platelet-activating factor acetylhydrolase IB subunit alpha; PAF acetylhydrolase 45 kD subunit; PAF-AH 45 kD subunit; PAF-AH alpha; PAFAH alpha; Lissencephaly-1 protein; LIS-1 (PAFAH1B1, LIS1, MDCR, MDS, PAFAHA)
Jump to navigation
Jump to search
Function
- required for proper activation of Rho GTPases & actin polymerization at the leading edge of locomoting cerebellar neurons & postmigratory hippocampal neurons in response to Ca+2 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 (putative)
- positively regulates 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- & microtubule-dependent processes such as maintenance of Golgi integrity, peripheral transport of microtubule fragments & coupling of the nucleus & centrosome
- required during brain development for proliferation of neuronal precursors & migration of newly formed neurons from the ventricular/subventricular zone toward the cortical plate
- may also play a role in other forms of cell locomotion including migration of fibroblasts during wound healing
- component of cytosolic PAF-AH IB, which is composed of PAFAH1B1 (alpha), PAFAH1B2 (beta) & PAFAH1B3 (gamma) subunits
- trimer formation is not essential for catalytic activity of the enzyme which is contributed solely by the PAFAH1B2 (beta) & PAFAH1B3 (gamma) subunits
- interacts with IQGAP1, KATNB1 & NUDC
- interacts with DAB1 when DAB1 is phosphorylated in response to RELN/reelin signaling (putative)
- can self-associate
- interacts with DCX, dynein, dynactin, NDE1, NDEL1 & RSN
- interacts with DISC1, & this interaction is enhanced by NDEL1
Structure
- dimerization mediated by the LisH domain may be required to activate dynein (putative)
- belongs to the WD repeat LIS1/nudF family
- contains 1 LisH domain
- contains 7 WD repeats
Compartment
- cytoplasm, cytoskeleton, spindle
- nuclear membrane (putative)
- centrosome
- redistributes to axons during neuronal development
- also localizes to the microtubules of the manchette in elongating spermatids & to the meiotic spindle in spermatocytes
- localizes to the plus end of microtubules & to the centrosome
- may localize to the nuclear membrane
Alternative splicing
named isoforms=2
Expression
-fairly ubiquitous expression in both the frontal & occipital areas of the brain
Pathology
- defects in PAFAH1B1 are the cause of
- defects in PAFAH1B1 are a cause of Miller-Dieker lissencephaly syndrome
More general terms
Additional terms
Component of
References
- ↑ Prosite :accession PS00678
- ↑ Hattori M, Adachi H, Tsujimoto M, Arai H, Inoue K. Miller-Dieker lissencephaly gene encodes a subunit of brain platelet-activating factor acetylhydrolase [corrected] Nature. 1994 Jul 21;370(6486):216-8. Erratum in: Nature 1994 Aug 4;370(6488):391. PMID: https://www.ncbi.nlm.nih.gov/pubmed/8028668
- ↑ UniProt http://www.uniprot.org/uniprot/P43034.html
- ↑ GeneReviews https://www.genecards.org/cgi-bin/carddisp.pl?gene=PAFAH1B1
Database
- Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=5048
- Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:5048
- OMIM: https://mirror.omim.org/entry/247200
- OMIM: https://mirror.omim.org/entry/601545
- OMIM: https://mirror.omim.org/entry/607432
- UniProt: http://www.uniprot.org/uniprot/P43034.html