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Q9HAT8

- PELI2_HUMAN

UniProt

Q9HAT8 - PELI2_HUMAN

Protein

E3 ubiquitin-protein ligase pellino homolog 2

Gene

PELI2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 101 (01 Oct 2014)
      Sequence version 1 (01 Mar 2001)
      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 IL1B-induced IRAK1 'Lys-63'-linked polyubiquitination and possibly 'Lys-48'-linked ubiquitination. May be important for LPS- and IL1B-induced MAP3K7-dependent, but not MAP3K3-dependent, NF-kappa-B activation. Can activate the MAP (mitogen activated protein) kinase pathway leading to activation of ELK1.5 Publications

    Pathwayi

    GO - Molecular functioni

    1. ligase activity Source: UniProtKB-KW
    2. protein binding Source: IntAct

    GO - Biological processi

    1. innate immune response Source: Reactome
    2. MyD88-dependent toll-like receptor signaling pathway Source: Reactome
    3. positive regulation of I-kappaB kinase/NF-kappaB signaling Source: Reactome
    4. positive regulation of MAPK cascade Source: MGI
    5. positive regulation of protein phosphorylation Source: MGI
    6. protein ubiquitination Source: UniProtKB-UniPathway
    7. toll-like receptor 10 signaling pathway Source: Reactome
    8. toll-like receptor 2 signaling pathway Source: Reactome
    9. toll-like receptor 4 signaling pathway Source: Reactome
    10. toll-like receptor 5 signaling pathway Source: Reactome
    11. toll-like receptor 9 signaling pathway Source: Reactome
    12. toll-like receptor signaling pathway Source: Reactome
    13. toll-like receptor TLR1:TLR2 signaling pathway Source: Reactome
    14. toll-like receptor TLR6:TLR2 signaling pathway Source: Reactome
    15. 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.
    UniPathwayiUPA00143.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    E3 ubiquitin-protein ligase pellino homolog 2 (EC:6.3.2.-)
    Short name:
    Pellino-2
    Gene namesi
    Name:PELI2
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 14

    Organism-specific databases

    HGNCiHGNC:8828. PELI2.

    Subcellular locationi

    GO - Cellular componenti

    1. cytosol Source: Reactome

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi106 – 1061R → A: Abolishes binding to IRAK1. 1 Publication
    Mutagenesisi187 – 1871T → A: Abolishes binding to IRAK1; when associated with A-188. 1 Publication
    Mutagenesisi188 – 1881N → A: Abolishes binding to IRAK1; when associated with A-187. 1 Publication
    Mutagenesisi397 – 3971C → A: Loss of IRAK1-polyubiquitination. 1 Publication
    Mutagenesisi400 – 4001C → A: Loss of IRAK1-polyubiquitination. 1 Publication

    Organism-specific databases

    PharmGKBiPA33173.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 420420E3 ubiquitin-protein ligase pellino homolog 2PRO_0000194174Add
    BLAST

    Post-translational modificationi

    Phosphorylated by IRAK1 and IRAK4 enhancing its E3 ligase activity.1 Publication

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiQ9HAT8.
    PaxDbiQ9HAT8.
    PRIDEiQ9HAT8.

    PTM databases

    PhosphoSiteiQ9HAT8.

    Expressioni

    Gene expression databases

    ArrayExpressiQ9HAT8.
    BgeeiQ9HAT8.
    CleanExiHS_PELI2.
    GenevestigatoriQ9HAT8.

    Interactioni

    Subunit structurei

    Interacts with TRAF6, IRAK1, IRAK4 and MAP3K7. Interacts with BCL10; this interaction is impaired by SOCS3 By similarity.By similarity

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    IRAK1P516173EBI-448407,EBI-358664
    IRAK4Q9NWZ33EBI-448407,EBI-448378

    Protein-protein interaction databases

    BioGridi121417. 18 interactions.
    DIPiDIP-31350N.
    IntActiQ9HAT8. 14 interactions.
    MINTiMINT-2845048.
    STRINGi9606.ENSP00000267460.

    Structurei

    Secondary structure

    1
    420
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi18 – 247
    Beta strandi41 – 466
    Beta strandi53 – 6311
    Beta strandi76 – 827
    Beta strandi84 – 9613
    Beta strandi99 – 1068
    Beta strandi113 – 1153
    Beta strandi141 – 1488
    Beta strandi153 – 1586
    Beta strandi164 – 1685
    Beta strandi174 – 1763
    Beta strandi182 – 1843
    Beta strandi190 – 1934
    Beta strandi208 – 2114
    Beta strandi215 – 2184
    Beta strandi222 – 2254
    Beta strandi245 – 2473
    Beta strandi252 – 2576
    Helixi258 – 2636
    Helixi266 – 2694
    Helixi270 – 2767

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    3EGAX-ray1.80A15-275[»]
    3EGBX-ray3.25A/B7-289[»]
    ProteinModelPortaliQ9HAT8.
    SMRiQ9HAT8. Positions 15-258.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ9HAT8.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini15 – 202188FHA; atypicalAdd
    BLAST

    Domaini

    The atypical FHA domain contains a 'wing' insert and mediates binding to threonine-phosphorylated IRAK1.1 Publication

    Sequence similaritiesi

    Belongs to the pellino family.Curated
    Contains 1 FHA domain.Curated

    Phylogenomic databases

    eggNOGiNOG258040.
    HOGENOMiHOG000234110.
    HOVERGENiHBG053559.
    InParanoidiQ9HAT8.
    KOiK11964.
    OMAiHAPTQKH.
    PhylomeDBiQ9HAT8.
    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.

    Q9HAT8-1 [UniParc]FASTAAdd to Basket

    « Hide

    MFSPGQEEHC APNKEPVKYG ELVVLGYNGA LPNGDRGRRK SRFALYKRPK    50
    ANGVKPSTVH VISTPQASKA ISCKGQHSIS YTLSRNQTVV VEYTHDKDTD 100
    MFQVGRSTES PIDFVVTDTI SGSQNTDEAQ ITQSTISRFA CRIVCDRNEP 150
    YTARIFAAGF DSSKNIFLGE KAAKWKNPDG HMDGLTTNGV LVMHPRGGFT 200
    EESQPGVWRE ISVCGDVYTL RETRSAQQRG KLVESETNVL QDGSLIDLCG 250
    ATLLWRTADG LFHTPTQKHI EALRQEINAA RPQCPVGLNT LAFPSINRKE 300
    VVEEKQPWAY LSCGHVHGYH NWGHRSDTEA NERECPMCRT VGPYVPLWLG 350
    CEAGFYVDAG PPTHAFTPCG HVCSEKSAKY WSQIPLPHGT HAFHAACPFC 400
    ATQLVGEQNC IKLIFQGPID 420
    Length:420
    Mass (Da):46,435
    Last modified:March 1, 2001 - v1
    Checksum:i2FC5E661C13BC11A
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF302502 mRNA. Translation: AAG15390.1.
    AK315727 mRNA. Translation: BAG38082.1.
    CH471061 Genomic DNA. Translation: EAW80689.1.
    BC009476 mRNA. Translation: AAH09476.1.
    CCDSiCCDS9726.1.
    RefSeqiNP_067078.1. NM_021255.2.
    UniGeneiHs.657926.

    Genome annotation databases

    EnsembliENST00000267460; ENSP00000267460; ENSG00000139946.
    GeneIDi57161.
    KEGGihsa:57161.
    UCSCiuc001xch.3. human.

    Polymorphism databases

    DMDMi37999785.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF302502 mRNA. Translation: AAG15390.1 .
    AK315727 mRNA. Translation: BAG38082.1 .
    CH471061 Genomic DNA. Translation: EAW80689.1 .
    BC009476 mRNA. Translation: AAH09476.1 .
    CCDSi CCDS9726.1.
    RefSeqi NP_067078.1. NM_021255.2.
    UniGenei Hs.657926.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    3EGA X-ray 1.80 A 15-275 [» ]
    3EGB X-ray 3.25 A/B 7-289 [» ]
    ProteinModelPortali Q9HAT8.
    SMRi Q9HAT8. Positions 15-258.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 121417. 18 interactions.
    DIPi DIP-31350N.
    IntActi Q9HAT8. 14 interactions.
    MINTi MINT-2845048.
    STRINGi 9606.ENSP00000267460.

    PTM databases

    PhosphoSitei Q9HAT8.

    Polymorphism databases

    DMDMi 37999785.

    Proteomic databases

    MaxQBi Q9HAT8.
    PaxDbi Q9HAT8.
    PRIDEi Q9HAT8.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000267460 ; ENSP00000267460 ; ENSG00000139946 .
    GeneIDi 57161.
    KEGGi hsa:57161.
    UCSCi uc001xch.3. human.

    Organism-specific databases

    CTDi 57161.
    GeneCardsi GC14P056585.
    HGNCi HGNC:8828. PELI2.
    MIMi 614798. gene.
    neXtProti NX_Q9HAT8.
    PharmGKBi PA33173.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG258040.
    HOGENOMi HOG000234110.
    HOVERGENi HBG053559.
    InParanoidi Q9HAT8.
    KOi K11964.
    OMAi HAPTQKH.
    PhylomeDBi Q9HAT8.
    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.

    Miscellaneous databases

    EvolutionaryTracei Q9HAT8.
    GeneWikii PELI2.
    GenomeRNAii 57161.
    NextBioi 63165.
    PROi Q9HAT8.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q9HAT8.
    Bgeei Q9HAT8.
    CleanExi HS_PELI2.
    Genevestigatori Q9HAT8.

    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. "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].
    2. "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].
      Tissue: Testis.
    3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    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: Lung.
    5. "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: FUNCTION, INTERACTION WITH TRAF6 AND MAP3K7.
    6. "Characterization of Pellino2, a substrate of IRAK1 and IRAK4."
      Strelow A., Kollewe C., Wesche H.
      FEBS Lett. 547:157-161(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, PHOSPHORYLATION, INTERACTION WITH IRAK1 AND IRAK4.
    7. "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.
    8. "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: FUNCTION.
    9. "Pellino 2 is critical for Toll-like receptor/interleukin-1 receptor (TLR/IL-1R)-mediated post-transcriptional control."
      Kim T.W., Yu M., Zhou H., Cui W., Wang J., DiCorleto P., Fox P., Xiao H., Li X.
      J. Biol. Chem. 287:25686-25695(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, MUTAGENESIS OF CYS-397 AND CYS-400.
    10. "Pellino proteins contain a cryptic FHA domain that mediates interaction with phosphorylated IRAK1."
      Lin C.C., Huoh Y.S., Schmitz K.R., Jensen L.E., Ferguson K.M.
      Structure 16:1806-1816(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 15-275, DOMAIN FHA, MUTAGENESIS OF ARG-106; THR-187 AND ASN-188.

    Entry informationi

    Entry nameiPELI2_HUMAN
    AccessioniPrimary (citable) accession number: Q9HAT8
    Secondary accession number(s): B2RDY5
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 24, 2003
    Last sequence update: March 1, 2001
    Last modified: October 1, 2014
    This is version 101 of the entry and version 1 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

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 14
      Human chromosome 14: 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. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    5. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3