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Q9HAT8 (PELI2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 99. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | 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 2

Short name=Pellino-2
EC=6.3.2.-
Gene names
Name:PELI2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length420 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 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. Ref.5 Ref.6 Ref.7 Ref.8 Ref.9

Pathway

Protein modification; protein ubiquitination.

Subunit structure

Interacts with TRAF6, IRAK1, IRAK4 and MAP3K7. Interacts with BCL10; this interaction is impaired by SOCS3 By similarity. Ref.5 Ref.6

Domain

The atypical FHA domain contains a 'wing' insert and mediates binding to threonine-phosphorylated IRAK1. Ref.10

Post-translational modification

Phosphorylated by IRAK1 and IRAK4 enhancing its E3 ligase activity. Ref.6

Sequence similarities

Belongs to the pellino family.

Contains 1 FHA domain.

Ontologies

Keywords
   Biological processUbl conjugation pathway
   Molecular functionLigase
   PTMPhosphoprotein
   Technical term3D-structure
Complete 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

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

Traceable author statement. Source: Reactome

positive regulation of MAPK cascade

Inferred from direct assay Ref.5. Source: MGI

positive regulation of protein phosphorylation

Inferred from direct assay Ref.5. Source: MGI

protein ubiquitination

Inferred from electronic annotation. Source: UniProtKB-UniPathway

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

   Molecular_functionligase activity

Inferred from electronic annotation. Source: UniProtKB-KW

protein binding

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

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

IRAK1P516173EBI-448407,EBI-358664
IRAK4Q9NWZ33EBI-448407,EBI-448378

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 420420E3 ubiquitin-protein ligase pellino homolog 2
PRO_0000194174

Regions

Domain15 – 202188FHA; atypical

Experimental info

Mutagenesis1061R → A: Abolishes binding to IRAK1. Ref.10
Mutagenesis1871T → A: Abolishes binding to IRAK1; when associated with A-188. Ref.10
Mutagenesis1881N → A: Abolishes binding to IRAK1; when associated with A-187. Ref.10
Mutagenesis3971C → A: Loss of IRAK1-polyubiquitination. Ref.9
Mutagenesis4001C → A: Loss of IRAK1-polyubiquitination. Ref.9

Secondary structure

......................................... 420
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q9HAT8 [UniParc].

Last modified March 1, 2001. Version 1.
Checksum: 2FC5E661C13BC11A

FASTA42046,435
        10         20         30         40         50         60 
MFSPGQEEHC APNKEPVKYG ELVVLGYNGA LPNGDRGRRK SRFALYKRPK ANGVKPSTVH 

        70         80         90        100        110        120 
VISTPQASKA ISCKGQHSIS YTLSRNQTVV VEYTHDKDTD MFQVGRSTES PIDFVVTDTI 

       130        140        150        160        170        180 
SGSQNTDEAQ ITQSTISRFA CRIVCDRNEP YTARIFAAGF DSSKNIFLGE KAAKWKNPDG 

       190        200        210        220        230        240 
HMDGLTTNGV LVMHPRGGFT EESQPGVWRE ISVCGDVYTL RETRSAQQRG KLVESETNVL 

       250        260        270        280        290        300 
QDGSLIDLCG ATLLWRTADG LFHTPTQKHI EALRQEINAA RPQCPVGLNT LAFPSINRKE 

       310        320        330        340        350        360 
VVEEKQPWAY LSCGHVHGYH NWGHRSDTEA NERECPMCRT VGPYVPLWLG CEAGFYVDAG 

       370        380        390        400        410        420 
PPTHAFTPCG HVCSEKSAKY WSQIPLPHGT HAFHAACPFC ATQLVGEQNC IKLIFQGPID 

« Hide

References

« Hide 'large scale' references
[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. 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].
Tissue: Testis.
[3]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF302502 mRNA. Translation: AAG15390.1.
AK315727 mRNA. Translation: BAG38082.1.
CH471061 Genomic DNA. Translation: EAW80689.1.
BC009476 mRNA. Translation: AAH09476.1.
CCDSCCDS9726.1.
RefSeqNP_067078.1. NM_021255.2.
UniGeneHs.657926.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3EGAX-ray1.80A15-275[»]
3EGBX-ray3.25A/B7-289[»]
ProteinModelPortalQ9HAT8.
SMRQ9HAT8. Positions 15-258.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid121417. 18 interactions.
DIPDIP-31350N.
IntActQ9HAT8. 14 interactions.
MINTMINT-2845048.
STRING9606.ENSP00000267460.

PTM databases

PhosphoSiteQ9HAT8.

Polymorphism databases

DMDM37999785.

Proteomic databases

MaxQBQ9HAT8.
PaxDbQ9HAT8.
PRIDEQ9HAT8.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000267460; ENSP00000267460; ENSG00000139946.
GeneID57161.
KEGGhsa:57161.
UCSCuc001xch.3. human.

Organism-specific databases

CTD57161.
GeneCardsGC14P056585.
HGNCHGNC:8828. PELI2.
MIM614798. gene.
neXtProtNX_Q9HAT8.
PharmGKBPA33173.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG258040.
HOGENOMHOG000234110.
HOVERGENHBG053559.
InParanoidQ9HAT8.
KOK11964.
OMAHAPTQKH.
PhylomeDBQ9HAT8.
TreeFamTF314338.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.
UniPathwayUPA00143.

Gene expression databases

ArrayExpressQ9HAT8.
BgeeQ9HAT8.
CleanExHS_PELI2.
GenevestigatorQ9HAT8.

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

EvolutionaryTraceQ9HAT8.
GeneWikiPELI2.
GenomeRNAi57161.
NextBio63165.
PROQ9HAT8.
SOURCESearch...

Entry information

Entry namePELI2_HUMAN
AccessionPrimary (citable) accession number: Q9HAT8
Secondary accession number(s): B2RDY5
Entry history
Integrated into UniProtKB/Swiss-Prot: October 24, 2003
Last sequence update: March 1, 2001
Last modified: July 9, 2014
This is version 99 of the entry and version 1 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

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 14

Human chromosome 14: entries, gene names and cross-references to MIM