InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: PAFAH1B1

Summary

InnateDB Protein

IDBP-235897.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

PAFAH1B1

Protein Name

platelet-activating factor acetylhydrolase 1b, regulatory subunit 1 (45kDa)

Synonyms

LIS1; LIS2; MDCR; MDS; PAFAH;

Species

Homo sapiens

Ensembl Protein

ENSP00000380378

InnateDB Gene

IDBG-16417 (PAFAH1B1)

Protein Structure

UniProt Annotation

Function

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. Non-catalytic subunit of an acetylhydrolase complex which inactivates platelet- activating factor (PAF) by removing the acetyl group at the SN-2 position (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. {ECO:0000250, ECO:0000269PubMed:15173193}.

Subcellular Localization

Cytoplasm, cytoskeleton. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Cytoplasm, cytoskeleton, spindle {ECO:0000255HAMAP- Rule:MF_03141}. Nucleus membrane {ECO:0000255HAMAP- Rule:MF_03141}. Note=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. {ECO:0000250}.

Disease Associations

Lissencephaly 1 (LIS1) [MIM:607432]: 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. {ECO:0000269PubMed:11502906, ECO:0000269PubMed:15007136, ECO:0000269PubMed:9063735}. Note=The disease is caused by mutations affecting the gene represented in this entry.Subcortical band heterotopia (SBH) [MIM:607432]: 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. {ECO:0000269PubMed:10441340, ECO:0000269PubMed:14581661}. Note=The disease is caused by mutations affecting the gene represented in this entry.Miller-Dieker lissencephaly syndrome (MDLS) [MIM:247200]: 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. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Fairly ubiquitous expression in both the frontal and occipital areas of the brain.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 75 experimentally validated interaction(s) in this database.
They are also associated with 8 interaction(s) predicted by orthology.

Experimentally validated
Total	75 [view]
Protein-Protein	75 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	8 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0005515	protein binding
GO:0008017	microtubule binding
GO:0008201	heparin binding
GO:0032403	protein complex binding
GO:0034452	dynactin binding
GO:0042803	protein homodimerization activity
GO:0043274	phospholipase binding
GO:0045502	dynein binding
GO:0045505	dynein intermediate chain binding
GO:0051219	phosphoprotein binding

Biological Process

GO:0000086	G2/M transition of mitotic cell cycle
GO:0000132	establishment of mitotic spindle orientation
GO:0000226	microtubule cytoskeleton organization
GO:0000278	mitotic cell cycle
GO:0001667	ameboidal cell migration
GO:0001675	acrosome assembly
GO:0001764	neuron migration
GO:0001961	positive regulation of cytokine-mediated signaling pathway
GO:0007017	microtubule-based process
GO:0007067	mitotic nuclear division
GO:0007097	nuclear migration
GO:0007268	synaptic transmission
GO:0007405	neuroblast proliferation
GO:0007420	brain development
GO:0007611	learning or memory
GO:0008090	retrograde axon cargo transport
GO:0008344	adult locomotory behavior
GO:0009306	protein secretion
GO:0010977	negative regulation of neuron projection development
GO:0016042	lipid catabolic process
GO:0016477	cell migration
GO:0017145	stem cell division
GO:0019226	transmission of nerve impulse
GO:0021540	corpus callosum morphogenesis
GO:0021766	hippocampus development
GO:0021819	layer formation in cerebral cortex
GO:0021895	cerebral cortex neuron differentiation
GO:0021987	cerebral cortex development
GO:0030036	actin cytoskeleton organization
GO:0031023	microtubule organizing center organization
GO:0032319	regulation of Rho GTPase activity
GO:0036035	osteoclast development
GO:0045773	positive regulation of axon extension
GO:0045931	positive regulation of mitotic cell cycle
GO:0046329	negative regulation of JNK cascade
GO:0046469	platelet activating factor metabolic process
GO:0047496	vesicle transport along microtubule
GO:0048854	brain morphogenesis
GO:0050885	neuromuscular process controlling balance
GO:0051081	nuclear envelope disassembly
GO:0051660	establishment of centrosome localization

Cellular Component

GO:0000235	astral microtubule
GO:0000776	kinetochore
GO:0005635	nuclear envelope
GO:0005737	cytoplasm
GO:0005813	centrosome
GO:0005829	cytosol
GO:0005871	kinesin complex
GO:0005875	microtubule associated complex
GO:0005938	cell cortex
GO:0015630	microtubule cytoskeleton
GO:0030424	axon
GO:0030426	growth cone
GO:0031252	cell leading edge
GO:0031512	motile primary cilium
GO:0031965	nuclear membrane
GO:0031982	vesicle
GO:0043005	neuron projection
GO:0043025	neuronal cell body
GO:0048471	perinuclear region of cytoplasm
GO:0070062	extracellular vesicular exosome

Protein Structure and Domains

PDB ID

InterPro

IPR001680 WD40 repeat
IPR006594 LisH dimerisation motif
IPR013720 LisH dimerisation motif, subgroup
IPR017252 Dynein regulator LIS1
IPR017986 WD40-repeat-containing domain
IPR020472 G-protein beta WD-40 repeat

PFAM

PF00400
PF08513

PRINTS

PR00320

PIRSF

PIRSF037647

SMART

SM00320
SM00667

TIGRFAMs

Post-translational Modifications

Modification

Cross-References