PAFAH1B1

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 acetylhydrolase, 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.

According to one study, PAFAH1B1 interacts with VLDL receptor activated by reelin.{{cite journal | vauthors = Zhang G, Assadi AH, McNeil RS, Beffert U, Wynshaw-Boris A, Herz J, Clark GD, D'Arcangelo G | title = The Pafah1b complex interacts with the reelin receptor VLDLR | journal = PLOS ONE | volume = 2 | issue = 2 | pages = e252 | year = 2007 | pmid = 17330141 | pmc = 1800349 | doi = 10.1371/journal.pone.0000252 | bibcode = 2007PLoSO...2..252Z | editor1-last = Mueller | editor1-first = Ulrich | doi-access = free }}

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).

PAFAH1B1 has been shown to interact with DYNC1H1,{{cite journal | vauthors = Tai CY, Dujardin DL, Faulkner NE, Vallee RB | title = Role of dynein, dynactin, and CLIP-170 interactions in LIS1 kinetochore function | journal = The Journal of Cell Biology | volume = 156 | issue = 6 | pages = 959–68 | date = Mar 2002 | pmid = 11889140 | pmc = 2173479 | doi = 10.1083/jcb.200109046 }} CLIP1,{{cite journal |author8-link=Casper Hoogenraad| vauthors = Coquelle FM, Caspi M, Cordelières FP, Dompierre JP, Dujardin DL, Koifman C, Martin P, Hoogenraad CC, Akhmanova A, Galjart N, De Mey JR, Reiner O | title = LIS1, CLIP-170's key to the dynein/dynactin pathway | journal = Molecular and Cellular Biology | volume = 22 | issue = 9 | pages = 3089–102 | date = May 2002 | pmid = 11940666 | pmc = 133759 | doi = 10.1128/MCB.22.9.3089-3102.2002 }} NDEL1,{{cite journal | vauthors = Toyo-oka K, Shionoya A, Gambello MJ, Cardoso C, Leventer R, Ward HL, Ayala R, Tsai LH, Dobyns W, Ledbetter D, Hirotsune S, Wynshaw-Boris A | title = 14-3-3epsilon is important for neuronal migration by binding to NUDEL: a molecular explanation for Miller-Dieker syndrome | journal = Nature Genetics | volume = 34 | issue = 3 | pages = 274–85 | date = Jul 2003 | pmid = 12796778 | doi = 10.1038/ng1169 | s2cid = 10301633 }}{{cite journal | vauthors = Niethammer M, Smith DS, Ayala R, Peng J, Ko J, Lee MS, Morabito M, Tsai LH | title = NUDEL is a novel Cdk5 substrate that associates with LIS1 and cytoplasmic dynein | journal = Neuron | volume = 28 | issue = 3 | pages = 697–711 | date = Dec 2000 | pmid = 11163260 | doi = 10.1016/S0896-6273(00)00147-1 | s2cid = 11154069 | doi-access = free }} NDE1,{{cite journal | vauthors = Efimov VP, Morris NR | title = The LIS1-related NUDF protein of Aspergillus nidulans interacts with the coiled-coil domain of the NUDE/RO11 protein | journal = The Journal of Cell Biology | volume = 150 | issue = 3 | pages = 681–8 | date = Aug 2000 | pmid = 10931877 | pmc = 2175200 | doi = 10.1083/jcb.150.3.681 }} PAFAH1B3,{{cite journal | vauthors = Sweeney KJ, Clark GD, Prokscha A, Dobyns WB, Eichele G | title = Lissencephaly associated mutations suggest a requirement for the PAFAH1B heterotrimeric complex in brain development | journal = Mechanisms of Development | volume = 92 | issue = 2 | pages = 263–71 | date = Apr 2000 | pmid = 10727864 | doi = 10.1016/S0925-4773(00)00242-2 | s2cid = 2447495 | doi-access = }} PAFAH1B2, NUDC,{{cite journal | vauthors = Morris SM, Albrecht U, Reiner O, Eichele G, Yu-Lee LY | title = The lissencephaly gene product Lis1, a protein involved in neuronal migration, interacts with a nuclear movement protein, NudC | journal = Current Biology | volume = 8 | issue = 10 | pages = 603–6 | date = May 1998 | pmid = 9601647 | doi = 10.1016/S0960-9822(98)70232-5 | doi-access = free | bibcode = 1998CBio....8..603M }} TUBA1A{{cite journal | vauthors = Sapir T, Elbaum M, Reiner O | title = Reduction of microtubule catastrophe events by LIS1, platelet-activating factor acetylhydrolase subunit | journal = The EMBO Journal | volume = 16 | issue = 23 | pages = 6977–84 | date = Dec 1997 | pmid = 9384577 | pmc = 1170301 | doi = 10.1093/emboj/16.23.6977 }} and Doublecortin.{{cite journal | vauthors = Caspi M, Atlas R, Kantor A, Sapir T, Reiner O | title = Interaction between LIS1 and doublecortin, two lissencephaly gene products | journal = Human Molecular Genetics | volume = 9 | issue = 15 | pages = 2205–13 | date = Sep 2000 | pmid = 11001923 | doi = 10.1093/oxfordjournals.hmg.a018911 | doi-access = free }}

• platelet-activating factor
• PAFAH1B2
• PAFAH1B3

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• {{cite book | vauthors = Tjoelker LW, Eberhardt C, Wilder C, Dietsch G, Trong HL, Cousens LS, Zimmerman GA, McIntyre TM, Stafforini DM, Prescott SM, Gray PW | chapter = Functional and Structural Features of Plasma Platelet-Activating Factor Acetylhydrolase | series = Advances in Experimental Medicine and Biology | date = 1996 | title = Platelet-Activating Factor and Related Lipid Mediators 2 | volume = 416 | pages = 107–11 | pmid = 9131135 | doi = 10.1007/978-1-4899-0179-8_19| isbn = 978-1-4899-0181-1 }}
• {{cite journal | vauthors = Stafforini DM, McIntyre TM, Zimmerman GA, Prescott SM | title = Platelet-activating factor acetylhydrolases | journal = The Journal of Biological Chemistry | volume = 272 | issue = 29 | pages = 17895–8 | date = Jul 1997 | pmid = 9218411 | doi = 10.1074/jbc.272.29.17895 | doi-access = free }}
• {{cite journal | vauthors = Yamada Y, Yokota M | title = Roles of plasma platelet-activating factor acetylhydrolase in allergic, inflammatory, and atherosclerotic diseases | journal = Japanese Circulation Journal | volume = 62 | issue = 5 | pages = 328–35 | date = May 1998 | pmid = 9626899 | doi = 10.1253/jcj.62.328 | doi-access = free }}
• {{cite journal | vauthors = Reiner O, Cahana A, Escamez T, Martinez S | title = LIS1-no more no less | journal = Molecular Psychiatry | volume = 7 | issue = 1 | pages = 12–6 | year = 2002 | pmid = 11803439 | doi = 10.1038/sj/mp/4000975 | doi-access = }}
• {{cite journal | vauthors = Guerrini R, Carrozzo R | title = Epileptogenic brain malformations: clinical presentation, malformative patterns and indications for genetic testing | journal = Seizure | volume = 11 Suppl A | issue = 7| pages = 532–43; quiz 544–7 | date = Apr 2002 | pmid = 12185771 | doi = 10.1053/seiz.2001.0650| s2cid = 18943418 | doi-access = free }}
• {{cite journal | vauthors = Wynshaw-Boris A | title = Lissencephaly and LIS1: insights into the molecular mechanisms of neuronal migration and development | journal = Clinical Genetics | volume = 72 | issue = 4 | pages = 296–304 | date = Oct 2007 | pmid = 17850624 | doi = 10.1111/j.1399-0004.2007.00888.x | s2cid = 25446883 }}
• {{cite journal | vauthors = Mizuguchi M, Takashima S, Kakita A, Yamada M, Ikeda K | title = Lissencephaly gene product. Localization in the central nervous system and loss of immunoreactivity in Miller-Dieker syndrome | journal = The American Journal of Pathology | volume = 147 | issue = 4 | pages = 1142–51 | date = Oct 1995 | pmid = 7573359 | pmc = 1870994 }}
• {{cite journal | vauthors = Hattori M, Adachi H, Tsujimoto M, Arai H, Inoue K | title = Miller-Dieker lissencephaly gene encodes a subunit of brain platelet-activating factor acetylhydrolase [corrected] | journal = Nature | volume = 370 | issue = 6486 | pages = 216–8 | date = Jul 1994 | pmid = 8028668 | doi = 10.1038/370216a0 | s2cid = 4261133 }}
• {{cite journal | vauthors = Reiner O, Bar-Am I, Sapir T, Shmueli O, Carrozzo R, Lindsay EA, Baldini A, Ledbetter DH, Cahana A | title = LIS2, gene and pseudogene, homologous to LIS1 (lissencephaly 1), located on the short and long arms of chromosome 2 | journal = Genomics | volume = 30 | issue = 2 | pages = 251–6 | date = Nov 1995 | pmid = 8586424 | doi = 10.1006/geno.1995.9880 }}
• {{cite journal | vauthors = Isumi H, Takashima S, Kakita A, Yamada M, Ikeda K, Mizuguchi M | title = Expression of the LIS-1 gene product in brain anomalies with a migration disorder | journal = Pediatric Neurology | volume = 16 | issue = 1 | pages = 42–4 | date = Jan 1997 | pmid = 9044400 | doi = 10.1016/S0887-8994(96)00260-3 }}
• {{cite journal | vauthors = Sapir T, Elbaum M, Reiner O | title = Reduction of microtubule catastrophe events by LIS1, platelet-activating factor acetylhydrolase subunit | journal = The EMBO Journal | volume = 16 | issue = 23 | pages = 6977–84 | date = Dec 1997 | pmid = 9384577 | pmc = 1170301 | doi = 10.1093/emboj/16.23.6977 }}
• {{cite journal | vauthors = Morris SM, Albrecht U, Reiner O, Eichele G, Yu-Lee LY | title = The lissencephaly gene product Lis1, a protein involved in neuronal migration, interacts with a nuclear movement protein, NudC | journal = Current Biology | volume = 8 | issue = 10 | pages = 603–6 | date = May 1998 | pmid = 9601647 | doi = 10.1016/S0960-9822(98)70232-5 | doi-access = free | bibcode = 1998CBio....8..603M }}
• {{cite journal | vauthors = Pilz DT, Kuc J, Matsumoto N, Bodurtha J, Bernadi B, Tassinari CA, Dobyns WB, Ledbetter DH | title = Subcortical band heterotopia in rare affected males can be caused by missense mutations in DCX (XLIS) or LIS1 | journal = Human Molecular Genetics | volume = 8 | issue = 9 | pages = 1757–60 | date = Sep 1999 | pmid = 10441340 | doi = 10.1093/hmg/8.9.1757 | doi-access = free }}
• {{cite journal | vauthors = Sapir T, Cahana A, Seger R, Nekhai S, Reiner O | title = LIS1 is a microtubule-associated phosphoprotein | journal = European Journal of Biochemistry | volume = 265 | issue = 1 | pages = 181–8 | date = Oct 1999 | pmid = 10491172 | doi = 10.1046/j.1432-1327.1999.00711.x | doi-access = free }}
• {{cite journal | vauthors = Sweeney KJ, Clark GD, Prokscha A, Dobyns WB, Eichele G | title = Lissencephaly associated mutations suggest a requirement for the PAFAH1B heterotrimeric complex in brain development | journal = Mechanisms of Development | volume = 92 | issue = 2 | pages = 263–71 | date = Apr 2000 | pmid = 10727864 | doi = 10.1016/S0925-4773(00)00242-2 | s2cid = 2447495 | doi-access = }}

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• [https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=chrom17-lis GeneReview/NIH/UW entry on LIS1-Associated Lissencephaly/Subcortical Band Heterotopia]

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{{PAF signaling}}