Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0045202 synapse	IBA GO_REF:0000033	KEEP AS NON CORE	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. Reason: Real but neuron-specific/secondary localization (also supported by IDA, PMID:17658481); not central to MAP1S's core microtubule/autophagy functions. Supporting Evidence: file:human/MAP1S/MAP1S-uniprot.txt Detected in filopodia-like protrusions and synapses
GO:0000226 microtubule cytoskeleton organization	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) assignment of microtubule cytoskeleton organization, a core MAP1-family function. Supported experimentally for MAP1S (microtubule bundling/stabilization). Reason: Core biological process; MAP1S binds, bundles and stabilizes microtubules. Supporting Evidence: PMID:15528209 Microtubule-associated protein 1S, a short and ubiquitously expressed member of the microtubule-associated protein 1 family
GO:0005874 microtubule	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) assignment of microtubule localization, the defining MAP1-family compartment. Strongly supported by multiple IDA studies for MAP1S. Reason: Core localization; MAP1S associates with and acts on microtubules. Supporting Evidence: PMID:15528209 Microtubule-associated protein 1S, a short and ubiquitously expressed member of the microtubule-associated protein 1 family
GO:0003779 actin binding	IBA GO_REF:0000033	KEEP AS NON CORE	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. 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. Supporting Evidence: file:human/MAP1S/MAP1S-uniprot.txt MAP1S light chain interacts with actin
GO:0005829 cytosol	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) assignment of cytosolic localization, consistent with MAP1S's cytoplasmic microtubule-associated distribution. Supported by IDA and the UniProt subcellular location. Reason: Core localization; MAP1S is a cytoplasmic, microtubule-associated protein. Supporting Evidence: file:human/MAP1S/MAP1S-uniprot.txt Cytoplasm, cytosol
GO:0005875 microtubule associated complex	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) assignment that MAP1S is part of a microtubule-associated complex, consistent with its heavy/light chain heterodimer that binds microtubules. Reason: Core cellular component; MAP1S forms a microtubule-associated heterodimer complex. Supporting Evidence: file:human/MAP1S/MAP1S-uniprot.txt Heterodimer of a heavy and a light chain. Interacts with microtubules and actin.
GO:0007409 axonogenesis	IBA GO_REF:0000033	KEEP AS NON CORE	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. Reason: Neuronal developmental role transferred from paralogs; secondary/peripheral for ubiquitously expressed MAP1S. Supporting Evidence: file:human/MAP1S/MAP1S-uniprot.txt Belongs to the MAP1 family.
GO:0008017 microtubule binding	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) assignment of microtubule binding, the defining MAP1-family molecular function. Strongly supported by IDA for MAP1S (two microtubule-binding sites). Reason: Core molecular function; MAP1S directly binds microtubules. Supporting Evidence: PMID:16297881 Microtubule-associated protein 8 contains two microtubule binding sites
GO:0016358 dendrite development	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Phylogenetic (IBA) propagation of dendrite development from the neuronal MAP1 paralogs. Neuron-specific developmental role inherited from the family tree. Reason: Neuronal developmental role transferred from paralogs; secondary for ubiquitously expressed MAP1S. Supporting Evidence: file:human/MAP1S/MAP1S-uniprot.txt Belongs to the MAP1 family.
GO:0030425 dendrite	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Phylogenetic (IBA) propagation of dendrite localization from neuronal MAP1 paralogs/mouse ortholog. Neuron-specific secondary localization. Reason: Neuron-specific localization transferred from paralogs/orthologs; secondary for ubiquitously expressed MAP1S. Supporting Evidence: file:human/MAP1S/MAP1S-uniprot.txt Belongs to the MAP1 family.
GO:0031114 regulation of microtubule depolymerization	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Phylogenetic (IBA) assignment of regulation of microtubule depolymerization, consistent with MAP1S's microtubule-stabilizing/bundling activity (MAPs typically suppress depolymerization). 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. Supporting Evidence: PMID:15528209 Microtubule-associated protein 1S, a short and ubiquitously expressed member of the microtubule-associated protein 1 family
GO:0043025 neuronal cell body	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Phylogenetic (IBA) propagation of neuronal cell body localization from neuronal MAP1 paralogs/orthologs. Neuron-specific secondary localization. Reason: Neuron-specific localization transferred from paralogs/orthologs; secondary for ubiquitously expressed MAP1S. Supporting Evidence: file:human/MAP1S/MAP1S-uniprot.txt Belongs to the MAP1 family.
GO:0000226 microtubule cytoskeleton organization	IEA GO_REF:0000002	ACCEPT	Summary: InterPro-based electronic assignment of microtubule cytoskeleton organization, redundant with the IBA and experimental support for this core process. Reason: Core biological process; consistent with experimental microtubule bundling/organization evidence. Supporting Evidence: PMID:15528209 Microtubule-associated protein 1S, a short and ubiquitously expressed member of the microtubule-associated protein 1 family
GO:0005634 nucleus	IEA GO_REF:0000044	KEEP AS NON CORE	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. Reason: Real but secondary localization (also IDA, PMID:12762840); MAP1S core functions are cytoplasmic (microtubule/autophagy). Supporting Evidence: file:human/MAP1S/MAP1S-uniprot.txt SUBCELLULAR LOCATION: Nucleus.
GO:0005819 spindle	IEA GO_REF:0000044	ACCEPT	Summary: Electronic transfer of spindle localization from the UniProt subcellular location, corroborated by IDA evidence that MAP1S localizes to the mitotic spindle. Reason: Correct localization; MAP1S is detected at spindle microtubules during mitosis and supports spindle organization. Supporting Evidence: file:human/MAP1S/MAP1S-uniprot.txt Cytoplasm, cytoskeleton, spindle
GO:0005829 cytosol	IEA GO_REF:0000044	ACCEPT	Summary: Electronic transfer of cytosolic localization from the UniProt subcellular location, redundant with the IBA and IDA cytosol annotations. Reason: Core localization; MAP1S is a cytoplasmic, microtubule-associated protein. Supporting Evidence: file:human/MAP1S/MAP1S-uniprot.txt Cytoplasm, cytosol
GO:0005856 cytoskeleton	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Electronic transfer of cytoskeleton localization from the UniProt subcellular location. Correct but generic parent of the specific microtubule localization. Reason: Correct but generic; subsumed by the specific microtubule (GO:0005874) annotation. Supporting Evidence: file:human/MAP1S/MAP1S-uniprot.txt Cytoplasm, cytoskeleton
GO:0005874 microtubule	IEA GO_REF:0000002	ACCEPT	Summary: InterPro-based electronic assignment of microtubule localization, redundant with IBA and multiple IDA annotations. Reason: Core localization; MAP1S associates with microtubules. Supporting Evidence: PMID:15528209 Microtubule-associated protein 1S, a short and ubiquitously expressed member of the microtubule-associated protein 1 family
GO:0008017 microtubule binding	IEA GO_REF:0000120	ACCEPT	Summary: Electronic (combined IEA methods) assignment of microtubule binding, redundant with the IBA and IDA support for this core molecular function. Reason: Core molecular function; MAP1S directly binds microtubules. Supporting Evidence: PMID:16297881 Microtubule-associated protein 8 contains two microtubule binding sites
GO:0005515 protein binding	IPI PMID:14627543 Identification and characterization of human VCY2-interactin...	KEEP AS NON CORE	Summary: IPI interaction with VCY2/BPY2 from the study that identified MAP1S as a VCY2-interacting protein. Bare protein binding is uninformative. Reason: Records a real interaction (VCY2) but bare protein binding is uninformative per curation guidelines. Supporting Evidence: file:human/MAP1S/MAP1S-uniprot.txt Q66K74; O14599: BPY2B; NbExp=3; IntAct=EBI-2133734, EBI-2133713
GO:0005515 protein binding	IPI PMID:19027008 The role of microtubule-associated protein 1S in SOCS3 regul...	KEEP AS NON CORE	Summary: IPI interaction with SOCS3 from a study on MAP1S in SOCS3 regulation of IL-6 signaling. Bare protein binding is uninformative. Reason: Records a real interaction (SOCS3) but bare protein binding is uninformative. Supporting Evidence: file:human/MAP1S/MAP1S-uniprot.txt Q66K74; O14543: SOCS3; NbExp=6; IntAct=EBI-2133734, EBI-714146
GO:0007399 nervous system development	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: Electronic assignment of nervous system development, transferred from the mouse ortholog/ARBA. Broad developmental term reflecting neuronal MAP1-family roles. Reason: Broad neuronal developmental process transferred electronically; secondary for ubiquitously expressed MAP1S. Supporting Evidence: file:human/MAP1S/MAP1S-uniprot.txt Belongs to the MAP1 family.
GO:0007420 brain development	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Electronic transfer of brain development from the mouse ortholog. Broad neuronal developmental term. Reason: Broad neuronal developmental process transferred from ortholog; secondary for ubiquitously expressed MAP1S. Supporting Evidence: file:human/MAP1S/MAP1S-uniprot.txt Belongs to the MAP1 family.
GO:0015630 microtubule cytoskeleton	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Electronic transfer of microtubule cytoskeleton localization from the mouse ortholog. Correct but generic parent of the specific microtubule localization. Reason: Correct but generic; subsumed by the specific microtubule (GO:0005874) annotation. Supporting Evidence: file:human/MAP1S/MAP1S-uniprot.txt Cytoplasm, cytoskeleton
GO:0015631 tubulin binding	IEA GO_REF:0000107	ACCEPT	Summary: Electronic transfer of tubulin binding from the mouse ortholog, redundant with the IDA evidence for MAP1S. Reason: Core molecular function; MAP1S binds tubulin (also IDA-supported, PMID:15528209). Supporting Evidence: PMID:15528209 Microtubule-associated protein 1S, a short and ubiquitously expressed member of the microtubule-associated protein 1 family
GO:0030425 dendrite	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Electronic transfer of dendrite localization from the mouse ortholog. Neuron-specific secondary localization. Reason: Neuron-specific localization transferred from ortholog; secondary for ubiquitously expressed MAP1S. Supporting Evidence: file:human/MAP1S/MAP1S-uniprot.txt Belongs to the MAP1 family.
GO:0042802 identical protein binding	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Electronic transfer of identical protein binding (self-association) from the mouse ortholog. Uninformative for the core function. Reason: Self-association is plausible but uninformative as a molecular function; non-core. Supporting Evidence: file:human/MAP1S/MAP1S-uniprot.txt Belongs to the MAP1 family.
GO:0043025 neuronal cell body	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Electronic transfer of neuronal cell body localization from the mouse ortholog. Neuron-specific secondary localization. Reason: Neuron-specific localization transferred from ortholog; secondary for ubiquitously expressed MAP1S. Supporting Evidence: file:human/MAP1S/MAP1S-uniprot.txt Belongs to the MAP1 family.
GO:0005654 nucleoplasm	IDA GO_REF:0000052	KEEP AS NON CORE	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. Reason: Real but secondary nuclear localization; MAP1S core functions are cytoplasmic. Supporting Evidence: file:human/MAP1S/MAP1S-uniprot.txt SUBCELLULAR LOCATION: Nucleus.
GO:0005730 nucleolus	IDA GO_REF:0000052	KEEP AS NON CORE	Summary: HPA immunofluorescence localization to the nucleolus. No functional literature places MAP1S activity in the nucleolus; likely reflects the nuclear shuttling pool/staining. Reason: Single high-throughput immunofluorescence localization with no supporting functional role; secondary at best. Supporting Evidence: file:human/MAP1S/MAP1S-uniprot.txt SUBCELLULAR LOCATION: Nucleus.
GO:0005829 cytosol	IDA GO_REF:0000052	ACCEPT	Summary: HPA immunofluorescence localization to the cytosol, consistent with MAP1S's cytoplasmic microtubule-associated distribution. Reason: Core localization; MAP1S is a cytoplasmic, microtubule-associated protein. Supporting Evidence: file:human/MAP1S/MAP1S-uniprot.txt Cytoplasm, cytosol
GO:0005874 microtubule	IDA PMID:22523538 Nemitin, a novel Map8/Map1s interacting protein with Wd40 re...	ACCEPT	Summary: Direct evidence of MAP1S microtubule localization from the Nemitin/WDR47 study. Reason: Core localization; MAP1S associates with microtubules. Supporting Evidence: file:human/MAP1S/MAP1S-uniprot.txt Interacts with WDR47
GO:0071987 WD40-repeat domain binding	IPI PMID:22523538 Nemitin, a novel Map8/Map1s interacting protein with Wd40 re...	KEEP AS NON CORE	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. Reason: Informative specific binding activity (WDR47/Nemitin), but a secondary interaction relative to MAP1S's core microtubule and autophagy-bridging functions. Supporting Evidence: file:human/MAP1S/MAP1S-uniprot.txt Interacts with WDR47 (via N-terminus of light chain)
GO:0005813 centrosome	IDA PMID:17234756 Depletion of the Ras association domain family 1, isoform A-...	ACCEPT	Summary: IDA localization to the centrosome from the study showing MAP1S depletion causes mitotic abnormalities. Consistent with its role anchoring the MTOC. Reason: Correct localization tied to MAP1S's microtubule-organizing-center anchoring function. Supporting Evidence: PMID:17234756 C19ORF5/MAP1S, causes mitotic abnormalities
GO:0005815 microtubule organizing center	IDA PMID:17234756 Depletion of the Ras association domain family 1, isoform A-...	ACCEPT	Summary: IDA localization to the microtubule organizing center, consistent with MAP1S's documented role in anchoring the MTOC to the centrosome. Reason: Correct localization tied to MAP1S's MTOC-anchoring function. Supporting Evidence: file:human/MAP1S/MAP1S-uniprot.txt Necessary for the microtubule-organizing center localization
GO:0007052 mitotic spindle organization	IMP PMID:17234756 Depletion of the Ras association domain family 1, isoform A-...	KEEP AS NON CORE	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. Reason: Well-supported mitotic role, but a distinct cellular function from the microtubule/autophagy-bridging core; retained as a non-core cytoskeletal/mitotic function. Supporting Evidence: file:human/MAP1S/MAP1S-uniprot.txt Depletion of MAP1S by RNAi causes mitotic abnormalities
GO:0034454 microtubule anchoring at centrosome	IMP PMID:17234756 Depletion of the Ras association domain family 1, isoform A-...	ACCEPT	Summary: IMP evidence that MAP1S anchors the microtubule-organizing center to the centrosome; its depletion disrupts this anchoring and causes mitotic defects. Reason: Specific, well-supported function (microtubule/MTOC anchoring at centrosome) directly within MAP1S's microtubule-organizing role. Supporting Evidence: file:human/MAP1S/MAP1S-uniprot.txt Plays a role in anchoring the microtubule organizing center to the centrosomes
GO:0051310 metaphase chromosome alignment	IMP PMID:17234756 Depletion of the Ras association domain family 1, isoform A-...	KEEP AS NON CORE	Summary: IMP evidence that MAP1S depletion impairs metaphase chromosome alignment (failure to form a stable metaphase plate, lagging chromosomes). Reason: Well-supported but a downstream consequence of MAP1S's mitotic spindle/MTOC role; non-core relative to the microtubule/autophagy-bridging function. Supporting Evidence: file:human/MAP1S/MAP1S-uniprot.txt failure to form a stable metaphase plate, premature sister chromatid separation, lagging chromosomes, and multipolar spindles
GO:1990498 mitotic spindle microtubule	IDA PMID:17234756 Depletion of the Ras association domain family 1, isoform A-...	KEEP AS NON CORE	Summary: IDA localization to mitotic spindle microtubules, consistent with MAP1S's mitotic role. Reason: Real localization during mitosis; secondary to the core cytoplasmic microtubule/autophagy functions. Supporting Evidence: file:human/MAP1S/MAP1S-uniprot.txt During the different stages of mitosis detected at the spindle microtubules
GO:0005819 spindle	IDA PMID:18445686 EML3 is a nuclear microtubule-binding protein required for t...	ACCEPT	Summary: IDA localization to the spindle (EML3 study). Consistent with MAP1S's mitotic spindle localization. Reason: Correct localization; MAP1S is detected at the spindle during mitosis. Supporting Evidence: file:human/MAP1S/MAP1S-uniprot.txt Cytoplasm, cytoskeleton, spindle
GO:0005874 microtubule	IDA PMID:18445686 EML3 is a nuclear microtubule-binding protein required for t...	ACCEPT	Summary: IDA microtubule localization (EML3 study). Redundant with the other IDA microtubule annotations. Reason: Core localization; MAP1S associates with microtubules. Supporting Evidence: file:human/MAP1S/MAP1S-uniprot.txt partial localization to the microtubules
GO:0006914 autophagy	TAS PMID:21262964 Microtubule-associated protein 1S (MAP1S) bridges autophagic...	ACCEPT	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. Reason: Core biological process; the MAP1S-LC3-microtubule-LRPPRC bridge is the functionally distinctive role of MAP1S in autophagy/selective autophagy of mitochondria. Supporting Evidence: PMID:21262964 MAP1S isoforms may play positive roles in integration of autophagic components with microtubules and mitochondria in both autophagosomal biogenesis and degradation
GO:0005515 protein binding	IPI PMID:17658481 The NMDAR subunit NR3A interacts with microtubule-associated...	KEEP AS NON CORE	Summary: IPI interaction with the NMDAR subunit NR3A/GRIN3A in brain. Bare protein binding is uninformative. Reason: Records a real neuronal interaction (NR3A) but bare protein binding is uninformative. Supporting Evidence: file:human/MAP1S/MAP1S-uniprot.txt Interacts with ESR1, LRPPRC, RASSF1 isoform A and isoform C, microtubules and VCY2
GO:0005874 microtubule	IDA PMID:17658481 The NMDAR subunit NR3A interacts with microtubule-associated...	ACCEPT	Summary: IDA microtubule localization in the NR3A/brain study. Redundant with the other IDA microtubule annotations. Reason: Core localization; MAP1S associates with microtubules. Supporting Evidence: file:human/MAP1S/MAP1S-uniprot.txt partial localization to the microtubules
GO:0042995 cell projection	IDA PMID:17658481 The NMDAR subunit NR3A interacts with microtubule-associated...	KEEP AS NON CORE	Summary: IDA localization to cell projections (neuronal). Secondary/neuronal localization. Reason: Real neuronal-context localization; secondary to MAP1S's core cytoplasmic microtubule/autophagy roles. Supporting Evidence: file:human/MAP1S/MAP1S-uniprot.txt Detected in filopodia-like protrusions and synapses
GO:0045202 synapse	IDA PMID:17658481 The NMDAR subunit NR3A interacts with microtubule-associated...	KEEP AS NON CORE	Summary: IDA localization to synapses in neurons (NR3A study). Consistent with the IBA synapse annotation; neuron-specific secondary localization. Reason: Real neuron-specific localization; secondary to MAP1S's core cytoplasmic functions. Supporting Evidence: file:human/MAP1S/MAP1S-uniprot.txt Detected in filopodia-like protrusions and synapses
GO:0005515 protein binding	IPI PMID:12762840 Novel complex integrating mitochondria and the microtubular ...	KEEP AS NON CORE	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. Reason: Records functionally relevant interactions (LRPPRC, RASSF1) but bare protein binding is uninformative; the autophagy/microtubule-bridging function captures these. Supporting Evidence: file:human/MAP1S/MAP1S-uniprot.txt Interacts with ESR1, LRPPRC, RASSF1 isoform A and isoform C, microtubules and VCY2
GO:0005634 nucleus	IDA PMID:12762840 Novel complex integrating mitochondria and the microtubular ...	KEEP AS NON CORE	Summary: IDA nuclear localization. MAP1S shuttles to the nucleus (it binds DNA), but the dominant functional pool is cytoplasmic/cytoskeletal. Reason: Real but secondary nuclear localization; MAP1S core functions are cytoplasmic. Supporting Evidence: file:human/MAP1S/MAP1S-uniprot.txt SUBCELLULAR LOCATION: Nucleus.
GO:0005829 cytosol	IDA PMID:12762840 Novel complex integrating mitochondria and the microtubular ...	ACCEPT	Summary: IDA cytosolic localization, consistent with MAP1S's cytoplasmic microtubule-associated distribution. Reason: Core localization; MAP1S is a cytoplasmic, microtubule-associated protein. Supporting Evidence: file:human/MAP1S/MAP1S-uniprot.txt Cytoplasm, cytosol
GO:0048487 beta-tubulin binding	IDA PMID:12762840 Novel complex integrating mitochondria and the microtubular ...	ACCEPT	Summary: IDA evidence that MAP1S binds beta-tubulin, a specific and informative molecular function underlying its microtubule association. Reason: Core molecular function; specific tubulin-binding activity of MAP1S. Supporting Evidence: file:human/MAP1S/MAP1S-uniprot.txt Interacts with microtubules and actin.
GO:0051015 actin filament binding	IDA NOT PMID:12762840 Novel complex integrating mitochondria and the microtubular ...	ACCEPT	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. 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. Supporting Evidence: file:human/MAP1S/MAP1S-uniprot.txt MAP1S light chain interacts with actin
GO:0008017 microtubule binding	TAS PMID:12762840 Novel complex integrating mitochondria and the microtubular ...	ACCEPT	Summary: TAS assignment of microtubule binding, redundant with the IBA/IEA/IDA support for this core molecular function. Reason: Core molecular function; MAP1S directly binds microtubules. Supporting Evidence: file:human/MAP1S/MAP1S-uniprot.txt Interacts with microtubules and actin.
GO:0008017 microtubule binding	IDA PMID:15528209 Microtubule-associated protein 1S, a short and ubiquitously ...	ACCEPT	Summary: IDA evidence of microtubule binding from the original MAP1S characterization paper. Core molecular function. Reason: Core molecular function; MAP1S directly binds microtubules. Supporting Evidence: PMID:15528209 Microtubule-associated protein 1S, a short and ubiquitously expressed member of the microtubule-associated protein 1 family
GO:0015631 tubulin binding	IDA PMID:15528209 Microtubule-associated protein 1S, a short and ubiquitously ...	ACCEPT	Summary: IDA evidence of tubulin binding from the original MAP1S characterization paper. Core molecular function. Reason: Core molecular function; MAP1S binds tubulin. Supporting Evidence: PMID:15528209 Microtubule-associated protein 1S, a short and ubiquitously expressed member of the microtubule-associated protein 1 family
GO:0047497 mitochondrion transport along microtubule	TAS PMID:12762840 Novel complex integrating mitochondria and the microtubular ...	KEEP AS NON CORE	Summary: TAS assignment of mitochondrion transport along microtubules, consistent with MAP1S integrating mitochondria (via LRPPRC) with the microtubule cytoskeleton. Reason: Consistent with MAP1S's mitochondria-microtubule bridging role; retained as a non-core aspect of the broader autophagy/mitochondria-cytoskeleton function. Supporting Evidence: PMID:21262964 MAP1S interacted with mitochondrion-associated leucine-rich PPR-motif containing protein (LRPPRC)
GO:0048471 perinuclear region of cytoplasm	IDA PMID:12762840 Novel complex integrating mitochondria and the microtubular ...	KEEP AS NON CORE	Summary: IDA localization to the perinuclear region, where MAP1S forms a punctate network corresponding to mitochondrial aggregates. Reason: Real cytoplasmic sub-localization tied to mitochondrial aggregation; a specific compartment within the core cytoplasmic distribution. Supporting Evidence: file:human/MAP1S/MAP1S-uniprot.txt Detected in perinuclear punctate network corresponding to mitochondrial aggregates
GO:0051015 actin filament binding	IDA PMID:15528209 Microtubule-associated protein 1S, a short and ubiquitously ...	KEEP AS NON CORE	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. 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. Supporting Evidence: file:human/MAP1S/MAP1S-uniprot.txt MAP1S light chain interacts with actin
GO:0001578 microtubule bundle formation	IMP PMID:15528209 Microtubule-associated protein 1S, a short and ubiquitously ...	ACCEPT	Summary: IMP evidence that MAP1S participates in microtubule bundle formation, a direct consequence of its microtubule cross-linking activity. Core process. Reason: Core biological process; MAP1S cross-links and bundles microtubules. Supporting Evidence: file:human/MAP1S/MAP1S-uniprot.txt Involved in the formation of microtubule bundles
GO:0003677 DNA binding	IDA PMID:15907802 Putative tumor suppressor RASSF1 interactive protein and cel...	KEEP AS NON CORE	Summary: IDA evidence that MAP1S (C19ORF5) binds DNA. A real but secondary molecular function relative to its microtubule/autophagy roles. Reason: Experimentally supported DNA binding, but secondary to MAP1S's core cytoskeletal/autophagy functions and of uncertain physiological role. Supporting Evidence: PMID:15907802 C19ORF5 is a DNA binding protein
GO:0004536 DNA nuclease activity	IDA NOT PMID:15907802 Putative tumor suppressor RASSF1 interactive protein and cel...	ACCEPT	Summary: Curated NOT (negated) annotation - the study showed MAP1S binds DNA but does NOT have DNA nuclease activity. The negation is appropriate and informative. Reason: Accept the curated negation; it correctly records that MAP1S lacks DNA nuclease activity despite binding DNA. Supporting Evidence: PMID:15907802 C19ORF5 is a DNA binding protein
GO:0005515 protein binding	IPI PMID:15907802 Putative tumor suppressor RASSF1 interactive protein and cel...	KEEP AS NON CORE	Summary: IPI interaction (RASSF1, P42704/LRPPRC) from the C19ORF5 DNA-binding study. Bare protein binding is uninformative. Reason: Records real interactions but bare protein binding is uninformative. Supporting Evidence: file:human/MAP1S/MAP1S-uniprot.txt Interacts with ESR1, LRPPRC, RASSF1 isoform A and isoform C, microtubules and VCY2
GO:0005874 microtubule	IDA PMID:15528209 Microtubule-associated protein 1S, a short and ubiquitously ...	ACCEPT	Summary: IDA microtubule localization from the original MAP1S characterization. Redundant with the other IDA microtubule annotations. Reason: Core localization; MAP1S associates with microtubules. Supporting Evidence: PMID:15528209 Microtubule-associated protein 1S, a short and ubiquitously expressed member of the microtubule-associated protein 1 family
GO:0007399 nervous system development	ISS PMID:16297881 Microtubule-associated protein 8 contains two microtubule bi...	KEEP AS NON CORE	Summary: ISS assignment of nervous system development by sequence similarity (to the mouse ortholog). Broad neuronal developmental role. Reason: Broad neuronal developmental process inferred by similarity; secondary for ubiquitously expressed MAP1S. Supporting Evidence: file:human/MAP1S/MAP1S-uniprot.txt Belongs to the MAP1 family.
GO:0007420 brain development	ISS PMID:15528209 Microtubule-associated protein 1S, a short and ubiquitously ...	KEEP AS NON CORE	Summary: ISS assignment of brain development by similarity to the mouse ortholog. Broad neuronal developmental role. Reason: Broad neuronal developmental process inferred by similarity; secondary for ubiquitously expressed MAP1S. Supporting Evidence: file:human/MAP1S/MAP1S-uniprot.txt Belongs to the MAP1 family.
GO:0030425 dendrite	ISS PMID:15528209 Microtubule-associated protein 1S, a short and ubiquitously ...	KEEP AS NON CORE	Summary: ISS assignment of dendrite localization by similarity to the mouse ortholog. Neuron-specific secondary localization. Reason: Neuron-specific localization inferred by similarity; secondary for ubiquitously expressed MAP1S. Supporting Evidence: file:human/MAP1S/MAP1S-uniprot.txt Belongs to the MAP1 family.
GO:0043025 neuronal cell body	ISS PMID:15528209 Microtubule-associated protein 1S, a short and ubiquitously ...	KEEP AS NON CORE	Summary: ISS assignment of neuronal cell body localization by similarity to the mouse ortholog. Neuron-specific secondary localization. Reason: Neuron-specific localization inferred by similarity; secondary for ubiquitously expressed MAP1S. Supporting Evidence: file:human/MAP1S/MAP1S-uniprot.txt Belongs to the MAP1 family.
GO:0048812 neuron projection morphogenesis	IEP PMID:15528209 Microtubule-associated protein 1S, a short and ubiquitously ...	KEEP AS NON CORE	Summary: IEP (expression-pattern) assignment of neuron projection morphogenesis. A neuronal developmental role consistent with MAP1S's microtubule function in neurons. Reason: Neuronal developmental role inferred from expression; secondary for ubiquitously expressed MAP1S. Supporting Evidence: file:human/MAP1S/MAP1S-uniprot.txt Expressed in neurons (at protein level)

Core Functions

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:

microtubule binding

Directly Involved In:

microtubule cytoskeleton organization microtubule bundle formation

Cellular Locations:

microtubule

Supporting Evidence:

PMID:16297881
Microtubule-associated protein 8 contains two microtubule binding sites

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:

microtubule binding

Directly Involved In:

autophagy

Cellular Locations:

microtubule perinuclear region of cytoplasm

Supporting Evidence:

PMID:21262964
MAP1S isoforms may play positive roles in integration of autophagic components with microtubules and mitochondria in both autophagosomal biogenesis and degradation

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:

microtubule binding

Directly Involved In:

microtubule anchoring at centrosome

Cellular Locations:

microtubule organizing center spindle

Supporting Evidence:

PMID:17234756
C19ORF5/MAP1S, causes mitotic abnormalities

References

GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt

GO_REF:0000052

Gene Ontology annotation based on curation of immunofluorescence data

GO_REF:0000107

Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

PMID:12762840

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.

PMID:14627543

Identification and characterization of human VCY2-interacting protein: VCY2IP-1, a microtubule-associated protein-like protein.

PMID:15528209

Microtubule-associated protein 1S, a short and ubiquitously expressed member of the microtubule-associated protein 1 family.

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.

PMID:15907802

Putative tumor suppressor RASSF1 interactive protein and cell death inducer C19ORF5 is a DNA binding protein.

PMID:16297881

Microtubule-associated protein 8 contains two microtubule binding sites.

PMID:17234756

Depletion of the Ras association domain family 1, isoform A-associated novel microtubule-associated protein, C19ORF5/MAP1S, causes mitotic abnormalities.

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.

PMID:17658481

The NMDAR subunit NR3A interacts with microtubule-associated protein 1S in the brain.

PMID:18445686

EML3 is a nuclear microtubule-binding protein required for the correct alignment of chromosomes in metaphase.

PMID:19027008

The role of microtubule-associated protein 1S in SOCS3 regulation of IL-6 signaling.

PMID:21262964

Microtubule-associated protein 1S (MAP1S) bridges autophagic components with microtubules and mitochondria to affect autophagosomal biogenesis and degradation.

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.

PMID:22523538

Nemitin, a novel Map8/Map1s interacting protein with Wd40 repeats.

Suggested Experiments

Experiment: 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.

Experiment: 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.

📚 Additional Documentation

Notes

(MAP1S-notes.md)

MAP1S (Microtubule-associated protein 1S; C19orf5; MAP8; VCY2IP1) — review notes

UniProt: Q66K74 (MAP1S_HUMAN), 1059 aa, HGNC:15715. Processed into a heavy chain
(1-829) and a light chain (830-1059), like other MAP1 family members.

Summary of function

MAP1S is the short, ubiquitously expressed member of the MAP1 family (paralogs MAP1A/MAP1B
are neuron-restricted). Like MAP1A/B it is synthesized as a precursor that is proteolytically
cleaved into heavy and light chains that re-associate as a heterodimer; both chains bind
microtubules and the light chain binds actin [UniProt SUBUNIT]. Its established core
molecular activity is binding to microtubules/tubulin and cross-linking/bundling them
[PMID:12762840 beta-tubulin binding; PMID:15528209 "Microtubule-associated protein 1S ... member of the microtubule-associated protein 1 family", microtubule binding/bundle formation].

The functionally distinctive role of MAP1S, and the reason it is of high interest, is as
a bridge that couples the autophagy machinery to the microtubule cytoskeleton and
mitochondria. MAP1S isoforms bind LC3 (the MAP1A/B light chain 3 / Atg8 homolog) and
recruit it to stable microtubules, and MAP1S binds the mitochondrion-associated protein
LRPPRC (which itself interacts with the mitophagy initiator Parkin); Map1s-knockout mice
show accumulation of defective mitochondria and severe defects in the nutritive-stress
response, indicating defects in autophagosomal biogenesis and clearance
PMID:21262964.
This is the basis of the TAS autophagy annotation (GO:0006914) and is the core distinctive
function to highlight.

MAP1S also has cytoskeletal/mitotic roles: it anchors the microtubule-organizing center
to centrosomes, and its depletion causes mitotic abnormalities (failure to form a stable
metaphase plate, lagging chromosomes, multipolar spindles)
PMID:17234756.
It interacts with RASSF1A and stabilizes microtubules [PMID:15753381, PMID:15899810],
with the estrogen receptor ESR1, the NMDAR subunit NR3A/GRIN3A PMID:17658481,
with LRPPRC [PMID:11827465, PMID:12762840], and with WDR47/Nemitin PMID:22523538.

DNA binding / nuclease

MAP1S was reported to bind DNA PMID:15907802, hence
the IDA DNA binding (GO:0003677) annotation. The same study reported it is NOT a DNA
nuclease — captured correctly as a NOT (negated) annotation to GO:0004536. There is a
nucleus localization (it shuttles), but the dominant functional pool is cytoplasmic/
cytoskeletal/mitochondrial.

Localization

Cytoplasm/cytosol, cytoskeleton (microtubules, spindle, mitotic spindle microtubules),
centrosome/microtubule organizing center, perinuclear region (mitochondrial aggregates),
nucleus/nucleoplasm/nucleolus, cell projection/synapse (neuronal). The neuronal-process
annotations (synapse, dendrite, neuronal cell body, axonogenesis, dendrite development,
brain/nervous system development) are largely IBA/ISS transferred from the neuronal
paralogs MAP1A/B or from mouse orthologs; MAP1S is ubiquitous and these neuronal roles
are secondary/peripheral for the human gene.

Annotation assessment highlights

Core MF: microtubule binding (GO:0008017), tubulin binding (GO:0015631), beta-tubulin
binding (GO:0048487) - ACCEPT (well-supported by IDA).
Core CC: microtubule (GO:0005874), cytosol/cytoskeleton, microtubule associated complex
(GO:0005875) - ACCEPT/KEEP.
Core BP: autophagy (GO:0006914, TAS PMID:21262964) - ACCEPT as the distinctive function;
microtubule cytoskeleton organization, microtubule bundle formation - ACCEPT/KEEP.
actin binding (GO:0003779 IBA) and actin filament binding (GO:0051015 IDA, PMID:15528209)
are positive; note there is also a NOT actin filament binding (GO:0051015 IDA,
PMID:12762840) - a real curated negation from a different study/construct. Both are
retained (the IDA-positive vs IDA-negated reflect different experimental contexts).
NOT DNA nuclease activity (GO:0004536, negated, PMID:15907802) - ACCEPT the negation.
DNA binding (GO:0003677 IDA) - KEEP_AS_NON_CORE (real but secondary).
mitochondrion transport along microtubule (GO:0047497 TAS) and perinuclear region -
consistent with the mitochondria/autophagy bridging role; KEEP/ACCEPT.
Neuronal/developmental IBA/ISS terms - KEEP_AS_NON_CORE (transferred from paralogs/orthologs).
Bare protein binding IPI entries - KEEP_AS_NON_CORE; informative partners captured elsewhere.
WD40-repeat domain binding (GO:0071987, IPI, PMID:22523538, WDR47/Nemitin) - informative
MF; KEEP_AS_NON_CORE.
nucleolus/nucleoplasm (HPA IDA) - KEEP_AS_NON_CORE (shuttling pool, no nucleolar function).

Pn Notes

(MAP1S-pn-notes.md)

MAP1S PN Consistency Notes

Generated: 2026-06-18
Project: PROTEOSTASIS
Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
UniProt: Q66K74
AIGR review status: COMPLETE
Review batch: proteostasis-batch-2026-06-14
Batch change status: added

Source Files Checked

AIGR review YAML: present - genes/human/MAP1S/MAP1S-ai-review.yaml
AIGR review HTML: missing - genes/human/MAP1S/MAP1S-ai-review.html
Gene notes: present - genes/human/MAP1S/MAP1S-notes.md
GOA TSV: present - genes/human/MAP1S/MAP1S-goa.tsv
UniProt record: present - genes/human/MAP1S/MAP1S-uniprot.txt
PN dossier: projects/PROTEOSTASIS/reports/phase1_dossiers/MAP1S.md
PN consistency section: projects/PROTEOSTASIS/reports/phase1_dossiers/_sections/MAP1S.md
PN projection report: projects/PROTEOSTASIS/reports/pn_projection/pn_projected_gene_go_summary.tsv
PN mapping audit: projects/PROTEOSTASIS/reports/pn_mapping_audit/current_mapping_scrutiny.tsv

Deep Research Files

No *-deep-research*.md file found in this gene directory.

AIGR Review Snapshot

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.
Existing/core annotation action counts: ACCEPT: 29; KEEP_AS_NON_CORE: 38

PN Consistency Summary

Consistency: Review YAML, notes and PN annotation agree on MAP1S as a microtubule-associated protein that bridges the autophagy machinery (LC3/Atg8 + LRPPRC→Parkin) to microtubules and mitochondria. Both PN and review trace this to PMID:21262964. The one mismatch: the review captures this only as the generic GO:0006914 autophagy (TAS), whereas PN projects the two specific children mitophagy and aggrephagy. No contradiction, just a granularity gap. PN's "selective autophagy receptor" framing is slightly stronger than the review's "bridge/adaptor" wording, but compatible.
PN story / NEW pressure: PN asserts mitophagy (GO:0000423) and aggrephagy (GO:0035973) — both verified real terms (OLS) and both more specific than the existing GO:0006914. Mitophagy is well supported (PMID:21262964: LRPPRC link to Parkin, Map1s-KO accumulates defective mitochondria). Aggrephagy is supported by the PN-cited Cancer Research paper (MAP1S enhances autophagy to remove aggresomes/aggregates). Existing GOA has ONLY GO:0006914, so both specifics are genuine ADD opportunities, not over-reaches.
Evidence alignment: Good overlap. The PN-cited "MAP1S enhances autophagy to suppress tumorigenesis" (tandfonline) and the Cancer Research hepatocarcinogenesis paper are the autophagy/aggrephagy basis; the review's autophagy annotation rests on PMID:21262964 (the LC3/LRPPRC bridging paper), which is the mechanistic core for mitophagy. The two PN tumor-suppression papers are NOT in the review references — divergence on the aggrephagy/tumor-suppression evidence specifically.
Verdict: Consistent and biologically sound; PN refines (not over-reaches) the review by proposing two verified specific autophagy children. Both are defensible ADDs over the existing generic GO:0006914.

Full Consistency Review

UniProt: Q66K74 · batch: proteostasis-batch-2026-06-14 · review status: COMPLETE
PN placement: two ALP rows under Autophagy substrate selection|Selective autophagy receptor → Mitophagy and Aggrephagy ; PN-node mapping: type Mitophagy mapped/ok_for_propagation = GO:0000423 mitophagy (more_specific_than_existing_goa); type Aggrephagy mapped/ok_for_propagation = GO:0035973 aggrephagy (more_specific_than_existing_goa). Group/class/branch all no_mapping.
Consistency: Review YAML, notes and PN annotation agree on MAP1S as a microtubule-associated protein that bridges the autophagy machinery (LC3/Atg8 + LRPPRC→Parkin) to microtubules and mitochondria. Both PN and review trace this to PMID:21262964. The one mismatch: the review captures this only as the generic GO:0006914 autophagy (TAS), whereas PN projects the two specific children mitophagy and aggrephagy. No contradiction, just a granularity gap. PN's "selective autophagy receptor" framing is slightly stronger than the review's "bridge/adaptor" wording, but compatible.
PN story / NEW pressure: PN asserts mitophagy (GO:0000423) and aggrephagy (GO:0035973) — both verified real terms (OLS) and both more specific than the existing GO:0006914. Mitophagy is well supported (PMID:21262964: LRPPRC link to Parkin, Map1s-KO accumulates defective mitochondria). Aggrephagy is supported by the PN-cited Cancer Research paper (MAP1S enhances autophagy to remove aggresomes/aggregates). Existing GOA has ONLY GO:0006914, so both specifics are genuine ADD opportunities, not over-reaches.
Mapping strategy: This gene does not change either node's status. Both type nodes are correctly mapped/ok_for_propagation. Unlike the rejected TOMM20/HSPA8/RAB7A broader-term precedents, here the PN-projected terms are NARROWER than the review's generic autophagy term, so propagation refines rather than over-reaches — consistent with the MAP1S KEY PATTERN (selective-autophagy regulator linking machinery to microtubules/aggregates). Scope is appropriate.
Evidence alignment: Good overlap. The PN-cited "MAP1S enhances autophagy to suppress tumorigenesis" (tandfonline) and the Cancer Research hepatocarcinogenesis paper are the autophagy/aggrephagy basis; the review's autophagy annotation rests on PMID:21262964 (the LC3/LRPPRC bridging paper), which is the mechanistic core for mitophagy. The two PN tumor-suppression papers are NOT in the review references — divergence on the aggrephagy/tumor-suppression evidence specifically.
Verdict: Consistent and biologically sound; PN refines (not over-reaches) the review by proposing two verified specific autophagy children. Both are defensible ADDs over the existing generic GO:0006914.
Recommended edits: [YAML] Add GO:0000423 mitophagy (involved_in) supported_by PMID:21262964 (LRPPRC/Parkin link; defective-mitochondria accumulation) and GO:0035973 aggrephagy (involved_in) supported_by the PN-cited tandfonline/Cancer Research MAP1S-autophagy papers — fetch and add those PMIDs to references first (verify the tandfonline "MAP1S enhances autophagy to suppress tumorigenesis" PMID and the AACR Cancer Research PMID before citing). [MAP] No mapping-status change needed; both type→GO propagations are correct.

PN Dossier Context

review_batch: proteostasis-batch-2026-06-14
review_yaml: genes/human/MAP1S/MAP1S-ai-review.yaml
PN workbook rows: 2

PN row 1: Autophagy-Lysosome Pathway | Autophagy substrate selection | Selective autophagy receptor | Mitophagy

UniProt: Q66K74
In branches: ALP
Notes: Bridges the autophagy machinery to dysfunctional mitochondria for mitophagy with microtubules and enhances autophagy to remove aggresomes and dysfunctional organelles
PN references (titles):
- Full article: MAP1S enhances autophagy to suppress tumorigenesis (tandfonline.com)
- Autophagy Enhanced by Microtubule- and Mitochondrion-Associated MAP1S Suppresses Genome Instability and Hepatocarcinogenesis | Cancer Research | American Association for Cancer Research (aacrjournals.org)
PN-node mapping records (path + ancestors):
- [type] Autophagy-Lysosome Pathway|Autophagy substrate selection|Selective autophagy receptor|Mitophagy
  status=mapped scope=ok_for_propagation_to_go GO=[GO:0000423 mitophagy]
  rationale: This PN path denotes selective-autophagy receptors for mitochondrial cargo. The source category is a mechanistic sub-role within mitophagy, so propagation rather than exact equivalence is the correct scope.
- [group] Autophagy-Lysosome Pathway|Autophagy substrate selection|Selective autophagy receptor
  status=no_mapping scope= GO=[]
  rationale: Reviewed as a broad PN taxonomy container. The descendants mix components, regulators, context labels, and mechanistic leaves, so propagation should come only from narrower curated nodes.
- [class] Autophagy-Lysosome Pathway|Autophagy substrate selection
  status=no_mapping scope= GO=[]
  rationale: Reviewed as a broad substrate-selection container. GO has useful targets for specific receptor, cargo-adaptor, and selective-autophagy leaves, but this class mixes marking, recognition, receptor regulation, and unknown roles and should not propagate as one term.
- [branch] Autophagy-Lysosome Pathway
  status=no_mapping scope= GO=[]
  rationale: Reviewed as the top-level PN branch. It is a project taxonomy umbrella rather than a direct GO assertion; all propagation must come from manually curated child nodes.

PN row 2: Autophagy-Lysosome Pathway | Autophagy substrate selection | Selective autophagy receptor | Aggrephagy

UniProt: Q66K74
In branches: ALP
Notes: Bridges the autophagy machinery to dysfunctional mitochondria for mitophagy with microtubules and enhances autophagy to remove aggresomes and dysfunctional organelles
PN references (titles):
- Full article: MAP1S enhances autophagy to suppress tumorigenesis (tandfonline.com)
- Autophagy Enhanced by Microtubule- and Mitochondrion-Associated MAP1S Suppresses Genome Instability and Hepatocarcinogenesis | Cancer Research | American Association for Cancer Research (aacrjournals.org)
PN-node mapping records (path + ancestors):
- [type] Autophagy-Lysosome Pathway|Autophagy substrate selection|Selective autophagy receptor|Aggrephagy
  status=mapped scope=ok_for_propagation_to_go GO=[GO:0035973 aggrephagy]
  rationale: This PN path denotes receptors that recognize aggregation cargo for the aggrephagy pathway. The category is not identical to the GO process term, but propagation to aggrephagy is appropriate because membership in this receptor class implies direct participation in that process.
- [group] Autophagy-Lysosome Pathway|Autophagy substrate selection|Selective autophagy receptor
  status=no_mapping scope= GO=[]
  rationale: Reviewed as a broad PN taxonomy container. The descendants mix components, regulators, context labels, and mechanistic leaves, so propagation should come only from narrower curated nodes.
- [class] Autophagy-Lysosome Pathway|Autophagy substrate selection
  status=no_mapping scope= GO=[]
  rationale: Reviewed as a broad substrate-selection container. GO has useful targets for specific receptor, cargo-adaptor, and selective-autophagy leaves, but this class mixes marking, recognition, receptor regulation, and unknown roles and should not propagate as one term.
- [branch] Autophagy-Lysosome Pathway
  status=no_mapping scope= GO=[]
  rationale: Reviewed as the top-level PN branch. It is a project taxonomy umbrella rather than a direct GO assertion; all propagation must come from manually curated child nodes.

Projected GO annotations (2)

GO:0000423 mitophagy | scope=ok_for_propagation_to_go | goa_status=more_specific_than_existing_goa | from=Autophagy-Lysosome Pathway|Autophagy substrate selection|Selective autophagy receptor|Mitophagy
GO:0035973 aggrephagy | scope=ok_for_propagation_to_go | goa_status=more_specific_than_existing_goa | from=Autophagy-Lysosome Pathway|Autophagy substrate selection|Selective autophagy receptor|Aggrephagy

Note

This file is generated from the current PROTEOSTASIS phase-1 dossier and local gene-review artifacts. Edit the source review, PN mapping, or dossier rather than this generated note when correcting the underlying curation.

📄 View Raw YAML

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.

MAP1S

Gene Description

Existing Annotations Review

Core Functions

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.

Anchors the microtubule-organizing center to the centrosome and supports proper mitotic spindle organization and chromosome alignment; depletion of MAP1S causes mitotic abnormalities.

References

Suggested Questions for Experts

Suggested Experiments

📚 Additional Documentation

Notes

MAP1S (Microtubule-associated protein 1S; C19orf5; MAP8; VCY2IP1) — review notes

Summary of function

DNA binding / nuclease

Localization

Annotation assessment highlights

Pn Notes

MAP1S PN Consistency Notes

Source Files Checked

Deep Research Files

AIGR Review Snapshot

PN Consistency Summary

Full Consistency Review

PN Dossier Context

PN row 1: Autophagy-Lysosome Pathway | Autophagy substrate selection | Selective autophagy receptor | Mitophagy

PN row 2: Autophagy-Lysosome Pathway | Autophagy substrate selection | Selective autophagy receptor | Aggrephagy

Projected GO annotations (2)

Note

📄 View Raw YAML