PELI1

Summary

PELI1 (pellino E3 ubiquitin protein ligase 1, HGNC:8827) is a protein-coding gene on chromosome 2p14, encoding E3 ubiquitin-protein ligase pellino homolog 1 (Q96FA3). E3 ubiquitin ligase catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins.

Enables ubiquitin-ubiquitin ligase activity. Involved in several processes, including negative regulation of TORC1 signaling; negative regulation of necroptotic process; and protein polyubiquitination. Is active in site of double-strand break. Implicated in colorectal cancer.

Source: NCBI Gene 57162 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 58 total
• Druggable target: yes
• MANE Select transcript: NM_020651

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8827
Approved symbol	PELI1
Name	pellino E3 ubiquitin protein ligase 1
Location	2p14
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000197329
Ensembl biotype	protein_coding
OMIM	614797
Entrez	57162

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 13 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000358912, ENST00000466177, ENST00000468869, ENST00000494203, ENST00000903228, ENST00000903229, ENST00000903230, ENST00000903231, ENST00000924985, ENST00000924986, ENST00000924987, ENST00000924988, ENST00000924989, ENST00000942852, ENST00000942853, ENST00000942854

RefSeq mRNA: 1 — MANE Select: NM_020651 NM_020651

CCDS: CCDS1876

Canonical transcript exons

ENST00000358912 — 7 exons

Exon	Start	End
ENSE00000932745	64096125	64096313
ENSE00000932746	64096413	64096610
ENSE00001719950	64092652	64095268
ENSE00001838495	64144081	64144420
ENSE00003631023	64100398	64100499
ENSE00003643268	64104701	64104830
ENSE00003647283	64108240	64108379

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 97.22.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 25.4765 / max 2962.2222, expressed in 1654 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
28740	20.2951	1610
28739	3.4218	670
202210	1.4537	495
28732	0.2384	84
28730	0.0675	21

Top tissues by expression

288 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
cartilage tissue	UBERON:0002418	97.22	gold quality
mucosa of paranasal sinus	UBERON:0005030	97.22	gold quality
pharyngeal mucosa	UBERON:0000355	97.08	gold quality
amniotic fluid	UBERON:0000173	96.77	gold quality
upper leg skin	UBERON:0004262	96.63	gold quality
vena cava	UBERON:0004087	96.43	gold quality
oral cavity	UBERON:0000167	96.09	gold quality
cervix squamous epithelium	UBERON:0006922	96.08	gold quality
cervix epithelium	UBERON:0004801	96.06	gold quality
tongue squamous epithelium	UBERON:0006919	96.03	gold quality
lower esophagus mucosa	UBERON:0035834	95.85	gold quality
esophagus squamous epithelium	UBERON:0006920	95.83	gold quality
epithelium of esophagus	UBERON:0001976	95.56	gold quality
penis	UBERON:0000989	95.54	gold quality
bone marrow	UBERON:0002371	95.51	gold quality
squamous epithelium	UBERON:0006914	95.34	gold quality
cortical plate	UBERON:0005343	95.24	gold quality
epithelium of nasopharynx	UBERON:0001951	95.18	gold quality
upper arm skin	UBERON:0004263	95.04	gold quality
oocyte	CL:0000023	94.77	gold quality
trigeminal ganglion	UBERON:0001675	94.75	gold quality
bone marrow cell	CL:0002092	94.54	gold quality
trachea	UBERON:0003126	94.39	gold quality
nasal cavity epithelium	UBERON:0005384	94.34	gold quality
blood	UBERON:0000178	94.18	gold quality
epithelium of mammary gland	UBERON:0003244	94.13	gold quality
monocyte	CL:0000576	94.08	gold quality
mononuclear cell	CL:0000842	94.06	gold quality
mammary duct	UBERON:0001765	94.03	gold quality
nasal cavity mucosa	UBERON:0001826	93.88	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-GEOD-106540	yes	480.03
E-MTAB-9221	yes	17.30
E-CURD-46	yes	13.33
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

198 targeting PELI1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AA	99.96	70.64	3753

Literature-anchored findings (GeneRIF, showing 39)

• role in interleukin-1-mediated signalling through interaction with interleukin-1 receptor-associated kinase 4-IRAK-tumor necrosis factor receptor-associated factor 6 complex (PMID:12496252)
• Smad6 bound to Pellino-1 promoted TGF-beta-mediated anti-inflammatory effects. (PMID:16951688)
• kinase-inactive IRAK proteins can associate with Pellino proteins, thus excluding the possibility that their inability to regulate Pellino degradation is due to lack of association with the Pellino proteins (PMID:17675297)
• incomplete KD, IVIG nonresponsiveness, long febrile days, and the rs7604693 genetic variant in the PELI1 gene are major risk factors for the development of CALs (PMID:22105492)
• Pellino1 interacts with the transcription factor Deformed Epidermal Autoregulatory Factor 1 (DEAF1). (PMID:23846693)
• GWAS study found two new SNPs associated with nickel dermatitis; SNPs are located in the NTN4 and PELI1 genes (PMID:23921680)
• Peptide PEL1 derived from the interleukin-1 receptor-associated kinase (IRAK)1-binding motif reveals a distinct phosphothreonine peptide binding preference. (PMID:25027698)
• Increased PELI1 expression and subsequent induction of BCL6 promotes lymphomagenesis. (PMID:25295537)
• The study results in the Chinese Han population showed that PELI1 is a member of a constellation of genetic factors that may contribute to the pathogenesis of systemic lupus erythematosus. (PMID:25712248)
• Our observations suggested that Peli-1 gene polymorphism rs329498 might contribute to SLE susceptibility in Chinese Han Population. (PMID:27018966)
• Results indicate that Pellino-1 contributes to lung oncogenesis through the overexpression of inhibitor of apoptosis protein 2 (cIAP2) and promotion of cell survival and chemoresistance. (PMID:27248820)
• The combination of low Pellino3 levels together with high and inducible Pellino1 expression may be an important determinant of the degree of inflammation triggered upon Toll-like receptor 2 engagement by Helicobacter pylori and/or its components, contributing to Helicobacter pylori-associated pathogenesis by directing the incoming signal toward an NF-kB-mediated proinflammatory response. (PMID:27302665)
• Our results suggest that PELI1 might participate in B-cell maturation or oncogenic activation of aggressive B-cell lymphomas, both during and after germinal center stages (PMID:27469333)
• Pellino-1 overexpression activated PI3K/Akt and ERK signaling pathways and elicited an epithelial-mesenchymal transition (EMT) phenotype of lung adenocarcinoma cells. Pellino-1-mediated EMT was demonstrated through morphology, the upregulation of Vimentin, Slug and Snail expression and the downregulation of E-cadherin and beta-catenin expression. (PMID:28009353)
• Pellino 1 expression acts as an inhibitory signal of the homeostatic regulation of mitotic cell cycle and checkpoint, and thus contributes to the initiation and progression of neoplastic chromosome aneuploidy. (PMID:28410192)
• The study demonstrates that cytosolic Pellino-1-mediated K63-linked ubiquitination of IRF5 in M1 macrophages regulates glucose intolerance in obesity, suggesting a cytosolic mediator function of Pellino-1 in TLR4/IFN-gamma receptor-IRF5 axis during M1 polarization. (PMID:28746869)
• This study demonstrates Pellino 1 (PELI1) as an important modulator that exerts opposite regulatory functions on apoptosis and necroptosis, two distinct forms of regulated cell death mechanisms. (PMID:29078411)
• Peli1-mediated regulation of Mdmx. (PMID:29523541)
• Overexpression of Peli1 inhibits noncanonical NF-kappaB activation and alleviates lupus-like disease. PELI1 levels negatively correlate with disease severity in SLE patients. (PMID:29555915)
• Pellino-1 may be critically important for cell survival. (PMID:29860626)
• PELI1 may function to control inadvertent activation of RIP3, thus preventing aberrant cell death and maintaining cellular homeostasis. (PMID:29883609)
• Pellino1 (Peli1) is a DSB-responsive ubiquitin ligase required for the accumulation of DNA damage response proteins and efficient homologous recombination (HR) repair. (PMID:30952868)
• Activation of the p21 gene by p53 in response to DNA damage requires Pellino1. (PMID:30987826)
• Peli1 controls the survival of dopaminergic neurons through modulating microglia-mediated neuroinflammation. (PMID:31142803)
• MiR-153-3p induces immune dysregulation by inhibiting PELI1 expression in umbilical cord-derived mesenchymal stem cells in patients with systemic lupus erythematosus. (PMID:32321315)
• miR-21 and Pellino-1 Expression Profiling in Autoimmune Premature Ovarian Insufficiency. (PMID:32352018)
• Peli1 signaling blockade attenuates congenital zika syndrome. (PMID:32544190)
• Resistomycin attenuates triple-negative breast cancer progression by inhibiting E3 ligase Pellino-1 and inducing SNAIL/SLUG degradation. (PMID:32728028)
• Redox DAPK1 destabilizes Pellino1 to govern inflammation-coupling tubular damage during septic AKI. (PMID:33052227)
• Immune-related genes STIM1, ITPKC and PELI1 polymorphisms are associated with risk of colorectal cancer. (PMID:33470690)
• PELI1 promotes radiotherapy sensitivity by inhibiting noncanonical NF-kappaB in esophageal squamous cancer. (PMID:34738714)
• MiR-301a-3p Advances IRAK1-Mediated Differentiation of Th17 Cells to Promote the Progression of Systemic Lupus Erythematosus via Targeting PELI1. (PMID:34931135)
• MiR-30c-5p loss-induced PELI1 accumulation regulates cell proliferation and migration via activating PI3K/AKT pathway in papillary thyroid carcinoma. (PMID:34991623)
• miR-590-5p Overexpression Alleviates beta-Amyloid-Induced Neuron Damage via Targeting Pellino-1. (PMID:35310934)
• Cardiomyocyte-specific Peli1 contributes to the pressure overload-induced cardiac fibrosis through miR-494-3p-dependent exosomal communication. (PMID:36520055)
• Aberrant expression of PELI1 caused by Jagged1 accelerates the malignant phenotype of pancreatic cancer. (PMID:37657587)
• PELI1: key players in the oncogenic characteristics of pancreatic Cancer. (PMID:38528516)
• Pellino1 orchestrates gut-kidney axis to perpetuate septic acute kidney injury through activation of STING pathway and NLRP3 inflammasome. (PMID:38580196)
• PELI1 overexpression contributes to pancreatic cancer progression through upregulating ubiquitination-mediated INPP5J degradation. (PMID:38685520)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	peli1b	ENSDARG00000044083
mus_musculus	Peli1	ENSMUSG00000020134
rattus_norvegicus	Peli1	ENSRNOG00000006329
drosophila_melanogaster	Pli	FBGN0025574
caenorhabditis_elegans		WBGENE00017766

Paralogs (2): PELI2 (ENSG00000139946), PELI3 (ENSG00000174516)

Protein

Protein identifiers

E3 ubiquitin-protein ligase pellino homolog 1 — Q96FA3 (reviewed: Q96FA3)

Alternative names: Pellino-related intracellular-signaling molecule, RING-type E3 ubiquitin transferase pellino homolog 1

All UniProt accessions (2): Q96FA3, Q53T26

UniProt curated annotations — full annotation on UniProt →

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. Acts as a positive regulator of inflammatory response in microglia through activation of NF-kappa-B and MAP kinase. Mediates ‘Lys-63’-linked polyubiquitination of IRAK1 allowing subsequent NF-kappa-B activation. Conjugates ‘Lys-63’-linked ubiquitin chains to the adapter protein ASC/PYCARD, which in turn is crucial for NLRP3 inflammasome activation. 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. Negatively regulates necroptosis by reducing RIPK3 expression. Mediates ‘Lys-63’-linked ubiquitination of RIPK1. Following phosphorylation by ATM, catalyzes ‘Lys-63’-linked ubiquitination of NBN, promoting DNA repair via homologous recombination. Negatively regulates activation of the metabolic mTORC1 signaling pathway by mediating ‘Lys-63’-linked ubiquitination of mTORC1-inhibitory protein TSC1 and thereby promoting TSC1/TSC2 complex stability.

Subunit / interactions. 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. Interacts (via atypical FHA domain) with RIPK3; preferentially binds to the ‘Thr-182’ phosphorylated form of RIPK3. Interacts with RIPK1 and IRAK1.

Subcellular location. Chromosome.

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

Post-translational modifications. Phosphorylation by IRAK1 and IRAK4 enhances its E3 ligase activity. Phosphorylated by ATM in response to DNA damage, promoting localization to DNA double-strand breaks (DSBs) and ability to mediate ‘Lys-63’-linked ubiquitination of NBN. Sumoylated.

Pathway. Protein modification; protein ubiquitination.

Similarity. Belongs to the pellino family.

RefSeq proteins (1): NP_065702* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006800	Pellino_fam	Family
IPR048334	Pellino_FHA	Domain
IPR048335	Pellino_RING	Domain

Pfam: PF04710, PF20723

UniProt features (33 total): strand 18, mutagenesis site 5, sequence conflict 3, modified residue 2, chain 1, domain 1, helix 1, region of interest 1, turn 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
9IF9	X-RAY DIFFRACTION	2.55

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96FA3-F1	89.65	0.75

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (2): 121, 127

Mutagenesis-validated functional residues (5):

Position	Phenotype
104	loss of ability to ubiquitinate ripk3. loss of interaction with ripk1, irak1 and ripk3.
121	decreased phosphorylation by atm in response to dna damage; when associated with a-127.
127	decreased phosphorylation by atm in response to dna damage; when associated with a-121.
313	loss of ability to ubiquitinate ripk3 and nbn. no loss of interaction with ripk3.
336	loss of ability to ubiquitinate ripk3 and nbn. no loss of interaction with ripk3.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-5675482	Regulation of necroptotic cell death
R-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

MSigDB gene sets: 514 (showing top): GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR, GOBP_REGULATION_OF_CELL_ACTIVATION, MODULE_97, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_DNA_RECOMBINATION, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, KOBAYASHI_EGFR_SIGNALING_24HR_UP, REACTOME_INNATE_IMMUNE_SYSTEM, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_B_CELL_ACTIVATION, GOBP_NEGATIVE_REGULATION_OF_LEUKOCYTE_PROLIFERATION, chr2p14, MATTIOLI_MGUS_VS_PCL, AAGCCAT_MIR135A_MIR135B, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION

GO Biological Process (28): protein polyubiquitination (GO:0000209), positive regulation of cytokine production (GO:0001819), DNA repair (GO:0006281), regulation of Toll signaling pathway (GO:0008592), positive regulation of B cell proliferation (GO:0030890), positive regulation of protein ubiquitination (GO:0031398), response to lipopolysaccharide (GO:0032496), positive regulation of toll-like receptor 3 signaling pathway (GO:0034141), positive regulation of toll-like receptor 4 signaling pathway (GO:0034145), T cell proliferation (GO:0042098), negative regulation of T cell proliferation (GO:0042130), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), response to dsRNA (GO:0043331), regulation of necroptotic process (GO:0060544), negative regulation of necroptotic process (GO:0060546), protein K63-linked ubiquitination (GO:0070534), protein K48-linked ubiquitination (GO:0070936), negative regulation of TORC1 signaling (GO:1904262), positive regulation of double-strand break repair via homologous recombination (GO:1905168), double-strand break repair via homologous recombination (GO:0000724), DNA damage response (GO:0006974), protein ubiquitination (GO:0016567), TORC1 signaling (GO:0038202), T cell activation (GO:0042110), negative regulation of T cell activation (GO:0050868), positive regulation of B cell activation (GO:0050871), positive regulation of TORC1 signaling (GO:1904263)

GO Molecular Function (5): ubiquitin-ubiquitin ligase activity (GO:0034450), ubiquitin protein ligase activity (GO:0061630), ubiquitin-protein transferase activity (GO:0004842), protein binding (GO:0005515), transferase activity (GO:0016740)

GO Cellular Component (5): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), site of double-strand break (GO:0035861), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
RIPK1-mediated regulated necrosis	1
Interleukin-1 family signaling	1
MyD88:MAL(TIRAP) cascade initiated on plasma membrane	1
MyD88 cascade initiated on plasma membrane	1
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein ubiquitination	2
positive regulation of pattern recognition receptor signaling pathway	2
positive regulation of intracellular signal transduction	2
necroptotic process	2
protein polyubiquitination	2
cellular anatomical structure	2
cytokine production	1
regulation of cytokine production	1
positive regulation of gene expression	1
positive regulation of multicellular organismal process	1
DNA metabolic process	1
DNA damage response	1
Toll signaling pathway	1
regulation of signal transduction	1
regulation of B cell proliferation	1
B cell proliferation	1
positive regulation of lymphocyte proliferation	1
positive regulation of B cell activation	1
regulation of protein ubiquitination	1
positive regulation of protein modification by small protein conjugation or removal	1
response to molecule of bacterial origin	1
response to lipid	1
response to oxygen-containing compound	1
toll-like receptor 3 signaling pathway	1
regulation of toll-like receptor 3 signaling pathway	1
toll-like receptor 4 signaling pathway	1
regulation of toll-like receptor 4 signaling pathway	1
T cell activation	1
lymphocyte proliferation	1
T cell proliferation	1
regulation of T cell proliferation	1
negative regulation of lymphocyte proliferation	1
negative regulation of T cell activation	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
response to nitrogen compound	1
regulation of programmed necrotic cell death	1
regulation of necroptotic process	1

Protein interactions and networks

STRING

996 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PELI1	IRAK1	P51617	982
PELI1	TRADD	Q15628	955
PELI1	IRAK4	Q9NWZ3	947
PELI1	TRAF6	Q9Y4K3	909
PELI1	SMAD6	O43541	767
PELI1	RIPK1	Q13546	759
PELI1	TOLLIP	Q9H0E2	690
PELI1	TAB1	Q15750	687
PELI1	TLR3	O15455	661
PELI1	TLR4	O00206	654
PELI1	IL1R1	P14778	636
PELI1	MYD88	P78397	631
PELI1	TBK1	Q9UHD2	619
PELI1	TAB2	Q9NYJ8	569
PELI1	SMAD7	O15105	544

IntAct

64 interactions, top by confidence:

A	B	Type	Score
PELI1	IRAK4	psi-mi:“MI:0217”(phosphorylation reaction)	0.770
IRAK4	PELI1	psi-mi:“MI:0915”(physical association)	0.770
PELI1	IRAK4	psi-mi:“MI:0915”(physical association)	0.770
PELI1	IRAK1	psi-mi:“MI:0217”(phosphorylation reaction)	0.730
PELI1	IRAK1	psi-mi:“MI:0914”(association)	0.730
PELI1	IRAK1	psi-mi:“MI:0915”(physical association)	0.730
VAC14	PELI1	psi-mi:“MI:0915”(physical association)	0.560
TRIP13	PELI1	psi-mi:“MI:0915”(physical association)	0.560
PELI1	TRIP13	psi-mi:“MI:0915”(physical association)	0.560
PELI1	VAC14	psi-mi:“MI:0915”(physical association)	0.560
PELI1	WASHC3	psi-mi:“MI:0915”(physical association)	0.560
PELI1	PDAP1	psi-mi:“MI:0915”(physical association)	0.560
PDAP1	PELI1	psi-mi:“MI:0915”(physical association)	0.560
PELI1	TP63	psi-mi:“MI:0915”(physical association)	0.560
CNTROB	PELI1	psi-mi:“MI:0915”(physical association)	0.560
CLEC17A	PELI1	psi-mi:“MI:0915”(physical association)	0.560
INPP5J	PELI1	psi-mi:“MI:0915”(physical association)	0.560
GOSR2	PELI1	psi-mi:“MI:0915”(physical association)	0.560
LCN2	PELI1	psi-mi:“MI:0915”(physical association)	0.560
PELI1	RIMS4	psi-mi:“MI:0915”(physical association)	0.560
LMNA	PELI1	psi-mi:“MI:0915”(physical association)	0.560
PELI1		psi-mi:“MI:0915”(physical association)	0.560
PELI1	PMP22	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (129): BCL6 (Reconstituted Complex), BCL6 (Affinity Capture-Western), BCL6 (Biochemical Activity), PELI1 (Two-hybrid), PELI1 (Two-hybrid), IRAK1 (Affinity Capture-Western), TBK1 (Affinity Capture-Western), PELI1 (Two-hybrid), BIRC3 (Affinity Capture-Western), BIRC3 (Reconstituted Complex), PELI1 (Reconstituted Complex), PELI1 (Affinity Capture-MS), PELI1 (Affinity Capture-Western), BUB1B (Affinity Capture-Western), BUB1B (Reconstituted Complex)

ESM2 similar proteins: A0JN39, A4FUD6, B1H2N3, D2SW95, D2XV59, O00178, O08582, O35218, O60941, O77237, P11029, P11497, P23514, P29144, P42694, P53618, Q0J035, Q0JNK5, Q13085, Q28559, Q53PC7, Q58DC5, Q5R4J9, Q5R922, Q5RCC1, Q5SWU9, Q5T5C0, Q5XGS8, Q5ZIA5, Q5ZM73, Q6DFV5, Q6NYU2, Q80UM3, Q80YV4, Q8BHL5, Q8BST6, Q8BXR6, Q8C669, Q8IZH2, Q8L5Y9

Diamond homologs: O77237, Q8BST6, Q8BXR6, Q8C669, Q8N2H9, Q96FA3, Q9HAT8

SIGNOR signaling

29 interactions.

A	Effect	B	Mechanism
PELI1	“up-regulates quantity by expression”	IRAK1	ubiquitination
SMAD6	up-regulates	PELI1	binding
PELI1	“up-regulates quantity by stabilization”	BIRC3	ubiquitination
DAPK1	“down-regulates quantity by destabilization”	PELI1	phosphorylation
EGFR	“up-regulates activity”	PELI1	phosphorylation
PELI1	“up-regulates quantity by stabilization”	EGFR	polyubiquitination
PELI1	“up-regulates activity”	MDM4	ubiquitination
IRAK1	“up-regulates activity”	PELI1	phosphorylation
PELI1	“down-regulates quantity by destabilization”	HPD	ubiquitination
IRAK4	“up-regulates activity”	PELI1	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

58 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	44
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1553 predictions. Top by Δscore:

Variant	Effect	Δscore
2:64095267:ACC:A	acceptor_loss	1.0000
2:64096443:T:TA	donor_gain	1.0000
2:64098043:A:AC	donor_gain	1.0000
2:64100392:TAATA:T	donor_loss	1.0000
2:64100393:AATAC:A	donor_loss	1.0000
2:64100394:ATAC:A	donor_loss	1.0000
2:64100395:TAC:T	donor_loss	1.0000
2:64100396:A:T	donor_loss	1.0000
2:64100397:C:CA	donor_loss	1.0000
2:64100506:A:AC	acceptor_gain	1.0000
2:64100506:A:C	acceptor_gain	1.0000
2:64106179:T:A	donor_gain	1.0000
2:64108233:ACCTT:A	donor_loss	1.0000
2:64108236:TTA:T	donor_loss	1.0000
2:64108237:TACC:T	donor_loss	1.0000
2:64108238:A:AC	donor_gain	1.0000
2:64108238:AC:A	donor_gain	1.0000
2:64108239:C:CC	donor_gain	1.0000
2:64108239:C:T	donor_loss	1.0000
2:64108239:CC:C	donor_gain	1.0000
2:64108267:A:AC	donor_gain	1.0000
2:64108268:C:CC	donor_gain	1.0000
2:64118420:CA:C	donor_gain	1.0000
2:64095265:CCAC:C	acceptor_gain	0.9900
2:64095266:CAC:C	acceptor_gain	0.9900
2:64095266:CACC:C	acceptor_gain	0.9900
2:64095269:C:CC	acceptor_gain	0.9900
2:64096122:TACCA:T	donor_loss	0.9900
2:64096123:A:AC	donor_gain	0.9900
2:64096123:ACCAT:A	donor_loss	0.9900

AlphaMissense

2747 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:64094720:A:C	F413L	1.000
2:64094720:A:T	F413L	1.000
2:64094722:A:G	F413L	1.000
2:64094727:A:G	L411P	1.000
2:64094727:A:T	L411H	1.000
2:64094765:A:C	C398W	1.000
2:64094766:C:T	C398Y	1.000
2:64094767:A:G	C398R	1.000
2:64094768:A:C	F397L	1.000
2:64094768:A:T	F397L	1.000
2:64094770:A:G	F397L	1.000
2:64094772:G:T	P396H	1.000
2:64094774:A:C	C395W	1.000
2:64094775:C:A	C395F	1.000
2:64094775:C:T	C395Y	1.000
2:64094776:A:G	C395R	1.000
2:64094799:C:T	G387D	1.000
2:64094800:C:G	G387R	1.000
2:64094805:G:T	P385H	1.000
2:64094806:G:A	P385S	1.000
2:64094806:G:T	P385T	1.000
2:64094822:C:A	W379C	1.000
2:64094822:C:G	W379C	1.000
2:64094824:A:G	W379R	1.000
2:64094824:A:T	W379R	1.000
2:64094835:G:T	T375K	1.000
2:64094856:C:T	G368E	1.000
2:64094857:C:A	G368W	1.000
2:64094858:A:C	C367W	1.000
2:64094859:C:T	C367Y	1.000

dbSNP variants (sampled 300 via entrez): RS1000038091 (2:64094190 G>C), RS1000061021 (2:64146380 A>C), RS1000091766 (2:64145921 A>G,T), RS1000129053 (2:64093284 C>T), RS1000185124 (2:64132872 A>C), RS1000258540 (2:64132597 C>A,G), RS1000338673 (2:64121874 C>G), RS1000528007 (2:64102531 G>A), RS1000603505 (2:64128815 T>A), RS1000643964 (2:64120704 A>G), RS1000799902 (2:64128087 T>C), RS1000907192 (2:64121437 A>C), RS1000967808 (2:64126922 G>C), RS1000996368 (2:64107875 A>G), RS1001047377 (2:64108271 G>A)

Disease associations

OMIM: gene MIM:614797 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST000939_1	Kawasaki disease	2.000000e-06
GCST002108_2	Allergic dermatitis (nickel)	7.000000e-06
GCST010724_5	HOMA-B (corrected for HOMA-IR)	2.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004469	HOMA-B

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066217 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

4 potent at pChembl≥5 of 28 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.28	Kd	5200	nM	CHEMBL5560298
5.24	Kd	5800	nM	CHEMBL5542921
5.15	Kd	7100	nM	CHEMBL5566406
5.09	Kd	8200	nM	CHEMBL5412968

PubChem BioAssay actives

4 with measured affinity, of 63 total; 4 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
5-[(E)-2-[4-hydroxy-2-(4-hydroxyphenyl)phenyl]ethenyl]benzene-1,3-diol	2079242: Binding affinity to PELI1 FHA domain (unknown origin) expressed in Escherichia coli BL21(DE3) competent cell measured after 1 min by fluorescence quenching assay	kd	5.2000	uM
5-[(E)-2-[4-hydroxy-2-(3-hydroxyphenyl)phenyl]ethenyl]benzene-1,3-diol	2079242: Binding affinity to PELI1 FHA domain (unknown origin) expressed in Escherichia coli BL21(DE3) competent cell measured after 1 min by fluorescence quenching assay	kd	5.8000	uM
5-[(E)-2-[2-(furan-3-yl)-4-hydroxyphenyl]ethenyl]benzene-1,3-diol	2079242: Binding affinity to PELI1 FHA domain (unknown origin) expressed in Escherichia coli BL21(DE3) competent cell measured after 1 min by fluorescence quenching assay	kd	7.1000	uM
5-[(E)-2-[2-hydroxy-5-(3-hydroxyphenyl)phenyl]ethenyl]benzene-1,3-diol	2079242: Binding affinity to PELI1 FHA domain (unknown origin) expressed in Escherichia coli BL21(DE3) competent cell measured after 1 min by fluorescence quenching assay	kd	8.2000	uM

CTD chemical–gene interactions

76 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
trichostatin A	increases expression, affects expression, affects cotreatment	6
Arsenic	affects cotreatment, increases expression, decreases expression, increases abundance	4
Valproic Acid	increases expression	4
sodium arsenite	increases expression, decreases expression, affects cotreatment, increases abundance	3
(+)-JQ1 compound	increases expression	3
bisphenol A	decreases expression, increases expression	2
Estradiol	affects cotreatment, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Cadmium Chloride	increases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
TL8-506	affects cotreatment, increases expression	1
ethylbenzene	increases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
sodium arsenate	decreases expression, increases abundance	1
2-methyl-4-isothiazolin-3-one	increases expression	1
arsenite	affects expression	1
o,p’-DDT	decreases expression	1
sulforaphane	increases expression	1
butyraldehyde	increases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
2-xylene	increases expression	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	affects cotreatment, increases expression	1
nickel sulfate	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
epigallocatechin gallate	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5519283	Binding	Binding affinity to PELI1 FHA domain (unknown origin) expressed in Escherichia coli BL21(DE3) competent cell measured after 1 min by fluorescence quenching assay	Resveratrol-derived inhibitors of the E3 ubiquitin ligase PELI1 inhibit the metastasis of triple-negative breast cancer. — Eur J Med Chem

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.