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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

Putative ATP-dependent protease. Plays a role in mitochondrial organization and mitochondrial protein metabolism, including degradation of PRELID1 and OPA1 (PubMed:18076378, 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. Required to control the accumulation of nonassembled respiratory chain subunits (NDUFB6, OX4 and ND1).3 Publications

Cofactori

Zn2+CuratedNote: Binds 1 zinc ion per subunit.Curated

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
  • misfolded or incompletely synthesized protein catabolic process Source: UniProtKB
  • mitochondrial calcium ion transmembrane transport Source: Reactome
  • mitochondrial protein catabolic process Source: UniProtKB
  • mitochondrion organization Source: UniProtKB
  • negative regulation of apoptotic process 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.-)
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

HGNCiHGNC:12843. YME1L1.

Subcellular locationi

Topology

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

GO - Cellular componenti

  • integral component of membrane Source: UniProtKB-KW
  • membrane Source: UniProtKB
  • mitochondrial inner membrane Source: UniProtKB
  • mitochondrion Source: UniProtKB
  • nuclear body Source: HPA

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; results in mitochondrial fragmentation. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi10730.
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

Exists in several complexes of 600-1100 kDa (PubMed:22262461). Interacts with AFG1L (PubMed:26759378).2 Publications

Protein-protein interaction databases

BioGridi115954. 46 interactors.
IntActiQ96TA2. 43 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.
PfamiView protein in Pfam
PF00004. AAA. 1 hit.
PF01434. Peptidase_M41. 1 hit.
SMARTiView protein in SMART
SM00382. AAA. 1 hit.
SUPFAMiSSF52540. 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; 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: August 30, 2017
This is version 153 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