Q8K4M5 · COMD1_MOUSE

  • Protein
    COMM domain-containing protein 1
  • Gene
    Commd1
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

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.

TypeIDPosition(s)Description
Binding site100Cu cation (UniProtKB | ChEBI)
Binding site109Cu cation (UniProtKB | ChEBI)
Binding site133Cu cation (UniProtKB | ChEBI)

GO annotations

AspectTerm
Cellular ComponentCul2-RING ubiquitin ligase complex
Cellular Componentcytoplasm
Cellular Componentearly endosome
Cellular Componentendosome
Cellular Componentendosome membrane
Cellular Componentnucleus
Cellular Componentrecycling endosome
Molecular Functioncopper ion binding
Molecular Functionlow-density lipoprotein particle receptor binding
Molecular Functionsodium channel inhibitor activity
Biological Processcholesterol homeostasis
Biological Processcopper ion homeostasis
Biological Processintracellular copper ion homeostasis
Biological Processlow-density lipoprotein particle clearance
Biological Processnegative regulation of hypoxia-inducible factor-1alpha signaling pathway
Biological Processnegative regulation of NF-kappaB transcription factor activity
Biological Processnegative regulation of protein localization to cell surface
Biological Processnegative regulation of sodium ion transmembrane transport
Biological Processpositive regulation of cholesterol import
Biological Processpositive regulation of endosome to plasma membrane protein transport
Biological Processpositive regulation of protein localization to cell surface
Biological Processpositive regulation of protein ubiquitination
Biological Processprotein destabilization
Biological Processprotein localization to cell surface
Biological Processprotein transport
Biological Processregulation of plasma lipoprotein particle levels
Biological Processregulation of proteasomal ubiquitin-dependent protein catabolic process

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    COMM domain-containing protein 1
  • Alternative names
    • Protein Murr1

Gene names

    • Name
      Commd1
    • Synonyms
      Murr1

Organism names

  • Taxonomic identifier
  • Strain
    • C57BL/6J
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus

Accessions

  • Primary accession
    Q8K4M5
  • Secondary accessions
    • Q3V012
    • Q80WG2
    • Q80Z41
    • Q8BNL9
    • Q8K2S9

Proteomes

Organism-specific databases

Subcellular Location

Nucleus
Cytoplasm
Endosome membrane
Cytoplasmic vesicle
Early endosome
Recycling endosome
Note: Shuttles between nucleus and cytosol. Detected in perinuclear foci that may be aggresomes containing misfolded, ubiquitinated proteins (By similarity).

Keywords

PTM/Processing

Features

Showing features for chain.

TypeIDPosition(s)Description
ChainPRO_00000773851-188COMM domain-containing protein 1

Post-translational modification

Ubiquitinated; undergoes both 'Lys-63'- and 'Lys-48'-linked polyubiquitination. Ubiquitinated by XIAP, leading to its proteasomal degradation (By similarity).

Keywords

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.

TypeIDPosition(s)Description
Region1-122Sufficient for interaction with SLC12A2
Domain117-185COMM
Region124-188Required for binding to PtdIns(4,5)P2

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    188
  • Mass (Da)
    20,996
  • Last updated
    2004-08-16 v2
  • Checksum
    EEEC6489BC59B483
MAGDLEGGKSLSGLLSGLAQNAFHGHSGVTEELLHSQLYPEVPPEEFRPFLAKMRGLLKSIASADMDFNQLEAFLTAQTKKQGGITSEQAAVISKFWKSHKIKIRESLMKQSRWDNGLRGLSWRVDGKSQSRHSTQIHSPVAIIELEFGKNGQESEFLCLEFDEVKVKQILKKLSEVEESINRLMQAA

Computationally mapped potential isoform sequences

There are 3 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
Q8VI86Q8VI86_MOUSECommd1243
G8JL54G8JL54_MOUSECommd193
F7BZY0F7BZY0_MOUSECommd1140

Features

Showing features for sequence conflict.

TypeIDPosition(s)Description
Sequence conflict5in Ref. 3; AAH51210

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
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

Genome annotation databases

Similar Proteins

Disclaimer

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