NIPI3_CAEEL
ID NIPI3_CAEEL Reviewed; 655 AA.
AC G5EED4;
DT 22-JUL-2015, integrated into UniProtKB/Swiss-Prot.
DT 14-DEC-2011, sequence version 1.
DT 03-AUG-2022, entry version 74.
DE RecName: Full=Protein nipi-3 {ECO:0000305};
DE AltName: Full=No induction of peptide after drechmeria infection protein 3 {ECO:0000312|WormBase:K09A9.1};
DE AltName: Full=Tribbles homolog nipi-3 {ECO:0000303|PubMed:27927200, ECO:0000303|PubMed:27927209, ECO:0000303|PubMed:34407394};
GN Name=nipi-3 {ECO:0000312|WormBase:K09A9.1};
GN ORFNames=K09A9.1 {ECO:0000312|WormBase:K09A9.1};
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|EMBL:ABW05091.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL
RP STAGE, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF ILE-307.
RX PubMed=18394898; DOI=10.1016/j.cub.2008.02.079;
RA Pujol N., Cypowyj S., Ziegler K., Millet A., Astrain A., Goncharov A.,
RA Jin Y., Chisholm A.D., Ewbank J.J.;
RT "Distinct innate immune responses to infection and wounding in the C.
RT elegans epidermis.";
RL Curr. Biol. 18:481-489(2008).
RN [2] {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 [3]
RP FUNCTION, INTERACTION WITH CEBP-1, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=27927209; DOI=10.1186/s12915-016-0320-z;
RA Kim K.W., Thakur N., Piggott C.A., Omi S., Polanowska J., Jin Y., Pujol N.;
RT "Coordinated inhibition of C/EBP by Tribbles in multiple tissues is
RT essential for Caenorhabditis elegans development.";
RL BMC Biol. 14:104-104(2016).
RN [4]
RP FUNCTION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF ILE-307.
RX PubMed=27927200; DOI=10.1186/s12915-016-0334-6;
RA McEwan D.L., Feinbaum R.L., Stroustrup N., Haas W., Conery A.L.,
RA Anselmo A., Sadreyev R., Ausubel F.M.;
RT "Tribbles ortholog NIPI-3 and bZIP transcription factor CEBP-1 regulate a
RT Caenorhabditis elegans intestinal immune surveillance pathway.";
RL BMC Biol. 14:105-105(2016).
RN [5]
RP FUNCTION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF ILE-307.
RX PubMed=34407394; DOI=10.1016/j.celrep.2021.109529;
RA Wu C., Karakuzu O., Garsin D.A.;
RT "Tribbles pseudokinase NIPI-3 regulates intestinal immunity in
RT Caenorhabditis elegans by controlling SKN-1/Nrf activity.";
RL Cell Rep. 36:109529-109529(2021).
CC -!- FUNCTION: Adapter protein that regulates different signaling pathways
CC (By similarity). Required for larval development and viability
CC (PubMed:27927209). Involved in negatively modulating pmk-1 p38/MAPK
CC signaling (PubMed:27927209). Involved in innate immunity, acting either
CC in a manner dependent upon, or independent of, the pmk-1 or pmk-3
CC p38/MAPK pathways (PubMed:18394898, PubMed:27927200, PubMed:34407394).
CC Has a protective role in response to infection by the Gram-negative
CC bacterium P.aeruginosa, acting by negatively modulating expression of
CC cebp-1, and regulating the pmk-1 p38/MAPK pathway, leading to
CC activation of transcription factor skn-1 (PubMed:27927200,
CC PubMed:34407394). Required to prevent P.aeruginosa toxin ToxA-mediated
CC lethality, probably acting via modulating the effects of translational
CC inhibition caused by the toxin (PubMed:27927200). By regulating the up-
CC regulation in the epidermis of antimicrobial peptides nlp-29 and nlp-
CC 31, plays a role in resistance to fungal infection (PubMed:18394898,
CC PubMed:27927200). {ECO:0000250|UniProtKB:Q9V3Z1,
CC ECO:0000269|PubMed:18394898, ECO:0000269|PubMed:27927200,
CC ECO:0000269|PubMed:27927209, ECO:0000269|PubMed:34407394}.
CC -!- SUBUNIT: May interact with transcription factor cebp-1 (via N-
CC terminus). {ECO:0000269|PubMed:27927209}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:27927209}.
CC -!- TISSUE SPECIFICITY: Expressed in epidermis, pharynx, intestine, a
CC subset of head neurons and motoneurons. {ECO:0000269|PubMed:18394898,
CC ECO:0000269|PubMed:27927209}.
CC -!- DEVELOPMENTAL STAGE: Expressed in the 3-fold stage embryo.
CC {ECO:0000269|PubMed:18394898}.
CC -!- DOMAIN: The protein kinase domain is predicted to be catalytically
CC inactive. {ECO:0000255|PROSITE-ProRule:PRU00159}.
CC -!- DISRUPTION PHENOTYPE: Arrested development at the second to third
CC larval stages (L2-L3) and lethality between 5-10 days after hatching
CC (PubMed:27927209). Small and dumpy body morphology at the second to
CC third larval stages (L2-L3), abnormal pharyngeal morphology, sterility
CC (PubMed:27927209). Growth and fertility defects are suppressed in a
CC cebp-1 mutant background (PubMed:27927209). Lethality is suppressed in
CC several mutant backgrounds, including tir-1, or kinases nsy-1, sek-1 or
CC mak-2 (PubMed:27927209). Levels of phosphorylated, active p38/MAPK pmk-
CC 1 are significantly increased (PubMed:27927209). Increased levels of
CC cebp-1 mRNA in multiple tissues (PubMed:27927209). RNAi-mediated
CC knockdown results in a loss of nlp-29 expression upon fungal infection
CC (PubMed:18394898). No other obvious phenotype (PubMed:18394898).
CC Knockdown results in a drastic reduction in transcription of gst-4 and
CC gcs-1 mRNAs during infection by P.aeruginosa or P.faecalis, or
CC treatment with the oxidant, arsenite (PubMed:34407394). RNAi-mediated
CC knockdown targeted to intestinal cells causes hypersusceptibility to
CC Gram-negative bacterium P.aeruginosa or to Gram-positive bacterium
CC E.faecalis and also to the P.aeruginosa toxin ToxA (PubMed:27927200,
CC PubMed:34407394). Simultaneous knockdown with vhp-1, targeted to
CC intestinal cells, results in partial rescue of the nipi-3 pathogen
CC sensitivity phenotype (PubMed:34407394). {ECO:0000269|PubMed:18394898,
CC ECO:0000269|PubMed:27927200, ECO:0000269|PubMed:27927209,
CC ECO:0000269|PubMed:34407394}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. {ECO:0000305}.
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DR EMBL; EU043523; ABW05091.1; -; mRNA.
DR EMBL; BX284606; CAB01883.3; -; Genomic_DNA.
DR RefSeq; NP_510573.3; NM_078172.6.
DR AlphaFoldDB; G5EED4; -.
DR SMR; G5EED4; -.
DR STRING; 6239.K09A9.1; -.
DR EPD; G5EED4; -.
DR PaxDb; G5EED4; -.
DR EnsemblMetazoa; K09A9.1.1; K09A9.1.1; WBGene00010700.
DR GeneID; 181650; -.
DR KEGG; cel:CELE_K09A9.1; -.
DR CTD; 181650; -.
DR WormBase; K09A9.1; CE42581; WBGene00010700; nipi-3.
DR eggNOG; ENOG502TG0H; Eukaryota.
DR HOGENOM; CLU_422256_0_0_1; -.
DR InParanoid; G5EED4; -.
DR OMA; GKYPFHE; -.
DR OrthoDB; 846202at2759; -.
DR PhylomeDB; G5EED4; -.
DR Reactome; R-CEL-1257604; PIP3 activates AKT signaling.
DR Reactome; R-CEL-165158; Activation of AKT2.
DR Reactome; R-CEL-199418; Negative regulation of the PI3K/AKT network.
DR Reactome; R-CEL-389357; CD28 dependent PI3K/Akt signaling.
DR Reactome; R-CEL-5218920; VEGFR2 mediated vascular permeability.
DR PRO; PR:G5EED4; -.
DR Proteomes; UP000001940; Chromosome X.
DR Bgee; WBGene00010700; Expressed in pharyngeal muscle cell (C elegans) and 4 other tissues.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0031434; F:mitogen-activated protein kinase kinase binding; IBA:GO_Central.
DR GO; GO:0004672; F:protein kinase activity; IEA:InterPro.
DR GO; GO:0050832; P:defense response to fungus; IMP:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR GO; GO:0043405; P:regulation of MAP kinase activity; IBA:GO_Central.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR024104; Tribbles/Ser_Thr_kinase_40.
DR PANTHER; PTHR22961; PTHR22961; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Nucleotide-binding; Nucleus; Reference proteome.
FT CHAIN 1..655
FT /note="Protein nipi-3"
FT /evidence="ECO:0000305"
FT /id="PRO_0000433603"
FT DOMAIN 200..470
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..35
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 20..34
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 206..214
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 235
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MUTAGEN 307
FT /note="I->N: In fr4; Susceptibility to fungal infection
FT characterized by a severe loss of nlp-29 and nlp-31
FT expression and a decrease in survival. Susceptibility to
FT bacterial pathogens P.aeruginosa or E.faecalis is
FT characterized by a decrease in survival rate; this
FT phenotype is abrogated in a cebp-1 mutant background.
FT Drastic reduction in transcription of gst-4 and gcs-1 mRNAs
FT during infection by P.aeruginosa or P.faecalis; this
FT phenotype is abrogated in a cebp-1 mutant background.
FT Increased level of vhp-1 mRNA during P.aeruginosa or
FT E.faecalis infection. Level of pmk-1 phosphorylation
FT reduced during E.faecalis infection, despite almost normal
FT overall level of pmk-1 protein. Animals have a temperature-
FT sensitive reduction in size. In absence of infection,
FT reduced survival rate. Dramatically reduced lifespan in
FT response to ToxA from Gram-negative bacterium P.aeruginosa.
FT Reduced viability in response to translational inhibitor,
FT G418."
FT /evidence="ECO:0000269|PubMed:18394898,
FT ECO:0000269|PubMed:27927200, ECO:0000269|PubMed:34407394"
SQ SEQUENCE 655 AA; 75748 MW; 8A19F1933A9F59AA CRC64;
MARTKCKTKT VANPRTGVRK TAKDLSEPVR QDAVSRRRPT TLPFVGNTSS RPRVFYDVLA
KKNVVFPNVK AEYHYRVRNA PKIDPKNFGT TLPICYSSIG PAKTLELRPL GRLPPHIIKA
LNDHYVQLTR GSMVPAADLY NNGDHPAEQR IPTMLNENEY LRLIQELEEE EKSKQFSATS
SSAPHVNPYS AQHLVNGEII GIFVIYGTGL VTRAVCSQTR EMFTAHVLPE WKASKVIDVI
RRLQIPTDIS SMTADEIRLS ELCISKRMEI IKSNDRYILM NPCESATIHS YATERLDEIT
ENDVMSIYQK VVEIVRFCHS RKVILQNFKP RSFYLKKDAH NKWVVRPCFL QDMSCEEDQS
EAQFTRRSVC VPFMAPEMLT AESRTHHSYS TELWGLGVLL YILLTGKYPF HENSMPLLFR
TIKFKQHRWP FNFISSKSRN IVNMLLKKAP ATRMNLEDLW NQVNGDFPEI RCRSNIILKK
QDMIVKMDLF EMYYNTYKDR LLPKNVLPMY EEMKACRNDS TILTEMAKRD FRSIQEQMKR
RIETKPTEYQ TLVMQVRLQQ INQLFFEKEV SQAQKQHRAP RLVQLKCSDI SKELLLPGDI
YPISEHYHPS QQPVDKVVYK LLSDANSLAF PTVMKGTVPK SYPPPVFKGL DISPS
