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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 protein catabolic process Source: UniProtKB
  • mitochondrion organization Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Metalloprotease, Protease

Keywords - Ligandi

ATP-binding, Metal-binding, Nucleotide-binding, Zinc

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
  • nucleoplasm Source: HPA
Complete GO annotation...

Keywords - Cellular componenti

Membrane, Mitochondrion, Mitochondrion inner membrane

Pathology & Biotechi

Involvement in diseasei

Defects in YME1L1 may cause a mitochondrial disorder characterized by infantile onset of intellectual disability, motor developmental delay, expressive speech delay, optic nerve atrophy associated with visual impairment, hearing impairment, but no facial dysmorphism. Lactate levels and lactate/pyruvate ratios are elevated in patients blood and/or cerebrospinal fluid. Muscle biopsy show mitochondria with altered cristae morphology and paracristalline inclusions.

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi10730.
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.1 Publication

Protein-protein interaction databases

BioGridi115954. 43 interactors.
IntActiQ96TA2. 32 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

Gene3Di3.40.50.300. 1 hit.
HAMAPiMF_01458. FtsH. 1 hit.
InterProiIPR003593. AAA+_ATPase.
IPR003959. ATPase_AAA_core.
IPR003960. ATPase_AAA_CS.
IPR005936. FtsH.
IPR027417. P-loop_NTPase.
IPR000642. Peptidase_M41.
[Graphical view]
PfamiPF00004. AAA. 1 hit.
PF01434. Peptidase_M41. 1 hit.
[Graphical view]
SMARTiSM00382. AAA. 1 hit.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 1 hit.
TIGRFAMsiTIGR01241. FtsH_fam. 1 hit.
PROSITEiPS00674. AAA. 1 hit.
[Graphical view]

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 Probable disease-associated mutation found in patients with an infantile-onset mitochondrial disorder; 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

Cross-referencesi

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.

3D structure databases

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

Protein-protein interaction databases

BioGridi115954. 43 interactors.
IntActiQ96TA2. 32 interactors.
MINTiMINT-3058738.
STRINGi9606.ENSP00000318480.

Protein family/group databases

MEROPSiM41.026.

PTM databases

iPTMnetiQ96TA2.
PhosphoSitePlusiQ96TA2.

Polymorphism and mutation databases

BioMutaiYME1L1.
DMDMi46397258.

Proteomic databases

EPDiQ96TA2.
MaxQBiQ96TA2.
PaxDbiQ96TA2.
PeptideAtlasiQ96TA2.
PRIDEiQ96TA2.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

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]

Organism-specific databases

CTDi10730.
DisGeNETi10730.
GeneCardsiYME1L1.
H-InvDBHIX0127242.
HGNCiHGNC:12843. YME1L1.
HPAiHPA066953.
MIMi607472. gene.
neXtProtiNX_Q96TA2.
OpenTargetsiENSG00000136758.
PharmGKBiPA37434.
GenAtlasiSearch...

Phylogenomic databases

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

Miscellaneous databases

ChiTaRSiYME1L1. human.
GeneWikiiYME1L1.
GenomeRNAii10730.
PROiQ96TA2.
SOURCEiSearch...

Gene expression databases

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

Family and domain databases

Gene3Di3.40.50.300. 1 hit.
HAMAPiMF_01458. FtsH. 1 hit.
InterProiIPR003593. AAA+_ATPase.
IPR003959. ATPase_AAA_core.
IPR003960. ATPase_AAA_CS.
IPR005936. FtsH.
IPR027417. P-loop_NTPase.
IPR000642. Peptidase_M41.
[Graphical view]
PfamiPF00004. AAA. 1 hit.
PF01434. Peptidase_M41. 1 hit.
[Graphical view]
SMARTiSM00382. AAA. 1 hit.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 1 hit.
TIGRFAMsiTIGR01241. FtsH_fam. 1 hit.
PROSITEiPS00674. AAA. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiYMEL1_HUMAN
AccessioniPrimary (citable) accession number: Q96TA2
Secondary accession number(s): B4DNM1
, D3DRV8, D3DRV9, Q5T8D9, Q9H1Q0, Q9UMR9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 13, 2004
Last sequence update: April 13, 2004
Last modified: November 30, 2016
This is version 146 of the entry and version 2 of the sequence. [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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.