PAFAH1B1

Platelet-activating factor acetylhydrolase 1b, regulatory subunit 1 (45kDa)

PDB rendering based on 1uuj.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
SymbolsPAFAH1B1 ; LIS1; LIS2; MDCR; MDS; PAFAH
External IDsOMIM: 601545 MGI: 109520 HomoloGene: 371 GeneCards: PAFAH1B1 Gene
EC number3.1.1.47
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez504818472
EnsemblENSG00000007168ENSMUSG00000020745
UniProtP43034P63005
RefSeq (mRNA)NM_000430NM_013625
RefSeq (protein)NP_000421NP_038653
Location (UCSC)Chr 17:
2.5 – 2.59 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]

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

References

  1. ↑ Reiner O, Carrozzo R, Shen Y, Wehnert M, Faustinella F, Dobyns WB, Caskey CT, Ledbetter DH (September 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 (August 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. ↑ 3.0 3.1 "Entrez Gene: PAFAH1B1 platelet-activating factor acetylhydrolase, isoform Ib, alpha subunit 45kDa".
  4. ↑ Kardon, Julia R.; Ronald Vale (2009). "Regulators of the cytoplasmic dynein motor". Nature Reviews Molecular Cell Biology 10 (12): 854–865. doi:10.1038/nrm2804. Retrieved 2013-10-27.
  5. ↑ Zhang G, Assadi AH, McNeil RS, Beffert U, Wynshaw-Boris A, Herz J, Clark GD, D’Arcangelo G. (2007). Mueller, Ulrich, 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, Chin-Yin; Dujardin Denis L; Faulkner Nicole E; Vallee Richard B (March 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.
  7. ↑ 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-170s 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.
  8. ↑ 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 (July 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.
  9. ↑ Niethammer, M; Smith D S; Ayala R; Peng J; Ko J; Lee M S; Morabito M; Tsai L H (December 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.
  10. ↑ Efimov, Vladmir; N. Ronald Morris (2000). "The LIS1-related NUDF protein of Aspergillu nidulans interacts with the coiled-coil domain of the NUDE/RO11 protein". J. Cell Biol 150 (3): 681–688. doi:10.1083/jcb.150.3.681. PMC 2175200. PMID 10931877.
  11. ↑ 11.0 11.1 Sweeney, K J; Clark G D; Prokscha A; Dobyns W B; Eichele G (April 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.
  12. ↑ 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.
  13. ↑ Sapir, T; Elbaum M; Reiner O (December 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.
  14. ↑ Caspi, M; Atlas R; Kantor A; Sapir T; Reiner O (September 2000). "Interaction between LIS1 and doublecortin, two lissencephaly gene products". Hum. Mol. Genet. (ENGLAND) 9 (15): 2205–13. doi:10.1093/oxfordjournals.hmg.a018911. ISSN 0964-6906. PMID 11001923.

External links

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.
  • 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.
  • 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.