id: Q9NVI1
gene_symbol: FANCI
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  Fanconi anemia group I protein (FANCI) is the obligate heterodimeric partner of
  FANCD2, with which it forms the FANCI-FANCD2 (ID2) complex, the central effector
  of the Fanconi anemia (FA) DNA interstrand crosslink (ICL) repair pathway. FANCI
  is a large, predominantly alpha-solenoid nuclear protein that binds double-stranded
  DNA with a preference for branched structures (Holliday junctions, overhangs and
  replication forks). During S phase and following genotoxic stress, FANCI is
  monoubiquitinated on Lys523 by the FANCL/UBE2T ubiquitin ligase acting downstream
  of the multi-subunit FA core complex; this event is mutually interdependent with,
  and required to promote, FANCD2 monoubiquitination. Monoubiquitination converts the
  open, trough-like ID2 complex into a closed sliding clamp that encircles duplex DNA
  at stalled replication forks and ICLs, coordinating downstream repair reactions
  including nucleolytic incision/unhooking, translesion synthesis and homologous
  recombination. ATR-dependent phosphorylation of a conserved S/TQ cluster in FANCI
  acts as a molecular switch that activates the pathway. FANCI also contributes to
  replication fork protection and S/G2 checkpoint signaling. Biallelic loss-of-function
  mutations cause Fanconi anemia complementation group I, characterized by bone marrow
  failure, congenital malformations, chromosomal instability, cellular hypersensitivity
  to crosslinking agents, and cancer predisposition.
alternative_products:
- name: '3'
  id: Q9NVI1-3
- name: '2'
  id: Q9NVI1-2
  sequence_note: VSP_026069, VSP_020257
- name: '1'
  id: Q9NVI1-1
  sequence_note: VSP_026069
- name: '4'
  id: Q9NVI1-4
  sequence_note: VSP_035606
existing_annotations:
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: >-
      FANCI is an active nuclear protein; it functions in the nucleoplasm/chromatin
      as part of the ID2 complex. IBA localization is appropriate and consistent with
      experimental data.
    action: ACCEPT
    reason: >-
      UniProt records nuclear localization (PubMed:17412408, 17460694), and the ID2
      complex acts on nuclear chromatin. Nucleoplasm is the correct compartment for
      FANCI's core activity.
    supported_by:
    - reference_id: PMID:18931676
      supporting_text: >-
        In turn, FancD2 and FancI are both targeted to chromatin and form colocalizing
        foci together with the HR proteins BRCA1 and Rad51
- term:
    id: GO:0006974
    label: DNA damage response
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: >-
      FANCI is a bona fide DNA damage response factor, activated by replication stress
      and ICLs and phosphorylated by ATR/ATM. Broad but correct.
    action: ACCEPT
    reason: >-
      The FA pathway responds to stalled replication forks and ICLs; FANCI is
      phosphorylated in response to DNA damage and participates in checkpoint signaling.
    supported_by:
    - reference_id: PMID:18931676
      supporting_text: >-
        In response to DNA damage or replication fork stress, the Fanconi anemia pathway
        is activated, leading to monoubiquitination of FANCD2 and FANCI and their
        colocalization in foci.
- term:
    id: GO:0031398
    label: positive regulation of protein ubiquitination
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: >-
      FANCI is required to promote the monoubiquitination of FANCD2 by FANCL/UBE2T; its
      phosphorylation acts as the activating switch for this event. A core FANCI function.
    action: ACCEPT
    reason: >-
      Loss of FANCI abrogates FANCD2 monoubiquitination, and FANCI phospho-mimic mutants
      induce constitutive FANCD2 monoubiquitination, demonstrating FANCI positively
      regulates protein (FANCD2) monoubiquitination.
    supported_by:
    - reference_id: PMID:18931676
      supporting_text: >-
        FANCI carrying phosphomimic mutations on the same six residues induces constitutive
        monoubiquitination and focus formation of FANCI and FANCD2
- term:
    id: GO:1990391
    label: DNA repair complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: part_of
  review:
    summary: >-
      FANCI is a subunit of the FANCI-FANCD2 (ID2) DNA repair complex. IBA complex
      membership is correct.
    action: ACCEPT
    reason: >-
      FANCI forms an obligate heterodimeric DNA repair complex with FANCD2 (ID2), a
      GO:0032991 protein-containing DNA repair complex.
    supported_by:
    - reference_id: PMID:32269332
      supporting_text: >-
        The ID complex, involving the proteins FANCI and FANCD2, is required for the
        repair of DNA interstrand crosslinks (ICL) and related lesions
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: >-
      Nuclear localization mapped from the UniProt subcellular location vocabulary.
      Correct, though less specific than nucleoplasm.
    action: ACCEPT
    reason: >-
      FANCI is a nuclear protein (UniProt Nucleus, PubMed:17412408, 17460694, 19465922).
      The broader 'nucleus' term is acceptable as an IEA mapping.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: >-
      Cytoplasm mapped from the UniProt subcellular-location vocabulary, which itself
      derives from a single incidental proteomic identification (PubMed:18445686). FANCI
      is overwhelmingly nuclear and executes its DNA-repair function on chromatin.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The cytoplasm assignment traces to PubMed:18445686, an EML3-focused mitotic-spindle
      proteomics paper in which FANCI was an incidental hit, not a focused localization
      study. Any cytoplasmic pool is minor and non-functional; the compartment relevant to
      FANCI's activity is the nucleus/chromatin.
- term:
    id: GO:0006281
    label: DNA repair
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: >-
      FANCI is a core DNA repair factor. Broad InterPro-based term is correct; the more
      specific interstrand cross-link repair term is captured elsewhere.
    action: ACCEPT
    reason: >-
      InterPro family IPR026171 (FANCI) maps to DNA repair, consistent with FANCI's
      established role in ICL and double-strand break repair.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17460694
  qualifier: enables
  review:
    summary: >-
      Captures the physical interaction with FANCD2 that forms the ID2 complex. The
      interaction is real and central, but 'protein binding' is uninformative as a
      molecular function; the functional consequence (ID2 complex / DNA clamp) is
      captured by the complex and DNA-binding annotations.
    action: KEEP_AS_NON_CORE
    reason: >-
      PubMed:17460694 (WITH FANCD2, Q9BXW9) documents FANCI-FANCD2 interaction. Retained
      as evidence of complex formation but not as a core molecular function per curation
      guidance to avoid 'protein binding'.
    supported_by:
    - reference_id: PMID:17460694
      supporting_text: >-
        FANCI, a second monoubiquitinated component of the FA pathway
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20603015
  qualifier: enables
  review:
    summary: >-
      Captures interaction with FAN1 (MTMR15; WITH Q9Y2M0/Q9BXW9), a nuclease recruited
      to the monoubiquitinated ID/FANCD2. Real interaction but uninformative MF term.
    action: KEEP_AS_NON_CORE
    reason: >-
      PubMed:20603015 identifies FAN1 as a partner of the monoubiquitinated FANCD2/ID
      complex. Retained as interaction evidence, non-core; 'protein binding' is too
      generic for a core molecular function.
    supported_by:
    - reference_id: PMID:20603015
      supporting_text: >-
        a highly conserved protein, KIAA1018/MTMR15/FAN1, that interacts with, and is
        recruited to sites of DNA damage by, the monoubiquitinated form of FANCD2
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:31240132
  qualifier: enables
  review:
    summary: >-
      Captures interaction with CTDP1 (WITH Q9Y5B0), a phosphatase that regulates FANCI
      chromatin localization and SQ-motif phosphorylation. Real interaction, uninformative MF.
    action: KEEP_AS_NON_CORE
    reason: >-
      PubMed:31240132 documents a direct CTDP1-FANCI (BRCT) interaction regulating FANCI
      activity. Retained as interaction evidence, non-core.
    supported_by:
    - reference_id: PMID:31240132
      supporting_text: >-
        CTDP1 was found to regulate multiple aspects of FANCI activity, including chromatin
        localization, interaction with γ-H2AX, and SQ motif phosphorylations.
- term:
    id: GO:0000785
    label: chromatin
  evidence_type: NAS
  original_reference_id: PMID:19965384
  qualifier: located_in
  review:
    summary: >-
      FANCI localizes to chromatin, where the monoubiquitinated ID2 complex acts. Correct
      and functionally important location.
    action: ACCEPT
    reason: >-
      Monoubiquitination targets FANCI/FANCD2 to chromatin foci; chromatin binding is
      required for DNA repair function.
    supported_by:
    - reference_id: PMID:18931676
      supporting_text: >-
        In turn, FancD2 and FancI are both targeted to chromatin and form colocalizing
        foci together with the HR proteins BRCA1 and Rad51
- term:
    id: GO:0036297
    label: interstrand cross-link repair
  evidence_type: NAS
  original_reference_id: PMID:19965384
  qualifier: involved_in
  review:
    summary: >-
      Interstrand cross-link repair is the defining biological process of FANCI/ID2. Strong,
      well-supported core annotation.
    action: ACCEPT
    reason: >-
      FANCI-FANCD2 is required for replication-coupled ICL repair in S phase; monoubiquitinated
      ID2 is essential for excision, translesion synthesis and homologous recombination during
      ICL repair.
    supported_by:
    - reference_id: PMID:19965384
      supporting_text: >-
        Using a cell-free system, we showed that FANCI-FANCD2 is required for
        replication-coupled ICL repair in S phase.
    - reference_id: PMID:32269332
      supporting_text: >-
        Monoubiquitination of ID is essential for ICL repair by excision, translesion synthesis
        and homologous recombination
- term:
    id: GO:1990391
    label: DNA repair complex
  evidence_type: IPI
  original_reference_id: PMID:32269332
  qualifier: part_of
  review:
    summary: >-
      Structural (cryo-EM) demonstration that FANCI is a subunit of the ID2 DNA repair complex
      that clamps DNA. Core complex membership.
    action: ACCEPT
    reason: >-
      Cryo-EM structures of the monoubiquitinated human FANCI-FANCD2 complex bound to DNA
      confirm FANCI as an integral subunit of this DNA repair complex.
    supported_by:
    - reference_id: PMID:32269332
      supporting_text: >-
        we report a cryo-electron microscopy structure of the monoubiquitinated human ID complex
        bound to DNA, and reveal that it forms a closed ring that encircles the DNA
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: >-
      Direct immunofluorescence (HPA) localizes FANCI to the nucleoplasm. Consistent with
      its nuclear DNA-repair function.
    action: ACCEPT
    reason: >-
      Immunofluorescence-based nucleoplasm localization agrees with all other evidence for
      FANCI being a nuclear protein.
- term:
    id: GO:0031398
    label: positive regulation of protein ubiquitination
  evidence_type: IDA
  original_reference_id: PMID:18931676
  qualifier: acts_upstream_of_or_within
  review:
    summary: >-
      Experimental demonstration that FANCI (via its phosphorylation switch) positively
      regulates FANCD2 monoubiquitination. Core FANCI function.
    action: ACCEPT
    reason: >-
      FANCI phospho-mimic mutants induce constitutive FANCD2 monoubiquitination while
      phospho-dead mutants abolish it, in both chicken DT40 and human cells, establishing
      FANCI as a positive regulator of protein (FANCD2) monoubiquitination.
    supported_by:
    - reference_id: PMID:18931676
      supporting_text: >-
        FANCI phosphorylation exerts an evolutionarily conserved function in inducing FANCD2
        monoubiqutination in human cells as well.
    - reference_id: PMID:22287633
      supporting_text: >-
        The DNA-binding activity of FANCI is required to stimulate FANCD2 monoubiquitylation
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:18445686
  qualifier: located_in
  review:
    summary: >-
      Cytoplasmic localization asserted from a proteomics screen focused on EML3 and the
      mitotic spindle, in which FANCI was an incidental identification. FANCI is a nuclear
      DNA-repair protein; a cytoplasmic pool, if present, is minor and not its functional site.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      PubMed:18445686 is a proteomic identification of spindle/nuclear microtubule-binding
      proteins centered on EML3, not a focused study of FANCI localization. All focused
      studies place FANCI in the nucleus/chromatin, so cytoplasm is an over-annotation.
    supported_by:
    - reference_id: PMID:18445686
      supporting_text: >-
        we used a proteomic approach to selectively identify proteins of this category and
        revealed 50 poorly characterised human gene products, among them the echinoderm
        microtubule-associated-protein-like gene product, EML3.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6785361
  qualifier: located_in
  review:
    summary: 'Reactome nucleoplasm localization for the FA/ICL repair reaction (Monoubiquitination of FANCD2:FANCI). Correct.'
    action: ACCEPT
    reason: FANCI acts in the nucleoplasm; consistent with all other localization evidence.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6785732
  qualifier: located_in
  review:
    summary: Reactome nucleoplasm localization for the ID/nuclease binding step. Correct.
    action: ACCEPT
    reason: FANCI acts in the nucleoplasm; consistent with all other localization evidence.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6785986
  qualifier: located_in
  review:
    summary: Reactome nucleoplasm localization for the ICL unhooking step. Correct.
    action: ACCEPT
    reason: FANCI acts in the nucleoplasm; consistent with all other localization evidence.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6786155
  qualifier: located_in
  review:
    summary: Reactome nucleoplasm localization for the POLN-ICL binding step. Correct.
    action: ACCEPT
    reason: FANCI acts in the nucleoplasm; consistent with all other localization evidence.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6786166
  qualifier: located_in
  review:
    summary: Reactome nucleoplasm localization for translesion synthesis across the unhooked ICL. Correct.
    action: ACCEPT
    reason: FANCI acts in the nucleoplasm; consistent with all other localization evidence.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6786171
  qualifier: located_in
  review:
    summary: 'Reactome nucleoplasm localization for FANCD2 deubiquitination by USP1:WDR48. Correct.'
    action: ACCEPT
    reason: FANCI acts in the nucleoplasm; consistent with all other localization evidence.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6788392
  qualifier: located_in
  review:
    summary: 'Reactome nucleoplasm localization for ATR phosphorylation of RPA2, FANCI, FANCD2, FANCM at ICL-DNA. Correct.'
    action: ACCEPT
    reason: FANCI acts in the nucleoplasm; consistent with all other localization evidence.
- term:
    id: GO:0016020
    label: membrane
  evidence_type: HDA
  original_reference_id: PMID:19946888
  qualifier: located_in
  review:
    summary: >-
      Membrane localization derives from a bulk NK-cell membrane-fraction mass-spectrometry
      survey. FANCI has no transmembrane region and is a soluble nuclear DNA-repair protein;
      this is a co-purification artifact of membrane-fraction proteomics.
    action: REMOVE
    reason: >-
      FANCI has no predicted or observed transmembrane domain (UniProt) and no biological
      role at membranes. The source paper itself states that only ~40% of identified proteins
      are plausible membrane proteins and the remainder are cellular-process proteins
      transiently associated with membranes; FANCI falls in the latter, non-membrane class.
      The annotation is demonstrably incorrect as a subcellular location.
    supported_by:
    - reference_id: PMID:19946888
      supporting_text: >-
        approximately 40% of the identified proteins were predicted as plausible membrane
        proteins. The remaining species were largely involved in cellular processes and
        molecular functions that could be predicted to be transiently associated with membranes.
- term:
    id: GO:0070182
    label: DNA polymerase binding
  evidence_type: IPI
  original_reference_id: PMID:19995904
  qualifier: enables
  review:
    summary: >-
      FANCI physically and functionally interacts with the translesion/HR polymerase POLN.
      A specific, informative binding term, but this interaction is peripheral to FANCI's
      core clamp/ubiquitination functions.
    action: KEEP_AS_NON_CORE
    reason: >-
      PubMed:19995904 (WITH POLN, Q7Z5Q5) documents FANCI-POLN interaction linking the FA
      pathway to translesion synthesis/HR. The term is accurate but reflects a downstream/
      accessory partnership rather than FANCI's defining activity.
    supported_by:
    - reference_id: PMID:19995904
      supporting_text: >-
        we obtained evidence for physical and functional interaction of POLN with factors
        belonging to the Fanconi anemia pathway, a master regulator of cross-link repair
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6785342
  qualifier: located_in
  review:
    summary: 'Reactome nucleoplasm localization for FANCD2:FANCI + UBE2T binding ICL-DNA. Correct.'
    action: ACCEPT
    reason: FANCI acts in the nucleoplasm; consistent with all other localization evidence.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6785594
  qualifier: located_in
  review:
    summary: Reactome nucleoplasm localization for the FANCD2 binds FANCI step. Correct.
    action: ACCEPT
    reason: FANCI acts in the nucleoplasm; consistent with all other localization evidence.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6788385
  qualifier: located_in
  review:
    summary: 'Reactome nucleoplasm localization for recruitment of ATR:ATRIP to ICL-DNA. Correct.'
    action: ACCEPT
    reason: FANCI acts in the nucleoplasm; consistent with all other localization evidence.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6797712
  qualifier: located_in
  review:
    summary: >-
      Reactome nucleoplasm localization for CDK12 stimulation of DNA-repair gene expression.
      Location correct for FANCI.
    action: ACCEPT
    reason: FANCI acts in the nucleoplasm; consistent with all other localization evidence.
- term:
    id: GO:0000217
    label: DNA secondary structure binding
  evidence_type: IDA
  original_reference_id: PMID:32269332
  qualifier: enables
  review:
    summary: >-
      Structure-selective DNA binding is FANCI's defining biochemical activity and is absent
      from the GOA export even though UniProt carries the DNA-binding keyword. FANCI (within
      ID2) binds duplex DNA with a preference for branched structures and, when
      monoubiquitinated, clamps around dsDNA.
    action: NEW
    reason: >-
      Structural and biochemical studies show FANCI binds DNA with a documented preference for
      branched structures - Holliday junctions, overhangs and replication forks - and the
      monoubiquitinated ID2 complex encircles duplex DNA as a sliding clamp. Bare GO:0003677
      DNA binding under-represents that evidence, so GO:0000217 DNA secondary structure binding
      is used instead. GO:0000400 four-way junction DNA binding (used elsewhere in this cohort
      for RAD51C and XRCC2) is its child and covers only the Holliday-junction part of the
      quoted preference, so the parent is the accurate fit for the full substrate set. The
      paralog FANCD2 correspondingly carries the specific GO:0003697.
    supported_by:
    - reference_id: PMID:32269332
      supporting_text: >-
        FANCI and FANCD2 are paralogs that bind to DNA with preference for branched structures
        including Holliday junction, overhang and replication fork DNA
    - reference_id: PMID:32269332
      supporting_text: >-
        the monoubiquitinated ID complex loses its preference for ICL and related branched DNA
        structures, and becomes a sliding DNA clamp that can coordinate the subsequent repair
        reactions
    - reference_id: PMID:19589784
      supporting_text: >-
        We show that FANCI and its C-terminal fragment possess a DNA binding activity that
        prefers branched structures.
    - reference_id: PMID:27694619
      supporting_text: >-
        The DNA binding activity of FANCI is required for the I-D complex-mediated
        stabilization of the RAD51-DNA filament.
core_functions:
- description: >-
    DNA-binding subunit of the FANCI-FANCD2 (ID2) complex: binds duplex DNA (preferring
    branched replication-fork/junction structures) and, upon FANCL/UBE2T-catalyzed
    monoubiquitination on Lys523, converts the complex into a closed sliding clamp that
    encircles DNA at stalled forks and interstrand crosslinks, coordinating downstream ICL
    repair; FANCI is itself required to promote FANCD2 monoubiquitination that activates
    the pathway.
  supported_by:
  - reference_id: PMID:32269332
    supporting_text: >-
      it forms a closed ring that encircles the DNA
  - reference_id: PMID:19965384
    supporting_text: >-
      Using a cell-free system, we showed that FANCI-FANCD2 is required for
      replication-coupled ICL repair in S phase.
  - reference_id: PMID:18931676
    supporting_text: >-
      FANCI phosphorylation exerts an evolutionarily conserved function in inducing FANCD2
      monoubiqutination in human cells as well.
  molecular_function:
    id: GO:0000217
    label: DNA secondary structure binding
  directly_involved_in:
  - id: GO:0036297
    label: interstrand cross-link repair
  - id: GO:0031398
    label: positive regulation of protein ubiquitination
  locations:
  - id: GO:0005654
    label: nucleoplasm
  - id: GO:0000785
    label: chromatin
  in_complex:
    id: GO:1990391
    label: DNA repair complex
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: PMID:17460694
  title: FANCI is a second monoubiquitinated member of the Fanconi anemia pathway.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified. Establishes FANCI as the second monoubiquitinated FA-pathway
      component and FANCD2 paralog/partner; underlies the FANCD2-interaction (protein
      binding) annotation.
- id: PMID:18445686
  title: EML3 is a nuclear microtubule-binding protein required for the correct alignment
    of chromosomes in metaphase.
  findings: []
  reference_review:
    relevance: LOW
    correctness: MISCITED
    review_notes: >-
      Correctly identified paper, but it is an EML3/mitotic-spindle proteomics study in
      which FANCI is only an incidental hit; it does not establish a genuine cytoplasmic
      function for FANCI. Basis for the over-annotated cytoplasm localization.
- id: PMID:18931676
  title: FANCI phosphorylation functions as a molecular switch to turn on the Fanconi
    anemia pathway.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified full text. Demonstrates FANCI S/TQ-cluster phosphorylation drives
      FANCD2 monoubiquitination in chicken DT40 and human cells; supports positive
      regulation of protein ubiquitination.
- id: PMID:19946888
  title: Defining the membrane proteome of NK cells.
  findings: []
  reference_review:
    relevance: NONE
    correctness: MISCITED
    review_notes: >-
      Bulk NK-cell membrane-fraction proteomics; FANCI has no transmembrane region and no
      membrane role. The paper itself flags most identified proteins as non-membrane. Basis
      for the removed membrane annotation.
- id: PMID:19965384
  title: The Fanconi anemia pathway promotes replication-dependent DNA interstrand
    cross-link repair.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified. Cell-free (Xenopus) system shows ubiquitinated FANCI-FANCD2 is
      required for replication-coupled ICL repair in S phase; supports ICL repair and
      chromatin annotations.
- id: PMID:19995904
  title: DNA polymerase POLN participates in cross-link repair and homologous recombination.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified. Documents physical/functional interaction of POLN with FA-pathway
      factors; supports the DNA polymerase binding annotation (accessory interaction).
- id: PMID:19589784
  title: FANCI binds branched DNA and is monoubiquitinated by UBE2T-FANCL.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified full text. Primary biochemistry showing FANCI itself (and its
      C-terminal fragment) has intrinsic DNA-binding activity preferring branched
      structures, and is monoubiquitinated on Lys523 by UBE2T-FANCL in vitro. Independent
      primary support for the DNA-binding (GO:0003677) core molecular function, which the
      structural PMID:32269332 otherwise carries alone.
- id: PMID:22287633
  title: DNA robustly stimulates FANCD2 monoubiquitylation in the complex with FANCI.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified full text. Reconstituted ID2 monoubiquitination shows DNA strongly
      stimulates FANCD2 monoubiquitylation strictly via FANCI, and a DNA-binding-defective
      FANCI mutant is defective in stimulating FANCD2 monoubiquitylation. Mechanistically
      links FANCI's DNA binding to its positive regulation of protein (FANCD2)
      monoubiquitination (GO:0031398).
- id: PMID:27694619
  title: FANCI-FANCD2 stabilizes the RAD51-DNA complex by binding RAD51 and protects
    the 5'-DNA end.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified full text. The I-D complex binds RAD51 and stabilizes the RAD51-DNA
      filament to protect the DNA end from FAN1 nucleolytic degradation at stalled forks;
      critically, FANCI's (not FANCD2's) DNA-binding activity is explicitly required.
      Supports FANCI-specific DNA binding (GO:0003677) as functionally essential. The
      fork-protection/RAD51-stabilization process itself is a downstream ID2-complex role
      with no clean matching GO biological-process term, so it is not added as a new BP
      annotation.
- id: PMID:20603015
  title: Identification of KIAA1018/FAN1, a DNA repair nuclease recruited to DNA damage
    by monoubiquitinated FANCD2.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified. Identifies FAN1 as a partner of the monoubiquitinated FANCD2/ID
      complex; basis for a FANCI protein-binding (interaction) annotation.
- id: PMID:31240132
  title: CTDP1 regulates breast cancer survival and DNA repair through BRCT-specific
    interactions with FANCI.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified. Direct CTDP1-FANCI interaction regulating FANCI chromatin
      localization and SQ-motif phosphorylation; basis for a protein-binding annotation.
- id: PMID:32269332
  title: DNA clamp function of the monoubiquitinated Fanconi anaemia ID complex.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified full text (cryo-EM, Nature 2020). Shows the monoubiquitinated ID2
      complex encircles DNA as a sliding clamp; supports DNA binding, DNA repair complex,
      and ICL repair core functions.
- id: Reactome:R-HSA-6785342
  title: FANCD2:FANCI complex and UBE2T bind ICL-DNA associated with the FA core complex
  findings: []
- id: Reactome:R-HSA-6785361
  title: Monoubiquitination of FANCD2:FANCI
  findings: []
- id: Reactome:R-HSA-6785594
  title: FANCD2 binds FANCI
  findings: []
- id: Reactome:R-HSA-6785732
  title: DNA nucleases bind monoubiquitinated ID2 complex
  findings: []
- id: Reactome:R-HSA-6785986
  title: DNA nucleases unhook the interstrand crosslink (ICL)
  findings: []
- id: Reactome:R-HSA-6786155
  title: POLN binds ICL-DNA
  findings: []
- id: Reactome:R-HSA-6786166
  title: Translesion synthesis across unhooked ICL by POLN
  findings: []
- id: Reactome:R-HSA-6786171
  title: FANCD2 deubiquitination by USP1:WDR48
  findings: []
- id: Reactome:R-HSA-6788385
  title: The complex of ATR and ATRIP is recruited to ICL-DNA
  findings: []
- id: Reactome:R-HSA-6788392
  title: ATR phosphorylates RPA2, FANCI, FANCD2 and FANCM at ICL-DNA
  findings: []
- id: Reactome:R-HSA-6797712
  title: CDK12 stimulates expression of DNA repair genes
  findings: []