ID LIS1_PANTR Reviewed; 410 AA.
AC Q5IS43;
DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 27-MAR-2024, entry version 125.
DE RecName: Full=Platelet-activating factor acetylhydrolase IB subunit alpha {ECO:0000250|UniProtKB:P43034, ECO:0000255|HAMAP-Rule:MF_03141};
DE AltName: Full=Lissencephaly-1 protein {ECO:0000255|HAMAP-Rule:MF_03141};
DE Short=LIS-1 {ECO:0000255|HAMAP-Rule:MF_03141};
DE AltName: Full=PAF acetylhydrolase 45 kDa subunit {ECO:0000255|HAMAP-Rule:MF_03141};
DE Short=PAF-AH 45 kDa subunit {ECO:0000255|HAMAP-Rule:MF_03141};
DE AltName: Full=PAF-AH alpha {ECO:0000255|HAMAP-Rule:MF_03141};
DE Short=PAFAH alpha {ECO:0000255|HAMAP-Rule:MF_03141};
GN Name=PAFAH1B1 {ECO:0000250|UniProtKB:P43034,
GN ECO:0000255|HAMAP-Rule:MF_03141};
GN Synonyms=LIS1 {ECO:0000255|HAMAP-Rule:MF_03141}, PAFAHA;
OS Pan troglodytes (Chimpanzee).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pan.
OX NCBI_TaxID=9598;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=15620360; DOI=10.1016/j.cell.2004.11.040;
RA Dorus S., Vallender E.J., Evans P.D., Anderson J.R., Gilbert S.L.,
RA Mahowald M., Wyckoff G.J., Malcom C.M., Lahn B.T.;
RT "Accelerated evolution of nervous system genes in the origin of Homo
RT sapiens.";
RL Cell 119:1027-1040(2004).
CC -!- FUNCTION: Regulatory subunit (beta subunit) of the cytosolic type I
CC platelet-activating factor (PAF) acetylhydrolase (PAF-AH (I)), an
CC enzyme that catalyzes the hydrolyze of the acetyl group at the sn-2
CC position of PAF and its analogs and participates in PAF inactivation.
CC Regulates the PAF-AH (I) activity in a catalytic dimer composition-
CC dependent manner (By similarity). Positively regulates the activity of
CC the minus-end directed microtubule motor protein dynein. May enhance
CC dynein-mediated microtubule sliding by targeting dynein to the
CC microtubule plus end. Required for several dynein- and microtubule-
CC dependent processes such as the maintenance of Golgi integrity, the
CC peripheral transport of microtubule fragments and the coupling of the
CC nucleus and centrosome. Required during brain development for the
CC proliferation of neuronal precursors and the migration of newly formed
CC neurons from the ventricular/subventricular zone toward the cortical
CC plate. Neuronal migration involves a process called nucleokinesis,
CC whereby migrating cells extend an anterior process into which the
CC nucleus subsequently translocates. During nucleokinesis dynein at the
CC nuclear surface may translocate the nucleus towards the centrosome by
CC exerting force on centrosomal microtubules. Also required for proper
CC activation of Rho GTPases and actin polymerization at the leading edge
CC of locomoting cerebellar neurons and postmigratory hippocampal neurons
CC in response to calcium influx triggered via NMDA receptors. May also
CC play a role in other forms of cell locomotion including the migration
CC of fibroblasts during wound healing. Required for dynein recruitment to
CC microtubule plus ends and BICD2-bound cargos. May modulate the Reelin
CC pathway through interaction of the PAF-AH (I) catalytic dimer with
CC VLDLR (By similarity). {ECO:0000250|UniProtKB:P43033,
CC ECO:0000250|UniProtKB:P43034, ECO:0000250|UniProtKB:P63005,
CC ECO:0000255|HAMAP-Rule:MF_03141}.
CC -!- SUBUNIT: Can self-associate. Component of the cytosolic PAF-AH (I)
CC heterotetrameric enzyme, which is composed of PAFAH1B1 (beta), PAFAH1B2
CC (alpha2) and PAFAH1B3 (alpha1) subunits. The catalytic activity of the
CC enzyme resides in the alpha1 (PAFAH1B3) and alpha2 (PAFAH1B2) subunits,
CC whereas the beta subunit (PAFAH1B1) has regulatory activity. Trimer
CC formation is not essential for the catalytic activity. Interacts with
CC the catalytic dimer of PAF-AH (I) heterotetrameric enzyme: interacts
CC with PAFAH1B2 homodimer (alpha2/alpha2 homodimer), PAFAH1B3 homodimer
CC (alpha1/alpha1 homodimer) and PAFAH1B2-PAFAH1B3 heterodimer
CC (alpha2/alpha1 heterodimer) (By similarity). Interacts with DCX,
CC dynein, dynactin, IQGAP1, KATNB1, NDE1, NDEL1, NUDC and RSN. Interacts
CC with DISC1, and this interaction is enhanced by NDEL1. Interacts with
CC DAB1 when DAB1 is phosphorylated in response to RELN/reelin signaling.
CC Interacts with INTS13. Interacts with DCDC1.
CC {ECO:0000250|UniProtKB:P43033, ECO:0000250|UniProtKB:P43034,
CC ECO:0000255|HAMAP-Rule:MF_03141}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton {ECO:0000255|HAMAP-
CC Rule:MF_03141}. Cytoplasm, cytoskeleton, microtubule organizing center,
CC centrosome {ECO:0000255|HAMAP-Rule:MF_03141}. Cytoplasm, cytoskeleton,
CC spindle {ECO:0000255|HAMAP-Rule:MF_03141}. Nucleus membrane
CC {ECO:0000255|HAMAP-Rule:MF_03141}. Note=Localizes to the plus end of
CC microtubules and to the centrosome. May localize to the nuclear
CC membrane. Redistributes to axons during neuronal development. Also
CC localizes to the microtubules of the manchette in elongating spermatids
CC and to the meiotic spindle in spermatocytes. {ECO:0000255|HAMAP-
CC Rule:MF_03141}.
CC -!- DOMAIN: Dimerization mediated by the LisH domain may be required to
CC activate dynein. {ECO:0000255|HAMAP-Rule:MF_03141}.
CC -!- MISCELLANEOUS: Originally the subunits of the type I platelet-
CC activating factor (PAF) acetylhydrolase was named alpha (PAFAH1B1),
CC beta (PAFAH1B2) and gamma (PAFAH1B3) (By similarity). Now these
CC subunits have been renamed beta (PAFAH1B1), alpha2 (PAFAH1B2) and
CC alpha1 (PAFAH1B3) respectively (By similarity).
CC {ECO:0000250|UniProtKB:P43034, ECO:0000250|UniProtKB:P68402,
CC ECO:0000250|UniProtKB:Q15102, ECO:0000250|UniProtKB:Q29460}.
CC -!- SIMILARITY: Belongs to the WD repeat LIS1/nudF family.
CC {ECO:0000255|HAMAP-Rule:MF_03141}.
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DR EMBL; AY665285; AAV74323.1; -; mRNA.
DR RefSeq; NP_001029263.1; NM_001034091.1.
DR AlphaFoldDB; Q5IS43; -.
DR SMR; Q5IS43; -.
DR STRING; 9598.ENSPTRP00000078363; -.
DR PaxDb; 9598-ENSPTRP00000014595; -.
DR GeneID; 454422; -.
DR KEGG; ptr:454422; -.
DR CTD; 5048; -.
DR eggNOG; KOG0295; Eukaryota.
DR InParanoid; Q5IS43; -.
DR OrthoDB; 1798470at2759; -.
DR Proteomes; UP000002277; Unplaced.
DR GO; GO:0008247; C:1-alkyl-2-acetylglycerophosphocholine esterase complex; ISS:UniProtKB.
DR GO; GO:1904115; C:axon cytoplasm; IEA:GOC.
DR GO; GO:0005813; C:centrosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005881; C:cytoplasmic microtubule; IBA:GO_Central.
DR GO; GO:0000776; C:kinetochore; IBA:GO_Central.
DR GO; GO:0005875; C:microtubule associated complex; IBA:GO_Central.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0043025; C:neuronal cell body; IBA:GO_Central.
DR GO; GO:0005635; C:nuclear envelope; IBA:GO_Central.
DR GO; GO:0031965; C:nuclear membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005819; C:spindle; IEA:UniProtKB-SubCell.
DR GO; GO:0070840; F:dynein complex binding; IBA:GO_Central.
DR GO; GO:0051010; F:microtubule plus-end binding; IBA:GO_Central.
DR GO; GO:0046982; F:protein heterodimerization activity; ISS:UniProtKB.
DR GO; GO:0048854; P:brain morphogenesis; IBA:GO_Central.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0000132; P:establishment of mitotic spindle orientation; IBA:GO_Central.
DR GO; GO:0007281; P:germ cell development; IBA:GO_Central.
DR GO; GO:0016042; P:lipid catabolic process; IEA:UniProtKB-KW.
DR GO; GO:0031023; P:microtubule organizing center organization; IBA:GO_Central.
DR GO; GO:0051012; P:microtubule sliding; IEA:UniProtKB-UniRule.
DR GO; GO:0007097; P:nuclear migration; IBA:GO_Central.
DR GO; GO:0038026; P:reelin-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0008090; P:retrograde axonal transport; IBA:GO_Central.
DR GO; GO:0047496; P:vesicle transport along microtubule; IBA:GO_Central.
DR CDD; cd00200; WD40; 1.
DR Gene3D; 1.20.960.30; -; 1.
DR Gene3D; 2.130.10.10; YVTN repeat-like/Quinoprotein amine dehydrogenase; 1.
DR HAMAP; MF_03141; lis1; 1.
DR InterPro; IPR017252; Dynein_regulator_LIS1.
DR InterPro; IPR020472; G-protein_beta_WD-40_rep.
DR InterPro; IPR037190; LIS1_N.
DR InterPro; IPR006594; LisH.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR019775; WD40_repeat_CS.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR InterPro; IPR001680; WD40_rpt.
DR PANTHER; PTHR44129:SF1; PLATELET-ACTIVATING FACTOR ACETYLHYDROLASE IB SUBUNIT BETA; 1.
DR PANTHER; PTHR44129; WD REPEAT-CONTAINING PROTEIN POP1; 1.
DR Pfam; PF08513; LisH; 1.
DR Pfam; PF00400; WD40; 7.
DR PIRSF; PIRSF037647; Dynein_regulator_Lis1; 1.
DR PRINTS; PR00320; GPROTEINBRPT.
DR SMART; SM00667; LisH; 1.
DR SMART; SM00320; WD40; 7.
DR SUPFAM; SSF109925; Lissencephaly-1 protein (Lis-1, PAF-AH alpha) N-terminal domain; 1.
DR SUPFAM; SSF50978; WD40 repeat-like; 1.
DR PROSITE; PS50896; LISH; 1.
DR PROSITE; PS00678; WD_REPEATS_1; 4.
DR PROSITE; PS50082; WD_REPEATS_2; 7.
DR PROSITE; PS50294; WD_REPEATS_REGION; 1.
PE 2: Evidence at transcript level;
KW Acetylation; Cell cycle; Cell division; Coiled coil; Cytoplasm;
KW Cytoskeleton; Developmental protein; Differentiation; Lipid degradation;
KW Lipid metabolism; Membrane; Microtubule; Mitosis; Neurogenesis; Nucleus;
KW Phosphoprotein; Reference proteome; Repeat; Transport; WD repeat.
FT CHAIN 1..410
FT /note="Platelet-activating factor acetylhydrolase IB
FT subunit alpha"
FT /id="PRO_0000051064"
FT DOMAIN 7..39
FT /note="LisH"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03141"
FT REPEAT 106..147
FT /note="WD 1"
FT REPEAT 148..187
FT /note="WD 2"
FT REPEAT 190..229
FT /note="WD 3"
FT REPEAT 232..271
FT /note="WD 4"
FT REPEAT 274..333
FT /note="WD 5"
FT REPEAT 336..377
FT /note="WD 6"
FT REPEAT 379..410
FT /note="WD 7"
FT REGION 1..102
FT /note="Interaction with NDEL1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03141"
FT REGION 1..66
FT /note="Interaction with NDE1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03141"
FT REGION 1..38
FT /note="Required for self-association and interaction with
FT PAFAH1B2 and PAFAH1B3"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03141"
FT REGION 83..410
FT /note="Interaction with dynein and dynactin"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03141"
FT REGION 367..409
FT /note="Interaction with DCX"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03141"
FT REGION 388..410
FT /note="Interaction with NDEL1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03141"
FT COILED 56..82
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03141"
FT MOD_RES 53
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P43034"
FT MOD_RES 109
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P43034"
SQ SEQUENCE 410 AA; 46730 MW; 4DBF6A34A7B131CD CRC64;
MVLSQRQRDE LNRAIADYLR SNGYEEAYSV FKKEAELDMN EELDKKYAGL LEKKWTSVIR
LQKKVMELES KLNEAKEEFT SGGPLGQKRD PKEWIPRPPE KYALSGHRSP VTRVIFHPVF
SVMVSASEDA TIKVWDYETG DFERTLKGHT DSVQDISFDH SGKLLASCSA DMTIKLWDFQ
GFECIRTMHG HDHNVSSVAI MPNGDHIVSA SRDKTIKMWE VQTGYCVKTF TGHREWVRMV
RPNQDGTLIA SCSNDQTVRV WVVATKECKA ELREHEHVVE CISWAPESSY SSISEATGSE
TKKSGKPGPF LLSGSRDKTI KMWDVSTGMC LMTLVGHDNW VRGVLFHSGG KFILSCADDK
TLRVWDYKNK RCMKTLNAHE HFVTSLDFHK TAPYVVTGFV DQTVKVWECR
//
