PAC1/YOR269W Summary Help

Standard Name PAC1 1
Systematic Name YOR269W
Feature Type ORF, Verified
Description Involved in nuclear migration, 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 (2, 3, 4 and see Summary Paragraph)
Name Description Perish in the Absence of Cin8p 1
Chromosomal Location
ChrXV:826385 to 827869 | ORF Map | GBrowse
Gbrowse
Gene Ontology Annotations All PAC1 GO evidence and references
  View Computational GO annotations for PAC1
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
High-throughput
Regulators 8 genes
Resources
Classical genetics
reduction of function
Large-scale survey
null
Resources
267 total interaction(s) for 144 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 4
  • Affinity Capture-RNA: 2
  • Affinity Capture-Western: 2
  • Co-fractionation: 1
  • Co-localization: 1
  • Co-purification: 2
  • Protein-RNA: 1
  • Reconstituted Complex: 2
  • Two-hybrid: 65

Genetic Interactions
  • Dosage Rescue: 1
  • Negative Genetic: 139
  • Phenotypic Suppression: 1
  • Positive Genetic: 5
  • Synthetic Growth Defect: 9
  • Synthetic Lethality: 32

Resources
Expression Summary
histogram
Resources
Length (a.a.) 494
Molecular Weight (Da) 56,900
Isoelectric Point (pI) 7.57
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrXV:826385 to 827869 | ORF Map | GBrowse
SGD ORF map
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..1485 826385..827869 2011-02-03 1996-07-31
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
Resources
External Links All Associated Seq | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000005795
SUMMARY PARAGRAPH for PAC1

During the budding process, the mitotic spindle must move into the narrow neck between the mother cell and the bud in order to segregate duplicated chromosomes accurately. Since the nuclear envelope does not break down during mitosis in S. cerevisiae, the movement of the spindle occurs as part of nuclear migration into the neck region, and it occurs in two main steps (reviewed in 3). First the nucleus moves to a position adjacent to the neck, a process that involves cytoplasmic microtubules, Kip3p, Kar9p, and other proteins involved in Kar9p function. Second, the mitotic spindle is moved into the neck. This requires cytoplasmic microtubules from the spindle pole body, which slide along the bud cortex and pull the nucleus and elongating spindle. Sliding depends on the heavy chain of cytoplasmic dynein (Dyn1p), the regulator dynactin complex (Arp1p, Jnm1p, and Nip100p), Num1p, and Ndl1p (5, reviewed in 3). Pac1p functions in this second step, aiding in recruitment of Dyn1p, a minus end-directed motor, to the plus ends of microtubules (3, 6).

The role of Pac1p in Dyn1p recruitment is supported by several lines of evidence. Localization studies indicate that both Pac1p and Dyn1p are found at the plus ends of micortubules; localization of Dyn1p requires functional Pac1p and Bik1p, but localization of Pac1p does not require Dyn1p (3, 6). Localization of Pac1p does require Ndl1p, which is thought to help promote recruitment of dynein by Pac1p (5). pac1 null mutants do not exhibit efficient movement of the mitotic spindle into the bud neck because the cells are defective for microtubule sliding along the bud cortex; dyn1 null mutants have the same phenotype (7, 3).

PAC1 encodes the S. cerevisiae homolog of human LIS1, a protein required for nuclear migration in neurons during development (1). Mutations in LIS1 cause brain malformations referred to as lissencephaly (smooth brain; see 8, 5 and references therein). Pac1p homologs have been indentified in a number of other organisms, including S. pombe, A. nidulans, D. melanogaster, and C. elegans (3). These proteins have a predicted coiled-coil region in the amino terminus and seven tandem WD40 repeats in the carboxy terminal two-thirds of the protein (3). The human and A. nidulans homologs have been shown to localize to the plus ends of microtubules, similar to Pac1p (see 3).

Last updated: 2007-07-11 Contact SGD

References cited on this page View Complete Literature Guide for PAC1
1) Geiser JR, et al.  (1997) Saccharomyces cerevisiae genes required in the absence of the CIN8-encoded spindle motor act in functionally diverse mitotic pathways. Mol Biol Cell 8(6):1035-50
2) Fujiwara T, et al.  (1999) Bni1p regulates microtubule-dependent nuclear migration through the actin cytoskeleton in Saccharomyces cerevisiae. Mol Cell Biol 19(12):8016-27
3) Lee WL, et al.  (2003) The role of the lissencephaly protein Pac1 during nuclear migration in budding yeast. J Cell Biol 160(3):355-64
4) Huang J, et al.  (2012) Lis1 Acts as a "Clutch" between the ATPase and Microtubule-Binding Domains of the Dynein Motor. Cell 150(5):975-86
5) Li J, et al.  (2005) NudEL targets dynein to microtubule ends through LIS1. Nat Cell Biol 7(7):686-90
6) Sheeman B, et al.  (2003) Determinants of S. cerevisiae dynein localization and activation: implications for the mechanism of spindle positioning. Curr Biol 13(5):364-72
7) Eshel D, et al.  (1993) Cytoplasmic dynein is required for normal nuclear segregation in yeast. Proc Natl Acad Sci U S A 90(23):11172-6
8) Xiang X  (2003) LIS1 at the microtubule plus end and its role in dynein-mediated nuclear migration. J Cell Biol 160(3):289-90