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

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