id: P38117
gene_symbol: ETFB
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: ETFB is the beta subunit of the electron-transfer flavoprotein (ETF),
  a soluble mitochondrial-matrix heterodimer (ETFA + ETFB) that carries a single FAD
  and one AMP. ETF is the common electron acceptor for a family of matrix FAD-dependent
  dehydrogenases acting in fatty-acid beta-oxidation, amino-acid catabolism, and choline
  degradation (including the acyl-CoA dehydrogenases, glutaryl-CoA dehydrogenase, and
  sarcosine dehydrogenase). Electrons abstracted from these dehydrogenases reduce the
  ETF-bound FAD, and ETF relays them to the inner-membrane ETF-ubiquinone oxidoreductase
  (ETFDH) and thence to the respiratory-chain ubiquinone pool, making ETF a third major
  electron entry point to ubiquinone alongside complexes I and II. The beta subunit
  provides the AMP-binding site (structural) and a solvent-exposed recognition loop that
  docks the partner dehydrogenases, positioning them for interprotein electron transfer.
  Biallelic loss-of-function variants in ETFB (like those in ETFA and ETFDH) cause multiple
  acyl-CoA dehydrogenase deficiency (MADD) / glutaric acidemia type II.
alternative_products:
- name: '1'
  id: P38117-1
- name: '2'
  id: P38117-2
  sequence_note: VSP_017850
existing_annotations:
- term:
    id: GO:0009055
    label: electron transfer activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: Phylogenetic (PAN-GO) inference that ETFB enables electron transfer activity.
      This is the core molecular function of the ETF heterodimer, in which the beta
      subunit is an integral partner. Well supported by structural, biochemical, and
      disease evidence.
    action: ACCEPT
    reason: Electron transfer activity is the defining, experimentally established molecular
      function of the ETF complex (accepting electrons from matrix dehydrogenases and
      relaying them to ETFDH), and ETFB is an obligate structural/recognition component
      of the electron-transferring heterodimer. The IBA is consistent with the human
      IDA/TAS annotations below.
    supported_by:
    - reference_id: PMID:8962055
      supporting_text: electron shuttles between primary flavoprotein dehydrogenases involved in
    - reference_id: PMID:25416781
      supporting_text: "ETF acts as a mobile electron carrier that shuttles electrons between several FAD-containing dehydrogenases present in the mitochondrial matrix and the membrane-bound ETF:quinone oxidoreductase"
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: Phylogenetic inference that ETFB is active in the mitochondrion. Correct
      but less precise than the mitochondrial matrix localization directly demonstrated
      for the human protein.
    action: KEEP_AS_NON_CORE
    reason: ETFB is a bona fide mitochondrial protein, but the specific and experimentally
      supported location is the mitochondrial matrix (GO:0005759, IDA below). Retain
      the broader mitochondrion term as non-core; the matrix term captures the precise
      location.
    supported_by:
    - reference_id: PMID:8504797
      supporting_text: contains the information necessary to reach the mitochondrial matrix
- term:
    id: GO:0033539
    label: fatty acid beta-oxidation using acyl-CoA dehydrogenase
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: Phylogenetic inference that ETFB is involved in fatty-acid beta-oxidation
      via acyl-CoA dehydrogenases. ETF is the obligatory electron acceptor for the
      matrix acyl-CoA dehydrogenases of fatty-acid beta-oxidation, so this is a core
      biological process for the gene.
    action: ACCEPT
    reason: Fatty-acid beta-oxidation via acyl-CoA dehydrogenases depends on ETF accepting
      electrons from those dehydrogenases; loss of ETFB blocks this flux and causes MADD.
      Consistent with the human IDA annotation (PMID:25416781) and disease evidence
      (PMID:7912128).
    supported_by:
    - reference_id: PMID:25416781
      supporting_text: "e.g. medium chain acyl-CoA dehydrogenase (MCAD), are involved in β-oxidation of fatty acids"
    - reference_id: PMID:7912128
      supporting_text: cDNA complements the genetic defect and restores the beta-oxidation flux to
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: located_in
  review:
    summary: ARBA machine-learning electronic annotation to mitochondrion. Correct but
      superseded in precision by the mitochondrial-matrix annotations.
    action: KEEP_AS_NON_CORE
    reason: Consistent with the experimentally supported mitochondrial-matrix localization;
      retain as a broader, non-core location term.
    supported_by:
    - reference_id: PMID:8504797
      supporting_text: contains the information necessary to reach the mitochondrial matrix
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Electronic annotation mapping the UniProt subcellular-location term
      (Mitochondrion matrix) to GO:0005759. Matches the experimentally demonstrated
      matrix localization of ETFB.
    action: ACCEPT
    reason: ETFB is imported into and resides in the mitochondrial matrix; this is the
      precise, core cellular location, directly supported by import assays (PMID:8504797)
      and UniProt.
    supported_by:
    - reference_id: PMID:8504797
      supporting_text: contains the information necessary to reach the mitochondrial matrix
- term:
    id: GO:0009055
    label: electron transfer activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: InterPro2GO electronic annotation of electron transfer activity based on
      the ETF beta-subunit domain signatures (IPR000049, IPR012255). Consistent with
      the core molecular function.
    action: ACCEPT
    reason: The InterPro-to-GO mapping correctly assigns the ETF electron transfer
      activity to ETFB via its family domains; redundant with, and supported by, the
      IDA/TAS/IBA annotations.
    supported_by:
    - reference_id: PMID:8962055
      supporting_text: electron shuttles between primary flavoprotein dehydrogenases involved in
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:27499296
  qualifier: enables
  review:
    summary: IntAct-curated physical interaction (IPI) of ETFB with ETFA (P13804) and
      ETFRF1/LYRM5 (Q6IPR1), from a mitochondrial interaction-mapping study. These are
      real, biologically meaningful interactions (ETFA is the partner subunit; ETFRF1
      is the ETF deflavinase), but the GO term itself is the uninformative generic
      "protein binding".
    action: MARK_AS_OVER_ANNOTATED
    reason: The underlying interactions are genuine and important, but bare protein
      binding (GO:0005515) conveys no specific molecular function. Per curation policy
      the experimental IPI is retained rather than removed; the informative content
      (partner-subunit assembly, ETFRF1-mediated deflavination) is captured in
      core_functions and the ETF-complex annotation.
    supported_by:
    - reference_id: PMID:27499296
      supporting_text: LYRM5 interacts with and deflavinates
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: IntAct-curated interactions of ETFB with ETFA (P13804) and ETFRF1 (Q6IPR1)
      from the proteome-scale BioPlex AP-MS interactome. Uninformative generic
      protein-binding term.
    action: MARK_AS_OVER_ANNOTATED
    reason: High-throughput AP-MS interactome data; the ETFA and ETFRF1 interactions
      are consistent with the known ETF complex biology, but the generic protein binding
      term adds no specific functional information. Retained as an experimental IPI per
      policy.
    supported_by:
    - reference_id: PMID:33961781
      supporting_text: BioPlex 3.0, results from affinity purification
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:40205054
  qualifier: enables
  review:
    summary: IntAct-curated interaction of ETFB with ETFA (P13804) from a multimodal
      (AP-MS + immunofluorescence) cell-map study. Generic protein-binding term.
    action: MARK_AS_OVER_ANNOTATED
    reason: The ETFA interaction reflects the constitutive ETF heterodimer, but the
      bare protein binding term is uninformative. Retained as an experimental IPI per
      policy; specific content is captured by the ETF-complex annotation.
    supported_by:
    - reference_id: PMID:40205054
      supporting_text: "interacting partners were identified by tandem MS (AP–MS)"
- term:
    id: GO:0033539
    label: fatty acid beta-oxidation using acyl-CoA dehydrogenase
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: involved_in
  review:
    summary: Combined multi-method electronic annotation (with mouse ortholog Q9DCW4)
      to fatty-acid beta-oxidation using acyl-CoA dehydrogenase. Consistent with the
      curated IDA/IBA annotations of the same term.
    action: ACCEPT
    reason: Redundant electronic support for a core biological process that is
      independently established experimentally (PMID:25416781) and by disease
      complementation (PMID:7912128).
    supported_by:
    - reference_id: PMID:25416781
      supporting_text: "e.g. medium chain acyl-CoA dehydrogenase (MCAD), are involved in β-oxidation of fatty acids"
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: NAS
  original_reference_id: PMID:8504797
  qualifier: located_in
  review:
    summary: ComplexPortal (CPX-2731) non-traceable-author-statement assignment of the
      matrix location, citing the ETFB cloning/import study. Correct core location.
    action: ACCEPT
    reason: The cited study demonstrated that beta-ETF is imported into the mitochondrial
      matrix; the matrix is the established core location of the ETF complex.
    supported_by:
    - reference_id: PMID:8504797
      supporting_text: contains the information necessary to reach the mitochondrial matrix
- term:
    id: GO:0009063
    label: amino acid catabolic process
  evidence_type: IDA
  original_reference_id: PMID:25416781
  qualifier: involved_in
  review:
    summary: ComplexPortal IDA assigning ETFB to amino-acid catabolism, reflecting that
      several ETF-partner dehydrogenases (e.g. glutaryl-CoA and isovaleryl-CoA
      dehydrogenases) act in amino-acid oxidation. ETF is their obligatory electron
      acceptor.
    action: ACCEPT
    reason: ETF accepts electrons from dehydrogenases involved in amino-acid catabolism
      (glutaryl-CoA, isovaleryl-CoA dehydrogenases), and ETFB methylation reduces
      electron uptake from GCDH; loss of ETFB disrupts amino-acid catabolic flux (part
      of the MADD phenotype). A core biological process, though broader than the
      fatty-acid term.
    supported_by:
    - reference_id: PMID:25416781
      supporting_text: "glutaryl-CoA dehydrogenase (GCDH) and isovaleryl-CoA dehydrogenase, are involved in the oxidation of amino acids"
- term:
    id: GO:0022904
    label: respiratory electron transport chain
  evidence_type: IDA
  original_reference_id: PMID:25416781
  qualifier: involved_in
  review:
    summary: ComplexPortal IDA linking ETFB to the respiratory electron transport chain.
      ETF relays electrons from matrix dehydrogenases into the ubiquinone pool via ETFDH,
      acting as a third major electron entry point after complexes I and II.
    action: ACCEPT
    reason: ETF feeds electrons into the respiratory-chain ubiquinone pool through ETFDH;
      the cited study explicitly frames ETF as the third major provider of electrons to
      the ubiquinone pool of the respiratory chain. Core process.
    supported_by:
    - reference_id: PMID:25416781
      supporting_text: it is the third major provider of electrons to the ubiquinone pool of the mitochondrial respiratory chain
- term:
    id: GO:0033539
    label: fatty acid beta-oxidation using acyl-CoA dehydrogenase
  evidence_type: IDA
  original_reference_id: PMID:25416781
  qualifier: involved_in
  review:
    summary: ComplexPortal IDA for fatty-acid beta-oxidation using acyl-CoA dehydrogenase.
      The cited study shows ETFB receives electrons from medium-chain acyl-CoA
      dehydrogenase (MCAD), a core beta-oxidation enzyme.
    action: ACCEPT
    reason: Directly supported experimental annotation for a core beta-oxidation process.
      ETF is the electron acceptor for the acyl-CoA dehydrogenases of fatty-acid
      beta-oxidation, and ETFB methylation modulates electron uptake from MCAD.
    supported_by:
    - reference_id: PMID:25416781
      supporting_text: reduced its ability to receive electrons from the medium chain acyl-CoA dehydrogenase and the glutaryl-CoA dehydrogenase
- term:
    id: GO:0045251
    label: electron transfer flavoprotein complex
  evidence_type: IPI
  original_reference_id: PMID:8962055
  qualifier: part_of
  review:
    summary: ComplexPortal part_of annotation to the electron transfer flavoprotein
      complex, based on the human ETF crystal structure showing the alpha/beta
      heterodimer. This is the specific, core complex for ETFB.
    action: ACCEPT
    reason: The 2.1-A crystal structure defines ETF as a heterodimer in which the beta
      subunit contributes the third structural domain and the AMP site; ETFB is an
      obligate part of the ETF complex (ComplexPortal CPX-2731). Precise and correct.
    supported_by:
    - reference_id: PMID:8962055
      supporting_text: third domain is made up entirely by the beta subunit
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: HPA immunofluorescence-based IDA placing ETFB in the mitochondrion.
      Consistent with the established mitochondrial-matrix localization.
    action: KEEP_AS_NON_CORE
    reason: Correct mitochondrial localization at organelle resolution; the more precise
      matrix term is the core location. Retain as non-core.
    supported_by:
    - reference_id: PMID:8504797
      supporting_text: contains the information necessary to reach the mitochondrial matrix
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:35362222
  qualifier: enables
  review:
    summary: UniProt/IntAct IPI recording interaction of ETFB with ETFA (P13804) and
      MBTPS1/S1P (Q14703). MBTPS1 forms a trimeric complex with ETFA/ETFB that promotes
      FAD incorporation and stabilizes the heterodimer. Real interactions, but the GO
      term is generic protein binding.
    action: MARK_AS_OVER_ANNOTATED
    reason: The MBTPS1 and ETFA interactions are genuine and functionally meaningful
      (MBTPS1 stabilizes and flavinates the ETF heterodimer), but the bare protein
      binding term is uninformative. Retained as an experimental IPI per policy; the
      regulatory content is noted in the notes and core functions rather than as protein
      binding.
    supported_by:
    - reference_id: PMID:35362222
      supporting_text: protein that forms a trimeric complex with ETFA/ETFB. S1P enhances ETFA/ETFB
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: HTP
  original_reference_id: PMID:34800366
  qualifier: located_in
  review:
    summary: High-throughput assignment of ETFB to the mitochondrion from a
      high-confidence quantitative mitochondrial-proteome study. Consistent with the
      established localization.
    action: KEEP_AS_NON_CORE
    reason: Corroborates mitochondrial localization at organelle resolution; the matrix
      term is the precise core location. Retain as non-core.
    supported_by:
    - reference_id: PMID:8504797
      supporting_text: contains the information necessary to reach the mitochondrial matrix
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8931858
  qualifier: located_in
  review:
    summary: Reactome traceable-author-statement (ETFBKMT/METTL20 methylation reaction)
      placing ETFB in the mitochondrial matrix. Correct core location.
    action: ACCEPT
    reason: Consistent with the experimentally established matrix localization; the
      Reactome reaction annotation correctly reflects the matrix compartment where ETFB
      is methylated and functions.
    supported_by:
    - reference_id: PMID:8504797
      supporting_text: contains the information necessary to reach the mitochondrial matrix
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: IDA
  original_reference_id: PMID:8504797
  qualifier: located_in
  review:
    summary: UniProt IDA for mitochondrial matrix, from the beta-ETF cloning study
      demonstrating energy-dependent import of the polypeptide into the matrix.
      Directly supports the core location.
    action: ACCEPT
    reason: The cited import experiments show that the cDNA-encoded beta-ETF reaches the
      mitochondrial matrix; this is the primary experimental evidence for the core
      location.
    supported_by:
    - reference_id: PMID:8504797
      supporting_text: contains the information necessary to reach the mitochondrial matrix
- term:
    id: GO:0009055
    label: electron transfer activity
  evidence_type: IDA
  original_reference_id: PMID:25416781
  qualifier: enables
  review:
    summary: UniProt IDA for electron transfer activity, from the METTL20/ETFB study
      that measured ETF-mediated electron transfer from acyl-CoA dehydrogenases to an
      artificial acceptor and showed methylation of ETFB reduces this activity. Core
      molecular function.
    action: ACCEPT
    reason: Direct assay evidence that ETFB participates in electron transfer (accepting
      electrons from MCAD and GCDH), and that modification of the ETFB recognition loop
      modulates the rate. This is the defining molecular function.
    supported_by:
    - reference_id: PMID:25416781
      supporting_text: reduced its ability to receive electrons from the medium chain acyl-CoA dehydrogenase and the glutaryl-CoA dehydrogenase
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-169260
  qualifier: located_in
  review:
    summary: Reactome TAS (electron transfer from fatty-acid beta-oxidation to ETF)
      placing ETFB in the matrix compartment. Correct core location.
    action: ACCEPT
    reason: Consistent with experimentally established matrix localization; Reactome
      correctly situates the ETF electron-uptake reaction in the mitochondrial matrix.
    supported_by:
    - reference_id: PMID:8504797
      supporting_text: contains the information necessary to reach the mitochondrial matrix
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-169270
  qualifier: located_in
  review:
    summary: Reactome TAS (ETFDH re-oxidizes reduced ETF, reducing CoQ) placing ETFB in
      the matrix. Correct core location.
    action: ACCEPT
    reason: Consistent with the established matrix localization of ETF; correctly
      reflects the compartment of the ETF/ETFDH electron-relay reaction.
    supported_by:
    - reference_id: PMID:8504797
      supporting_text: contains the information necessary to reach the mitochondrial matrix
- term:
    id: GO:0009055
    label: electron transfer activity
  evidence_type: TAS
  original_reference_id: PMID:7912128
  qualifier: enables
  review:
    summary: TAS for electron transfer activity, citing the ETFB glutaric-acidemia-II
      mutation study. The GA2B mutation R164Q reduces ETF electron transfer activity,
      supporting the core molecular function.
    action: ACCEPT
    reason: Disease-mutation evidence corroborates that ETFB is required for ETF
      electron transfer activity; complementation with wild-type beta-ETF cDNA restores
      beta-oxidation flux. Consistent with the IDA/IBA annotations.
    supported_by:
    - reference_id: PMID:7912128
      supporting_text: cDNA complements the genetic defect and restores the beta-oxidation flux to
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: TAS
  original_reference_id: PMID:8617498
  qualifier: located_in
  review:
    summary: TAS for mitochondrial matrix, citing the mouse Etf/Etfdh chromosomal
      mapping paper, which states ETF is located in the mitochondrial matrix and is an
      obligatory electron acceptor for several dehydrogenases. Correct core location.
    action: ACCEPT
    reason: The cited review-style statement correctly places ETF in the mitochondrial
      matrix, consistent with human experimental import data.
    supported_by:
    - reference_id: PMID:8617498
      supporting_text: obligatory electron acceptor for several dehydrogenases
core_functions:
- description: Beta subunit of the electron-transfer flavoprotein (ETF) heterodimer;
    together with ETFA it accepts electrons from matrix FAD-dependent dehydrogenases
    and relays them to ETF-ubiquinone oxidoreductase, functioning as a mobile electron
    carrier.
  molecular_function:
    id: GO:0009055
    label: electron transfer activity
  directly_involved_in:
  - id: GO:0022904
    label: respiratory electron transport chain
  supported_by:
  - reference_id: PMID:25416781
    supporting_text: it is the third major provider of electrons to the ubiquinone pool of the mitochondrial respiratory chain
  - reference_id: PMID:8962055
    supporting_text: electron shuttles between primary flavoprotein dehydrogenases involved in
  in_complex:
    id: GO:0045251
    label: electron transfer flavoprotein complex
  locations:
  - id: GO:0005759
    label: mitochondrial matrix
- description: As part of ETF, accepts electrons from acyl-CoA dehydrogenases of
    mitochondrial fatty-acid beta-oxidation (e.g. medium-chain acyl-CoA dehydrogenase),
    coupling beta-oxidation to the respiratory chain; the ETFB recognition loop docks
    these dehydrogenases.
  molecular_function:
    id: GO:0009055
    label: electron transfer activity
  directly_involved_in:
  - id: GO:0033539
    label: fatty acid beta-oxidation using acyl-CoA dehydrogenase
  supported_by:
  - reference_id: PMID:25416781
    supporting_text: reduced its ability to receive electrons from the medium chain acyl-CoA dehydrogenase and the glutaryl-CoA dehydrogenase
  - reference_id: PMID:7912128
    supporting_text: cDNA complements the genetic defect and restores the beta-oxidation flux to
  in_complex:
    id: GO:0045251
    label: electron transfer flavoprotein complex
  locations:
  - id: GO:0005759
    label: mitochondrial matrix
references:
- 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:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping, accompanied by conservative changes to GO terms applied by
    UniProt
  findings: []
- id: GO_REF:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  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:25416781
  title: Human METTL20 is a mitochondrial lysine methyltransferase that targets the
    β subunit of electron transfer flavoprotein (ETFβ) and modulates its activity.
  findings:
  - statement: ETF is a mobile electron carrier that shuttles electrons from matrix
      FAD-containing dehydrogenases to the membrane-bound ETF quinone oxidoreductase,
      and is the third major provider of electrons to the respiratory-chain ubiquinone
      pool after complexes I and II. METTL20/ETFBKMT trimethylates ETFB Lys-200/Lys-203
      near the recognition loop, reducing electron uptake from MCAD and GCDH.
    supporting_text: it is the third major provider of electrons to the ubiquinone pool of the mitochondrial respiratory chain
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PMC full text; directly establishes ETFB electron-transfer function,
      the recognition loop, and its methylation-based regulation. Verified verbatim.
- id: PMID:27499296
  title: Mitochondrial Protein Interaction Mapping Identifies Regulators of Respiratory
    Chain Function.
  findings:
  - statement: ETFB interacts with ETFA and ETFRF1/LYRM5; LYRM5 acts as an ETF
      deflavinase, removing FAD from the electron-transferring flavoprotein that
      shuttles electrons to coenzyme Q.
    supporting_text: LYRM5 interacts with and deflavinates
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: PMC full text; supports the ETFA/ETFRF1 interactions underlying the
      IntAct protein-binding IPIs and the regulation of ETF flavination.
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human
    interactome.
  findings:
  - statement: Proteome-scale BioPlex AP-MS interactome; source of the IntAct-curated
      ETFB interactions with ETFA and ETFRF1.
    supporting_text: BioPlex 3.0, results from affinity purification
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: High-throughput interactome; supports the generic protein-binding
      IPIs only (marked over-annotated).
- id: PMID:34800366
  title: Quantitative high-confidence human mitochondrial proteome and its dynamics
    in cellular context.
  findings:
  - statement: High-confidence quantitative human mitochondrial proteome; supports
      mitochondrial localization of ETFB (HTP).
    supporting_text: Quantitative high-confidence human mitochondrial proteome
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: HTP proteomics; corroborates mitochondrial localization at organelle
      resolution.
- id: PMID:35362222
  title: S1P defects cause a new entity of cataract, alopecia, oral mucosal disorder,
    and psoriasis-like syndrome.
  findings:
  - statement: MBTPS1/S1P is a mitochondrial protein that forms a trimeric complex with
      ETFA/ETFB, enhancing ETF flavination (FAD incorporation) and stabilizing the
      heterodimer; loss impairs mitochondrial respiration and fatty-acid beta-oxidation.
    supporting_text: protein that forms a trimeric complex with ETFA/ETFB. S1P enhances ETFA/ETFB
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: PMC full text; supports the ETFA/MBTPS1 protein-binding IPI and the
      regulation of ETF stability/flavination.
- id: PMID:40205054
  title: Multimodal cell maps as a foundation for structural and functional genomics.
  findings:
  - statement: Multimodal (AP-MS + immunofluorescence) cell map; source of the
      IntAct-curated ETFB-ETFA interaction.
    supporting_text: "interacting partners were identified by tandem MS (AP–MS)"
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: High-throughput cell-mapping study; supports the generic
      protein-binding IPI only (marked over-annotated).
- id: PMID:7912128
  title: Mutations and polymorphisms of the gene encoding the beta-subunit of the
    electron transfer flavoprotein in three patients with glutaric acidemia type II.
  findings:
  - statement: Beta-ETF (ETFB) mutations cause glutaric acidemia type II; the R164Q
      mutation reduces electron transfer activity, and wild-type beta-ETF cDNA restores
      beta-oxidation flux in patient fibroblasts.
    supporting_text: cDNA complements the genetic defect and restores the beta-oxidation flux to
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Abstract-only cache; establishes disease relevance and functional
      requirement of ETFB for beta-oxidation flux. Verified verbatim from abstract.
- id: PMID:8504797
  title: cDNA cloning and mitochondrial import of the beta-subunit of the human electron-transfer
    flavoprotein.
  findings:
  - statement: The cloned beta-ETF (255 aa) polypeptide contains the information
      necessary to reach the mitochondrial matrix via energy-dependent import, and
      lacks a cleavable leader peptide; the mRNA is abundant in liver, heart, and
      skeletal muscle.
    supporting_text: contains the information necessary to reach the mitochondrial matrix
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Abstract-only cache; primary evidence for ETFB matrix localization.
      Verified verbatim from abstract.
- id: PMID:8617498
  title: 'Assignment of Etfdh, Etfb, and Etfa to chromosomes 3, 7, and 13: the mouse
    homologs of genes responsible for glutaric acidemia type II in human.'
  findings:
  - statement: ETF (alpha/beta) is an obligatory electron acceptor for several
      dehydrogenases and is located in the mitochondrial matrix; electrons are
      transferred to the respiratory chain via ETFDH, and deficiency causes glutaric
      acidemia type II.
    supporting_text: obligatory electron acceptor for several dehydrogenases
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Abstract-only cache; supports matrix localization and obligatory
      electron-acceptor role. Verified verbatim from abstract.
- id: PMID:8962055
  title: Three-dimensional structure of human electron transfer flavoprotein to 2.1-A
    resolution.
  findings:
  - statement: The 2.1-A crystal structure of human ETF shows a heterodimer of three
      domains, the third contributed entirely by the beta subunit, with FAD in a cleft
      between subunits; ETF functions as an electron shuttle between primary
      flavoprotein dehydrogenases and ETF-ubiquinone oxidoreductase.
    supporting_text: third domain is made up entirely by the beta subunit
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Abstract-only cache; structural basis for the ETF complex and the
      beta-subunit domain. Verified verbatim from abstract.
- id: Reactome:R-HSA-169260
  title: Reducing equivalents from beta-oxidation of fatty acids transfer to ETF
  findings: []
- id: Reactome:R-HSA-169270
  title: ETFDH oxidises ETF (reduced) to ETF, reduces CoQ to CoQH2
  findings: []
- id: Reactome:R-HSA-8931858
  title: ETFBKMT transfers 3xCH3 from 3xAdoMet to ETFB
  findings: []