Protein: Platelet-activating factor acetylhydrolase IB subunit beta (Lissencephaly-1 protein) (LIS-1) (PAF acetylhydrolase 45 kDa subunit) (PAF-AH 45 kDa subunit) (PAF-AH alpha) (PAFAH alpha) (P63005)
Organism: Mus musculus (Mouse)
Function: Regulatory subunit (beta subunit) of the cytosolic type I platelet-activating factor (PAF) acetylhydrolase (PAF-AH (I)), an enzyme that catalyzes the hydrolyze of the acetyl group at the sn-2 position of PAF and its analogs and participates in PAF inactivation. Regulates the PAF-AH (I) activity in a catalytic dimer composition-dependent manner (By similarity). Positively regulates the activity of the minus-end directed microtubule motor protein dynein. May enhance dynein-mediated microtubule sliding by targeting dynein to the microtubule plus end. 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. 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. Neuronal migration involves a process called nucleokinesis, whereby migrating cells extend an anterior process into which the nucleus subsequently translocates. During nucleokinesis dynein at the nuclear surface may translocate the nucleus towards the centrosome by exerting force on centrosomal microtubules. Also required for proper activation of Rho GTPases and actin polymerization at the leading edge of locomoting cerebellar neurons and postmigratory hippocampal neurons in response to calcium influx triggered via NMDA receptors. May also play a role in other forms of cell locomotion including the migration of fibroblasts during wound healing. Non-catalytic subunit of an acetylhydrolase complex which inactivates platelet-activating factor (PAF) by removing the acetyl group at the SN-2 position. Required for dynein recruitment to microtubule plus ends and BICD2-bound cargos (By similarity). May modulate the Reelin pathway through interaction of the PAF-AH (I) catalytic dimer with VLDLR.
Subcellular location: Cytoplasm, cytoskeleton. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Cytoplasm, cytoskeleton, spindle. Nucleus membrane {ECO:0000255|HAMAP-Rule:MF_03141}. Note=May localize to the nuclear membrane (By similarity). Localizes to the plus end of microtubules and to the centrosome. Redistributes to axons during neuronal development. Also localizes to the microtubules of the manchette in elongating spermatids and to the meiotic spindle in spermatocytes. {ECO:0000250}.
Sequence: MVLSQRQRDELNRAIADYLRSNGYEEAYSVFKKEAELDMNEELDKKYAGLLEKKWTSVIRLQKKVMELESKLNEAKEEFTSGGPLGQKRDPKEWIPRPPEKYALSGHRSPVTRVIFHPVFSVMVSASEDATIKVWDYETGDFERTLKGHTDSVQDISFDHSGKLLASCSADMTIKLWDFQGFECIRTMHGHDHNVSSVAIMPNGDHIVSASRDKTIKMWEVQTGYCVKTFTGHREWVRMVRPNQDGTLIASCSNDQTVRVWVVATKECKAELREHEHVVECISWAPESSYSSISEATGSETKKSGKPGPFLLSGSRDKTIKMWDVSTGMCLMTLVGHDNWVRGVLFHSGGKFILSCADDKTLRVWDYKNKRCMKTLNAHEHFVTSLDFHKTAPYVVTGSVDQTVKVWECR
InterPro domains: - IPR019775: WD40 repeat, conserved site (conserved_site) [165-409]
- IPR001680: WD40 repeat (repeat) [97-410]
- IPR020472: PAC1/LIS1-like, WD-40 repeat (repeat) [123-325]
- IPR015943: WD40/YVTN repeat-like-containing domain superfamily (homologous_superfamily) [101-410]
- IPR017252: Dynein regulator LIS1 (family) [1-409]
- IPR050349: WD repeat LIS1/nudF dynein regulation (family) [54-409]
- IPR056795: PAC1-like, LisH-like dimerisation domain (domain) [5-39]
- IPR037190: LIS1, N-terminal (homologous_superfamily) [2-76]
- IPR036322: WD40-repeat-containing domain superfamily (homologous_superfamily) [94-407]
- IPR006594: LIS1 homology motif (conserved_site) [7-39]
Interaction partners: - Nuclear distribution protein nudE-like 1
- Platelet-activating factor acetylhydrolase IB subunit alpha2
- Platelet-activating factor acetylhydrolase IB subunit alpha1
- Cytoplasmic dynein 1 heavy chain 1
- Dynactin subunit 2
- Nuclear distribution protein nudE homolog 1
- 14-3-3 protein epsilon
- Nuclear migration protein nudC
- Cytoplasmic dynein 1 intermediate chain 2
- Platelet-activating factor acetylhydrolase 2, cytoplasmic
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0044877 (protein-containing complex binding), GO:0005515 (protein binding), GO:0070840 (dynein complex binding)
Biological Process (BP): GO:0008150 (biological process), GO:0051179 (localization), GO:0048518 (positive regulation of biological process), GO:0050789 (regulation of biological process), GO:0023052 (signaling), GO:0032501 (multicellular organismal process), GO:0065007 (biological regulation), GO:0050896 (response to stimulus), GO:0032502 (developmental process), GO:0009987 (cellular process), GO:0008152 (metabolic process), GO:0042592 (homeostatic process), GO:0048519 (negative regulation of biological process), GO:0009605 (response to external stimulus), GO:0051641 (cellular localization), GO:0048856 (anatomical structure development), GO:0048870 (cell motility), GO:0009653 (anatomical structure morphogenesis), GO:0042221 (response to chemical), GO:0090130 (tissue migration), GO:0008283 (cell population proliferation), GO:0022402 (cell cycle process), GO:0051240 (positive regulation of multicellular organismal process), GO:0006807 (nitrogen compound metabolic process), GO:0071840 (cellular component organization or biogenesis), GO:0051239 (regulation of multicellular organismal process), GO:0048646 (anatomical structure formation involved in morphogenesis), GO:0009892 (negative regulation of metabolic process), GO:0007267 (cell-cell signaling), GO:0050793 (regulation of developmental process), GO:0065008 (regulation of biological quality), GO:0019725 (cellular homeostasis), GO:0009719 (response to endogenous stimulus), GO:0050794 (regulation of cellular process), GO:0051716 (cellular response to stimulus), GO:0023051 (regulation of signaling), GO:0048523 (negative regulation of cellular process), GO:0007165 (signal transduction), GO:0048869 (cellular developmental process), GO:0009628 (response to abiotic stimulus), GO:0023056 (positive regulation of signaling), GO:0007275 (multicellular organism development), GO:0009058 (biosynthetic process), GO:0048584 (positive regulation of response to stimulus), GO:0019222 (regulation of metabolic process), GO:0007049 (cell cycle), GO:0051234 (establishment of localization), GO:0071704 (organic substance metabolic process), GO:0003008 (system process), GO:0033036 (macromolecule localization), GO:0048878 (chemical homeostasis), GO:0044237 (cellular metabolic process), GO:0009893 (positive regulation of metabolic process), GO:0044238 (primary metabolic process), GO:0006950 (response to stress), GO:0051606 (detection of stimulus), GO:0051094 (positive regulation of developmental process), GO:0007154 (cell communication), GO:0048522 (positive regulation of cellular process), GO:0009581 (detection of external stimulus), GO:0001101 (response to acid chemical), GO:0000910 (cytokinesis), GO:0090068 (positive regulation of cell cycle process), GO:0060548 (negative regulation of cell death), GO:0048468 (cell development), GO:0030154 (cell differentiation), GO:0048731 (system development), GO:0048513 (animal organ development), GO:0070848 (response to growth factor), GO:0044255 (cellular lipid metabolic process), GO:0071495 (cellular response to endogenous stimulus), GO:0060255 (regulation of macromolecule metabolic process), GO:0009582 (detection of abiotic stimulus), GO:0006725 (cellular aromatic compound metabolic process), GO:0001817 (regulation of cytokine production), GO:0045787 (positive regulation of cell cycle), GO:0006793 (phosphorus metabolic process), GO:0035295 (tube development), GO:0051726 (regulation of cell cycle), GO:0009894 (regulation of catabolic process), GO:0055082 (intracellular chemical homeostasis), GO:0009887 (animal organ morphogenesis), GO:1901360 (organic cyclic compound metabolic process), GO:0010605 (negative regulation of macromolecule metabolic process), GO:0007186 (G protein-coupled receptor signaling pathway), GO:0022603 (regulation of anatomical structure morphogenesis), GO:0051171 (regulation of nitrogen compound metabolic process), GO:0016043 (cellular component organization), GO:0051128 (regulation of cellular component organization), GO:0044260 (cellular macromolecule metabolic process), GO:0010564 (regulation of cell cycle process), GO:0008284 (positive regulation of cell population proliferation), GO:0016477 (cell migration), GO:0051173 (positive regulation of nitrogen compound metabolic process), GO:0035239 (tube morphogenesis), GO:0050801 (monoatomic ion homeostasis), GO:0009967 (positive regulation of signal transduction), GO:0051172 (negative regulation of nitrogen compound metabolic process), GO:1901576 (organic substance biosynthetic process), GO:1903047 (mitotic cell cycle process), GO:0010604 (positive regulation of macromolecule metabolic process), GO:0198738 (cell-cell signaling by wnt), GO:0046483 (heterocycle metabolic process), GO:0090132 (epithelium migration), GO:0044249 (cellular biosynthetic process), GO:1901700 (response to oxygen-containing compound), GO:0098771 (inorganic ion homeostasis), GO:0034641 (cellular nitrogen compound metabolic process), GO:0031324 (negative regulation of cellular metabolic process), GO:0043170 (macromolecule metabolic process), GO:0010033 (response to organic substance), GO:0060249 (anatomical structure homeostasis), GO:0009891 (positive regulation of biosynthetic process), GO:0048872 (homeostasis of number of cells), GO:0003012 (muscle system process), GO:0055082 (intracellular chemical homeostasis), GO:0042127 (regulation of cell population proliferation), GO:0006629 (lipid metabolic process), GO:0010941 (regulation of cell death), GO:0009888 (tissue development), GO:0006139 (nucleobase-containing compound metabolic process), GO:1901698 (response to nitrogen compound), GO:0060322 (head development), GO:0010646 (regulation of cell communication), GO:0031325 (positive regulation of cellular metabolic process), GO:0070887 (cellular response to chemical stimulus), GO:0050673 (epithelial cell proliferation), GO:0009889 (regulation of biosynthetic process), GO:0070727 (cellular macromolecule localization), GO:0031323 (regulation of cellular metabolic process), GO:0010647 (positive regulation of cell communication), GO:0009890 (negative regulation of biosynthetic process), GO:0050877 (nervous system process), GO:0080090 (regulation of primary metabolic process), GO:0000278 (mitotic cell cycle), GO:1901652 (response to peptide), GO:0009059 (macromolecule biosynthetic process), GO:1901362 (organic cyclic compound biosynthetic process), GO:0007346 (regulation of mitotic cell cycle), GO:0007088 (regulation of mitotic nuclear division), GO:0010556 (regulation of macromolecule biosynthetic process), GO:0051246 (regulation of protein metabolic process), GO:0043069 (negative regulation of programmed cell death), GO:0043067 (regulation of programmed cell death), GO:0016055 (Wnt signaling pathway), GO:0001944 (vasculature development), GO:0061448 (connective tissue development), GO:0048545 (response to steroid hormone), GO:0010001 (glial cell differentiation), GO:0043588 (skin development), GO:0010468 (regulation of gene expression), GO:0007420 (brain development), GO:0007399 (nervous system development), GO:0001764 (neuron migration), GO:0090304 (nucleic acid metabolic process), GO:0008544 (epidermis development), GO:0072359 (circulatory system development), GO:0018130 (heterocycle biosynthetic process), GO:0003015 (heart process), GO:0007417 (central nervous system development), GO:1902533 (positive regulation of intracellular signal transduction), GO:0031327 (negative regulation of cellular biosynthetic process), GO:0051252 (regulation of RNA metabolic process), GO:1901701 (cellular response to oxygen-containing compound), GO:0045934 (negative regulation of nucleobase-containing compound metabolic process), GO:0010467 (gene expression), GO:0007507 (heart development), GO:0071417 (cellular response to organonitrogen compound), GO:0043491 (protein kinase B signaling), GO:0009743 (response to carbohydrate), GO:0007167 (enzyme-linked receptor protein signaling pathway), GO:0031344 (regulation of cell projection organization), GO:0042176 (regulation of protein catabolic process), GO:0051052 (regulation of DNA metabolic process), GO:0051054 (positive regulation of DNA metabolic process), GO:0071310 (cellular response to organic substance), GO:0019438 (aromatic compound biosynthetic process), GO:0140014 (mitotic nuclear division), GO:1901699 (cellular response to nitrogen compound), GO:0071774 (response to fibroblast growth factor), GO:0006796 (phosphate-containing compound metabolic process), GO:0006873 (intracellular monoatomic ion homeostasis), GO:0001667 (ameboidal-type cell migration), GO:0034654 (nucleobase-containing compound biosynthetic process), GO:0043434 (response to peptide hormone), GO:0044772 (mitotic cell cycle phase transition), GO:0010557 (positive regulation of macromolecule biosynthetic process), GO:0045935 (positive regulation of nucleobase-containing compound metabolic process), GO:0022008 (neurogenesis), GO:0051254 (positive regulation of RNA metabolic process), GO:0032870 (cellular response to hormone stimulus), GO:0010243 (response to organonitrogen compound), GO:0055080 (monoatomic cation homeostasis), GO:1901987 (regulation of cell cycle phase transition), GO:0031326 (regulation of cellular biosynthetic process), GO:0031214 (biomineral tissue development), GO:0019219 (regulation of nucleobase-containing compound metabolic process), GO:0033043 (regulation of organelle organization), GO:0010558 (negative regulation of macromolecule biosynthetic process), GO:0044271 (cellular nitrogen compound biosynthetic process)
Cellular Component (CC): GO:0005575 (cellular component), GO:0032991 (protein-containing complex), GO:0110165 (cellular anatomical entity), GO:0005875 (microtubule associated complex), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0150034 (distal axon), GO:0042995 (cell projection), GO:0044297 (cell body), GO:0005829 (cytosol), GO:0030427 (site of polarized growth), GO:0031975 (envelope), GO:1902494 (catalytic complex), GO:0036477 (somatodendritic compartment), GO:0005737 (cytoplasm), GO:0012505 (endomembrane system), GO:0031967 (organelle envelope), GO:0120025 (plasma membrane bounded cell projection), GO:0005871 (kinesin complex), GO:0043229 (intracellular organelle), GO:0043228 (non-membrane-bounded organelle), GO:0043025 (neuronal cell body), GO:0005635 (nuclear envelope), GO:0030426 (growth cone), GO:0043227 (membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle), GO:0043232 (intracellular non-membrane-bounded organelle), GO:0043005 (neuron projection), GO:0031982 (vesicle), GO:0005634 (nucleus), GO:0005856 (cytoskeleton), GO:0030424 (axon), GO:0015630 (microtubule cytoskeleton)