General Information:

Id: 222
Diseases: Amyotrophic lateral sclerosis
Homo sapiens
SOD1G85R or SOD1G93A transgenic cells
BTO:0000007 HEK-293 cell
article
Reference: Ying Z et al.(2009) Gp78, an ER associated E3, promotes SOD1 and ataxin-3 degradation. Hum. Mol. Genet. 18: 4268-4281 [PMID: 19661182]

Interaction Information:

Comment GP78 is an E3 ubiquitin ligase involved in ER-associated degradation (ERAD).
Formal Description
Interaction-ID: 966

gene/protein

AMFR

increases_activity of

process

ERAD pathway

Comment Gp78 specifically stimulates the degradation of SOD1, (SOD1WT, SOD1G85R, SOD1G93A). As degradation of SOD1 could be inhibited by MG132 (a proteasome inhibitor) the data suggested that gp78-mediated degradation of SOD1 is proteasome-dependent.
Formal Description
Interaction-ID: 967

gene/protein

AMFR

decreases_quantity of

gene/protein

SOD1

Drugbank entries Show/Hide entries for SOD1
Comment Gp78 interacts with and ubiquitinates SOD1. The amounts of gp78 co-immunoprecipitated were higher in cells co-transfected with mutant SOD1s than in that co-transfected with wild-type SOD1, suggesting stronger interactions between endogenous gp78 and mutant SOD1.
Formal Description
Interaction-ID: 971

gene/protein

AMFR

interacts (colocalizes) with

gene/protein

SOD1

Drugbank entries Show/Hide entries for SOD1
Comment Gp78 interacts with and ubiquitinates SOD1, but more ubiquitinated mutant SOD1 (SOD1G85R, SOD1G93A) than wild-type SOD1 was observed.
Formal Description
Interaction-ID: 974

gene/protein

AMFR

increases_ubiquitination/sumoylation of

gene/protein

SOD1

Drugbank entries Show/Hide entries for SOD1
Comment Gp78, the E3 ubiquitin ligase ubiquitinates SOD1 and UBE2G2 was shown as a E2 ligase for SOD1 ubiquitination.
Formal Description
Interaction-ID: 975

gene/protein

UBE2G2

increases_activity of

gene/protein

AMFR

Comment Gp78 inhibits aggregate formation of mutant SOD1 and protects cells from death mediated by ER stress induced by mutant SOD1.
Formal Description
Interaction-ID: 990

gene/protein

AMFR

decreases_quantity of

phenotype

SOD1 protein aggregates

Comment Gp78 specifically promotes SOD1 and ataxin-3 degradation and has no effects on other neurodegenerative disease protein degradation, as analysed for alpha-synuclein or DJ-1.
Formal Description
Interaction-ID: 994

gene/protein

AMFR

NOT decreases_quantity of

gene/protein

SNCA

Comment The aggregates formed by mutant SOD1G85R were localized in the ER, but not mitochondria.
Formal Description
Interaction-ID: 13319

gene/protein mutant

SOD1-p.G85R

increases_quantity of

phenotype

SOD1 protein aggregates

Comment The aggregates formed by mutant SOD1G85R were localized in the ER, but not mitochondria.
Formal Description
Interaction-ID: 13321

phenotype

SOD1 protein aggregates

is localized in

cellular component

endoplasmic reticulum

Comment Gp78 interacts with and ubiquitinates SOD1, but more ubiquitinated mutant SOD1 (SOD1G85R, SOD1G93A) than wild-type SOD1 was observed.
Formal Description
Interaction-ID: 13322

gene/protein

AMFR

increases_ubiquitination/sumoylation of

gene/protein mutant

SOD1-p.G85R

Comment Gp78 interacts with and ubiquitinates SOD1. The amounts of gp78 co-immunoprecipitated were higher in cells co-transfected with mutant SOD1s than in that co-transfected with wild-type SOD1, suggesting stronger interactions between endogenous gp78 and mutant SOD1.
Formal Description
Interaction-ID: 13326

gene/protein

AMFR

interacts (colocalizes) with

gene/protein mutant

SOD1-p.G85R

Comment Gp78 specifically stimulates the degradation of SOD1, (SOD1WT, SOD1G85R, SOD1G93A). As degradation of SOD1 could be inhibited by MG132 (a proteasome inhibitor) the data suggested that gp78-mediated degradation of SOD1 is proteasome-dependent.
Formal Description
Interaction-ID: 13328

gene/protein

AMFR

decreases_quantity of

gene/protein mutant

SOD1-p.G85R

Comment Transfection of FLAG-gp78 significantly decreased endogenous protein levels of SOD1 and ataxin-3, but not endogenous DJ-1.
Formal Description
Interaction-ID: 13330

gene/protein

AMFR

NOT decreases_quantity of

gene/protein

PARK7

Drugbank entries Show/Hide entries for PARK7
Comment Gp78 interacts with and ubiquitinates SOD1, but more ubiquitinated mutant SOD1 (SOD1G85R, SOD1G93A) than wild-type SOD1 was observed.
Formal Description
Interaction-ID: 13337

gene/protein

AMFR

increases_ubiquitination/sumoylation of

gene/protein mutant

SOD1-p.G93A

Comment Gp78 interacts with and ubiquitinates SOD1. The amounts of gp78 co-immunoprecipitated were higher in cells co-transfected with mutant SOD1s than in that co-transfected with wild-type SOD1, suggesting stronger interactions between endogenous gp78 and mutant SOD1.
Formal Description
Interaction-ID: 13338

gene/protein

AMFR

interacts (colocalizes) with

gene/protein mutant

SOD1-p.G93A

Comment Gp78 specifically stimulates the degradation of SOD1, (SOD1WT, SOD1G85R, SOD1G93A). As degradation of SOD1 could be inhibited by MG132 (a proteasome inhibitor) the data suggested that gp78-mediated degradation of SOD1 is proteasome-dependent.
Formal Description
Interaction-ID: 13339

gene/protein

AMFR

decreases_quantity of

gene/protein mutant

SOD1-p.G93A

Comment In cells expressing SOD1G85R increases of Bip, a ER stress marker protein and Gp78 were observed.
Formal Description
Interaction-ID: 13349

gene/protein mutant

SOD1-p.G85R

increases_quantity of

gene/protein

HSPA5

Drugbank entries Show/Hide entries for HSPA5
Comment In cells expressing SOD1G85R increases of Bip, a ER stress marker protein and Gp78 were observed.
Formal Description
Interaction-ID: 13350

gene/protein mutant

SOD1-p.G85R

increases_quantity of

gene/protein

AMFR