MUL1 mitochondrial E3 ubiquitin protein ligase 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: MUL1provided by HGNC
Official Full Name: mitochondrial E3 ubiquitin protein ligase 1provided by HGNC
Primary source: HGNC:HGNC:25762
See related: Ensembl:ENSG00000090432 MIM:612037; AllianceGenome:HGNC:25762
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: GIDE; MAPL; MULAN; RNF218; C1orf166
Summary: Enables several functions, including p53 binding activity; ubiquitin protein ligase binding activity; and ubiquitin-like protein transferase activity. Involved in several processes, including negative regulation of defense response; positive regulation of cellular protein metabolic process; and regulation of mitochondrion organization. Located in several cellular components, including mitochondrion; neuronal cell body; and peroxisome. Is integral component of mitochondrial outer membrane. [provided by Alliance of Genome Resources, Apr 2022]
Expression: Ubiquitous expression in kidney (RPKM 8.0), heart (RPKM 7.9) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 1p36.12

Exon count:: 4

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (20499448..20508151, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (20324399..20333109, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (20825941..20834644, complement)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

A new functional role of mitochondria-anchored protein ligase in peroxisome morphology in mammalian cells.
Title: A new functional role of mitochondria-anchored protein ligase in peroxisome morphology in mammalian cells.
A risk signature of three autophagy-related genes for predicting lower grade glioma survival is associated with tumor immune microenvironment.
Title: A risk signature of three autophagy-related genes for predicting lower grade glioma survival is associated with tumor immune microenvironment.
Mitochondrial MUL1 E3 ubiquitin ligase regulates Hypoxia Inducible Factor (HIF-1alpha) and metabolic reprogramming by modulating the UBXN7 cofactor protein.
Title: Mitochondrial MUL1 E3 ubiquitin ligase regulates Hypoxia Inducible Factor (HIF-1α) and metabolic reprogramming by modulating the UBXN7 cofactor protein.
These results provide a molecular basis for the novel recognition mechanism of the p53-transactivation domain substrate by the MUL1-RING domain.
Title: Solution structure of MUL1-RING domain and its interaction with p53 transactivation domain.
The three-dimensional structures of MUL1-RING and of its complex with the cognate E2 enzyme has been determined.
Title: The RING domain of mitochondrial E3 ubiquitin ligase 1 and its complex with Ube2D2: crystallization and X-ray diffraction.
The allele T in the rs529974(+) MUL1 gene was susceptible to Parkinson's disease
Title: MUL1 gene polymorphisms and Parkinson's disease risk.
HSPA5 negatively regulates lysosomal activity through ubiquitination of MUL1 in head and neck cancer
Title: HSPA5 negatively regulates lysosomal activity through ubiquitination of MUL1 in head and neck cancer.
Data demonstrate a clear role for MAPL and mitochondrial SUMOylation in the activation of RIG-I, a modification essential for the mitochondrial antiviral signaling response.
Title: The dynamic interacting landscape of MAPL reveals essential functions for SUMOylation in innate immunity.
MULAN regulates NF-kappaappaB activation to protect cells from endoplasmic reticulum stress-induced apoptosis.
Title: Mitochondrial ubiquitin ligase activator of NF-κB regulates NF-κB signaling in cells subjected to ER stress.
MUL1 ubiquitinates ULK1 and regulates selenite-induced mitophagy
Title: Mitochondrial outer-membrane E3 ligase MUL1 ubiquitinates ULK1 and regulates selenite-induced mitophagy.

Submit: New GeneRIF Correction See all GeneRIFs (27)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D1S1766E (e-PCR)
- UniSTS:25090

SHGC-31990 (e-PCR)
- UniSTS:76557

D1S2547 (e-PCR)
- UniSTS:58340

SHGC-74330 (e-PCR)
- UniSTS:61163

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables SUMO transferase activity	IDA Inferred from Direct Assay more info	PubMed
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables p53 binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables ubiquitin protein ligase activity	IDA Inferred from Direct Assay more info	PubMed
enables ubiquitin protein ligase binding	IPI Inferred from Physical Interaction more info	PubMed
enables ubiquitin-protein transferase activity	IBA Inferred from Biological aspect of Ancestor more info

Process	Evidence Code	Pubs
involved_in activation of cysteine-type endopeptidase activity involved in apoptotic process	IDA Inferred from Direct Assay more info	PubMed
involved_in apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in cellular response to exogenous dsRNA	IDA Inferred from Direct Assay more info	PubMed
involved_in mitochondrial fission	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in mitochondrion localization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of cell growth	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of chemokine (C-C motif) ligand 5 production	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of defense response to virus by host	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of innate immune response	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of mitochondrial fusion	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of type I interferon-mediated signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of autophagy of mitochondrion in response to mitochondrial depolarization	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of canonical NF-kappaB signal transduction	HMP more info	PubMed
involved_in positive regulation of dendrite extension	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of mitochondrial fission	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of protein sumoylation	IDA Inferred from Direct Assay more info	PubMed
involved_in protein destabilization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein polyubiquitination	IDA Inferred from Direct Assay more info	PubMed
involved_in protein stabilization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein sumoylation	IEA Inferred from Electronic Annotation more info
involved_in protein ubiquitination	IBA Inferred from Biological aspect of Ancestor more info
involved_in protein ubiquitination	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of mitochondrial membrane potential	IEA Inferred from Electronic Annotation more info
involved_in regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of mitochondrion organization	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in axon	IMP Inferred from Mutant Phenotype more info	PubMed
located_in membrane	HDA more info	PubMed
located_in mitochondrial outer membrane	IDA Inferred from Direct Assay more info	PubMed
located_in mitochondrial outer membrane	TAS Traceable Author Statement more info
is_active_in mitochondrion	IBA Inferred from Biological aspect of Ancestor more info
located_in mitochondrion	IDA Inferred from Direct Assay more info	PubMed
located_in mitochondrion	IMP Inferred from Mutant Phenotype more info	PubMed
located_in neuronal cell body	IMP Inferred from Mutant Phenotype more info	PubMed
located_in peroxisome	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: mitochondrial ubiquitin ligase activator of NFKB 1

Names: E3 SUMO-protein ligase MUL1; E3 ubiquitin ligase; E3 ubiquitin-protein ligase MUL1; RING-type E3 ubiquitin transferase NFKB 1; growth inhibition and death E3 ligase; mitochondria-anchored protein ligase; mitochondrial E3 ubiquitin ligase 1; mitochondrial ubiquitin ligase activator of NF-kB; mitochondrial-anchored protein ligase; protein Hades; putative NF-kappa-B-activating protein 266; ring finger protein 218

NP_078820.2

EC 2.3.2.27

XP_011540439.1

EC 2.3.2.27

XP_054194709.1

EC 2.3.2.27

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_024544.3 → NP_078820.2 mitochondrial ubiquitin ligase activator of NFKB 1

See identical proteins and their annotated locations for NP_078820.2

Status: VALIDATED

Source sequence(s)

AL391357, BC014010

Consensus CDS

CCDS208.1

UniProtKB/Swiss-Prot

B5M497, Q7Z431, Q969V5, Q9H9B5

Related

ENSP00000264198.3, ENST00000264198.5

Conserved Domains (3) summary

COG5574
Location:260 → 341

PEX10; RING-finger-containing E3 ubiquitin ligase [Posttranslational modification, protein turnover, chaperones]

cd16648
Location:301 → 340

mRING-HC-C3HC5_MAPL; Modified RING finger, HC subclass (C3HC5-type), found in mitochondrial-anchored protein ligase (MAPL) and similar proteins

pfam12483
Location:97 → 253

GIDE; E3 Ubiquitin ligase

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000001.11 Reference GRCh38.p14 Primary Assembly

Range

20499448..20508151 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011542137.3 → XP_011540439.1 mitochondrial ubiquitin ligase activator of NFKB 1 isoform X1

See identical proteins and their annotated locations for XP_011540439.1

UniProtKB/TrEMBL

B7Z8S4

Conserved Domains (3) summary

COG5574
Location:221 → 302

PEX10; RING-finger-containing E3 ubiquitin ligase [Posttranslational modification, protein turnover, chaperones]

cd16648
Location:262 → 301

mRING-HC-C3HC5_MAPL; Modified RING finger, HC subclass (C3HC5-type), found in mitochondrial-anchored protein ligase (MAPL) and similar proteins

pfam12483
Location:58 → 214

GIDE; E3 Ubiquitin ligase