Q9HAT8 (PELI2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
E3 ubiquitin-protein ligase pellino homolog 2
Short name=Pellino-2
EC=6.3.2.-

Gene names

Name:

PELI2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	420 AA.
Sequence status	Complete.
Protein existence	Evidence 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. Can activate the MAP (mitogen activated protein) kinase pathway leading to activation of ELK1. Not required for NF-kappa-B activation. Ref.5 Ref.6 Ref.7 Ref.8
Pathway	Protein modification; protein ubiquitination.
Subunit structure	Interacts with TRAF6, IRAK1, IRAK4 and MAP3K7. Ref.5 Ref.6
Post-translational modification	Phosphorylated by IRAK1 and IRAK4 enhancing its E3 ligase activity. Ref.6
Sequence similarities	Belongs to the pellino family.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Molecular function	Ligase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	MyD88-dependent toll-like receptor signaling pathway Traceable author statement. Source: Reactome Toll signaling pathway Traceable author statement. Source: Reactome innate immune response Traceable author statement. Source: Reactome positive regulation of I-kappaB kinase/NF-kappaB cascade Traceable author statement. Source: Reactome positive regulation of MAPKKK cascade Inferred from direct assay Ref.5. Source: MGI positive regulation of protein phosphorylation Inferred from direct assay Ref.5. Source: MGI toll-like receptor 1 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
Cellular component	cytosol Traceable author statement. Source: Reactome
Molecular function	ligase activity Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction Ref.6. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
IRAK1	P51617	2	EBI-448407,EBI-358664
IRAK4	Q9NWZ3	3	EBI-448407,EBI-448378

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 420

420

E3 ubiquitin-protein ligase pellino homolog 2

PRO_0000194174

Amino acid modifications

Modified residue

176

1

N6-acetyllysine Ref.9

Secondary structure

1

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420

Helix Strand Turn

Details...

Beta strand

22 – 24

3

Beta strand

41 – 43

3

Beta strand

55 – 63

9

Beta strand

77 – 82

6

Beta strand

84 – 94

11

Beta strand

99 – 104

6

Beta strand

138 – 148

11

Beta strand

153 – 157

5

Beta strand

164 – 168

5

Beta strand

191 – 193

3

Beta strand

208 – 211

4

Beta strand

245 – 247

3

Beta strand

252 – 255

4

Sequences

	Sequence		Length	Mass (Da)
	Q9HAT8 [UniParc]. Last modified March 1, 2001. Version 1. Checksum: 2FC5E661C13BC11A	FASTA	420	46,435
	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

References

	« Hide 'large scale' referencesShow '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: 11306823] [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: 14702039] [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. , 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: 15489334] [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: 12804775] [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: 12860405] [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: 17675297] [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: 17997719] [Abstract] Cited for: FUNCTION.
[9]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-176, MASS SPECTROMETRY.
+	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.

IPI

IPI00009753.

RefSeq

NP_067078.1. NM_021255.2.

UniGene

Hs.657926.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3EGA	X-ray	1.80	A	15-275	[»]
3EGB	X-ray	3.25	A/B	7-289	[»]

ProteinModelPortal

Q9HAT8.

SMR

Q9HAT8. Positions 15-258.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-31350N.

IntAct

Q9HAT8. 13 interactions.

MINT

MINT-2845048.

STRING

Q9HAT8.

PTM databases

PhosphoSite

Q9HAT8.

Polymorphism databases

DMDM

37999785.

Proteomic databases

PRIDE

Q9HAT8.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000267460; ENSP00000267460; ENSG00000139946.

GeneID

57161.

KEGG

hsa:57161.

UCSC

uc001xch.1. human.

Organism-specific databases

CTD

57161.

GeneCards

GC14P056585.

H-InvDB

HIX0011690.

HGNC

HGNC:8828. PELI2.

neXtProt

NX_Q9HAT8.

PharmGKB

PA33173.

GenAtlas

Search...

Phylogenomic databases

GeneTree

ENSGT00390000007680.

HOGENOM

HBG385966.

HOVERGEN

HBG053559.

InParanoid

Q9HAT8.

OMA

ESKPGVW.

OrthoDB

EOG466VKV.

PhylomeDB

Q9HAT8.

Enzyme and pathway databases

Reactome

REACT_6900. Immune System.

Gene expression databases

ArrayExpress

Q9HAT8.

Bgee

Q9HAT8.

CleanEx

HS_PELI2.

Genevestigator

Q9HAT8.

GermOnline

ENSG00000139946. Homo sapiens.

Family and domain databases

InterPro

IPR006800. Pellino.
[Graphical view]

KO

K11964.

Pfam

PF04710. Pellino. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

63165.

Entry information

Entry name

PELI2_HUMAN

Accession

Primary (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:	January 25, 2012
This is version 75 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.