PAFAH1B1

Platelet-activating factor acetylhydrolase 1b, regulatory subunit 1 (45kDa)
PDB rendering based on 1uuj.
Available structures PDB 1uuj, 1vyh
Identifiers
Symbols	PAFAH1B1; LIS1; LIS2; MDCR; MDS; PAFAH
External IDs	OMIM: 601545 MGI: 109520 HomoloGene: 371 GeneCards: PAFAH1B1 Gene
EC number	3.1.1.47
Gene Ontology Molecular function • protein binding • microtubule binding • heparin binding • protein complex binding • dynactin binding • protein homodimerization activity • phospholipase binding • dynein binding • dynein intermediate chain binding • phosphoprotein binding Cellular component • astral microtubule • kinetochore • soluble fraction • insoluble fraction • nucleus • nuclear envelope • nucleolus • cytoplasm • centrosome • centrosome • spindle • cytosol • cytosol • cytosol • kinesin complex • microtubule • microtubule associated complex • cell cortex • membrane • growth cone • cell leading edge • motile primary cilium • nonmotile primary cilium • nuclear membrane • axon part • vesicular fraction • neuronal cell body • perinuclear region of cytoplasm Biological process • G2/M transition of mitotic cell cycle • M phase of mitotic cell cycle • establishment of mitotic spindle orientation • microtubule cytoskeleton organization • mitotic prometaphase • mitotic cell cycle • acrosome assembly • neuron migration • neuron migration • transport • microtubule-based process • nuclear migration • synaptic transmission • multicellular organismal development • nervous system development • neuroblast proliferation • learning or memory • retrograde axon cargo transport • adult locomotory behavior • negative regulation of neuron projection development • lipid catabolic process • stem cell division • transmission of nerve impulse • corpus callosum morphogenesis • hippocampus development • layer formation in cerebral cortex • cerebral cortex neuron differentiation • cerebral cortex development • actin cytoskeleton organization • cell differentiation • microtubule organizing center organization • regulation of Rho GTPase activity • positive regulation of axon extension • positive regulation of mitotic cell cycle • platelet activating factor metabolic process • vesicle transport along microtubule • brain morphogenesis • neuromuscular process controlling balance • nuclear envelope disassembly • establishment of centrosome localization • cellular response to protein stimulus Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	5048	18472
Ensembl	ENSG00000007168	ENSMUSG00000020745
UniProt	P43034	Q3TUH5
RefSeq (mRNA)	NM_000430.3	XM_982651
RefSeq (protein)	NP_000421.1	NP_038653.1
Location (UCSC)	Chr 17: 2.5 – 2.59 Mb	Chr 11: 74.49 – 74.54 Mb
PubMed search	[1]	[2]

Platelet-activating factor acetylhydrolase IB subunit alpha is an enzyme that in humans is encoded by the PAFAH1B1 gene.^[1][2][3]

PAFAH1B1 was identified as encoding a gene that when mutated or lost caused the lissencephaly associated with Miller-Dieker syndrome. PAFAH1B1 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.^[3]

According to one study, PAFAH1B1 interacts with VLDLR receptor activated by reelin.^[4]

Genomics

The gene is located at chromosome 17p13.3 on the Watson (plus) strand. The gene is 91,953 bases in length and encodes a protein of 410 amino acids (predicted molecular weight 46.638 kiloDaltons).

Interactions

PAFAH1B1 has been shown to interact with DYNC1H1,^[5] CLIP1,^[6] NDEL1,^[7][8] PAFAH1B3,^[9] PAFAH1B2,^[9] NUDC,^[10] TUBA1A^[11] and Doublecortin.^[12]

See also

• platelet-activating factor
• PAFAH1B2
• PAFAH1B3

References

1. ^ Reiner O, Carrozzo R, Shen Y, Wehnert M, Faustinella F, Dobyns WB, Caskey CT, Ledbetter DH (Sep 1993). "Isolation of a Miller-Dieker lissencephaly gene containing G protein beta-subunit-like repeats". Nature 364 (6439): 717–21. doi:10.1038/364717a0. PMID 8355785. 
2. ^ Lo Nigro C, Chong CS, Smith AC, Dobyns WB, Carrozzo R, Ledbetter DH (Aug 1997). "Point mutations and an intragenic deletion in LIS1, the lissencephaly causative gene in isolated lissencephaly sequence and Miller-Dieker syndrome". Hum Mol Genet 6 (2): 157–64. doi:10.1093/hmg/6.2.157. PMID 9063735. 
3. ^ ^{a b} "Entrez Gene: PAFAH1B1 platelet-activating factor acetylhydrolase, isoform Ib, alpha subunit 45kDa". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5048. 
4. ^ Zhang G, Assadi AH, McNeil RS, Beffert U, Wynshaw-Boris A, Herz J, Clark GD, D’Arcangelo G. (2007). "The Pafah1b complex interacts with the Reelin receptor VLDLR". PLoS ONE 2 (2): e252. doi:10.1371/journal.pone.0000252. PMC 1800349. PMID 17330141. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1800349. 
5. ^ Tai, Chin-Yin; Dujardin Denis L, Faulkner Nicole E, Vallee Richard B (Mar. 2002). "Role of dynein, dynactin, and CLIP-170 interactions in LIS1 kinetochore function". J. Cell Biol. (United States) 156 (6): 959–68. doi:10.1083/jcb.200109046. ISSN 0021-9525. PMC 2173479. PMID 11889140. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2173479. 
6. ^ Coquelle, Frédéric M; Caspi Michal, Cordelières Fabrice P, Dompierre Jim P, Dujardin Denis L, Koifman Cynthia, Martin Patrick, Hoogenraad Casper C, Akhmanova Anna, Galjart Niels, De Mey Jan R, Reiner Orly (May. 2002). "LIS1, CLIP-170's key to the dynein/dynactin pathway". Mol. Cell. Biol. (United States) 22 (9): 3089–102. doi:10.1128/MCB.22.9.3089-3102.2002. ISSN 0270-7306. PMC 133759. PMID 11940666. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=133759. 
7. ^ Toyo-oka, Kazuhito; Shionoya Aki, Gambello Michael J, Cardoso Carlos, Leventer Richard, Ward Heather L, Ayala Ramses, Tsai Li-Huei, Dobyns William, Ledbetter David, Hirotsune Shinji, Wynshaw-Boris Anthony (Jul. 2003). "14-3-3epsilon is important for neuronal migration by binding to NUDEL: a molecular explanation for Miller-Dieker syndrome". Nat. Genet. (United States) 34 (3): 274–85. doi:10.1038/ng1169. ISSN 1061-4036. PMID 12796778. 
8. ^ Niethammer, M; Smith D S, Ayala R, Peng J, Ko J, Lee M S, Morabito M, Tsai L H (Dec. 2000). "NUDEL is a novel Cdk5 substrate that associates with LIS1 and cytoplasmic dynein". Neuron (United States) 28 (3): 697–711. doi:10.1016/S0896-6273(00)00147-1. ISSN 0896-6273. PMID 11163260. 
9. ^ ^{a b} Sweeney, K J; Clark G D, Prokscha A, Dobyns W B, Eichele G (Apr. 2000). "Lissencephaly associated mutations suggest a requirement for the PAFAH1B heterotrimeric complex in brain development". Mech. Dev. (IRELAND) 92 (2): 263–71. doi:10.1016/S0925-4773(00)00242-2. ISSN 0925-4773. PMID 10727864. 
10. ^ Morris, S M; Albrecht U, Reiner O, Eichele G, Yu-Lee L Y (May. 1998). "The lissencephaly gene product Lis1, a protein involved in neuronal migration, interacts with a nuclear movement protein, NudC". Curr. Biol. (ENGLAND) 8 (10): 603–6. doi:10.1016/S0960-9822(98)70232-5. ISSN 0960-9822. PMID 9601647. 
11. ^ Sapir, T; Elbaum M, Reiner O (Dec. 1997). "Reduction of microtubule catastrophe events by LIS1, platelet-activating factor acetylhydrolase subunit". EMBO J. (ENGLAND) 16 (23): 6977–84. doi:10.1093/emboj/16.23.6977. ISSN 0261-4189. PMC 1170301. PMID 9384577. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1170301. 
12. ^ Caspi, M; Atlas R, Kantor A, Sapir T, Reiner O (Sep. 2000). "Interaction between LIS1 and doublecortin, two lissencephaly gene products". Hum. Mol. Genet. (ENGLAND) 9 (15): 2205–13. ISSN 0964-6906. PMID 11001923. 

External links

• GeneReview/NIH/UW entry on LIS1-Associated Lissencephaly/Subcortical Band Heterotopia

Further reading

• Tjoelker LW, Eberhardt C, Wilder C, et al. (1997). "Functional and structural features of plasma platelet-activating factor acetylhydrolase.". Adv. Exp. Med. Biol. 416: 107–11. PMID 9131135. 
• Stafforini DM, McIntyre TM, Zimmerman GA, Prescott SM (1997). "Platelet-activating factor acetylhydrolases.". J. Biol. Chem. 272 (29): 17895–8. doi:10.1074/jbc.272.29.17895. PMID 9218411. 
• Yamada Y, Yokota M (1998). "Roles of plasma platelet-activating factor acetylhydrolase in allergic, inflammatory, and atherosclerotic diseases.". Jpn. Circ. J. 62 (5): 328–35. doi:10.1253/jcj.62.328. PMID 9626899. 
• Reiner O, Cahana A, Escamez T, Martinez S (2002). "LIS1-no more no less.". Mol. Psychiatry 7 (1): 12–6. doi:10.1038/sj/mp/4000975. PMID 11803439. 
• Guerrini R, Carrozzo R (2002). "Epileptogenic brain malformations: clinical presentation, malformative patterns and indications for genetic testing.". Seizure : the journal of the British Epilepsy Association 11 Suppl A: 532–43; quiz 544–7. PMID 12185771. 
• Wynshaw-Boris A (2007). "Lissencephaly and LIS1: insights into the molecular mechanisms of neuronal migration and development.". Clin. Genet. 72 (4): 296–304. doi:10.1111/j.1399-0004.2007.00888.x. PMID 17850624. 
• Mizuguchi M, Takashima S, Kakita A, et al. (1995). "Lissencephaly gene product. Localization in the central nervous system and loss of immunoreactivity in Miller-Dieker syndrome.". Am. J. Pathol. 147 (4): 1142–51. PMC 1870994. PMID 7573359. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1870994. 
• Hattori M, Adachi H, Tsujimoto M, et al. (1994). "Miller-Dieker lissencephaly gene encodes a subunit of brain platelet-activating factor acetylhydrolase [corrected]". Nature 370 (6486): 216–8. doi:10.1038/370216a0. PMID 8028668. 
• Reiner O, Bar-Am I, Sapir T, et al. (1996). "LIS2, gene and pseudogene, homologous to LIS1 (lissencephaly 1), located on the short and long arms of chromosome 2.". Genomics 30 (2): 251–6. doi:10.1006/geno.1995.9880. PMID 8586424. 
• Isumi H, Takashima S, Kakita A, et al. (1997). "Expression of the LIS-1 gene product in brain anomalies with a migration disorder.". Pediatr. Neurol. 16 (1): 42–4. doi:10.1016/S0887-8994(96)00260-3. PMID 9044400. 
• Sapir T, Elbaum M, Reiner O (1998). "Reduction of microtubule catastrophe events by LIS1, platelet-activating factor acetylhydrolase subunit.". EMBO J. 16 (23): 6977–84. doi:10.1093/emboj/16.23.6977. PMC 1170301. PMID 9384577. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1170301. 
• Morris SM, Albrecht U, Reiner O, et al. (1998). "The lissencephaly gene product Lis1, a protein involved in neuronal migration, interacts with a nuclear movement protein, NudC.". Curr. Biol. 8 (10): 603–6. doi:10.1016/S0960-9822(98)70232-5. PMID 9601647. 
• Pilz DT, Kuc J, Matsumoto N, et al. (2000). "Subcortical band heterotopia in rare affected males can be caused by missense mutations in DCX (XLIS) or LIS1.". Hum. Mol. Genet. 8 (9): 1757–60. doi:10.1093/hmg/8.9.1757. PMID 10441340. 
• Sapir T, Cahana A, Seger R, et al. (1999). "LIS1 is a microtubule-associated phosphoprotein.". Eur. J. Biochem. 265 (1): 181–8. doi:10.1046/j.1432-1327.1999.00711.x. PMID 10491172. 
• Sweeney KJ, Clark GD, Prokscha A, et al. (2000). "Lissencephaly associated mutations suggest a requirement for the PAFAH1B heterotrimeric complex in brain development.". Mech. Dev. 92 (2): 263–71. doi:10.1016/S0925-4773(00)00242-2. PMID 10727864.