PAFAH1B1

Platelet-activating factor acetylhydrolase 1b, regulatory subunit 1 (45kDa)
PDB rendering based on 1uuj.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 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 • dynactin binding • protein homodimerization activity • phospholipase binding • dynein binding • dynein intermediate chain binding • phosphoprotein binding Cellular component • astral microtubule • kinetochore • nuclear envelope • centrosome • cytosol • kinesin complex • microtubule associated complex • cell cortex • axon • growth cone • cell leading edge • motile primary cilium • nuclear membrane • neuronal cell body • perinuclear region of cytoplasm • extracellular exosome Biological process • G2/M transition of mitotic cell cycle • establishment of mitotic spindle orientation • microtubule cytoskeleton organization • mitotic cell cycle • ameboidal-type cell migration • acrosome assembly • neuron migration • positive regulation of cytokine-mediated signaling pathway • organelle organization • microtubule-based process • mitotic nuclear division • nuclear migration • small GTPase mediated signal transduction • synaptic transmission • germ cell development • neuroblast proliferation • learning or memory • retrograde axon cargo transport • adult locomotory behavior • protein secretion • 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 • microtubule organizing center organization • osteoclast development • positive regulation of embryonic development • establishment of planar polarity of embryonic epithelium • regulation of GTPase activity • cortical microtubule organization • positive regulation of axon extension • positive regulation of mitotic cell cycle • negative regulation of JNK cascade • platelet activating factor metabolic process • vesicle transport along microtubule • brain morphogenesis • neuromuscular process controlling balance • nuclear envelope disassembly • establishment of centrosome localization • auditory receptor cell development • positive regulation of dendritic spine morphogenesis • regulation of microtubule cytoskeleton organization • cochlea development • microtubule cytoskeleton organization involved in establishment of planar polarity • regulation of microtubule motor activity Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	5048	18472
Ensembl	ENSG00000007168	ENSMUSG00000020745
UniProt	P43034	P63005
RefSeq (mRNA)	NM_000430	NM_013625
RefSeq (protein)	NP_000421	NP_038653
Location (UCSC)	Chr 17: 2.59 – 2.69 Mb	Chr 11: 74.67 – 74.72 Mb
PubMed search

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 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).

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

1. 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. PMID 8355785.
2. 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. PMID 9063735.
3. "Entrez Gene: PAFAH1B1 platelet-activating factor acetylhydrolase, isoform Ib, alpha subunit 45kDa".
4. Kardon JR, Vale RD (Dec 2009). "Regulators of the cytoplasmic dynein motor". Nature Reviews Molecular Cell Biology 10 (12): 854–65. doi:10.1038/nrm2804. PMID 19935668.
5. Zhang G, Assadi AH, McNeil RS, Beffert U, Wynshaw-Boris A, Herz J, Clark GD, D'Arcangelo G (2007). Mueller U, ed. "The Pafah1b complex interacts with the reelin receptor VLDLR". PLOS ONE 2 (2): e252. doi:10.1371/journal.pone.0000252. PMC 1800349. PMID 17330141.
6. Tai CY, Dujardin DL, Faulkner NE, Vallee RB (Mar 2002). "Role of dynein, dynactin, and CLIP-170 interactions in LIS1 kinetochore function". The Journal of Cell Biology 156 (6): 959–68. doi:10.1083/jcb.200109046. PMC 2173479. PMID 11889140.
7. 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 (May 2002). "LIS1, CLIP-170's key to the dynein/dynactin pathway". Molecular and Cellular Biology 22 (9): 3089–102. doi:10.1128/MCB.22.9.3089-3102.2002. PMC 133759. PMID 11940666.
8. 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. PMID 12796778.
9. 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. PMID 11163260.
10. Efimov VP, Morris NR (Aug 2000). "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. doi:10.1083/jcb.150.3.681. PMC 2175200. PMID 10931877.
11. 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. PMID 10727864.
12. 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. PMID 9601647.
13. Sapir T, Elbaum M, Reiner O (Dec 1997). "Reduction of microtubule catastrophe events by LIS1, platelet-activating factor acetylhydrolase subunit". The EMBO Journal 16 (23): 6977–84. doi:10.1093/emboj/16.23.6977. PMC 1170301. PMID 9384577.
14. 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. PMID 11001923.

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. PMID 9131135.
• 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. PMID 9218411.
• 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. PMID 9626899.
• 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. PMID 11803439.
• 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. PMID 12185771.
• 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. PMID 17850624.
• Mizuguchi M, Takashima S, Kakita A, Yamada M, Ikeda K (Oct 1995). "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. PMC 1870994. PMID 7573359.
• 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. PMID 8028668.
• 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. PMID 8586424.
• 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. PMID 9044400.
• Sapir T, Elbaum M, Reiner O (Dec 1997). "Reduction of microtubule catastrophe events by LIS1, platelet-activating factor acetylhydrolase subunit". The EMBO Journal 16 (23): 6977–84. doi:10.1093/emboj/16.23.6977. PMC 1170301. PMID 9384577.
• 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. PMID 9601647.
• 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. PMID 10441340.
• 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. PMID 10491172.
• 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. PMID 10727864.

External links

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