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Q96FA3 (PELI1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 102. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
E3 ubiquitin-protein ligase pellino homolog 1

Short name=Pellino-1
EC=6.3.2.-
Alternative name(s):
Pellino-related intracellular-signaling molecule
Gene names
Name:PELI1
Synonyms:PRISM
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length418 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.6 Ref.9

Pathway

Protein modification; protein ubiquitination.

Subunit structure

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. Ref.6 Ref.7 Ref.8

Post-translational modification

Phosphorylation by IRAK1 and IRAK4 enhances its E3 ligase activity.

Sumoylated. Ref.11

Sequence similarities

Belongs to the pellino family.

Sequence caution

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.

Ontologies

Keywords
   Biological processUbl conjugation pathway
   Molecular functionLigase
   PTMPhosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processMyD88-dependent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

Toll signaling pathway

Inferred from electronic annotation. Source: InterPro

innate immune response

Traceable author statement. Source: Reactome

negative regulation of NF-kappaB transcription factor activity

Inferred from electronic annotation. Source: Ensembl

negative regulation of T cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of B cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of I-kappaB kinase/NF-kappaB signaling

Traceable author statement. Source: Reactome

positive regulation of cytokine production

Inferred from electronic annotation. Source: Ensembl

positive regulation of protein ubiquitination

Inferred from electronic annotation. Source: Ensembl

positive regulation of toll-like receptor 3 signaling pathway

Inferred from electronic annotation. Source: Ensembl

positive regulation of toll-like receptor 4 signaling pathway

Inferred from electronic annotation. Source: Ensembl

protein K48-linked ubiquitination

Inferred from electronic annotation. Source: Ensembl

response to dsRNA

Inferred from electronic annotation. Source: Ensembl

response to lipopolysaccharide

Inferred from electronic annotation. Source: Ensembl

toll-like receptor 10 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 4 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 5 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 9 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor TLR1:TLR2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor TLR6:TLR2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

   Cellular_componentcytosol

Traceable author statement. Source: Reactome

nucleus

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionprotein binding

Inferred from physical interaction Ref.6PubMed 16884718. Source: IntAct

ubiquitin-protein transferase activity

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

IRAK1P516173EBI-448369,EBI-358664

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 418418E3 ubiquitin-protein ligase pellino homolog 1
PRO_0000194172

Experimental info

Sequence conflict111S → F in CAC04320. Ref.1
Sequence conflict1001F → S in BAB55280. Ref.5
Sequence conflict2601S → P in BAB55280. Ref.5

Sequences

Sequence LengthMass (Da)Tools
Q96FA3 [UniParc].

Last modified October 24, 2003. Version 2.
Checksum: 233318A45E7546F7

FASTA41846,286
        10         20         30         40         50         60 
MFSPDQENHP SKAPVKYGEL IVLGYNGSLP NGDRGRRKSR FALFKRPKAN GVKPSTVHIA 

        70         80         90        100        110        120 
CTPQAAKAIS NKDQHSISYT LSRAQTVVVE YTHDSNTDMF QIGRSTESPI DFVVTDTVPG 

       130        140        150        160        170        180 
SQSNSDTQSV QSTISRFACR IICERNPPFT ARIYAAGFDS SKNIFLGEKA AKWKTSDGQM 

       190        200        210        220        230        240 
DGLTTNGVLV MHPRNGFTED SKPGIWREIS VCGNVFSLRE TRSAQQRGKM VEIETNQLQD 

       250        260        270        280        290        300 
GSLIDLCGAT LLWRTAEGLS HTPTVKHLEA LRQEINAARP QCPVGFNTLA FPSMKRKDVV 

       310        320        330        340        350        360 
DEKQPWVYLN CGHVHGYHNW GNKEERDGKD RECPMCRSVG PYVPLWLGCE AGFYVDAGPP 

       370        380        390        400        410 
THAFSPCGHV CSEKTTAYWS QIPLPHGTHT FHAACPFCAH QLAGEQGYIR LIFQGPLD 

« Hide

References

« Hide 'large scale' references
[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. expand/collapse author list , 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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS1876.1.
RefSeqNP_065702.2. NM_020651.3.
UniGeneHs.7886.

3D structure databases

ProteinModelPortalQ96FA3.
SMRQ96FA3. Positions 14-256.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid121418. 21 interactions.
DIPDIP-32488N.
IntActQ96FA3. 6 interactions.
MINTMINT-2844985.
STRING9606.ENSP00000351789.

PTM databases

PhosphoSiteQ96FA3.

Polymorphism databases

DMDM37999756.

Proteomic databases

MaxQBQ96FA3.
PaxDbQ96FA3.
PRIDEQ96FA3.

Protocols and materials databases

DNASU57162.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000358912; ENSP00000351789; ENSG00000197329.
GeneID57162.
KEGGhsa:57162.
UCSCuc002scr.4. human.

Organism-specific databases

CTD57162.
GeneCardsGC02M064319.
HGNCHGNC:8827. PELI1.
HPAHPA053182.
MIM614797. gene.
neXtProtNX_Q96FA3.
PharmGKBPA33172.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG258040.
HOGENOMHOG000234110.
HOVERGENHBG053559.
InParanoidQ96FA3.
KOK11964.
OMAGKMVENE.
OrthoDBEOG751NFB.
PhylomeDBQ96FA3.
TreeFamTF314338.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.
SignaLinkQ96FA3.
UniPathwayUPA00143.

Gene expression databases

ArrayExpressQ96FA3.
BgeeQ96FA3.
CleanExHS_PELI1.
GenevestigatorQ96FA3.

Family and domain databases

InterProIPR006800. Pellino_fam.
[Graphical view]
PANTHERPTHR12098. PTHR12098. 1 hit.
PfamPF04710. Pellino. 1 hit.
[Graphical view]
PIRSFPIRSF038886. Pellino. 1 hit.
ProtoNetSearch...

Other

GeneWikiPELI1.
GenomeRNAi57162.
NextBio63169.
PROQ96FA3.
SOURCESearch...

Entry information

Entry namePELI1_HUMAN
AccessionPrimary (citable) accession number: Q96FA3
Secondary accession number(s): Q96SM0, Q9GZY5, Q9HCX0
Entry history
Integrated into UniProtKB/Swiss-Prot: October 24, 2003
Last sequence update: October 24, 2003
Last modified: July 9, 2014
This is version 102 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM