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)
End	2,685,615 bp
Gene location (Mouse)
Chr.	Chromosome 11 (mouse)
End	74,615,496 bp
RNA expression pattern
	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
	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
	5048
	18472
	ENSG00000007168
	ENSMUSG00000020745
	P43034
	P63005
	NM_000430
	NM_013625
	NP_000421
	NP_038653
	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]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000007168 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000020745 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ 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.
^ 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.
^ ^a ^b "Entrez Gene: PAFAH1B1 platelet-activating factor acetylhydrolase, isoform Ib, alpha subunit 45kDa".
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ ^a ^b 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.
^ 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.
^ 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.
^ 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.

External links

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

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000007168 – Ensembl, May 2017

[refGRCm38Ensembl-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.

[pmid8355785-5] 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.

[pmid9063735-6] 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.

[entrez-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.

[Zhang_2007_Pafah1b-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.

[pmid11889140-10] 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.

[pmid11940666-11] 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.

[pmid12796778-12] 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.

[pmid11163260-13] 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.

[pmid10727864-15] 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.

[pmid9601647-16] 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.

[pmid9384577-17] 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.

[pmid11001923-18] 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.

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