DegronMD - Q8N668(COMMD1)

FUNCTION: Proposed scaffold protein that is implicated in diverse physiological processes and whose function may be in part linked to its ability to regulate ubiquitination of specific cellular proteins. Can modulate activity of cullin-RING E3 ubiquitin ligase (CRL) complexes by displacing CAND1; in vitro promotes CRL E3 activity and dissociates CAND1 from CUL1 and CUL2 (PubMed:21778237). Promotes ubiquitination of NF-kappa-B subunit RELA and its subsequent proteasomal degradation. Down-regulates NF-kappa-B activity (PubMed:15799966, PubMed:17183367, PubMed:20048074). Involved in the regulation of membrane expression and ubiquitination of SLC12A2 (PubMed:23515529). Modulates Na(+) transport in epithelial cells by regulation of apical cell surface expression of amiloride-sensitive sodium channel (ENaC) subunits and by promoting their ubiquitination presumably involving NEDD4L. Promotes the localization of SCNN1D to recycling endosomes (PubMed:14645214, PubMed:20237237, PubMed:21741370). Promotes CFTR cell surface expression through regulation of its ubiquitination (PubMed:21483833). Down-regulates SOD1 activity by interfering with its homodimerization (PubMed:20595380). Plays a role in copper ion homeostasis. Involved in copper-dependent ATP7A trafficking between the trans-Golgi network and vesicles in the cell periphery; the function is proposed to depend on its association within the CCC complex and cooperation with the WASH complex on early endosomes (PubMed:25355947). Can bind one copper ion per monomer (PubMed:17309234). May function to facilitate biliary copper excretion within hepatocytes. Binds to phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) (PubMed:18940794). Involved in the regulation of HIF1A-mediated transcription; competes with ARNT/Hif-1-beta for binding to HIF1A resulting in decreased DNA binding and impaired transcriptional activation by HIF-1 (PubMed:20458141). Negatively regulates neuroblastoma G1/S phase cell cycle progression and cell proliferation by stimulating ubiquitination of NF-kappa-B subunit RELA and NF-kappa-B degradation in a FAM107A- and actin-dependent manner (PubMed:28604741). {ECO:0000269|PubMed:14645214, ECO:0000269|PubMed:14685266, ECO:0000269|PubMed:15799966, ECO:0000269|PubMed:16573520, ECO:0000269|PubMed:17183367, ECO:0000269|PubMed:17309234, ECO:0000269|PubMed:20048074, ECO:0000269|PubMed:20237237, ECO:0000269|PubMed:20458141, ECO:0000269|PubMed:20595380, ECO:0000269|PubMed:21483833, ECO:0000269|PubMed:21741370, ECO:0000269|PubMed:21778237, ECO:0000269|PubMed:23515529, ECO:0000269|PubMed:25355947, ECO:0000269|PubMed:28604741}. View more >>

GO - Biological processes (BP): View more >>

GO - Molecular function (MF): View more >>

GO - Cellular component (CC): View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.P41Q	TCGA-DO-A1JZ	THCA	TCGA	RSQLYPE	LIG_APCC_ABBAyCdc20_2	36:42	Mutation altering degron motif	0.5924
p.P41Q	DO40472	THCA	ICGC	RSQLYPE	LIG_APCC_ABBAyCdc20_2	36:42	Mutation altering degron motif	0.5924
p.P41S	TCGA-EE-A181	SKCM	TCGA	RSQLYPE	LIG_APCC_ABBAyCdc20_2	36:42	Mutation altering degron motif	0.5641
p.P41S	DO37444	SKCM	ICGC	RSQLYPE	LIG_APCC_ABBAyCdc20_2	36:42	Mutation altering degron motif	0.5641
p.P28H	TCGA-EE-A2M7	SKCM	TCGA	RSQLYPE	LIG_APCC_ABBAyCdc20_2	36:42	Mutation rewiring degron network	0.1111
p.P28H	DO37847	SKCM	ICGC	RSQLYPE	LIG_APCC_ABBAyCdc20_2	36:42	Mutation rewiring degron network	0.1111

DegronMD: protein-targeted degradation, mutation and drug response to degrons

COMMD1

UniProt ID: Q8N668

Entrez ID: 150684

Protein name: COMM domain-containing protein 1 (Protein Murr1)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for COMMD1 in