PIKI1_CAEEL
ID PIKI1_CAEEL Reviewed; 1607 AA.
AC G5EDY0;
DT 11-MAY-2016, integrated into UniProtKB/Swiss-Prot.
DT 14-DEC-2011, sequence version 1.
DT 03-AUG-2022, entry version 89.
DE RecName: Full=Phosphatidylinositol 3-kinase piki-1 {ECO:0000305|PubMed:22272187};
DE EC=2.7.1.137 {ECO:0000305|PubMed:22272187};
DE AltName: Full=Phosphoinositide-3-kinase class 2 {ECO:0000303|PubMed:22272187};
DE Short=PI3-kinase class 2 {ECO:0000303|PubMed:22272187};
DE Short=PI3K class 2 {ECO:0000303|PubMed:22272187};
GN Name=piki-1 {ECO:0000312|WormBase:F39B1.1};
GN ORFNames=F39B1.1 {ECO:0000312|WormBase:F39B1.1};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF LYS-1059.
RX PubMed=22272187; DOI=10.1371/journal.pbio.1001245;
RA Lu N., Shen Q., Mahoney T.R., Neukomm L.J., Wang Y., Zhou Z.;
RT "Two PI 3-kinases and one PI 3-phosphatase together establish the cyclic
RT waves of phagosomal PtdIns(3)P critical for the degradation of apoptotic
RT cells.";
RL PLoS Biol. 10:E1001245-E1001245(2012).
CC -!- FUNCTION: Phosphatidylinositol 3-kinase involved in clearance of
CC apoptotic cell corpses by phagosomes. Phagosome maturation requires two
CC sequential and non-overlapping pulses of phosphatidylinositol-3-
CC phosphate (PI3P) on the vesicle surface which mediates recruitment of
CC sortins snx-1 and lst-4 and small GTPases rab-5, rab-2 and rab-7. The
CC first pulse is initiated by piki-1, then maintained by vps-34 which
CC also produces the second pulse. Unlike vps-34, not involved in the
CC formation of PI3P in early endosomes. {ECO:0000269|PubMed:22272187}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol) + ATP = a
CC 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3-phosphate) + ADP +
CC H(+); Xref=Rhea:RHEA:12709, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:57880, ChEBI:CHEBI:58088, ChEBI:CHEBI:456216;
CC EC=2.7.1.137; Evidence={ECO:0000305|PubMed:22272187};
CC -!- INTERACTION:
CC G5EDY0; Q21648: CELE_R02F2.5; NbExp=3; IntAct=EBI-321433, EBI-314179;
CC -!- SUBCELLULAR LOCATION: Cell projection, phagocytic cup
CC {ECO:0000269|PubMed:22272187}. Cytoplasmic vesicle, phagosome membrane
CC {ECO:0000269|PubMed:22272187}; Peripheral membrane protein
CC {ECO:0000269|PubMed:22272187}. Cytoplasm {ECO:0000269|PubMed:22272187}.
CC Note=Localizes transiently to pseudopods and nascent phagosomes during
CC cell corpse engulfment. {ECO:0000269|PubMed:22272187}.
CC -!- SIMILARITY: Belongs to the PI3/PI4-kinase family. {ECO:0000255|PROSITE-
CC ProRule:PRU00879}.
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DR EMBL; BX284606; CAA93489.1; -; Genomic_DNA.
DR PIR; T21982; T21982.
DR RefSeq; NP_510529.1; NM_078128.3.
DR AlphaFoldDB; G5EDY0; -.
DR SMR; G5EDY0; -.
DR IntAct; G5EDY0; 2.
DR STRING; 6239.F39B1.1; -.
DR EPD; G5EDY0; -.
DR PaxDb; G5EDY0; -.
DR PeptideAtlas; G5EDY0; -.
DR EnsemblMetazoa; F39B1.1.1; F39B1.1.1; WBGene00009552.
DR GeneID; 181618; -.
DR KEGG; cel:CELE_F39B1.1; -.
DR CTD; 181618; -.
DR WormBase; F39B1.1; CE05832; WBGene00009552; piki-1.
DR eggNOG; KOG0905; Eukaryota.
DR GeneTree; ENSGT00940000169868; -.
DR HOGENOM; CLU_002191_0_0_1; -.
DR InParanoid; G5EDY0; -.
DR OMA; QMAAGFR; -.
DR OrthoDB; 204282at2759; -.
DR PhylomeDB; G5EDY0; -.
DR Reactome; R-CEL-1660499; Synthesis of PIPs at the plasma membrane.
DR Reactome; R-CEL-1660514; Synthesis of PIPs at the Golgi membrane.
DR Reactome; R-CEL-1660516; Synthesis of PIPs at the early endosome membrane.
DR Reactome; R-CEL-1660517; Synthesis of PIPs at the late endosome membrane.
DR Reactome; R-CEL-432722; Golgi Associated Vesicle Biogenesis.
DR Reactome; R-CEL-8856828; Clathrin-mediated endocytosis.
DR PRO; PR:G5EDY0; -.
DR Proteomes; UP000001940; Chromosome X.
DR Bgee; WBGene00009552; Expressed in pharyngeal muscle cell (C elegans) and 3 other tissues.
DR GO; GO:0005737; C:cytoplasm; IDA:WormBase.
DR GO; GO:0032009; C:early phagosome; IDA:WormBase.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0001891; C:phagocytic cup; IEA:UniProtKB-SubCell.
DR GO; GO:0030670; C:phagocytic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005942; C:phosphatidylinositol 3-kinase complex; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0031143; C:pseudopodium; IDA:WormBase.
DR GO; GO:0016303; F:1-phosphatidylinositol-3-kinase activity; ISS:WormBase.
DR GO; GO:0035005; F:1-phosphatidylinositol-4-phosphate 3-kinase activity; IBA:GO_Central.
DR GO; GO:0035091; F:phosphatidylinositol binding; IEA:InterPro.
DR GO; GO:0052742; F:phosphatidylinositol kinase activity; IBA:GO_Central.
DR GO; GO:0016477; P:cell migration; IBA:GO_Central.
DR GO; GO:0002119; P:nematode larval development; IGI:WormBase.
DR GO; GO:0090386; P:phagosome maturation involved in apoptotic cell clearance; IMP:WormBase.
DR GO; GO:0014065; P:phosphatidylinositol 3-kinase signaling; IBA:GO_Central.
DR GO; GO:0046854; P:phosphatidylinositol phosphate biosynthetic process; IBA:GO_Central.
DR GO; GO:0036092; P:phosphatidylinositol-3-phosphate biosynthetic process; IMP:WormBase.
DR GO; GO:0048015; P:phosphatidylinositol-mediated signaling; IBA:GO_Central.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0060100; P:positive regulation of phagocytosis, engulfment; IMP:WormBase.
DR Gene3D; 1.10.1070.11; -; 1.
DR Gene3D; 1.25.40.70; -; 1.
DR Gene3D; 2.60.40.150; -; 2.
DR Gene3D; 3.30.1520.10; -; 1.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000403; PI3/4_kinase_cat_dom.
DR InterPro; IPR036940; PI3/4_kinase_cat_sf.
DR InterPro; IPR018936; PI3/4_kinase_CS.
DR InterPro; IPR002420; PI3K-type_C2_dom.
DR InterPro; IPR001263; PI3K_accessory_dom.
DR InterPro; IPR042236; PI3K_accessory_sf.
DR InterPro; IPR000341; PI3K_Ras-bd_dom.
DR InterPro; IPR015433; PI_Kinase.
DR InterPro; IPR001683; PX_dom.
DR InterPro; IPR036871; PX_dom_sf.
DR InterPro; IPR003903; UIM_dom.
DR PANTHER; PTHR10048; PTHR10048; 1.
DR Pfam; PF00168; C2; 1.
DR Pfam; PF00454; PI3_PI4_kinase; 1.
DR Pfam; PF00613; PI3Ka; 1.
DR Pfam; PF00787; PX; 1.
DR SMART; SM00239; C2; 1.
DR SMART; SM00142; PI3K_C2; 1.
DR SMART; SM00144; PI3K_rbd; 1.
DR SMART; SM00145; PI3Ka; 1.
DR SMART; SM00146; PI3Kc; 1.
DR SMART; SM00312; PX; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
DR SUPFAM; SSF49562; SSF49562; 2.
DR SUPFAM; SSF56112; SSF56112; 1.
DR SUPFAM; SSF64268; SSF64268; 1.
DR PROSITE; PS50004; C2; 1.
DR PROSITE; PS51547; C2_PI3K; 1.
DR PROSITE; PS00916; PI3_4_KINASE_2; 1.
DR PROSITE; PS50290; PI3_4_KINASE_3; 1.
DR PROSITE; PS51546; PI3K_RBD; 1.
DR PROSITE; PS51545; PIK_HELICAL; 1.
DR PROSITE; PS50195; PX; 1.
DR PROSITE; PS50330; UIM; 1.
PE 1: Evidence at protein level;
KW Cell projection; Cytoplasm; Cytoplasmic vesicle; Kinase;
KW Lipid biosynthesis; Lipid metabolism; Membrane; Phagocytosis;
KW Reference proteome; Transferase.
FT CHAIN 1..1607
FT /note="Phosphatidylinositol 3-kinase piki-1"
FT /evidence="ECO:0000305"
FT /id="PRO_0000436266"
FT DOMAIN 2..21
FT /note="UIM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00213"
FT DOMAIN 362..453
FT /note="PI3K-RBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00879"
FT DOMAIN 598..766
FT /note="C2 PI3K-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00880"
FT DOMAIN 776..953
FT /note="PIK helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00878"
FT DOMAIN 1029..1303
FT /note="PI3K/PI4K catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT DOMAIN 1344..1458
FT /note="PX"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00147"
FT DOMAIN 1472..1601
FT /note="C2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT REGION 54..91
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 105..128
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 142..182
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1035..1041
FT /note="G-loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 1168..1176
FT /note="Catalytic loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 1187..1213
FT /note="Activation loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT COMPBIAS 54..69
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 108..128
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 142..168
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 1059
FT /note="K->A: May disrupt ATP binding. Severe defect in
FT apoptotic cell corpse clearance in gonads."
FT /evidence="ECO:0000269|PubMed:22272187"
SQ SEQUENCE 1607 AA; 185305 MW; 77153B9F760C8DC1 CRC64;
MSDDEELQLA IEISKKTFKD EQKLRSNDLD LIRFESPDEP ARQRKINQIK QLYEANSPGP
SSYSGSLATS PIDFRPVYNE PRAGPIPHSQ SYPRNYFQDW SAIASTSQPP AFPPPPRPPK
PEQYKFPPAP SVPLLHDRYF VPPPPPVPPR HSRVQQSPPV PIHPTPPVSS TPLRHSAPSF
ASDSQQFLSP IKPFEISFNS TVDTSSNQTG SHDHSIQYQP LTHLYVPYVM HSLNSSYGAL
LNGDLIDLSA FEDSSNASQD EIRKEFDPLF ISTYSTDTPS PDNSMPAVNA YFSKPIDEPE
CVGGAKLIQE NIEFPSSSFC LIDCPNGIEE QVKKLCKRNL IRKDMTPDFF IAPTVDYMVT
TASTVKVVVY KDHSWKANKS NGKAMICAID EKMDIITTQA LSLFDSELPT DKEYGLKIYG
LNQFLSSDSL LGSNLYTGHC LLNGDDVKLD LGVFAPNSRI YEQTLESWNL MKSQVKYSTV
VDKEDVENTL GHLASEMSQY EIAFNDGSTL KLSSSSQRVK QVIMLLCKCL HGIVPEKLYN
EMQKYLASTT EDQLVHHRND FLREIHSFLE LYCRCTVSRY NIPPLQIITK PKVEVLSKMD
FLQIMLNSVH SIPEHWQSQY SEFYMSLDLY HGTQVLDGFS NKVPKTIKND HFFPRIPLDL
YAKFKRLNLC QYPRETRIVV SISGTVRNSA QAANEYNPDI VMLGYCSVPL YDENLFMRQG
PLFLPLTLLK KQPMLKPFGP YPYIKDARDP ILIMSFKIWD TEIYFPNVVI DMQCIPQDFA
TLDIETQEYL LELIENQDTS TLETDDQDLI WQKRLHLTNQ PEALPLVLSS LQDWSFGFVM
RVYQILEEWA PLRPEIAMEF LLPKYPDERI RAHAVQSLAR GSTDFLYHTI PQFIEALRFE
LYEKSALADF ILELSFVSLD FTFEIYWQLQ QRVDHCAVDD LPYAIRCQNL QQKMIDEHEN
PNLKTDIKLQ HELLNELDSI QDDLRSKSGD SEIERLHRLR TRLGILDSKL LQNKVRLPIC
PAFDCTGVRI EECSVFNSNA KPLKIVFRGL NMNYSIIHKR DDDMRQDAFV MKMLNEMDRI
WKSNGLDLRM ITFRIMPVGY RRGMGELVLN CATLMEIQKE EGLRGVLNDE ILRKWLMKHN
SDEFAYKEAQ ENFIRSCAGW CIVTYVLGIG DRHNDNILFT KNGHVFHIDF GKYMGDWQMA
AGFRRDRVPF VFTTEMFHVI NNGRAPTQYN QKFIDYCCKA FNHLRRNKNT LTNLLRIMAC
SDIPGINMDS LAFVENNLML DLSDTDATVQ FTAMIQNSLG SAFVRLNFVA HTVAQFISSR
PSFSKQDPNK LSFVPELYTE NSDGRISRVT VLKFEKHCIP NKIYMYKVEV HRKNVAVSSF
IYRSFAEFEE LHTKLRARFP MMAVSLNTIS NLRSNVRAVA QKRIIHVQKF LIYLFNQVDE
ICHCDLVYTF FHSILRDNKC DTYIDESLDM PSQCQIYLKI EYNSVKETLS VFIGHAKYLA
LLQNNQQPDP YVKTYVRPDL RNQSKQKTQV VRGTRHPTFN QDLNYTEFPI EILSTRVLEV
SIWNNGGYLV KHKMYMLCIP LLKVKKLAES RKNCRTLEGW FNCEKCV
