PAFAH1B1

PAFAH1B1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1UUJ, 1VYH
Identifiers
Aliases	PAFAH1B1 , LIS1, LIS2, MDCR, MDS, PAFAH, platelet-activating factor acetylhydrolase 1b, regulatory subunit 1 (45kDa), NudF, platelet activating factor acetylhydrolase 1b regulatory subunit 1
External IDs	OMIM: 601545; MGI: 109520; HomoloGene: 371; GeneCards: PAFAH1B1; OMA:PAFAH1B1 - orthologs
Gene location (Human) Chr. Chromosome 17 (human) [1] Band 17p13.3 Start 2,593,210 bp [1] End 2,685,615 bp [1]
Gene location (Mouse) Chr. Chromosome 11 (mouse) [2] Band 11 B5|11 45.76 cM Start 74,564,775 bp [2] End 74,615,496 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in sperm middle temporal gyrus left testis right testis cerebellar vermis frontal pole pons paraflocculus of cerebellum orbitofrontal cortex lateral nuclear group of thalamus Top expressed in seminiferous tubule dentate gyrus of hippocampal formation granule cell primary visual cortex superior frontal gyrus CA3 field cingulate gyrus substantia nigra cerebellar cortex perirhinal cortex entorhinal cortex More reference expression data BioGPS More reference expression data
Gene ontology Molecular function heparin binding phospholipase binding dynactin binding protein-containing complex binding protein homodimerization activity protein binding dynein intermediate chain binding microtubule binding phosphoprotein binding phospholipase A2 activity dynein complex binding microtubule plus-end binding Cellular component cytoplasm cytosol nuclear membrane nuclear envelope membrane microtubule organizing center perinuclear region of cytoplasm neuron projection microtubule cytoskeleton nucleus kinetochore centrosome astral microtubule microtubule associated complex extracellular exosome kinesin complex microtubule cytoskeleton growth cone spindle axon soma cell cortex vesicle cell leading edge axon cytoplasm motile cilium stereocilium central region of growth cone cytoplasmic microtubule Biological process germ cell development positive regulation of cytokine-mediated signaling pathway neuromuscular process controlling balance nuclear migration microtubule cytoskeleton organization involved in establishment of planar polarity G2/M transition of mitotic cell cycle stem cell division acrosome assembly cell cycle osteoclast development positive regulation of embryonic development microtubule organizing center organization cochlea development platelet activating factor metabolic process regulation of GTPase activity adult locomotory behavior transmission of nerve impulse regulation of microtubule cytoskeleton organization positive regulation of cellular component organization positive regulation of mitotic cell cycle protein secretion cortical microtubule organization learning or memory neuroblast proliferation positive regulation of axon extension auditory receptor cell development brain morphogenesis chemical synaptic transmission retrograde axonal transport cell differentiation negative regulation of neuron projection development neuron migration nervous system development cerebral cortex development establishment of centrosome localization ameboidal-type cell migration positive regulation of dendritic spine morphogenesis microtubule cytoskeleton organization actin cytoskeleton organization vesicle transport along microtubule lipid metabolism establishment of planar polarity of embryonic epithelium cell division multicellular organism development lipid catabolic process negative regulation of JNK cascade brain development layer formation in cerebral cortex nuclear membrane disassembly cerebral cortex neuron differentiation corpus callosum morphogenesis hippocampus development cell migration sister chromatid cohesion establishment of mitotic spindle orientation microtubule-based process maintenance of centrosome location ciliary basal body-plasma membrane docking regulation of G2/M transition of mitotic cell cycle transport microtubule sliding Sources:Amigo / QuickGO
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: 74.56 – 74.62 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Platelet-activating factor acetylhydrolase IB subunit alpha or Lisencephaly protein-1 (LIS-1) is an enzyme that in humans is encoded by the PAFAH1B1 gene. ^{[5] [6] [7]} The protein plays an important role in regulating the motor protein dynein. ^[8]

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. ^[7]

According to one study, PAFAH1B1 interacts with VLDL receptor activated by reelin. ^[9]

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, ^[10] CLIP1, ^[11] NDEL1, ^{[12] [13]} NDE1, ^[14] PAFAH1B3, ^[15] PAFAH1B2, ^[15] NUDC, ^[16] TUBA1A ^[17] and Doublecortin. ^[18]

See also

• platelet-activating factor
• PAFAH1B2
• PAFAH1B3

References

1. GRCh38: Ensembl release 89: ENSG00000007168 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000020745 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. 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. Bibcode:1993Natur.364..717R. doi:10.1038/364717a0. PMID   8355785. S2CID   4247668.
6. 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.
7. "Entrez Gene: PAFAH1B1 platelet-activating factor acetylhydrolase, isoform Ib, alpha subunit 45kDa".
8. 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. PMC   3394690 . PMID   19935668.
9. 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. Bibcode:2007PLoSO...2..252Z. doi: 10.1371/journal.pone.0000252 . PMC   1800349 . PMID   17330141.
10. 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.
11. 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.
12. 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. S2CID   10301633.
13. 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. S2CID   11154069.
14. 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.
15. 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. S2CID   2447495.
16. 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. Bibcode:1998CBio....8..603M. doi: 10.1016/S0960-9822(98)70232-5 . PMID   9601647.
17. 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.
18. 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 (1996). "Functional and Structural Features of Plasma Platelet-Activating Factor Acetylhydrolase". Platelet-Activating Factor and Related Lipid Mediators 2. Advances in Experimental Medicine and Biology. Vol. 416. pp. 107–11. doi:10.1007/978-1-4899-0179-8_19. ISBN   978-1-4899-0181-1. 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 (7): 532–43, quiz 544–7. doi: 10.1053/seiz.2001.0650 . PMID   12185771. S2CID   18943418.
• 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. S2CID   25446883.
• 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. S2CID   4261133.
• 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. Bibcode:1998CBio....8..603M. 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. 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. S2CID   2447495.

External links

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