PELI2_HUMAN
ID PELI2_HUMAN Reviewed; 420 AA.
AC Q9HAT8; B2RDY5;
DT 24-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=E3 ubiquitin-protein ligase pellino homolog 2;
DE Short=Pellino-2;
DE EC=2.3.2.27;
DE AltName: Full=RING-type E3 ubiquitin transferase pellino homolog 2 {ECO:0000305};
GN Name=PELI2;
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].
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
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 GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=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 FUNCTION, AND 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 [6]
RP FUNCTION, PHOSPHORYLATION, AND INTERACTION WITH IRAK1 AND IRAK4.
RX PubMed=12860405; DOI=10.1016/s0014-5793(03)00697-5;
RA Strelow A., Kollewe C., Wesche H.;
RT "Characterization of Pellino2, a substrate of IRAK1 and IRAK4.";
RL FEBS Lett. 547:157-161(2003).
RN [7]
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 [8]
RP FUNCTION.
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 [9]
RP FUNCTION, AND MUTAGENESIS OF CYS-397 AND CYS-400.
RX PubMed=22669975; DOI=10.1074/jbc.m112.352625;
RA Kim T.W., Yu M., Zhou H., Cui W., Wang J., DiCorleto P., Fox P., Xiao H.,
RA Li X.;
RT "Pellino 2 is critical for Toll-like receptor/interleukin-1 receptor
RT (TLR/IL-1R)-mediated post-transcriptional control.";
RL J. Biol. Chem. 287:25686-25695(2012).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 15-275, DOMAIN FHA, AND
RP MUTAGENESIS OF ARG-106; THR-187 AND ASN-188.
RX PubMed=19081057; DOI=10.1016/j.str.2008.09.011;
RA Lin C.C., Huoh Y.S., Schmitz K.R., Jensen L.E., Ferguson K.M.;
RT "Pellino proteins contain a cryptic FHA domain that mediates interaction
RT with phosphorylated IRAK1.";
RL Structure 16:1806-1816(2008).
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 IL1B-induced IRAK1 'Lys-63'-linked
CC polyubiquitination and possibly 'Lys-48'-linked ubiquitination. May be
CC important for LPS- and IL1B-induced MAP3K7-dependent, but not MAP3K3-
CC dependent, NF-kappa-B activation. Can activate the MAP (mitogen
CC activated protein) kinase pathway leading to activation of ELK1.
CC {ECO:0000269|PubMed:12804775, ECO:0000269|PubMed:12860405,
CC ECO:0000269|PubMed:17675297, ECO:0000269|PubMed:17997719,
CC ECO:0000269|PubMed:22669975}.
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, IRAK4 and MAP3K7. Interacts with
CC BCL10; this interaction is impaired by SOCS3 (By similarity).
CC {ECO:0000250}.
CC -!- INTERACTION:
CC Q9HAT8; Q6ZS10: CLEC17A; NbExp=3; IntAct=EBI-448407, EBI-11977093;
CC Q9HAT8; Q12891: HYAL2; NbExp=3; IntAct=EBI-448407, EBI-2806068;
CC Q9HAT8; P51617: IRAK1; NbExp=4; IntAct=EBI-448407, EBI-358664;
CC Q9HAT8; Q9NWZ3: IRAK4; NbExp=3; IntAct=EBI-448407, EBI-448378;
CC Q9HAT8; Q9NQ48: LZTFL1; NbExp=3; IntAct=EBI-448407, EBI-2824799;
CC Q9HAT8; Q99750: MDFI; NbExp=3; IntAct=EBI-448407, EBI-724076;
CC Q9HAT8; P50221: MEOX1; NbExp=3; IntAct=EBI-448407, EBI-2864512;
CC Q9HAT8; P37198: NUP62; NbExp=3; IntAct=EBI-448407, EBI-347978;
CC Q9HAT8; Q96RA2: OR7D2; NbExp=3; IntAct=EBI-448407, EBI-12826231;
CC Q9HAT8; P35227: PCGF2; NbExp=3; IntAct=EBI-448407, EBI-2129767;
CC Q9HAT8; Q15276: RABEP1; NbExp=3; IntAct=EBI-448407, EBI-447043;
CC Q9HAT8; Q04864-2: REL; NbExp=3; IntAct=EBI-448407, EBI-10829018;
CC Q9HAT8; Q96TC7: RMDN3; NbExp=3; IntAct=EBI-448407, EBI-1056589;
CC Q9HAT8; Q9UH03: SEPTIN3; NbExp=3; IntAct=EBI-448407, EBI-727037;
CC Q9HAT8; Q02446: SP4; NbExp=3; IntAct=EBI-448407, EBI-10198587;
CC Q9HAT8; Q9BSE2: TMEM79; NbExp=3; IntAct=EBI-448407, EBI-8649725;
CC Q9HAT8; Q9H3D4: TP63; NbExp=3; IntAct=EBI-448407, EBI-2337775;
CC Q9HAT8; Q13049: TRIM32; NbExp=3; IntAct=EBI-448407, EBI-742790;
CC -!- DOMAIN: The atypical FHA domain contains a 'wing' insert and mediates
CC binding to threonine-phosphorylated IRAK1.
CC {ECO:0000269|PubMed:19081057}.
CC -!- PTM: Phosphorylated by IRAK1 and IRAK4 enhancing its E3 ligase
CC activity. {ECO:0000269|PubMed:12860405}.
CC -!- SIMILARITY: Belongs to the pellino family. {ECO:0000305}.
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DR EMBL; AF302502; AAG15390.1; -; mRNA.
DR EMBL; AK315727; BAG38082.1; -; mRNA.
DR EMBL; CH471061; EAW80689.1; -; Genomic_DNA.
DR EMBL; BC009476; AAH09476.1; -; mRNA.
DR CCDS; CCDS9726.1; -.
DR RefSeq; NP_067078.1; NM_021255.2.
DR PDB; 3EGA; X-ray; 1.80 A; A=15-275.
DR PDB; 3EGB; X-ray; 3.25 A; A/B=7-289.
DR PDBsum; 3EGA; -.
DR PDBsum; 3EGB; -.
DR AlphaFoldDB; Q9HAT8; -.
DR SMR; Q9HAT8; -.
DR BioGRID; 121417; 36.
DR DIP; DIP-31350N; -.
DR IntAct; Q9HAT8; 33.
DR MINT; Q9HAT8; -.
DR STRING; 9606.ENSP00000267460; -.
DR iPTMnet; Q9HAT8; -.
DR PhosphoSitePlus; Q9HAT8; -.
DR BioMuta; PELI2; -.
DR DMDM; 37999785; -.
DR EPD; Q9HAT8; -.
DR MassIVE; Q9HAT8; -.
DR MaxQB; Q9HAT8; -.
DR PaxDb; Q9HAT8; -.
DR PeptideAtlas; Q9HAT8; -.
DR PRIDE; Q9HAT8; -.
DR ProteomicsDB; 81433; -.
DR Antibodypedia; 11214; 92 antibodies from 20 providers.
DR DNASU; 57161; -.
DR Ensembl; ENST00000267460.9; ENSP00000267460.4; ENSG00000139946.10.
DR GeneID; 57161; -.
DR KEGG; hsa:57161; -.
DR MANE-Select; ENST00000267460.9; ENSP00000267460.4; NM_021255.3; NP_067078.1.
DR UCSC; uc001xch.4; human.
DR CTD; 57161; -.
DR DisGeNET; 57161; -.
DR GeneCards; PELI2; -.
DR HGNC; HGNC:8828; PELI2.
DR HPA; ENSG00000139946; Low tissue specificity.
DR MIM; 614798; gene.
DR neXtProt; NX_Q9HAT8; -.
DR OpenTargets; ENSG00000139946; -.
DR PharmGKB; PA33173; -.
DR VEuPathDB; HostDB:ENSG00000139946; -.
DR eggNOG; KOG3842; Eukaryota.
DR GeneTree; ENSGT00950000183050; -.
DR HOGENOM; CLU_029221_2_0_1; -.
DR InParanoid; Q9HAT8; -.
DR OMA; IMHPRGQ; -.
DR OrthoDB; 837213at2759; -.
DR PhylomeDB; Q9HAT8; -.
DR TreeFam; TF314338; -.
DR PathwayCommons; Q9HAT8; -.
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; Q9HAT8; -.
DR SIGNOR; Q9HAT8; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 57161; 9 hits in 1104 CRISPR screens.
DR ChiTaRS; PELI2; human.
DR EvolutionaryTrace; Q9HAT8; -.
DR GeneWiki; PELI2; -.
DR GenomeRNAi; 57161; -.
DR Pharos; Q9HAT8; Tbio.
DR PRO; PR:Q9HAT8; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q9HAT8; protein.
DR Bgee; ENSG00000139946; Expressed in ventricular zone and 178 other tissues.
DR ExpressionAtlas; Q9HAT8; baseline and differential.
DR Genevisible; Q9HAT8; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IBA:GO_Central.
DR GO; GO:0034450; F:ubiquitin-ubiquitin ligase activity; TAS:Reactome.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; TAS:Reactome.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IDA:MGI.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IDA:MGI.
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 3D-structure; Phosphoprotein; Reference proteome; Transferase;
KW Ubl conjugation pathway.
FT CHAIN 1..420
FT /note="E3 ubiquitin-protein ligase pellino homolog 2"
FT /id="PRO_0000194174"
FT DOMAIN 15..202
FT /note="FHA; atypical"
FT MUTAGEN 106
FT /note="R->A: Abolishes binding to IRAK1."
FT /evidence="ECO:0000269|PubMed:19081057"
FT MUTAGEN 187
FT /note="T->A: Abolishes binding to IRAK1; when associated
FT with A-188."
FT /evidence="ECO:0000269|PubMed:19081057"
FT MUTAGEN 188
FT /note="N->A: Abolishes binding to IRAK1; when associated
FT with A-187."
FT /evidence="ECO:0000269|PubMed:19081057"
FT MUTAGEN 397
FT /note="C->A: Loss of IRAK1-polyubiquitination."
FT /evidence="ECO:0000269|PubMed:22669975"
FT MUTAGEN 400
FT /note="C->A: Loss of IRAK1-polyubiquitination."
FT /evidence="ECO:0000269|PubMed:22669975"
FT STRAND 18..24
FT /evidence="ECO:0007829|PDB:3EGA"
FT STRAND 41..46
FT /evidence="ECO:0007829|PDB:3EGA"
FT STRAND 53..63
FT /evidence="ECO:0007829|PDB:3EGA"
FT STRAND 76..82
FT /evidence="ECO:0007829|PDB:3EGA"
FT STRAND 84..96
FT /evidence="ECO:0007829|PDB:3EGA"
FT STRAND 99..106
FT /evidence="ECO:0007829|PDB:3EGA"
FT STRAND 113..115
FT /evidence="ECO:0007829|PDB:3EGA"
FT STRAND 141..148
FT /evidence="ECO:0007829|PDB:3EGA"
FT STRAND 153..158
FT /evidence="ECO:0007829|PDB:3EGA"
FT STRAND 164..168
FT /evidence="ECO:0007829|PDB:3EGA"
FT STRAND 174..176
FT /evidence="ECO:0007829|PDB:3EGA"
FT STRAND 182..184
FT /evidence="ECO:0007829|PDB:3EGA"
FT STRAND 190..193
FT /evidence="ECO:0007829|PDB:3EGA"
FT STRAND 208..211
FT /evidence="ECO:0007829|PDB:3EGA"
FT STRAND 215..218
FT /evidence="ECO:0007829|PDB:3EGB"
FT STRAND 222..225
FT /evidence="ECO:0007829|PDB:3EGB"
FT STRAND 245..247
FT /evidence="ECO:0007829|PDB:3EGA"
FT STRAND 252..257
FT /evidence="ECO:0007829|PDB:3EGA"
FT HELIX 258..263
FT /evidence="ECO:0007829|PDB:3EGB"
FT HELIX 266..269
FT /evidence="ECO:0007829|PDB:3EGB"
FT HELIX 270..276
FT /evidence="ECO:0007829|PDB:3EGB"
SQ SEQUENCE 420 AA; 46435 MW; 2FC5E661C13BC11A CRC64;
MFSPGQEEHC APNKEPVKYG ELVVLGYNGA LPNGDRGRRK SRFALYKRPK ANGVKPSTVH
VISTPQASKA ISCKGQHSIS YTLSRNQTVV VEYTHDKDTD MFQVGRSTES PIDFVVTDTI
SGSQNTDEAQ ITQSTISRFA CRIVCDRNEP YTARIFAAGF DSSKNIFLGE KAAKWKNPDG
HMDGLTTNGV LVMHPRGGFT EESQPGVWRE ISVCGDVYTL RETRSAQQRG KLVESETNVL
QDGSLIDLCG ATLLWRTADG LFHTPTQKHI EALRQEINAA RPQCPVGLNT LAFPSINRKE
VVEEKQPWAY LSCGHVHGYH NWGHRSDTEA NERECPMCRT VGPYVPLWLG CEAGFYVDAG
PPTHAFTPCG HVCSEKSAKY WSQIPLPHGT HAFHAACPFC ATQLVGEQNC IKLIFQGPID
