Biology:PAFAH1B1
 Generic protein structure example |
Platelet-activating factor acetylhydrolase IB subunit alpha is an enzyme that in humans is encoded by the PAFAH1B1 gene.[1][2][3] The protein is often referred to as Lis1 and plays an important role in regulating the motor protein Dynein.[4]
Function
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.[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).
Interactions
PAFAH1B1 has been shown to interact with DYNC1H1,[6] CLIP1,[7] NDEL1,[8][9] NDE1,[10] PAFAH1B3,[11] PAFAH1B2,[11] NUDC,[12] TUBA1A[13] and Doublecortin.[14]
See also
- platelet-activating factor
- PAFAH1B2
- PAFAH1B3
References
- ↑ "Isolation of a Miller-Dieker lissencephaly gene containing G protein beta-subunit-like repeats". Nature 364 (6439): 717–21. Aug 1993. doi:10.1038/364717a0. PMID 8355785. Bibcode: 1993Natur.364..717R.
- ↑ "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. Feb 1997. doi:10.1093/hmg/6.2.157. PMID 9063735.
- ↑ 3.0 3.1 "Entrez Gene: PAFAH1B1 platelet-activating factor acetylhydrolase, isoform Ib, alpha subunit 45kDa". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5048.
- ↑ "Regulators of the cytoplasmic dynein motor". Nature Reviews Molecular Cell Biology 10 (12): 854–65. Dec 2009. doi:10.1038/nrm2804. PMID 19935668.
- ↑ Mueller, Ulrich, ed (2007). "The Pafah1b complex interacts with the reelin receptor VLDLR". PLOS ONE 2 (2): e252. doi:10.1371/journal.pone.0000252. PMID 17330141. Bibcode: 2007PLoSO...2..252Z.
- ↑ "Role of dynein, dynactin, and CLIP-170 interactions in LIS1 kinetochore function". The Journal of Cell Biology 156 (6): 959–68. Mar 2002. doi:10.1083/jcb.200109046. PMID 11889140.
- ↑ "LIS1, CLIP-170's key to the dynein/dynactin pathway". Molecular and Cellular Biology 22 (9): 3089–102. May 2002. doi:10.1128/MCB.22.9.3089-3102.2002. PMID 11940666.
- ↑ "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. Jul 2003. doi:10.1038/ng1169. PMID 12796778.
- ↑ "NUDEL is a novel Cdk5 substrate that associates with LIS1 and cytoplasmic dynein". Neuron 28 (3): 697–711. Dec 2000. doi:10.1016/S0896-6273(00)00147-1. PMID 11163260.
- ↑ "The LIS1-related NUDF protein of Aspergillus nidulans interacts with the coiled-coil domain of the NUDE/RO11 protein". The Journal of Cell Biology 150 (3): 681–8. Aug 2000. doi:10.1083/jcb.150.3.681. PMID 10931877.
- ↑ 11.0 11.1 "Lissencephaly associated mutations suggest a requirement for the PAFAH1B heterotrimeric complex in brain development". Mechanisms of Development 92 (2): 263–71. Apr 2000. doi:10.1016/S0925-4773(00)00242-2. PMID 10727864.
- ↑ "The lissencephaly gene product Lis1, a protein involved in neuronal migration, interacts with a nuclear movement protein, NudC". Current Biology 8 (10): 603–6. May 1998. doi:10.1016/S0960-9822(98)70232-5. PMID 9601647.
- ↑ "Reduction of microtubule catastrophe events by LIS1, platelet-activating factor acetylhydrolase subunit". The EMBO Journal 16 (23): 6977–84. Dec 1997. doi:10.1093/emboj/16.23.6977. PMID 9384577.
- ↑ "Interaction between LIS1 and doublecortin, two lissencephaly gene products". Human Molecular Genetics 9 (15): 2205–13. Sep 2000. doi:10.1093/oxfordjournals.hmg.a018911. PMID 11001923.
Further reading
- "Functional and structural features of plasma platelet-activating factor acetylhydrolase". Platelet-Activating Factor and Related Lipid Mediators 2. 416. 1997. 107–11. doi:10.1007/978-1-4899-0179-8_19. ISBN 978-1-4899-0181-1.
- "Platelet-activating factor acetylhydrolases". The Journal of Biological Chemistry 272 (29): 17895–8. Jul 1997. doi:10.1074/jbc.272.29.17895. PMID 9218411.
- "Roles of plasma platelet-activating factor acetylhydrolase in allergic, inflammatory, and atherosclerotic diseases". Japanese Circulation Journal 62 (5): 328–35. May 1998. doi:10.1253/jcj.62.328. PMID 9626899.
- "LIS1-no more no less". Molecular Psychiatry 7 (1): 12–6. 2002. doi:10.1038/sj/mp/4000975. PMID 11803439.
- "Epileptogenic brain malformations: clinical presentation, malformative patterns and indications for genetic testing". Seizure 11 Suppl A (7): 532–43; quiz 544–7. Apr 2002. doi:10.1053/seiz.2001.0650. PMID 12185771.
- "Lissencephaly and LIS1: insights into the molecular mechanisms of neuronal migration and development". Clinical Genetics 72 (4): 296–304. Oct 2007. doi:10.1111/j.1399-0004.2007.00888.x. PMID 17850624.
- "Lissencephaly gene product. Localization in the central nervous system and loss of immunoreactivity in Miller-Dieker syndrome". The American Journal of Pathology 147 (4): 1142–51. Oct 1995. PMID 7573359.
- "Miller-Dieker lissencephaly gene encodes a subunit of brain platelet-activating factor acetylhydrolase [corrected]". Nature 370 (6486): 216–8. Jul 1994. doi:10.1038/370216a0. PMID 8028668.
- "LIS2, gene and pseudogene, homologous to LIS1 (lissencephaly 1), located on the short and long arms of chromosome 2". Genomics 30 (2): 251–6. Nov 1995. doi:10.1006/geno.1995.9880. PMID 8586424.
- "Expression of the LIS-1 gene product in brain anomalies with a migration disorder". Pediatric Neurology 16 (1): 42–4. Jan 1997. doi:10.1016/S0887-8994(96)00260-3. PMID 9044400.
- "Reduction of microtubule catastrophe events by LIS1, platelet-activating factor acetylhydrolase subunit". The EMBO Journal 16 (23): 6977–84. Dec 1997. doi:10.1093/emboj/16.23.6977. PMID 9384577.
- "The lissencephaly gene product Lis1, a protein involved in neuronal migration, interacts with a nuclear movement protein, NudC". Current Biology 8 (10): 603–6. May 1998. doi:10.1016/S0960-9822(98)70232-5. PMID 9601647.
- "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. Sep 1999. doi:10.1093/hmg/8.9.1757. PMID 10441340.
- "LIS1 is a microtubule-associated phosphoprotein". European Journal of Biochemistry 265 (1): 181–8. Oct 1999. doi:10.1046/j.1432-1327.1999.00711.x. PMID 10491172.
- "Lissencephaly associated mutations suggest a requirement for the PAFAH1B heterotrimeric complex in brain development". Mechanisms of Development 92 (2): 263–71. Apr 2000. doi:10.1016/S0925-4773(00)00242-2. PMID 10727864.
External links
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