WWP1_CAEEL
ID WWP1_CAEEL Reviewed; 794 AA.
AC Q9N2Z7; Q95XU3; V6CJJ8; V6CLY4;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 2.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=E3 ubiquitin-protein ligase wwp-1 {ECO:0000255|PIRNR:PIRNR001569, ECO:0000305};
DE EC=2.3.2.26 {ECO:0000255|PIRNR:PIRNR001569};
GN Name=wwp-1 {ECO:0000312|WormBase:Y65B4BR.4a};
GN ORFNames=Y65B4BR.4 {ECO:0000312|WormBase:Y65B4BR.4a};
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, CATALYTIC ACTIVITY, PATHWAY, INTERACTION WITH UBC-18, TISSUE
RP SPECIFICITY, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF CYS-762.
RX PubMed=19553937; DOI=10.1038/nature08130;
RA Carrano A.C., Liu Z., Dillin A., Hunter T.;
RT "A conserved ubiquitination pathway determines longevity in response to
RT diet restriction.";
RL Nature 460:396-399(2009).
RN [3] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=20209166; DOI=10.1371/journal.pone.0009494;
RA Chen C.S., Bellier A., Kao C.Y., Yang Y.L., Chen H.D., Los F.C.,
RA Aroian R.V.;
RT "WWP-1 is a novel modulator of the DAF-2 insulin-like signaling network
RT involved in pore-forming toxin cellular defenses in Caenorhabditis
RT elegans.";
RL PLoS ONE 5:e9494-e9494(2010).
RN [4] {ECO:0000305}
RP FUNCTION, INTERACTION WITH KLF-1, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF
RP CYS-762.
RX PubMed=24805825; DOI=10.1038/ncomms4772;
RA Carrano A.C., Dillin A., Hunter T.;
RT "A Krueppel-like factor downstream of the E3 ligase WWP-1 mediates dietary-
RT restriction-induced longevity in Caenorhabditis elegans.";
RL Nat. Commun. 5:3772-3772(2014).
CC -!- FUNCTION: E3 ubiquitin-protein ligase which accepts ubiquitin from an
CC E2 ubiquitin-conjugating enzyme in the form of a thioester and then
CC directly transfers the ubiquitin to targeted substrates
CC (PubMed:24805825, PubMed:19553937). Ubiquitinates klf-1
CC (PubMed:24805825). Required for diet restriction-mediated lifespan
CC extension, acting in concert with Kruppel-like factor klf-1 in the
CC intestine to perhaps modulate genes involved in lipid metabolism
CC (PubMed:24805825, PubMed:19553937). Probably acting downstream of the
CC Insulin/IGF-1-like signaling (IIS) mediated pathway, plays a role in
CC the immune response to infection by the Gram-negative bacterium
CC P.aeruginosa, at least partly in response to bacterial pore-forming
CC toxins (PubMed:20209166). {ECO:0000269|PubMed:19553937,
CC ECO:0000269|PubMed:20209166, ECO:0000269|PubMed:24805825}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.26; Evidence={ECO:0000255|PIRNR:PIRNR001569,
CC ECO:0000269|PubMed:19553937};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000255|PIRNR:PIRNR001569, ECO:0000269|PubMed:19553937}.
CC -!- SUBUNIT: Interacts (via WW domains) with Kruppel-like factor klf-1
CC (PubMed:24805825). Interacts with ubiquitin-conjugating enzyme E2 ubc-
CC 18 (PubMed:19553937). {ECO:0000269|PubMed:19553937,
CC ECO:0000269|PubMed:24805825}.
CC -!- INTERACTION:
CC Q9N2Z7; Q9XXI4: arrd-7; NbExp=3; IntAct=EBI-317369, EBI-330020;
CC Q9N2Z7; P39055: dyn-1; NbExp=3; IntAct=EBI-317369, EBI-317945;
CC Q9N2Z7; G5ED33: eps-8; NbExp=3; IntAct=EBI-317369, EBI-2315916;
CC Q9N2Z7; Q21633: ubc-18; NbExp=3; IntAct=EBI-317369, EBI-325980;
CC Q9N2Z7; Q18966: wbp-2; NbExp=3; IntAct=EBI-317369, EBI-318634;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=a {ECO:0000312|WormBase:Y65B4BR.4a};
CC IsoId=Q9N2Z7-1; Sequence=Displayed;
CC Name=b {ECO:0000312|WormBase:Y65B4BR.4b};
CC IsoId=Q9N2Z7-2; Sequence=VSP_061030;
CC Name=c {ECO:0000312|WormBase:Y65B4BR.4c};
CC IsoId=Q9N2Z7-3; Sequence=VSP_061029;
CC Name=d {ECO:0000312|WormBase:Y65B4BR.4d};
CC IsoId=Q9N2Z7-4; Sequence=VSP_061029, VSP_061030;
CC -!- TISSUE SPECIFICITY: Expressed in neurons localized in the head and tail
CC of adults. {ECO:0000269|PubMed:19553937}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown increases sensitivity to
CC paraquat, and reduces lifespan at 25 degrees Celsius, but not at 20
CC degrees Celsius (PubMed:19553937). Causes reduced ability of dietary
CC restriction to extend lifespan (PubMed:24805825, PubMed:19553937).
CC Abolishes lifespan extension completely on an eat-2 mutant background,
CC independent of whether knockdown is ubiquitous, or targeted only to the
CC intestine (PubMed:24805825, PubMed:19553937). Does not suppress
CC extended lifespans of isp-1 or daf-2 mutants (PubMed:19553937).
CC Hypersensitive to bacterial pore-forming toxin (PubMed:20209166).
CC {ECO:0000269|PubMed:19553937, ECO:0000269|PubMed:20209166,
CC ECO:0000269|PubMed:24805825}.
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DR EMBL; BX284601; CCD71932.1; -; Genomic_DNA.
DR EMBL; BX284601; CCD71931.1; -; Genomic_DNA.
DR EMBL; BX284601; CDK13616.1; -; Genomic_DNA.
DR EMBL; BX284601; CDK13617.1; -; Genomic_DNA.
DR RefSeq; NP_001293271.1; NM_001306342.1. [Q9N2Z7-3]
DR RefSeq; NP_001293272.1; NM_001306343.1. [Q9N2Z7-4]
DR RefSeq; NP_740775.1; NM_170794.6. [Q9N2Z7-1]
DR RefSeq; NP_740776.1; NM_171831.3. [Q9N2Z7-2]
DR AlphaFoldDB; Q9N2Z7; -.
DR SMR; Q9N2Z7; -.
DR DIP; DIP-25758N; -.
DR IntAct; Q9N2Z7; 40.
DR MINT; Q9N2Z7; -.
DR STRING; 6239.Y65B4BR.4a; -.
DR EPD; Q9N2Z7; -.
DR PaxDb; Q9N2Z7; -.
DR PeptideAtlas; Q9N2Z7; -.
DR EnsemblMetazoa; Y65B4BR.4a.1; Y65B4BR.4a.1; WBGene00007009. [Q9N2Z7-1]
DR EnsemblMetazoa; Y65B4BR.4b.1; Y65B4BR.4b.1; WBGene00007009. [Q9N2Z7-2]
DR EnsemblMetazoa; Y65B4BR.4c.1; Y65B4BR.4c.1; WBGene00007009. [Q9N2Z7-3]
DR EnsemblMetazoa; Y65B4BR.4d.1; Y65B4BR.4d.1; WBGene00007009. [Q9N2Z7-4]
DR GeneID; 171647; -.
DR KEGG; cel:CELE_Y65B4BR.4; -.
DR UCSC; Y65B4BR.4b; c. elegans.
DR CTD; 171647; -.
DR WormBase; Y65B4BR.4a; CE31384; WBGene00007009; wwp-1.
DR WormBase; Y65B4BR.4b; CE31385; WBGene00007009; wwp-1.
DR WormBase; Y65B4BR.4c; CE49230; WBGene00007009; wwp-1.
DR WormBase; Y65B4BR.4d; CE49306; WBGene00007009; wwp-1.
DR eggNOG; KOG0940; Eukaryota.
DR GeneTree; ENSGT00940000154635; -.
DR HOGENOM; CLU_002173_0_0_1; -.
DR InParanoid; Q9N2Z7; -.
DR OMA; NMAIEMT; -.
DR OrthoDB; 167687at2759; -.
DR PhylomeDB; Q9N2Z7; -.
DR Reactome; R-CEL-1253288; Downregulation of ERBB4 signaling.
DR Reactome; R-CEL-2672351; Stimuli-sensing channels.
DR Reactome; R-CEL-5610780; Degradation of GLI1 by the proteasome.
DR Reactome; R-CEL-5632684; Hedgehog 'on' state.
DR Reactome; R-CEL-8948751; Regulation of PTEN stability and activity.
DR Reactome; R-CEL-9013420; RHOU GTPase cycle.
DR Reactome; R-CEL-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; Q9N2Z7; -.
DR UniPathway; UPA00143; -.
DR Proteomes; UP000001940; Chromosome I.
DR Bgee; WBGene00007009; Expressed in embryo and 4 other tissues.
DR ExpressionAtlas; Q9N2Z7; baseline and differential.
DR GO; GO:0005737; C:cytoplasm; IDA:WormBase.
DR GO; GO:0061631; F:ubiquitin conjugating enzyme activity; IDA:WormBase.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IBA:GO_Central.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; IMP:UniProtKB.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IMP:UniProtKB.
DR GO; GO:0008340; P:determination of adult lifespan; IMP:UniProtKB.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR GO; GO:0000209; P:protein polyubiquitination; IBA:GO_Central.
DR GO; GO:0016567; P:protein ubiquitination; IDA:WormBase.
DR GO; GO:0042176; P:regulation of protein catabolic process; IMP:WormBase.
DR CDD; cd00078; HECTc; 1.
DR CDD; cd00201; WW; 4.
DR Gene3D; 2.60.40.150; -; 1.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR024928; E3_ub_ligase_SMURF1.
DR InterPro; IPR000569; HECT_dom.
DR InterPro; IPR035983; Hect_E3_ubiquitin_ligase.
DR InterPro; IPR001202; WW_dom.
DR InterPro; IPR036020; WW_dom_sf.
DR Pfam; PF00168; C2; 1.
DR Pfam; PF00632; HECT; 1.
DR Pfam; PF00397; WW; 4.
DR PIRSF; PIRSF001569; E3_ub_ligase_SMURF1; 1.
DR SMART; SM00239; C2; 1.
DR SMART; SM00119; HECTc; 1.
DR SMART; SM00456; WW; 4.
DR SUPFAM; SSF49562; SSF49562; 1.
DR SUPFAM; SSF51045; SSF51045; 4.
DR SUPFAM; SSF56204; SSF56204; 1.
DR PROSITE; PS50004; C2; 1.
DR PROSITE; PS50237; HECT; 1.
DR PROSITE; PS01159; WW_DOMAIN_1; 4.
DR PROSITE; PS50020; WW_DOMAIN_2; 4.
PE 1: Evidence at protein level;
KW Alternative splicing; Reference proteome; Repeat; Transferase;
KW Ubl conjugation pathway.
FT CHAIN 1..794
FT /note="E3 ubiquitin-protein ligase wwp-1"
FT /id="PRO_0000452646"
FT DOMAIN 10..124
FT /note="C2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 219..252
FT /note="WW 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00224"
FT DOMAIN 253..286
FT /note="WW 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00224"
FT DOMAIN 324..358
FT /note="WW 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00224"
FT DOMAIN 366..399
FT /note="WW 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00224"
FT DOMAIN 460..794
FT /note="HECT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00104"
FT REGION 1..31
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 155..198
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 162..187
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 762
FT /note="Glycyl thioester intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00104"
FT VAR_SEQ 1..287
FT /note="Missing (in isoform c and isoform d)"
FT /id="VSP_061029"
FT VAR_SEQ 361..362
FT /note="Missing (in isoform b and isoform d)"
FT /id="VSP_061030"
FT MUTAGEN 762
FT /note="C->A: Abolishes ubiquitin ligation activity;
FT prevents ubiquitination of Kruppel-like factor klf-1."
FT /evidence="ECO:0000269|PubMed:19553937,
FT ECO:0000269|PubMed:24805825"
SQ SEQUENCE 794 AA; 90922 MW; 2080537AF4630BE5 CRC64;
MARNEPSSQQ PSSSGSNGTP AQQNGSAKPS KVTVKVVNAS FTKAADCYVE ITSDTSSAAP
KKTTVKKKTM APEWNEHLNV HANESSTISF RLLQKAKLFD DTCLGMAKLK LSSLTRNENG
EFKNDINNIS LLAKDSSKIG TLNIIFSGYP ERKRRSAGVR AETAASASSE ASTSNGVATS
SSARRPATAK RDTLAAPTST AAAAAAATAG GTPAAGAEEQ LPDGWEMRFD QYGRKYYVDH
TTKSTTWERP STQPLPQGWE MRRDPRGRVY YVDHNTRTTT WQRPTADMLE AHEQWQSGRD
QAMLQWEQRF LLQQNNFSAD DPLGPLPEGW EKRQDPNTSR MYFVNHVNRT TQWEDPRTQG
FRGSDQPLPD GWEMRFTEQG VPFFIDHQSK TTTYNDPRTG KPVGPLGVVG VQMAMEKSFR
WKIAQFRYLC LSNSVPNHVK ITVSRNNVFE DSFQEIMRKN AVDLRRRLYI QFRGEEGLDY
GGVAREWFFL LSHEVLNPMY CLFMYAGNNN YSLQINPASF VNPDHLKYFE YIGRFIAMAL
FHGKFIYSGF TMPFYKKMLN KKIVLKDIEQ VDSEIYNSLM WIKDNNIDEC DMELYFVADY
ELLGELKTYE LKEGGTEIAV TEENKLEYIE LLVEWRFNRG VEQQTKAFFT GFNSVFPLEW
MQYFDERELE LLLCGMQDVD VDDWQRNTVY RHYAPQSKQV TWFWQWVRSL DQEKRARLLQ
FVTGTCRVPV GGFSELMGST GPQLFCIERV GKENWLPRSH TCFNRLDLPP YRSYDQLVEK
LSMAIEMTEG FGNE
