PELI1_HUMAN
ID PELI1_HUMAN Reviewed; 418 AA.
AC Q96FA3; Q96SM0; Q9GZY5; Q9HCX0;
DT 24-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 24-OCT-2003, sequence version 2.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=E3 ubiquitin-protein ligase pellino homolog 1;
DE Short=Pellino-1;
DE EC=2.3.2.27 {ECO:0000269|PubMed:29883609};
DE AltName: Full=Pellino-related intracellular-signaling molecule;
DE AltName: Full=RING-type E3 ubiquitin transferase pellino homolog 1 {ECO:0000305};
GN Name=PELI1; Synonyms=PRISM;
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].
RC TISSUE=Thymus;
RX PubMed=11132151; DOI=10.1007/s002510000249;
RA Rich T., Allen R.L., Lucas A.-M., Trowsdale J.;
RT "Pellino-related sequences from Caenorhabditis elegans and Homo sapiens.";
RL Immunogenetics 52:145-149(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=11306823; DOI=10.1159/000056895;
RA Resch K., Jockusch H., Schmitt-John T.;
RT "Assignment of homologous genes, Peli1/PELI1 and Peli2/PELI2, for the Pelle
RT adaptor protein Pellino to mouse chromosomes 11 and 14 and human
RT chromosomes 2p13.3 and 14q21, respectively, by physical and radiation
RT hybrid mapping.";
RL Cytogenet. Cell Genet. 92:172-174(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Kennedy E.J., Moynagh P.N.;
RT "PRISM, a novel mediator of Toll/IL-1 signalling.";
RL Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Ovary, Placenta, and Testis;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 78-418.
RC TISSUE=Teratocarcinoma;
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 [6]
RP FUNCTION, AND INTERACTION WITH IRAK1; IRAK4 AND TRAF6.
RX PubMed=12496252; DOI=10.1074/jbc.m212112200;
RA Jiang Z., Johnson H.J., Nie H., Qin J., Bird T.A., Li X.;
RT "Pellino 1 is required for interleukin-1 (IL-1)-mediated signaling through
RT its interaction with the IL-1 receptor-associated kinase 4 (IRAK4)-IRAK-
RT tumor necrosis factor receptor-associated factor 6 (TRAF6) complex.";
RL J. Biol. Chem. 278:10952-10956(2003).
RN [7]
RP INTERACTION WITH TRAF6 AND MAP3K7.
RX PubMed=12804775; DOI=10.1016/s0014-5793(03)00533-7;
RA Jensen L.E., Whitehead A.S.;
RT "Pellino2 activates the mitogen activated protein kinase pathway.";
RL FEBS Lett. 545:199-202(2003).
RN [8]
RP INTERACTION WITH IRAK1; IRAK4; MYD88; SMAD6 AND TRAF6.
RX PubMed=16951688; DOI=10.1038/ni1383;
RA Choi K.C., Lee Y.S., Lim S., Choi H.K., Lee C.H., Lee E.K., Hong S.,
RA Kim I.H., Kim S.J., Park S.H.;
RT "Smad6 negatively regulates interleukin 1-receptor-Toll-like receptor
RT signaling through direct interaction with the adapter Pellino-1.";
RL Nat. Immunol. 7:1057-1065(2006).
RN [9]
RP FUNCTION AS E3 UBIQUITIN LIGASE.
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 [10]
RP PHOSPHORYLATION BY IRAK1 AND IRAK4.
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 [11]
RP SUMOYLATION.
RX PubMed=21120624; DOI=10.1007/s10059-011-0006-x;
RA Kim J.H., Sung K.S., Jung S.M., Lee Y.S., Kwon J.Y., Choi C.Y., Park S.H.;
RT "Pellino-1, an adaptor protein of interleukin-1 receptor/toll-like receptor
RT signaling, is sumoylated by Ubc9.";
RL Mol. Cells 31:85-89(2011).
RN [12]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH RIPK1; IRAK1 AND RIPK3,
RP MUTAGENESIS OF ARG-104; HIS-313 AND CYS-336, REGION RING-LIKE DOMAIN, AND
RP TISSUE SPECIFICITY.
RX PubMed=29883609; DOI=10.1016/j.molcel.2018.05.016;
RA Choi S.W., Park H.H., Kim S., Chung J.M., Noh H.J., Kim S.K., Song H.K.,
RA Lee C.W., Morgan M.J., Kang H.C., Kim Y.S.;
RT "PELI1 selectively targets kinase-active RIP3 for ubiquitylation-dependent
RT proteasomal degradation.";
RL Mol. Cell 70:920-935(2018).
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 IRAK1
CC allowing subsequent NF-kappa-B activation (PubMed:12496252,
CC PubMed:17675297). Mediates 'Lys-48'-linked polyubiquitination of RIPK3
CC leading to its subsequent proteasome-dependent degradation;
CC preferentially recognizes and mediates the degradation of the 'Thr-182'
CC phosphorylated form of RIPK3 (PubMed:29883609). Negatively regulates
CC necroptosis by reducing RIPK3 expression (PubMed:29883609). Mediates
CC 'Lys-63'-linked ubiquitination of RIPK1 (PubMed:29883609).
CC {ECO:0000269|PubMed:12496252, ECO:0000269|PubMed:17675297,
CC ECO:0000269|PubMed:29883609}.
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:29883609};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts with MAP3K7. Upon IL1B treatment, forms a complex
CC with TRAF6, IRAK1, IRAK4 and MYD88; this complex recruits MAP3K7/TAK1,
CC TAB1 and TAB2 to mediate NF-kappa-B activation. Direct binding of SMAD6
CC to PELI1 prevents the complex formation and hence negatively regulates
CC IL1R-TLR signaling and eventually NF-kappa-B-mediated gene expression
CC (PubMed:12496252, PubMed:12804775, PubMed:16951688). Interacts (via
CC atypical FHA domain) with RIPK3; preferentially binds to the 'Thr-182'
CC phosphorylated form of RIPK3 (PubMed:29883609). Interacts with RIPK1
CC and IRAK1 (PubMed:29883609). {ECO:0000269|PubMed:12496252,
CC ECO:0000269|PubMed:12804775, ECO:0000269|PubMed:16951688,
CC ECO:0000269|PubMed:29883609}.
CC -!- INTERACTION:
CC Q96FA3; Q6ZS10: CLEC17A; NbExp=3; IntAct=EBI-448369, EBI-11977093;
CC Q96FA3; Q8N137: CNTROB; NbExp=3; IntAct=EBI-448369, EBI-947360;
CC Q96FA3; O14653: GOSR2; NbExp=3; IntAct=EBI-448369, EBI-4401517;
CC Q96FA3; P42858: HTT; NbExp=3; IntAct=EBI-448369, EBI-466029;
CC Q96FA3; Q15735: INPP5J; NbExp=3; IntAct=EBI-448369, EBI-10236940;
CC Q96FA3; P51617: IRAK1; NbExp=4; IntAct=EBI-448369, EBI-358664;
CC Q96FA3; Q9NWZ3: IRAK4; NbExp=6; IntAct=EBI-448369, EBI-448378;
CC Q96FA3; P80188: LCN2; NbExp=3; IntAct=EBI-448369, EBI-11911016;
CC Q96FA3; P02545: LMNA; NbExp=3; IntAct=EBI-448369, EBI-351935;
CC Q96FA3; Q13442: PDAP1; NbExp=3; IntAct=EBI-448369, EBI-1390763;
CC Q96FA3; D3DTS7: PMP22; NbExp=3; IntAct=EBI-448369, EBI-25882629;
CC Q96FA3; Q9H426: RIMS4; NbExp=3; IntAct=EBI-448369, EBI-6660974;
CC Q96FA3; Q9H3D4: TP63; NbExp=3; IntAct=EBI-448369, EBI-2337775;
CC Q96FA3; Q15645: TRIP13; NbExp=3; IntAct=EBI-448369, EBI-358993;
CC Q96FA3; Q08AM6: VAC14; NbExp=3; IntAct=EBI-448369, EBI-2107455;
CC Q96FA3; Q9Y3C0: WASHC3; NbExp=3; IntAct=EBI-448369, EBI-712969;
CC -!- TISSUE SPECIFICITY: Expressed at high levels in normal skin but
CC decreased in keratinocytes from toxic epidermal necrolysis (TEN)
CC patients (at protein level). {ECO:0000269|PubMed:29883609}.
CC -!- PTM: Phosphorylation by IRAK1 and IRAK4 enhances its E3 ligase
CC activity. {ECO:0000269|PubMed:17997719}.
CC -!- PTM: Sumoylated. {ECO:0000269|PubMed:21120624}.
CC -!- SIMILARITY: Belongs to the pellino family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH11419.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAB55280.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AJ278859; CAC04320.1; -; mRNA.
DR EMBL; AF302505; AAG15393.1; -; mRNA.
DR EMBL; AF300987; AAG17451.1; -; mRNA.
DR EMBL; BC011419; AAH11419.1; ALT_INIT; mRNA.
DR EMBL; BC050019; AAH50019.1; -; mRNA.
DR EMBL; BC063611; AAH63611.1; -; mRNA.
DR EMBL; AK027668; BAB55280.1; ALT_INIT; mRNA.
DR CCDS; CCDS1876.1; -.
DR RefSeq; NP_065702.2; NM_020651.3.
DR RefSeq; XP_011531296.1; XM_011532994.2.
DR RefSeq; XP_016860009.1; XM_017004520.1.
DR AlphaFoldDB; Q96FA3; -.
DR SMR; Q96FA3; -.
DR BioGRID; 121418; 60.
DR CORUM; Q96FA3; -.
DR DIP; DIP-32488N; -.
DR IntAct; Q96FA3; 28.
DR MINT; Q96FA3; -.
DR STRING; 9606.ENSP00000351789; -.
DR iPTMnet; Q96FA3; -.
DR PhosphoSitePlus; Q96FA3; -.
DR BioMuta; PELI1; -.
DR DMDM; 37999756; -.
DR EPD; Q96FA3; -.
DR MassIVE; Q96FA3; -.
DR MaxQB; Q96FA3; -.
DR PaxDb; Q96FA3; -.
DR PeptideAtlas; Q96FA3; -.
DR PRIDE; Q96FA3; -.
DR ProteomicsDB; 76505; -.
DR Antibodypedia; 16046; 245 antibodies from 29 providers.
DR DNASU; 57162; -.
DR Ensembl; ENST00000358912.5; ENSP00000351789.4; ENSG00000197329.12.
DR GeneID; 57162; -.
DR KEGG; hsa:57162; -.
DR MANE-Select; ENST00000358912.5; ENSP00000351789.4; NM_020651.4; NP_065702.2.
DR UCSC; uc002sct.5; human.
DR CTD; 57162; -.
DR DisGeNET; 57162; -.
DR GeneCards; PELI1; -.
DR HGNC; HGNC:8827; PELI1.
DR HPA; ENSG00000197329; Tissue enriched (bone).
DR MIM; 614797; gene.
DR neXtProt; NX_Q96FA3; -.
DR OpenTargets; ENSG00000197329; -.
DR PharmGKB; PA33172; -.
DR VEuPathDB; HostDB:ENSG00000197329; -.
DR eggNOG; KOG3842; Eukaryota.
DR GeneTree; ENSGT00950000183050; -.
DR HOGENOM; CLU_029221_2_0_1; -.
DR InParanoid; Q96FA3; -.
DR OMA; GFMQDSK; -.
DR OrthoDB; 837213at2759; -.
DR PhylomeDB; Q96FA3; -.
DR TreeFam; TF314338; -.
DR PathwayCommons; Q96FA3; -.
DR Reactome; R-HSA-5675482; Regulation of necroptotic cell death.
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; Q96FA3; -.
DR SIGNOR; Q96FA3; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 57162; 10 hits in 1122 CRISPR screens.
DR ChiTaRS; PELI1; human.
DR GeneWiki; PELI1; -.
DR GenomeRNAi; 57162; -.
DR Pharos; Q96FA3; Tbio.
DR PRO; PR:Q96FA3; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q96FA3; protein.
DR Bgee; ENSG00000197329; Expressed in mucosa of paranasal sinus and 203 other tissues.
DR ExpressionAtlas; Q96FA3; baseline and differential.
DR Genevisible; Q96FA3; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IEA:Ensembl.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:UniProtKB.
DR GO; GO:0034450; F:ubiquitin-ubiquitin ligase activity; TAS:Reactome.
DR GO; GO:0060546; P:negative regulation of necroptotic process; IMP:UniProtKB.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; IEA:Ensembl.
DR GO; GO:0042130; P:negative regulation of T cell proliferation; IEA:Ensembl.
DR GO; GO:0030890; P:positive regulation of B cell proliferation; IEA:Ensembl.
DR GO; GO:0001819; P:positive regulation of cytokine production; IEA:Ensembl.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; TAS:Reactome.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IEA:Ensembl.
DR GO; GO:0034141; P:positive regulation of toll-like receptor 3 signaling pathway; IEA:Ensembl.
DR GO; GO:0034145; P:positive regulation of toll-like receptor 4 signaling pathway; IEA:Ensembl.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR GO; GO:0070936; P:protein K48-linked ubiquitination; IMP:UniProtKB.
DR GO; GO:0070534; P:protein K63-linked ubiquitination; IMP:UniProtKB.
DR GO; GO:0000209; P:protein polyubiquitination; IBA:GO_Central.
DR GO; GO:0060544; P:regulation of necroptotic process; TAS:Reactome.
DR GO; GO:0008592; P:regulation of Toll signaling pathway; IEA:InterPro.
DR GO; GO:0043331; P:response to dsRNA; IEA:Ensembl.
DR GO; GO:0032496; P:response to lipopolysaccharide; IDA:ARUK-UCL.
DR GO; GO:0042098; P:T cell proliferation; IEA:Ensembl.
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 Phosphoprotein; Reference proteome; Transferase; Ubl conjugation;
KW Ubl conjugation pathway.
FT CHAIN 1..418
FT /note="E3 ubiquitin-protein ligase pellino homolog 1"
FT /id="PRO_0000194172"
FT DOMAIN 13..200
FT /note="FHA; atypical"
FT /evidence="ECO:0000250|UniProtKB:Q9HAT8"
FT REGION 311..399
FT /note="Ring-like domain; necessary for ubiqitination of
FT RIPK3"
FT /evidence="ECO:0000269|PubMed:29883609"
FT MUTAGEN 104
FT /note="R->A: Loss of ability to ubiquitinate RIPK3. Loss of
FT interaction with RIPK1, IRAK1 and RIPK3."
FT /evidence="ECO:0000269|PubMed:29883609"
FT MUTAGEN 313
FT /note="H->A: Loss of ability to ubiquitinate RIPK3. No loss
FT of interaction with RIPK3."
FT /evidence="ECO:0000269|PubMed:29883609"
FT MUTAGEN 336
FT /note="C->A: Loss of ability to ubiquitinate RIPK3. No loss
FT of interaction with RIPK3."
FT /evidence="ECO:0000269|PubMed:29883609"
FT CONFLICT 11
FT /note="S -> F (in Ref. 1; CAC04320)"
FT /evidence="ECO:0000305"
FT CONFLICT 100
FT /note="F -> S (in Ref. 5; BAB55280)"
FT /evidence="ECO:0000305"
FT CONFLICT 260
FT /note="S -> P (in Ref. 5; BAB55280)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 418 AA; 46286 MW; 233318A45E7546F7 CRC64;
MFSPDQENHP SKAPVKYGEL IVLGYNGSLP NGDRGRRKSR FALFKRPKAN GVKPSTVHIA
CTPQAAKAIS NKDQHSISYT LSRAQTVVVE YTHDSNTDMF QIGRSTESPI DFVVTDTVPG
SQSNSDTQSV QSTISRFACR IICERNPPFT ARIYAAGFDS SKNIFLGEKA AKWKTSDGQM
DGLTTNGVLV MHPRNGFTED SKPGIWREIS VCGNVFSLRE TRSAQQRGKM VEIETNQLQD
GSLIDLCGAT LLWRTAEGLS HTPTVKHLEA LRQEINAARP QCPVGFNTLA FPSMKRKDVV
DEKQPWVYLN CGHVHGYHNW GNKEERDGKD RECPMCRSVG PYVPLWLGCE AGFYVDAGPP
THAFSPCGHV CSEKTTAYWS QIPLPHGTHT FHAACPFCAH QLAGEQGYIR LIFQGPLD
