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Q96FA3

- PELI1_HUMAN

UniProt

Q96FA3 - PELI1_HUMAN

Protein

E3 ubiquitin-protein ligase pellino homolog 1

Gene

PELI1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 104 (01 Oct 2014)
      Sequence version 2 (24 Oct 2003)
      Previous versions | rss
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    Functioni

    E3 ubiquitin ligase catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins. Involved in the TLR and IL-1 signaling pathways via interaction with the complex containing IRAK kinases and TRAF6. Mediates 'Lys-63'-linked polyubiquitination of IRAK1 allowing subsequent NF-kappa-B activation.2 Publications

    Pathwayi

    GO - Molecular functioni

    1. ligase activity Source: UniProtKB-KW
    2. protein binding Source: IntAct
    3. ubiquitin-protein transferase activity Source: Ensembl

    GO - Biological processi

    1. innate immune response Source: Reactome
    2. MyD88-dependent toll-like receptor signaling pathway Source: Reactome
    3. negative regulation of NF-kappaB transcription factor activity Source: Ensembl
    4. negative regulation of T cell proliferation Source: Ensembl
    5. positive regulation of B cell proliferation Source: Ensembl
    6. positive regulation of cytokine production Source: Ensembl
    7. positive regulation of I-kappaB kinase/NF-kappaB signaling Source: Reactome
    8. positive regulation of protein ubiquitination Source: Ensembl
    9. positive regulation of toll-like receptor 3 signaling pathway Source: Ensembl
    10. positive regulation of toll-like receptor 4 signaling pathway Source: Ensembl
    11. protein K48-linked ubiquitination Source: Ensembl
    12. response to dsRNA Source: Ensembl
    13. response to lipopolysaccharide Source: Ensembl
    14. toll-like receptor 10 signaling pathway Source: Reactome
    15. toll-like receptor 2 signaling pathway Source: Reactome
    16. toll-like receptor 4 signaling pathway Source: Reactome
    17. toll-like receptor 5 signaling pathway Source: Reactome
    18. toll-like receptor 9 signaling pathway Source: Reactome
    19. toll-like receptor signaling pathway Source: Reactome
    20. toll-like receptor TLR1:TLR2 signaling pathway Source: Reactome
    21. toll-like receptor TLR6:TLR2 signaling pathway Source: Reactome
    22. Toll signaling pathway Source: InterPro

    Keywords - Molecular functioni

    Ligase

    Keywords - Biological processi

    Ubl conjugation pathway

    Enzyme and pathway databases

    ReactomeiREACT_22442. Interleukin-1 signaling.
    REACT_24918. IRAK1 recruits IKK complex.
    REACT_25354. IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation.
    SignaLinkiQ96FA3.
    UniPathwayiUPA00143.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    E3 ubiquitin-protein ligase pellino homolog 1 (EC:6.3.2.-)
    Short name:
    Pellino-1
    Alternative name(s):
    Pellino-related intracellular-signaling molecule
    Gene namesi
    Name:PELI1
    Synonyms:PRISM
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 2

    Organism-specific databases

    HGNCiHGNC:8827. PELI1.

    Subcellular locationi

    GO - Cellular componenti

    1. cytosol Source: Reactome
    2. nucleus Source: Ensembl

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA33172.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 418418E3 ubiquitin-protein ligase pellino homolog 1PRO_0000194172Add
    BLAST

    Post-translational modificationi

    Phosphorylation by IRAK1 and IRAK4 enhances its E3 ligase activity.1 Publication
    Sumoylated.1 Publication

    Keywords - PTMi

    Phosphoprotein, Ubl conjugation

    Proteomic databases

    MaxQBiQ96FA3.
    PaxDbiQ96FA3.
    PRIDEiQ96FA3.

    PTM databases

    PhosphoSiteiQ96FA3.

    Expressioni

    Gene expression databases

    ArrayExpressiQ96FA3.
    BgeeiQ96FA3.
    CleanExiHS_PELI1.
    GenevestigatoriQ96FA3.

    Organism-specific databases

    HPAiHPA053182.

    Interactioni

    Subunit structurei

    Interacts with MAP3K7. Upon IL1B treatment, forms a complex with TRAF6, IRAK1, IRAK4 and MYD88; this complex recruits MAP3K7/TAK1, TAB1 and TAB2 to mediate NF-kappa-B activation. Direct binding of SMAD6 to PELI1 prevents the complex formation and hence negatively regulates IL1R-TLR signaling and eventually NF-kappa-B-mediated gene expression.3 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    IRAK1P516173EBI-448369,EBI-358664

    Protein-protein interaction databases

    BioGridi121418. 21 interactions.
    DIPiDIP-32488N.
    IntActiQ96FA3. 6 interactions.
    MINTiMINT-2844985.
    STRINGi9606.ENSP00000351789.

    Structurei

    3D structure databases

    ProteinModelPortaliQ96FA3.
    SMRiQ96FA3. Positions 14-256.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the pellino family.Curated

    Phylogenomic databases

    eggNOGiNOG258040.
    HOGENOMiHOG000234110.
    HOVERGENiHBG053559.
    InParanoidiQ96FA3.
    KOiK11964.
    OMAiGKMVENE.
    OrthoDBiEOG751NFB.
    PhylomeDBiQ96FA3.
    TreeFamiTF314338.

    Family and domain databases

    InterProiIPR006800. Pellino_fam.
    [Graphical view]
    PANTHERiPTHR12098. PTHR12098. 1 hit.
    PfamiPF04710. Pellino. 1 hit.
    [Graphical view]
    PIRSFiPIRSF038886. Pellino. 1 hit.

    Sequencei

    Sequence statusi: Complete.

    Q96FA3-1 [UniParc]FASTAAdd to Basket

    « Hide

    MFSPDQENHP SKAPVKYGEL IVLGYNGSLP NGDRGRRKSR FALFKRPKAN    50
    GVKPSTVHIA CTPQAAKAIS NKDQHSISYT LSRAQTVVVE YTHDSNTDMF 100
    QIGRSTESPI DFVVTDTVPG SQSNSDTQSV QSTISRFACR IICERNPPFT 150
    ARIYAAGFDS SKNIFLGEKA AKWKTSDGQM DGLTTNGVLV MHPRNGFTED 200
    SKPGIWREIS VCGNVFSLRE TRSAQQRGKM VEIETNQLQD GSLIDLCGAT 250
    LLWRTAEGLS HTPTVKHLEA LRQEINAARP QCPVGFNTLA FPSMKRKDVV 300
    DEKQPWVYLN CGHVHGYHNW GNKEERDGKD RECPMCRSVG PYVPLWLGCE 350
    AGFYVDAGPP THAFSPCGHV CSEKTTAYWS QIPLPHGTHT FHAACPFCAH 400
    QLAGEQGYIR LIFQGPLD 418
    Length:418
    Mass (Da):46,286
    Last modified:October 24, 2003 - v2
    Checksum:i233318A45E7546F7
    GO

    Sequence cautioni

    The sequence AAH11419.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.
    The sequence BAB55280.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti11 – 111S → F in CAC04320. (PubMed:11132151)Curated
    Sequence conflicti100 – 1001F → S in BAB55280. (PubMed:14702039)Curated
    Sequence conflicti260 – 2601S → P in BAB55280. (PubMed:14702039)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AJ278859 mRNA. Translation: CAC04320.1.
    AF302505 mRNA. Translation: AAG15393.1.
    AF300987 mRNA. Translation: AAG17451.1.
    BC011419 mRNA. Translation: AAH11419.1. Different initiation.
    BC050019 mRNA. Translation: AAH50019.1.
    BC063611 mRNA. Translation: AAH63611.1.
    AK027668 mRNA. Translation: BAB55280.1. Different initiation.
    CCDSiCCDS1876.1.
    RefSeqiNP_065702.2. NM_020651.3.
    UniGeneiHs.7886.

    Genome annotation databases

    EnsembliENST00000358912; ENSP00000351789; ENSG00000197329.
    GeneIDi57162.
    KEGGihsa:57162.
    UCSCiuc002scr.4. human.

    Polymorphism databases

    DMDMi37999756.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AJ278859 mRNA. Translation: CAC04320.1 .
    AF302505 mRNA. Translation: AAG15393.1 .
    AF300987 mRNA. Translation: AAG17451.1 .
    BC011419 mRNA. Translation: AAH11419.1 . Different initiation.
    BC050019 mRNA. Translation: AAH50019.1 .
    BC063611 mRNA. Translation: AAH63611.1 .
    AK027668 mRNA. Translation: BAB55280.1 . Different initiation.
    CCDSi CCDS1876.1.
    RefSeqi NP_065702.2. NM_020651.3.
    UniGenei Hs.7886.

    3D structure databases

    ProteinModelPortali Q96FA3.
    SMRi Q96FA3. Positions 14-256.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 121418. 21 interactions.
    DIPi DIP-32488N.
    IntActi Q96FA3. 6 interactions.
    MINTi MINT-2844985.
    STRINGi 9606.ENSP00000351789.

    PTM databases

    PhosphoSitei Q96FA3.

    Polymorphism databases

    DMDMi 37999756.

    Proteomic databases

    MaxQBi Q96FA3.
    PaxDbi Q96FA3.
    PRIDEi Q96FA3.

    Protocols and materials databases

    DNASUi 57162.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000358912 ; ENSP00000351789 ; ENSG00000197329 .
    GeneIDi 57162.
    KEGGi hsa:57162.
    UCSCi uc002scr.4. human.

    Organism-specific databases

    CTDi 57162.
    GeneCardsi GC02M064319.
    HGNCi HGNC:8827. PELI1.
    HPAi HPA053182.
    MIMi 614797. gene.
    neXtProti NX_Q96FA3.
    PharmGKBi PA33172.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG258040.
    HOGENOMi HOG000234110.
    HOVERGENi HBG053559.
    InParanoidi Q96FA3.
    KOi K11964.
    OMAi GKMVENE.
    OrthoDBi EOG751NFB.
    PhylomeDBi Q96FA3.
    TreeFami TF314338.

    Enzyme and pathway databases

    UniPathwayi UPA00143 .
    Reactomei REACT_22442. Interleukin-1 signaling.
    REACT_24918. IRAK1 recruits IKK complex.
    REACT_25354. IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation.
    SignaLinki Q96FA3.

    Miscellaneous databases

    GeneWikii PELI1.
    GenomeRNAii 57162.
    NextBioi 63169.
    PROi Q96FA3.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q96FA3.
    Bgeei Q96FA3.
    CleanExi HS_PELI1.
    Genevestigatori Q96FA3.

    Family and domain databases

    InterProi IPR006800. Pellino_fam.
    [Graphical view ]
    PANTHERi PTHR12098. PTHR12098. 1 hit.
    Pfami PF04710. Pellino. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF038886. Pellino. 1 hit.
    ProtoNeti Search...

    Publicationsi

    1. "Pellino-related sequences from Caenorhabditis elegans and Homo sapiens."
      Rich T., Allen R.L., Lucas A.-M., Trowsdale J.
      Immunogenetics 52:145-149(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Thymus.
    2. "Assignment of homologous genes, Peli1/PELI1 and Peli2/PELI2, for the Pelle adaptor protein Pellino to mouse chromosomes 11 and 14 and human chromosomes 2p13.3 and 14q21, respectively, by physical and radiation hybrid mapping."
      Resch K., Jockusch H., Schmitt-John T.
      Cytogenet. Cell Genet. 92:172-174(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    3. "PRISM, a novel mediator of Toll/IL-1 signalling."
      Kennedy E.J., Moynagh P.N.
      Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Ovary, Placenta and Testis.
    5. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 78-418.
      Tissue: Teratocarcinoma.
    6. "Pellino 1 is required for interleukin-1 (IL-1)-mediated signaling through its interaction with the IL-1 receptor-associated kinase 4 (IRAK4)-IRAK-tumor necrosis factor receptor-associated factor 6 (TRAF6) complex."
      Jiang Z., Johnson H.J., Nie H., Qin J., Bird T.A., Li X.
      J. Biol. Chem. 278:10952-10956(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH IRAK1; IRAK4 AND TRAF6.
    7. "Pellino2 activates the mitogen activated protein kinase pathway."
      Jensen L.E., Whitehead A.S.
      FEBS Lett. 545:199-202(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH TRAF6 AND MAP3K7.
    8. "Smad6 negatively regulates interleukin 1-receptor-Toll-like receptor signaling through direct interaction with the adaptor Pellino-1."
      Choi K.C., Lee Y.S., Lim S., Choi H.K., Lee C.H., Lee E.K., Hong S., Kim I.H., Kim S.J., Park S.H.
      Nat. Immunol. 7:1057-1065(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH IRAK1; IRAK4; MYD88; SMAD6 AND TRAF6.
    9. "Kinase-active interleukin-1 receptor-associated kinases promote polyubiquitination and degradation of the Pellino family: direct evidence for PELLINO proteins being ubiquitin-protein isopeptide ligases."
      Butler M.P., Hanly J.A., Moynagh P.N.
      J. Biol. Chem. 282:29729-29737(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION AS E3 UBIQUITIN LIGASE.
    10. "The IRAK-catalysed activation of the E3 ligase function of Pellino isoforms induces the Lys63-linked polyubiquitination of IRAK1."
      Ordureau A., Smith H., Windheim M., Peggie M., Carrick E., Morrice N., Cohen P.
      Biochem. J. 409:43-52(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION BY IRAK1 AND IRAK4.
    11. "Pellino-1, an adaptor protein of interleukin-1 receptor/toll-like receptor signaling, is sumoylated by Ubc9."
      Kim J.H., Sung K.S., Jung S.M., Lee Y.S., Kwon J.Y., Choi C.Y., Park S.H.
      Mol. Cells 31:85-89(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUMOYLATION.

    Entry informationi

    Entry nameiPELI1_HUMAN
    AccessioniPrimary (citable) accession number: Q96FA3
    Secondary accession number(s): Q96SM0, Q9GZY5, Q9HCX0
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 24, 2003
    Last sequence update: October 24, 2003
    Last modified: October 1, 2014
    This is version 104 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 2
      Human chromosome 2: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    4. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3