InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: MUL1

Summary

InnateDB Protein

IDBP-92890.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

MUL1

Protein Name

mitochondrial E3 ubiquitin protein ligase 1

Synonyms

Species

Homo sapiens

Ensembl Protein

ENSP00000264198

InnateDB Gene

IDBG-92888 (MUL1)

Protein Structure

UniProt Annotation

Function

Exhibits weak E3 ubiquitin-protein ligase activity. 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. 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. Proposed to preferentially act as a SUMO E3 ligase at physiological concentrations. Plays a role in the control of mitochondrial morphology. Promotes mitochondrial fragmentation and influences mitochondrial localization. The function may implicate its abilty to sumoylate DNM1L. Inhibits cell growth. When overexpressed, activates JNK through MAP3K7/TAK1 and induces caspase-dependent apoptosis. Involved in the modulation of innate immune defense against viruses by inhibiting DDX58-dependent antiviral response. Can mediate DDX58 sumoylation and disrupt its polyubiquitination. {ECO:0000269PubMed:18207745, ECO:0000269PubMed:18213395, ECO:0000269PubMed:18591963, ECO:0000269PubMed:19407830, ECO:0000269PubMed:22410793, ECO:0000269PubMed:23399697}.

Subcellular Localization

Mitochondrion outer membrane; Multi-pass membrane protein. Peroxisome. Note=Transported in mitochondrion- derived vesicles from the mitochondrion to the peroxisome.

Disease Associations

Tissue Specificity

Widely expressed with highest levels in the heart, skeletal muscle, placenta, kidney and liver. Barely detectable in colon and thymus. {ECO:0000269PubMed:18213395, ECO:0000269PubMed:18591963}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 33 experimentally validated interaction(s) in this database.
They are also associated with 1 interaction(s) predicted by orthology.

Experimentally validated
Total	33 [view]
Protein-Protein	33 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	1 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004842	ubiquitin-protein transferase activity
GO:0004871	signal transducer activity
GO:0005515	protein binding
GO:0008270	zinc ion binding
GO:0019789	SUMO ligase activity
GO:0031625	ubiquitin protein ligase binding
GO:0042802	identical protein binding

Biological Process

GO:0000266	mitochondrial fission
GO:0006919	activation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0007005	mitochondrion organization
GO:0007257	activation of JUN kinase activity
GO:0010637	negative regulation of mitochondrial fusion
GO:0016567	protein ubiquitination
GO:0016925	protein sumoylation
GO:0030308	negative regulation of cell growth
GO:0033235	positive regulation of protein sumoylation
GO:0043123	positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:0045087	innate immune response (InnateDB)
GO:0045824	negative regulation of innate immune response
GO:0050689	negative regulation of defense response to virus by host
GO:0050821	protein stabilization
GO:0051646	mitochondrion localization
GO:0051898	negative regulation of protein kinase B signaling
GO:0060339	negative regulation of type I interferon-mediated signaling pathway
GO:0071360	cellular response to exogenous dsRNA
GO:0071650	negative regulation of chemokine (C-C motif) ligand 5 production
GO:0090141	positive regulation of mitochondrial fission
GO:1901028	regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway

Cellular Component

GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005739	mitochondrion
GO:0005777	peroxisome
GO:0016020	membrane
GO:0031307	integral component of mitochondrial outer membrane