The protein encoded by this gene is the human ortholog of yeast mitochondrial AAA metalloprotease, Yme1p. It is localized in the mitochondria and can functionally complement a yme1 disruptant yeast strain. It is proposed that this gene plays a role in mitochondrial protein metabolism and could be involved in mitochondrial pathologies. Three transcript variants encoding differen... See more...

Aliases for YME1L1 Gene

Aliases for YME1L1 Gene

  • YME1 Like 1 ATPase 2 3 5
  • ATP-Dependent Zinc Metalloprotease YME1L1 3 4
  • Presenilin-Associated Metalloprotease 3 4
  • YME1-Like Protein 1 3 4
  • Meg-4 3 4
  • YME1L 3 4
  • PAMP 3 4
  • ATP-Dependent Metalloprotease FtsH1 Homolog 3
  • ATP-Dependent Metalloprotease FtsH1 4
  • YME1-Like 1 (S. Cerevisiae) 2
  • YME1 (S.Cerevisiae)-Like 1 2
  • YME1-Like 1 ATPase 2
  • EC 3.4.24.- 4
  • EC 3.4.24 54
  • OPA11 3
  • FTSH1 4
  • FTSH 3
  • MEG4 3

External Ids for YME1L1 Gene

Previous GeneCards Identifiers for YME1L1 Gene

  • GC10M027134
  • GC10M027549
  • GC10M027403
  • GC10M027439
  • GC10M027068

Summaries for YME1L1 Gene

Entrez Gene Summary for YME1L1 Gene

  • The protein encoded by this gene is the human ortholog of yeast mitochondrial AAA metalloprotease, Yme1p. It is localized in the mitochondria and can functionally complement a yme1 disruptant yeast strain. It is proposed that this gene plays a role in mitochondrial protein metabolism and could be involved in mitochondrial pathologies. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

GeneCards Summary for YME1L1 Gene

YME1L1 (YME1 Like 1 ATPase) is a Protein Coding gene. Diseases associated with YME1L1 include Optic Atrophy 11 and Spastic Paraplegia 7, Autosomal Recessive. Gene Ontology (GO) annotations related to this gene include metalloendopeptidase activity. An important paralog of this gene is AFG3L2.

UniProtKB/Swiss-Prot Summary for YME1L1 Gene

  • 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).

Gene Wiki entry for YME1L1 Gene

Additional gene information for YME1L1 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for YME1L1 Gene

Genomics for YME1L1 Gene

GeneHancer (GH) Regulatory Elements for YME1L1 Gene

Promoters and enhancers for YME1L1 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around YME1L1 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the YME1L1 gene promoter:
  • ATF-2
  • c-Jun

Genomic Locations for YME1L1 Gene

Genomic Locations for YME1L1 Gene
chr10:27,110,111-27,155,278
(GRCh38/hg38)
Size:
45,168 bases
Orientation:
Minus strand
chr10:27,399,383-27,444,195
(GRCh37/hg19)
Size:
44,813 bases
Orientation:
Minus strand

Genomic View for YME1L1 Gene

Genes around YME1L1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
YME1L1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for YME1L1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for YME1L1 Gene

Proteins for YME1L1 Gene

  • Protein details for YME1L1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q96TA2-YMEL1_HUMAN
    Recommended name:
    ATP-dependent zinc metalloprotease YME1L1
    Protein Accession:
    Q96TA2
    Secondary Accessions:
    • B4DNM1
    • D3DRV8
    • D3DRV9
    • Q5T8D9
    • Q9H1Q0
    • Q9UMR9

    Protein attributes for YME1L1 Gene

    Size:
    773 amino acids
    Molecular mass:
    86455 Da
    Cofactor:
    Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
    Quaternary structure:
    • Homohexamer; may also form heterohexamers (PubMed:27786171). Exists in several complexes of 600-1100 kDa (PubMed:22262461, PubMed:27495975). Interacts with AFG1L (PubMed:26759378).

    Alternative splice isoforms for YME1L1 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for YME1L1 Gene

Selected DME Specific Peptides for YME1L1 Gene

Q96TA2:
  • QTINQLL
  • AKANAPC
  • GRVAEELIFG
  • EMFVGVG
  • LLVGPPGTGKTLLA
  • LGGKLPKG
  • IIIGATNFPEALD
  • GRTEILK

Post-translational modifications for YME1L1 Gene

  • Proteolytically processed by mitochondrial processing peptidase (MPP) to generate the mature form.
  • Ubiquitination at Lys237, Lys253, Lys258, Lys269, Lys363, Lys385, Lys446, Lys524, and Lys568
  • Modification sites at PhosphoSitePlus

Domains & Families for YME1L1 Gene

Gene Families for YME1L1 Gene

HGNC:
Human Protein Atlas (HPA):
  • Disease related genes
  • Enzymes
  • Potential drug targets
  • Predicted intracellular proteins
  • Predicted membrane proteins

Suggested Antigen Peptide Sequences for YME1L1 Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ58153, highly similar to ATP-dependent metalloprotease YME1L1 (EC 3.4.24.-) (B4DNM1_HUMAN)
  • YME1-like 1 (S. cerevisiae) (Q5T8D1_HUMAN)
  • YME1-like 1 (S. cerevisiae) (Q5T8D2_HUMAN)
  • YME1L1 protein (Q6PJ89_HUMAN)
  • YME1-like 1 (S. cerevisiae) (Q96I63_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q96TA2

UniProtKB/Swiss-Prot:

YMEL1_HUMAN :
  • In the N-terminal section; belongs to the AAA ATPase family.
Family:
  • In the N-terminal section; belongs to the AAA ATPase family.
  • In the C-terminal section; belongs to the peptidase M41 family.
genes like me logo Genes that share domains with YME1L1: view

Function for YME1L1 Gene

Molecular function for YME1L1 Gene

UniProtKB/Swiss-Prot Function:
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).
UniProtKB/Swiss-Prot BiophysicochemicalProperties:
Kinetic parameters: KM=1.4 mM for ATP {ECO:0000269 PubMed:27786171};

Enzyme Numbers (IUBMB) for YME1L1 Gene

Phenotypes From GWAS Catalog for YME1L1 Gene

Gene Ontology (GO) - Molecular Function for YME1L1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004176 ATP-dependent peptidase activity IBA,IMP 27495975
GO:0004222 metalloendopeptidase activity IEA --
GO:0005515 protein binding IPI 26759378
GO:0005524 ATP binding IEA --
GO:0008233 peptidase activity IEA --
genes like me logo Genes that share ontologies with YME1L1: view
genes like me logo Genes that share phenotypes with YME1L1: view

Human Phenotype Ontology for YME1L1 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for YME1L1 Gene

MGI Knock Outs for YME1L1:

Animal Model Products

  • Taconic Biosciences Mouse Models for YME1L1

CRISPR Products

miRNA for YME1L1 Gene

miRTarBase miRNAs that target YME1L1

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for YME1L1

Clone Products

No data available for Transcription Factor Targets and HOMER Transcription for YME1L1 Gene

Localization for YME1L1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for YME1L1 Gene

Mitochondrion inner membrane. Mitochondrion.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for YME1L1 gene
Compartment Confidence
mitochondrion 5
nucleus 4
cytosol 3
plasma membrane 2
extracellular 1
peroxisome 1
endoplasmic reticulum 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Mitochondria (3)
  • Nuclear bodies (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for YME1L1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005739 mitochondrion IDA 27495975
GO:0005743 mitochondrial inner membrane TAS --
GO:0016020 membrane IEA,HDA 19946888
GO:0016021 integral component of membrane IEA --
GO:0016604 nuclear body IDA --
genes like me logo Genes that share ontologies with YME1L1: view

Pathways & Interactions for YME1L1 Gene

PathCards logo

SuperPathways for YME1L1 Gene

No Data Available

Gene Ontology (GO) - Biological Process for YME1L1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006508 proteolysis IEA,IBA 21873635
GO:0006515 protein quality control for misfolded or incompletely synthesized proteins IMP,IBA 22262461
GO:0006851 mitochondrial calcium ion transmembrane transport TAS --
GO:0007005 mitochondrion organization IMP,IBA 22262461
GO:0008283 cell proliferation IMP 22262461
genes like me logo Genes that share ontologies with YME1L1: view

No data available for Pathways by source and SIGNOR curated interactions for YME1L1 Gene

Drugs & Compounds for YME1L1 Gene

(1) Drugs for YME1L1 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
genes like me logo Genes that share compounds with YME1L1: view

Transcripts for YME1L1 Gene

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for YME1L1

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for YME1L1 Gene

No ASD Table

Relevant External Links for YME1L1 Gene

GeneLoc Exon Structure for
YME1L1
ECgene alternative splicing isoforms for
YME1L1

Expression for YME1L1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for YME1L1 Gene

Protein differential expression in normal tissues from HIPED for YME1L1 Gene

This gene is overexpressed in Nasal epithelium (27.4), Breast (16.9), Heart (7.3), and Lung (6.5).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for YME1L1 Gene



Protein tissue co-expression partners for YME1L1 Gene

NURSA nuclear receptor signaling pathways regulating expression of YME1L1 Gene:

YME1L1

SOURCE GeneReport for Unigene cluster for YME1L1 Gene:

Hs.74647

mRNA Expression by UniProt/SwissProt for YME1L1 Gene:

Q96TA2-YMEL1_HUMAN
Tissue specificity: High expression in cardiac and skeletal muscle mitochondria.

Evidence on tissue expression from TISSUES for YME1L1 Gene

  • Nervous system(4.9)
  • Muscle(4.6)
  • Blood(3.5)
  • Skin(2.7)
  • Kidney(2.5)
  • Lung(2.4)
  • Eye(2.2)
  • Liver(2)
genes like me logo Genes that share expression patterns with YME1L1: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for YME1L1 Gene

Orthologs for YME1L1 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for YME1L1 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia YME1L1 33 32
  • 99.66 (n)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia YME1L1 33
  • 93 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia YME1L1 33
  • 93 (a)
OneToOne
cow
(Bos Taurus)
Mammalia YME1L1 33 32
  • 92.42 (n)
OneToOne
dog
(Canis familiaris)
Mammalia YME1L1 33 32
  • 92.26 (n)
OneToOne
rat
(Rattus norvegicus)
Mammalia LOC100910779 32
  • 90.86 (n)
mouse
(Mus musculus)
Mammalia Yme1l1 17 33 32
  • 89.09 (n)
chicken
(Gallus gallus)
Aves YME1L1 33 32
  • 77.08 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia YME1L1 33
  • 88 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia yme1l1 32
  • 74.83 (n)
zebrafish
(Danio rerio)
Actinopterygii yme1l1a 33
  • 71 (a)
OneToMany
yme1l1b 33 32
  • 69.41 (n)
OneToMany
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP009973 32
  • 57.36 (n)
fruit fly
(Drosophila melanogaster)
Insecta CG3499 33 34 32
  • 57.07 (n)
OneToOne
worm
(Caenorhabditis elegans)
Secernentea ymel-1 33 32
  • 58.55 (n)
OneToOne
M03C11.5 34
  • 55 (a)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes YME1 35 33
  • 36 (a)
wheat
(Triticum aestivum)
Liliopsida Ta.3718 32
sea squirt
(Ciona savignyi)
Ascidiacea -- 33
  • 43 (a)
OneToOne
Species where no ortholog for YME1L1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)

Evolution for YME1L1 Gene

ENSEMBL:
Gene Tree for YME1L1 (if available)
TreeFam:
Gene Tree for YME1L1 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for YME1L1: view image

Paralogs for YME1L1 Gene

Paralogs for YME1L1 Gene

(8) SIMAP similar genes for YME1L1 Gene using alignment to 6 proteins:

  • YMEL1_HUMAN
  • Q5T8D1_HUMAN
  • Q5T8D2_HUMAN
  • Q6PJ89_HUMAN
  • Q96I63_HUMAN
  • R4GNA5_HUMAN
genes like me logo Genes that share paralogs with YME1L1: view

Variants for YME1L1 Gene

Sequence variations from dbSNP and Humsavar for YME1L1 Gene

SNP ID Clin Chr 10 pos Variation AA Info Type
rs1057519312 pathogenic, Optic atrophy 11, Optic atrophy 11 (OPA11) [MIM:617302] 27,136,371(-) G/A/C coding_sequence_variant, missense_variant
rs150868633 likely-benign, Thrombocytopenia 27,155,312(-) GGGG/GGGGG upstream_transcript_variant
rs28365962 likely-benign, Thrombocytopenia 27,154,946(-) C/T 5_prime_UTR_variant, genic_upstream_transcript_variant, upstream_transcript_variant
rs3824593 likely-benign, Thrombocytopenia 27,155,374(-) G/A/T upstream_transcript_variant
rs3824594 likely-benign, Thrombocytopenia 27,155,321(-) T/C upstream_transcript_variant

Structural Variations from Database of Genomic Variants (DGV) for YME1L1 Gene

Variant ID Type Subtype PubMed ID
esv2422253 CNV deletion 17116639
esv2664616 CNV deletion 23128226
esv3622707 CNV gain 21293372
esv3622708 CNV gain 21293372
nsv1116452 OTHER inversion 24896259

Variation tolerance for YME1L1 Gene

Residual Variation Intolerance Score: 12.7% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 5.85; 73.98% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for YME1L1 Gene

Human Gene Mutation Database (HGMD)
YME1L1
SNPedia medical, phenotypic, and genealogical associations of SNPs for
YME1L1

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for YME1L1 Gene

Disorders for YME1L1 Gene

MalaCards: The human disease database

(6) MalaCards diseases for YME1L1 Gene - From: HGMD, OMIM, ClinVar, GTR, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
optic atrophy 11
  • opa11
spastic paraplegia 7, autosomal recessive
  • spg7
asphyxia neonatorum
  • asphyxia - birth
trichomoniasis
  • trichomonas infection
urethritis
  • non-gonococcal urethritis
- elite association - COSMIC cancer census association via MalaCards

UniProtKB/Swiss-Prot

YMEL1_HUMAN
  • Optic atrophy 11 (OPA11) [MIM:617302]: An 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. {ECO:0000269 PubMed:27495975}. Note=The disease may be caused by mutations affecting the gene represented in this entry.

Additional Disease Information for YME1L1

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with YME1L1: view

No data available for Genatlas for YME1L1 Gene

Publications for YME1L1 Gene

  1. YME1L controls the accumulation of respiratory chain subunits and is required for apoptotic resistance, cristae morphogenesis, and cell proliferation. (PMID: 22262461) Stiburek L … Zeman J (Molecular biology of the cell 2012) 2 3 4 56
  2. Identification and characterization of YME1L1, a novel paraplegin-related gene. (PMID: 10843804) Coppola M … Incerti B (Genomics 2000) 3 4 23 56
  3. The mammalian homologue of yeast Afg1 ATPase (lactation elevated 1) mediates degradation of nuclear-encoded complex IV subunits. (PMID: 26759378) Cesnekova J … Stiburek L (The Biochemical journal 2016) 3 4 56
  4. Reciprocal Degradation of YME1L and OMA1 Adapts Mitochondrial Proteolytic Activity during Stress. (PMID: 26923599) Rainbolt TK … Wiseman RL (Cell reports 2016) 3 4 56
  5. Homozygous YME1L1 mutation causes mitochondriopathy with optic atrophy and mitochondrial network fragmentation. (PMID: 27495975) Hartmann B … Kaindl AM (eLife 2016) 3 4 56

Products for YME1L1 Gene

Sources for YME1L1 Gene