AGE1_CAEEL
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 03-AUG-2022, entry version 180.
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};
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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; 2.
DR STRING; 6239.B0334.8; -.
DR EPD; Q94125; -.
DR PaxDb; Q94125; -.
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 CTD; 174762; -.
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; FFASELW; -.
DR OrthoDB; 204282at2759; -.
DR PhylomeDB; Q94125; -.
DR BRENDA; 2.7.1.137; 1045.
DR Reactome; R-CEL-109704; PI3K Cascade.
DR Reactome; R-CEL-114604; GPVI-mediated activation cascade.
DR Reactome; R-CEL-1257604; PIP3 activates AKT signaling.
DR Reactome; R-CEL-1660499; Synthesis of PIPs at the plasma membrane.
DR Reactome; R-CEL-186763; Downstream signal transduction.
DR Reactome; R-CEL-201556; Signaling by ALK.
DR Reactome; R-CEL-210993; Tie2 Signaling.
DR Reactome; R-CEL-392451; G beta:gamma signalling through PI3Kgamma.
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-912631; Regulation of signaling by CBL.
DR Reactome; R-CEL-983695; Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
DR SignaLink; Q94125; -.
DR PRO; PR:Q94125; -.
DR Proteomes; UP000001940; Chromosome II.
DR Bgee; WBGene00000090; Expressed in germ line (C elegans) and 4 other tissues.
DR GO; GO:0005737; C:cytoplasm; IDA:WormBase.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
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:0052742; F:phosphatidylinositol kinase activity; IBA:GO_Central.
DR GO; GO:0007568; P:aging; IMP:UniProtKB.
DR GO; GO:0016477; P:cell migration; IBA:GO_Central.
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: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; IBA:GO_Central.
DR GO; GO:0048015; P:phosphatidylinositol-mediated signaling; 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 Gene3D; 1.10.1070.11; -; 1.
DR Gene3D; 1.25.40.70; -; 1.
DR Gene3D; 2.60.40.150; -; 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; PTHR10048; 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; SSF48371; 1.
DR SUPFAM; SSF49562; SSF49562; 1.
DR SUPFAM; SSF54236; SSF54236; 1.
DR SUPFAM; SSF56112; SSF56112; 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
