PELI1_MOUSE
ID PELI1_MOUSE Reviewed; 418 AA.
AC Q8C669; Q91YL9; Q9CV22; Q9ERJ8;
DT 24-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 24-OCT-2003, sequence version 2.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=E3 ubiquitin-protein ligase pellino homolog 1;
DE Short=Pellino-1;
DE EC=2.3.2.27;
DE AltName: Full=RING-type E3 ubiquitin transferase pellino homolog 1 {ECO:0000305};
GN Name=Peli1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C57BL/6J;
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 STRAIN=C57BL/6J; TISSUE=Brain, Head, and Tongue;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Mammary tumor;
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 [4]
RP FUNCTION, AND INTERACTION WITH IRAK1; IRAK4; 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 [5]
RP FUNCTION, AND INTERACTION WITH RIPK1 AND RIPK3.
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 (By similarity). Involved in
CC the TLR and IL-1 signaling pathways via interaction with the complex
CC containing IRAK kinases and TRAF6. Mediates 'Lys-63'-linked
CC polyubiquitination of IRAK1 allowing subsequent NF-kappa-B activation
CC (PubMed:16951688). 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 (By similarity).
CC {ECO:0000250|UniProtKB:Q96FA3, ECO:0000269|PubMed:16951688,
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:0000250|UniProtKB:Q96FA3};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts with MAP3K7 (By similarity). Upon IL1B treatment,
CC forms a complex with TRAF6, IRAK1, IRAK4 and MYD88; this complex
CC recruits MAP3K7/TAK1, TAB1 and TAB2 to mediate NF-kappa-B activation.
CC Direct binding of SMAD6 to PELI1 prevents the complex formation and
CC hence negatively regulates IL1R-TLR signaling and eventually NF-kappa-
CC B-mediated gene expression (PubMed:16951688). Interacts (via atypical
CC FHA domain) with RIPK3 (PubMed:29883609). Binds preferentially to the
CC 'Thr-182' phosphorylated form of RIPK3 (By similarity). Interacts with
CC RIPK1 (PubMed:29883609). {ECO:0000250|UniProtKB:Q96FA3,
CC ECO:0000269|PubMed:16951688, ECO:0000269|PubMed:29883609}.
CC -!- PTM: Phosphorylated by IRAK1 and IRAK4 enhancing its E3 ligase
CC activity. {ECO:0000250}.
CC -!- PTM: Sumoylated. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the pellino family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC36351.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF302503; AAG15391.1; -; mRNA.
DR EMBL; AK009945; BAB26600.1; -; mRNA.
DR EMBL; AK045673; BAC32452.1; -; mRNA.
DR EMBL; AK076458; BAC36351.1; ALT_INIT; mRNA.
DR EMBL; BC016515; AAH16515.1; -; mRNA.
DR CCDS; CCDS24462.1; -.
DR RefSeq; NP_075813.2; NM_023324.2.
DR AlphaFoldDB; Q8C669; -.
DR SMR; Q8C669; -.
DR BioGRID; 212043; 6.
DR DIP; DIP-48336N; -.
DR IntAct; Q8C669; 2.
DR STRING; 10090.ENSMUSP00000090979; -.
DR iPTMnet; Q8C669; -.
DR PhosphoSitePlus; Q8C669; -.
DR MaxQB; Q8C669; -.
DR PaxDb; Q8C669; -.
DR PRIDE; Q8C669; -.
DR ProteomicsDB; 287824; -.
DR Antibodypedia; 16046; 245 antibodies from 29 providers.
DR DNASU; 67245; -.
DR Ensembl; ENSMUST00000093290; ENSMUSP00000090979; ENSMUSG00000020134.
DR Ensembl; ENSMUST00000101477; ENSMUSP00000099018; ENSMUSG00000020134.
DR GeneID; 67245; -.
DR KEGG; mmu:67245; -.
DR UCSC; uc007idl.1; mouse.
DR CTD; 57162; -.
DR MGI; MGI:1914495; Peli1.
DR VEuPathDB; HostDB:ENSMUSG00000020134; -.
DR eggNOG; KOG3842; Eukaryota.
DR GeneTree; ENSGT00950000183050; -.
DR HOGENOM; CLU_029221_2_0_1; -.
DR InParanoid; Q8C669; -.
DR OMA; GFMQDSK; -.
DR OrthoDB; 837213at2759; -.
DR PhylomeDB; Q8C669; -.
DR TreeFam; TF314338; -.
DR Reactome; R-MMU-5675482; Regulation of necroptotic cell death.
DR Reactome; R-MMU-9020702; Interleukin-1 signaling.
DR Reactome; R-MMU-937039; IRAK1 recruits IKK complex.
DR Reactome; R-MMU-975144; IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 67245; 6 hits in 74 CRISPR screens.
DR ChiTaRS; Peli1; mouse.
DR PRO; PR:Q8C669; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q8C669; protein.
DR Bgee; ENSMUSG00000020134; Expressed in medial ganglionic eminence and 263 other tissues.
DR ExpressionAtlas; Q8C669; baseline and differential.
DR Genevisible; Q8C669; MM.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:MGI.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:MGI.
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; IMP:MGI.
DR GO; GO:0050868; P:negative regulation of T cell activation; IMP:MGI.
DR GO; GO:0042130; P:negative regulation of T cell proliferation; IMP:MGI.
DR GO; GO:0050871; P:positive regulation of B cell activation; IMP:MGI.
DR GO; GO:0030890; P:positive regulation of B cell proliferation; IMP:MGI.
DR GO; GO:0001819; P:positive regulation of cytokine production; IMP:MGI.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IMP:MGI.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IMP:MGI.
DR GO; GO:0034141; P:positive regulation of toll-like receptor 3 signaling pathway; IMP:MGI.
DR GO; GO:0034145; P:positive regulation of toll-like receptor 4 signaling pathway; IMP:MGI.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR GO; GO:0070936; P:protein K48-linked ubiquitination; IDA:MGI.
DR GO; GO:0070534; P:protein K63-linked ubiquitination; ISS:UniProtKB.
DR GO; GO:0000209; P:protein polyubiquitination; IMP:MGI.
DR GO; GO:0008592; P:regulation of Toll signaling pathway; IEA:InterPro.
DR GO; GO:0043331; P:response to dsRNA; IMP:MGI.
DR GO; GO:0032496; P:response to lipopolysaccharide; IMP:MGI.
DR GO; GO:0042110; P:T cell activation; IMP:MGI.
DR GO; GO:0042098; P:T cell proliferation; IMP:MGI.
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_0000194173"
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 ubiquitination of
FT RIPK3"
FT /evidence="ECO:0000250|UniProtKB:Q96FA3"
FT CONFLICT 5..7
FT /note="DQE -> GSR (in Ref. 1; AAG15391)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 418 AA; 46259 MW; 26072654577EBBF7 CRC64;
MFSPDQENHP SKAPVKYGEL IVLGYNGSLP NGDRGRRKSR FALFKRPKAN GVKPSTVHIA
CTPQAAKAIS NKDQHSISYT LSRAQTVVVE YTHDSNTDMF QIGRSTESPI DFVVTDTVPG
SQSNSDTQSV QSTISRFACR IICERSPPFT 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
