PAFAH1B1 encodes LIS1, a conserved WD40 beta-propeller protein with an N-terminal LisH dimerization domain. Its principal function is regulation of cytoplasmic dynein-1: LIS1 dimers bind the dynein motor domain and dynactin p150, promote assembly of active dynein-dynactin-adaptor complexes and dynein targeting to microtubule plus ends, cargos, kinetochores, the cell cortex and the nuclear envelope, and sustain dynein force production under load. Acting with NDEL1/NDE1 at the centrosome, LIS1 couples the nucleus to the centrosome during neuronal migration (nucleokinesis), drives interkinetic nuclear migration and division of neural progenitors, and supports mitotic spindle orientation, chromosome attachment and retrograde axonal transport. Heterozygous loss of PAFAH1B1 causes classical lissencephaly and subcortical band heterotopia, and deletion with neighbouring genes causes Miller-Dieker syndrome. Independently, LIS1 is the non-catalytic regulatory beta subunit of cytosolic platelet-activating factor acetylhydrolase Ib, binding the PAFAH1B2/PAFAH1B3 catalytic dimer that hydrolyses the sn-2 acetyl group of PAF.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000132 establishment of mitotic spindle orientation | IEA GO_REF:0000104 | ACCEPT | Summary: Establishment of mitotic spindle orientation is a well-supported dynein-dependent LIS1 function. Reason: LIS1 localizes to the cell cortex and kinetochores, and perturbation of LIS1 levels causes spindle misorientation; cortical dynein pulling on astral microtubules requires LIS1. This electronic transfer agrees with human experimental data. Supporting Evidence: PMID:11056532 LIS1 protein co-immunoprecipitates with cytoplasmic dynein and dynactin, and localizes to the cell cortex and to mitotic kinetochores PMID:11056532 Overexpression of LIS1 in cultured mammalian cells interferes with mitotic progression and leads to spindle misorientation |
| GO:0000132 establishment of mitotic spindle orientation | IMP PMID:11056532 A role for the lissencephaly gene LIS1 in mitosis and cytopl... | ACCEPT | Summary: Faulkner et al. showed LIS1 overexpression and antibody injection disrupt spindle orientation and mitotic progression in mammalian cells. Reason: Direct human/mammalian cell perturbation evidence for a dynein-dependent mitotic role of LIS1 in spindle orientation. Supporting Evidence: PMID:11056532 Overexpression of LIS1 in cultured mammalian cells interferes with mitotic progression and leads to spindle misorientation PMID:11056532 We conclude that LIS1 participates in a subset of dynein functions |
| GO:0000226 microtubule cytoskeleton organization | ISS PMID:10729324 Hippocampal abnormalities and enhanced excitability in a mur... | ACCEPT | Summary: LIS1 regulates dynein-dependent microtubule organization (MTOC organization, microtubule transport). Reason: Microtubule cytoskeleton organization is a reasonable (if broad) process for a dynein regulator that controls MTOC organization and the peripheral transport of microtubule fragments. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Required for several dynein- and microtubule-dependent processes such as the maintenance of Golgi integrity, the peripheral transport of microtubule fragments and the coupling of the nucleus and centrosome PMID:11163258 LIS1-mNudE interactions may regulate neuronal migration through dynamic reorganization of the MTOC |
| GO:0000235 astral microtubule | IDA PMID:11940666 LIS1, CLIP-170's key to the dynein/dynactin pathway. | ACCEPT | Summary: LIS1 localizes to microtubule plus ends, including astral microtubules, where it accompanies dynein and CLIP-170. Reason: Consistent with UniProt plus-end localization and the CLIP-170/dynein plus-end pathway reported in the cited paper. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Localizes to the plus end of microtubules and to the centrosome PMID:11940666 LIS1 is a regulated adapter between CLIP-170 and cytoplasmic dynein |
| GO:0000776 kinetochore | IBA GO_REF:0000033 | ACCEPT | Summary: Kinetochore localization of LIS1 is conserved and experimentally established. Reason: Human IDA evidence (Faulkner 2000; Tai 2002; Coquelle 2002) supports kinetochore localization, recruited via dynein/dynactin; the PAINT node placement is consistent. Supporting Evidence: PMID:11889140 We report here that LIS1 associates with kinetochores through its WD repeat domain. PMID:11056532 LIS1 protein co-immunoprecipitates with cytoplasmic dynein and dynactin, and localizes to the cell cortex and to mitotic kinetochores |
| GO:0000776 kinetochore | IDA PMID:11056532 A role for the lissencephaly gene LIS1 in mitosis and cytopl... | ACCEPT | Summary: LIS1 localizes to mitotic kinetochores (Faulkner et al. 2000). Reason: Direct localization evidence in mammalian cells. Supporting Evidence: PMID:11056532 LIS1 protein co-immunoprecipitates with cytoplasmic dynein and dynactin, and localizes to the cell cortex and to mitotic kinetochores |
| GO:0000776 kinetochore | IDA PMID:11889140 Role of dynein, dynactin, and CLIP-170 interactions in LIS1 ... | ACCEPT | Summary: Tai et al. showed LIS1 is targeted to prometaphase kinetochores through its WD repeat domain via dynein/dynactin. Reason: Full-text localization evidence. Supporting Evidence: PMID:11889140 We report here that LIS1 associates with kinetochores through its WD repeat domain. PMID:11889140 LIS1 localized prominently to prometaphase kinetochores and to the cell cortex of dividing vertebrate cultured cells |
| GO:0000776 kinetochore | IDA PMID:11940666 LIS1, CLIP-170's key to the dynein/dynactin pathway. | ACCEPT | Summary: Coquelle et al. showed LIS1 recruitment to kinetochores is dynein/dynactin dependent. Reason: Direct localization evidence. Supporting Evidence: PMID:11940666 LIS1 recruitment to kinetochores is dynein/dynactin dependent |
| GO:0001675 acrosome assembly | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Mouse Lis1 localizes to the spermatid manchette and is required for spermatogenesis; acrosome assembly is a tissue-specific consequence. Reason: Plausible ortholog-transferred developmental role reflecting general microtubule/dynein function in spermatids; not a core LIS1 activity. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Also localizes to the microtubules of the manchette in elongating spermatids and to the meiotic spindle in spermatocytes |
| GO:0001764 neuron migration | IBA GO_REF:0000033 | ACCEPT | Summary: Neuron migration is the defining LIS1 process; the IBA is consistent with conserved LIS1/NudF function in nuclear movement. Reason: LIS1 haploinsufficiency causes lissencephaly, an arrest of neuronal migration; LIS1 regulates dynein to couple the nucleus to the centrosome (nucleokinesis) in migrating neurons. Neuron migration is a core LIS1 process. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Required during brain development for the proliferation of neuronal precursors and the migration of newly formed neurons from the ventricular/subventricular zone toward the cortical plate PMID:15173193 Lis1 and Dcx function with dynein to mediate N-C coupling during migration PMID:20007476 Complete loss of Lis1 or Ndel1 resulted in the total inhibition of nuclear movement in cortical slice assays |
| GO:0001764 neuron migration | IEA GO_REF:0000120 | ACCEPT | Summary: Neuron migration (electronic) agrees with extensive experimental evidence. Reason: LIS1 haploinsufficiency causes lissencephaly, an arrest of neuronal migration; LIS1 regulates dynein to couple the nucleus to the centrosome (nucleokinesis) in migrating neurons. Neuron migration is a core LIS1 process. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Required during brain development for the proliferation of neuronal precursors and the migration of newly formed neurons from the ventricular/subventricular zone toward the cortical plate PMID:9063735 Classical lissencephaly (smooth brain) or generalized agyria-pachygyria is a severe brain malformation which results from an arrest of neuronal migration at 9-13 weeks gestation |
| GO:0001764 neuron migration | IMP PMID:11163258 LIS1 regulates CNS lamination by interacting with mNudE, a c... | ACCEPT | Summary: Feng et al. linked LIS1-mNudE interaction to neuronal migration and CNS lamination. Reason: LIS1 haploinsufficiency causes lissencephaly, an arrest of neuronal migration; LIS1 regulates dynein to couple the nucleus to the centrosome (nucleokinesis) in migrating neurons. Neuron migration is a core LIS1 process. Supporting Evidence: PMID:11163258 LIS1, a microtubule-associated protein, is required for neuronal migration PMID:11163258 LIS1-mNudE interactions may regulate neuronal migration through dynamic reorganization of the MTOC |
| GO:0001764 neuron migration | ISS PMID:10729324 Hippocampal abnormalities and enhanced excitability in a mur... | ACCEPT | Summary: Lis1+/- mouse hippocampal neurons fail to migrate into a defined cell layer; transferred by similarity. Reason: LIS1 haploinsufficiency causes lissencephaly, an arrest of neuronal migration; LIS1 regulates dynein to couple the nucleus to the centrosome (nucleokinesis) in migrating neurons. Neuron migration is a core LIS1 process. Supporting Evidence: PMID:10729324 neurons in Lis1+/- murine hippocampus are born at the appropriate time but fail in migration to form a defined cell layer |
| GO:0005515 protein binding | IPI PMID:10931877 The LIS1-related NUDF protein of Aspergillus nidulans intera... | REMOVE | Summary: Human LIS1 interacts with the human NudE/RO11 homologue (NDEL1/NDE1) in a two-hybrid assay reported in an Aspergillus NUDF-NUDE paper. Reason: Generic protein binding is uninformative. The LIS1-NudE interaction is real and functionally central (NudE tethers LIS1 to dynein), but GO has no informative NudE-binding MF term; the functional consequence is captured by dynein regulation terms. Supporting Evidence: PMID:10931877 a similar interaction occurs between the human NUDE/RO11 homologue and human LIS1 |
| GO:0005515 protein binding | IPI PMID:11163258 LIS1 regulates CNS lamination by interacting with mNudE, a c... | REMOVE | Summary: LIS1 interaction with mouse NudC (UniProtKB:O35685), a dynein pathway co-chaperone, reported by Feng et al.; protein binding is uninformative. Reason: The interaction is plausible (NudC is a conserved LIS1/dynein partner) but generic protein binding adds no functional information about LIS1. Supporting Evidence: PMID:11163258 LIS1, a microtubule-associated protein, is required for neuronal migration |
| GO:0005515 protein binding | IPI PMID:11163258 LIS1 regulates CNS lamination by interacting with mNudE, a c... | REMOVE | Summary: LIS1 binds mNudE and other centrosomal partners; protein binding is uninformative. Reason: As above; interaction retained in the literature, but the generic term is uninformative. Supporting Evidence: PMID:11163258 Missense mutations that disrupt LIS1 function block LIS1-mNudE binding |
| GO:0005515 protein binding | IPI PMID:11940666 LIS1, CLIP-170's key to the dynein/dynactin pathway. | REMOVE | Summary: LIS1 binds CLIP-170 directly (Coquelle et al. 2002); protein binding is uninformative. Reason: Direct CLIP-170 binding supports LIS1 acting as an adapter linking CLIP-170 to dynein, but there is no specific MF term for this and the generic term adds nothing. Supporting Evidence: PMID:11940666 Here we demonstrate colocalization and direct interaction between CLIP-170 and LIS1 PMID:11940666 LIS1 is a regulated adapter between CLIP-170 and cytoplasmic dynein |
| GO:0005515 protein binding | IPI PMID:16754861 A mammalian NudC-like protein essential for dynein stability... | REMOVE | Summary: NudCL co-purifies with Lis1 and dynein IC; protein binding is uninformative. Reason: Generic protein binding with a dynein-stabilizing co-chaperone; not informative about LIS1 activity. Supporting Evidence: PMID:16754861 Purified GST-NudCL protein bound to endogenous Lis1 and the dynein intermediate chain (IC) in cell extracts |
| GO:0005515 protein binding | IPI PMID:20133715 NudC-like protein 2 regulates the LIS1/dynein pathway by sta... | REMOVE | Summary: LIS1 binds HSP90 in a NudCL2-enhanced chaperone complex that stabilizes LIS1; protein binding is uninformative. Reason: The interaction reflects LIS1 being a chaperone client (its stabilization), not a LIS1 activity. Supporting Evidence: PMID:20133715 NudCL2 complexed with and enhanced the interaction between LIS1 and Hsp90 |
| GO:0005515 protein binding | IPI PMID:20133715 NudC-like protein 2 regulates the LIS1/dynein pathway by sta... | REMOVE | Summary: LIS1 binds NudCL2 (NUDCD2); protein binding is uninformative. Reason: NudCL2 regulates LIS1 stability via HSP90; the generic binding term describes LIS1 as a client, not a LIS1 function. Supporting Evidence: PMID:20133715 NudCL2 complexed with and enhanced the interaction between LIS1 and Hsp90 |
| GO:0005515 protein binding | IPI PMID:20360068 Systematic analysis of human protein complexes identifies ch... | REMOVE | Summary: High-throughput complex purification (MitoCheck) recovered LIS1 with NudE; protein binding is uninformative. Reason: Generic protein binding from a high-throughput interaction screen is uninformative about LIS1 function; the interaction itself is not disputed. The informative LIS1 activities (dynein complex binding, dynactin binding, dynein regulation) are captured by other terms. |
| GO:0005515 protein binding | IPI PMID:22159412 Linking cytoplasmic dynein and transport of Rab8 vesicles to... | REMOVE | Summary: Interaction with DCDC5/DCDC1 (M0R2J8) reported by Kaplan & Reiner; UniProt records the LIS1-DCDC1 interaction from this paper. Reason: The interaction is recorded by UniProt from this paper and is not disputed, but generic protein binding is uninformative about LIS1 function. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Interacts with DCDC1 (PubMed:22159412) |
| GO:0005515 protein binding | IPI PMID:27173435 An organelle-specific protein landscape identifies novel dis... | REMOVE | Summary: Organelle/cilia-proteome interaction screen found LIS1 with PAFAH1B2; protein binding is uninformative. Reason: The LIS1-PAF-AH alpha2 interaction is real (structural evidence, PMID:15572112) and is better captured by PAF-AH complex membership. Generic protein binding from a high-throughput interaction screen is uninformative about LIS1 function; the interaction itself is not disputed. The informative LIS1 activities (dynein complex binding, dynactin binding, dynein regulation) are captured by other terms. |
| GO:0005515 protein binding | IPI PMID:27173435 An organelle-specific protein landscape identifies novel dis... | REMOVE | Summary: High-throughput interaction of LIS1 with NDEL1; protein binding is uninformative. Reason: Generic protein binding from a high-throughput interaction screen is uninformative about LIS1 function; the interaction itself is not disputed. The informative LIS1 activities (dynein complex binding, dynactin binding, dynein regulation) are captured by other terms. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: BioPlex interaction of LIS1 with PAFAH1B3; protein binding is uninformative. Reason: Captured more informatively by PAF-AH (I) complex membership. Generic protein binding from a high-throughput interaction screen is uninformative about LIS1 function; the interaction itself is not disputed. The informative LIS1 activities (dynein complex binding, dynactin binding, dynein regulation) are captured by other terms. |
| GO:0005515 protein binding | IPI PMID:29961565 Endogenous Cell Type-Specific Disrupted in Schizophrenia 1 I... | REMOVE | Summary: DISC1 endogenous interactome in iPSC-derived neural cells includes LIS1; protein binding is uninformative. Reason: Generic protein binding from a high-throughput interaction screen is uninformative about LIS1 function; the interaction itself is not disputed. The informative LIS1 activities (dynein complex binding, dynactin binding, dynein regulation) are captured by other terms. |
| GO:0005515 protein binding | IPI PMID:31413325 HENA, heterogeneous network-based data set for Alzheimer's d... | REMOVE | Summary: Aggregated Alzheimer's network dataset (HENA) lists a LIS1-DISC1 interaction; protein binding is uninformative. Reason: Generic protein binding from a high-throughput interaction screen is uninformative about LIS1 function; the interaction itself is not disputed. The informative LIS1 activities (dynein complex binding, dynactin binding, dynein regulation) are captured by other terms. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: BioPlex HEK293T/HCT116 interaction with PAFAH1B2; protein binding is uninformative. Reason: Captured by PAF-AH (I) complex membership. Generic protein binding from a high-throughput interaction screen is uninformative about LIS1 function; the interaction itself is not disputed. The informative LIS1 activities (dynein complex binding, dynactin binding, dynein regulation) are captured by other terms. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: BioPlex interaction with PAFAH1B3; protein binding is uninformative. Reason: Captured by PAF-AH (I) complex membership. Generic protein binding from a high-throughput interaction screen is uninformative about LIS1 function; the interaction itself is not disputed. The informative LIS1 activities (dynein complex binding, dynactin binding, dynein regulation) are captured by other terms. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: BioPlex interaction with NDEL1; protein binding is uninformative. Reason: Generic protein binding from a high-throughput interaction screen is uninformative about LIS1 function; the interaction itself is not disputed. The informative LIS1 activities (dynein complex binding, dynactin binding, dynein regulation) are captured by other terms. |
| GO:0005515 protein binding | IPI PMID:36692009 Structures of human dynein in complex with the lissencephaly... | MODIFY | Summary: Cryo-EM structures of human dynein-LIS1 complexes show LIS1 binding the dynein-1 heavy chain motor domain. Reason: The IPI partner is DYNC1H1 and the paper structurally defines the LIS1-motor domain interface; dynein heavy chain binding is the informative MF. Proposed replacements: dynein heavy chain binding Supporting Evidence: PMID:36692009 is a key regulator of cytoplasmic dynein-1 PMID:36692009 Here, we report cryo-EM structures of human dynein-LIS1 complexes PMID:11163259 LIS1 directly interacts with the cytoplasmic dynein heavy chain (CDHC) |
| GO:0005515 protein binding | IPI PMID:38547289 Molecular mechanism of dynein-dynactin complex assembly by L... | MODIFY | Summary: Cryo-EM of dynein-dynactin-JIP3-LIS1 on microtubules shows LIS1 bound to the dynein heavy chain and to dynactin p150. Reason: IPI partner is DYNC1H1; the structure also reveals LIS1 binding to dynactin p150, so dynein heavy chain binding and dynactin binding are informative replacements. Proposed replacements: dynein heavy chain binding dynactin binding Supporting Evidence: PMID:38547289 Unexpectedly, LIS1 binds dynactin's p150 subunit, tethering it along the length of dynein. PMID:38547289 LIS1 and p150 constrain dynein-dynactin to ensure efficient complex formation |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: Multimodal cell-map proteomics recovered LIS1 with NDEL1; protein binding is uninformative. Reason: Generic protein binding from a high-throughput interaction screen is uninformative about LIS1 function; the interaction itself is not disputed. The informative LIS1 activities (dynein complex binding, dynactin binding, dynein regulation) are captured by other terms. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: Multimodal cell-map proteomics recovered LIS1 with DISC1; protein binding is uninformative. Reason: Generic protein binding from a high-throughput interaction screen is uninformative about LIS1 function; the interaction itself is not disputed. The informative LIS1 activities (dynein complex binding, dynactin binding, dynein regulation) are captured by other terms. |
| GO:0005634 nucleus | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: LIS1 is predominantly cytoplasmic/cytoskeletal; a nuclear pool is weakly supported (nuclear-envelope association, reported INTS13 interaction). Reason: The PAINT node includes human LIS1 among its donors. LIS1 associates with the nuclear envelope with dynein during nucleus-centrosome coupling, and UniProt records an interaction with the nuclear Integrator subunit INTS13, but nucleoplasmic function is not established; retained as non-core. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Nucleus membrane file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Cytoplasm, cytoskeleton |
| GO:0005635 nuclear envelope | IDA PMID:11940666 LIS1, CLIP-170's key to the dynein/dynactin pathway. | ACCEPT | Summary: LIS1 associates with the nuclear envelope, consistent with dynein-mediated nucleus-centrosome coupling. Reason: Nuclear envelope association of dynein/LIS1 is the site of force transmission for nucleokinesis; defer to the curator's IDA from the full text. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Nucleus membrane file:human/PAFAH1B1/PAFAH1B1-uniprot.txt During nucleokinesis dynein at the nuclear surface may translocate the nucleus towards the centrosome by exerting force on centrosomal microtubules |
| GO:0005635 nuclear envelope | IEA GO_REF:0000107 | ACCEPT | Summary: Nuclear envelope (electronic) is consistent with UniProt nucleus-membrane localization and the dynein-LIS1 nuclear envelope role. Reason: Consistent with experimental IDA row. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Nucleus membrane |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: LIS1 is a cytoplasmic protein. Reason: Well supported. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Cytoplasm, cytoskeleton |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: LIS1 is a cytoplasmic protein. Reason: Well supported. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Cytoplasm, cytoskeleton |
| GO:0005737 cytoplasm | NAS PMID:15572112 Coupling PAF signaling to dynein regulation: structure of LI... | ACCEPT | Summary: LIS1 and the PAF-AH (I) enzyme are cytosolic. Reason: Cytosolic PAF-AH (I) and cytoplasmic dynein regulation. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Regulatory subunit (beta subunit) of the cytosolic type I platelet-activating factor (PAF) acetylhydrolase (PAF-AH (I)) |
| GO:0005813 centrosome | IBA GO_REF:0000033 | ACCEPT | Summary: Centrosome localization is conserved and well supported. Reason: LIS1 localizes predominantly to the centrosome in neurons and non-neuronal cells, where it acts with NDEL1/NDE1 and dynein. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Localizes to the plus end of microtubules and to the centrosome PMID:15173193 Lis1 localized predominantly to the centrosome, and after disruption of microtubules, redistributed to the perinuclear region |
| GO:0005813 centrosome | IDA GO_REF:0000052 | ACCEPT | Summary: Immunofluorescence (HPA-style) centrosome localization. Reason: LIS1 localizes predominantly to the centrosome in neurons and non-neuronal cells, where it acts with NDEL1/NDE1 and dynein. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Localizes to the plus end of microtubules and to the centrosome |
| GO:0005813 centrosome | IDA PMID:21399614 Novel asymmetrically localizing components of human centroso... | ACCEPT | Summary: Centrosome proteomics identified LIS1 among centrosomal components. Reason: LIS1 localizes predominantly to the centrosome in neurons and non-neuronal cells, where it acts with NDEL1/NDE1 and dynein. Supporting Evidence: PMID:21399614 we distinguished 126 known and 40 candidate centrosomal proteins PMID:15173193 Lis1 localized predominantly to the centrosome, and after disruption of microtubules, redistributed to the perinuclear region |
| GO:0005813 centrosome | IEA GO_REF:0000120 | ACCEPT | Summary: Centrosome localization (electronic) is consistent with experimental data. Reason: LIS1 localizes predominantly to the centrosome in neurons and non-neuronal cells, where it acts with NDEL1/NDE1 and dynein. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Localizes to the plus end of microtubules and to the centrosome |
| GO:0005813 centrosome | ISS GO_REF:0000024 | ACCEPT | Summary: Centrosome localization transferred from orthologs is consistent with human data. Reason: LIS1 localizes predominantly to the centrosome in neurons and non-neuronal cells, where it acts with NDEL1/NDE1 and dynein. Supporting Evidence: PMID:15173193 Lis1 localized predominantly to the centrosome, and after disruption of microtubules, redistributed to the perinuclear region |
| GO:0005819 spindle | IEA GO_REF:0000044 | ACCEPT | Summary: LIS1 localizes to the mitotic/meiotic spindle. Reason: Consistent with UniProt and mitotic dynein function. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Cytoplasm, cytoskeleton, spindle |
| GO:0005829 cytosol | ISS PMID:8028668 Miller-Dieker lissencephaly gene encodes a subunit of brain ... | ACCEPT | Summary: PAF-AH (I), of which LIS1 is the beta subunit, is a cytosolic enzyme. Reason: The bovine brain cytosolic PAF-AH purification identified the 45 kDa subunit as LIS1. Supporting Evidence: PMID:8028668 This indicates that the LIS-1 gene product is a human homologue of the 45K subunit of intracellular PAF acetylhydrolase PMID:8028668 PAF acetylhydrolase, which inactivates PAF by removing the acetyl group at the sn-2 position, is widely distributed in plasma and tissue cytosols |
| GO:0005829 cytosol | TAS Reactome:R-HSA-141409 | ACCEPT | Summary: Reactome places LIS1 in the cytosol in dynein-, centrosome-, kinetochore- and cilium-related reactions. Reason: LIS1 is a cytosolic dynein regulator; cytosol is an accurate generic location. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Cytoplasm, cytoskeleton |
| GO:0005829 cytosol | TAS Reactome:R-HSA-141422 | ACCEPT | Summary: Reactome places LIS1 in the cytosol in dynein-, centrosome-, kinetochore- and cilium-related reactions. Reason: LIS1 is a cytosolic dynein regulator; cytosol is an accurate generic location. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Cytoplasm, cytoskeleton |
| GO:0005829 cytosol | TAS Reactome:R-HSA-141431 | ACCEPT | Summary: Reactome places LIS1 in the cytosol in dynein-, centrosome-, kinetochore- and cilium-related reactions. Reason: LIS1 is a cytosolic dynein regulator; cytosol is an accurate generic location. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Cytoplasm, cytoskeleton |
| GO:0005829 cytosol | TAS Reactome:R-HSA-141439 | ACCEPT | Summary: Reactome places LIS1 in the cytosol in dynein-, centrosome-, kinetochore- and cilium-related reactions. Reason: LIS1 is a cytosolic dynein regulator; cytosol is an accurate generic location. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Cytoplasm, cytoskeleton |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1638803 | ACCEPT | Summary: Reactome places LIS1 in the cytosol in dynein-, centrosome-, kinetochore- and cilium-related reactions. Reason: LIS1 is a cytosolic dynein regulator; cytosol is an accurate generic location. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Cytoplasm, cytoskeleton |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1638821 | ACCEPT | Summary: Reactome places LIS1 in the cytosol in dynein-, centrosome-, kinetochore- and cilium-related reactions. Reason: LIS1 is a cytosolic dynein regulator; cytosol is an accurate generic location. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Cytoplasm, cytoskeleton |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2467809 | ACCEPT | Summary: Reactome places LIS1 in the cytosol in dynein-, centrosome-, kinetochore- and cilium-related reactions. Reason: LIS1 is a cytosolic dynein regulator; cytosol is an accurate generic location. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Cytoplasm, cytoskeleton |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2467811 | ACCEPT | Summary: Reactome places LIS1 in the cytosol in dynein-, centrosome-, kinetochore- and cilium-related reactions. Reason: LIS1 is a cytosolic dynein regulator; cytosol is an accurate generic location. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Cytoplasm, cytoskeleton |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2468287 | ACCEPT | Summary: Reactome places LIS1 in the cytosol in dynein-, centrosome-, kinetochore- and cilium-related reactions. Reason: LIS1 is a cytosolic dynein regulator; cytosol is an accurate generic location. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Cytoplasm, cytoskeleton |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2484822 | ACCEPT | Summary: Reactome places LIS1 in the cytosol in dynein-, centrosome-, kinetochore- and cilium-related reactions. Reason: LIS1 is a cytosolic dynein regulator; cytosol is an accurate generic location. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Cytoplasm, cytoskeleton |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2574840 | ACCEPT | Summary: Reactome places LIS1 in the cytosol in dynein-, centrosome-, kinetochore- and cilium-related reactions. Reason: LIS1 is a cytosolic dynein regulator; cytosol is an accurate generic location. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Cytoplasm, cytoskeleton |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2574845 | ACCEPT | Summary: Reactome places LIS1 in the cytosol in dynein-, centrosome-, kinetochore- and cilium-related reactions. Reason: LIS1 is a cytosolic dynein regulator; cytosol is an accurate generic location. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Cytoplasm, cytoskeleton |
| GO:0005829 cytosol | TAS Reactome:R-HSA-3000310 | ACCEPT | Summary: Reactome places LIS1 in the cytosol in dynein-, centrosome-, kinetochore- and cilium-related reactions. Reason: LIS1 is a cytosolic dynein regulator; cytosol is an accurate generic location. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Cytoplasm, cytoskeleton |
| GO:0005829 cytosol | TAS Reactome:R-HSA-3000319 | ACCEPT | Summary: Reactome places LIS1 in the cytosol in dynein-, centrosome-, kinetochore- and cilium-related reactions. Reason: LIS1 is a cytosolic dynein regulator; cytosol is an accurate generic location. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Cytoplasm, cytoskeleton |
| GO:0005829 cytosol | TAS Reactome:R-HSA-375302 | ACCEPT | Summary: Reactome places LIS1 in the cytosol in dynein-, centrosome-, kinetochore- and cilium-related reactions. Reason: LIS1 is a cytosolic dynein regulator; cytosol is an accurate generic location. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Cytoplasm, cytoskeleton |
| GO:0005829 cytosol | TAS Reactome:R-HSA-380272 | ACCEPT | Summary: Reactome places LIS1 in the cytosol in dynein-, centrosome-, kinetochore- and cilium-related reactions. Reason: LIS1 is a cytosolic dynein regulator; cytosol is an accurate generic location. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Cytoplasm, cytoskeleton |
| GO:0005829 cytosol | TAS Reactome:R-HSA-380283 | ACCEPT | Summary: Reactome places LIS1 in the cytosol in dynein-, centrosome-, kinetochore- and cilium-related reactions. Reason: LIS1 is a cytosolic dynein regulator; cytosol is an accurate generic location. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Cytoplasm, cytoskeleton |
| GO:0005829 cytosol | TAS Reactome:R-HSA-380294 | ACCEPT | Summary: Reactome places LIS1 in the cytosol in dynein-, centrosome-, kinetochore- and cilium-related reactions. Reason: LIS1 is a cytosolic dynein regulator; cytosol is an accurate generic location. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Cytoplasm, cytoskeleton |
| GO:0005829 cytosol | TAS Reactome:R-HSA-380303 | ACCEPT | Summary: Reactome places LIS1 in the cytosol in dynein-, centrosome-, kinetochore- and cilium-related reactions. Reason: LIS1 is a cytosolic dynein regulator; cytosol is an accurate generic location. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Cytoplasm, cytoskeleton |
| GO:0005829 cytosol | TAS Reactome:R-HSA-380311 | ACCEPT | Summary: Reactome places LIS1 in the cytosol in dynein-, centrosome-, kinetochore- and cilium-related reactions. Reason: LIS1 is a cytosolic dynein regulator; cytosol is an accurate generic location. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Cytoplasm, cytoskeleton |
| GO:0005829 cytosol | TAS Reactome:R-HSA-380316 | ACCEPT | Summary: Reactome places LIS1 in the cytosol in dynein-, centrosome-, kinetochore- and cilium-related reactions. Reason: LIS1 is a cytosolic dynein regulator; cytosol is an accurate generic location. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Cytoplasm, cytoskeleton |
| GO:0005829 cytosol | TAS Reactome:R-HSA-380455 | ACCEPT | Summary: Reactome places LIS1 in the cytosol in dynein-, centrosome-, kinetochore- and cilium-related reactions. Reason: LIS1 is a cytosolic dynein regulator; cytosol is an accurate generic location. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Cytoplasm, cytoskeleton |
| GO:0005829 cytosol | TAS Reactome:R-HSA-380508 | ACCEPT | Summary: Reactome places LIS1 in the cytosol in dynein-, centrosome-, kinetochore- and cilium-related reactions. Reason: LIS1 is a cytosolic dynein regulator; cytosol is an accurate generic location. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Cytoplasm, cytoskeleton |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5617816 | ACCEPT | Summary: Reactome places LIS1 in the cytosol in dynein-, centrosome-, kinetochore- and cilium-related reactions. Reason: LIS1 is a cytosolic dynein regulator; cytosol is an accurate generic location. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Cytoplasm, cytoskeleton |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5626220 | ACCEPT | Summary: Reactome places LIS1 in the cytosol in dynein-, centrosome-, kinetochore- and cilium-related reactions. Reason: LIS1 is a cytosolic dynein regulator; cytosol is an accurate generic location. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Cytoplasm, cytoskeleton |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5626223 | ACCEPT | Summary: Reactome places LIS1 in the cytosol in dynein-, centrosome-, kinetochore- and cilium-related reactions. Reason: LIS1 is a cytosolic dynein regulator; cytosol is an accurate generic location. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Cytoplasm, cytoskeleton |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5626227 | ACCEPT | Summary: Reactome places LIS1 in the cytosol in dynein-, centrosome-, kinetochore- and cilium-related reactions. Reason: LIS1 is a cytosolic dynein regulator; cytosol is an accurate generic location. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Cytoplasm, cytoskeleton |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5626228 | ACCEPT | Summary: Reactome places LIS1 in the cytosol in dynein-, centrosome-, kinetochore- and cilium-related reactions. Reason: LIS1 is a cytosolic dynein regulator; cytosol is an accurate generic location. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Cytoplasm, cytoskeleton |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5626681 | ACCEPT | Summary: Reactome places LIS1 in the cytosol in dynein-, centrosome-, kinetochore- and cilium-related reactions. Reason: LIS1 is a cytosolic dynein regulator; cytosol is an accurate generic location. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Cytoplasm, cytoskeleton |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5626699 | ACCEPT | Summary: Reactome places LIS1 in the cytosol in dynein-, centrosome-, kinetochore- and cilium-related reactions. Reason: LIS1 is a cytosolic dynein regulator; cytosol is an accurate generic location. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Cytoplasm, cytoskeleton |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5638009 | ACCEPT | Summary: Reactome places LIS1 in the cytosol in dynein-, centrosome-, kinetochore- and cilium-related reactions. Reason: LIS1 is a cytosolic dynein regulator; cytosol is an accurate generic location. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Cytoplasm, cytoskeleton |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5666129 | ACCEPT | Summary: Reactome places LIS1 in the cytosol in dynein-, centrosome-, kinetochore- and cilium-related reactions. Reason: LIS1 is a cytosolic dynein regulator; cytosol is an accurate generic location. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Cytoplasm, cytoskeleton |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5666160 | ACCEPT | Summary: Reactome places LIS1 in the cytosol in dynein-, centrosome-, kinetochore- and cilium-related reactions. Reason: LIS1 is a cytosolic dynein regulator; cytosol is an accurate generic location. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Cytoplasm, cytoskeleton |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5666169 | ACCEPT | Summary: Reactome places LIS1 in the cytosol in dynein-, centrosome-, kinetochore- and cilium-related reactions. Reason: LIS1 is a cytosolic dynein regulator; cytosol is an accurate generic location. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Cytoplasm, cytoskeleton |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8848484 | ACCEPT | Summary: Reactome places LIS1 in the cytosol in dynein-, centrosome-, kinetochore- and cilium-related reactions. Reason: LIS1 is a cytosolic dynein regulator; cytosol is an accurate generic location. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Cytoplasm, cytoskeleton |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8849350 | ACCEPT | Summary: Reactome places LIS1 in the cytosol in dynein-, centrosome-, kinetochore- and cilium-related reactions. Reason: LIS1 is a cytosolic dynein regulator; cytosol is an accurate generic location. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Cytoplasm, cytoskeleton |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8853405 | ACCEPT | Summary: Reactome places LIS1 in the cytosol in dynein-, centrosome-, kinetochore- and cilium-related reactions. Reason: LIS1 is a cytosolic dynein regulator; cytosol is an accurate generic location. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Cytoplasm, cytoskeleton |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8853419 | ACCEPT | Summary: Reactome places LIS1 in the cytosol in dynein-, centrosome-, kinetochore- and cilium-related reactions. Reason: LIS1 is a cytosolic dynein regulator; cytosol is an accurate generic location. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Cytoplasm, cytoskeleton |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9648114 | ACCEPT | Summary: Reactome places LIS1 in the cytosol in dynein-, centrosome-, kinetochore- and cilium-related reactions. Reason: LIS1 is a cytosolic dynein regulator; cytosol is an accurate generic location. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Cytoplasm, cytoskeleton |
| GO:0005856 cytoskeleton | IEA GO_REF:0000044 | ACCEPT | Summary: LIS1 is a microtubule/cytoskeleton-associated protein. Reason: Well supported. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Cytoplasm, cytoskeleton |
| GO:0005871 kinesin complex | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: LIS1 is not a kinesin complex subunit. Reason: LIS1 can travel with dynein as kinesin cargo during anterograde transport of dynein, but this does not make it part of the kinesin complex; its complex memberships are dynein-dynactin and PAF-AH (I). Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Interacts with DCX, dynein, dynactin, NDE1, NDEL1 and RSN |
| GO:0005875 microtubule associated complex | IBA GO_REF:0000033 | ACCEPT | Summary: LIS1 is part of microtubule-associated dynein-dynactin-LIS1-NDEL1 complexes. Reason: LIS1 forms part of dynein-dynactin/NudE microtubule-associated complexes; its WD domain binds dynein and dynactin subunits. Supporting Evidence: PMID:11889140 We find that the WD repeat domain of LIS1 interacts with three distinct subunits of the dynein and dynactin complexes, representing both motor and cargo-binding regions. PMID:11163259 LIS1 directly interacts with the cytoplasmic dynein heavy chain (CDHC) |
| GO:0005875 microtubule associated complex | IDA PMID:11889140 Role of dynein, dynactin, and CLIP-170 interactions in LIS1 ... | ACCEPT | Summary: Tai et al. showed LIS1 interacts with dynein and dynactin subunits. Reason: LIS1 forms part of dynein-dynactin/NudE microtubule-associated complexes; its WD domain binds dynein and dynactin subunits. Supporting Evidence: PMID:11889140 We find that the WD repeat domain of LIS1 interacts with three distinct subunits of the dynein and dynactin complexes, representing both motor and cargo-binding regions. |
| GO:0005875 microtubule associated complex | IEA GO_REF:0000120 | ACCEPT | Summary: Microtubule associated complex (electronic) is consistent with experimental data. Reason: LIS1 forms part of dynein-dynactin/NudE microtubule-associated complexes; its WD domain binds dynein and dynactin subunits. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Interacts with DCX, dynein, dynactin, NDE1, NDEL1 and RSN |
| GO:0005938 cell cortex | IDA PMID:11940666 LIS1, CLIP-170's key to the dynein/dynactin pathway. | ACCEPT | Summary: LIS1 localizes to the cell cortex, a dynein anchoring site. Reason: Consistent with the Faulkner and Tai papers. Supporting Evidence: PMID:11056532 LIS1 protein co-immunoprecipitates with cytoplasmic dynein and dynactin, and localizes to the cell cortex and to mitotic kinetochores PMID:11889140 LIS1 localized prominently to prometaphase kinetochores and to the cell cortex of dividing vertebrate cultured cells |
| GO:0007017 microtubule-based process | IDA PMID:11940666 LIS1, CLIP-170's key to the dynein/dynactin pathway. | ACCEPT | Summary: LIS1 participates in dynein-driven microtubule-based processes. Reason: Broad but correct; more specific terms (nuclear migration, retrograde axonal transport, spindle orientation) are also annotated. Supporting Evidence: PMID:11940666 LIS1 is a regulated adapter between CLIP-170 and cytoplasmic dynein |
| GO:0007017 microtubule-based process | IEA GO_REF:0000104 | ACCEPT | Summary: Microtubule-based process (electronic) is correct though broad. Reason: As above. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Positively regulates the activity of the minus-end directed microtubule motor protein dynein |
| GO:0007097 nuclear migration | IEA GO_REF:0000107 | MODIFY | Summary: Nuclear migration is a core LIS1-dynein process (nucleokinesis, interkinetic nuclear migration); the microtubule-dependent child terms are more precise. Reason: LIS1 knockdown blocks somal translocation and interkinetic nuclear oscillations, and complete Lis1 loss abolishes nuclear movement; LIS1 acts through the minus-end motor dynein pulling the nucleus along microtubules. Nuclear migration along microtubule and interkinetic nuclear migration capture this precisely. Proposed replacements: nuclear migration along microtubule interkinetic nuclear migration Supporting Evidence: PMID:16144905 interkinetic nuclear oscillations in the radial glial progenitors were also abolished PMID:16144905 These results identify multiple distinct and novel roles for LIS1 in nucleokinesis and process dynamics PMID:20007476 Complete loss of Lis1 or Ndel1 resulted in the total inhibition of nuclear movement in cortical slice assays PMID:20007476 regulates nucleokinesis via the regulation of dynein motor function and localization |
| GO:0007268 chemical synaptic transmission | ISS PMID:10729324 Hippocampal abnormalities and enhanced excitability in a mur... | MARK AS OVER ANNOTATED | Summary: Synaptic transmission defects in Lis1+/- hippocampus are secondary to neuronal heterotopia. Reason: The phenotype is a downstream consequence of migration/dysplasia; LIS1 has no demonstrated direct role in synaptic transmission. Supporting Evidence: PMID:10729324 neurons in Lis1+/- murine hippocampus are born at the appropriate time but fail in migration to form a defined cell layer PMID:10729324 Mechanisms of synaptic transmission were severely disrupted |
| GO:0007399 nervous system development | IEA GO_REF:0000104 | ACCEPT | Summary: Nervous system development is a broad but valid process for LIS1. Reason: Lissencephaly gene; broad parent of neuron migration. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Required during brain development for the proliferation of neuronal precursors and the migration of newly formed neurons from the ventricular/subventricular zone toward the cortical plate |
| GO:0007405 neuroblast proliferation | ISS PMID:10729324 Hippocampal abnormalities and enhanced excitability in a mur... | KEEP AS NON CORE | Summary: LIS1 is required for neural progenitor proliferation via dynein-dependent mitosis and interkinetic nuclear migration. Reason: Real but reflects the mitotic/nuclear-positioning dynein role in progenitors. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Required during brain development for the proliferation of neuronal precursors and the migration of newly formed neurons from the ventricular/subventricular zone toward the cortical plate PMID:16144905 interkinetic nuclear oscillations in the radial glial progenitors were also abolished |
| GO:0007611 learning or memory | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Learning/memory deficits in Lis1 mutant mice are indirect consequences of brain malformation. Reason: No direct role for LIS1 in learning or memory mechanisms. Supporting Evidence: PMID:10729324 neurons in Lis1+/- murine hippocampus are born at the appropriate time but fail in migration to form a defined cell layer |
| GO:0008017 microtubule binding | IBA GO_REF:0000033 | ACCEPT | Summary: Microtubule binding is supported as a conserved LIS1-family property. Reason: LIS1 is described as a microtubule-associated protein and localizes to microtubule plus ends and the manchette; direct microtubule binding is modest compared with its dynein binding, but microtubule association is conserved. Supporting Evidence: PMID:11163258 LIS1, a microtubule-associated protein, is required for neuronal migration file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Localizes to the plus end of microtubules and to the centrosome |
| GO:0008017 microtubule binding | IEA GO_REF:0000107 | ACCEPT | Summary: Microtubule binding (electronic) is consistent. Reason: LIS1 is described as a microtubule-associated protein and localizes to microtubule plus ends and the manchette; direct microtubule binding is modest compared with its dynein binding, but microtubule association is conserved. Supporting Evidence: PMID:11163258 LIS1, a microtubule-associated protein, is required for neuronal migration |
| GO:0008017 microtubule binding | ISS PMID:10729324 Hippocampal abnormalities and enhanced excitability in a mur... | ACCEPT | Summary: Microtubule binding transferred from mouse Lis1. Reason: LIS1 is described as a microtubule-associated protein and localizes to microtubule plus ends and the manchette; direct microtubule binding is modest compared with its dynein binding, but microtubule association is conserved. Supporting Evidence: PMID:11163258 LIS1, a microtubule-associated protein, is required for neuronal migration |
| GO:0008090 retrograde axonal transport | IBA GO_REF:0000033 | ACCEPT | Summary: Retrograde axonal transport is a dynein-dependent process regulated by LIS1. Reason: LIS1 and NUDEL redistribute to axons with retrograde dynein and regulate dynein heavy chain activity during axonal retrograde transport. Supporting Evidence: PMID:11163259 redistribute to axons in association with retrograde dynein motor proteins PMID:11163259 LIS1 and NUDEL regulate CDHC activity during neuronal migration and axonal retrograde transport |
| GO:0008090 retrograde axonal transport | ISS PMID:10729324 Hippocampal abnormalities and enhanced excitability in a mur... | ACCEPT | Summary: Retrograde axonal transport transferred from mouse Lis1. Reason: LIS1 and NUDEL redistribute to axons with retrograde dynein and regulate dynein heavy chain activity during axonal retrograde transport. Supporting Evidence: PMID:11163259 LIS1 and NUDEL regulate CDHC activity during neuronal migration and axonal retrograde transport |
| GO:0008201 heparin binding | ISS PMID:8028668 Miller-Dieker lissencephaly gene encodes a subunit of brain ... | UNDECIDED | Summary: Heparin binding is transferred from a bovine IDA annotation to the 1994 PAF-AH purification paper. Reason: The cached abstract does not mention heparin; any heparin interaction probably reflects heparin-affinity behaviour of the purified heterotrimer rather than a physiological LIS1 function. Without the full text this cannot be adjudicated. Supporting Evidence: PMID:8028668 This indicates that the LIS-1 gene product is a human homologue of the 45K subunit of intracellular PAF acetylhydrolase |
| GO:0008247 1-alkyl-2-acetylglycerophosphocholine esterase complex | EXP PMID:15572112 Coupling PAF signaling to dynein regulation: structure of LI... | ACCEPT | Summary: Crystal structure of LIS1 bound to the PAF-AH alpha2/alpha2 dimer. Reason: LIS1 is the non-catalytic regulatory beta subunit of cytosolic PAF-AH (I); a LIS1 homodimer binds the alpha2/alpha2 (or alpha1/alpha2) catalytic dimer. Supporting Evidence: PMID:15572112 One LIS1 homodimer binds symmetrically to one alpha2/alpha2 homodimer via the highly conserved top faces of the LIS1 beta propellers file:human/PAFAH1B1/PAFAH1B1-uniprot.txt The catalytic activity of the enzyme resides in the alpha1 (PAFAH1B3) and alpha2 (PAFAH1B2) subunits, whereas the beta subunit (PAFAH1B1) has regulatory activity |
| GO:0008247 1-alkyl-2-acetylglycerophosphocholine esterase complex | IEA GO_REF:0000107 | ACCEPT | Summary: PAF-AH (I) complex membership (electronic). Reason: LIS1 is the non-catalytic regulatory beta subunit of cytosolic PAF-AH (I); a LIS1 homodimer binds the alpha2/alpha2 (or alpha1/alpha2) catalytic dimer. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Component of the cytosolic PAF-AH (I) heterotetrameric enzyme file:human/PAFAH1B1/PAFAH1B1-uniprot.txt The catalytic activity of the enzyme resides in the alpha1 (PAFAH1B3) and alpha2 (PAFAH1B2) subunits, whereas the beta subunit (PAFAH1B1) has regulatory activity |
| GO:0008247 1-alkyl-2-acetylglycerophosphocholine esterase complex | ISS GO_REF:0000024 | ACCEPT | Summary: PAF-AH (I) complex membership transferred from bovine/mouse. Reason: LIS1 is the non-catalytic regulatory beta subunit of cytosolic PAF-AH (I); a LIS1 homodimer binds the alpha2/alpha2 (or alpha1/alpha2) catalytic dimer. Supporting Evidence: PMID:8028668 This indicates that the LIS-1 gene product is a human homologue of the 45K subunit of intracellular PAF acetylhydrolase file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Component of the cytosolic PAF-AH (I) heterotetrameric enzyme |
| GO:0008247 1-alkyl-2-acetylglycerophosphocholine esterase complex | ISS GO_REF:0000024 | ACCEPT | Summary: PAF-AH (I) complex membership transferred from bovine/mouse. Reason: LIS1 is the non-catalytic regulatory beta subunit of cytosolic PAF-AH (I); a LIS1 homodimer binds the alpha2/alpha2 (or alpha1/alpha2) catalytic dimer. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Component of the cytosolic PAF-AH (I) heterotetrameric enzyme |
| GO:0008247 1-alkyl-2-acetylglycerophosphocholine esterase complex | NAS PMID:15572112 Coupling PAF signaling to dynein regulation: structure of LI... | ACCEPT | Summary: PAF-AH (I) complex membership (author statement). Reason: LIS1 is the non-catalytic regulatory beta subunit of cytosolic PAF-AH (I); a LIS1 homodimer binds the alpha2/alpha2 (or alpha1/alpha2) catalytic dimer. Supporting Evidence: PMID:15572112 as well as the catalytic alpha dimers of brain cytosolic platelet activating factor acetylhydrolase (PAF-AH) |
| GO:0008344 adult locomotory behavior | IMP PMID:9063735 Point mutations and an intragenic deletion in LIS1, the liss... | MARK AS OVER ANNOTATED | Summary: Adult locomotory behaviour is not addressed by this human mutation-screening paper and is at most an indirect consequence of lissencephaly. Reason: The paper identifies LIS1 point mutations in lissencephaly; motor phenotypes of patients are downstream of cortical malformation. Supporting Evidence: PMID:9063735 Classical lissencephaly (smooth brain) or generalized agyria-pachygyria is a severe brain malformation which results from an arrest of neuronal migration at 9-13 weeks gestation PMID:9063735 These data thus confirm LIS1 as the gene responsible for classical lissencephaly in ILS and MDS |
| GO:0010977 negative regulation of neuron projection development | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Negative regulation of neuron projection development conflicts with evidence that LIS1 supports axon growth. Reason: LIS1 knockdown arrests axonal growth; neurite elongation in Lis1 mutant slices is context-specific. The ortholog-derived negative-regulation term over-interprets a dosage phenotype. Supporting Evidence: PMID:16144905 Finally, axonal growth also ceased. |
| GO:0015630 microtubule cytoskeleton | IBA GO_REF:0000033 | ACCEPT | Summary: LIS1 acts on the microtubule cytoskeleton. Reason: Well supported. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Cytoplasm, cytoskeleton file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Localizes to the plus end of microtubules and to the centrosome |
| GO:0015630 microtubule cytoskeleton | IEA GO_REF:0000107 | ACCEPT | Summary: LIS1 acts on the microtubule cytoskeleton. Reason: Well supported. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Cytoplasm, cytoskeleton |
| GO:0017145 stem cell division | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: LIS1 is required for neural stem/progenitor division. Reason: Reflects the mitotic dynein role; non-core. Supporting Evidence: PMID:16144905 interkinetic nuclear oscillations in the radial glial progenitors were also abolished file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Required during brain development for the proliferation of neuronal precursors and the migration of newly formed neurons from the ventricular/subventricular zone toward the cortical plate |
| GO:0019226 transmission of nerve impulse | ISS PMID:10729324 Hippocampal abnormalities and enhanced excitability in a mur... | MARK AS OVER ANNOTATED | Summary: Transmission of nerve impulse is an indirect consequence of hippocampal dysplasia in Lis1+/- mice. Reason: Same reasoning as synaptic transmission. Supporting Evidence: PMID:10729324 Mechanisms of synaptic transmission were severely disrupted |
| GO:0021540 corpus callosum morphogenesis | IMP PMID:9063735 Point mutations and an intragenic deletion in LIS1, the liss... | KEEP AS NON CORE | Summary: Corpus callosum hypoplasia accompanies LIS1 lissencephaly. Reason: Developmental phenotype downstream of neuronal migration/axon growth defects; retained as non-core. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt hypoplasia of the corpus callosum |
| GO:0021766 hippocampus development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Hippocampal lamination depends on LIS1-dependent neuronal migration. Reason: Tissue-level developmental consequence. Supporting Evidence: PMID:10729324 neurons in Lis1+/- murine hippocampus are born at the appropriate time but fail in migration to form a defined cell layer |
| GO:0021819 layer formation in cerebral cortex | ISS GO_REF:0000024 | ACCEPT | Summary: Cortical layer formation directly depends on LIS1-mediated radial migration. Reason: Lissencephaly disorganizes cortical lamination. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt disorganization of the clear neuronal lamination of normal six-layered cortex PMID:11163258 LIS1-mNudE interactions may regulate neuronal migration through dynamic reorganization of the MTOC |
| GO:0021895 cerebral cortex neuron differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Cerebral cortex neuron differentiation (progenitor-to-bipolar transition) requires LIS1. Reason: Developmental, non-core. Supporting Evidence: PMID:16144905 These results identify multiple distinct and novel roles for LIS1 in nucleokinesis and process dynamics |
| GO:0021987 cerebral cortex development | IMP PMID:9063735 Point mutations and an intragenic deletion in LIS1, the liss... | KEEP AS NON CORE | Summary: LIS1 mutations cause lissencephaly, a cerebral cortex malformation. Reason: Organ-level developmental role; non-core. Supporting Evidence: PMID:9063735 Classical lissencephaly (smooth brain) or generalized agyria-pachygyria is a severe brain malformation which results from an arrest of neuronal migration at 9-13 weeks gestation PMID:9063735 These data thus confirm LIS1 as the gene responsible for classical lissencephaly in ILS and MDS |
| GO:0030036 actin cytoskeleton organization | ISS PMID:10729324 Hippocampal abnormalities and enhanced excitability in a mur... | KEEP AS NON CORE | Summary: LIS1 is required for Rho GTPase activation and actin polymerization at the leading edge of migrating neurons (mouse data). Reason: Real but secondary to the microtubule/dynein role. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Required for proper activation of Rho GTPases and actin polymerization at the leading edge of locomoting cerebellar neurons |
| GO:0030424 axon | IEA GO_REF:0000107 | ACCEPT | Summary: LIS1 redistributes to axons during neuronal development. Reason: Consistent with axonal dynein association. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Redistributes to axons during neuronal development PMID:11163259 redistribute to axons in association with retrograde dynein motor proteins |
| GO:0030426 growth cone | IEA GO_REF:0000107 | ACCEPT | Summary: LIS1 localizes to growth cones where it supports dynein-dependent growth cone advance. Reason: Ortholog transfer; plausible. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Redistributes to axons during neuronal development |
| GO:0030900 forebrain development | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Forebrain development is a broad developmental consequence of LIS1 function. Reason: Retained because LIS1 is required for neuronal precursor proliferation and radial migration in the developing cortex, and its haploinsufficiency causes lissencephaly, a forebrain malformation. Non-core because forebrain development is an organ-level outcome of the core dynein-regulator function, not an activity LIS1 performs directly. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Required during brain development for the proliferation of neuronal precursors and the migration of newly formed neurons from the ventricular/subventricular zone toward the cortical plate |
| GO:0031023 microtubule organizing center organization | IMP PMID:11163258 LIS1 regulates CNS lamination by interacting with mNudE, a c... | KEEP AS NON CORE | Summary: LIS1-mNudE interaction is proposed to regulate MTOC organization. Reason: Defer to the curator's IMP (full text not cached); MTOC organization is a consequence of the LIS1-NudE-dynein module. Supporting Evidence: PMID:11163258 LIS1-mNudE interactions may regulate neuronal migration through dynamic reorganization of the MTOC |
| GO:0031252 cell leading edge | IEA GO_REF:0000107 | ACCEPT | Summary: LIS1 acts at the leading edge of migrating cells. Reason: Consistent with Rho/actin and dynein roles at the leading edge. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Required for proper activation of Rho GTPases and actin polymerization at the leading edge of locomoting cerebellar neurons |
| GO:0031252 cell leading edge | ISS GO_REF:0000024 | ACCEPT | Summary: LIS1 colocalizes with leading-edge structures of migrating cells. Reason: As above. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Required for proper activation of Rho GTPases and actin polymerization at the leading edge of locomoting cerebellar neurons |
| GO:0031514 motile cilium | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: LIS1 has been localized in motile cilia and is implicated in axonemal dynein function in model systems. Reason: Non-core location. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Also localizes to the microtubules of the manchette in elongating spermatids and to the meiotic spindle in spermatocytes |
| GO:0031514 motile cilium | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Motile cilium localization transferred from orthologs. Reason: Non-core location. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Also localizes to the microtubules of the manchette in elongating spermatids and to the meiotic spindle in spermatocytes |
| GO:0031965 nuclear membrane | IEA GO_REF:0000044 | ACCEPT | Summary: LIS1 may localize to the nuclear membrane. Reason: Consistent with the nucleus-centrosome coupling role. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Nucleus membrane |
| GO:0031982 vesicle | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: LIS1 accompanies dynein on vesicular cargoes. Reason: Vesicle association reflects cargo transport; non-core. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Required for dynein recruitment to microtubule plus ends and BICD2-bound cargos |
| GO:0032420 stereocilium | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Stereocilium localization comes from mouse hair-cell studies. Reason: Tissue-specific location; non-core. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Cytoplasm, cytoskeleton |
| GO:0034452 dynactin binding | ISS PMID:11056532 A role for the lissencephaly gene LIS1 in mitosis and cytopl... | ACCEPT | Summary: LIS1 binds dynactin. Reason: Supported by co-immunoprecipitation and structural data (LIS1-p150 contact). Supporting Evidence: PMID:11056532 LIS1 protein co-immunoprecipitates with cytoplasmic dynein and dynactin, and localizes to the cell cortex and to mitotic kinetochores PMID:38547289 Unexpectedly, LIS1 binds dynactin's p150 subunit, tethering it along the length of dynein. |
| GO:0038026 reelin-mediated signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: LIS1 binds phosphorylated DAB1 and PAF-AH (I) links to VLDLR in reelin signaling (mouse data). Reason: Modulatory role; non-core. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Interacts with DAB1 when DAB1 is phosphorylated in response to RELN/reelin signaling file:human/PAFAH1B1/PAFAH1B1-uniprot.txt May modulate the Reelin pathway through interaction of the PAF-AH (I) catalytic dimer with VLDLR |
| GO:0038026 reelin-mediated signaling pathway | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Reelin pathway modulation transferred from mouse. Reason: Modulatory role; non-core. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Interacts with DAB1 when DAB1 is phosphorylated in response to RELN/reelin signaling file:human/PAFAH1B1/PAFAH1B1-uniprot.txt May modulate the Reelin pathway through interaction of the PAF-AH (I) catalytic dimer with VLDLR |
| GO:0040019 positive regulation of embryonic development | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Positive regulation of embryonic development is a vague consequence of Lis1-null embryonic lethality. Reason: Uninformative high-level process for a dynein regulator. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Required during brain development for the proliferation of neuronal precursors and the migration of newly formed neurons from the ventricular/subventricular zone toward the cortical plate |
| GO:0042249 establishment of planar polarity of embryonic epithelium | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Mouse Lis1 is required for planar polarity of cochlear hair cells via microtubule organization. Reason: Tissue-specific, non-core. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Positively regulates the activity of the minus-end directed microtubule motor protein dynein |
| GO:0042802 identical protein binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: LIS1 homodimerizes through its LisH domain. Reason: Self-association is required for dynein regulation; retained as non-core MF. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Can self-associate file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Dimerization mediated by the LisH domain may be required to activate dynein |
| GO:0042802 identical protein binding | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: LIS1 homodimerizes through its LisH domain. Reason: As above. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Can self-associate file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Dimerization mediated by the LisH domain may be required to activate dynein |
| GO:0043025 neuronal cell body | IEA GO_REF:0000107 | ACCEPT | Summary: LIS1 is present in neuronal cell bodies. Reason: Consistent with centrosomal/perinuclear localization in neurons. Supporting Evidence: PMID:15173193 Lis1 localized predominantly to the centrosome, and after disruption of microtubules, redistributed to the perinuclear region |
| GO:0043274 phospholipase binding | ISS PMID:8028668 Miller-Dieker lissencephaly gene encodes a subunit of brain ... | KEEP AS NON CORE | Summary: LIS1 binds the catalytic PAF-AH alpha subunits (phospholipase A2-type acetylhydrolases). Reason: Accurate description of the PAF-AH (I) regulatory interaction; non-core. Supporting Evidence: PMID:15572112 One LIS1 homodimer binds symmetrically to one alpha2/alpha2 homodimer via the highly conserved top faces of the LIS1 beta propellers |
| GO:0043622 cortical microtubule organization | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Cortical microtubule organization in hair-cell planar polarity (mouse). Reason: Tissue-specific; non-core. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Positively regulates the activity of the minus-end directed microtubule motor protein dynein |
| GO:0044877 protein-containing complex binding | IEA GO_REF:0000107 | MODIFY | Summary: LIS1 binds the dynein and dynactin complexes; protein-containing complex binding is too general. Reason: Replace with the specific child dynein complex binding. Proposed replacements: dynein complex binding Supporting Evidence: PMID:11889140 We find that the WD repeat domain of LIS1 interacts with three distinct subunits of the dynein and dynactin complexes, representing both motor and cargo-binding regions. |
| GO:0045505 dynein intermediate chain binding | IEA GO_REF:0000107 | ACCEPT | Summary: LIS1 WD repeats bind the dynein intermediate chain. Reason: Tai et al. mapped LIS1 binding to dynein and dynactin subunits. Supporting Evidence: PMID:11889140 We find that the WD repeat domain of LIS1 interacts with three distinct subunits of the dynein and dynactin complexes, representing both motor and cargo-binding regions. |
| GO:0045773 positive regulation of axon extension | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: LIS1 supports axon growth. Reason: LIS1 knockdown arrests axonal growth; non-core. Supporting Evidence: PMID:16144905 Finally, axonal growth also ceased. |
| GO:0045931 positive regulation of mitotic cell cycle | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Positive regulation of mitotic cell cycle over-generalizes LIS1's role in dynein-dependent mitotic mechanics. Reason: LIS1 is needed for spindle orientation and chromosome attachment, not for cell cycle regulation per se. Supporting Evidence: PMID:11056532 Overexpression of LIS1 in cultured mammalian cells interferes with mitotic progression and leads to spindle misorientation |
| GO:0046469 platelet activating factor metabolic process | ISS PMID:8028668 Miller-Dieker lissencephaly gene encodes a subunit of brain ... | KEEP AS NON CORE | Summary: As PAF-AH (I) beta subunit LIS1 contributes to PAF metabolism. Reason: Non-catalytic regulatory role; non-core. Supporting Evidence: PMID:8028668 This indicates that the LIS-1 gene product is a human homologue of the 45K subunit of intracellular PAF acetylhydrolase file:human/PAFAH1B1/PAFAH1B1-uniprot.txt The catalytic activity of the enzyme resides in the alpha1 (PAFAH1B3) and alpha2 (PAFAH1B2) subunits, whereas the beta subunit (PAFAH1B1) has regulatory activity |
| GO:0046982 protein heterodimerization activity | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: LIS1 binds the PAF-AH (I) catalytic alpha dimer. Reason: Accurate for the PAF-AH (I) heterocomplex; non-core. Supporting Evidence: PMID:15572112 One LIS1 homodimer binds symmetrically to one alpha2/alpha2 homodimer via the highly conserved top faces of the LIS1 beta propellers |
| GO:0047496 vesicle transport along microtubule | ISS PMID:10729324 Hippocampal abnormalities and enhanced excitability in a mur... | KEEP AS NON CORE | Summary: LIS1 supports dynein-driven vesicle/cargo transport. Reason: Consistent with BICD2-cargo data; non-core relative to nuclear migration. Supporting Evidence: PMID:22956769 LIS1 is required for dynein-mediated transport induced by membrane tethering of BICD2-N file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Required for dynein recruitment to microtubule plus ends and BICD2-bound cargos |
| GO:0048471 perinuclear region of cytoplasm | IEA GO_REF:0000107 | ACCEPT | Summary: LIS1 redistributes to the perinuclear region in migrating neurons. Reason: Relevant to nucleus-centrosome coupling. Supporting Evidence: PMID:15173193 Lis1 localized predominantly to the centrosome, and after disruption of microtubules, redistributed to the perinuclear region |
| GO:0048471 perinuclear region of cytoplasm | ISS GO_REF:0000024 | ACCEPT | Summary: Perinuclear localization transferred from orthologs. Reason: As above. Supporting Evidence: PMID:15173193 Lis1 localized predominantly to the centrosome, and after disruption of microtubules, redistributed to the perinuclear region |
| GO:0048854 brain morphogenesis | IMP PMID:9063735 Point mutations and an intragenic deletion in LIS1, the liss... | KEEP AS NON CORE | Summary: LIS1 mutations cause smooth-brain malformation. Reason: Organ-level consequence of neuronal migration failure. Supporting Evidence: PMID:9063735 Classical lissencephaly (smooth brain) or generalized agyria-pachygyria is a severe brain malformation which results from an arrest of neuronal migration at 9-13 weeks gestation |
| GO:0050804 modulation of chemical synaptic transmission | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Modulation of chemical synaptic transmission is indirect. Reason: Secondary to migration defects. Supporting Evidence: PMID:10729324 Mechanisms of synaptic transmission were severely disrupted |
| GO:0050885 neuromuscular process controlling balance | IMP PMID:9063735 Point mutations and an intragenic deletion in LIS1, the liss... | MARK AS OVER ANNOTATED | Summary: Balance/neuromuscular phenotypes are not addressed by this paper and would be indirect consequences of lissencephaly. Reason: Human mutation paper; phenotype downstream of cortical malformation. Supporting Evidence: PMID:9063735 These data thus confirm LIS1 as the gene responsible for classical lissencephaly in ILS and MDS |
| GO:0051012 microtubule sliding | IEA GO_REF:0000104 | KEEP AS NON CORE | Summary: LIS1 may enhance dynein-mediated microtubule sliding. Reason: Plausible dynein-regulator consequence; non-core. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt May enhance dynein-mediated microtubule sliding by targeting dynein to the microtubule plus end |
| GO:0051130 positive regulation of cellular component organization | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Positive regulation of cellular component organization is uninformatively broad. Reason: More specific terms capture LIS1 activity. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Positively regulates the activity of the minus-end directed microtubule motor protein dynein |
| GO:0051219 phosphoprotein binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: LIS1 binds tyrosine-phosphorylated DAB1. Reason: Real interaction in reelin signaling; non-core. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Interacts with DAB1 when DAB1 is phosphorylated in response to RELN/reelin signaling |
| GO:0051219 phosphoprotein binding | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: LIS1 binds tyrosine-phosphorylated DAB1. Reason: As above. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Interacts with DAB1 when DAB1 is phosphorylated in response to RELN/reelin signaling |
| GO:0051660 establishment of centrosome localization | IEA GO_REF:0000107 | ACCEPT | Summary: LIS1 is required for centrosome positioning/nucleus-centrosome coupling. Reason: Core dynein-dependent function. Supporting Evidence: PMID:15173193 Lis1 and Dcx function with dynein to mediate N-C coupling during migration PMID:20007476 Complete loss of Lis1 or Ndel1 resulted in the total inhibition of nuclear movement in cortical slice assays |
| GO:0060117 auditory receptor cell development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Auditory hair cell development in mouse Lis1 mutants. Reason: Tissue-specific; non-core. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Positively regulates the activity of the minus-end directed microtubule motor protein dynein |
| GO:0061003 positive regulation of dendritic spine morphogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Dendritic spine morphogenesis (mouse). Reason: Tissue-specific; non-core. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Required for proper activation of Rho GTPases and actin polymerization at the leading edge of locomoting cerebellar neurons |
| GO:0062234 platelet activating factor catabolic process | NAS PMID:15572112 Coupling PAF signaling to dynein regulation: structure of LI... | KEEP AS NON CORE | Summary: PAF catabolism is catalysed by the PAF-AH (I) alpha subunits; LIS1 is the regulatory subunit of the enzyme complex. Reason: LIS1 does not catalyse PAF hydrolysis but, as the regulatory beta subunit of the heterotetrameric enzyme, is part of the complex that performs it; non-core. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt The catalytic activity of the enzyme resides in the alpha1 (PAFAH1B3) and alpha2 (PAFAH1B2) subunits, whereas the beta subunit (PAFAH1B1) has regulatory activity PMID:15572112 as well as the catalytic alpha dimers of brain cytosolic platelet activating factor acetylhydrolase (PAF-AH) |
| GO:0070062 extracellular exosome | HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... | KEEP AS NON CORE | Summary: Detected in urinary exosome proteomics. Reason: High-throughput detection; not a functional location. Supporting Evidence: PMID:19056867 Here, we used LC-MS/MS to profile the proteome of human urinary exosomes |
| GO:0070507 regulation of microtubule cytoskeleton organization | IEA GO_REF:0000107 | ACCEPT | Summary: LIS1 regulates microtubule cytoskeleton organization via dynein. Reason: Consistent with MTOC and microtubule transport roles. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Required for several dynein- and microtubule-dependent processes such as the maintenance of Golgi integrity, the peripheral transport of microtubule fragments and the coupling of the nucleus and centrosome |
| GO:0070840 dynein complex binding | IDA PMID:11889140 Role of dynein, dynactin, and CLIP-170 interactions in LIS1 ... | ACCEPT | Summary: Tai et al. showed LIS1 binds dynein and dynactin subunits. Reason: LIS1 binds dynein (heavy chain motor domain, intermediate chain) and dynactin; dynein complex binding is a core MF. Supporting Evidence: PMID:11889140 We find that the WD repeat domain of LIS1 interacts with three distinct subunits of the dynein and dynactin complexes, representing both motor and cargo-binding regions. |
| GO:0070840 dynein complex binding | IEA GO_REF:0000104 | ACCEPT | Summary: Dynein complex binding (electronic) is consistent. Reason: LIS1 binds dynein (heavy chain motor domain, intermediate chain) and dynactin; dynein complex binding is a core MF. Supporting Evidence: PMID:11163259 LIS1 directly interacts with the cytoplasmic dynein heavy chain (CDHC) |
| GO:0090102 cochlea development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Cochlea development (mouse). Reason: Tissue-specific; non-core. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Positively regulates the activity of the minus-end directed microtubule motor protein dynein |
| GO:0090176 microtubule cytoskeleton organization involved in establishment of planar polarity | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Microtubule organization in planar polarity (mouse hair cells). Reason: Tissue-specific; non-core. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Positively regulates the activity of the minus-end directed microtubule motor protein dynein |
| GO:0090724 central region of growth cone | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Growth cone central region (mouse). Reason: Plausible; non-core location. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Redistributes to axons during neuronal development |
| GO:0098685 Schaffer collateral - CA1 synapse | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Schaffer collateral-CA1 synapse (ortholog). Reason: Synaptic location without demonstrated synaptic function; non-core. Supporting Evidence: PMID:10729324 Mechanisms of synaptic transmission were severely disrupted |
| GO:0098978 glutamatergic synapse | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Glutamatergic synapse (ortholog). Reason: Retained because Lis1-deficient mouse neurons show severely disrupted synaptic transmission, consistent with LIS1 acting in neurons after migration. Non-core because this is a transferred location (mouse ortholog) reflecting postmigratory neuronal roles rather than the central dynein regulatory function. Supporting Evidence: PMID:10729324 Mechanisms of synaptic transmission were severely disrupted |
| GO:0099175 regulation of postsynapse organization | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Regulation of postsynapse organization (ortholog). Reason: Retained because LIS1 regulates Rho GTPase activation and actin polymerization in neurons, a plausible route to postsynaptic structure. Non-core because the evidence is transferred from the mouse ortholog and is downstream of, not part of, LIS1's dynein-regulator function. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Required for proper activation of Rho GTPases and actin polymerization at the leading edge of locomoting cerebellar neurons |
| GO:1904115 axon cytoplasm | IEA GO_REF:0000108 | ACCEPT | Summary: Axon cytoplasm, consistent with axonal localization with retrograde dynein. Reason: Logical inference from axonal localization. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Redistributes to axons during neuronal development |
| GO:0140659 cytoskeletal motor regulator activity | IDA PMID:20403325 LIS1 and NudE induce a persistent dynein force-producing sta... | NEW | Summary: LIS1 directly regulates cytoplasmic dynein-1 motor mechanics: it binds the motor domain in the pre-powerstroke state and induces a persistent-force state, and promotes dynein-dynactin-adaptor assembly. Reason: Single-molecule and structural data establish LIS1 as a direct regulator of the dynein motor (neither activator nor inhibitor alone in all contexts), so the parent cytoskeletal motor regulator activity is the appropriate MF. This is the informative MF behind the dynein complex binding annotations. Supporting Evidence: PMID:20403325 LIS1 interacts with the motor domain during the prepowerstroke state of the dynein crossbridge cycle PMID:20403325 LIS1 alone or with NudE induces a persistent-force dynein state that improves ensemble function of multiple dyneins for transport under high-load conditions PMID:36692009 is a key regulator of cytoplasmic dynein-1 PMID:38547289 LIS1 and p150 constrain dynein-dynactin to ensure efficient complex formation file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Positively regulates the activity of the minus-end directed microtubule motor protein dynein |
| GO:0030234 enzyme regulator activity | ISS file:human/PAFAH1B1/PAFAH1B1-uniprot.txt | NEW | Summary: LIS1 is the non-catalytic regulatory beta subunit of PAF-AH (I) and modulates the activity of the PAFAH1B2/PAFAH1B3 catalytic dimer. Reason: UniProt (by similarity to bovine/mouse) states the beta subunit has regulatory activity towards the catalytic dimer; the LIS1-alpha2 dimer crystal structure provides the physical basis. The broad enzyme regulator term is used because the direction of regulation depends on catalytic dimer composition. Captures the PAF-AH role without implying LIS1 catalysis. Supporting Evidence: file:human/PAFAH1B1/PAFAH1B1-uniprot.txt The catalytic activity of the enzyme resides in the alpha1 (PAFAH1B3) and alpha2 (PAFAH1B2) subunits, whereas the beta subunit (PAFAH1B1) has regulatory activity file:human/PAFAH1B1/PAFAH1B1-uniprot.txt Regulatory subunit (beta subunit) of the cytosolic type I platelet-activating factor (PAF) acetylhydrolase (PAF-AH (I)) PMID:15572112 One LIS1 homodimer binds symmetrically to one alpha2/alpha2 homodimer via the highly conserved top faces of the LIS1 beta propellers |
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Download this section (compressed HTML)Q: Does binding of the PAF-AH alpha2/alpha2 dimer to LIS1 regulate the pool of LIS1 available to NDEL1/dynein in neurons, i.e. is there physiological cross-talk between PAF signalling and dynein-driven nucleokinesis?
Suggested experts: dynein/LIS1 structural biologists, PAF-AH biochemists
Q: Should LIS1's dynein role be captured as cytoskeletal motor activator activity (GO:0140660) rather than the regulator parent, given that LIS1 promotes dynein-dynactin assembly but also restrains motility in some assays?
Suggested experts: GO molecular-function editors, dynein motor biophysicists
Q: Is there evidence for a nucleoplasmic LIS1 pool (e.g. via INTS13) that would support the IBA nucleus annotation?
Suggested experts: PAINT curators
Experiment: Express LIS1 mutants that selectively disrupt PAF-AH alpha-dimer binding versus dynein/NDEL1 binding in cortical slices and image nucleus-centrosome coupling.
Hypothesis: Nucleokinesis requires the dynein-binding surface but not PAF-AH binding.
Type: in utero electroporation with separation-of-function mutants and live imaging
Experiment: Reconstitute dynein-dynactin-BICD2 motility with wild-type or lissencephaly-mutant LIS1 under optical-trap load.
Hypothesis: Lissencephaly mutations impair LIS1-dependent dynein complex assembly and high-load force persistence.
Type: single-molecule reconstitution/optical trapping
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