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Q96FA3

- PELI1_HUMAN

UniProt

Q96FA3 - PELI1_HUMAN

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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

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. 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
Complete GO annotation...

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
Complete GO annotation...

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

BgeeiQ96FA3.
CleanExiHS_PELI1.
ExpressionAtlasiQ96FA3. baseline and differential.
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. 7 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.
GeneTreeiENSGT00390000007680.
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

        10         20         30         40         50
MFSPDQENHP SKAPVKYGEL IVLGYNGSLP NGDRGRRKSR FALFKRPKAN
60 70 80 90 100
GVKPSTVHIA CTPQAAKAIS NKDQHSISYT LSRAQTVVVE YTHDSNTDMF
110 120 130 140 150
QIGRSTESPI DFVVTDTVPG SQSNSDTQSV QSTISRFACR IICERNPPFT
160 170 180 190 200
ARIYAAGFDS SKNIFLGEKA AKWKTSDGQM DGLTTNGVLV MHPRNGFTED
210 220 230 240 250
SKPGIWREIS VCGNVFSLRE TRSAQQRGKM VEIETNQLQD GSLIDLCGAT
260 270 280 290 300
LLWRTAEGLS HTPTVKHLEA LRQEINAARP QCPVGFNTLA FPSMKRKDVV
310 320 330 340 350
DEKQPWVYLN CGHVHGYHNW GNKEERDGKD RECPMCRSVG PYVPLWLGCE
360 370 380 390 400
AGFYVDAGPP THAFSPCGHV CSEKTTAYWS QIPLPHGTHT FHAACPFCAH
410
QLAGEQGYIR LIFQGPLD
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. 7 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.
GeneTreei ENSGT00390000007680.
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

Bgeei Q96FA3.
CleanExi HS_PELI1.
ExpressionAtlasi Q96FA3. baseline and differential.
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

« Hide 'large scale' publications
  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 29, 2014
This is version 105 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