ID AGE1_CAEEL Reviewed; 1182 AA. AC Q94125; A0A0K3ARF0; Q17482; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 22-SEP-2009, sequence version 6. DT 27-MAR-2024, entry version 189. DE RecName: Full=Phosphatidylinositol 3-kinase age-1; DE Short=PI3-kinase age-1; DE Short=PI3K age-1; DE Short=PtdIns-3-kinase age-1; DE EC=2.7.1.137; DE AltName: Full=Aging alteration protein 1; GN Name=age-1 {ECO:0000312|WormBase:B0334.8a}; GN ORFNames=B0334.8 {ECO:0000312|WormBase:B0334.8a}; OS Caenorhabditis elegans. OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida; OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae; OC Caenorhabditis. OX NCBI_TaxID=6239; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Bristol N2; 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] RP NUCLEOTIDE SEQUENCE [MRNA] OF 16-1182, FUNCTION, DEVELOPMENTAL STAGE, AND RP MUTAGENESIS OF PRO-842 AND SER-862. RC STRAIN=Bristol N2; RX PubMed=8700226; DOI=10.1038/382536a0; RA Morris J.Z., Tissenbaum H.A., Ruvkun G.; RT "A phosphatidylinositol-3-OH kinase family member regulating longevity and RT diapause in Caenorhabditis elegans."; RL Nature 382:536-539(1996). RN [3] RP SEQUENCE REVISION. RA Morris J.Z., Tissenbaum H.A., Ruvkun G.; RL Submitted (JUN-1997) to the EMBL/GenBank/DDBJ databases. RN [4] RP FUNCTION. RX PubMed=16091039; DOI=10.1111/j.1365-2958.2005.04739.x; RA Anyanful A., Dolan-Livengood J.M., Lewis T., Sheth S., Dezalia M.N., RA Sherman M.A., Kalman L.V., Benian G.M., Kalman D.; RT "Paralysis and killing of Caenorhabditis elegans by enteropathogenic RT Escherichia coli requires the bacterial tryptophanase gene."; RL Mol. Microbiol. 57:988-1007(2005). RN [5] RP MUTAGENESIS OF PRO-842. RX PubMed=16950159; DOI=10.1016/j.neuron.2006.07.024; RA Tomioka M., Adachi T., Suzuki H., Kunitomo H., Schafer W.R., Iino Y.; RT "The insulin/PI 3-kinase pathway regulates salt chemotaxis learning in RT Caenorhabditis elegans."; RL Neuron 51:613-625(2006). RN [6] RP FUNCTION. RX PubMed=22069193; DOI=10.1242/dev.069062; RA Christensen R., de la Torre-Ubieta L., Bonni A., Colon-Ramos D.A.; RT "A conserved PTEN/FOXO pathway regulates neuronal morphology during C. RT elegans development."; RL Development 138:5257-5267(2011). RN [7] RP FUNCTION, AND MUTAGENESIS OF GLU-761 AND PRO-842. RX PubMed=21750263; DOI=10.1534/genetics.111.130450; RA Hughes S.E., Huang C., Kornfeld K.; RT "Identification of mutations that delay somatic or reproductive aging of RT Caenorhabditis elegans."; RL Genetics 189:341-356(2011). RN [8] RP FUNCTION. RX PubMed=25383666; DOI=10.1038/nsmb.2915; RA Nakagawa A., Sullivan K.D., Xue D.; RT "Caspase-activated phosphoinositide binding by CNT-1 promotes apoptosis by RT inhibiting the AKT pathway."; RL Nat. Struct. Mol. Biol. 21:1082-1090(2014). RN [9] RP FUNCTION, AND MUTAGENESIS OF PRO-842. RX PubMed=27383131; DOI=10.7554/elife.14000; RA Cho C.E., Brueggemann C., L'Etoile N.D., Bargmann C.I.; RT "Parallel encoding of sensory history and behavioral preference during RT Caenorhabditis elegans olfactory learning."; RL Elife 5:14000-14000(2016). CC -!- FUNCTION: Phosphatidylinositol 3-kinase homolog that regulates CC longevity and diapause (PubMed:8700226, PubMed:21750263). Promotes cell CC survival during embryonic development by recruiting akt-1/2 to the CC plasma membrane through the production of PtdIns(3,4,5)P3 CC (PubMed:25383666). Could function in the development or neuroendocrine CC signaling of the dauer pathway (PubMed:8700226). Mediates CC susceptibility to enteropathogenic E.coli infection (PubMed:16091039). CC May negatively regulate AYI interneuron neurite outgrowth CC (PubMed:22069193). Plays a role in aversive olfactory learning when an CC odor is associated with food deprivation (PubMed:27383131). Regulates CC this process by promoting the nuclear relocalization of egl-4 in AWC CC olfactory neurons after odor conditioning (PubMed:27383131). CC {ECO:0000269|PubMed:16091039, ECO:0000269|PubMed:21750263, CC ECO:0000269|PubMed:22069193, ECO:0000269|PubMed:25383666, CC ECO:0000269|PubMed:27383131, ECO:0000269|PubMed:8700226}. 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; CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=a {ECO:0000312|WormBase:B0334.8a}; CC IsoId=Q94125-1; Sequence=Displayed; CC Name=b {ECO:0000312|WormBase:B0334.8b}; CC IsoId=Q94125-3; Sequence=VSP_060474; CC -!- DEVELOPMENTAL STAGE: Expressed both maternally and zygotically. CC {ECO:0000269|PubMed:8700226}. CC -!- SIMILARITY: Belongs to the PI3/PI4-kinase family. {ECO:0000255|PROSITE- CC ProRule:PRU00877, ECO:0000255|PROSITE-ProRule:PRU00879, CC ECO:0000255|PROSITE-ProRule:PRU00880}. CC -!- SEQUENCE CAUTION: CC Sequence=AAC47459.1; Type=Frameshift; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U56101; AAC47459.1; ALT_FRAME; mRNA. DR EMBL; BX284602; CAA91377.3; -; Genomic_DNA. DR EMBL; AL110499; CAA91377.3; JOINED; Genomic_DNA. DR EMBL; BX284602; CTQ86427.1; -; Genomic_DNA. DR PIR; B88318; B88318. DR PIR; S71792; S71792. DR RefSeq; NP_001300488.1; NM_001313559.1. [Q94125-3] DR RefSeq; NP_496462.2; NM_064061.4. [Q94125-1] DR AlphaFoldDB; Q94125; -. DR SMR; Q94125; -. DR BioGRID; 40069; 3. DR STRING; 6239.B0334.8a.1; -. DR EPD; Q94125; -. DR PaxDb; 6239-B0334-8; -. DR PeptideAtlas; Q94125; -. DR EnsemblMetazoa; B0334.8a.1; B0334.8a.1; WBGene00000090. [Q94125-1] DR EnsemblMetazoa; B0334.8b.1; B0334.8b.1; WBGene00000090. [Q94125-3] DR GeneID; 174762; -. DR KEGG; cel:CELE_B0334.8; -. DR UCSC; B0334.8; c. elegans. [Q94125-1] DR AGR; WB:WBGene00000090; -. DR WormBase; B0334.8a; CE43431; WBGene00000090; age-1. [Q94125-1] DR WormBase; B0334.8b; CE02940; WBGene00000090; age-1. [Q94125-3] DR eggNOG; KOG0904; Eukaryota. DR GeneTree; ENSGT00940000170080; -. DR HOGENOM; CLU_002191_1_3_1; -. DR InParanoid; Q94125; -. DR OMA; SKSLWTI; -. DR OrthoDB; 10350at2759; -. DR PhylomeDB; Q94125; -. DR BRENDA; 2.7.1.137; 1045. DR Reactome; R-CEL-114604; GPVI-mediated activation cascade. DR Reactome; R-CEL-1250342; PI3K events in ERBB4 signaling. DR Reactome; R-CEL-1257604; PIP3 activates AKT signaling. DR Reactome; R-CEL-1433557; Signaling by SCF-KIT. DR Reactome; R-CEL-1660499; Synthesis of PIPs at the plasma membrane. DR Reactome; R-CEL-180292; GAB1 signalosome. DR Reactome; R-CEL-186763; Downstream signal transduction. DR Reactome; R-CEL-1963642; PI3K events in ERBB2 signaling. DR Reactome; R-CEL-201556; Signaling by ALK. DR Reactome; R-CEL-392451; G beta:gamma signalling through PI3Kgamma. DR Reactome; R-CEL-416476; G alpha (q) signalling events. DR Reactome; R-CEL-5654689; PI-3K cascade:FGFR1. DR Reactome; R-CEL-5654720; PI-3K cascade:FGFR4. DR Reactome; R-CEL-5673001; RAF/MAP kinase cascade. DR Reactome; R-CEL-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling. DR Reactome; R-CEL-8851907; MET activates PI3K/AKT signaling. DR Reactome; R-CEL-9009391; Extra-nuclear estrogen signaling. DR Reactome; R-CEL-9013149; RAC1 GTPase cycle. DR Reactome; R-CEL-912631; Regulation of signaling by CBL. DR SignaLink; Q94125; -. DR PRO; PR:Q94125; -. DR Proteomes; UP000001940; Chromosome II. DR Bgee; WBGene00000090; Expressed in germ line (C elegans) and 4 other cell types or tissues. DR GO; GO:0005737; C:cytoplasm; IDA:WormBase. DR GO; GO:0097730; C:non-motile cilium; IDA:WormBase. DR GO; GO:0005942; C:phosphatidylinositol 3-kinase complex; IDA:WormBase. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. 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:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:1902075; P:cellular response to salt; IMP:UniProtKB. DR GO; GO:0007635; P:chemosensory behavior; IGI:UniProtKB. DR GO; GO:0006935; P:chemotaxis; IGI:UniProtKB. DR GO; GO:0043053; P:dauer entry; IMP:WormBase. DR GO; GO:0040024; P:dauer larval development; IMP:UniProtKB. DR GO; GO:0008340; P:determination of adult lifespan; IMP:UniProtKB. DR GO; GO:0009792; P:embryo development ending in birth or egg hatching; IMP:WormBase. DR GO; GO:0007611; P:learning or memory; IMP:WormBase. DR GO; GO:0043491; P:phosphatidylinositol 3-kinase/protein kinase B signal transduction; IBA:GO_Central. DR GO; GO:0036092; P:phosphatidylinositol-3-phosphate biosynthetic process; IBA:GO_Central. DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW. DR GO; GO:0050920; P:regulation of chemotaxis; IMP:WormBase. DR GO; GO:0008582; P:regulation of synaptic assembly at neuromuscular junction; IGI:UniProtKB. DR GO; GO:0000003; P:reproduction; IMP:WormBase. DR GO; GO:0046686; P:response to cadmium ion; IMP:WormBase. DR GO; GO:0006979; P:response to oxidative stress; IMP:WormBase. DR GO; GO:1902074; P:response to salt; IGI:UniProtKB. DR CDD; cd08380; C2_PI3K_like; 1. DR CDD; cd00864; PI3Ka; 1. DR Gene3D; 3.10.20.770; -; 1. DR Gene3D; 2.60.40.150; C2 domain; 1. DR Gene3D; 1.10.1070.11; Phosphatidylinositol 3-/4-kinase, catalytic domain; 1. DR Gene3D; 1.25.40.70; Phosphatidylinositol 3-kinase, accessory domain (PIK); 1. DR InterPro; IPR016024; ARM-type_fold. 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; IPR003113; PI3K_ABD. 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; IPR029071; Ubiquitin-like_domsf. DR PANTHER; PTHR10048:SF111; PHOSPHATIDYLINOSITOL 3-KINASE AGE-1; 1. DR PANTHER; PTHR10048; PHOSPHATIDYLINOSITOL KINASE; 1. DR Pfam; PF00454; PI3_PI4_kinase; 1. DR Pfam; PF00792; PI3K_C2; 1. DR Pfam; PF02192; PI3K_p85B; 1. DR Pfam; PF00794; PI3K_rbd; 1. DR Pfam; PF00613; PI3Ka; 1. DR SMART; SM00142; PI3K_C2; 1. DR SMART; SM00143; PI3K_p85B; 1. DR SMART; SM00144; PI3K_rbd; 1. DR SMART; SM00145; PI3Ka; 1. DR SMART; SM00146; PI3Kc; 1. DR SUPFAM; SSF48371; ARM repeat; 1. DR SUPFAM; SSF49562; C2 domain (Calcium/lipid-binding domain, CaLB); 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR SUPFAM; SSF54236; Ubiquitin-like; 1. DR PROSITE; PS51547; C2_PI3K; 1. DR PROSITE; PS00915; PI3_4_KINASE_1; 1. DR PROSITE; PS00916; PI3_4_KINASE_2; 1. DR PROSITE; PS50290; PI3_4_KINASE_3; 1. DR PROSITE; PS51544; PI3K_ABD; 1. DR PROSITE; PS51546; PI3K_RBD; 1. DR PROSITE; PS51545; PIK_HELICAL; 1. PE 1: Evidence at protein level; KW Alternative splicing; ATP-binding; Kinase; Nucleotide-binding; KW Reference proteome; Transferase. FT CHAIN 1..1182 FT /note="Phosphatidylinositol 3-kinase age-1" FT /id="PRO_0000088807" FT DOMAIN 74..174 FT /note="PI3K-ABD" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00877" FT DOMAIN 266..358 FT /note="PI3K-RBD" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00879" FT DOMAIN 425..577 FT /note="C2 PI3K-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00880" FT DOMAIN 601..788 FT /note="PIK helical" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00878" FT DOMAIN 853..1168 FT /note="PI3K/PI4K catalytic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269" FT REGION 1..24 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 859..865 FT /note="G-loop" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269" FT REGION 1028..1036 FT /note="Catalytic loop" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269" FT REGION 1047..1073 FT /note="Activation loop" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269" FT COMPBIAS 1..16 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT VAR_SEQ 1..1106 FT /note="Missing (in isoform b)" FT /evidence="ECO:0000305" FT /id="VSP_060474" FT MUTAGEN 761 FT /note="E->L: In am88; extends lifespan, increases FT pharyngeal pumping, and causes faster body movements. Also FT increases dauer formation." FT /evidence="ECO:0000269|PubMed:21750263" FT MUTAGEN 842 FT /note="P->S: In hx546; increases lifespan. Increases dauer FT formation. Fails to avoid NaCl after exposure to NaCl under FT starvation conditions. Defective in aversive olfactory FT learning. Reduces nuclear enrichment of egl-4 in the AWC FT neurons after odor conditioning." FT /evidence="ECO:0000269|PubMed:16950159, FT ECO:0000269|PubMed:21750263, ECO:0000269|PubMed:27383131, FT ECO:0000269|PubMed:8700226" FT MUTAGEN 862 FT /note="S->N: In mg109." FT /evidence="ECO:0000269|PubMed:8700226" FT CONFLICT 1046 FT /note="F -> V (in Ref. 2; AAC47459)" FT /evidence="ECO:0000305" SQ SEQUENCE 1182 AA; 136873 MW; C82DA6F98A383EAC CRC64; MSMGRSPSTT FRSRTGSHGA RDLIAGHGRN SRRISQMHVN ILHPQLQTMV EQWQMRERPS LETENGKGSL LLENEGVADI ITMCPFGEVI SVVFPWFLAN VRTSLEIKLS DFKHQLFELI APMKWGTYSV KPQDYVFRQL NNFGEIEVIF NDDQPLSKLE LHGTFPMLFL YQPDGINRDK ELMSDISHCL GYSLDKLEES LDEELRQFRA SLWARTKKTC LTRGLEGTSH YAFPEEQYLC VGESCPKDLE SKVKAAKLSY QMFWRKRKAE INGVCEKMMK IQIEFNPNET PKSLLHTFLY EMRKLDVYDT DDPADEGWFL QLAGRTTFVT NPDVKLTSYD GVRSELESYR CPGFVVRRQS LVLKDYCRPK PLYEPHYVRA HERKLALDVL SVSIDSTPKQ SKNSDMVMTD FRPTASLKQV SLWDLDANLM IRPVNISGFD FPADVDMYVR IEFSVYVGTL TLASKSTTKV NAQFAKWNKE MYTFDLYMKD MPPSAVLSIR VLYGKVKLKS EEFEVGWVNM SLTDWRDELR QGQFLFHLWA PEPTANRSRI GENGARIGTN AAVTIEISSY GGRVRMPSQG QYTYLVKHRS TWTETLNIMG DDYESCIRDP GYKKLQMLVK KHESGIVLEE DEQRHVWMWR RYIQKQEPDL LIVLSELAFV WTDRENFSEL YVMLEKWKPP SVAAALTLLG KRCTDRVIRK FAVEKLNEQL SPVTFHLFIL PLIQALKYEP RAQSEVGMML LTRALCDYRI GHRLFWLLRA EIARLRDCDL KSEEYRRISL LMEAYLRGNE EHIKIITRQV DMVDELTRIS TLVKGMPKDV ATMKLRDELR SISHKMENMD SPLDPVYKLG EMIIDKAIVL GSAKRPLMLH WKNKNPKSDL HLPFCAMIFK NGDDLRQDML VLQVLEVMDN IWKAANIDCC LNPYAVLPMG EMIGIIEVVP NCKTIFEIQV GTGFMNTAVR SIDPSFMNKW IRKQCGIEDE KKKSKKDSTK NPIEKKIDNT QAMKKYFESV DRFLYSCVGY SVATYIMGIK DRHSDNLMLT EDGKYFHIDF GHILGHGKTK LGIQRDRQPF ILTEHFMTVI RSGKSVDGNS HELQKFKTLC VEAYEVMWNN RDLFVSLFTL MLGMELPELS TKADLDHLKK TLFCNGESKE EARKFFAGIY EEAFNGSWST KTNWLFHAVK HY //