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 27-MAR-2024, entry version 162. DE RecName: Full=E3 ubiquitin-protein ligase pellino homolog 3 {ECO:0000305}; DE Short=Pellino-3 {ECO:0000303|PubMed:12874243}; DE EC=2.3.2.27 {ECO:0000269|PubMed:12874243, ECO:0000269|PubMed:17675297}; GN Name=PELI3 {ECO:0000312|HGNC:HGNC:30010}; 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, CATALYTIC RP ACTIVITY, PATHWAY, TISSUE SPECIFICITY, AND INTERACTION WITH TRAF6; MAP3K7 RP 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, CATALYTIC ACTIVITY, AND PATHWAY. 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 (PubMed:12874243, CC PubMed:17675297). Involved in the TLR and IL-1 signaling pathways via CC interaction with the complex containing IRAK kinases and TRAF6 CC (PubMed:12874243). Mediates 'Lys-63'-linked polyubiquitination of IRAK1 CC (PubMed:12874243). Can activate AP1/JUN and ELK1 (PubMed:12874243). CC Acts as a regulator of innate immunity by mediating 'Lys-63'-linked CC polyubiquitination of RIPK2 downstream of NOD1 and NOD2, thereby CC transforming RIPK2 into a scaffolding protein for downstream effectors, CC ultimately leading to activation of the NF-kappa-B and MAP kinases CC signaling (By similarity). Catalyzes 'Lys-63'-linked polyubiquitination CC of RIPK2 in parallel of XIAP (By similarity). CC {ECO:0000250|UniProtKB:Q8BXR6, ECO:0000269|PubMed:12874243, CC 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; Evidence={ECO:0000269|PubMed:12874243, CC ECO:0000269|PubMed:17675297}; CC -!- PATHWAY: Protein modification; protein ubiquitination. CC {ECO:0000269|PubMed:12874243, ECO:0000269|PubMed:17675297}. CC -!- SUBUNIT: Interacts with TRAF6, 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 {ECO:0000303|PubMed:12874243}, A CC {ECO:0000303|PubMed:12874243}; CC IsoId=Q8N2H9-1; Sequence=Displayed; CC Name=2; Synonyms=Beta {ECO:0000303|PubMed:12874243}, B CC {ECO:0000303|PubMed:12874243}; 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}; 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; 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; 45. 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; 9606-ENSP00000322532; -. DR PeptideAtlas; Q8N2H9; -. DR ProteomicsDB; 71701; -. [Q8N2H9-1] DR ProteomicsDB; 71702; -. [Q8N2H9-2] DR ProteomicsDB; 71703; -. [Q8N2H9-3] DR ProteomicsDB; 71704; -. [Q8N2H9-4] DR Antibodypedia; 30168; 156 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 AGR; HGNC:30010; -. DR CTD; 246330; -. DR DisGeNET; 246330; -. DR GeneCards; PELI3; -. DR HGNC; HGNC:30010; PELI3. DR HPA; ENSG00000174516; Tissue enhanced (brain). 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; VICERWP; -. DR OrthoDB; 4002880at2759; -. 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; 17 hits in 1187 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 186 other cell types or tissues. DR ExpressionAtlas; Q8N2H9; baseline and differential. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0061630; F:ubiquitin protein ligase activity; IBA:GO_Central. DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW. 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:0008592; P:regulation of Toll signaling pathway; IEA:InterPro. DR InterPro; IPR006800; Pellino_fam. DR InterPro; IPR048334; Pellino_FHA. DR InterPro; IPR048335; Pellino_RING. DR PANTHER; PTHR12098:SF9; E3 UBIQUITIN-PROTEIN LIGASE PELLINO HOMOLOG 3; 1. DR PANTHER; PTHR12098; E3 UBIQUITIN-PROTEIN LIGASE PELLINO-RELATED; 1. DR Pfam; PF04710; Pellino_FHA; 1. DR Pfam; PF20723; Pellino_RING; 1. DR PIRSF; PIRSF038886; Pellino; 1. DR Genevisible; Q8N2H9; HS. PE 1: Evidence at protein level; KW Alternative splicing; Immunity; Innate immunity; Phosphoprotein; KW Reference proteome; Transferase; 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 //