PELI3_HUMAN
ID PELI3_HUMAN Reviewed; 469 AA.
AC Q8N2H9; Q8N3E1; Q8N9Q6; Q8TAW7; Q8TED5;
DT 24-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 24-OCT-2003, sequence version 2.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=E3 ubiquitin-protein ligase pellino homolog 3;
DE Short=Pellino-3;
DE EC=2.3.2.27;
DE AltName: Full=RING-type E3 ubiquitin transferase pellino homolog 3 {ECO:0000305};
GN Name=PELI3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, TISSUE
RP SPECIFICITY, AND INTERACTION WITH IRAK1; TRAF6; MAP3K7 AND MAP3K14.
RX PubMed=12874243; DOI=10.4049/jimmunol.171.3.1500;
RA Jensen L.E., Whitehead A.S.;
RT "Pellino3, a novel member of the Pellino protein family, promotes
RT activation of c-Jun and Elk-1 and may act as a scaffolding protein.";
RL J. Immunol. 171:1500-1506(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Adipose tissue, Thyroid, and Uterus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Amygdala;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 4).
RC TISSUE=Brain, and Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP PHOSPHORYLATION BY IRAK1.
RX PubMed=17997719; DOI=10.1042/bj20071365;
RA Ordureau A., Smith H., Windheim M., Peggie M., Carrick E., Morrice N.,
RA Cohen P.;
RT "The IRAK-catalysed activation of the E3 ligase function of Pellino
RT isoforms induces the Lys63-linked polyubiquitination of IRAK1.";
RL Biochem. J. 409:43-52(2008).
RN [6]
RP FUNCTION.
RX PubMed=17675297; DOI=10.1074/jbc.m704558200;
RA Butler M.P., Hanly J.A., Moynagh P.N.;
RT "Kinase-active interleukin-1 receptor-associated kinases promote
RT polyubiquitination and degradation of the Pellino family: direct evidence
RT for PELLINO proteins being ubiquitin-protein isopeptide ligases.";
RL J. Biol. Chem. 282:29729-29737(2007).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-11, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
CC -!- FUNCTION: E3 ubiquitin ligase catalyzing the covalent attachment of
CC ubiquitin moieties onto substrate proteins. Involved in the TLR and IL-
CC 1 signaling pathways via interaction with the complex containing IRAK
CC kinases and TRAF6. Mediates 'Lys-63'-linked polyubiquitination of
CC IRAK1. Can activate AP1/JUN and ELK1. Not required for NF-kappa-B
CC activation. {ECO:0000269|PubMed:12874243, ECO:0000269|PubMed:17675297}.
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=2.3.2.27;
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts with TRAF6, IRAK1, MAP3K14 and MAP3K7.
CC {ECO:0000269|PubMed:12874243}.
CC -!- INTERACTION:
CC Q8N2H9; Q92569: PIK3R3; NbExp=3; IntAct=EBI-448457, EBI-79893;
CC Q8N2H9-2; P51617: IRAK1; NbExp=2; IntAct=EBI-448472, EBI-358664;
CC Q8N2H9-4; P41091: EIF2S3; NbExp=3; IntAct=EBI-25852006, EBI-1054228;
CC Q8N2H9-4; O75460-2: ERN1; NbExp=3; IntAct=EBI-25852006, EBI-25852368;
CC Q8N2H9-4; Q0VDC6: FKBP1A; NbExp=3; IntAct=EBI-25852006, EBI-10226858;
CC Q8N2H9-4; P54652: HSPA2; NbExp=3; IntAct=EBI-25852006, EBI-356991;
CC Q8N2H9-4; P49591: SARS1; NbExp=3; IntAct=EBI-25852006, EBI-1053431;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=Alpha, A;
CC IsoId=Q8N2H9-1; Sequence=Displayed;
CC Name=2; Synonyms=Beta, B;
CC IsoId=Q8N2H9-2; Sequence=VSP_008640;
CC Name=3;
CC IsoId=Q8N2H9-3; Sequence=VSP_008639;
CC Name=4;
CC IsoId=Q8N2H9-4; Sequence=VSP_008641, VSP_008642;
CC -!- TISSUE SPECIFICITY: Highly expressed in brain, heart and testis, and at
CC lower level in kidney, liver, lung, placenta, small intestine, spleen
CC and stomach. Isoform 1 is not expressed in lung.
CC {ECO:0000269|PubMed:12874243}.
CC -!- PTM: Phosphorylated by IRAK1 enhancing its E3 ligase activity.
CC {ECO:0000269|PubMed:17997719}.
CC -!- SIMILARITY: Belongs to the pellino family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC11499.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF487456; AAO49465.1; -; mRNA.
DR EMBL; AF487457; AAO49466.1; -; mRNA.
DR EMBL; AK074201; BAB85015.1; -; mRNA.
DR EMBL; AK075253; BAC11499.1; ALT_INIT; mRNA.
DR EMBL; AK094060; BAC04275.1; -; mRNA.
DR EMBL; AL834395; CAD39057.1; -; mRNA.
DR EMBL; BC021256; AAH21256.1; -; mRNA.
DR EMBL; BC025723; AAH25723.1; -; mRNA.
DR CCDS; CCDS31615.1; -. [Q8N2H9-1]
DR CCDS; CCDS41675.1; -. [Q8N2H9-2]
DR CCDS; CCDS73328.1; -. [Q8N2H9-3]
DR RefSeq; NP_001091980.1; NM_001098510.1. [Q8N2H9-2]
DR RefSeq; NP_001230064.1; NM_001243135.1. [Q8N2H9-3]
DR RefSeq; NP_001230065.1; NM_001243136.1.
DR RefSeq; NP_659502.2; NM_145065.2. [Q8N2H9-1]
DR RefSeq; XP_011543186.1; XM_011544884.2. [Q8N2H9-1]
DR RefSeq; XP_016872954.1; XM_017017465.1.
DR AlphaFoldDB; Q8N2H9; -.
DR SMR; Q8N2H9; -.
DR BioGRID; 128900; 43.
DR DIP; DIP-31770N; -.
DR IntAct; Q8N2H9; 11.
DR MINT; Q8N2H9; -.
DR STRING; 9606.ENSP00000322532; -.
DR iPTMnet; Q8N2H9; -.
DR PhosphoSitePlus; Q8N2H9; -.
DR BioMuta; PELI3; -.
DR DMDM; 37999712; -.
DR EPD; Q8N2H9; -.
DR jPOST; Q8N2H9; -.
DR MassIVE; Q8N2H9; -.
DR PaxDb; Q8N2H9; -.
DR PeptideAtlas; Q8N2H9; -.
DR PRIDE; Q8N2H9; -.
DR ProteomicsDB; 71701; -. [Q8N2H9-1]
DR ProteomicsDB; 71702; -. [Q8N2H9-2]
DR ProteomicsDB; 71703; -. [Q8N2H9-3]
DR ProteomicsDB; 71704; -. [Q8N2H9-4]
DR Antibodypedia; 30168; 139 antibodies from 19 providers.
DR DNASU; 246330; -.
DR Ensembl; ENST00000320740.12; ENSP00000322532.7; ENSG00000174516.15. [Q8N2H9-1]
DR Ensembl; ENST00000349459.10; ENSP00000309848.8; ENSG00000174516.15. [Q8N2H9-2]
DR Ensembl; ENST00000524466.5; ENSP00000434677.1; ENSG00000174516.15. [Q8N2H9-4]
DR Ensembl; ENST00000618547.4; ENSP00000484220.1; ENSG00000174516.15. [Q8N2H9-3]
DR GeneID; 246330; -.
DR KEGG; hsa:246330; -.
DR MANE-Select; ENST00000320740.12; ENSP00000322532.7; NM_145065.3; NP_659502.2.
DR UCSC; uc001oib.3; human. [Q8N2H9-1]
DR CTD; 246330; -.
DR DisGeNET; 246330; -.
DR GeneCards; PELI3; -.
DR HGNC; HGNC:30010; PELI3.
DR HPA; ENSG00000174516; Low tissue specificity.
DR MIM; 609827; gene.
DR neXtProt; NX_Q8N2H9; -.
DR OpenTargets; ENSG00000174516; -.
DR PharmGKB; PA142671185; -.
DR VEuPathDB; HostDB:ENSG00000174516; -.
DR eggNOG; KOG3842; Eukaryota.
DR GeneTree; ENSGT00950000183050; -.
DR HOGENOM; CLU_029221_0_0_1; -.
DR InParanoid; Q8N2H9; -.
DR OMA; LLWRTPT; -.
DR PhylomeDB; Q8N2H9; -.
DR TreeFam; TF314338; -.
DR PathwayCommons; Q8N2H9; -.
DR Reactome; R-HSA-9020702; Interleukin-1 signaling.
DR Reactome; R-HSA-937039; IRAK1 recruits IKK complex.
DR Reactome; R-HSA-975144; IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation.
DR SignaLink; Q8N2H9; -.
DR SIGNOR; Q8N2H9; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 246330; 16 hits in 1108 CRISPR screens.
DR ChiTaRS; PELI3; human.
DR GenomeRNAi; 246330; -.
DR Pharos; Q8N2H9; Tbio.
DR PRO; PR:Q8N2H9; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q8N2H9; protein.
DR Bgee; ENSG00000174516; Expressed in Brodmann (1909) area 23 and 184 other tissues.
DR ExpressionAtlas; Q8N2H9; baseline and differential.
DR Genevisible; Q8N2H9; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IBA:GO_Central.
DR GO; GO:2001237; P:negative regulation of extrinsic apoptotic signaling pathway; IMP:MGI.
DR GO; GO:0010804; P:negative regulation of tumor necrosis factor-mediated signaling pathway; IMP:MGI.
DR GO; GO:0070534; P:protein K63-linked ubiquitination; IBA:GO_Central.
DR GO; GO:0000209; P:protein polyubiquitination; IBA:GO_Central.
DR GO; GO:0008592; P:regulation of Toll signaling pathway; IEA:InterPro.
DR InterPro; IPR006800; Pellino_fam.
DR PANTHER; PTHR12098; PTHR12098; 1.
DR Pfam; PF04710; Pellino; 1.
DR PIRSF; PIRSF038886; Pellino; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Phosphoprotein; Reference proteome; Transferase;
KW Ubl conjugation pathway.
FT CHAIN 1..469
FT /note="E3 ubiquitin-protein ligase pellino homolog 3"
FT /id="PRO_0000194176"
FT REGION 1..39
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 11..25
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 11
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 48..110
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_008639"
FT VAR_SEQ 52..75
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12874243,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_008640"
FT VAR_SEQ 282..331
FT /note="ENESNVLQDGSLIDLCGATLLWRTPAGLLRAPTLKQLEAQRQEANAARPQ
FT -> GGPLHSPPLSLPGPHKLPIPLPKPGDDLQSFCPREPQQAPYQGIPGPGGS (in
FT isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_008641"
FT VAR_SEQ 332..469
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_008642"
FT VARIANT 287
FT /note="V -> M (in dbSNP:rs34989499)"
FT /id="VAR_061502"
FT CONFLICT 73
FT /note="H -> L (in Ref. 2; BAB85015)"
FT /evidence="ECO:0000305"
FT CONFLICT 109
FT /note="H -> L (in Ref. 2; BAB85015)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 469 AA; 50755 MW; 7E14D1405B023F96 CRC64;
MVLEGNPEVG SPRTSDLQHR GNKGSCVLSS PGEDAQPGEE PIKYGELIVL GCCEEGGEET
EAQRGEVTGP RAHSCYNGCL ASGDKGRRRS RLALSRRSHA NGVKPDVMHH ISTPLVSKAL
SNRGQHSISY TLSRSHSVIV EYTHDSDTDM FQIGRSTENM IDFVVTDTSP GGGAAEGPSA
QSTISRYACR ILCDRRPPYT ARIYAAGFDA SSNIFLGERA AKWRTPDGLM DGLTTNGVLV
MHPAGGFSED SAPGVWREIS VCGNVYTLRD SRSAQQRGKL VENESNVLQD GSLIDLCGAT
LLWRTPAGLL RAPTLKQLEA QRQEANAARP QCPVGLSTLA FPSPARGRTA PDKQQPWVYV
RCGHVHGYHG WGCRRERGPQ ERECPLCRLV GPYVPLWLGQ EAGLCLDPGP PSHAFAPCGH
VCSEKTARYW AQTPLPHGTH AFHAACPFCG AWLTGEHGCV RLIFQGPLD
