Pac1 is the Saccharomyces cerevisiae ortholog of LIS1 (Aspergillus NudF), a dimeric WD40 beta-propeller protein with an N-terminal LisH dimerization domain that binds the motor domain of cytoplasmic dynein (Dyn1). In budding yeast dynein's principal role is to pull the mitotic spindle into the bud neck: dynein is carried to the plus ends of astral microtubules, off-loaded to cortical Num1 receptors in the bud, and then walks toward the spindle pole body so that microtubules slide along the bud cortex. Pac1 localizes to the plus ends of cytoplasmic microtubules (with help from Bik1/CLIP-170 and the NudE homolog Ndl1) and is required for dynein's plus-end accumulation and hence for microtubule sliding, spindle movement into the neck and nuclear segregation; pac1 mutants are synthetically lethal with loss of the kinesin-5 Cin8 and sick with loss of the parallel Kar9 pathway. Biochemically, Pac1 engages the dynein motor at the interface between the AAA+ ring and stalk, prolonging microtubule attachment, and it stabilizes an uninhibited (open) conformation of dynein, coordinating dynein's plus-end localization with its later activation at the cortex.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000132 establishment of mitotic spindle orientation | IEA GO_REF:0000104 | ACCEPT | Summary: UniRule establishment of mitotic spindle orientation. Reason: In budding yeast the dynein pathway, including Pac1, positions and orients the mitotic spindle at the bud neck; pac1 mutants fail to move the spindle into the neck. This is a core process for Pac1. Supporting Evidence: PMID:12566428 Second, cells lacking Pac1 failed to display microtubule sliding in the bud, resulting in defective mitotic spindle movement and nuclear segregation. PMID:12566428 Our results suggest that Pac1 targets dynein to microtubule tips, which is necessary for sliding of microtubules along the bud cortex. |
| GO:0000922 spindle pole | IEA GO_REF:0000044 | UNDECIDED | Summary: UniProt subcellular location spindle pole. Reason: The spindle pole location in UniProt reflects the LIS1/nudF family (A. nidulans NudF is at spindle pole bodies). In yeast, Pac1 is required for dynein's localization to spindle pole bodies, but the cached yeast studies image Pac1 itself at microtubule plus ends (and infer cortical off-loading), not at the SPB. The location is plausible but not directly shown for Pac1. Supporting Evidence: PMID:34994688 In yeast, Lis1 is required for dyneinβs localization to SPBs, microtubule plus ends, and the cell cortex PMID:12566428 Third, Pac1 localized to the plus ends (distal tips) of cytoplasmic microtubules in the bud. |
| GO:0005515 protein binding | IPI PMID:11087867 A computationally directed screen identifying interacting co... | REMOVE | Summary: Two-hybrid interactions (Kel1, Nnf1) from a computational screen for interacting coiled coils. Reason: Generic protein binding from a large-scale two-hybrid screen; the partners (Kel1, Nnf1) have no established functional link to Pac1's dynein-regulatory role, and the annotation conveys no functional information. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:11087867 A computationally directed screen identifying interacting co... | REMOVE | Summary: Two-hybrid interactions (Kel1, Nnf1) from a computational screen for interacting coiled coils. Reason: Generic protein binding from a large-scale two-hybrid screen; the partners (Kel1, Nnf1) have no established functional link to Pac1's dynein-regulatory role, and the annotation conveys no functional information. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:37968396 The social and structural architecture of the yeast protein ... | REMOVE | Summary: Large-scale interactome detection with Rsc4. Reason: Generic protein binding from a proteome-scale interaction map with a chromatin-remodeling subunit; uninformative and without functional context for Pac1. |
| GO:0005634 nucleus | IDA PMID:15965467 NudEL targets dynein to microtubule ends through LIS1. | KEEP AS NON CORE | Summary: Nucleus localization from the Ndl1 discovery paper (Pac1-13Myc/Ndl1-6HA distributions). Reason: The cached text does not state nuclear localization explicitly, but both SGD (this IDA) and UniProt (Subcellular location: Nucleus, citing this paper) extracted it, most likely from immunofluorescence figures describing the overlapping but distinct distributions of tagged Pac1 and Ndl1. Deferring to the curators, the location is kept; no nuclear function of Pac1 is known, so it is non-core. Supporting Evidence: PMID:15965467 The overlapping but different distributions of Pac1β13Myc and Ndl1β6HA could result from the existence of one complex with both proteins, or from two different complexes. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: UniProt subcellular location nucleus. Reason: Mapped from the UniProt location, which cites PMID:15965467; same reasoning as the IDA row. No nuclear function known. Supporting Evidence: file:yeast/PAC1/PAC1-uniprot.txt spindle pole. Nucleus. Note=Localizes to the plus ends of cytoplasmic |
| GO:0005737 cytoplasm | HDA PMID:11914276 Subcellular localization of the yeast proteome. | ACCEPT | Summary: Proteome-wide GFP localization: cytoplasm. Reason: Consistent with Pac1 acting on cytoplasmic microtubules. |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA cytoplasm. Reason: Correct; Pac1 is a cytoplasmic dynein regulator. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN008687761 Β· PTN008687761 SUPPORTS TRANSFER This broad eukaryotic cytoplasm assertion correctly transfers to Pac1, a cytoplasmic LIS1-family regulator that functions on cytoplasmic dynein at cytoplasmic microtubule plus ends. Supporting Evidence: PMID:12566428 Third, Pac1 localized to the plus ends (distal tips) of cytoplasmic microtubules in the bud. |
| GO:0005737 cytoplasm | IEA GO_REF:0000104 | ACCEPT | Summary: UniRule cytoplasm. Reason: Correct. Supporting Evidence: PMID:12566428 Third, Pac1 localized to the plus ends (distal tips) of cytoplasmic microtubules in the bud. |
| GO:0005856 cytoskeleton | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular location cytoskeleton. Reason: Correct but general. Supporting Evidence: PMID:12566428 Third, Pac1 localized to the plus ends (distal tips) of cytoplasmic microtubules in the bud. |
| GO:0005875 microtubule associated complex | IEA GO_REF:0000104 | ACCEPT | Summary: UniRule microtubule associated complex. Reason: Pac1 forms plus-end complexes with dynein, dynactin and Ndl1 on cytoplasmic microtubules. Supporting Evidence: PMID:15965467 All Ndl1β3GFP foci at plus ends contained Dyn3β3CFP, and all Dyn3β3CFP foci at plus ends contained Pac1β3GFP |
| GO:0005881 cytoplasmic microtubule | IDA PMID:12566428 The role of the lissencephaly protein Pac1 during nuclear mi... | ACCEPT | Summary: Pac1-GFP at plus ends of cytoplasmic microtubules. Reason: Direct localization. Supporting Evidence: PMID:12566428 Third, Pac1 localized to the plus ends (distal tips) of cytoplasmic microtubules in the bud. |
| GO:0005881 cytoplasmic microtubule | IDA PMID:15965467 NudEL targets dynein to microtubule ends through LIS1. | ACCEPT | Summary: Pac1-3GFP at cytoplasmic microtubule plus ends, reduced in ndl1 mutants. Reason: Direct localization. Supporting Evidence: PMID:15965467 In the absence of Ndl1, the fluorescence intensity of Pac1β3GFP at the plus ends was decreased by ~ 50% |
| GO:0007017 microtubule-based process | IEA GO_REF:0000104 | ACCEPT | Summary: UniRule microtubule-based process. Reason: Broad but correct. Supporting Evidence: PMID:12566428 Second, cells lacking Pac1 failed to display microtubule sliding in the bud, resulting in defective mitotic spindle movement and nuclear segregation. |
| GO:0015630 microtubule cytoskeleton | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA microtubule cytoskeleton (Pac1 itself and NudF among sources). Reason: Correct; Pac1's own plus-end localization is one of the node's experimental sources, as expected. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002891245 Β· PTN002891245 SUPPORTS TRANSFER The PTN002891245 microtubule-cytoskeleton node includes Pac1-specific experimental evidence and correctly transfers the LIS1-family plus-end/microtubule-cytoskeleton localization to budding-yeast Pac1. Supporting Evidence: PMID:12566428 Third, Pac1 localized to the plus ends (distal tips) of cytoplasmic microtubules in the bud. |
| GO:0030473 nuclear migration along microtubule | IMP PMID:12566428 The role of the lissencephaly protein Pac1 during nuclear mi... | ACCEPT | Summary: pac1 deletion abolishes microtubule sliding and spindle movement into the bud neck. Reason: Core process: in budding yeast, dynein-dependent nuclear migration is the movement of the nucleus/spindle into the neck by microtubule sliding along the bud cortex, and Pac1 is required for it. Supporting Evidence: PMID:12566428 Second, cells lacking Pac1 failed to display microtubule sliding in the bud, resulting in defective mitotic spindle movement and nuclear segregation. PMID:12566428 First, genetic interactions placed Pac1 in the dynein/dynactin pathway. |
| GO:0042802 identical protein binding | IPI PMID:18719252 High-quality binary protein interaction map of the yeast int... | KEEP AS NON CORE | Summary: Pac1 self-interaction in a proteome-scale two-hybrid screen. Reason: Pac1, like all LIS1 proteins, is a LisH-mediated dimer. Dimerization supports but is not strictly required for dynein regulation (a monomeric beta-propeller can regulate dynein at high concentration), so it is retained as a non-core structural property. Supporting Evidence: PMID:22939623 Like cytoplasmic dynein's force-generating subunit, Lis1 is dimeric. |
| GO:0042802 identical protein binding | IPI PMID:22939623 Lis1 acts as a "clutch" between the ATPase and microtubule-b... | KEEP AS NON CORE | Summary: Pac1/Lis1 dimerization via the N-terminal domain. Reason: Dimerization is a conserved LIS1 property; monomeric Lis1 lacking the dimerization domain still regulates dynein when overexpressed. Supporting Evidence: PMID:22939623 Like cytoplasmic dynein's force-generating subunit, Lis1 is dimeric. PMID:22939623 This suggests that a monomeric Lis1 construct comprising the Ξ²-propeller domain can regulate dynein both in vitro and in vivo, provided its concentration is sufficiently high. |
| GO:0051010 microtubule plus-end binding | IDA PMID:15965467 NudEL targets dynein to microtubule ends through LIS1. | KEEP AS NON CORE | Summary: Pac1 at microtubule plus ends. Reason: Pac1 localizes to plus ends independently of dynein, but its plus-end targeting depends partly on Ndl1 (and Bik1), so the evidence is localization rather than a demonstration of direct plus-end binding. Deferring to the SGD curator, the annotation is kept, but plus-end localization (added as a NEW location) and dynein binding better describe Pac1's role. Supporting Evidence: PMID:15965467 Thus, Ndl1 is required for the efficient targeting of LIS1/Pac1 but not CLIP170/Bik1 to the microtubule plus ends. PMID:12566423 Although Pac1's plus end localization is not Dyn1 dependent, lack of Pac1 results in the loss of Dyn1's MT plus end localization. |
| GO:0051012 microtubule sliding | IEA GO_REF:0000104 | ACCEPT | Summary: UniRule microtubule sliding. Reason: Directly supported in yeast: pac1 cells fail to slide microtubules along the bud cortex. Pac1 contributes the dynein-targeting and regulatory activity on which cortical dynein-driven sliding depends. Supporting Evidence: PMID:12566428 Second, cells lacking Pac1 failed to display microtubule sliding in the bud, resulting in defective mitotic spindle movement and nuclear segregation. PMID:12566428 Our results suggest that Pac1 targets dynein to microtubule tips, which is necessary for sliding of microtubules along the bud cortex. |
| GO:0070840 dynein complex binding | IEA GO_REF:0000104 | ACCEPT | Summary: UniRule dynein complex binding. Reason: Pac1/Lis1 binds the dynein motor domain via its beta-propeller, at a ring site and a stalk site; structure-guided mutations at these sites impair dynein localization in yeast. Core molecular function. Supporting Evidence: file:yeast/PAC1/PAC1-deep-research-falcon.md Pac1 binds directly to the motor domain of the dynein heavy chain Dyn1. PMID:22939623 We show that rather than binding to the main ATPase site within dynein's AAA+ ring or its microtubule-binding stalk directly, Lis1 engages the interface between these elements. |
| GO:0140659 cytoskeletal motor regulator activity | IDA PMID:22939623 Lis1 acts as a "clutch" between the ATPase and microtubule-b... | NEW | Summary: Purified Pac1/Lis1 alters the mechanochemistry of yeast dynein (prolonged microtubule attachment), and stabilizes its uninhibited conformation. Reason: Direct in vitro and in vivo evidence that Pac1 regulates the dynein motor; matches the module and human LIS1 term GO:0140659. Whether the net effect is inhibitory (holding dynein at plus ends until Num1 releases it) or activating (stabilizing the open conformation) depends on context, which the regulator parent term accommodates. Supporting Evidence: PMID:22939623 Thus, Lis1 operates like a "clutch" that prevents dynein's ATPase domain from transmitting a detachment signal to its track-binding domain. PMID:32341548 Our studies demonstrate that, rather than inhibiting dynein motility, Pac1/LIS1 promotes dynein activity by stabilizing the uninhibited conformation, which ensures appropriate dynein localization and activity in cells. PMID:41571912 Our results support a model in which Lis1 can indeed open and/or stabilize an uninhibited conformation of dynein but only when the AAA domains are in specific nucleotide-bound states. |
| GO:0035371 microtubule plus-end | IDA PMID:12566428 The role of the lissencephaly protein Pac1 during nuclear mi... | NEW | Summary: Pac1-GFP localizes to the distal tips of cytoplasmic microtubules. Reason: Plus-end localization is the defining location for Pac1 function (targeting dynein to plus ends before off-loading). Supporting Evidence: PMID:12566428 Third, Pac1 localized to the plus ends (distal tips) of cytoplasmic microtubules in the bud. |
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Download this section (compressed HTML)Q: Is Pac1 found in the nucleus under physiological conditions, and if so does it have a nuclear function (e.g. related to its sumoylation or Rsc4 interaction) distinct from dynein regulation?
Suggested experts: yeast cell biologists, SGD curators
Experiment: Quantitative imaging of endogenously tagged Pac1 with nuclear markers across the cell cycle and under stress, with nuclear-export-defective backgrounds.
Hypothesis: Pac1 is exclusively cytoplasmic; apparent nuclear signal reflects overexpression or background.
Type: live-cell imaging
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Download this section (compressed HTML)Regulator of dynein, involved in intracellular transport; part of the dynein/dynactin pathway; targets dynein to microtubule tips, which is necessary for sliding of microtubules along bud cortex; serves at interface between dynein's ATPase site and its microtubule binding stalk, causing individual dynein motors to remain attached to microtubules for long periods; synthetic lethal with bni1; homolog of human LIS1, mutations in which cause the severe brain disorder lissencephaly
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