Tbio COMMD1 COMM domain-containing protein 1

Protein Summary

Description

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). COMMD1 is a regulator of copper homeostasis, sodium uptake, and NF-kappa-B (see MIM 164011) signaling (de Bie et al., 2005 [PubMed 16267171]).[supplied by OMIM, Sep 2009]

Uniprot Accession IDs

• Q8N668
• B4DFQ4
• Q96GS0

Gene Name

• COMMD1

Ensembl ID

• ENST00000311832
• ENSP00000308236
• ENSG00000173163

Symbol

• C2orf5
• MURR1
• MURR1
• C2orf5

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
histone modification site profile	0.89
biological process	0.84
kinase perturbation	0.84
transcription factor perturbation	0.84
molecular function	0.76

Protein Classes

No PANTHER Classes or DTO Classes found

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 92.07   (req: < 5)

Gene RIFs: 51   (req: <= 3)

Antibodies: 380   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 92.07   (req: >= 5)

Gene RIFs: 51   (req: > 3)

Antibodies: 380   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 18

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0