PAFAH1B1

This locus was identified as encoding a gene that when mutated or lost caused the lissencephaly associated with Miller-Dieker lissencephaly syndrome. This gene encodes the non-catalytic alpha subunit of the intracellular Ib isoform of platelet-activating factor acteylhydrolase, a heterotrimeric enzyme that specifically catalyzes the removal of the acetyl group at the SN-2 position of platelet-activating factor (identified as 1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine). Two other isoforms of intracellular platelet-activating factor acetylhydrolase exist: one composed of multiple subunits, the other, a single subunit. In addition, a single-subunit isoform of this enzyme is found in serum. [provided by RefSeq]

platelet-activating factor acetylhydrolase, isoform Ib, alpha subunit 45kDa

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).
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 (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. May also play a role in other forms of cell locomotion including the migration of fibroblasts during wound healing. Required for dynein recruitment to microtubule plus ends and BICD2-bound cargos (PubMed:22956769).
May modulate the Reelin pathway through interaction of the PAF-AH (I) catalytic dimer with VLDLR (By similarity).

Acrosome assemblyISS:BHF-UCL
Actin cytoskeleton organizationBy SimilarityISS:BHF-UCL
Adult locomotory behaviorManual Assertion Based On ExperimentIMP:BHF-UCL
Ameboidal-type cell migrationIEA:Ensembl
Auditory receptor cell developmentIEA:Ensembl
Brain morphogenesisManual Assertion Based On ExperimentIMP:BHF-UCL
Cerebral cortex developmentManual Assertion Based On ExperimentIMP:BHF-UCL
Cerebral cortex neuron differentiationIEA:Ensembl
Chemical synaptic transmissionBy SimilarityISS:BHF-UCL
Cochlea developmentIEA:Ensembl
Corpus callosum morphogenesisManual Assertion Based On ExperimentIMP:BHF-UCL
Cortical microtubule organizationIEA:Ensembl
Establishment of centrosome localizationIEA:Ensembl
Establishment of mitotic spindle orientationManual Assertion Based On ExperimentIMP:UniProtKB
Establishment of planar polarity of embryonic epitheliumIEA:Ensembl
Germ cell developmentManual Assertion Based On ExperimentIBA:GO_Central
Hippocampus developmentISS:BHF-UCL
Layer formation in cerebral cortexISS:BHF-UCL
Learning or memoryISS:BHF-UCL
Lipid catabolic processIEA:UniProtKB-KW
Maintenance of centrosome locationIEA:Ensembl
Microtubule cytoskeleton organizationBy SimilarityISS:BHF-UCL
Microtubule cytoskeleton organization involved in establishment of planar polarityIEA:Ensembl
Microtubule organizing center organizationManual Assertion Based On ExperimentIMP:UniProtKB
Microtubule slidingIEA:UniProtKB-UniRule
Microtubule-based processManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of JNK cascadeIEA:Ensembl
Negative regulation of neuron projection developmentIEA:Ensembl
Neuroblast proliferationBy SimilarityISS:BHF-UCL
Neuromuscular process controlling balanceManual Assertion Based On ExperimentIMP:BHF-UCL
Neuron migrationManual Assertion Based On ExperimentIMP:UniProtKB
Nuclear membrane disassemblyIEA:Ensembl
Nuclear migrationManual Assertion Based On ExperimentIBA:GO_Central
Osteoclast developmentIEA:Ensembl
Platelet activating factor metabolic processBy SimilarityISS:BHF-UCL
Positive regulation of axon extensionIEA:Ensembl
Positive regulation of cytokine-mediated signaling pathwayIEA:Ensembl
Positive regulation of dendritic spine morphogenesisIEA:Ensembl
Positive regulation of embryonic developmentIEA:Ensembl
Positive regulation of mitotic cell cycleIEA:Ensembl
Protein secretionIEA:Ensembl
Reelin-mediated signaling pathwayISS:UniProtKB
Regulation of GTPase activityIEA:Ensembl
Regulation of microtubule cytoskeleton organizationIEA:Ensembl
Retrograde axonal transportBy SimilarityISS:BHF-UCL
Stem cell divisionIEA:Ensembl
Transmission of nerve impulseBy SimilarityISS:BHF-UCL
Vesicle transport along microtubuleBy SimilarityISS:BHF-UCL

Cytoplasm, cytoskeleton
Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
Cytoplasm, cytoskeleton, spindle
Nucleus membrane
Redistributes to axons during neuronal development. Also localizes to the microtubules of the manchette in elongating spermatids and to the meiotic spindle in spermatocytes (By similarity).
Localizes to the plus end of microtubules and to the centrosome. May localize to the nuclear membrane.

Lissencephaly 1 (LIS1):
A classical lissencephaly. It is characterized by agyria or pachygyria and disorganization of the clear neuronal lamination of normal six-layered cortex. The cortex is abnormally thick and poorly organized with 4 primitive layers. Associated with enlarged and dysmorphic ventricles and often hypoplasia of the corpus callosum.
Subcortical band heterotopia (SBH):
SBH is a mild brain malformation of the lissencephaly spectrum. It is characterized by bilateral and symmetric plates or bands of gray matter found in the central white matter between the cortex and cerebral ventricles, cerebral convolutions usually appearing normal.
Miller-Dieker lissencephaly syndrome (MDLS):
A contiguous gene deletion syndrome of chromosome 17p13.3, characterized by classical lissencephaly and distinct facial features. Additional congenital malformations can be part of the condition.