id: P00044
gene_symbol: CYC1
aliases:
- YJR048W
- J1653
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:559292
  label: Saccharomyces cerevisiae
description: Cytochrome c isoform 1 is a small heme-containing electron carrier 
  protein central to mitochondrial aerobic respiration. It functions as the 
  critical link between Complex III and Complex IV in the electron transport 
  chain. CYC1 is predominantly expressed during aerobic growth, with its 
  heme-bound iron center accepting electrons from Complex III and donating them 
  to Complex IV, driving oxidative phosphorylation and ATP synthesis. Secondary 
  roles include interaction with cardiolipin and involvement in apoptotic 
  signaling pathways.
core_functions:
- description: Electron transfer between Complex III and Complex IV in 
    mitochondrial electron transport chain via redox cycling of heme-bound iron 
    center
  molecular_function:
    id: GO:0009055
    label: electron transfer activity
  directly_involved_in:
  - id: GO:0006122
    label: mitochondrial electron transport, ubiquinol to cytochrome c
  - id: GO:0006123
    label: mitochondrial electron transport, cytochrome c to oxygen
  locations:
  - id: GO:0005758
    label: mitochondrial intermembrane space
  supported_by:
  - reference_id: file:yeast/CYC1/CYC1-deep-research-falcon.md
    supporting_text: >-
      CYC1 encodes iso-1-cytochrome c, the major soluble c-type cytochrome in
      yeast mitochondria, shuttling electrons from complex III to complex IV.
existing_annotations:
- term:
    id: GO:0009055
    label: electron transfer activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: Cytochrome c is a core electron carrier protein that shuttles 
      electrons between Complex III and Complex IV in the mitochondrial electron
      transport chain. The IBA evidence is appropriate for this molecular 
      function annotation.
    action: ACCEPT
    reason: This is the quintessential function of cytochrome c. UniProt 
      describes CYC1 as an electron carrier protein where the heme group accepts
      electrons from cytochrome c1 and transfers them to cytochrome c oxidase. 
      Both IDA evidence from PMID:7851399 and PMID:18975895 directly support 
      electron transfer activity through kinetic measurements and 
      electrochemical analysis. IBA annotation is appropriate given the highly 
      conserved nature of this function across cytochrome c family members 
      (PTHR11961). This represents a core primary metabolic role.
    supported_by:
    - reference_id: PMID:7851399
      supporting_text: The purified enzyme had a turnover number of 1500 s-1 and
        the ionic-strength dependence of the Km value for cytochrome-c was 
        similar to that described for other preparations of cytochrome-c 
        oxidase.
    - reference_id: PMID:18975895
      supporting_text: The apparent electron transfer rate constants of YCC on 
        MUA/MU and MU/MH at pH 6.0 were determined to be 8 and 18 s(-1), 
        respectively.
    - reference_id: file:yeast/CYC1/CYC1-deep-research-falcon.md
      supporting_text: >-
        Cyc1p's precise biochemical role is single-electron transfer between
        the bc1 complex and cytochrome c oxidase.
- term:
    id: GO:0006122
    label: mitochondrial electron transport, ubiquinol to cytochrome c
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: Cytochrome c is the direct electron acceptor from Complex III, 
      receiving electrons from ubiquinol and transferring them to Complex IV. 
      This biological process annotation accurately describes CYC1's 
      participation in the electron transport chain.
    action: ACCEPT
    reason: This annotation correctly identifies CYC1's specific role in 
      mitochondrial electron transport. CYC1 is the electron acceptor from 
      ubiquinol-cytochrome c oxidoreductase (Complex III, the cytochrome bc1 
      complex). UniProt FUNCTION states CYC1 accepts electrons from the heme 
      group of cytochrome c1 of ubiquinol-cytochrome c oxidoreductase. IDA 
      evidence from PMID:7851399 characterizes the kinetic properties of 
      cytochrome c as a substrate, demonstrating this electron transport step. 
      This is a core primary metabolic function.
    supported_by:
    - reference_id: PMID:7851399
      supporting_text: The purified enzyme had a turnover number of 1500 s-1 and
        the ionic-strength dependence of the Km value for cytochrome-c was 
        similar to that described for other preparations of cytochrome-c 
        oxidase.
- term:
    id: GO:0005758
    label: mitochondrial intermembrane space
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: Cytochrome c is localized to the mitochondrial intermembrane space 
      (IMS), the aqueous compartment between the inner and outer mitochondrial 
      membranes, where it functions as an electron shuttle between 
      membrane-bound protein complexes.
    action: ACCEPT
    reason: This is the correct cellular compartment localization for CYC1. 
      UniProt explicitly states SUBCELLULAR LOCATION is Mitochondrion 
      intermembrane space. PMID:9866716 describes the purification of 
      intermembrane space fractions with cytochrome c as a key marker protein. 
      IBA annotation is appropriate given the universal localization of 
      cytochrome c to the IMS across eukaryotes.
    supported_by:
    - reference_id: PMID:9866716
      supporting_text: "Two distinct fractions were obtained: a soluble IMS with cytochrome
        b2 as key marker and a salt-extractable IMS with cytochrome c as key marker."
- term:
    id: GO:0006123
    label: mitochondrial electron transport, cytochrome c to oxygen
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: Cytochrome c donates electrons to Complex IV (cytochrome c 
      oxidase), where oxygen serves as the final electron acceptor. This 
      biological process annotation describes the second major step of CYC1's 
      participation in the electron transport chain.
    action: ACCEPT
    reason: This annotation correctly identifies CYC1's specific role as the 
      electron donor to cytochrome c oxidase (Complex IV). UniProt states CYC1 
      transfers electrons to the dinuclear copper A center of the COX2 subunit 
      of cytochrome oxidase, the final protein carrier in the mitochondrial 
      electron-transport chain. PMID:7851399 provides kinetic evidence for this 
      interaction. IBA annotation is appropriate. This is a core primary 
      metabolic function.
    supported_by:
    - reference_id: PMID:7851399
      supporting_text: The purified enzyme had a turnover number of 1500 s-1 and
        the ionic-strength dependence of the Km value for cytochrome-c was 
        similar to that described for other preparations of cytochrome-c 
        oxidase.
- term:
    id: GO:0005758
    label: mitochondrial intermembrane space
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: IEA annotation of mitochondrial intermembrane space localization 
      derived from automated sequence analysis and subcellular location 
      databases. Consistent with experimental evidence.
    action: ACCEPT
    reason: IEA annotation correctly predicts CYC1 localization based on UniProt
      subcellular location annotations. This is fully supported by experimental 
      IDA evidence (PMID:9866716). Redundant with other mitochondrial 
      intermembrane space annotations but acceptable as it represents automated 
      annotation pipelines that independently confirm the localization.
    supported_by:
    - reference_id: PMID:9866716
      supporting_text: "Two distinct fractions were obtained: a soluble IMS with cytochrome
        b2 as key marker and a salt-extractable IMS with cytochrome c as key marker."
- term:
    id: GO:0006122
    label: mitochondrial electron transport, ubiquinol to cytochrome c
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: IEA annotation by ARBA machine learning model predicting CYC1 
      involvement in ubiquinol-to-cytochrome c electron transport. Consistent 
      with experimental evidence and core function.
    action: ACCEPT
    reason: IEA annotation correctly predicts this core metabolic process based 
      on sequence homology and association rules. Fully consistent with 
      experimental IDA evidence (PMID:7851399) and IBA annotations. ARBA models 
      are trained on well-characterized annotations, and this prediction is 
      mechanistically sound for the cytochrome c family.
    supported_by:
    - reference_id: PMID:7851399
      supporting_text: The purified enzyme had a turnover number of 1500 s-1 and
        the ionic-strength dependence of the Km value for cytochrome-c was 
        similar to that described for other preparations of cytochrome-c 
        oxidase.
- term:
    id: GO:0006123
    label: mitochondrial electron transport, cytochrome c to oxygen
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: IEA annotation by ARBA machine learning model predicting CYC1 
      involvement in cytochrome c-to-oxygen electron transport. Consistent with 
      experimental evidence and core function.
    action: ACCEPT
    reason: IEA annotation correctly predicts this core metabolic process based 
      on sequence homology and association rules. Fully consistent with 
      experimental IDA evidence (PMID:7851399) and IBA annotations. ARBA models 
      work well for well-characterized metabolic processes like the electron 
      transport chain.
    supported_by:
    - reference_id: PMID:7851399
      supporting_text: The purified enzyme had a turnover number of 1500 s-1 and
        the ionic-strength dependence of the Km value for cytochrome-c was 
        similar to that described for other preparations of cytochrome-c 
        oxidase.
- term:
    id: GO:0009055
    label: electron transfer activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: IEA annotation of electron transfer activity derived from combined 
      automated methods and InterPro domain analysis. Represents predicted 
      molecular function based on heme-binding domain membership.
    action: ACCEPT
    reason: IEA annotation correctly predicts electron transfer activity based 
      on InterPro domain membership (IPR002327, IPR009056, IPR036909 - 
      cytochrome c domains). This is the most direct inference from sequence 
      structure. Fully supported by multiple IDA evidence entries. IEA based on 
      protein family membership is appropriate for such well-characterized 
      functions.
    supported_by:
    - reference_id: PMID:18975895
      supporting_text: The apparent electron transfer rate constants of YCC on 
        MUA/MU and MU/MH at pH 6.0 were determined to be 8 and 18 s(-1), 
        respectively.
- term:
    id: GO:0020037
    label: heme binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: Heme binding activity inferred from InterPro domain analysis of 
      cytochrome c protein structure. CYC1 contains covalent heme c group 
      essential for electron transfer.
    action: ACCEPT
    reason: IEA annotation based on InterPro domain membership correctly 
      identifies heme binding as a molecular function of CYC1. UniProt 
      explicitly states CYC1 binds 1 heme c group covalently per subunit, with 
      covalent binding at His-18 and His-81 and axial iron coordination by 
      His-86 and Met-80. This molecular function is fundamental to the redox 
      chemistry enabling electron transfer. IEA from protein family annotation 
      is appropriate for this well-characterized feature.
    supported_by:
    - reference_id: PMID:18390544
      supporting_text: Structure of complex III with bound cytochrome c in 
        reduced state and definition of a minimal core interface for electron 
        transfer.
- term:
    id: GO:0022904
    label: respiratory electron transport chain
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: Respiratory electron transport chain participation inferred from 
      UniProtKB keyword mapping. CYC1 is a component of the electron transport 
      chain that couples redox reactions to ATP synthesis.
    action: ACCEPT
    reason: IEA annotation based on UniProtKB-KW (keyword) mapping correctly 
      identifies CYC1 as a component of the respiratory electron transport 
      chain. UniProt keywords include Respiratory chain and Electron transport, 
      reflecting CYC1's role as a central hub between Complexes III and IV. This
      is appropriate for identifying participation in the broader pathway 
      context while more specific electron transport processes are annotated 
      separately.
    supported_by:
    - reference_id: PMID:7851399
      supporting_text: The purified enzyme had a turnover number of 1500 s-1 and
        the ionic-strength dependence of the Km value for cytochrome-c was 
        similar to that described for other preparations of cytochrome-c 
        oxidase.
- term:
    id: GO:0046872
    label: metal ion binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: Metal ion binding inferred from UniProtKB keyword mapping (KW-0479)
      reflecting the iron coordination in CYC1's heme c group. The Fe center is 
      essential for redox cycling.
    action: ACCEPT
    reason: IEA annotation based on UniProtKB keyword mapping correctly 
      identifies metal ion binding as a molecular function. CYC1 binds iron (Fe)
      as the central atom of heme c through axial coordination by His-86 and 
      Met-80, as documented in UniProt feature annotation. This is a more 
      general annotation than GO:0020037 (heme binding) but appropriately 
      identifies the metal cofactor requirement. For a protein with such 
      well-characterized iron coordination, IEA from keyword mapping is 
      justified.
    supported_by:
    - reference_id: PMID:18390544
      supporting_text: Structure of complex III with bound cytochrome c in 
        reduced state and definition of a minimal core interface for electron 
        transfer.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15071191
  review:
    summary: Cytochrome c peroxidase (CCP) interaction demonstrated through 
      structural and kinetic studies of the electron transfer complex. This 
      represents a secondary protein-protein interaction not central to CYC1's 
      primary metabolic role.
    action: MARK_AS_OVER_ANNOTATED
    reason: While CYC1 does interact with cytochrome c peroxidase (CCP) as 
      demonstrated by PMID:15071191, the generic term protein binding is not 
      informative and represents an over-annotation. The CCP interaction is a 
      non-physiological interaction used for research purposes. More 
      importantly, the physiological protein interactions with Complex III 
      (cytochrome c1) and Complex IV (cytochrome c oxidase subunit IV) are far 
      more significant but already captured by the electron transport process 
      annotations. A vague protein binding term obscures rather than clarifies 
      the functional role. For a protein with such well-defined biochemistry, 
      more specific binding terms would be preferable if capturing this 
      interaction is important. CCP interaction should not be prioritized over 
      the core metabolic functions.
    supported_by:
    - reference_id: PMID:15071191
      supporting_text: A specific covalently cross-linked complex between redox 
        partners yeast cytochrome c peroxidase (CCP) and cytochrome c (cyt. c) 
        has been made by engineering cysteines into CCP and cyt. c that form an 
        intermolecular disulfide bond in high yield.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15339156
  review:
    summary: Electron transfer between cytochrome c and cytochrome c peroxidase 
      in single crystals. IPI evidence for protein-protein interaction with CCP.
    action: MARK_AS_OVER_ANNOTATED
    reason: PMID:15339156 studies electron transfer kinetics between CYC1 and 
      CCP in single crystal systems, demonstrating physical interaction. 
      However, as with PMID:15071191, this CCP interaction is not central to 
      CYC1's primary physiological role. The generic term protein binding is 
      uninformative and represents an over-annotation. The critical 
      physiological interactions are with Complex III and Complex IV proteins, 
      already captured by process annotations. CCP is a research tool for 
      studying electron transfer kinetics, not a core functional partner. This 
      annotation should be deprioritized in favor of core metabolic functions.
    supported_by:
    - reference_id: PMID:15339156
      supporting_text: "Electron transfer between cytochrome c and cytochome c peroxidase
        in single crystals"
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17146057
  review:
    summary: Solution structure and dynamics of the complex between cytochrome c
      and cytochrome c peroxidase by paramagnetic NMR spectroscopy. IPI evidence
      for protein-protein interaction.
    action: MARK_AS_OVER_ANNOTATED
    reason: PMID:17146057 characterizes the complex between CYC1 and CCP using 
      structural biology methods. However, this represents a non-physiological 
      research interaction rather than a core functional interaction. The CCP is
      not a natural substrate or cofactor partner in yeast metabolism. The 
      generic term protein binding is uninformative. More significant 
      physiological protein interactions (Complex III and IV) are already 
      represented in the electron transport process annotations. This annotation
      over-represents peripheral research interactions at the expense of core 
      functions.
    supported_by:
    - reference_id: PMID:17146057
      supporting_text: Solution structure and dynamics of the complex between 
        cytochrome c and cytochrome c peroxidase determined by paramagnetic NMR.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24726731
  review:
    summary: Cytochrome c peroxidase and cytochrome c encounter complex 
      characterized through structural and kinetic studies.
    action: MARK_AS_OVER_ANNOTATED
    reason: PMID:24726731 characterizes the CCP-cytochrome c encounter complex. 
      However, this remains a non-physiological research interaction with CCP, 
      not a core functional partner. The generic protein binding term lacks 
      specificity and represents peripheral rather than core function. CCP 
      interactions, while scientifically interesting for studying electron 
      transfer mechanisms, should not dominate the annotation profile of CYC1. 
      The primary physiological interactions with Complex III (cytochrome c1) 
      and Complex IV are more important and already captured in process 
      annotations. This is over-annotation that dilutes focus on core metabolic 
      role.
    supported_by:
    - reference_id: PMID:24726731
      supporting_text: "The cytochrome c peroxidase and cytochrome c encounter complex:
        the other side of the story."
- term:
    id: GO:1901612
    label: cardiolipin binding
  evidence_type: IDA
  original_reference_id: PMID:30182710
  review:
    summary: CYC1 binds to cardiolipin (CL), an anionic mitochondrial lipid, 
      through electrostatic interactions mediated by lysine residues at site A. 
      This interaction is relevant during apoptosis when CYC1 oxidizes CL.
    action: KEEP_AS_NON_CORE
    reason: PMID:30182710 provides direct experimental evidence (IDA) that CYC1 
      binds cardiolipin at multiple lysine residues (positions 72, 73, 86, 87). 
      Cardiolipin binding is well-documented and mechanistically characterized. 
      However, this represents a secondary function associated with apoptotic 
      signaling rather than the primary aerobic metabolic role. In yeast under 
      normal aerobic growth, cardiolipin binding relates to apoptotic peroxidase
      activity, not the primary electron transport function. For a primarily 
      metabolic protein, this should be retained as a supported annotation but 
      marked as non-core to distinguish from the central electron transport 
      functions. The apoptotic role of CYC1 is less central in yeast compared to
      mammals.
    supported_by:
    - reference_id: PMID:30182710
      supporting_text: A set of single, double, and quadruple lysine to alanine 
        variants of yeast iso-1-cytochrome c, at sequence positions 72, 73, 86, 
        and 87, show that all contribute to the site A-mediated interaction with
        CL.
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: HDA
  original_reference_id: PMID:16823961
  review:
    summary: CYC1 is a mitochondrial protein identified through large-scale 
      mitochondrial proteomics analysis. HDA (homology-derived assertion) 
      evidence from PMID:16823961 contributes to broader cellular component 
      annotation.
    action: ACCEPT
    reason: HDA annotation correctly identifies CYC1 as a mitochondrial protein.
      PMID:16823961 is a large-scale proteomic analysis of the yeast 
      mitochondrial proteome that identified CYC1 among intermembrane space 
      proteins. However, GO:0005758 (mitochondrial intermembrane space) is more 
      specific and informative than the broader GO:0005739 (mitochondrion). Both
      are technically correct, but the more specific localization is more 
      useful. HDA annotation is appropriate for broad compartment 
      classification, though the intermembrane space annotations are more 
      precise and should be prioritized.
    supported_by:
    - reference_id: PMID:16823961
      supporting_text: "Toward the complete yeast mitochondrial proteome: multidimensional
        separation techniques for mitochondrial proteomics"
- term:
    id: GO:0005758
    label: mitochondrial intermembrane space
  evidence_type: IDA
  original_reference_id: PMID:9866716
  review:
    summary: Direct experimental evidence that CYC1 is localized to the 
      mitochondrial intermembrane space. PMID:9866716 describes the purification
      of distinct IMS fractions with CYC1 as a key marker protein.
    action: ACCEPT
    reason: IDA annotation provides direct experimental evidence for CYC1 
      localization. PMID:9866716 is a landmark study that fractionally purified 
      mitochondrial intermembrane space content, identifying CYC1 as a defining 
      marker of the salt-extractable IMS fraction. This is the most specific and
      accurate cellular localization, superior to the broader mitochondrion 
      (GO:0005739) annotation. This is a core, well-supported annotation of 
      CYC1's subcellular localization.
    supported_by:
    - reference_id: PMID:9866716
      supporting_text: "Two distinct fractions were obtained: a soluble IMS with cytochrome
        b2 as key marker and a salt-extractable IMS with cytochrome c as key marker."
- term:
    id: GO:0006122
    label: mitochondrial electron transport, ubiquinol to cytochrome c
  evidence_type: IDA
  original_reference_id: PMID:7851399
  review:
    summary: Direct kinetic and biochemical evidence that CYC1 functions in 
      mitochondrial electron transport from ubiquinol to the final electron 
      acceptor at Complex IV. PMID:7851399 characterizes kinetic properties of 
      cytochrome c as a substrate for cytochrome c oxidase.
    action: ACCEPT
    reason: IDA annotation provides direct experimental evidence for CYC1's role
      in electron transport. PMID:7851399 is a seminal biochemical study 
      characterizing the purified eleven-subunit cytochrome c oxidase complex 
      with kinetic analysis of cytochrome c as a substrate. The demonstrated Km 
      values and turnover numbers (1500 s-1) represent direct functional 
      evidence that CYC1 participates in this electron transport step. This is a
      core primary metabolic function with the highest quality evidence.
    supported_by:
    - reference_id: PMID:7851399
      supporting_text: The purified enzyme had a turnover number of 1500 s-1 and
        the ionic-strength dependence of the Km value for cytochrome-c was 
        similar to that described for other preparations of cytochrome-c 
        oxidase.
- term:
    id: GO:0006123
    label: mitochondrial electron transport, cytochrome c to oxygen
  evidence_type: IDA
  original_reference_id: PMID:7851399
  review:
    summary: Direct kinetic and biochemical evidence that CYC1 functions in 
      mitochondrial electron transport from cytochrome c to the final electron 
      acceptor (oxygen). PMID:7851399 characterizes kinetic properties of 
      cytochrome c oxidase interaction with cytochrome c.
    action: ACCEPT
    reason: IDA annotation provides direct experimental evidence for CYC1's role
      as electron donor to cytochrome c oxidase. PMID:7851399 demonstrates 
      quantitatively that cytochrome c is a substrate for Complex IV (cytochrome
      c oxidase), with measured kinetic parameters reflecting true enzyme 
      kinetics. This electron transfer to oxygen is the final step in the 
      respiratory chain and a core primary metabolic function of CYC1. This is 
      one of the most important functional annotations for this protein.
    supported_by:
    - reference_id: PMID:7851399
      supporting_text: The purified enzyme had a turnover number of 1500 s-1 and
        the ionic-strength dependence of the Km value for cytochrome-c was 
        similar to that described for other preparations of cytochrome-c 
        oxidase.
- term:
    id: GO:0009055
    label: electron transfer activity
  evidence_type: IDA
  original_reference_id: PMID:18975895
  review:
    summary: Direct electrochemical evidence demonstrating electron transfer 
      activity of yeast CYC1. PMID:18975895 measures electron transfer rate 
      constants using surface-enhanced resonance Raman spectroscopy.
    action: ACCEPT
    reason: IDA annotation provides direct biophysical evidence for CYC1's 
      electron transfer activity. PMID:18975895 employs sophisticated 
      electrochemical methods to measure electron transfer rate constants (8-18 
      s-1) and demonstrates that protein reorientation is rate-limiting for 
      interfacial electron transfer. This represents direct, quantitative 
      molecular evidence of the electron transfer mechanism central to CYC1's 
      function. This is a core primary molecular function with excellent 
      experimental support.
    supported_by:
    - reference_id: PMID:18975895
      supporting_text: The apparent electron transfer rate constants of YCC on 
        MUA/MU and MU/MH at pH 6.0 were determined to be 8 and 18 s(-1), 
        respectively.
- term:
    id: GO:0009055
    label: electron transfer activity
  evidence_type: IDA
  original_reference_id: PMID:7851399
  review:
    summary: Direct biochemical evidence for electron transfer activity through 
      kinetic characterization of cytochrome c as a functional substrate in 
      electron transport chain complexes.
    action: ACCEPT
    reason: IDA annotation provides direct biochemical evidence for electron 
      transfer activity from a landmark kinetic analysis. PMID:7851399 
      demonstrates that cytochrome c functions as a true kinetic substrate for 
      both Complex III (ubiquinol-cytochrome c oxidoreductase) and Complex IV 
      (cytochrome c oxidase), with measured turnover numbers and Km values 
      reflecting physiological kinetics. This dual IDA evidence from different 
      experimental approaches (electrochemistry and enzyme kinetics) provides 
      robust support for this fundamental molecular function.
    supported_by:
    - reference_id: PMID:7851399
      supporting_text: The purified enzyme had a turnover number of 1500 s-1 and
        the ionic-strength dependence of the Km value for cytochrome-c was 
        similar to that described for other preparations of cytochrome-c 
        oxidase.
references:
- id: file:yeast/CYC1/CYC1-deep-research-falcon.md
  title: Falcon deep research report for CYC1
  findings:
  - statement: >-
      Falcon supports CYC1 as yeast iso-1-cytochrome c, the principal mobile
      electron carrier between respiratory complexes III and IV.
    supporting_text: >-
      Cyc1p's precise biochemical role is single-electron transfer between the
      bc1 complex and cytochrome c oxidase.
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with 
    GO terms
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000043
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning 
    models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:15071191
  title: Crystal structure and characterization of a cytochrome c 
    peroxidase-cytochrome c site-specific cross-link.
  findings: []
- id: PMID:15339156
  title: Electron transfer between cytochrome c and cytochome c peroxidase in 
    single crystals.
  findings: []
- id: PMID:16823961
  title: Toward the complete yeast mitochondrial proteome - multidimensional 
    separation techniques for mitochondrial proteomics.
  findings: []
- id: PMID:17146057
  title: Solution structure and dynamics of the complex between cytochrome c and
    cytochrome c peroxidase determined by paramagnetic NMR.
  findings: []
- id: PMID:18390544
  title: Structure of complex III with bound cytochrome c in reduced state and 
    definition of a minimal core interface for electron transfer.
  findings: []
- id: PMID:18975895
  title: Gated electron transfer of yeast iso-1 cytochrome c on self-assembled 
    monolayer-coated electrodes.
  findings: []
- id: PMID:24726731
  title: The cytochrome c peroxidase and cytochrome c encounter complex - the 
    other side of the story.
  findings: []
- id: PMID:30182710
  title: Electrostatic Constituents of the Interaction of Cardiolipin with Site 
    A of Cytochrome c.
  findings: []
- id: PMID:7851399
  title: Kinetic properties and ligand binding of the eleven-subunit 
    cytochrome-c oxidase from Saccharomyces cerevisiae isolated with a novel 
    large-scale purification method.
  findings: []
- id: PMID:9866716
  title: The yeast mitochondrial intermembrane space - purification and analysis
    of two distinct fractions.
  findings: []
proposed_new_terms: []
suggested_questions:
- question: Does CYC1 have distinct redox potential states in different 
    microenvironments (membrane-bound vs. soluble) that affect electron transfer
    efficiency?
- question: What is the functional significance of CYC1's methylation at lysines
    78-79 in regulating its apoptotic signaling role versus its metabolic role?
- question: Are there regulatory post-translational modifications of CYC1 that 
    modulate its interaction with Complex III or Complex IV during metabolic 
    transitions?
suggested_experiments:
- description: Measure electron transfer kinetics between purified Complex III 
    and Complex IV using reconstituted CYC1 in liposomes to establish turnover 
    rates in a membrane context
- description: Characterize how mutations affecting cardiolipin-binding lysines 
    (K72, K73, K86, K87) impact aerobic growth and respiration rates
- description: Investigate whether CYC1 undergoes conformational changes upon 
    binding to cardiolipin that influence its peroxidase activity during 
    apoptosis