Affinage

COMMD1

COMM domain-containing protein 1 · UniProt Q8N668

Length
190 aa
Mass
21.2 kDa
Annotated
2026-06-09
94 papers in source corpus 39 papers cited in narrative 39 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

COMMD1 (originally MURR1) is a copper-binding scaffold protein that couples copper homeostasis to endosomal protein trafficking and ubiquitin-proteasome-dependent degradation of multiple membrane and signaling substrates (PMID:12968035, PMID:17309234, PMID:25355947). It binds Cu(II) with 1:1 stoichiometry through His101, His134, and Met110 in its exon-2-encoded region (PMID:17309234) and is recruited to endocytic-pathway vesicles by binding PtdIns(4,5)P2 through its C-terminal domain, where it forms large oligomeric complexes (PMID:18940794). Through the conserved COMM domain it engages homo- and heteromeric partners (PMID:15799966), and it directly links to early endosomes via the CCC complex (CCDC22/CCDC93/C16orf62), which connects to the WASH-complex subunit FAM21 to drive copper-dependent endosomal movement of ATP7A; loss of CCC components causes intracellular copper accumulation (PMID:25355947). COMMD1 binds the copper-binding amino terminus of the Wilson disease protein ATP7B (PMID:12968035, PMID:17919502) and a PtdIns(4,5)P2-dependent mechanism governs copper-responsive ATP7B trafficking (PMID:31515276); it promotes proteasomal degradation of newly synthesized ATP7B, with disease-associated N-terminal mutations enhancing COMMD1 binding and accelerating degradation (PMID:17919502, PMID:39389536). Liver-specific Commd1 deletion produces marked hepatic copper accumulation, establishing an essential in vivo role in copper homeostasis (PMID:22216203). In parallel, COMMD1 negatively regulates NF-κB: it acts at the chromatin level on NF-κB association (PMID:15799966), and TNF-induced Ser468 phosphorylation of RelA/p65 recruits COMMD1 and Cullin 2 into a multimeric ubiquitin ligase that targets p65 for degradation and stress-induced nucleolar translocation (PMID:19270718, PMID:20048074). COMMD1 also represses HIF signaling by binding the amino terminus of HIF-1α, competing with HSP90β and blocking HIF-1α/HIF-1β dimerization and transactivation (PMID:19802386, PMID:20458141); Commd1-null embryos die with placental vascularization defects and elevated HIF-1α (PMID:17371845). Its own abundance is set by competing post-translational marks: XIAP binds the COMM domain and catalyzes K48-linked polyubiquitination driving degradation (PMID:14685266, PMID:18795889), while p300-mediated acetylation stabilizes it (PMID:25074812). More broadly, COMMD1 controls ubiquitination, surface expression, and trafficking of multiple ion channels and transporters including ENaC, CFTR, and NKCC1 (PMID:14645214, PMID:20237237, PMID:21483833, PMID:23515529), and antagonizes CAND1 to activate Cullin-RING ligases (PMID:21778237).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2003 High

    Established COMMD1/MURR1 as a negative regulator of NF-κB, defining its first signaling function via control of IκB-α stability.

    Evidence RNAi knockdown in primary resting CD4+ T cells with proteasome inhibition and NF-κB reporters

    PMID:14685242

    Open questions at the time
    • Did not define the direct molecular target or whether the effect was cytoplasmic versus nuclear
    • Mechanism of IκB-α stabilization left unresolved
  2. 2003 High

    Connected COMMD1 to copper biology by demonstrating direct interaction with the Wilson disease transporter ATP7B and opposing regulation by the ubiquitin ligase XIAP.

    Evidence In vitro binding and Co-IP for ATP7B; reciprocal Co-IP, K48 ubiquitin chain typing, Xiap-knockout mice and copper measurements

    PMID:12968035 PMID:14685266

    Open questions at the time
    • Did not establish where in the copper-excretion pathway COMMD1 acts
    • Did not resolve whether COMMD1 affects ATP7B trafficking or stability
  3. 2003 High

    Extended COMMD1's substrate range to ion channels by showing it inhibits ENaC-mediated sodium current, hinting at a general role in transporter regulation.

    Evidence Yeast two-hybrid, GST pulldown, Co-IP, and Xenopus oocyte electrophysiology with domain deletion

    PMID:14645214

    Open questions at the time
    • Mechanism of channel inhibition not defined
    • Performed in heterologous oocyte system rather than native epithelium
  4. 2005 High

    Defined COMMD1 as the founding member of the COMM-domain family and localized its NF-κB effect to chromatin association rather than nuclear import.

    Evidence Biochemical interaction screen, Co-IP for complex formation, and ChIP

    PMID:15799966

    Open questions at the time
    • Did not identify the ligase converting chromatin binding to p65 turnover
    • Functional consequences of homo/heteromeric COMMD complexes unresolved
  5. 2006 High

    Provided the first structural view of COMMD1, showing a novel alpha-helical N-terminal fold with surfaces suited to protein interactions.

    Evidence NMR solution structure of residues 1–108

    PMID:17097678

    Open questions at the time
    • Structure of the COMM domain and full-length protein not determined
    • No partner-bound structure to define interaction interfaces
  6. 2007 High

    Identified COMMD1 as a copper(II)-specific binding protein and clarified its role in ATP7B degradation, linking metal binding to substrate stability.

    Evidence EPR, UV-vis, fluorescence, DEPC modification, MS mapping, and mutagenesis for Cu(II) binding; GST pulldown, Co-IP, mutagenesis, and biosynthetic labeling for ATP7B

    PMID:17309234 PMID:17919502

    Open questions at the time
    • Did not link copper binding mechanistically to ATP7B degradation or trafficking
    • Did not identify the E3 ligase degrading ATP7B
  7. 2007 High

    Demonstrated an essential developmental role and a HIF-1α-regulatory function, broadening COMMD1 beyond NF-κB and copper.

    Evidence Commd1 knockout mice, microarray, Co-IP, HIF-1 reporter and protein stability assays

    PMID:17371845

    Open questions at the time
    • Mechanism of HIF-1α destabilization not defined
    • Embryonic lethality precluded analysis of adult phenotypes
  8. 2008 High

    Established the membrane-recruitment basis of COMMD1 function by identifying PtdIns(4,5)P2 binding through the C-terminus and endosomal localization with oligomerization.

    Evidence Co-localization, fractionation, lipid arrays, liposome binding, native PAGE, and modeling

    PMID:18940794

    Open questions at the time
    • Did not connect lipid binding to a specific trafficking step
    • Stoichiometry and composition of the oligomers unresolved
  9. 2008 Medium

    Refined the regulation of COMMD1 stability, showing ARF promotes non-degradative K63 ubiquitination distinct from XIAP's degradative K48 marks.

    Evidence Co-IP, K63/K48 chain typing, ARF deletion mapping, DNA damage induction

    PMID:18305112

    Open questions at the time
    • Functional consequence of K63 ubiquitination on COMMD1 activity not defined
    • Single lab, ubiquitin chain typing not orthogonally confirmed
  10. 2009 High

    Defined a phosphorylation-gated ubiquitin ligase mechanism: Ser468-phosphorylated p65 recruits COMMD1 and Cullin 2 to drive p65 ubiquitination and degradation at target promoters.

    Evidence Phospho-specific mutagenesis, Co-IP, ChIP, ubiquitination assays, proteasome inhibition

    PMID:19270718

    Open questions at the time
    • Full subunit composition and substrate specificity of the ligase not enumerated
    • Did not establish promoter selectivity rules
  11. 2009 Medium

    Identified upstream regulators and additional pathways controlling COMMD1 levels and HIF repression, including HSCARG-driven degradation and HSP90-competitive HIF-1α destabilization.

    Evidence Yeast two-hybrid, Co-IP, ubiquitination and redox assays (HSCARG); Co-IP competition, 17-AAG, ubiquitin-independent stability assays (HIF-1α/HSP90β)

    PMID:19433587 PMID:19802386

    Open questions at the time
    • HSCARG-COMMD1 ligase identity not defined
    • Ubiquitin-independent HIF-1α degradation route mechanistically incomplete
  12. 2010 High

    Consolidated mechanism across NF-κB, HIF, ENaC, and SOD1: COMMD1 blocks HIF-1α/HIF-1β dimerization, drives stress-induced RelA nucleolar targeting, regulates ENaC via Nedd4-2, and limits SOD1 activity.

    Evidence Co-IP, dimerization/luciferase assays and xenograft/metastasis models (HIF); nucleolar fractionation and ubiquitination (RelA); electrophysiology, biotinylation, Co-IP, dominant-negative Nedd4-2 (ENaC); SOD1 activity and dimerization assays

    PMID:20048074 PMID:20068069 PMID:20237237 PMID:20458141 PMID:20595380

    Open questions at the time
    • Whether a single COMMD1 complex serves all substrates is unresolved
    • SOD1 and clusterin links rest on single-lab data
  13. 2011 High

    Provided genetic proof of COMMD1's hepatic copper role and broadened its transporter clientele while defining its action on Cullin-RING ligases via CAND1 antagonism.

    Evidence Liver-specific conditional knockout with copper analyses; Co-IP and pathway-specific inhibitors (ATP7A/ATP7B, clusterin); endogenous Co-IP and biotinylation (CFTR, δENaC); CAND1 displacement assays

    PMID:21483833 PMID:21741370 PMID:21778237 PMID:22130675 PMID:22216203

    Open questions at the time
    • Mechanistic basis for substrate-specific degradation route choice unclear
    • CRL regulation not linked to a defined cellular output
  14. 2014 High

    Anchored COMMD1 in the CCC-WASH endosomal trafficking machinery and clarified acetylation-controlled stability and stimulus-specific NF-κB regulation.

    Evidence Co-IP, siRNA, endosomal co-localization and copper assays (CCC/WASH); acetylation assays and stimulus-specific RelA assays (p300)

    PMID:25074812 PMID:25355947

    Open questions at the time
    • How COMMD1 selects copper-transporter cargo within the CCC complex remains undefined
    • Acetylation site and its interplay with XIAP ubiquitination not fully mapped
  15. 2017 High

    Linked COMMD1 to physiological inflammatory and proliferative control in vivo through macrophage NF-κB/E2F1 regulation and a nuclear DRR1-actin complex.

    Evidence Myeloid-specific knockout mice with arthritis/osteolysis models and eQTL (macrophages); Co-IP, nuclear fractionation, cell-cycle assays (DRR1)

    PMID:28604741 PMID:28723554

    Open questions at the time
    • Mechanistic connection between copper trafficking and inflammatory phenotypes not established
    • DRR1 complex function rests on single-lab data
  16. 2024 Medium

    Extended the ATP7B-degradation paradigm to a clinical mechanism, showing N-terminus-altering variants gain enhanced COMMD1 binding and accelerated proteasomal turnover.

    Evidence Splicing assay, RNA pulldown, ATP7B-knockout cells, Atp7b-/- mice, Co-IP, ubiquitin-proteasome and copper assays

    PMID:39389536

    Open questions at the time
    • Generalizability across all N-terminal variants relies on a single representative mutation
    • Single-lab confirmation
  17. 2025 Medium

    Implicated COMMD1 in genome maintenance and copper-dependent SOD1 disease pathways, including a HIF-1α/FASN-CCS palmitoylation axis in ALS models.

    Evidence DSB reporter assays with siRNA (NHEJ/HR); palmitoylation, fractionation, pathway analysis and hSOD1G93A mice (CCS axis)

    PMID:33669398 PMID:42156174

    Open questions at the time
    • Direct molecular role of COMMD1 in DSB repair not defined
    • Connection between DNA repair and copper/trafficking functions unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single PtdIns(4,5)P2- and copper-binding scaffold integrates endosomal trafficking, multi-substrate ubiquitination, transcription-factor degradation, and DNA repair into one mechanistic logic remains unresolved.
  • No unified structural model of substrate selection within the Commander/CCC assembly
  • Whether copper binding directly gates COMMD1's signaling functions is untested
  • Physiological hierarchy among COMMD1's NF-κB, HIF, copper, and DNA-repair roles is undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 3 GO:0008289 lipid binding 2 GO:0140313 molecular sequestering activity 2
Localization
GO:0005634 nucleus 3 GO:0005768 endosome 3 GO:0005829 cytosol 2 GO:0031410 cytoplasmic vesicle 2 GO:0005730 nucleolus 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-382551 Transport of small molecules 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-168256 Immune System 2
Partners
ATP7BCCDC22CFTRCUL2HIF1ANKCC1RELAXIAP
Complex memberships
CCC complex (COMMD1/CCDC22/CCDC93/C16orf62)COMMD1-Cullin 2 ubiquitin ligaseDRR1-F-actin-COMMD1 nuclear complex

Evidence

Reading pass · 39 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 MURR1/COMMD1 inhibits NF-κB activity in resting CD4+ T cells by stabilizing IκB-α and preventing its proteasomal degradation; knockdown of MURR1 increased NF-κB activity and decreased IκB-α by facilitating phospho-IκB-α degradation by the proteasome, resulting in increased HIV-1 replication in primary resting CD4+ lymphocytes. RNA interference knockdown in primary resting CD4+ T cells, proteasome inhibitor assays, NF-κB reporter assays Nature High 14685242
2003 XIAP interacts with MURR1/COMMD1 and acts as its ubiquitin ligase, forming K48-linked polyubiquitin chains on MURR1 that promote its proteasomal degradation; XIAP-deficient mice had reduced copper levels while MURR1 suppression increased intracellular copper, indicating XIAP and MURR1 have opposing effects on copper homeostasis. Co-immunoprecipitation, ubiquitin chain analysis, Xiap-knockout mouse tissues, copper measurements in cells and tissues The EMBO journal High 14685266
2003 MURR1/COMMD1 directly interacts with the Wilson disease protein ATP7B in vitro and in vivo; this interaction is mediated via the copper-binding amino terminus of ATP7B and is specific for this copper transporter, placing MURR1 in the pathway of hepatic biliary copper excretion. In vitro binding assay, co-immunoprecipitation The Journal of biological chemistry High 12968035
2003 MURR1/COMMD1 interacts with delta, beta, and gamma subunits of the epithelial sodium channel (ENaC) and inhibits amiloride-sensitive sodium current in a dose-dependent manner when co-expressed in Xenopus oocytes; deletion of the last 59 amino acids of deltaENaC abolished inhibition. Yeast two-hybrid screen, GST pulldown, co-immunoprecipitation, Xenopus oocyte electrophysiology The Journal of biological chemistry High 14645214
2003 MURR1/COMMD1 protein is absent in livers of copper toxicosis-affected Bedlington terriers; in cells the protein localizes to cytosol and membrane fractions and is associated with a vesicular compartment, suggesting a role in vesicular copper sequestration. Western blot with polyclonal antibodies, indirect immunofluorescence, cell fractionation Journal of hepatology Medium 14568250
2005 COMMD proteins form a novel family defined by the conserved COMM domain, which functions as an interface for protein-protein interactions including homo- and heteromeric complex formation. COMMD1 (MURR1) suppresses NF-κB not by affecting nuclear translocation or DNA binding but by acting in the nucleus to affect NF-κB association with chromatin. Biochemical screen for MURR1-associated factors, co-immunoprecipitation, chromatin immunoprecipitation, NF-κB reporter assays The Journal of biological chemistry High 15799966
2006 The solution structure of the N-terminal domain of COMMD1 (residues 1–108) was determined by NMR; it adopts a compact alpha-helical fold with no resemblance to other known helical proteins, and complementary electrostatic surfaces suggest protein-protein interactions occur via this domain. NMR solution structure determination Journal of molecular biology High 17097678
2007 COMMD1 specifically interacts with the amino-terminal region of ATP7B independent of copper levels or ATOX1; four Wilson disease patient-derived mutations in this region significantly increased ATP7B binding to COMMD1, and COMMD1 markedly decreased the stability of newly synthesized ATP7B via proteasomal degradation. GST pulldown, co-immunoprecipitation, site-directed mutagenesis, biosynthetic labeling, immunofluorescence microscopy Gastroenterology High 17919502
2007 COMMD1 directly binds copper as Cu(II) with 1:1 stoichiometry via residues His101, His134, and Met110 in the exon-2-encoded region; it does not bind other divalent metals, identifying it as a Cu(II)-specific binding protein. EPR spectroscopy, UV-visible absorption, intrinsic fluorescence spectroscopy, DEPC modification of histidines, MALDI MS mapping, site-directed mutagenesis of full-length protein Biochemistry High 17309234
2007 Commd1 knockout mice die in utero between 9.5 and 10.5 dpc with placenta vascularization defects; Commd1-deficient embryos show transcriptional upregulation of HIF-1 target genes associated with increased Hif-1α stability, and COMMD1 physically associates with HIF-1α and inhibits HIF-1α stability and HIF-1 transactivation in vitro. Homozygous Commd1 knockout mouse generation, microarray analysis, co-immunoprecipitation, HIF-1 reporter assay, protein stability assay Molecular and cellular biology High 17371845
2008 COMMD1 localizes to vesicles of the endocytic pathway (not trans-Golgi network or lysosomes) and specifically binds phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) via its C-terminal domain to mediate membrane recruitment; endogenous COMMD1 forms large oligomeric complexes both in cytosol and at membranes, with PtdIns(4,5)P2 interaction increasing oligomer stability. Co-localization with organelle markers, cell fractionation, lipid-spotted arrays, liposome binding assays, native PAGE, molecular modeling, proteolytic sensitivity The Journal of biological chemistry High 18940794
2008 Copper-induced translocation of ATP7B is independent of MURR1/COMMD1: COMMD1 does not co-localize with ATP7B during trafficking and siRNA depletion of COMMD1 does not impair ATP7B translocation, indicating COMMD1 acts at a later step in copper excretion rather than in the initial translocation of ATP7B. Confocal microscopy, RNA interference, siRNA depletion, dominant-negative Rab7 mutant The American journal of pathology Medium 18974300
2009 TNF-induced phosphorylation of NF-κB p65 at Ser468 allows binding of COMMD1 and Cullin 2 as components of a multimeric ubiquitin ligase complex mediating p65 ubiquitination and proteasomal degradation; mutation of p65 at Ser468 prevents p65 ubiquitination and degradation, and ChIP experiments show selective recruitment of Ser468-phosphorylated p65 and COMMD1 to the Icam1 promoter. Site-directed mutagenesis, co-immunoprecipitation, chromatin immunoprecipitation, ubiquitination assays, proteasome inhibition EMBO reports High 19270718
2009 HSCARG associates with COMMD1 (via yeast two-hybrid and Co-IP) and negatively regulates it by accelerating COMMD1 ubiquitination and proteasome-dependent degradation in the cytoplasm; under redox changes HSCARG translocates to the nucleus to promote ubiquitination and degradation of RelA, while cytoplasmic COMMD1 levels are restored. Yeast two-hybrid screen, co-immunoprecipitation, ubiquitination assays, proteasome inhibition, cellular redox manipulation The Journal of biological chemistry Medium 19433587
2009 COMMD1 expression is controlled by its interaction with XIAP; the COMM domain of COMMD1 is required for XIAP binding, specifically two conserved leucine repeats within the COMM domain; a COMMD1 mutant unable to bind XIAP shows complete loss of basal ubiquitination and greatly stabilized protein levels. Co-immunoprecipitation, site-directed mutagenesis (leucine repeat mutations), ubiquitination assays, protein stability assays The Biochemical journal High 18795889
2009 COMMD1 promotes pVHL- and O2-independent degradation of HIF-1α by competing with chaperone HSP90β for binding to the NH2-terminal DNA-binding and heterodimerization domain of HIF-1α; inhibition of HSP90 activity increased COMMD1-mediated HIF-1α degradation independent of ubiquitin and pVHL, with HSP70 also involved. Co-immunoprecipitation, competition binding assay, HSP90 inhibitor (17-AAG) treatment, protein stability assays, ubiquitin-independent degradation assays PloS one Medium 19802386
2010 COMMD1 inhibits HIF-mediated gene expression by binding directly to the amino terminus of HIF-1α, preventing its dimerization with HIF-1β and subsequent DNA binding and transcriptional activation; repression of COMMD1 in human cell lines increased tumor invasion in a chick xenograft model. Co-immunoprecipitation, dimerization assays, luciferase reporter assay, chick xenograft model, mouse melanoma lung metastasis model The Journal of clinical investigation High 20458141
2010 Stress-induced nucleolar translocation of RelA requires ubiquitination of RelA, and COMMD1 is the rate-limiting component of the RelA ubiquitin ligase complex; overexpression of COMMD1 promotes stress-mediated nucleolar targeting of RelA, while knockdown blocks this effect and causes RelA to remain in the nucleoplasm. The RelA nucleolar localization signal (aa 27–30) is critical for ubiquitination. Overexpression and siRNA knockdown, immunofluorescence/nucleolar fractionation, ubiquitination assays, domain deletion analysis Cancer research Medium 20048074
2010 COMMD1 inhibits amiloride-sensitive current in mammalian epithelial cells via its COMM domain; COMMD1 increases ubiquitin modification of ENaC and decreases ENaC cell surface expression; COMMD1 interacts with SGK1 and Akt1, and its effects require Nedd4-2 (dominant-negative Nedd4-2 abolishes COMMD1 effects). Amiloride-sensitive current measurements in mammalian epithelial cells, surface biotinylation, co-immunoprecipitation, siRNA knockdown, dominant-negative constructs, ENaC PY-motif mutation American journal of physiology. Renal physiology High 20237237
2010 Secretory clusterin (sCLU) acts as a ubiquitin-binding protein that enhances COMMD1 and IκB proteasomal degradation by interacting with SCF-βTrCP E3 ligase family members, thereby increasing NF-κB nuclear translocation; knockdown of sCLU stabilizes COMMD1 and IκB, sequestering NF-κB in the cytoplasm. Co-immunoprecipitation, proteasome inhibitor assays, siRNA knockdown, NF-κB reporter assay, microarray profiling Molecular cancer research : MCR Medium 20068069
2010 COMMD1 interacts with SOD1 in a manner that requires CCS-mediated copper incorporation into SOD1; COMMD1 reduces the level of SOD1 homodimers without affecting disulfide oxidation; RNAi knockdown of COMMD1 significantly increases SOD1 activity and decreases superoxide concentrations, while overexpression has the opposite effect. Co-immunoprecipitation, SOD1 activity assay, RNAi knockdown and overexpression, superoxide measurement, dimerization assay The Journal of biological chemistry Medium 20595380
2011 Liver-specific Commd1 knockout mice (Commd1^Δhep) develop hepatic copper accumulation (up to 20-fold on copper-enriched diet), providing the first genetic evidence for COMMD1's essential role in hepatic copper homeostasis in vivo. Liver-specific conditional knockout mice, biochemical and histological copper analyses, gene expression analysis PloS one High 22216203
2011 COMMD1 and clusterin independently regulate degradation of both ATP7A and ATP7B: COMMD1 facilitates ATP7B degradation via the proteasomal pathway while clusterin uses the lysosomal pathway; both proteins interact with ATP7B independently and non-competitively, and endogenous ATP7B exists in a complex containing both. Co-immunoprecipitation, overexpression and knockdown, pathway-specific inhibitors (proteasome vs lysosome), endogenous complex analysis The Journal of biological chemistry High 22130675
2011 COMMD1 regulates Cullin RING Ligases (CRLs) by antagonizing CAND1 binding: COMMD1 interacts with multiple Cullins, the COMMD1-Cul2 complex cannot bind CAND1, and COMMD1 can actively displace CAND1 from CRLs, promoting CRL activation. Co-immunoprecipitation, competitive binding assay, CAND1 displacement assay The Journal of biological chemistry Medium 21778237
2011 COMMD1 interacts with CFTR endogenously, promotes CFTR cell surface expression by protecting CFTR from ubiquitination, sustaining CFTR at the plasma membrane. Genetic screen, co-immunoprecipitation in cells with endogenous expression, surface biotinylation, ubiquitination assay PloS one Medium 21483833
2011 COMMD1 regulates δENaC through its COMM domain; co-expression of COMMD1 reduces δENaC surface expression and increases δENaC ubiquitination; COMMD1 promotes localization of δENaC to early/recycling endosomes. Co-immunoprecipitation, surface expression assay, ubiquitination assay, immunocytochemistry and confocal microscopy with endosomal markers Biochemical and biophysical research communications Medium 21741370
2008 Tumor suppressor ARF associates with COMMD1 and promotes non-classic Lys63-mediated polyubiquitination of COMMD1 in a p53-independent manner; this Lys63-linked ubiquitination does not target COMMD1 for proteasomal degradation; ARF redistributes from nucleolus to nucleoplasm upon DNA damage to interact with COMMD1. Co-immunoprecipitation, ubiquitin chain-specific (K63/K48) analysis, deletion mapping of ARF, actinomycin D DNA damage, proteasome assays The Journal of biological chemistry Medium 18305112
2013 COMMD1 binds to the C-terminal domain of NKCC1 (aa 1040–1134) via its N-terminus (aa 1–47) in airway epithelial cells and modulates NKCC1 ubiquitination and membrane expression; COMMD1 loss reduces baseline NKCC1 membrane expression and blunts hyperosmolarity-stimulated NKCC1 trafficking. Yeast two-hybrid, GST pulldown, Co-IP with endogenous proteins, siRNA knockdown, membrane expression assay, ubiquitination assay American journal of physiology. Cell physiology Medium 23515529
2014 COMMD1 is directly linked to early endosomes through interaction with the CCC complex (CCDC22/CCDC93/C16orf62); the CCC complex interacts with the WASH complex subunit FAM21 via C-terminal ends of CCDC22 and CCDC93; depletion of CCC complex components prevents copper-dependent movement of ATP7A from endosomes, causing intracellular copper accumulation. Co-immunoprecipitation, siRNA knockdown, endosomal co-localization, copper accumulation assays, domain mapping Molecular biology of the cell High 25355947
2014 p300 acetylates COMMD1, protecting it from XIAP-mediated proteasomal degradation; p300-mediated COMMD1 acetylation is required for COMMD1 to bind RelA under aspirin-mediated stress conditions but not TNF stimulation; this controls stress-specific (but not cytokine-driven) ubiquitination and nucleolar translocation of RelA. Co-immunoprecipitation, acetylation assays, siRNA knockdown, RelA nucleolar localization assay, stimulus-specific comparison Journal of cell science Medium 25074812
2014 COMMD1 modulates aggregation of misfolded SOD1 in a client-specific manner: COMMD1 enhances formation of mutant SOD1 (mSOD1) aggregates and co-localizes to mSOD1 inclusion sites, forming high molecular weight complexes; in contrast, COMMD1 decreases abundance of mutant Parkin inclusions and does not affect polyglutamine-expanded Huntingtin aggregation. Co-immunoprecipitation, co-localization by confocal microscopy, high molecular weight complex analysis, overexpression in cell models of ALS and PD PloS one Medium 24691167
2017 DRR1, F-actin, and COMMD1 form a novel nuclear complex; stability of COMMD1 is enhanced within this complex; increased nuclear COMMD1 promotes NF-κB degradation; DRR1 and COMMD1 together suppress cyclin D1 expression, G1/S transition, and cell proliferation in neuroblastoma cells, with the DRR1-F-actin interaction being required. Co-immunoprecipitation, nuclear fractionation, NF-κB activity assay, cell cycle analysis, proliferation assay, DRR1-actin binding mutants Oncogene Medium 28604741
2017 COMMD1 in human macrophages restrains RANKL-induced NF-κB signaling and an E2F1-dependent metabolic pathway; hypoxia suppresses COMMD1 protein expression, augmenting RANKL-induced inflammatory and E2F1 target gene expression and osteoclastogenesis; myeloid-specific Commd1 deletion in mice increased osteoclastogenesis in arthritis and inflammatory osteolysis models. Myeloid-specific conditional knockout mice, RANKL stimulation, NF-κB reporter assays, E2F1 target gene analysis, arthritis and osteolysis mouse models, eQTL analysis Immunity High 28723554
2019 COMMD1 modulates copper-responsive ATP7B trafficking through recruitment to PtdIns(4,5)P2; decreased COMMD1 results in loss of ATP7B from lysosomes and trans-Golgi network under high copper; overexpression of a COMMD1 mutant deficient in PtdIns(4,5)P2 binding has little impact on ATP7B trafficking, demonstrating a PtdIns(4,5)P2-dependent mechanism. Quantitative colocalization analysis, COMMD1 PtdIns(4,5)P2-binding mutant, siRNA knockdown, copper export assay, organelle markers Journal of cell science Medium 31515276
2021 COMMD1 is required for efficient repair of DNA double strand breaks and functions in both non-homologous end joining (NHEJ) and homologous recombination (HR) pathways, as determined by DSB reporter assays in COMMD1-siRNA-depleted cells. siRNA depletion, DSB repair reporter assays for NHEJ and HR, cell viability and cell cycle assays Cancers Medium 33669398
2014 COMMD1 reinforces HIV-1 latency in myeloid cells through IκB-α stabilization: COMMD1 induction in latently HIV-1-infected myeloid cells (via PI3K-JAK pathway) inhibits proteasomal degradation of IκB-α by increasing COMMD1-IκB-α interaction, attenuating NF-κB signaling during innate immune stimulation. Four pairs of latently HIV-1-infected and parental cells, Western blot, Co-IP, siRNA knockdown, PI3K-JAK pathway inhibitors Journal of virology Medium 25520503
2024 An ATP7B splicing mutation (c.1543+1G>C) causes skipping of exon 3, producing mutant ATP7B with altered N-terminus that shows enhanced interaction with COMMD1 and is consequently degraded via the ubiquitin-proteasome pathway; this enhanced COMMD1 binding represents a universal pathogenic mechanism for ATP7B variants with altered N-terminus. Splicing assay, RNA pulldown, ATP7B-knockout HuH-7 cells, Atp7b-/- mice, co-immunoprecipitation, ubiquitin-proteasome pathway assay, intracellular copper measurement Cellular and molecular gastroenterology and hepatology Medium 39389536
2025 COMMD1 knockdown in ALS models enhances palmitoylation of the copper chaperone CCS via activation of the HIF-1α/FASN signaling axis, facilitating CCS membrane translocation and promoting copper loading into SOD1; in vivo, COMMD1 deficiency in hSOD1G93A transgenic mice ameliorates motor function deterioration and prolongs survival. siRNA knockdown, palmitoylation assay, membrane fractionation, HIF-1α/FASN pathway analysis, transgenic mouse model (hSOD1G93A), behavioral/survival assays The Journal of neuroscience Medium 42156174
2025 Crystal and cryo-EM structures of bacterial and archaeal COMMD-like proteins reveal homooligomeric ring assemblies of 8 or 10 subunits built from core dimeric building blocks with inter-dimer interactions analogous to the eukaryotic heterodecameric Commander complex COMMD ring; phylogenetic analysis indicates the closest relatives to eukaryotic COMMD proteins are found in Myxococcota bacteria. Cryo-EM structure determination, crystal structure determination, biophysical characterization, phylogenetic analysis (sequence + FoldSeek 3Di structural alphabet) bioRxivpreprint Medium bio_10.1101_2025.09.01.673571

Source papers

Stage 0 corpus · 94 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 COMMD proteins, a novel family of structural and functional homologs of MURR1. The Journal of biological chemistry 233 15799966
2003 The gene product Murr1 restricts HIV-1 replication in resting CD4+ lymphocytes. Nature 191 14685242
2014 COMMD1 is linked to the WASH complex and regulates endosomal trafficking of the copper transporter ATP7A. Molecular biology of the cell 186 25355947
2003 A novel role for XIAP in copper homeostasis through regulation of MURR1. The EMBO journal 179 14685266
2009 Phosphorylation of NF-kappaB p65 at Ser468 controls its COMMD1-dependent ubiquitination and target gene-specific proteasomal elimination. EMBO reports 140 19270718
2003 The copper toxicosis gene product Murr1 directly interacts with the Wilson disease protein. The Journal of biological chemistry 132 12968035
2007 Distinct Wilson's disease mutations in ATP7B are associated with enhanced binding to COMMD1 and reduced stability of ATP7B. Gastroenterology 127 17919502
2003 The ubiquitously expressed MURR1 protein is absent in canine copper toxicosis. Journal of hepatology 115 14568250
2010 COMMD1 disrupts HIF-1alpha/beta dimerization and inhibits human tumor cell invasion. The Journal of clinical investigation 112 20458141
2010 Clusterin facilitates COMMD1 and I-kappaB degradation to enhance NF-kappaB activity in prostate cancer cells. Molecular cancer research : MCR 110 20068069
2007 Increased activity of hypoxia-inducible factor 1 is associated with early embryonic lethality in Commd1 null mice. Molecular and cellular biology 101 17371845
2017 Hypoxia-Sensitive COMMD1 Integrates Signaling and Cellular Metabolism in Human Macrophages and Suppresses Osteoclastogenesis. Immunity 84 28723554
2003 Identification of Murr1 as a regulator of the human delta epithelial sodium channel. The Journal of biological chemistry 75 14645214
2011 Clusterin and COMMD1 independently regulate degradation of the mammalian copper ATPases ATP7A and ATP7B. The Journal of biological chemistry 74 22130675
2004 The mouse Murr1 gene is imprinted in the adult brain, presumably due to transcriptional interference by the antisense-oriented U2af1-rs1 gene. Molecular and cellular biology 66 14673161
2010 Nucleolar targeting of RelA(p65) is regulated by COMMD1-dependent ubiquitination. Cancer research 58 20048074
2005 The many faces of the copper metabolism protein MURR1/COMMD1. The Journal of heredity 56 16267171
2004 Analysis of the human homologue of the canine copper toxicosis gene MURR1 in Wilson disease patients. Journal of molecular medicine (Berlin, Germany) 56 15205742
2011 Liver-specific Commd1 knockout mice are susceptible to hepatic copper accumulation. PloS one 55 22216203
2009 COMMD1 Promotes pVHL and O2-Independent Proteolysis of HIF-1alpha via HSP90/70. PloS one 50 19802386
2007 Characterization and copper binding properties of human COMMD1 (MURR1). Biochemistry 50 17309234
2017 COMMD1: A Multifunctional Regulatory Protein. Journal of cellular biochemistry 49 28543362
2011 COMMD1-mediated ubiquitination regulates CFTR trafficking. PloS one 47 21483833
2020 Long-Term Survival of Transplanted Autologous Canine Liver Organoids in a COMMD1-Deficient Dog Model of Metabolic Liver Disease. Cells 46 32053895
2012 Molecular analysis of Wilson patients: direct sequencing and MLPA analysis in the ATP7B gene and Atox1 and COMMD1 gene analysis. Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) 45 22677543
2009 COMMD1 expression is controlled by critical residues that determine XIAP binding. The Biochemical journal 45 18795889
2015 Downregulation of COMMD1 by miR-205 promotes a positive feedback loop for amplifying inflammatory- and stemness-associated properties of cancer cells. Cell death and differentiation 44 26586569
2006 Mutation analysis of 218 Chinese patients with Wilson disease revealed no correlation between the canine copper toxicosis gene MURR1 and Wilson disease. Journal of molecular medicine (Berlin, Germany) 44 16649058
2010 COMMD1 downregulates the epithelial sodium channel through Nedd4-2. American journal of physiology. Renal physiology 42 20237237
2003 The canine copper toxicosis gene MURR1 does not cause non-Wilsonian hepatic copper toxicosis. Journal of hepatology 42 12547404
2008 COMMD1 forms oligomeric complexes targeted to the endocytic membranes via specific interactions with phosphatidylinositol 4,5-bisphosphate. The Journal of biological chemistry 41 18940794
2005 Characterization of the COMMD1 (MURR1) mutation causing copper toxicosis in Bedlington terriers. Animal genetics 38 16293123
2012 COMMD1-deficient dogs accumulate copper in hepatocytes and provide a good model for chronic hepatitis and fibrosis. PloS one 36 22879914
2011 COMMD1 (copper metabolism MURR1 domain-containing protein 1) regulates Cullin RING ligases by preventing CAND1 (Cullin-associated Nedd8-dissociated protein 1) binding. The Journal of biological chemistry 36 21778237
2010 Cu,Zn superoxide dismutase maturation and activity are regulated by COMMD1. The Journal of biological chemistry 34 20595380
2008 Copper-induced translocation of the Wilson disease protein ATP7B independent of Murr1/COMMD1 and Rab7. The American journal of pathology 33 18974300
2017 A novel nuclear complex of DRR1, F-actin and COMMD1 involved in NF-κB degradation and cell growth suppression in neuroblastoma. Oncogene 32 28604741
2014 Functional understanding of the versatile protein copper metabolism MURR1 domain 1 (COMMD1) in copper homeostasis. Annals of the New York Academy of Sciences 31 24697840
2014 The Copper Metabolism MURR1 domain protein 1 (COMMD1) modulates the aggregation of misfolded protein species in a client-specific manner. PloS one 30 24691167
2006 Copper toxicosis gene MURR1 is not changed in Wilson disease patients with normal blood ceruloplasmin levels. World journal of gastroenterology 30 16610028
2013 The Antitumor Peptide CIGB-552 Increases COMMD1 and Inhibits Growth of Human Lung Cancer Cells. Journal of amino acids 29 23401744
2011 COMMD1 regulates the delta epithelial sodium channel (δENaC) through trafficking and ubiquitination. Biochemical and biophysical research communications 29 21741370
2021 COMMD1, a multi-potent intracellular protein involved in copper homeostasis, protein trafficking, inflammation, and cancer. Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) 28 33482423
2014 Loss of COMMD1 and copper overload disrupt zinc homeostasis and influence an autism-associated pathway at glutamatergic synapses. Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine 25 25007851
2007 Functional consequences of RNA interference targeting COMMD1 in a canine hepatic cell line in relation to copper toxicosis. Animal genetics 25 17355395
2019 COMMD1 and PtdIns(4,5)P2 interaction maintain ATP7B copper transporter trafficking fidelity in HepG2 cells. Journal of cell science 24 31515276
2010 A novel COMMD1 mutation Thr174Met associated with elevated urinary copper and signs of enhanced apoptotic cell death in a Wilson Disease patient. Behavioral and brain functions : BBF 24 20550661
2006 The canine copper toxicosis gene MURR1 is not implicated in the pathogenesis of Wilson disease. Journal of gastroenterology 24 16868807
2016 Copper toxicosis in non-COMMD1 Bedlington terriers is associated with metal transport gene ABCA12. Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) 23 27049130
2014 p300-mediated acetylation of COMMD1 regulates its stability, and the ubiquitylation and nucleolar translocation of the RelA NF-κB subunit. Journal of cell science 23 25074812
2009 HSCARG regulates NF-kappaB activation by promoting the ubiquitination of RelA or COMMD1. The Journal of biological chemistry 23 19433587
2011 The puzzle posed by COMMD1, a newly discovered protein binding Cu(II). Metallomics : integrated biometal science 21 21275100
2006 Solution structure of the COMMD1 N-terminal domain. Journal of molecular biology 21 17097678
2005 Comparative analyses of genomic imprinting and CpG island-methylation in mouse Murr1 and human MURR1 loci revealed a putative imprinting control region in mice. Gene 21 16305817
2007 Expression and localization of cellular prion and COMMD1 proteins in human placenta throughout pregnancy. Placenta 19 17254632
2013 COMMD1 interacts with the COOH terminus of NKCC1 in Calu-3 airway epithelial cells to modulate NKCC1 ubiquitination. American journal of physiology. Cell physiology 18 23515529
2008 Tumor suppressor ARF promotes non-classic proteasome-independent polyubiquitination of COMMD1. The Journal of biological chemistry 18 18305112
2014 COMMD1/Murr1 reinforces HIV-1 latent infection through IκB-α stabilization. Journal of virology 17 25520503
2007 COMMD1: a novel protein involved in the proteolysis of proteins. Cell cycle (Georgetown, Tex.) 17 17786049
2014 Aberrant expression of copper associated genes after copper accumulation in COMMD1-deficient dogs. Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) 15 25053573
2014 A cell-type-specific role for murine Commd1 in liver inflammation. Biochimica et biophysica acta 15 25072958
2016 Nuclear COMMD1 Is Associated with Cisplatin Sensitivity in Ovarian Cancer. PloS one 13 27788210
2020 COMMD1 upregulation is involved in copper efflux from ischemic hearts. Experimental biology and medicine (Maywood, N.J.) 12 33653183
2014 COMMD1 regulates inflammation and colitis-associated cancer progression. Oncoimmunology 11 25610735
2023 Lead exposure disturbs ATP7B-mediated copper export from brain barrier cells by inhibiting XIAP-regulated COMMD1 protein degradation. Ecotoxicology and environmental safety 10 37027943
2020 Long non-coding RNA SNHG5 suppresses the development of acute respiratory distress syndrome by targeting miR-205/COMMD1 axis. Molecular and cellular biochemistry 10 33170429
2007 Developmental expression of Commd1 in the liver of the Jackson toxic milk mouse. Biochemical and biophysical research communications 10 17910951
2023 Disruption of COMMD1 accelerates diabetic atherosclerosis by promoting glycolysis. Diabetes & vascular disease research 8 36803109
2020 The Anticancer Peptide CIGB-552 Exerts Anti-Inflammatory and Anti-Angiogenic Effects through COMMD1. Molecules (Basel, Switzerland) 8 33396282
2005 Quantitative PCR method to detect a 13-kb deletion in the MURR1 gene associated with copper toxicosis and HIV-1 replication. Mammalian genome : official journal of the International Mammalian Genome Society 7 16075372
2024 Dysfunction of ATP7B Splicing Variant Caused by Enhanced Interaction With COMMD1 in Wilson Disease. Cellular and molecular gastroenterology and hepatology 6 39389536
2021 COMMD1, from the Repair of DNA Double Strand Breaks, to a Novel Anti-Cancer Therapeutic Target. Cancers 6 33669398
2019 COMMD1 regulates cell proliferation and cell cycle progression by modulating p21 Cip1 levels. Bioscience, biotechnology, and biochemistry 6 30667321
2019 Identification of COMMD1 as a novel lamin A binding partner. Molecular medicine reports 6 31257505
2021 A first-in-class, first-in-human, phase I trial of CIGB-552, a synthetic peptide targeting COMMD1 to inhibit the oncogenic activity of NF-κB in patients with advanced solid tumors. International journal of cancer 5 34019700
2020 Evaluation of COMMD1 in copper toxicosis in Labrador retrievers and Dobermans. Veterinary journal (London, England : 1997) 5 33129558
2013 COMMD1 modulates noxious inflammation in cystic fibrosis. The international journal of biochemistry & cell biology 5 23892095
2021 COMMD1 Exemplifies the Power of Inbred Dogs to Dissect Genetic Causes of Rare Copper-Related Disorders. Animals : an open access journal from MDPI 4 33668783
2018 Transcriptional regulation of HIV-1 host factor COMMD1 by the Sp family. International journal of molecular medicine 4 29336469
2009 Antisense transcription occurs at the promoter of a mouse imprinted gene, commd1, on the repressed paternal allele. Journal of biochemistry 4 19762339
2002 Identification of a novel isoform of Murr1 transcript, U2mu, which is transcribed from the portions of two closely located but oppositely oriented genes. Genes & genetic systems 4 12441649
2025 Elevated COMMD1 Contributes to Cardiomyocyte Copper Efflux in Chronic Myocardial Ischemia: Insights From Rhesus Monkey. Cell proliferation 3 40032621
2019 Association of Variants in the CP, ATOX1 and COMMD1 Genes with Wilson Disease Symptoms in Latvia. Balkan journal of medical genetics : BJMG 3 31942415
2016 Prevalence and Clinical Relevance of Exon 2 Deletion of COMMD1 in Bedlington Terriers in Korea. Journal of veterinary internal medicine 3 27727471
2025 Cuproptosis involvement in neonatal ischemic-hypoxic encephalopathy through the COMMD1/ATP7A signaling axis. Biochemical pharmacology 2 40545047
2025 COMMD1 Regulates Osteoclast Differentiation in Talaromyces marneffei-Induced Osteomyelitis via the NF-κB Pathway. Infection and drug resistance 2 41306130
2024 Novel therapeutic targets for atherosclerosis: Targeting the FOSB-MECP2-Commd1 pathway. International immunopharmacology 2 39566383
2021 Cardiomyocyte-Specific COMMD1 Deletion Suppresses Ischemia-Induced Myocardial Apoptosis. Cardiovascular toxicology 2 33900545
2020 Behavioral Effects of Neuronal, Parent-specific Commd1 Knockout in Mice. Neuroscience 1 32200079
2013 Expression and localization of COMMD1 proteins in human placentas from women with preeclampsia. Yonsei medical journal 1 23364987
2026 COMMD1 Induces Copper Deficiency of SOD1 by Inhibiting the Palmitoylation of CCS in ALS. The Journal of neuroscience : the official journal of the Society for Neuroscience 0 42156174
2026 Copper nanoregulator with organelle-level precision reprograms COMMD1-Mediated copper homeostasis for myocardial infarction repair. Biomaterials 0 42258904
2025 COMMD1 Inhibits Epithelial Mesenchymal Transition (EMT) and Liver Metastasis in Cervical Cancer Through Modulation of the Twist1/E-Cadherin Pathway. Cell biology international 0 40616572
2024 Association between COMMD1 gene polymorphism rs11125908 and rheumatoid arthritis in the Cuban population. Reumatismo 0 38916163

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