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Protein

E3 ubiquitin-protein ligase pellino homolog 1

Gene

PELI1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: 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 Componenti: 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.

Polymorphism and mutation databases

BioMutaiPELI1.
DMDMi37999756.

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.

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
TRIP13Q156453EBI-448369,EBI-358993
VAC14Q08AM63EBI-448369,EBI-2107455

Protein-protein interaction databases

BioGridi121418. 23 interactions.
DIPiDIP-32488N.
IntActiQ96FA3. 12 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.
OMAiSGEQGYI.
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.Curated
The sequence BAB55280.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

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:
EMBLi
GenBanki
DDBJi
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 and mutation databases

BioMutaiPELI1.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

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

Protein-protein interaction databases

BioGridi121418. 23 interactions.
DIPiDIP-32488N.
IntActiQ96FA3. 12 interactions.
MINTiMINT-2844985.
STRINGi9606.ENSP00000351789.

PTM databases

PhosphoSiteiQ96FA3.

Polymorphism and mutation databases

BioMutaiPELI1.
DMDMi37999756.

Proteomic databases

MaxQBiQ96FA3.
PaxDbiQ96FA3.
PRIDEiQ96FA3.

Protocols and materials databases

DNASUi57162.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi57162.
GeneCardsiGC02M064319.
HGNCiHGNC:8827. PELI1.
MIMi614797. gene.
neXtProtiNX_Q96FA3.
PharmGKBiPA33172.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG258040.
GeneTreeiENSGT00390000007680.
HOGENOMiHOG000234110.
HOVERGENiHBG053559.
InParanoidiQ96FA3.
KOiK11964.
OMAiSGEQGYI.
OrthoDBiEOG751NFB.
PhylomeDBiQ96FA3.
TreeFamiTF314338.

Enzyme and pathway databases

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

Miscellaneous databases

GeneWikiiPELI1.
GenomeRNAii57162.
NextBioi63169.
PROiQ96FA3.
SOURCEiSearch...

Gene expression databases

BgeeiQ96FA3.
CleanExiHS_PELI1.
ExpressionAtlasiQ96FA3. baseline and differential.
GenevestigatoriQ96FA3.

Family and domain databases

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

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: April 29, 2015
This is version 109 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.