id: Q66K74
gene_symbol: MAP1S
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  MAP1S (microtubule-associated protein 1S; also known as C19orf5, MAP8 and VCY2IP1)
  is the short, ubiquitously expressed member of the MAP1 family, whose other members
  (MAP1A and MAP1B) are largely neuron-specific. Like its paralogs, MAP1S is synthesized
  as a precursor that is proteolytically processed into a heavy chain and a light chain
  which re-associate into a heterodimer; both chains bind microtubules, and the light
  chain additionally binds actin. Its core molecular activity is binding tubulin/microtubules
  and cross-linking and bundling them, contributing to microtubule cytoskeleton organization
  and stabilization. MAP1S is distinguished functionally by acting as a bridge that couples
  the autophagy machinery to the microtubule cytoskeleton and to mitochondria: it binds
  the autophagosome-associated Atg8/LC3 protein and recruits it to stable microtubules,
  and it binds the mitochondrion-associated protein LRPPRC (which links to the mitophagy
  initiator Parkin), thereby promoting autophagosome biogenesis, trafficking and
  degradation and the clearance of defective mitochondria. Consistent with this, loss of
  MAP1S causes accumulation of defective mitochondria and impaired responses to nutrient
  stress. MAP1S also has cytoskeletal and mitotic roles, anchoring the microtubule-organizing
  center to the centrosome and supporting proper spindle organization and chromosome
  alignment; its depletion causes mitotic abnormalities. It interacts with the microtubule-
  stabilizing tumor suppressor RASSF1A, with WDR47/Nemitin, with the estrogen receptor ESR1,
  and with the NMDA-receptor subunit NR3A, and it binds DNA (but has no nuclease activity).
  MAP1S localizes to the cytosol, microtubules, mitotic spindle, centrosome/microtubule-
  organizing center, the perinuclear region (where mitochondrial aggregates form), and,
  as a shuttling pool, to the nucleus; in neurons it is found in cell projections and synapses.
alternative_products:
- name: '1'
  id: Q66K74-1
- name: '2'
  id: Q66K74-2
  sequence_note: VSP_056043
existing_annotations:
- term:
    id: GO:0045202
    label: synapse
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: Phylogenetic (IBA) propagation of synapse localization across the MAP1 family. MAP1S is detected in synapses in neurons, but it is ubiquitously expressed and this is a neuron-specific secondary localization.
    action: KEEP_AS_NON_CORE
    reason: Real but neuron-specific/secondary localization (also supported by IDA, PMID:17658481); not central to MAP1S's core microtubule/autophagy functions.
    supported_by:
    - reference_id: file:human/MAP1S/MAP1S-uniprot.txt
      supporting_text: Detected in filopodia-like protrusions and synapses
- term:
    id: GO:0000226
    label: microtubule cytoskeleton organization
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: Phylogenetic (IBA) assignment of microtubule cytoskeleton organization, a core MAP1-family function. Supported experimentally for MAP1S (microtubule bundling/stabilization).
    action: ACCEPT
    reason: Core biological process; MAP1S binds, bundles and stabilizes microtubules.
    supported_by:
    - reference_id: PMID:15528209
      supporting_text: Microtubule-associated protein 1S, a short and ubiquitously expressed member of the microtubule-associated protein 1 family
- term:
    id: GO:0005874
    label: microtubule
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: Phylogenetic (IBA) assignment of microtubule localization, the defining MAP1-family compartment. Strongly supported by multiple IDA studies for MAP1S.
    action: ACCEPT
    reason: Core localization; MAP1S associates with and acts on microtubules.
    supported_by:
    - reference_id: PMID:15528209
      supporting_text: Microtubule-associated protein 1S, a short and ubiquitously expressed member of the microtubule-associated protein 1 family
- term:
    id: GO:0003779
    label: actin binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: Phylogenetic (IBA) assignment of actin binding. The MAP1S light chain binds actin/actin filaments (supported by IDA, GO:0051015), so generic actin binding is plausible, but actin binding is secondary to MAP1S's microtubule function.
    action: KEEP_AS_NON_CORE
    reason: Supported (light chain binds actin) but secondary; the primary cytoskeletal role of MAP1S is on microtubules. Note one study reported NOT actin filament binding under different conditions, so this activity is context-dependent.
    supported_by:
    - reference_id: file:human/MAP1S/MAP1S-uniprot.txt
      supporting_text: MAP1S light chain interacts with actin
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: Phylogenetic (IBA) assignment of cytosolic localization, consistent with MAP1S's cytoplasmic microtubule-associated distribution. Supported by IDA and the UniProt subcellular location.
    action: ACCEPT
    reason: Core localization; MAP1S is a cytoplasmic, microtubule-associated protein.
    supported_by:
    - reference_id: file:human/MAP1S/MAP1S-uniprot.txt
      supporting_text: Cytoplasm, cytosol
- term:
    id: GO:0005875
    label: microtubule associated complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: part_of
  review:
    summary: Phylogenetic (IBA) assignment that MAP1S is part of a microtubule-associated complex, consistent with its heavy/light chain heterodimer that binds microtubules.
    action: ACCEPT
    reason: Core cellular component; MAP1S forms a microtubule-associated heterodimer complex.
    supported_by:
    - reference_id: file:human/MAP1S/MAP1S-uniprot.txt
      supporting_text: Heterodimer of a heavy and a light chain. Interacts with microtubules and actin.
- term:
    id: GO:0007409
    label: axonogenesis
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: Phylogenetic (IBA) propagation of axonogenesis from the neuronal MAP1 paralogs (MAP1A/B). This is a neuron-specific developmental role inherited from the family tree, not an established human MAP1S function.
    action: KEEP_AS_NON_CORE
    reason: Neuronal developmental role transferred from paralogs; secondary/peripheral for ubiquitously expressed MAP1S.
    supported_by:
    - reference_id: file:human/MAP1S/MAP1S-uniprot.txt
      supporting_text: Belongs to the MAP1 family.
- term:
    id: GO:0008017
    label: microtubule binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: Phylogenetic (IBA) assignment of microtubule binding, the defining MAP1-family molecular function. Strongly supported by IDA for MAP1S (two microtubule-binding sites).
    action: ACCEPT
    reason: Core molecular function; MAP1S directly binds microtubules.
    supported_by:
    - reference_id: PMID:16297881
      supporting_text: Microtubule-associated protein 8 contains two microtubule binding sites
- term:
    id: GO:0016358
    label: dendrite development
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: Phylogenetic (IBA) propagation of dendrite development from the neuronal MAP1 paralogs. Neuron-specific developmental role inherited from the family tree.
    action: KEEP_AS_NON_CORE
    reason: Neuronal developmental role transferred from paralogs; secondary for ubiquitously expressed MAP1S.
    supported_by:
    - reference_id: file:human/MAP1S/MAP1S-uniprot.txt
      supporting_text: Belongs to the MAP1 family.
- term:
    id: GO:0030425
    label: dendrite
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: Phylogenetic (IBA) propagation of dendrite localization from neuronal MAP1 paralogs/mouse ortholog. Neuron-specific secondary localization.
    action: KEEP_AS_NON_CORE
    reason: Neuron-specific localization transferred from paralogs/orthologs; secondary for ubiquitously expressed MAP1S.
    supported_by:
    - reference_id: file:human/MAP1S/MAP1S-uniprot.txt
      supporting_text: Belongs to the MAP1 family.
- term:
    id: GO:0031114
    label: regulation of microtubule depolymerization
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: Phylogenetic (IBA) assignment of regulation of microtubule depolymerization, consistent with MAP1S's microtubule-stabilizing/bundling activity (MAPs typically suppress depolymerization).
    action: KEEP_AS_NON_CORE
    reason: Plausible and consistent with the microtubule-stabilizing role, but only phylogenetically inferred for MAP1S; retained as a non-core aspect of its microtubule function.
    supported_by:
    - reference_id: PMID:15528209
      supporting_text: Microtubule-associated protein 1S, a short and ubiquitously expressed member of the microtubule-associated protein 1 family
- term:
    id: GO:0043025
    label: neuronal cell body
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: Phylogenetic (IBA) propagation of neuronal cell body localization from neuronal MAP1 paralogs/orthologs. Neuron-specific secondary localization.
    action: KEEP_AS_NON_CORE
    reason: Neuron-specific localization transferred from paralogs/orthologs; secondary for ubiquitously expressed MAP1S.
    supported_by:
    - reference_id: file:human/MAP1S/MAP1S-uniprot.txt
      supporting_text: Belongs to the MAP1 family.
- term:
    id: GO:0000226
    label: microtubule cytoskeleton organization
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: InterPro-based electronic assignment of microtubule cytoskeleton organization, redundant with the IBA and experimental support for this core process.
    action: ACCEPT
    reason: Core biological process; consistent with experimental microtubule bundling/organization evidence.
    supported_by:
    - reference_id: PMID:15528209
      supporting_text: Microtubule-associated protein 1S, a short and ubiquitously expressed member of the microtubule-associated protein 1 family
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Electronic transfer of nuclear localization from the UniProt subcellular location. MAP1S is detected in the nucleus (it shuttles and binds DNA), but the dominant functional pool is cytoplasmic/cytoskeletal.
    action: KEEP_AS_NON_CORE
    reason: Real but secondary localization (also IDA, PMID:12762840); MAP1S core functions are cytoplasmic (microtubule/autophagy).
    supported_by:
    - reference_id: file:human/MAP1S/MAP1S-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Nucleus.'
- term:
    id: GO:0005819
    label: spindle
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Electronic transfer of spindle localization from the UniProt subcellular location, corroborated by IDA evidence that MAP1S localizes to the mitotic spindle.
    action: ACCEPT
    reason: Correct localization; MAP1S is detected at spindle microtubules during mitosis and supports spindle organization.
    supported_by:
    - reference_id: file:human/MAP1S/MAP1S-uniprot.txt
      supporting_text: Cytoplasm, cytoskeleton, spindle
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Electronic transfer of cytosolic localization from the UniProt subcellular location, redundant with the IBA and IDA cytosol annotations.
    action: ACCEPT
    reason: Core localization; MAP1S is a cytoplasmic, microtubule-associated protein.
    supported_by:
    - reference_id: file:human/MAP1S/MAP1S-uniprot.txt
      supporting_text: Cytoplasm, cytosol
- term:
    id: GO:0005856
    label: cytoskeleton
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Electronic transfer of cytoskeleton localization from the UniProt subcellular location. Correct but generic parent of the specific microtubule localization.
    action: KEEP_AS_NON_CORE
    reason: Correct but generic; subsumed by the specific microtubule (GO:0005874) annotation.
    supported_by:
    - reference_id: file:human/MAP1S/MAP1S-uniprot.txt
      supporting_text: Cytoplasm, cytoskeleton
- term:
    id: GO:0005874
    label: microtubule
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: located_in
  review:
    summary: InterPro-based electronic assignment of microtubule localization, redundant with IBA and multiple IDA annotations.
    action: ACCEPT
    reason: Core localization; MAP1S associates with microtubules.
    supported_by:
    - reference_id: PMID:15528209
      supporting_text: Microtubule-associated protein 1S, a short and ubiquitously expressed member of the microtubule-associated protein 1 family
- term:
    id: GO:0008017
    label: microtubule binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: Electronic (combined IEA methods) assignment of microtubule binding, redundant with the IBA and IDA support for this core molecular function.
    action: ACCEPT
    reason: Core molecular function; MAP1S directly binds microtubules.
    supported_by:
    - reference_id: PMID:16297881
      supporting_text: Microtubule-associated protein 8 contains two microtubule binding sites
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:14627543
  qualifier: enables
  review:
    summary: IPI interaction with VCY2/BPY2 from the study that identified MAP1S as a VCY2-interacting protein. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records a real interaction (VCY2) but bare protein binding is uninformative per curation guidelines.
    supported_by:
    - reference_id: file:human/MAP1S/MAP1S-uniprot.txt
      supporting_text: 'Q66K74; O14599: BPY2B; NbExp=3; IntAct=EBI-2133734, EBI-2133713'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19027008
  qualifier: enables
  review:
    summary: IPI interaction with SOCS3 from a study on MAP1S in SOCS3 regulation of IL-6 signaling. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records a real interaction (SOCS3) but bare protein binding is uninformative.
    supported_by:
    - reference_id: file:human/MAP1S/MAP1S-uniprot.txt
      supporting_text: 'Q66K74; O14543: SOCS3; NbExp=6; IntAct=EBI-2133734, EBI-714146'
- term:
    id: GO:0007399
    label: nervous system development
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: involved_in
  review:
    summary: Electronic assignment of nervous system development, transferred from the mouse ortholog/ARBA. Broad developmental term reflecting neuronal MAP1-family roles.
    action: KEEP_AS_NON_CORE
    reason: Broad neuronal developmental process transferred electronically; secondary for ubiquitously expressed MAP1S.
    supported_by:
    - reference_id: file:human/MAP1S/MAP1S-uniprot.txt
      supporting_text: Belongs to the MAP1 family.
- term:
    id: GO:0007420
    label: brain development
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Electronic transfer of brain development from the mouse ortholog. Broad neuronal developmental term.
    action: KEEP_AS_NON_CORE
    reason: Broad neuronal developmental process transferred from ortholog; secondary for ubiquitously expressed MAP1S.
    supported_by:
    - reference_id: file:human/MAP1S/MAP1S-uniprot.txt
      supporting_text: Belongs to the MAP1 family.
- term:
    id: GO:0015630
    label: microtubule cytoskeleton
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: Electronic transfer of microtubule cytoskeleton localization from the mouse ortholog. Correct but generic parent of the specific microtubule localization.
    action: KEEP_AS_NON_CORE
    reason: Correct but generic; subsumed by the specific microtubule (GO:0005874) annotation.
    supported_by:
    - reference_id: file:human/MAP1S/MAP1S-uniprot.txt
      supporting_text: Cytoplasm, cytoskeleton
- term:
    id: GO:0015631
    label: tubulin binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    summary: Electronic transfer of tubulin binding from the mouse ortholog, redundant with the IDA evidence for MAP1S.
    action: ACCEPT
    reason: Core molecular function; MAP1S binds tubulin (also IDA-supported, PMID:15528209).
    supported_by:
    - reference_id: PMID:15528209
      supporting_text: Microtubule-associated protein 1S, a short and ubiquitously expressed member of the microtubule-associated protein 1 family
- term:
    id: GO:0030425
    label: dendrite
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: Electronic transfer of dendrite localization from the mouse ortholog. Neuron-specific secondary localization.
    action: KEEP_AS_NON_CORE
    reason: Neuron-specific localization transferred from ortholog; secondary for ubiquitously expressed MAP1S.
    supported_by:
    - reference_id: file:human/MAP1S/MAP1S-uniprot.txt
      supporting_text: Belongs to the MAP1 family.
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    summary: Electronic transfer of identical protein binding (self-association) from the mouse ortholog. Uninformative for the core function.
    action: KEEP_AS_NON_CORE
    reason: Self-association is plausible but uninformative as a molecular function; non-core.
    supported_by:
    - reference_id: file:human/MAP1S/MAP1S-uniprot.txt
      supporting_text: Belongs to the MAP1 family.
- term:
    id: GO:0043025
    label: neuronal cell body
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: Electronic transfer of neuronal cell body localization from the mouse ortholog. Neuron-specific secondary localization.
    action: KEEP_AS_NON_CORE
    reason: Neuron-specific localization transferred from ortholog; secondary for ubiquitously expressed MAP1S.
    supported_by:
    - reference_id: file:human/MAP1S/MAP1S-uniprot.txt
      supporting_text: Belongs to the MAP1 family.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: HPA immunofluorescence localization to the nucleoplasm. Consistent with the known nuclear/shuttling pool of MAP1S (it binds DNA), but secondary to its cytoplasmic functions.
    action: KEEP_AS_NON_CORE
    reason: Real but secondary nuclear localization; MAP1S core functions are cytoplasmic.
    supported_by:
    - reference_id: file:human/MAP1S/MAP1S-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Nucleus.'
- term:
    id: GO:0005730
    label: nucleolus
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: HPA immunofluorescence localization to the nucleolus. No functional literature places MAP1S activity in the nucleolus; likely reflects the nuclear shuttling pool/staining.
    action: KEEP_AS_NON_CORE
    reason: Single high-throughput immunofluorescence localization with no supporting functional role; secondary at best.
    supported_by:
    - reference_id: file:human/MAP1S/MAP1S-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Nucleus.'
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: HPA immunofluorescence localization to the cytosol, consistent with MAP1S's cytoplasmic microtubule-associated distribution.
    action: ACCEPT
    reason: Core localization; MAP1S is a cytoplasmic, microtubule-associated protein.
    supported_by:
    - reference_id: file:human/MAP1S/MAP1S-uniprot.txt
      supporting_text: Cytoplasm, cytosol
- term:
    id: GO:0005874
    label: microtubule
  evidence_type: IDA
  original_reference_id: PMID:22523538
  qualifier: located_in
  review:
    summary: Direct evidence of MAP1S microtubule localization from the Nemitin/WDR47 study.
    action: ACCEPT
    reason: Core localization; MAP1S associates with microtubules.
    supported_by:
    - reference_id: file:human/MAP1S/MAP1S-uniprot.txt
      supporting_text: Interacts with WDR47
- term:
    id: GO:0071987
    label: WD40-repeat domain binding
  evidence_type: IPI
  original_reference_id: PMID:22523538
  qualifier: enables
  review:
    summary: IPI evidence that MAP1S binds the WD40 repeats of WDR47/Nemitin. An informative molecular function (specific binding activity), but secondary to the core microtubule/autophagy roles.
    action: KEEP_AS_NON_CORE
    reason: Informative specific binding activity (WDR47/Nemitin), but a secondary interaction relative to MAP1S's core microtubule and autophagy-bridging functions.
    supported_by:
    - reference_id: file:human/MAP1S/MAP1S-uniprot.txt
      supporting_text: Interacts with WDR47 (via N-terminus of light chain)
- term:
    id: GO:0005813
    label: centrosome
  evidence_type: IDA
  original_reference_id: PMID:17234756
  qualifier: located_in
  review:
    summary: IDA localization to the centrosome from the study showing MAP1S depletion causes mitotic abnormalities. Consistent with its role anchoring the MTOC.
    action: ACCEPT
    reason: Correct localization tied to MAP1S's microtubule-organizing-center anchoring function.
    supported_by:
    - reference_id: PMID:17234756
      supporting_text: C19ORF5/MAP1S, causes mitotic abnormalities
- term:
    id: GO:0005815
    label: microtubule organizing center
  evidence_type: IDA
  original_reference_id: PMID:17234756
  qualifier: located_in
  review:
    summary: IDA localization to the microtubule organizing center, consistent with MAP1S's documented role in anchoring the MTOC to the centrosome.
    action: ACCEPT
    reason: Correct localization tied to MAP1S's MTOC-anchoring function.
    supported_by:
    - reference_id: file:human/MAP1S/MAP1S-uniprot.txt
      supporting_text: Necessary for the microtubule-organizing center localization
- term:
    id: GO:0007052
    label: mitotic spindle organization
  evidence_type: IMP
  original_reference_id: PMID:17234756
  qualifier: involved_in
  review:
    summary: IMP evidence that MAP1S depletion causes mitotic spindle abnormalities (multipolar spindles, failure to form a stable metaphase plate), indicating a role in mitotic spindle organization.
    action: KEEP_AS_NON_CORE
    reason: Well-supported mitotic role, but a distinct cellular function from the microtubule/autophagy-bridging core; retained as a non-core cytoskeletal/mitotic function.
    supported_by:
    - reference_id: file:human/MAP1S/MAP1S-uniprot.txt
      supporting_text: Depletion of MAP1S by RNAi causes mitotic abnormalities
- term:
    id: GO:0034454
    label: microtubule anchoring at centrosome
  evidence_type: IMP
  original_reference_id: PMID:17234756
  qualifier: involved_in
  review:
    summary: IMP evidence that MAP1S anchors the microtubule-organizing center to the centrosome; its depletion disrupts this anchoring and causes mitotic defects.
    action: ACCEPT
    reason: Specific, well-supported function (microtubule/MTOC anchoring at centrosome) directly within MAP1S's microtubule-organizing role.
    supported_by:
    - reference_id: file:human/MAP1S/MAP1S-uniprot.txt
      supporting_text: Plays a role in anchoring the microtubule organizing center to the centrosomes
- term:
    id: GO:0051310
    label: metaphase chromosome alignment
  evidence_type: IMP
  original_reference_id: PMID:17234756
  qualifier: involved_in
  review:
    summary: IMP evidence that MAP1S depletion impairs metaphase chromosome alignment (failure to form a stable metaphase plate, lagging chromosomes).
    action: KEEP_AS_NON_CORE
    reason: Well-supported but a downstream consequence of MAP1S's mitotic spindle/MTOC role; non-core relative to the microtubule/autophagy-bridging function.
    supported_by:
    - reference_id: file:human/MAP1S/MAP1S-uniprot.txt
      supporting_text: failure to form a stable metaphase plate, premature sister chromatid separation, lagging chromosomes, and multipolar spindles
- term:
    id: GO:1990498
    label: mitotic spindle microtubule
  evidence_type: IDA
  original_reference_id: PMID:17234756
  qualifier: located_in
  review:
    summary: IDA localization to mitotic spindle microtubules, consistent with MAP1S's mitotic role.
    action: KEEP_AS_NON_CORE
    reason: Real localization during mitosis; secondary to the core cytoplasmic microtubule/autophagy functions.
    supported_by:
    - reference_id: file:human/MAP1S/MAP1S-uniprot.txt
      supporting_text: During the different stages of mitosis detected at the spindle microtubules
- term:
    id: GO:0005819
    label: spindle
  evidence_type: IDA
  original_reference_id: PMID:18445686
  qualifier: located_in
  review:
    summary: IDA localization to the spindle (EML3 study). Consistent with MAP1S's mitotic spindle localization.
    action: ACCEPT
    reason: Correct localization; MAP1S is detected at the spindle during mitosis.
    supported_by:
    - reference_id: file:human/MAP1S/MAP1S-uniprot.txt
      supporting_text: Cytoplasm, cytoskeleton, spindle
- term:
    id: GO:0005874
    label: microtubule
  evidence_type: IDA
  original_reference_id: PMID:18445686
  qualifier: located_in
  review:
    summary: IDA microtubule localization (EML3 study). Redundant with the other IDA microtubule annotations.
    action: ACCEPT
    reason: Core localization; MAP1S associates with microtubules.
    supported_by:
    - reference_id: file:human/MAP1S/MAP1S-uniprot.txt
      supporting_text: partial localization to the microtubules
- term:
    id: GO:0006914
    label: autophagy
  evidence_type: TAS
  original_reference_id: PMID:21262964
  qualifier: involved_in
  review:
    summary: TAS evidence that MAP1S participates in autophagy by bridging LC3/Atg8 and LRPPRC (mitochondria) to microtubules, promoting autophagosome biogenesis, trafficking and degradation. This is MAP1S's distinctive core biological process.
    action: ACCEPT
    reason: Core biological process; the MAP1S-LC3-microtubule-LRPPRC bridge is the functionally distinctive role of MAP1S in autophagy/selective autophagy of mitochondria.
    supported_by:
    - reference_id: PMID:21262964
      supporting_text: MAP1S isoforms may play positive roles in integration of autophagic components with microtubules and mitochondria in both autophagosomal biogenesis and degradation
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17658481
  qualifier: enables
  review:
    summary: IPI interaction with the NMDAR subunit NR3A/GRIN3A in brain. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records a real neuronal interaction (NR3A) but bare protein binding is uninformative.
    supported_by:
    - reference_id: file:human/MAP1S/MAP1S-uniprot.txt
      supporting_text: Interacts with ESR1, LRPPRC, RASSF1 isoform A and isoform C, microtubules and VCY2
- term:
    id: GO:0005874
    label: microtubule
  evidence_type: IDA
  original_reference_id: PMID:17658481
  qualifier: located_in
  review:
    summary: IDA microtubule localization in the NR3A/brain study. Redundant with the other IDA microtubule annotations.
    action: ACCEPT
    reason: Core localization; MAP1S associates with microtubules.
    supported_by:
    - reference_id: file:human/MAP1S/MAP1S-uniprot.txt
      supporting_text: partial localization to the microtubules
- term:
    id: GO:0042995
    label: cell projection
  evidence_type: IDA
  original_reference_id: PMID:17658481
  qualifier: located_in
  review:
    summary: IDA localization to cell projections (neuronal). Secondary/neuronal localization.
    action: KEEP_AS_NON_CORE
    reason: Real neuronal-context localization; secondary to MAP1S's core cytoplasmic microtubule/autophagy roles.
    supported_by:
    - reference_id: file:human/MAP1S/MAP1S-uniprot.txt
      supporting_text: Detected in filopodia-like protrusions and synapses
- term:
    id: GO:0045202
    label: synapse
  evidence_type: IDA
  original_reference_id: PMID:17658481
  qualifier: located_in
  review:
    summary: IDA localization to synapses in neurons (NR3A study). Consistent with the IBA synapse annotation; neuron-specific secondary localization.
    action: KEEP_AS_NON_CORE
    reason: Real neuron-specific localization; secondary to MAP1S's core cytoplasmic functions.
    supported_by:
    - reference_id: file:human/MAP1S/MAP1S-uniprot.txt
      supporting_text: Detected in filopodia-like protrusions and synapses
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:12762840
  qualifier: enables
  review:
    summary: IPI interactions (including LRPPRC and RASSF1) from the study integrating mitochondria and the microtubule cytoskeleton. The LRPPRC interaction is functionally important (links to mitophagy), but bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records functionally relevant interactions (LRPPRC, RASSF1) but bare protein binding is uninformative; the autophagy/microtubule-bridging function captures these.
    supported_by:
    - reference_id: file:human/MAP1S/MAP1S-uniprot.txt
      supporting_text: Interacts with ESR1, LRPPRC, RASSF1 isoform A and isoform C, microtubules and VCY2
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:12762840
  qualifier: located_in
  review:
    summary: IDA nuclear localization. MAP1S shuttles to the nucleus (it binds DNA), but the dominant functional pool is cytoplasmic/cytoskeletal.
    action: KEEP_AS_NON_CORE
    reason: Real but secondary nuclear localization; MAP1S core functions are cytoplasmic.
    supported_by:
    - reference_id: file:human/MAP1S/MAP1S-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Nucleus.'
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: PMID:12762840
  qualifier: located_in
  review:
    summary: IDA cytosolic localization, consistent with MAP1S's cytoplasmic microtubule-associated distribution.
    action: ACCEPT
    reason: Core localization; MAP1S is a cytoplasmic, microtubule-associated protein.
    supported_by:
    - reference_id: file:human/MAP1S/MAP1S-uniprot.txt
      supporting_text: Cytoplasm, cytosol
- term:
    id: GO:0048487
    label: beta-tubulin binding
  evidence_type: IDA
  original_reference_id: PMID:12762840
  qualifier: enables
  review:
    summary: IDA evidence that MAP1S binds beta-tubulin, a specific and informative molecular function underlying its microtubule association.
    action: ACCEPT
    reason: Core molecular function; specific tubulin-binding activity of MAP1S.
    supported_by:
    - reference_id: file:human/MAP1S/MAP1S-uniprot.txt
      supporting_text: Interacts with microtubules and actin.
- term:
    id: GO:0051015
    label: actin filament binding
  evidence_type: IDA
  original_reference_id: PMID:12762840
  qualifier: enables
  negated: true
  review:
    summary: Curated NOT (negated) annotation - this study found MAP1S does NOT bind actin filaments under the tested conditions. Note a separate study (PMID:15528209) reported positive actin filament binding (light chain), so this activity is context/construct-dependent.
    action: ACCEPT
    reason: Accept the curated negation as-is; it records that MAP1S did not show actin-filament binding in this assay. The apparent conflict with the positive IDA reflects different experimental contexts (full-length versus light-chain constructs) and should be left for expert resolution.
    supported_by:
    - reference_id: file:human/MAP1S/MAP1S-uniprot.txt
      supporting_text: MAP1S light chain interacts with actin
- term:
    id: GO:0008017
    label: microtubule binding
  evidence_type: TAS
  original_reference_id: PMID:12762840
  qualifier: enables
  review:
    summary: TAS assignment of microtubule binding, redundant with the IBA/IEA/IDA support for this core molecular function.
    action: ACCEPT
    reason: Core molecular function; MAP1S directly binds microtubules.
    supported_by:
    - reference_id: file:human/MAP1S/MAP1S-uniprot.txt
      supporting_text: Interacts with microtubules and actin.
- term:
    id: GO:0008017
    label: microtubule binding
  evidence_type: IDA
  original_reference_id: PMID:15528209
  qualifier: enables
  review:
    summary: IDA evidence of microtubule binding from the original MAP1S characterization paper. Core molecular function.
    action: ACCEPT
    reason: Core molecular function; MAP1S directly binds microtubules.
    supported_by:
    - reference_id: PMID:15528209
      supporting_text: Microtubule-associated protein 1S, a short and ubiquitously expressed member of the microtubule-associated protein 1 family
- term:
    id: GO:0015631
    label: tubulin binding
  evidence_type: IDA
  original_reference_id: PMID:15528209
  qualifier: enables
  review:
    summary: IDA evidence of tubulin binding from the original MAP1S characterization paper. Core molecular function.
    action: ACCEPT
    reason: Core molecular function; MAP1S binds tubulin.
    supported_by:
    - reference_id: PMID:15528209
      supporting_text: Microtubule-associated protein 1S, a short and ubiquitously expressed member of the microtubule-associated protein 1 family
- term:
    id: GO:0047497
    label: mitochondrion transport along microtubule
  evidence_type: TAS
  original_reference_id: PMID:12762840
  qualifier: involved_in
  review:
    summary: TAS assignment of mitochondrion transport along microtubules, consistent with MAP1S integrating mitochondria (via LRPPRC) with the microtubule cytoskeleton.
    action: KEEP_AS_NON_CORE
    reason: Consistent with MAP1S's mitochondria-microtubule bridging role; retained as a non-core aspect of the broader autophagy/mitochondria-cytoskeleton function.
    supported_by:
    - reference_id: PMID:21262964
      supporting_text: MAP1S interacted with mitochondrion-associated leucine-rich PPR-motif containing protein (LRPPRC)
- term:
    id: GO:0048471
    label: perinuclear region of cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:12762840
  qualifier: located_in
  review:
    summary: IDA localization to the perinuclear region, where MAP1S forms a punctate network corresponding to mitochondrial aggregates.
    action: KEEP_AS_NON_CORE
    reason: Real cytoplasmic sub-localization tied to mitochondrial aggregation; a specific compartment within the core cytoplasmic distribution.
    supported_by:
    - reference_id: file:human/MAP1S/MAP1S-uniprot.txt
      supporting_text: Detected in perinuclear punctate network corresponding to mitochondrial aggregates
- term:
    id: GO:0051015
    label: actin filament binding
  evidence_type: IDA
  original_reference_id: PMID:15528209
  qualifier: enables
  review:
    summary: IDA evidence that MAP1S (light chain) binds actin filaments. Note a separate study reported NOT actin filament binding under different conditions; the activity appears context/construct-dependent.
    action: KEEP_AS_NON_CORE
    reason: Supported actin-filament-binding activity of the light chain, but secondary to MAP1S's core microtubule role and partly contradicted by a curated NOT annotation; retained as non-core pending expert resolution.
    supported_by:
    - reference_id: file:human/MAP1S/MAP1S-uniprot.txt
      supporting_text: MAP1S light chain interacts with actin
- term:
    id: GO:0001578
    label: microtubule bundle formation
  evidence_type: IMP
  original_reference_id: PMID:15528209
  qualifier: involved_in
  review:
    summary: IMP evidence that MAP1S participates in microtubule bundle formation, a direct consequence of its microtubule cross-linking activity. Core process.
    action: ACCEPT
    reason: Core biological process; MAP1S cross-links and bundles microtubules.
    supported_by:
    - reference_id: file:human/MAP1S/MAP1S-uniprot.txt
      supporting_text: Involved in the formation of microtubule bundles
- term:
    id: GO:0003677
    label: DNA binding
  evidence_type: IDA
  original_reference_id: PMID:15907802
  qualifier: enables
  review:
    summary: IDA evidence that MAP1S (C19ORF5) binds DNA. A real but secondary molecular function relative to its microtubule/autophagy roles.
    action: KEEP_AS_NON_CORE
    reason: Experimentally supported DNA binding, but secondary to MAP1S's core cytoskeletal/autophagy functions and of uncertain physiological role.
    supported_by:
    - reference_id: PMID:15907802
      supporting_text: C19ORF5 is a DNA binding protein
- term:
    id: GO:0004536
    label: DNA nuclease activity
  evidence_type: IDA
  original_reference_id: PMID:15907802
  qualifier: enables
  negated: true
  review:
    summary: Curated NOT (negated) annotation - the study showed MAP1S binds DNA but does NOT have DNA nuclease activity. The negation is appropriate and informative.
    action: ACCEPT
    reason: Accept the curated negation; it correctly records that MAP1S lacks DNA nuclease activity despite binding DNA.
    supported_by:
    - reference_id: PMID:15907802
      supporting_text: C19ORF5 is a DNA binding protein
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15907802
  qualifier: enables
  review:
    summary: IPI interaction (RASSF1, P42704/LRPPRC) from the C19ORF5 DNA-binding study. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records real interactions but bare protein binding is uninformative.
    supported_by:
    - reference_id: file:human/MAP1S/MAP1S-uniprot.txt
      supporting_text: Interacts with ESR1, LRPPRC, RASSF1 isoform A and isoform C, microtubules and VCY2
- term:
    id: GO:0005874
    label: microtubule
  evidence_type: IDA
  original_reference_id: PMID:15528209
  qualifier: located_in
  review:
    summary: IDA microtubule localization from the original MAP1S characterization. Redundant with the other IDA microtubule annotations.
    action: ACCEPT
    reason: Core localization; MAP1S associates with microtubules.
    supported_by:
    - reference_id: PMID:15528209
      supporting_text: Microtubule-associated protein 1S, a short and ubiquitously expressed member of the microtubule-associated protein 1 family
- term:
    id: GO:0007399
    label: nervous system development
  evidence_type: ISS
  original_reference_id: PMID:16297881
  qualifier: involved_in
  review:
    summary: ISS assignment of nervous system development by sequence similarity (to the mouse ortholog). Broad neuronal developmental role.
    action: KEEP_AS_NON_CORE
    reason: Broad neuronal developmental process inferred by similarity; secondary for ubiquitously expressed MAP1S.
    supported_by:
    - reference_id: file:human/MAP1S/MAP1S-uniprot.txt
      supporting_text: Belongs to the MAP1 family.
- term:
    id: GO:0007420
    label: brain development
  evidence_type: ISS
  original_reference_id: PMID:15528209
  qualifier: involved_in
  review:
    summary: ISS assignment of brain development by similarity to the mouse ortholog. Broad neuronal developmental role.
    action: KEEP_AS_NON_CORE
    reason: Broad neuronal developmental process inferred by similarity; secondary for ubiquitously expressed MAP1S.
    supported_by:
    - reference_id: file:human/MAP1S/MAP1S-uniprot.txt
      supporting_text: Belongs to the MAP1 family.
- term:
    id: GO:0030425
    label: dendrite
  evidence_type: ISS
  original_reference_id: PMID:15528209
  qualifier: located_in
  review:
    summary: ISS assignment of dendrite localization by similarity to the mouse ortholog. Neuron-specific secondary localization.
    action: KEEP_AS_NON_CORE
    reason: Neuron-specific localization inferred by similarity; secondary for ubiquitously expressed MAP1S.
    supported_by:
    - reference_id: file:human/MAP1S/MAP1S-uniprot.txt
      supporting_text: Belongs to the MAP1 family.
- term:
    id: GO:0043025
    label: neuronal cell body
  evidence_type: ISS
  original_reference_id: PMID:15528209
  qualifier: located_in
  review:
    summary: ISS assignment of neuronal cell body localization by similarity to the mouse ortholog. Neuron-specific secondary localization.
    action: KEEP_AS_NON_CORE
    reason: Neuron-specific localization inferred by similarity; secondary for ubiquitously expressed MAP1S.
    supported_by:
    - reference_id: file:human/MAP1S/MAP1S-uniprot.txt
      supporting_text: Belongs to the MAP1 family.
- term:
    id: GO:0048812
    label: neuron projection morphogenesis
  evidence_type: IEP
  original_reference_id: PMID:15528209
  qualifier: involved_in
  review:
    summary: IEP (expression-pattern) assignment of neuron projection morphogenesis. A neuronal developmental role consistent with MAP1S's microtubule function in neurons.
    action: KEEP_AS_NON_CORE
    reason: Neuronal developmental role inferred from expression; secondary for ubiquitously expressed MAP1S.
    supported_by:
    - reference_id: file:human/MAP1S/MAP1S-uniprot.txt
      supporting_text: Expressed in neurons (at protein level)
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:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to
    orthologs using Ensembl Compara
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:12762840
  title: Novel complex integrating mitochondria and the microtubular cytoskeleton
    with chromosome remodeling and tumor suppressor RASSF1 deduced by in silico homology
    analysis, interaction cloning in yeast, and colocalization in cultured cells.
  findings: []
- id: PMID:14627543
  title: 'Identification and characterization of human VCY2-interacting protein: VCY2IP-1,
    a microtubule-associated protein-like protein.'
  findings: []
- id: PMID:15528209
  title: Microtubule-associated protein 1S, a short and ubiquitously expressed member
    of the microtubule-associated protein 1 family.
  findings:
  - statement: MAP1S (C19ORF5) is the short, ubiquitously expressed MAP1 family member; it associates with stabilized microtubules, binds microtubules and tubulin, forms microtubule bundles, and (light chain) binds actin filaments.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Original MAP1S characterization (also indexed under the C19ORF5/MAP8 names). Source of the core microtubule/tubulin binding and bundle-formation annotations.
- id: PMID:15907802
  title: Putative tumor suppressor RASSF1 interactive protein and cell death inducer
    C19ORF5 is a DNA binding protein.
  findings: []
- id: PMID:16297881
  title: Microtubule-associated protein 8 contains two microtubule binding sites.
  findings: []
- id: PMID:17234756
  title: Depletion of the Ras association domain family 1, isoform A-associated novel
    microtubule-associated protein, C19ORF5/MAP1S, causes mitotic abnormalities.
  findings:
  - statement: MAP1S localizes to the centrosome/microtubule-organizing center and mitotic spindle; its depletion causes mitotic abnormalities (failure to form a stable metaphase plate, lagging chromosomes, multipolar spindles) and disrupts microtubule anchoring at the centrosome.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Source of the centrosome/MTOC localization and mitotic-role annotations (spindle organization, MTOC anchoring, metaphase chromosome alignment).
- id: PMID:17658481
  title: The NMDAR subunit NR3A interacts with microtubule-associated protein 1S in
    the brain.
  findings: []
- id: PMID:18445686
  title: EML3 is a nuclear microtubule-binding protein required for the correct alignment
    of chromosomes in metaphase.
  findings: []
- id: PMID:19027008
  title: The role of microtubule-associated protein 1S in SOCS3 regulation of IL-6
    signaling.
  findings: []
- id: PMID:21262964
  title: Microtubule-associated protein 1S (MAP1S) bridges autophagic components with
    microtubules and mitochondria to affect autophagosomal biogenesis and degradation.
  findings:
  - statement: MAP1S isoforms bind the autophagosome-associated LC3 (Atg8 homolog) and recruit it to stable microtubules, and bind the mitochondrion-associated protein LRPPRC (which links to the mitophagy initiator Parkin), integrating autophagic components with microtubules and mitochondria in autophagosome biogenesis and degradation. Map1s-knockout mice show accumulation of defective mitochondria and severe defects in the nutritive-stress response.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Full text available in cache. Defines MAP1S's distinctive core function bridging the autophagy machinery (LC3/Atg8, LRPPRC) to microtubules and mitochondria; basis of the autophagy (GO:0006914) annotation.
- id: PMID:22523538
  title: Nemitin, a novel Map8/Map1s interacting protein with Wd40 repeats.
  findings: []
core_functions:
- description: Binds tubulin and microtubules and cross-links/bundles them, contributing
    to organization and stabilization of the microtubule cytoskeleton. MAP1S is processed
    into heavy and light chains that re-associate as a microtubule-associated heterodimer.
  molecular_function:
    id: GO:0008017
    label: microtubule binding
  locations:
  - id: GO:0005874
    label: microtubule
  supported_by:
  - reference_id: PMID:16297881
    supporting_text: Microtubule-associated protein 8 contains two microtubule binding sites
  directly_involved_in:
  - id: GO:0000226
    label: microtubule cytoskeleton organization
  - id: GO:0001578
    label: microtubule bundle formation
- description: Acts as a bridge coupling the autophagy machinery to the microtubule
    cytoskeleton and mitochondria - binding the Atg8/LC3 protein and recruiting it to
    stable microtubules, and binding the mitochondrion-associated protein LRPPRC - to
    promote autophagosome biogenesis, trafficking and degradation and the clearance of
    defective mitochondria (selective autophagy/mitophagy).
  molecular_function:
    id: GO:0008017
    label: microtubule binding
  locations:
  - id: GO:0005874
    label: microtubule
  - id: GO:0048471
    label: perinuclear region of cytoplasm
  supported_by:
  - reference_id: PMID:21262964
    supporting_text: MAP1S isoforms may play positive roles in integration of autophagic components with microtubules and mitochondria in both autophagosomal biogenesis and degradation
  directly_involved_in:
  - id: GO:0006914
    label: autophagy
- description: Anchors the microtubule-organizing center to the centrosome and supports
    proper mitotic spindle organization and chromosome alignment; depletion of MAP1S
    causes mitotic abnormalities.
  molecular_function:
    id: GO:0008017
    label: microtubule binding
  locations:
  - id: GO:0005815
    label: microtubule organizing center
  - id: GO:0005819
    label: spindle
  supported_by:
  - reference_id: PMID:17234756
    supporting_text: C19ORF5/MAP1S, causes mitotic abnormalities
  directly_involved_in:
  - id: GO:0034454
    label: microtubule anchoring at centrosome
suggested_questions:
- question: Is the MAP1S-LC3-microtubule-LRPPRC bridge selective for mitophagy (clearance
    of defective mitochondria) or does it support bulk autophagosome trafficking more
    generally, and how is its activity regulated by the extensive phosphorylation of
    MAP1S?
- question: How are MAP1S's distinct functional pools (microtubule/autophagy cytoplasmic
    pool versus the mitotic spindle/MTOC pool versus the DNA-binding nuclear pool)
    partitioned across the cell cycle and differentiation?
suggested_experiments:
- description: Live-cell imaging of LC3/autophagosome trafficking along microtubules
    in MAP1S-knockout versus wild-type cells under nutrient starvation and mitochondrial
    depolarization (CCCP) to quantify the contribution of MAP1S to autophagosome
    motility and mitophagic flux.
- description: Structure-function dissection using separation-of-function MAP1S mutants
    (LC3-binding-deficient versus LRPPRC-binding-deficient versus microtubule-binding-deficient)
    to dissociate the autophagy-bridging role from the mitotic/MTOC-anchoring role.