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Protein

E3 ubiquitin-protein ligase pellino homolog 1

Gene

PELI1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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 (PubMed:12496252, PubMed:17675297). Mediates 'Lys-48'-linked polyubiquitination of RIPK3 leading to its subsequent proteasome-dependent degradation; preferentially recognizes and mediates the degradation of the 'Thr-182' phosphorylated form of RIPK3 (PubMed:29883609). Negatively regulates necroptosis by reducing RIPK3 expression (PubMed:29883609). Mediates 'Lys-63'-linked ubiquitination of RIPK1 (PubMed:29883609).3 Publications

Catalytic activityi

S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-ubiquitinyl-[acceptor protein]-L-lysine.1 Publication

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionTransferase
Biological processUbl conjugation pathway

Enzyme and pathway databases

ReactomeiR-HSA-9020702 Interleukin-1 signaling
R-HSA-937039 IRAK1 recruits IKK complex
R-HSA-975144 IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation
SignaLinkiQ96FA3
SIGNORiQ96FA3
UniPathwayi
UPA00143

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase pellino homolog 1 (EC:2.3.2.271 Publication)
Short name:
Pellino-1
Alternative name(s):
Pellino-related intracellular-signaling molecule
RING-type E3 ubiquitin transferase pellino homolog 1Curated
Gene namesi
Name:PELI1
Synonyms:PRISM
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000197329.11
HGNCiHGNC:8827 PELI1
MIMi614797 gene
neXtProtiNX_Q96FA3

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi104R → A: Loss of ability to ubiquitinate RIPK3. Loss of interaction with RIPK1, IRAK1 and RIPK3. 1 Publication1
Mutagenesisi313H → A: Loss of ability to ubiquitinate RIPK3. No loss of interaction with RIPK3. 1 Publication1
Mutagenesisi336C → A: Loss of ability to ubiquitinate RIPK3. No loss of interaction with RIPK3. 1 Publication1

Organism-specific databases

DisGeNETi57162
OpenTargetsiENSG00000197329
PharmGKBiPA33172

Polymorphism and mutation databases

BioMutaiPELI1
DMDMi37999756

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001941721 – 418E3 ubiquitin-protein ligase pellino homolog 1Add BLAST418

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

EPDiQ96FA3
MaxQBiQ96FA3
PaxDbiQ96FA3
PeptideAtlasiQ96FA3
PRIDEiQ96FA3
ProteomicsDBi76505

PTM databases

iPTMnetiQ96FA3
PhosphoSitePlusiQ96FA3

Expressioni

Tissue specificityi

Expressed at high levels in normal skin but decreased in keratinocytes from toxic epidermal necrolysis (TEN) patients (at protein level).1 Publication

Gene expression databases

BgeeiENSG00000197329 Expressed in 225 organ(s), highest expression level in bone marrow
CleanExiHS_PELI1
ExpressionAtlasiQ96FA3 baseline and differential
GenevisibleiQ96FA3 HS

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 (PubMed:12496252, PubMed:12804775, PubMed:16951688). Interacts (via atypical FHA domain) with RIPK3; preferentially binds to the 'Thr-182' phosphorylated form of RIPK3 (PubMed:29883609). Interacts with RIPK1 and IRAK1 (PubMed:29883609).4 Publications

Binary interactionsi

Protein-protein interaction databases

BioGridi121418, 26 interactors
DIPiDIP-32488N
IntActiQ96FA3, 23 interactors
MINTiQ96FA3
STRINGi9606.ENSP00000351789

Structurei

3D structure databases

ProteinModelPortaliQ96FA3
SMRiQ96FA3
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini13 – 200FHA; atypicalBy similarityAdd BLAST188

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni311 – 399Ring-like domain; necessary for ubiqitination of RIPK31 PublicationAdd BLAST89

Sequence similaritiesi

Belongs to the pellino family.Curated

Phylogenomic databases

eggNOGiKOG3842 Eukaryota
ENOG410XP3S LUCA
GeneTreeiENSGT00390000007680
HOGENOMiHOG000234110
HOVERGENiHBG053559
InParanoidiQ96FA3
KOiK11964
OMAiCPFCAQQ
OrthoDBiEOG091G0631
PhylomeDBiQ96FA3
TreeFamiTF314338

Family and domain databases

InterProiView protein in InterPro
IPR006800 Pellino_fam
PANTHERiPTHR12098 PTHR12098, 1 hit
PfamiView protein in Pfam
PF04710 Pellino, 1 hit
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 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAB55280 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti11S → F in CAC04320 (PubMed:11132151).Curated1
Sequence conflicti100F → S in BAB55280 (PubMed:14702039).Curated1
Sequence conflicti260S → P in BAB55280 (PubMed:14702039).Curated1

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
XP_011531296.1, XM_011532994.2
XP_016860009.1, XM_017004520.1
UniGeneiHs.7886

Genome annotation databases

EnsembliENST00000358912; ENSP00000351789; ENSG00000197329
GeneIDi57162
KEGGihsa:57162
UCSCiuc002sct.5 human

Similar proteinsi

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
XP_011531296.1, XM_011532994.2
XP_016860009.1, XM_017004520.1
UniGeneiHs.7886

3D structure databases

ProteinModelPortaliQ96FA3
SMRiQ96FA3
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi121418, 26 interactors
DIPiDIP-32488N
IntActiQ96FA3, 23 interactors
MINTiQ96FA3
STRINGi9606.ENSP00000351789

PTM databases

iPTMnetiQ96FA3
PhosphoSitePlusiQ96FA3

Polymorphism and mutation databases

BioMutaiPELI1
DMDMi37999756

Proteomic databases

EPDiQ96FA3
MaxQBiQ96FA3
PaxDbiQ96FA3
PeptideAtlasiQ96FA3
PRIDEiQ96FA3
ProteomicsDBi76505

Protocols and materials databases

DNASUi57162
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000358912; ENSP00000351789; ENSG00000197329
GeneIDi57162
KEGGihsa:57162
UCSCiuc002sct.5 human

Organism-specific databases

CTDi57162
DisGeNETi57162
EuPathDBiHostDB:ENSG00000197329.11
GeneCardsiPELI1
HGNCiHGNC:8827 PELI1
MIMi614797 gene
neXtProtiNX_Q96FA3
OpenTargetsiENSG00000197329
PharmGKBiPA33172
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3842 Eukaryota
ENOG410XP3S LUCA
GeneTreeiENSGT00390000007680
HOGENOMiHOG000234110
HOVERGENiHBG053559
InParanoidiQ96FA3
KOiK11964
OMAiCPFCAQQ
OrthoDBiEOG091G0631
PhylomeDBiQ96FA3
TreeFamiTF314338

Enzyme and pathway databases

UniPathwayi
UPA00143

ReactomeiR-HSA-9020702 Interleukin-1 signaling
R-HSA-937039 IRAK1 recruits IKK complex
R-HSA-975144 IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation
SignaLinkiQ96FA3
SIGNORiQ96FA3

Miscellaneous databases

ChiTaRSiPELI1 human
GeneWikiiPELI1
GenomeRNAii57162
PROiPR:Q96FA3
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000197329 Expressed in 225 organ(s), highest expression level in bone marrow
CleanExiHS_PELI1
ExpressionAtlasiQ96FA3 baseline and differential
GenevisibleiQ96FA3 HS

Family and domain databases

InterProiView protein in InterPro
IPR006800 Pellino_fam
PANTHERiPTHR12098 PTHR12098, 1 hit
PfamiView protein in Pfam
PF04710 Pellino, 1 hit
PIRSFiPIRSF038886 Pellino, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiPELI1_HUMAN
AccessioniPrimary (citable) accession number: Q96FA3
Secondary accession number(s): Q96SM0, Q9GZY5, Q9HCX0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 24, 2003
Last sequence update: October 24, 2003
Last modified: November 7, 2018
This is version 137 of the entry and version 2 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. PATHWAY comments
    Index of metabolic and biosynthesis pathways
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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