ID:LIS1_HUMAN DESCRIPTION: RecName: Full=Platelet-activating factor acetylhydrolase IB subunit alpha; AltName: Full=Lissencephaly-1 protein; Short=LIS-1; AltName: Full=PAF acetylhydrolase 45 kDa subunit; Short=PAF-AH 45 kDa subunit; AltName: Full=PAF-AH alpha; Short=PAFAH alpha; FUNCTION: Required for proper activation of Rho GTPases and actin polymerization at the leading edge of locomoting cerebellar neurons and postmigratory hippocampal neurons in response to calcium influx triggered via NMDA receptors. Non-catalytic subunit of an acetylhydrolase complex which inactivates platelet- activating factor (PAF) by removing the acetyl group at the SN-2 position (By similarity). Positively regulates the activity of the minus-end directed microtubule motor protein dynein. May enhance dynein-mediated microtubule sliding by targeting dynein to the microtubule plus end. Required for several dynein- and microtubule-dependent processes such as the maintenance of Golgi integrity, the peripheral transport of microtubule fragments and the coupling of the nucleus and centrosome. Required during brain development for the proliferation of neuronal precursors and the migration of newly formed neurons from the ventricular/subventricular zone toward the cortical plate. Neuronal migration involves a process called nucleokinesis, whereby migrating cells extend an anterior process into which the nucleus subsequently translocates. During nucleokinesis dynein at the nuclear surface may translocate the nucleus towards the centrosome by exerting force on centrosomal microtubules. May also play a role in other forms of cell locomotion including the migration of fibroblasts during wound healing. SUBUNIT: Component of cytosolic PAF-AH IB, which is composed of PAFAH1B1 (alpha), PAFAH1B2 (beta) and PAFAH1B3 (gamma) subunits. Trimer formation is not essential for the catalytic activity of the enzyme which is contributed solely by the PAFAH1B2 (beta) and PAFAH1B3 (gamma) subunits. Interacts with IQGAP1, KATNB1 and NUDC. Interacts with DAB1 when DAB1 is phosphorylated in response to RELN/reelin signaling (By similarity). Can self-associate. Interacts with DCX, dynein, dynactin, NDE1, NDEL1 and RSN. Interacts with DISC1, and this interaction is enhanced by NDEL1. INTERACTION: Q9CZA6:Nde1 (xeno); NbExp=6; IntAct=EBI-720620, EBI-309934; SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton. Cytoplasm, cytoskeleton, centrosome. Cytoplasm, cytoskeleton, spindle (By similarity). Nucleus membrane (Potential). Note=Redistributes to axons during neuronal development. Also localizes to the microtubules of the manchette in elongating spermatids and to the meiotic spindle in spermatocytes (By similarity). Localizes to the plus end of microtubules and to the centrosome. May localize to the nuclear membrane. TISSUE SPECIFICITY: Fairly ubiquitous expression in both the frontal and occipital areas of the brain. DOMAIN: Dimerization mediated by the LisH domain may be required to activate dynein (By similarity). DISEASE: Defects in PAFAH1B1 are the cause of lissencephaly type 1 (LIS1) [MIM:607432]; also known as classic lissencephaly. LIS1 is characterized by agyria or pachgyria and disorganization of the clear neuronal lamination of normal six-layered cortex. The cortex is abnormally thick and poorly organized with 4 primitive layers. LIS1 is associated with enlarged and dysmorphic ventricles and often hypoplasia of the corpus callosum. DISEASE: Defects in PAFAH1B1 are the cause of subcortical band heterotopia (SBH) [MIM:607432]. SBH is a mild brain malformation of the lissencephaly spectrum. It is characterized by bilateral and symmetric ribbons of gray matter found in the central white matter between the cortex and the ventricular surface. DISEASE: Defects in PAFAH1B1 are a cause of Miller-Dieker lissencephaly syndrome (MDLS) [MIM:247200]. MDLS is a contiguous gene deletion syndrome of chromosome 17p13.3, characterized by classical lissencephaly and distinct facial features. Additional congenital malformations can be part of the condition. SIMILARITY: Belongs to the WD repeat LIS1/nudF family. SIMILARITY: Contains 1 LisH domain. SIMILARITY: Contains 7 WD repeats. SEQUENCE CAUTION: Sequence=AAA02882.1; Type=Miscellaneous discrepancy; Note=Chimeric cDNA; WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/PAFAH1B1";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P43034
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
L13387 - Homo sapiens (clone 6-1) Miller-Dieker lissencephaly protein (LIS1) mRNA, complete cds. LP895335 - Sequence 199 from Patent EP3253886. JD520600 - Sequence 501624 from Patent EP1572962. JD443884 - Sequence 424908 from Patent EP1572962. L13386 - Homo sapiens (clone 47) Miller-Dieker lissencephaly protein (LIS1) mRNA, complete cds. JD443223 - Sequence 424247 from Patent EP1572962. JD128840 - Sequence 109864 from Patent EP1572962. JD464378 - Sequence 445402 from Patent EP1572962. JD163975 - Sequence 144999 from Patent EP1572962. JD555521 - Sequence 536545 from Patent EP1572962. JD416099 - Sequence 397123 from Patent EP1572962. BX538346 - Homo sapiens mRNA; cDNA DKFZp686E02158 (from clone DKFZp686E02158). JD468573 - Sequence 449597 from Patent EP1572962. JD043845 - Sequence 24869 from Patent EP1572962. AK313078 - Homo sapiens cDNA, FLJ93559, Homo sapiens platelet-activating factor acetylhydrolase, isoformIb, alpha subunit 45kDa (PAFAH1B1), mRNA. L13385 - Homo sapiens(clone 71) Miller-Dieker lissencephaly protein (LIS1) mRNA, complete cds. BC064638 - Homo sapiens platelet-activating factor acetylhydrolase, isoform Ib, alpha subunit 45kDa, mRNA (cDNA clone MGC:70757 IMAGE:5786560), complete cds. AF400434 - Homo sapiens platelet-activating factor acetyl hydrolase isoform Ib alpha subunit (PHFAH1B1) mRNA, complete cds. JD037849 - Sequence 18873 from Patent EP1572962. JD036615 - Sequence 17639 from Patent EP1572962. AB463175 - Synthetic construct DNA, clone: pF1KB3064, Homo sapiens PAFAH1B1 gene for platelet-activating factor acetylhydrolase, isoform Ib, alpha subunit 45kDa, without stop codon, in Flexi system. KJ891747 - Synthetic construct Homo sapiens clone ccsbBroadEn_01141 PAFAH1B1 gene, encodes complete protein. KR711128 - Synthetic construct Homo sapiens clone CCSBHm_00020560 PAFAH1B1 (PAFAH1B1) mRNA, encodes complete protein. KR711129 - Synthetic construct Homo sapiens clone CCSBHm_00020563 PAFAH1B1 (PAFAH1B1) mRNA, encodes complete protein. KR711130 - Synthetic construct Homo sapiens clone CCSBHm_00020570 PAFAH1B1 (PAFAH1B1) mRNA, encodes complete protein. KR711131 - Synthetic construct Homo sapiens clone CCSBHm_00020576 PAFAH1B1 (PAFAH1B1) mRNA, encodes complete protein. AF208835 - Homo sapiens isolate 1 Miller-Dieker lissencephaly protein-like mRNA, complete sequence. AF208836 - Homo sapiens isolate 2 Miller-Dieker lissencephaly protein-like mRNA, complete sequence. AF208837 - Homo sapiens isolate 3 Miller-Dieker lissencephaly protein (MDCR) mRNA, complete cds. AF208838 - Homo sapiens isolate 4 Miller-Dieker lissencephaly protein (MDCR) mRNA, complete cds. L25107 - Human LIS mRNA. S81396 - LIS2 [human, hybrid cell line A9 + 2, GM11712, mRNA RNA Partial, 1345 nt]. AK303015 - Homo sapiens cDNA FLJ51164 complete cds, highly similar to Platelet-activating factor acetylhydrolase IB alpha subunit. AK293918 - Homo sapiens cDNA FLJ52123 complete cds, highly similar to Platelet-activating factor acetylhydrolase IB alpha subunit. JD027272 - Sequence 8296 from Patent EP1572962. JD036081 - Sequence 17105 from Patent EP1572962. JD232671 - Sequence 213695 from Patent EP1572962. JD210456 - Sequence 191480 from Patent EP1572962. JD563130 - Sequence 544154 from Patent EP1572962. JD425997 - Sequence 407021 from Patent EP1572962. JD232019 - Sequence 213043 from Patent EP1572962. JD154746 - Sequence 135770 from Patent EP1572962. JD320296 - Sequence 301320 from Patent EP1572962. JD244004 - Sequence 225028 from Patent EP1572962. JD539729 - Sequence 520753 from Patent EP1572962. JD415878 - Sequence 396902 from Patent EP1572962. JD110079 - Sequence 91103 from Patent EP1572962. JD230370 - Sequence 211394 from Patent EP1572962. JD190502 - Sequence 171526 from Patent EP1572962. JD491121 - Sequence 472145 from Patent EP1572962. JD084877 - Sequence 65901 from Patent EP1572962. JD049933 - Sequence 30957 from Patent EP1572962. JD350450 - Sequence 331474 from Patent EP1572962. JD412615 - Sequence 393639 from Patent EP1572962. JD304650 - Sequence 285674 from Patent EP1572962. JD510726 - Sequence 491750 from Patent EP1572962. JD263017 - Sequence 244041 from Patent EP1572962. JD331702 - Sequence 312726 from Patent EP1572962. JD098346 - Sequence 79370 from Patent EP1572962. JD550169 - Sequence 531193 from Patent EP1572962. JD501454 - Sequence 482478 from Patent EP1572962. JD512176 - Sequence 493200 from Patent EP1572962. JD233377 - Sequence 214401 from Patent EP1572962. JD198727 - Sequence 179751 from Patent EP1572962. JD531357 - Sequence 512381 from Patent EP1572962. JD229812 - Sequence 210836 from Patent EP1572962. JD427375 - Sequence 408399 from Patent EP1572962. JD375775 - Sequence 356799 from Patent EP1572962. JD021932 - Sequence 2956 from Patent EP1572962. JD034701 - Sequence 15725 from Patent EP1572962. JD530964 - Sequence 511988 from Patent EP1572962. JD071666 - Sequence 52690 from Patent EP1572962. JD475593 - Sequence 456617 from Patent EP1572962. JD170284 - Sequence 151308 from Patent EP1572962. JD554716 - Sequence 535740 from Patent EP1572962.
Biochemical and Signaling Pathways
BioCarta from NCI Cancer Genome Anatomy Project h_Lis1Pathway - Lissencephaly gene (LIS1) in neuronal migration and development
Reactome (by CSHL, EBI, and GO)
Protein P43034 (Reactome details) participates in the following event(s):
R-HSA-8849350 RAB6:GTP displaces PAFAH1B1 from dynein:dynactin complex R-HSA-141409 Mad1 binds kinetochore R-HSA-375302 Kinetochore capture of astral microtubules R-HSA-5666129 CDC42:GTP recruits DIAPH2-2 to kinetochores R-HSA-5666169 Kinetochore capture of astral microtubules is positively regulated by CDC42:GTP:p-S196-DIAPH2-2 R-HSA-380272 Plk1-mediated phosphorylation of Nlp R-HSA-380283 Recruitment of additional gamma tubulin/ gamma TuRC to the centrosome R-HSA-380294 Loss of C-Nap-1 from centrosomes R-HSA-380311 Recruitment of Plk1 to centrosomes R-HSA-380455 Recruitment of CDK11p58 to the centrosomes R-HSA-380303 Dissociation of Phospho-Nlp from the centrosome R-HSA-5626220 C2CD3 binds the mother centriole R-HSA-141431 MAD2 associates with the Mad1 kinetochore complex R-HSA-141439 Release of activated MAD2 from kinetochores R-HSA-2467811 Separation of sister chromatids R-HSA-2467809 ESPL1 (Separase) cleaves centromeric cohesin R-HSA-5666160 AURKB phosphorylates DIAPH2-2 at kinetochores R-HSA-380508 Translocation of NuMA to the centrosomes R-HSA-2574845 AJUBA binds centrosome-associated AURKA R-HSA-8853405 TPX2 binds AURKA at centrosomes R-HSA-3000319 BORA binds PLK1 and AURKA R-HSA-2574840 AJUBA facilitates AURKA autophosphorylation R-HSA-3000310 AURKA phosphorylates PLK1 R-HSA-5626223 C2CD3 and OFD1 recruit 5 distal appendage proteins to the centriole R-HSA-5626681 Recruitment of transition zone proteins R-HSA-5626227 CP110 and CEP97 dissociate from the centriole R-HSA-141422 MAD2 converted to an inhibitory state via interaction with Mad1 R-HSA-1638821 PP2A-B56 dephosphorylates centromeric cohesin R-HSA-1638803 Phosphorylation of cohesin by PLK1 at centromeres R-HSA-2468287 CDK1 phosphorylates CDCA5 (Sororin) at centromeres R-HSA-380316 Association of NuMA with microtubules R-HSA-8853419 TPX2 promotes AURKA autophosphorylation R-HSA-5626228 The distal appendage proteins recruit TTBK2 R-HSA-5638009 CEP164 recruits RAB3IP-carrying Golgi-derived vesicles to the basal body R-HSA-8848484 PLA2s hydrolyze phospholipids at the Golgi membrane R-HSA-5626699 MARK4 binds ODF2 in the centriole R-HSA-5617816 RAB3IP stimulates nucleotide exchange on RAB8A R-HSA-6811436 COPI-independent Golgi-to-ER retrograde traffic R-HSA-141444 Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal R-HSA-68877 Mitotic Prometaphase R-HSA-5663220 RHO GTPases Activate Formins R-HSA-380259 Loss of Nlp from mitotic centrosomes R-HSA-380270 Recruitment of mitotic centrosome proteins and complexes R-HSA-380284 Loss of proteins required for interphase microtubule organization from the centrosome R-HSA-5620912 Anchoring of the basal body to the plasma membrane R-HSA-8856688 Golgi-to-ER retrograde transport R-HSA-2500257 Resolution of Sister Chromatid Cohesion R-HSA-2467813 Separation of Sister Chromatids R-HSA-141424 Amplification of signal from the kinetochores R-HSA-68886 M Phase R-HSA-195258 RHO GTPase Effectors R-HSA-380320 Recruitment of NuMA to mitotic centrosomes R-HSA-2565942 Regulation of PLK1 Activity at G2/M Transition R-HSA-8854518 AURKA Activation by TPX2 R-HSA-380287 Centrosome maturation R-HSA-5617833 Cilium Assembly R-HSA-6811442 Intra-Golgi and retrograde Golgi-to-ER traffic R-HSA-68882 Mitotic Anaphase R-HSA-69618 Mitotic Spindle Checkpoint R-HSA-69278 Cell Cycle (Mitotic) R-HSA-194315 Signaling by Rho GTPases R-HSA-69275 G2/M Transition R-HSA-1852241 Organelle biogenesis and maintenance R-HSA-199991 Membrane Trafficking R-HSA-2555396 Mitotic Metaphase and Anaphase R-HSA-69620 Cell Cycle Checkpoints R-HSA-1640170 Cell Cycle R-HSA-162582 Signal Transduction R-HSA-453274 Mitotic G2-G2/M phases R-HSA-5653656 Vesicle-mediated transport
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
