
DR VEuPathDB; HostDB:ENSMUSG00000026775; -.
DR eggNOG; KOG0734; Eukaryota.
DR GeneTree; ENSGT00550000074836; -.
DR HOGENOM; CLU_000688_19_2_1; -.
DR InParanoid; O88967; -.
DR OMA; WHTSYIS; -.
DR OrthoDB; 217929at2759; -.
DR PhylomeDB; O88967; -.
DR TreeFam; TF105005; -.
DR BRENDA; 3.4.24.B19; 3474.
DR Reactome; R-MMU-8949664; Processing of SMDT1.
DR BioGRID-ORCS; 27377; 18 hits in 75 CRISPR screens.
DR ChiTaRS; Yme1l1; mouse.
DR PRO; PR:O88967; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; O88967; protein.
DR Bgee; ENSMUSG00000026775; Expressed in embryonic brain and 256 other tissues.
DR Genevisible; O88967; MM.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005743; C:mitochondrial inner membrane; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0016604; C:nuclear body; ISO:MGI.
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; IMP: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; ISS:UniProtKB.
DR GO; GO:0035694; P:mitochondrial protein catabolic process; ISO:MGI.
DR GO; GO:0034982; P:mitochondrial protein processing; IMP:UniProtKB.
DR GO; GO:0007005; P:mitochondrion organization; ISS:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0034214; P:protein hexamerization; ISO:MGI.
DR GO; GO:0006515; P:protein quality control for misfolded or incompletely synthesized proteins; ISS: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 ATP-binding; Hydrolase; Membrane; Metal-binding; Metalloprotease;
KW Mitochondrion; Mitochondrion inner membrane; Nucleotide-binding; Protease;
KW Reference proteome; Transmembrane; Transmembrane helix; Zinc.
FT CHAIN 1..715
FT /note="ATP-dependent zinc metalloprotease YME1L1"
FT /id="PRO_0000084668"
FT TOPO_DOM 1..237
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000255"
FT TRANSMEM 238..258
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 259..715
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000255"
FT REGION 34..54
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 542
FT /evidence="ECO:0000250|UniProtKB:P0AAI3"
FT BINDING 321..328
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255"
FT BINDING 541
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P0AAI3"
FT BINDING 545
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P0AAI3"
FT BINDING 619
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01458"
SQ SEQUENCE 715 AA; 80028 MW; 28A861C55B305106 CRC64;
MFSLSSTVQP QVTIPLSHLI NAFHSPKNIS VSVNTPVSQK QHRDTVPEHE APSSEPVLNL
RDLGLSELKI GQIDKMVENL LPGFYKDKRV SSCWHTSHIS AQSFFENKYG HLDMFSTLRS
SSLYRQHPKT LRSICSDLQY FPVFIQSRGF KTLKSRTRRL QSTSERLVEA QNIAPSFVKG
FLLRDRGTDL ESLDKLMKTK NIPEAHQDAF KTGFAEGFLK AQALTQKTND SLRRTRLILF
VLLLFGIYGL LKNPFLSVRF RTTTGLDSAV DPVQMKNVTF EHVKGVEEAK QELQEVVEFL
KNPQKFTVLG GKLPKGILLV GPPGTGKTLL ARAVAGEADV PFYYASGSEF DEMFVGVGAS
RIRNLFREAK ANAPCVIFID ELDSVGGKRI ESPMHPYSRQ TINQLLAEMD GFKPNEGVII
IGATNFPEAL DNALIRPGRF DMQVTVPRPD VKGRTEILKW YLNKIKFDKS VDPEIIARGT
VGFSGAELEN LVNQAALKAA VDGKEMVTMK ELEFSKDKIL MGPERRSVEI DNKNKTITAY
HESGHAIIAY YTKDAMPINK ATIMPRGPTL GHVSLLPEND RWNETRAQLL AQMDVSMGGR
VAEELIFGTD HITTGASSDF DNATKIAKRM VTKFGMSEKL GVMTYSDTGK LSPETQSAIE
QEIRILLRES YERAKHILKT HAKEHKNLAE ALLTYETLDA KEIQIVLEGK KLEVR
