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Protein

ATP-dependent zinc metalloprotease YME1L1

Gene

YME1L1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

ATP-dependent metalloprotease that catalyzes the degradation of folded and unfolded proteins with a suitable degron sequence in the mitochondrial intermembrane region (PubMed:26923599, PubMed:27786171). Plays an important role in regulating mitochondrial morphology and function by cleaving OPA1 at position S2, giving rise to a form of OPA1 that promotes maintenance of normal mitochondrial structure and mitochondrial protein metabolism (PubMed:18076378, PubMed:26923599, PubMed:27495975). Ensures cell proliferation, maintains normal cristae morphology and complex I respiration activity, promotes antiapoptotic activity and protects mitochondria from the accumulation of oxidatively damaged membrane proteins (PubMed:22262461). Required for normal, constitutive degradation of PRELID1 (PubMed:27495975). Catalyzes the degradation of OMA1 in response to membrane depolarization (PubMed:26923599). Required to control the accumulation of nonassembled respiratory chain subunits (NDUFB6, OX4 and ND1) (PubMed:22262461).5 Publications

Cofactori

Zn2+1 PublicationNote: Binds 1 zinc ion per subunit.1 Publication

Kineticsi

  1. KM=1.4 mM for ATP1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Metal bindingi599Zinc; catalyticBy similarity1
    Active sitei600By similarity1
    Metal bindingi603Zinc; catalyticBy similarity1
    Metal bindingi677Zinc; catalyticBy similarity1

    Regions

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Nucleotide bindingi379 – 386ATPSequence analysis8

    GO - Molecular functioni

    GO - Biological processi

    • cell proliferation Source: UniProtKB
    • mitochondrial calcium ion transmembrane transport Source: Reactome
    • mitochondrial protein catabolic process Source: UniProtKB
    • mitochondrial protein processing Source: UniProtKB
    • mitochondrion organization Source: UniProtKB
    • negative regulation of apoptotic process Source: UniProtKB
    • protein hexamerization Source: UniProtKB
    • protein quality control by the ubiquitin-proteasome system Source: UniProtKB

    Keywordsi

    Molecular functionHydrolase, Metalloprotease, Protease
    LigandATP-binding, Metal-binding, Nucleotide-binding, Zinc

    Enzyme and pathway databases

    ReactomeiR-HSA-8949664. Processing of SMDT1.

    Protein family/group databases

    MEROPSiM41.026.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    ATP-dependent zinc metalloprotease YME1L1 (EC:3.4.24.-3 Publications)
    Alternative name(s):
    ATP-dependent metalloprotease FtsH1
    Meg-4
    Presenilin-associated metalloprotease
    Short name:
    PAMP
    YME1-like protein 1
    Gene namesi
    Name:YME1L1
    Synonyms:FTSH1, YME1L
    ORF Names:UNQ1868/PRO4304
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 10

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000136758.18.
    HGNCiHGNC:12843. YME1L1.

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    Topology

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Topological domaini1 – 295Mitochondrial matrixSequence analysisAdd BLAST295
    Transmembranei296 – 316HelicalSequence analysisAdd BLAST21
    Topological domaini317 – 773Mitochondrial intermembrane1 PublicationAdd BLAST457

    Keywords - Cellular componenti

    Membrane, Mitochondrion, Mitochondrion inner membrane

    Pathology & Biotechi

    Involvement in diseasei

    Optic atrophy 11 (OPA11)1 Publication
    The disease may be caused by mutations affecting the gene represented in this entry.
    Disease descriptionAn autosomal recessive disease characterized by progressive visual loss in association with optic atrophy. Atrophy of the optic disk indicates a deficiency in the number of nerve fibers which arise in the retina and converge to form the optic disk, optic nerve, optic chiasm and optic tracts. OPA11 patients also manifest delayed psychomotor development, intellectual disability, ataxia, and leukoencephalopathy on brain imaging.
    See also OMIM:617302
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_076869206R → W in OPA11; does not affect localization to mitochondria; abolishes processing to mature form by MPP; results in decreased mitochondrial protein catabolism; has very low protease activity; results in mitochondrial fragmentation. 1 Publication1

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi439E → Q: Loss of ATPase and protease activity. Loss of PRELID1 degradation. Cannot restore OMA1 degradation in YME1L-depleted cells. 3 Publications1
    Mutagenesisi600E → Q: Loss of protease activity. Cannot restore OMA1 degradation in YME1L-depleted cells. 1 Publication1

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    DisGeNETi10730.
    MalaCardsiYME1L1.
    MIMi617302. phenotype.
    OpenTargetsiENSG00000136758.
    PharmGKBiPA37434.

    Polymorphism and mutation databases

    BioMutaiYME1L1.
    DMDMi46397258.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00000846671 – 773ATP-dependent zinc metalloprotease YME1L1Add BLAST773

    Post-translational modificationi

    Proteolytically processed by mitochondrial processing peptidase (MPP) to generate the mature form.1 Publication

    Proteomic databases

    EPDiQ96TA2.
    MaxQBiQ96TA2.
    PaxDbiQ96TA2.
    PeptideAtlasiQ96TA2.
    PRIDEiQ96TA2.

    PTM databases

    iPTMnetiQ96TA2.
    PhosphoSitePlusiQ96TA2.

    Expressioni

    Tissue specificityi

    High expression in cardiac and skeletal muscle mitochondria.1 Publication

    Gene expression databases

    BgeeiENSG00000136758.
    CleanExiHS_YME1L1.
    ExpressionAtlasiQ96TA2. baseline and differential.
    GenevisibleiQ96TA2. HS.

    Organism-specific databases

    HPAiHPA066953.

    Interactioni

    Subunit structurei

    Homohexamer; may also form heterohexamers (PubMed:27786171). Exists in several complexes of 600-1100 kDa (PubMed:22262461, PubMed:27495975). Interacts with AFG1L (PubMed:26759378).4 Publications

    Protein-protein interaction databases

    BioGridi115954. 47 interactors.
    IntActiQ96TA2. 44 interactors.
    MINTiMINT-3058738.
    STRINGi9606.ENSP00000318480.

    Structurei

    3D structure databases

    ProteinModelPortaliQ96TA2.
    SMRiQ96TA2.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    In the N-terminal section; belongs to the AAA ATPase family.Curated
    In the C-terminal section; belongs to the peptidase M41 family.Curated

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiKOG0734. Eukaryota.
    COG0465. LUCA.
    GeneTreeiENSGT00550000074836.
    HOGENOMiHOG000217276.
    HOVERGENiHBG057127.
    InParanoidiQ96TA2.
    KOiK08955.
    OMAiCLYRQHS.
    OrthoDBiEOG091G02Y9.
    PhylomeDBiQ96TA2.
    TreeFamiTF105005.

    Family and domain databases

    HAMAPiMF_01458. FtsH. 1 hit.
    InterProiView protein in InterPro
    IPR003593. AAA+_ATPase.
    IPR003959. ATPase_AAA_core.
    IPR003960. ATPase_AAA_CS.
    IPR005936. FtsH.
    IPR027417. P-loop_NTPase.
    IPR000642. Peptidase_M41.
    IPR037219. Peptidase_M41-like.
    PfamiView protein in Pfam
    PF00004. AAA. 1 hit.
    PF01434. Peptidase_M41. 1 hit.
    SMARTiView protein in SMART
    SM00382. AAA. 1 hit.
    SUPFAMiSSF140990. SSF140990. 1 hit.
    SSF52540. SSF52540. 1 hit.
    TIGRFAMsiTIGR01241. FtsH_fam. 1 hit.
    PROSITEiView protein in PROSITE
    PS00674. AAA. 1 hit.

    Sequences (3)i

    Sequence statusi: Complete.

    This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform 1 (identifier: Q96TA2-1) [UniParc]FASTAAdd to basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

            10         20         30         40         50
    MFSLSSTVQP QVTVPLSHLI NAFHTPKNTS VSLSGVSVSQ NQHRDVVPEH
    60 70 80 90 100
    EAPSSECMFS DFLTKLNIVS IGKGKIFEGY RSMFMEPAKR MKKSLDTTDN
    110 120 130 140 150
    WHIRPEPFSL SIPPSLNLRD LGLSELKIGQ IDQLVENLLP GFCKGKNISS
    160 170 180 190 200
    HWHTSHVSAQ SFFENKYGNL DIFSTLRSSC LYRHHSRALQ SICSDLQYWP
    210 220 230 240 250
    VFIQSRGFKT LKSRTRRLQS TSERLAETQN IAPSFVKGFL LRDRGSDVES
    260 270 280 290 300
    LDKLMKTKNI PEAHQDAFKT GFAEGFLKAQ ALTQKTNDSL RRTRLILFVL
    310 320 330 340 350
    LLFGIYGLLK NPFLSVRFRT TTGLDSAVDP VQMKNVTFEH VKGVEEAKQE
    360 370 380 390 400
    LQEVVEFLKN PQKFTILGGK LPKGILLVGP PGTGKTLLAR AVAGEADVPF
    410 420 430 440 450
    YYASGSEFDE MFVGVGASRI RNLFREAKAN APCVIFIDEL DSVGGKRIES
    460 470 480 490 500
    PMHPYSRQTI NQLLAEMDGF KPNEGVIIIG ATNFPEALDN ALIRPGRFDM
    510 520 530 540 550
    QVTVPRPDVK GRTEILKWYL NKIKFDQSVD PEIIARGTVG FSGAELENLV
    560 570 580 590 600
    NQAALKAAVD GKEMVTMKEL EFSKDKILMG PERRSVEIDN KNKTITAYHE
    610 620 630 640 650
    SGHAIIAYYT KDAMPINKAT IMPRGPTLGH VSLLPENDRW NETRAQLLAQ
    660 670 680 690 700
    MDVSMGGRVA EELIFGTDHI TTGASSDFDN ATKIAKRMVT KFGMSEKLGV
    710 720 730 740 750
    MTYSDTGKLS PETQSAIEQE IRILLRDSYE RAKHILKTHA KEHKNLAEAL
    760 770
    LTYETLDAKE IQIVLEGKKL EVR
    Length:773
    Mass (Da):86,455
    Last modified:April 13, 2004 - v2
    Checksum:iFB77990F4D7B3A58
    GO
    Isoform 2 (identifier: Q96TA2-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         57-113: Missing.

    Note: Mutagenesis of Glu-543 to Gln does not complement excessive accumulation of subunits (NDUFB6, COX4,ND1) due to YME1 deletion mutant. Probably has no ATPase activity.
    Show »
    Length:716
    Mass (Da):79,832
    Checksum:i17828316886DF7C5
    GO
    Isoform 3 (identifier: Q96TA2-3) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         57-113: Missing.
         168-200: Missing.

    Show »
    Length:683
    Mass (Da):75,982
    Checksum:i8A037ED99ED7D2E3
    GO

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti12V → F in AAK57555 (Ref. 1) Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_076869206R → W in OPA11; does not affect localization to mitochondria; abolishes processing to mature form by MPP; results in decreased mitochondrial protein catabolism; has very low protease activity; results in mitochondrial fragmentation. 1 Publication1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_01001757 – 113Missing in isoform 2 and isoform 3. 4 PublicationsAdd BLAST57
    Alternative sequenceiVSP_045336168 – 200Missing in isoform 3. 1 PublicationAdd BLAST33

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF151782 mRNA. Translation: AAK57555.1.
    AJ132637 mRNA. Translation: CAB51858.1.
    AY358484 mRNA. Translation: AAQ88848.1.
    AK297973 mRNA. Translation: BAG60283.1.
    AL162272 Genomic DNA. Translation: CAC19650.2.
    AL162272, AL160291 Genomic DNA. Translation: CAI12217.1.
    AL160291, AL162272 Genomic DNA. Translation: CAI16906.1.
    AL160291, AL162272 Genomic DNA. Translation: CAI16907.1.
    CH471072 Genomic DNA. Translation: EAW86068.1.
    CH471072 Genomic DNA. Translation: EAW86069.1.
    CH471072 Genomic DNA. Translation: EAW86070.1.
    CH471072 Genomic DNA. Translation: EAW86071.1.
    CH471072 Genomic DNA. Translation: EAW86072.1.
    BC023507 mRNA. Translation: AAH23507.1.
    BC024032 mRNA. Translation: AAH24032.1.
    CCDSiCCDS58072.1. [Q96TA2-3]
    CCDS7151.1. [Q96TA2-2]
    CCDS7152.1. [Q96TA2-1]
    RefSeqiNP_001240795.1. NM_001253866.1. [Q96TA2-3]
    NP_055078.1. NM_014263.3. [Q96TA2-2]
    NP_647473.1. NM_139312.2. [Q96TA2-1]
    UniGeneiHs.499145.
    Hs.74647.

    Genome annotation databases

    EnsembliENST00000326799; ENSP00000318480; ENSG00000136758. [Q96TA2-1]
    ENST00000376016; ENSP00000365184; ENSG00000136758. [Q96TA2-2]
    ENST00000613434; ENSP00000481724; ENSG00000136758. [Q96TA2-3]
    GeneIDi10730.
    KEGGihsa:10730.
    UCSCiuc001iti.4. human. [Q96TA2-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Similar proteinsi

    Entry informationi

    Entry nameiYMEL1_HUMAN
    AccessioniPrimary (citable) accession number: Q96TA2
    Secondary accession number(s): B4DNM1
    , D3DRV8, D3DRV9, Q5T8D9, Q9H1Q0, Q9UMR9
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 13, 2004
    Last sequence update: April 13, 2004
    Last modified: October 25, 2017
    This is version 155 of the entry and version 2 of the sequence. See complete history.
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 10
      Human chromosome 10: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. Peptidase families
      Classification of peptidase families and list of entries
    6. SIMILARITY comments
      Index of protein domains and families