Component

Human copper chaperone for SOD1 / CCS

Human CCS protein; copper delivery and disulfide formation partners of SOD1.

6 recorded relationships. Experimental role, claim status and evidence remain attached to each record.

Read recorded mechanisms Open recursive mind map

How nutrients influence it

Every nutrient with a recorded effect on this component, credited to the nutrient that acted rather than the chapter that recorded it. Open a nutrient to see the findings and the conditions they were measured under.

How nutrients reach it in more than one step

Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.

Tracing routes…

What it does

Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.

Recorded relationships

What it acts on

  1. The copper chaperone for superoxide dismutase is necessary for expression of an active copper-bound superoxide dismutase in vivo despite the enzyme’s 6 femtomolar dissociation constant for copper, and purified Cu(I)-CCS was sufficient to activate the apo-enzyme but necessary only when free copper was strictly limited.

    Human copper chaperone for SOD1 / CCS → Activation of superoxide dismutase 1 by copper insertion source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_span
    {"source_cache": "artifacts/hbot-research/10221913.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8f6658330988f9b33331f49c1599734e070075a33fa8f32a3a6025d9f0fbc0b8", "start_char": 0, "end_char": 1176, "text_sha256": "8f6658330988f9b33331f49c1599734e070075a33fa8f32a3a6025d9f0fbc0b8"}
    experimental_model
    Yeast genetics with purified copper chaperone and apo-enzyme reconstitution
    exposure
    CCS deletion, elevated copper, and abrogation of metallothioneins
    limitations
    A yeast system with purified protein reconstitution. The free-copper conclusion is drawn from this system and its metallothionein manipulations.
    nutrient_topic
    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy
    organism
    Saccharomyces cerevisiae and purified proteins
    plain_language
    Copper is handed over by a dedicated carrier, not picked up loose.
    primary_references
    [hbot-p10221913] Undetectable intracellular free copper: the requirement of a copper chaperone for superoxide dismutase. (1999). https://pubmed.ncbi.nlm.nih.gov/10221913/ DOI: 10.1126/science.284.5415.805
    tissue_or_cell_type
    Cytosol
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 504–515

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Yeast genetics with purified copper chaperone and apo-enzyme reconstitution · source_derived_draft · unverified_draft

    ### hbot-ccs-required The copper chaperone for superoxide dismutase is necessary for expression of an active copper-bound superoxide dismutase in vivo despite the enzyme’s 6 femtomolar dissociation constant for copper, and purified Cu(I)-CCS was sufficient to activate the apo-enzyme but necessary only when free copper was strictly limited. Condition category: machinery_impairment nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Copper is handed over by a dedicated carrier, not picked up loose. organism: Saccharomyces cerevisiae and purified proteins tissue_or_cell_type: Cytosol experimental_model: Yeast genetics with purified copper chaperone and apo-enzyme reconstitution limitations: A yeast system with purified protein reconstitution. The free-copper conclusion is drawn from this system and its metallothionein manipulations. exposure: CCS deletion, elevated copper, and abrogation of metallothioneins evidence_span: {"source_cache": "artifacts/hbot-research/10221913.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8f6658330988f9b33331f49c1599734e070075a33fa8f32a3a6025d9f0fbc0b8", "start_char": 0, "end_char": 1176, "text_sha256": "8f6658330988f9b33331f49c1599734e070075a33fa8f32a3a6025d9f0fbc0b8"} [hbot-p10221913] Undetectable intracellular free copper: the requirement of a copper chaperone for superoxide dismutase. (1999). https://pubmed.ncbi.nlm.nih.gov/10221913/ DOI: 10.1126/science.284.5415.805
    Complete structured claim and evidence

  2. In the purified human protein system, CCS domain 1 was necessary for loading SOD1 with Cu(I).

    Human copper chaperone for SOD1 / CCS → Human copper-zinc superoxide dismutase / SOD1 source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    true
    experimental_model
    Purified human SOD1 and full-length, mutant or truncated human CCS; ESI-MS and NMR
    exposure
    Human CCS domain constructs and SOD1; ESI-MS and NMR.
    limitations
    Reconstituted human proteins studied in vitro; domain contributions do not imply CCS carries zinc to SOD1 or that zinc supplementation completes copper loading.
    nutrient_topic
    Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
    organism
    Homo sapiens
    plain_language
    SOD1 needs copper delivery as well as zinc binding.
    primary_references
    [zinc-enz-ccs-2012] Human superoxide dismutase 1 (hSOD1) maturation through interaction with human copper chaperone for SOD1 (hCCS). (2012). https://pubmed.ncbi.nlm.nih.gov/22869735/ DOI: 10.1073/pnas.1207493109
    tissue_or_cell_type
    Purified protein; cell-free assay

    Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 690–701

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human SOD1 and full-length, mutant or truncated human CCS; ESI-MS and NMR · source_derived_draft · unverified_draft

    ### zinc-enz-ccs-copper In the purified human protein system, CCS domain 1 was necessary for loading SOD1 with Cu(I). Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: SOD1 needs copper delivery as well as zinc binding. organism: Homo sapiens tissue_or_cell_type: Purified protein; cell-free assay experimental_model: Purified human SOD1 and full-length, mutant or truncated human CCS; ESI-MS and NMR limitations: Reconstituted human proteins studied in vitro; domain contributions do not imply CCS carries zinc to SOD1 or that zinc supplementation completes copper loading. exposure: Human CCS domain constructs and SOD1; ESI-MS and NMR. cross_nutrient: true [zinc-enz-ccs-2012] Human superoxide dismutase 1 (hSOD1) maturation through interaction with human copper chaperone for SOD1 (hCCS). (2012). https://pubmed.ncbi.nlm.nih.gov/22869735/ DOI: 10.1073/pnas.1207493109
    Complete structured claim and evidence

  3. Human CCS domain 3 catalyzed formation of the SOD1 Cys57-Cys146 disulfide through a transfer mechanism involving CCS Cys244 and Cys246.

    Human copper chaperone for SOD1 / CCS → Human copper-zinc superoxide dismutase / SOD1 source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    true
    experimental_model
    Purified human SOD1 and full-length, mutant or truncated human CCS; ESI-MS and NMR
    exposure
    Human CCS mutants/domain constructs examined by ESI-MS and NMR.
    limitations
    Reconstituted human proteins studied in vitro; domain contributions do not imply CCS carries zinc to SOD1 or that zinc supplementation completes copper loading.
    nutrient_topic
    Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
    organism
    Homo sapiens
    plain_language
    SOD1 maturation also requires forming a specific internal disulfide bond.
    primary_references
    [zinc-enz-ccs-2012] Human superoxide dismutase 1 (hSOD1) maturation through interaction with human copper chaperone for SOD1 (hCCS). (2012). https://pubmed.ncbi.nlm.nih.gov/22869735/ DOI: 10.1073/pnas.1207493109
    tissue_or_cell_type
    Purified protein; cell-free assay

    Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 716–727

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human SOD1 and full-length, mutant or truncated human CCS; ESI-MS and NMR · source_derived_draft · unverified_draft

    ### zinc-enz-ccs-disulfide Human CCS domain 3 catalyzed formation of the SOD1 Cys57-Cys146 disulfide through a transfer mechanism involving CCS Cys244 and Cys246. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: SOD1 maturation also requires forming a specific internal disulfide bond. organism: Homo sapiens tissue_or_cell_type: Purified protein; cell-free assay experimental_model: Purified human SOD1 and full-length, mutant or truncated human CCS; ESI-MS and NMR limitations: Reconstituted human proteins studied in vitro; domain contributions do not imply CCS carries zinc to SOD1 or that zinc supplementation completes copper loading. exposure: Human CCS mutants/domain constructs examined by ESI-MS and NMR. cross_nutrient: true [zinc-enz-ccs-2012] Human superoxide dismutase 1 (hSOD1) maturation through interaction with human copper chaperone for SOD1 (hCCS). (2012). https://pubmed.ncbi.nlm.nih.gov/22869735/ DOI: 10.1073/pnas.1207493109
    Complete structured claim and evidence

  4. Human CCS domain 2 promoted the CCS-SOD1 heterodimer interaction required for copper loading in the in-vitro study.

    Human copper chaperone for SOD1 / CCS → Human copper-zinc superoxide dismutase / SOD1 source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    true
    experimental_model
    Purified human SOD1 and full-length, mutant or truncated human CCS; ESI-MS and NMR
    exposure
    Full-length and domain-truncated human CCS with human SOD1.
    limitations
    Reconstituted human proteins studied in vitro; domain contributions do not imply CCS carries zinc to SOD1 or that zinc supplementation completes copper loading.
    nutrient_topic
    Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
    organism
    Homo sapiens
    plain_language
    The copper-delivery protein first has to engage SOD1.
    primary_references
    [zinc-enz-ccs-2012] Human superoxide dismutase 1 (hSOD1) maturation through interaction with human copper chaperone for SOD1 (hCCS). (2012). https://pubmed.ncbi.nlm.nih.gov/22869735/ DOI: 10.1073/pnas.1207493109
    tissue_or_cell_type
    Purified protein; cell-free assay

    Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 703–714

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human SOD1 and full-length, mutant or truncated human CCS; ESI-MS and NMR · source_derived_draft · unverified_draft

    ### zinc-enz-ccs-recognition Human CCS domain 2 promoted the CCS-SOD1 heterodimer interaction required for copper loading in the in-vitro study. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: The copper-delivery protein first has to engage SOD1. organism: Homo sapiens tissue_or_cell_type: Purified protein; cell-free assay experimental_model: Purified human SOD1 and full-length, mutant or truncated human CCS; ESI-MS and NMR limitations: Reconstituted human proteins studied in vitro; domain contributions do not imply CCS carries zinc to SOD1 or that zinc supplementation completes copper loading. exposure: Full-length and domain-truncated human CCS with human SOD1. cross_nutrient: true [zinc-enz-ccs-2012] Human superoxide dismutase 1 (hSOD1) maturation through interaction with human copper chaperone for SOD1 (hCCS). (2012). https://pubmed.ncbi.nlm.nih.gov/22869735/ DOI: 10.1073/pnas.1207493109
    Complete structured claim and evidence

  5. Coexpression of CCS increased Cu(I) incorporation into SOD1 after Cu(II) exposure in zinc-supplemented HEK293T cells; at higher expression the Cu(I),Zn-SOD1:E,Zn-SOD1 ratio reached about 1:1.

    Human copper chaperone for SOD1 / CCS → Human copper-zinc superoxide dismutase / SOD1 source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    true
    experimental_model
    Transient expression of human SOD1 and CCS in human HEK293T cells; in-cell NMR
    exposure
    10 µM ZnSO4 in expression medium; 100 µM CuCl2 added after 48 h and incubated 24 h.
    limitations
    HEK293T cells overexpressed SOD1/CCS above endogenous levels; these medium concentrations are experimental exposures, not dietary targets. Copper transfer and disulfide oxidation need not occur in a fixed coupled step in every cellular context.
    nutrient_topic
    Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
    organism
    Homo sapiens
    plain_language
    The copper chaperone increased copper loading into zinc-containing SOD1.
    primary_references
    [zinc-enz-sod1-live2013] Atomic-resolution monitoring of protein maturation in live human cells by NMR. (2013). https://pubmed.ncbi.nlm.nih.gov/23455544/ DOI: 10.1038/nchembio.1202
    tissue_or_cell_type
    Human HEK293T cytoplasm

    Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 742–753

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transient expression of human SOD1 and CCS in human HEK293T cells; in-cell NMR · source_derived_draft · unverified_draft

    ### zinc-enz-sod1-copper-loading Coexpression of CCS increased Cu(I) incorporation into SOD1 after Cu(II) exposure in zinc-supplemented HEK293T cells; at higher expression the Cu(I),Zn-SOD1:E,Zn-SOD1 ratio reached about 1:1. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: The copper chaperone increased copper loading into zinc-containing SOD1. organism: Homo sapiens tissue_or_cell_type: Human HEK293T cytoplasm experimental_model: Transient expression of human SOD1 and CCS in human HEK293T cells; in-cell NMR limitations: HEK293T cells overexpressed SOD1/CCS above endogenous levels; these medium concentrations are experimental exposures, not dietary targets. Copper transfer and disulfide oxidation need not occur in a fixed coupled step in every cellular context. exposure: 10 µM ZnSO4 in expression medium; 100 µM CuCl2 added after 48 h and incubated 24 h. cross_nutrient: true [zinc-enz-sod1-live2013] Atomic-resolution monitoring of protein maturation in live human cells by NMR. (2013). https://pubmed.ncbi.nlm.nih.gov/23455544/ DOI: 10.1038/nchembio.1202
    Complete structured claim and evidence

  6. In zinc-supplemented HEK293T cells, CCS coexpression promoted SOD1 disulfide oxidation without detectable additional SOD1 copper loading.

    Human copper chaperone for SOD1 / CCS → Zinc-bound disulfide-reduced human SOD1 source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    true
    experimental_model
    Transient expression of human SOD1 and CCS in human HEK293T cells; in-cell NMR
    exposure
    10 µM ZnSO4 and SOD1/CCS coexpression; no added CuCl2 in this comparison.
    limitations
    HEK293T cells overexpressed SOD1/CCS above endogenous levels; these medium concentrations are experimental exposures, not dietary targets. Copper transfer and disulfide oxidation need not occur in a fixed coupled step in every cellular context. This is not proof that all copper is absent from the cell.
    nutrient_topic
    Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
    organism
    Homo sapiens
    plain_language
    CCS can help form the SOD1 disulfide before copper is inserted.
    primary_references
    [zinc-enz-sod1-live2013] Atomic-resolution monitoring of protein maturation in live human cells by NMR. (2013). https://pubmed.ncbi.nlm.nih.gov/23455544/ DOI: 10.1038/nchembio.1202
    tissue_or_cell_type
    Human HEK293T cytoplasm

    Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 755–766

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transient expression of human SOD1 and CCS in human HEK293T cells; in-cell NMR · source_derived_draft · unverified_draft

    ### zinc-enz-sod1-disulfide-independent In zinc-supplemented HEK293T cells, CCS coexpression promoted SOD1 disulfide oxidation without detectable additional SOD1 copper loading. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: CCS can help form the SOD1 disulfide before copper is inserted. organism: Homo sapiens tissue_or_cell_type: Human HEK293T cytoplasm experimental_model: Transient expression of human SOD1 and CCS in human HEK293T cells; in-cell NMR limitations: HEK293T cells overexpressed SOD1/CCS above endogenous levels; these medium concentrations are experimental exposures, not dietary targets. Copper transfer and disulfide oxidation need not occur in a fixed coupled step in every cellular context. This is not proof that all copper is absent from the cell. exposure: 10 µM ZnSO4 and SOD1/CCS coexpression; no added CuCl2 in this comparison. cross_nutrient: true [zinc-enz-sod1-live2013] Atomic-resolution monitoring of protein maturation in live human cells by NMR. (2013). https://pubmed.ncbi.nlm.nih.gov/23455544/ DOI: 10.1038/nchembio.1202
    Complete structured claim and evidence

In the sources

Preserved passages that mention this component, quoted exactly. Open one to read it in context.

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