Aliases for MUL1 Gene

Aliases for MUL1 Gene

  • Mitochondrial E3 Ubiquitin Protein Ligase 1 2 3 5
  • Mitochondrial Ubiquitin Ligase Activator Of NFKB 1 2 3 4
  • Growth Inhibition And Death E3 Ligase 2 3 4
  • RNF218 2 3 4
  • MULAN 2 3 4
  • GIDE 2 3 4
  • MAPL 2 3 4
  • Putative NF-Kappa-B-Activating Protein 266 3 4
  • RING-Type E3 Ubiquitin Transferase NFKB 1 3 4
  • Mitochondrial-Anchored Protein Ligase 3 4
  • Mitochondria-Anchored Protein Ligase 2 3
  • E3 Ubiquitin-Protein Ligase MUL1 3 4
  • E3 SUMO-Protein Ligase MUL1 3 4
  • Ring Finger Protein 218 2 3
  • Protein Hades 3 4
  • C1orf166 3 4
  • Mitochondrial Ubiquitin Ligase Activator Of NF-KB 3
  • Chromosome 1 Open Reading Frame 166 2
  • Mitochondrial E3 Ubiquitin Ligase 1 3
  • RING Finger Protein 218 4
  • E3 Ubiquitin Ligase 3
  • EC 2.3.2.27 4
  • FLJ12875 2
  • EC 6.3.2 50
  • MUL1 5

External Ids for MUL1 Gene

Previous HGNC Symbols for MUL1 Gene

  • C1orf166

Previous GeneCards Identifiers for MUL1 Gene

  • GC01M020699
  • GC01M020825
  • GC01M019072

Summaries for MUL1 Gene

GeneCards Summary for MUL1 Gene

MUL1 (Mitochondrial E3 Ubiquitin Protein Ligase 1) is a Protein Coding gene. Diseases associated with MUL1 include Mulibrey Nanism and Optic Atrophy 1. Among its related pathways are Deubiquitination and Metabolism of proteins. Gene Ontology (GO) annotations related to this gene include identical protein binding and ubiquitin-protein transferase activity.

UniProtKB/Swiss-Prot Summary for MUL1 Gene

  • Exhibits weak E3 ubiquitin-protein ligase activity (PubMed:18591963, PubMed:19407830, PubMed:22410793). E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfer the ubiquitin to targeted substrates (PubMed:18591963, PubMed:19407830, PubMed:22410793). Can ubiquitinate AKT1 preferentially at 'Lys-284' involving 'Lys-48'-linked polyubiquitination and seems to be involved in regulation of Akt signaling by targeting phosphorylated Akt to proteosomal degradation (PubMed:22410793). Mediates polyubiquitination of cytoplasmic TP53 at 'Lys-24' which targets TP53 for proteasomal degradation, thus reducing TP53 levels in the cytoplasm and mitochondrion (PubMed:21597459). Proposed to preferentially act as a SUMO E3 ligase at physiological concentrations (PubMed:19407830). Plays a role in the control of mitochondrial morphology by promoting mitochondrial fragmentation, and influences mitochondrial localization (PubMed:19407830, PubMed:18207745, PubMed:18213395). Likely to promote mitochondrial fission through negatively regulating the mitochondrial fusion proteins MFN1 and MFN2, acting in a pathway that is parallel to the PRKN/PINK1 regulatory pathway (PubMed:24898855). May also be involved in the sumoylation of the membrane fission protein DNM1L (PubMed:18207745, PubMed:19407830). Inhibits cell growth (PubMed:18591963, PubMed:22410793). When overexpressed, activates JNK through MAP3K7/TAK1 and induces caspase-dependent apoptosis (PubMed:23399697). Involved in the modulation of innate immune defense against viruses by inhibiting DDX58-dependent antiviral response (PubMed:23399697). Can mediate DDX58 sumoylation and disrupt its polyubiquitination (PubMed:23399697).

No data available for Entrez Gene Summary , CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for MUL1 Gene

Genomics for MUL1 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for MUL1 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 MUL1 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for MUL1

Top Transcription factor binding sites by QIAGEN in the MUL1 gene promoter:
  • AML1a
  • c-Ets-1
  • C/EBPalpha
  • CUTL1
  • FAC1
  • HSF1 (long)
  • HSF1short
  • Pax-4a
  • RORalpha1

Genomic Locations for MUL1 Gene

Latest Assembly
chr1:20,499,448-20,508,483
(GRCh38/hg38)
Size:
9,036 bases
Orientation:
Minus strand

Previous Assembly
chr1:20,825,941-20,834,644
(GRCh37/hg19 by Entrez Gene)
Size:
8,704 bases
Orientation:
Minus strand

chr1:20,825,943-20,834,654
(GRCh37/hg19 by Ensembl)
Size:
8,712 bases
Orientation:
Minus strand

Genomic View for MUL1 Gene

Genes around MUL1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
MUL1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for MUL1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for MUL1 Gene

Proteins for MUL1 Gene

  • Protein details for MUL1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q969V5-MUL1_HUMAN
    Recommended name:
    Mitochondrial ubiquitin ligase activator of NFKB 1
    Protein Accession:
    Q969V5
    Secondary Accessions:
    • B5M497
    • Q7Z431
    • Q9H9B5

    Protein attributes for MUL1 Gene

    Size:
    352 amino acids
    Molecular mass:
    39800 Da
    Quaternary structure:
    • Homooligomer (PubMed:18591963). Interacts with MAP3K7/TAK1 (PubMed:18591963). Interacts with UBC9 (PubMed:19407830). Interacts with and sumoylates DNM1L (PubMed:19407830). Interacts with MAVS (PubMed:23399697). Interacts with TP53 (via N-terminus); the interaction leads to ubiquitination and proteasomal degradation of TP53 (PubMed:21597459).

    Three dimensional structures from OCA and Proteopedia for MUL1 Gene

neXtProt entry for MUL1 Gene

Selected DME Specific Peptides for MUL1 Gene

Q969V5:
  • EHKMVWNRTTHLWND
  • PGKCVPYAVIEGAV
  • KSCVFLECGHVCSC

Post-translational modifications for MUL1 Gene

  • Ubiquitinated by PRKN during mitophagy, leading to its degradation and enhancement of mitophagy. Deubiquitinated by USP30.
  • Ubiquitination at Lys52, Lys273, and Lys299
  • Modification sites at PhosphoSitePlus

Other Protein References for MUL1 Gene

ENSEMBL proteins:
REFSEQ proteins:

Domains & Families for MUL1 Gene

Gene Families for MUL1 Gene

HGNC:
Human Protein Atlas (HPA):
  • Enzymes
  • Predicted membrane proteins

Protein Domains for MUL1 Gene

InterPro:
Blocks:
  • Zn-finger, RING

Suggested Antigen Peptide Sequences for MUL1 Gene

GenScript: Design optimal peptide antigens:
  • RING finger protein 218 (MUL1_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q969V5

UniProtKB/Swiss-Prot:

MUL1_HUMAN :
  • The zinc finger domain is required for E3 ligase activity.
Domain:
  • The zinc finger domain is required for E3 ligase activity.
genes like me logo Genes that share domains with MUL1: view

Function for MUL1 Gene

Molecular function for MUL1 Gene

UniProtKB/Swiss-Prot Function:
Exhibits weak E3 ubiquitin-protein ligase activity (PubMed:18591963, PubMed:19407830, PubMed:22410793). E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfer the ubiquitin to targeted substrates (PubMed:18591963, PubMed:19407830, PubMed:22410793). Can ubiquitinate AKT1 preferentially at 'Lys-284' involving 'Lys-48'-linked polyubiquitination and seems to be involved in regulation of Akt signaling by targeting phosphorylated Akt to proteosomal degradation (PubMed:22410793). Mediates polyubiquitination of cytoplasmic TP53 at 'Lys-24' which targets TP53 for proteasomal degradation, thus reducing TP53 levels in the cytoplasm and mitochondrion (PubMed:21597459). Proposed to preferentially act as a SUMO E3 ligase at physiological concentrations (PubMed:19407830). Plays a role in the control of mitochondrial morphology by promoting mitochondrial fragmentation, and influences mitochondrial localization (PubMed:19407830, PubMed:18207745, PubMed:18213395). Likely to promote mitochondrial fission through negatively regulating the mitochondrial fusion proteins MFN1 and MFN2, acting in a pathway that is parallel to the PRKN/PINK1 regulatory pathway (PubMed:24898855). May also be involved in the sumoylation of the membrane fission protein DNM1L (PubMed:18207745, PubMed:19407830). Inhibits cell growth (PubMed:18591963, PubMed:22410793). When overexpressed, activates JNK through MAP3K7/TAK1 and induces caspase-dependent apoptosis (PubMed:23399697). Involved in the modulation of innate immune defense against viruses by inhibiting DDX58-dependent antiviral response (PubMed:23399697). Can mediate DDX58 sumoylation and disrupt its polyubiquitination (PubMed:23399697).
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.; EC=2.3.2.27; Evidence={ECO:0000269|PubMed:18591963, ECO:0000269|PubMed:21597459, ECO:0000269|PubMed:22410793};.

Enzyme Numbers (IUBMB) for MUL1 Gene

Phenotypes From GWAS Catalog for MUL1 Gene

Gene Ontology (GO) - Molecular Function for MUL1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002039 p53 binding IPI 21597459
GO:0004842 ubiquitin-protein transferase activity IBA 21873635
GO:0005515 protein binding IPI 16189514
GO:0016740 transferase activity IEA --
GO:0019789 SUMO transferase activity IDA 19407830
genes like me logo Genes that share ontologies with MUL1: view
genes like me logo Genes that share phenotypes with MUL1: view

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for MUL1

No data available for Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for MUL1 Gene

Localization for MUL1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for MUL1 Gene

Mitochondrion outer membrane. Multi-pass membrane protein. Peroxisome. Note=Transported in mitochondrion-derived vesicles from the mitochondrion to the peroxisome. {ECO:0000269 PubMed:18207745}.

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 MUL1 gene
Compartment Confidence
mitochondrion 5
peroxisome 5
nucleus 3
cytosol 3
plasma membrane 2
extracellular 2
cytoskeleton 2
endoplasmic reticulum 2
endosome 2
lysosome 2
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Mitochondria (3)
  • Cytosol (2)
  • Nucleoplasm (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for MUL1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005739 mitochondrion IMP 24898855
GO:0005741 mitochondrial outer membrane IEA --
GO:0005777 peroxisome IEA,IDA 18207745
GO:0016020 membrane IEA,HDA 19946888
GO:0016021 integral component of membrane IEA --
genes like me logo Genes that share ontologies with MUL1: view

Pathways & Interactions for MUL1 Gene

genes like me logo Genes that share pathways with MUL1: view

UniProtKB/Swiss-Prot Q969V5-MUL1_HUMAN

  • Pathway: Protein modification; protein ubiquitination.
  • Pathway: Protein modification; protein sumoylation.

SIGNOR curated interactions for MUL1 Gene

Inactivates:

Gene Ontology (GO) - Biological Process for MUL1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000209 protein polyubiquitination IDA 21597459
GO:0000266 mitochondrial fission IMP 18207745
GO:0006915 apoptotic process IEA --
GO:0006919 activation of cysteine-type endopeptidase activity involved in apoptotic process IDA 18591963
GO:0006996 organelle organization IEA --
genes like me logo Genes that share ontologies with MUL1: view

Drugs & Compounds for MUL1 Gene

No Compound Related Data Available

Transcripts for MUL1 Gene

mRNA/cDNA for MUL1 Gene

1 REFSEQ mRNAs :
8 NCBI additional mRNA sequence :
1 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for MUL1

Alternative Splicing Database (ASD) splice patterns (SP) for MUL1 Gene

ExUns: 1a · 1b ^ 2 ^ 3 ^ 4a · 4b ^ 5a · 5b
SP1: -
SP2: - -
SP3: -

Relevant External Links for MUL1 Gene

GeneLoc Exon Structure for
MUL1

Expression for MUL1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for MUL1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for MUL1 Gene

This gene is overexpressed in Lung (27.4), Testis (9.3), Placenta (8.2), and Fetal heart (6.7).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for MUL1 Gene



Protein tissue co-expression partners for MUL1 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for MUL1

SOURCE GeneReport for Unigene cluster for MUL1 Gene:

Hs.10101

mRNA Expression by UniProt/SwissProt for MUL1 Gene:

Q969V5-MUL1_HUMAN
Tissue specificity: Widely expressed with highest levels in the heart, skeletal muscle, placenta, kidney and liver. Barely detectable in colon and thymus.

Evidence on tissue expression from TISSUES for MUL1 Gene

  • Nervous system(5)
  • Skin(4.5)
  • Lung(4.4)
  • Muscle(2.8)
  • Kidney(2.6)
  • Heart(2.3)
genes like me logo Genes that share expression patterns with MUL1: view

Primer products for research

No data available for mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for MUL1 Gene

Orthologs for MUL1 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for MUL1 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia MUL1 29 30
  • 99.62 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia MUL1 29 30
  • 90.15 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Mul1 29
  • 87.59 (n)
Mouse
(Mus musculus)
Mammalia Mul1 29 16 30
  • 86.93 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia MUL1 30
  • 85 (a)
OneToOne
Cow
(Bos Taurus)
Mammalia MUL1 29 30
  • 82.9 (n)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia MUL1 30
  • 79 (a)
OneToOne
Chicken
(Gallus gallus)
Aves MUL1 29 30
  • 73.39 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia MUL1 30
  • 39 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia mul1 29
  • 67.05 (n)
Zebrafish
(Danio rerio)
Actinopterygii mul1b 29 30
  • 62.5 (n)
OneToOne
Fruit Fly
(Drosophila melanogaster)
Insecta Mul1 30
  • 29 (a)
OneToOne
Thale Cress
(Arabidopsis thaliana)
eudicotyledons AT1G63900 29
  • 40.23 (n)
Rice
(Oryza sativa)
Liliopsida Os07g0647800 29
  • 41.15 (n)
Species where no ortholog for MUL1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • 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 Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for MUL1 Gene

ENSEMBL:
Gene Tree for MUL1 (if available)
TreeFam:
Gene Tree for MUL1 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for MUL1: view image
Alliance of Genome Resources:
Additional Orthologs for MUL1

Paralogs for MUL1 Gene

No data available for Paralogs for MUL1 Gene

Variants for MUL1 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for MUL1 Gene

SNP ID Clinical significance and condition Chr 01 pos Variation AA Info Type
rs115435412 Benign: not provided 20,501,113(-) C/T
NM_024544.3(MUL1):c.636G>A (p.Pro212=)
SYNONYMOUS
rs12061027 Benign: not provided 20,507,996(-) C/T
NM_024544.3(MUL1):c.29G>A (p.Cys10Tyr)
MISSENSE
rs138851946 Likely Benign: not provided 20,500,792(-) G/A
NM_024544.3(MUL1):c.957C>T (p.His319=)
SYNONYMOUS
rs139475946 Benign: not provided 20,501,194(-) G/A
NM_024544.3(MUL1):c.555C>T (p.Thr185=)
SYNONYMOUS
rs199912398 Benign: not provided 20,503,316(-) A/T
NM_024544.3(MUL1):c.121-7T>A
INTRON

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for MUL1 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for MUL1 Gene

Variant ID Type Subtype PubMed ID
nsv545731 CNV gain 21841781

Variation tolerance for MUL1 Gene

Residual Variation Intolerance Score: 45.3% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.20; 39.80% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for MUL1 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
MUL1
Leiden Open Variation Database (LOVD)
MUL1

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for MUL1 Gene

Disorders for MUL1 Gene

MalaCards: The human disease database

(3) MalaCards diseases for MUL1 Gene - From: COP

Disorder Aliases PubMed IDs
mulibrey nanism
  • muscle-liver-brain-eye nanism
optic atrophy 1
  • opa1
3-methylglutaconic aciduria, type iii
  • mgca3
- elite association - COSMIC cancer census association via MalaCards
Search MUL1 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for MUL1

Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with MUL1: view

No data available for UniProtKB/Swiss-Prot and Genatlas for MUL1 Gene

Publications for MUL1 Gene

  1. GIDE is a mitochondrial E3 ubiquitin ligase that induces apoptosis and slows growth. (PMID: 18591963) Zhang B … Shu HB (Cell research 2008) 2 3 4
  2. Genome-wide and functional annotation of human E3 ubiquitin ligases identifies MULAN, a mitochondrial E3 that regulates the organelle's dynamics and signaling. (PMID: 18213395) Li W … Joazeiro CA (PloS one 2008) 2 3 4
  3. Cargo-selected transport from the mitochondria to peroxisomes is mediated by vesicular carriers. (PMID: 18207745) Neuspiel M … McBride HM (Current biology : CB 2008) 2 3 4
  4. Large-scale identification and characterization of human genes that activate NF-kappaB and MAPK signaling pathways. (PMID: 12761501) Matsuda A … Sugano S (Oncogene 2003) 2 3 4
  5. MUL1 acts in parallel to the PINK1/parkin pathway in regulating mitofusin and compensates for loss of PINK1/parkin. (PMID: 24898855) Yun J … Guo M (eLife 2014) 3 4

Products for MUL1 Gene

Sources for MUL1 Gene