NEURL3

Summary

NEURL3 (neuralized E3 ubiquitin protein ligase 3, HGNC:25162) is a protein-coding gene on chromosome 2q11.2, encoding E3 ubiquitin-protein ligase NEURL3 (Q96EH8). E3 ubiquitin-protein ligase that plays a role in various biological processes such as lung development or innate immunity.

Enables ubiquitin protein ligase activity. Involved in positive regulation of proteasomal protein catabolic process. Is active in cytoplasm.

Source: NCBI Gene 93082 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 4 total
• MANE Select transcript: NM_001285485

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25162
Approved symbol	NEURL3
Name	neuralized E3 ubiquitin protein ligase 3
Location	2q11.2
Locus type	gene with protein product
Status	Approved
Aliases	Lincr, LOC93082, RNF132
Ensembl gene	ENSG00000163121
Ensembl biotype	protein_coding
OMIM	617206
Entrez	93082

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 retained_intron

ENST00000310865, ENST00000435380, ENST00000444588, ENST00000451794, ENST00000905950

RefSeq mRNA: 2 — MANE Select: NM_001285485 NM_001285485, NM_001285486

CCDS: CCDS74541, CCDS74542

Canonical transcript exons

ENST00000451794 — 4 exons

Exon	Start	End
ENSE00001611974	96497646	96498446
ENSE00001616021	96505259	96505357
ENSE00003602863	96500439	96500924
ENSE00003743593	96499378	96499449

Expression profiles

Bgee: expression breadth ubiquitous, 159 present calls, max score 90.89.

FANTOM5 (CAGE): breadth broad, TPM avg 2.8860 / max 453.4805, expressed in 253 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
29745	2.8685	251
29746	0.0175	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
nasal cavity epithelium	UBERON:0005384	90.89	silver quality
olfactory segment of nasal mucosa	UBERON:0005386	88.41	gold quality
kidney epithelium	UBERON:0004819	87.76	silver quality
epithelial cell of pancreas	CL:0000083	87.36	silver quality
parotid gland	UBERON:0001831	86.89	gold quality
body of pancreas	UBERON:0001150	86.44	gold quality
metanephros cortex	UBERON:0010533	85.89	gold quality
pancreas	UBERON:0001264	83.90	gold quality
nasal cavity mucosa	UBERON:0001826	81.36	gold quality
cartilage tissue	UBERON:0002418	81.06	gold quality
pancreatic ductal cell	CL:0002079	80.99	silver quality
left ventricle myocardium	UBERON:0006566	80.45	gold quality
cardiac muscle of right atrium	UBERON:0003379	80.10	gold quality
islet of Langerhans	UBERON:0000006	79.90	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	79.15	gold quality
metanephros	UBERON:0000081	78.56	gold quality
epithelium of nasopharynx	UBERON:0001951	78.19	gold quality
upper arm skin	UBERON:0004263	77.70	gold quality
myocardium	UBERON:0002349	77.47	gold quality
ileal mucosa	UBERON:0000331	76.76	silver quality
saliva-secreting gland	UBERON:0001044	76.76	gold quality
vastus lateralis	UBERON:0001379	76.73	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	76.18	gold quality
quadriceps femoris	UBERON:0001377	76.10	gold quality
adult mammalian kidney	UBERON:0000082	75.68	gold quality
minor salivary gland	UBERON:0001830	74.27	gold quality
mouth mucosa	UBERON:0003729	73.07	gold quality
superficial temporal artery	UBERON:0001614	72.90	gold quality
trachea	UBERON:0003126	72.87	gold quality
kidney	UBERON:0002113	72.68	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.44

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• The E3 ligase NEURL3 suppresses epithelial-mesenchymal transition and metastasis in nasopharyngeal carcinoma by promoting vimentin degradation. (PMID:38191501)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Neurl3	ENSMUSG00000047180
rattus_norvegicus	Neurl3	ENSRNOG00000015366

Paralogs (3): NEURL1 (ENSG00000107954), NEURL1B (ENSG00000214357), NEURL4 (ENSG00000215041)

Protein

Protein identifiers

E3 ubiquitin-protein ligase NEURL3 — Q96EH8 (reviewed: Q96EH8)

Alternative names: Lung-inducible neuralized-related C3CH4 RING domain protein, Neuralized-like protein 3, RING-type E3 ubiquitin transferase NEURL3

All UniProt accessions (3): A0A087WVI2, A0A087WXE0, Q96EH8

UniProt curated annotations — full annotation on UniProt →

Function. E3 ubiquitin-protein ligase that plays a role in various biological processes such as lung development or innate immunity. Seems to utilize UBE2E1. Promotes innate antiviral response by catalyzing ‘Lys-63’-linked ubiquitination of IRF7. Also inhibits hepatitis C virus assembly by directly binding to viral E1 envelope glycoprotein to disrupt its interaction with E2. Plays an essential role in TLR4-mediated activation of MAPK pathways by promoting ‘Lys-48’-linked polyubiquitination of the phosphatase DUSP1/MKP1.

Subunit / interactions. (Microbial infection) Interacts with hepatitis C virus protein E1; this interaction prevents E1 interaction with E2 and subsequently inhibits viral infection.

Subcellular location. Cytoplasm.

Induction. By hepatitis C virus.

Pathway. Protein modification; protein ubiquitination.

RefSeq proteins (2): NP_001272414, NP_001272415 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001841	Znf_RING	Domain
IPR006573	NHR_dom	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR037962	Neuralized	Family
IPR043136	B30.2/SPRY_sf	Homologous_superfamily

Pfam: PF07177, PF13920

UniProt features (6 total): mutagenesis site 2, chain 1, domain 1, zinc finger region 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96EH8-F1	81.64	0.56

Functional residue map

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

Mutagenesis-validated functional residues (2):

Position	Phenotype
202	complete loss of e3 ligase activity; when associated with s-205.
205	complete loss of e3 ligase activity; when associated with s-202.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 110 (showing top): GOBP_POSITIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_CATABOLIC_PROCESS, GOBP_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_POSITIVE_REGULATION_OF_PROTEOLYSIS, GOBP_PROTEASOMAL_PROTEIN_CATABOLIC_PROCESS, CERVERA_SDHB_TARGETS_1_UP, GOBP_IMPORT_INTO_CELL, GOBP_REGULATION_OF_PROTEOLYSIS

GO Biological Process (7): protein ubiquitination (GO:0016567), innate immune response (GO:0045087), ubiquitin-dependent endocytosis (GO:0070086), positive regulation of proteasomal protein catabolic process (GO:1901800), immune system process (GO:0002376), negative regulation of MAPK cascade (GO:0043409), ERK1 and ERK2 cascade (GO:0070371)

GO Molecular Function (5): zinc ion binding (GO:0008270), ubiquitin protein ligase activity (GO:0061630), ubiquitin-protein transferase activity (GO:0004842), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (2): cytoplasm (GO:0005737), early endosome (GO:0005769)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
MAPK cascade	2
protein modification by small protein conjugation	1
immune response	1
defense response to symbiont	1
endocytosis	1
protein transport	1
protein localization to organelle	1
establishment of protein localization to organelle	1
proteasomal protein catabolic process	1
positive regulation of protein catabolic process	1
regulation of proteasomal protein catabolic process	1
biological_process	1
regulation of MAPK cascade	1
negative regulation of intracellular signal transduction	1
transition metal ion binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
ubiquitin-like protein transferase activity	1
catalytic activity	1
cation binding	1
intracellular anatomical structure	1
cellular anatomical structure	1
endosome	1

Protein interactions and networks

STRING

402 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NEURL3	CCR2	P41597	446
NEURL3	PIWIL2	Q8TC59	413
NEURL3	GATA3	P23771	382
NEURL3	GNG2	P59768	370
NEURL3	RCHY1	Q96PM5	368
NEURL3	GATA6	P78327	316
NEURL3	CCR3	P51677	313
NEURL3	WDR5	P61964	311
NEURL3	FAM43A	Q8N2R8	307
NEURL3	STAT4	Q14765	300
NEURL3	RNF19B	Q6ZMZ0	295
NEURL3	CYB561D1	Q8N8Q1	287
NEURL3	XKR7	Q5GH72	280
NEURL3	ARID5A	Q03989	275
NEURL3	HNRNPAB	Q99729	274

IntAct

0 interactions, top by confidence:

BioGRID (33): NEURL3 (Two-hybrid), NEURL3 (Reconstituted Complex), NEURL3 (Affinity Capture-Western), IRF7 (Affinity Capture-Western), NEURL3 (Affinity Capture-Western), NEURL3 (Affinity Capture-MS), DUSP1 (Affinity Capture-Western), NEURL3 (Affinity Capture-Western), DUSP1 (Biochemical Activity), NEURL3 (Affinity Capture-MS), ACTB (Affinity Capture-MS), ACTG1 (Affinity Capture-MS), EFHD2 (Affinity Capture-MS), KRT17 (Affinity Capture-MS), KRT2 (Affinity Capture-MS)

ESM2 similar proteins: A0A8C2MDK8, A0PJX2, A2ACG1, D3ZBP4, E2RDP2, F1MH07, O08644, O75038, O75064, O75636, P0C0K7, P0DPD7, P0DPE0, P0DPE1, P52824, Q00653, Q0IID2, Q1LWV7, Q3SYT1, Q3U1Y4, Q4KM32, Q4R380, Q5NCQ5, Q5RKI3, Q62137, Q684M2, Q68DD2, Q6ZSI9, Q86TL0, Q86XP0, Q8BGV9, Q8BX80, Q8C9V1, Q8NFF5, Q8NFI3, Q8R5G7, Q8TDZ2, Q8VDP3, Q8WWN8, Q91ZJ0

Diamond homologs: A8MQ27, O60291, O76050, Q0MW30, Q0WS06, Q3TEL6, Q4FE47, Q557E7, Q5M870, Q5XIQ4, Q6INH1, Q6R7D2, Q7ZUL9, Q84ME1, Q8CJC5, Q8VCM5, Q923S6, Q94HV7, Q96EH8, Q96PX1, Q9BR09, Q9D074, Q9D0S4, Q8L7N4, P29503, Q24746, A1L3F4, Q69Z36, Q6ZN04, Q6ZQM0, Q8CIN9, Q8WZ73, Q05A36, Q3UE17, Q5NCX5, Q5U5Q3, Q7M3S9, Q8LA32, Q99675, Q9FPH0

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	NEURL3	ubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

600 predictions. Top by Δscore:

Variant	Effect	Δscore
2:96499445:GGGAT:G	acceptor_gain	1.0000
2:96499446:GGAT:G	acceptor_gain	1.0000
2:96499447:GAT:G	acceptor_gain	1.0000
2:96499448:AT:A	acceptor_gain	1.0000
2:96499450:C:CC	acceptor_gain	1.0000
2:96500437:A:AC	donor_gain	1.0000
2:96500438:C:CC	donor_gain	1.0000
2:96500438:CCCAG:C	donor_gain	1.0000
2:96498447:C:CC	acceptor_gain	0.9900
2:96499373:CTCA:C	donor_loss	0.9900
2:96499374:TCA:T	donor_loss	0.9900
2:96499375:CA:C	donor_loss	0.9900
2:96499376:A:T	donor_loss	0.9900
2:96499456:C:CT	acceptor_gain	0.9900
2:96500434:CTCA:C	donor_loss	0.9900
2:96500435:TCA:T	donor_loss	0.9900
2:96500437:AC:A	donor_gain	0.9900
2:96500438:CC:C	donor_gain	0.9900
2:96500442:G:C	donor_gain	0.9900
2:96500921:GCGT:G	acceptor_gain	0.9900
2:96500922:CGT:C	acceptor_gain	0.9900
2:96500922:CGTC:C	acceptor_gain	0.9900
2:96500925:C:CC	acceptor_gain	0.9900
2:96505257:A:AC	donor_gain	0.9900
2:96505257:ACTGG:A	donor_gain	0.9900
2:96505258:C:CC	donor_gain	0.9900
2:96505258:CTG:C	donor_gain	0.9900
2:96505258:CTGG:C	donor_gain	0.9900
2:96505258:CTGGC:C	donor_gain	0.9900
2:96498445:GG:G	acceptor_gain	0.9800

AlphaMissense

1679 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:96500800:G:C	S51R	0.990
2:96500800:G:T	S51R	0.990
2:96500802:T:G	S51R	0.990
2:96500821:G:C	F44L	0.990
2:96500821:G:T	F44L	0.990
2:96500823:A:G	F44L	0.990
2:96500804:A:G	F50S	0.985
2:96500578:G:C	F125L	0.983
2:96500578:G:T	F125L	0.983
2:96500580:A:G	F125L	0.983
2:96500713:G:C	F80L	0.983
2:96500713:G:T	F80L	0.983
2:96500714:A:G	F80S	0.983
2:96500715:A:G	F80L	0.983
2:96500893:G:C	F20L	0.982
2:96500893:G:T	F20L	0.982
2:96500895:A:G	F20L	0.982
2:96500803:G:C	F50L	0.981
2:96500803:G:T	F50L	0.981
2:96500805:A:G	F50L	0.981
2:96500894:A:G	F20S	0.979
2:96500475:C:G	D160H	0.977
2:96500579:A:G	F125S	0.977
2:96500450:A:T	I168N	0.970
2:96498324:A:G	C237R	0.969
2:96500665:G:C	F96L	0.968
2:96500665:G:T	F96L	0.968
2:96500667:A:G	F96L	0.968
2:96500454:C:G	A167P	0.966
2:96500485:C:A	W156C	0.966

dbSNP variants (sampled 300 via entrez): RS1000210496 (2:96498095 T>A), RS1000238652 (2:96509913 G>T), RS1000291548 (2:96504321 T>C), RS1000388226 (2:96504052 G>T), RS1000503627 (2:96503415 T>A,C), RS1000592483 (2:96510007 G>C), RS1000627191 (2:96505846 C>T), RS1000667761 (2:96497583 C>T), RS1000679406 (2:96505530 T>A), RS1000952912 (2:96499535 G>A,C), RS1001061158 (2:96509761 G>A), RS1001134269 (2:96504432 C>A), RS1001147908 (2:96499764 A>C), RS1001739276 (2:96505019 T>C), RS1001749202 (2:96504750 C>T)

Disease associations

OMIM: gene MIM:617206 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST007269_44	Pulse pressure	2.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005763	pulse pressure measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression	2
Benzo(a)pyrene	affects methylation, increases expression	2
Silicon Dioxide	increases expression	2
Tobacco Smoke Pollution	decreases expression	2
Aflatoxin B1	decreases methylation, increases expression	2
aristolochic acid I	increases expression	1
sotorasib	affects cotreatment, decreases expression	1
dicrotophos	decreases expression	1
propionaldehyde	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	increases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, increases expression, decreases reaction	1
pentanal	increases expression	1
15-acetyldeoxynivalenol	increases expression	1
cylindrospermopsin	increases expression	1
abrine	increases expression	1
jinfukang	increases expression	1
trametinib	affects cotreatment, decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
2,3,5-trichloro-6-phenyl-(1,4)benzoquinone	decreases expression	1
Temozolomide	increases expression	1
Aldehydes	increases expression	1
Allergens	decreases expression	1
Camptothecin	increases expression	1
Demecolcine	increases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Lipopolysaccharides	increases expression, affects cotreatment, decreases reaction	1

Clinical trials (associated diseases)

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