Platelet-activating factor acetylhydrolase IB subunit alpha is an enzyme that in humans is encoded by the PAFAH1B1gene.[1][2][3] The protein is often referred to as Lis1 and plays an important role in regulating the motor protein Dynein.[4]
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.[5]
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).
↑Reiner O, Carrozzo R, Shen Y, Wehnert M, Faustinella F, Dobyns WB, Caskey CT, Ledbetter DH (Aug 1993). "Isolation of a Miller-Dieker lissencephaly gene containing G protein beta-subunit-like repeats". Nature. 364 (6439): 717–21. doi:10.1038/364717a0. PMID8355785.
↑Lo Nigro C, Chong CS, Smith AC, Dobyns WB, Carrozzo R, Ledbetter DH (Feb 1997). "Point mutations and an intragenic deletion in LIS1, the lissencephaly causative gene in isolated lissencephaly sequence and Miller-Dieker syndrome". Human Molecular Genetics. 6 (2): 157–64. doi:10.1093/hmg/6.2.157. PMID9063735.
↑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 (Jul 2003). "14-3-3epsilon is important for neuronal migration by binding to NUDEL: a molecular explanation for Miller-Dieker syndrome". Nature Genetics. 34 (3): 274–85. doi:10.1038/ng1169. PMID12796778.
↑Niethammer M, Smith DS, Ayala R, Peng J, Ko J, Lee MS, Morabito M, Tsai LH (Dec 2000). "NUDEL is a novel Cdk5 substrate that associates with LIS1 and cytoplasmic dynein". Neuron. 28 (3): 697–711. doi:10.1016/S0896-6273(00)00147-1. PMID11163260.
↑ 11.011.1Sweeney KJ, Clark GD, Prokscha A, Dobyns WB, Eichele G (Apr 2000). "Lissencephaly associated mutations suggest a requirement for the PAFAH1B heterotrimeric complex in brain development". Mechanisms of Development. 92 (2): 263–71. doi:10.1016/S0925-4773(00)00242-2. PMID10727864.
↑Morris SM, Albrecht U, Reiner O, Eichele G, Yu-Lee LY (May 1998). "The lissencephaly gene product Lis1, a protein involved in neuronal migration, interacts with a nuclear movement protein, NudC". Current Biology. 8 (10): 603–6. doi:10.1016/S0960-9822(98)70232-5. PMID9601647.
↑Caspi M, Atlas R, Kantor A, Sapir T, Reiner O (Sep 2000). "Interaction between LIS1 and doublecortin, two lissencephaly gene products". Human Molecular Genetics. 9 (15): 2205–13. doi:10.1093/oxfordjournals.hmg.a018911. PMID11001923.
Further reading
Tjoelker LW, Eberhardt C, Wilder C, Dietsch G, Trong HL, Cousens LS, Zimmerman GA, McIntyre TM, Stafforini DM, Prescott SM, Gray PW (1997). "Functional and structural features of plasma platelet-activating factor acetylhydrolase". Advances in Experimental Medicine and Biology. 416: 107–11. doi:10.1007/978-1-4899-0179-8_19. PMID9131135.
Stafforini DM, McIntyre TM, Zimmerman GA, Prescott SM (Jul 1997). "Platelet-activating factor acetylhydrolases". The Journal of Biological Chemistry. 272 (29): 17895–8. doi:10.1074/jbc.272.29.17895. PMID9218411.
Yamada Y, Yokota M (May 1998). "Roles of plasma platelet-activating factor acetylhydrolase in allergic, inflammatory, and atherosclerotic diseases". Japanese Circulation Journal. 62 (5): 328–35. doi:10.1253/jcj.62.328. PMID9626899.
Reiner O, Cahana A, Escamez T, Martinez S (2002). "LIS1-no more no less". Molecular Psychiatry. 7 (1): 12–6. doi:10.1038/sj/mp/4000975. PMID11803439.
Guerrini R, Carrozzo R (Apr 2002). "Epileptogenic brain malformations: clinical presentation, malformative patterns and indications for genetic testing". Seizure. 11 Suppl A: 532–43, quiz 544–7. doi:10.1053/seiz.2001.0650. PMID12185771.
Wynshaw-Boris A (Oct 2007). "Lissencephaly and LIS1: insights into the molecular mechanisms of neuronal migration and development". Clinical Genetics. 72 (4): 296–304. doi:10.1111/j.1399-0004.2007.00888.x. PMID17850624.
Hattori M, Adachi H, Tsujimoto M, Arai H, Inoue K (Jul 1994). "Miller-Dieker lissencephaly gene encodes a subunit of brain platelet-activating factor acetylhydrolase [corrected]". Nature. 370 (6486): 216–8. doi:10.1038/370216a0. PMID8028668.
Reiner O, Bar-Am I, Sapir T, Shmueli O, Carrozzo R, Lindsay EA, Baldini A, Ledbetter DH, Cahana A (Nov 1995). "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. PMID8586424.
Isumi H, Takashima S, Kakita A, Yamada M, Ikeda K, Mizuguchi M (Jan 1997). "Expression of the LIS-1 gene product in brain anomalies with a migration disorder". Pediatric Neurology. 16 (1): 42–4. doi:10.1016/S0887-8994(96)00260-3. PMID9044400.
Morris SM, Albrecht U, Reiner O, Eichele G, Yu-Lee LY (May 1998). "The lissencephaly gene product Lis1, a protein involved in neuronal migration, interacts with a nuclear movement protein, NudC". Current Biology. 8 (10): 603–6. doi:10.1016/S0960-9822(98)70232-5. PMID9601647.
Pilz DT, Kuc J, Matsumoto N, Bodurtha J, Bernadi B, Tassinari CA, Dobyns WB, Ledbetter DH (Sep 1999). "Subcortical band heterotopia in rare affected males can be caused by missense mutations in DCX (XLIS) or LIS1". Human Molecular Genetics. 8 (9): 1757–60. doi:10.1093/hmg/8.9.1757. PMID10441340.
Sapir T, Cahana A, Seger R, Nekhai S, Reiner O (Oct 1999). "LIS1 is a microtubule-associated phosphoprotein". European Journal of Biochemistry / FEBS. 265 (1): 181–8. doi:10.1046/j.1432-1327.1999.00711.x. PMID10491172.
Sweeney KJ, Clark GD, Prokscha A, Dobyns WB, Eichele G (Apr 2000). "Lissencephaly associated mutations suggest a requirement for the PAFAH1B heterotrimeric complex in brain development". Mechanisms of Development. 92 (2): 263–71. doi:10.1016/S0925-4773(00)00242-2. PMID10727864.
