Q8K4M5 · COMD1_MOUSE
- ProteinCOMM domain-containing protein 1
- GeneCommd1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids188 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
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. Promotes ubiquitination of NF-kappa-B subunit RELA and its subsequent proteasomal degradation. Down-regulates NF-kappa-B activity. Involved in the regulation of membrane expression and ubiquitination of SLC12A2. 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. Promotes CFTR cell surface expression through regulation of its ubiquitination. Down-regulates SOD1 activity by interfering with its homodimerization. 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. Can bind one copper ion per monomer. May function to facilitate biliary copper excretion within hepatocytes. Binds to phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). 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. 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.
Features
Showing features for binding site.
GO annotations
Keywords
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameCOMM domain-containing protein 1
- Alternative names
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ8K4M5
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Shuttles between nucleus and cytosol. Detected in perinuclear foci that may be aggresomes containing misfolded, ubiquitinated proteins (By similarity).
Keywords
- Cellular component
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000077385 | 1-188 | COMM domain-containing protein 1 | |||
Sequence: MAGDLEGGKSLSGLLSGLAQNAFHGHSGVTEELLHSQLYPEVPPEEFRPFLAKMRGLLKSIASADMDFNQLEAFLTAQTKKQGGITSEQAAVISKFWKSHKIKIRESLMKQSRWDNGLRGLSWRVDGKSQSRHSTQIHSPVAIIELEFGKNGQESEFLCLEFDEVKVKQILKKLSEVEESINRLMQAA |
Post-translational modification
Ubiquitinated; undergoes both 'Lys-63'- and 'Lys-48'-linked polyubiquitination. Ubiquitinated by XIAP, leading to its proteasomal degradation (By similarity).
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Gene expression databases
Interaction
Subunit
Monomer, homodimer. Can form heterodimers with other COMM domain-containing proteins but only certain combinations may exist in vivo. Interacts (via COMM domain) with COMMD2, COMMD3, COMMD4, COMMD5, COMMD6, COMMD7, COMMD8 and COMMD10 (via COMM domain). Identified in a complex with an E3 ubiquitin ligase complex composed of TCEB1/elongin C, CUL2, SOCS1 and RBX1; in the complex interacts directly with SOCS1 and CUL2. Interacts directly with ATP7B (via the N-terminal region). Interacts with CCS, CDKN2A, RELA, REL, RELB, NFKB1/p105, NFKB2/p100, NFKBIB, SCNN1D, SCNN1B, CFTR, CLU, SGK1, AKT1, CUL1, CUL2, CUL3, CUL4A, CUL4B, CUL5, CUL7, HIF1A. Identified in a complex with NF-kappa-B. Interacts directly with SLC12A2. Interacts with CCDC22 and CCDC93; proposed to be a component of the CCC (COMMD/CCDC22/CCDC93) complex which contains at least COMMD1 (and possibly other COMM domain-containing proteins), CCDC22, CCDC93. Interacts with VPS35L; the interaction associates CCC complex with retriever complex. Interacts with ATP7A. Interacts with FAM107A; this interaction stabilizes COMMD1 in the nucleus.
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-122 | Sufficient for interaction with SLC12A2 | ||||
Sequence: MAGDLEGGKSLSGLLSGLAQNAFHGHSGVTEELLHSQLYPEVPPEEFRPFLAKMRGLLKSIASADMDFNQLEAFLTAQTKKQGGITSEQAAVISKFWKSHKIKIRESLMKQSRWDNGLRGLS | ||||||
Domain | 117-185 | COMM | ||||
Sequence: GLRGLSWRVDGKSQSRHSTQIHSPVAIIELEFGKNGQESEFLCLEFDEVKVKQILKKLSEVEESINRLM | ||||||
Region | 124-188 | Required for binding to PtdIns(4,5)P2 | ||||
Sequence: RVDGKSQSRHSTQIHSPVAIIELEFGKNGQESEFLCLEFDEVKVKQILKKLSEVEESINRLMQAA |
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length188
- Mass (Da)20,996
- Last updated2004-08-16 v2
- ChecksumEEEC6489BC59B483
Computationally mapped potential isoform sequences
There are 3 potential isoforms mapped to this entry
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 5 | in Ref. 3; AAH51210 | ||||
Sequence: L → H |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AK133507 EMBL· GenBank· DDBJ | BAE21693.1 EMBL· GenBank· DDBJ | mRNA | ||
AB089806 EMBL· GenBank· DDBJ | BAC07535.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AB104816 EMBL· GenBank· DDBJ | BAC57942.1 EMBL· GenBank· DDBJ | mRNA | ||
BC030052 EMBL· GenBank· DDBJ | AAH30052.1 EMBL· GenBank· DDBJ | mRNA | ||
BC051210 EMBL· GenBank· DDBJ | AAH51210.1 EMBL· GenBank· DDBJ | mRNA |