platelet-activating factor acetylhydrolase IB subunit alpha selections

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)

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 a) lissencephaly type 1 b) subcortical band heterotopia - defects in PAFAH1B1 are a cause of Miller-Dieker lissencephaly syndrome

General

enzyme regulatory subunit phosphoprotein WD repeat protein family

Properties

SIZE: entity length = 410 aa MW = 47 kD COMPARTMENT: cytoplasm nuclear membrane MOTIF: NDEL1 interaction {2-102} MOTIF: NDE1 interaction {2-66} self-association and interaction with PAFAH1B2 and PAFAH1B3 {2-38} LisH {7-39} Tyr phosphorylation site {Y28} coiled coil {51-82} dynein and dynactin interaction {83-410} MOTIF: WD repeat {106-147} WD repeat {148-187} WD repeat {190-229} Tyr phosphorylation site {Y225} WD repeat {232-271} WD repeat {274-333} WD repeat {336-377} DCX interaction {367-409} WD repeat {378-409} NDEL1 interaction {388-410}

Database Correlations

OMIM correlations MORBIDMAP 601545 UniProt P43034 PFAM correlations Entrez Gene 5048 Kegg hsa:5048

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: 8028668
UniProt :accession P43034
GeneReviews https://www.genecards.org/cgi-bin/carddisp.pl?gene=PAFAH1B1

Component-of

PAF acetylhydrolase (cytoplasmic) or LIS-1 type PAF acetylhydrolase

Contents