TAB3

Summary

TAB3 (TGF-beta activated kinase 1 (MAP3K7) binding protein 3, HGNC:30681) is a protein-coding gene on chromosome Xp21.2, encoding TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 (Q8N5C8). Adapter required to activate the JNK and NF-kappa-B signaling pathways through the specific recognition of ‘Lys-63’-linked polyubiquitin chains by its RanBP2-type zinc finger (NZF).

The product of this gene functions in the NF-kappaB signal transduction pathway. The encoded protein, and the similar and functionally redundant protein MAP3K7IP2/TAB2, forms a ternary complex with the protein kinase MAP3K7/TAK1 and either TRAF2 or TRAF6 in response to stimulation with the pro-inflammatory cytokines TNF or IL-1. Subsequent MAP3K7/TAK1 kinase activity triggers a signaling cascade leading to activation of the NF-kappaB transcription factor. The human genome contains a related pseudogene. Alternatively spliced transcript variants have been described, but their biological validity has not been determined.

Source: NCBI Gene 257397 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 163 total — 1 likely-pathogenic
• Druggable target: yes
• MANE Select transcript: NM_152787

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30681
Approved symbol	TAB3
Name	TGF-beta activated kinase 1 (MAP3K7) binding protein 3
Location	Xp21.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000157625
Ensembl biotype	protein_coding
OMIM	300480
Entrez	257397

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 8 protein_coding, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000288422, ENST00000378928, ENST00000378930, ENST00000378932, ENST00000378933, ENST00000467136, ENST00000867603, ENST00000867604, ENST00000867605, ENST00000867606

RefSeq mRNA: 4 — MANE Select: NM_152787 NM_001399870, NM_001399872, NM_001399873, NM_152787

CCDS: CCDS14226, CCDS94584

Canonical transcript exons

ENST00000288422 — 11 exons

Exon	Start	End
ENSE00001034015	30854116	30855562
ENSE00001218563	30834051	30834152
ENSE00001218567	30842966	30843049
ENSE00001479304	30867115	30867218
ENSE00001479305	30867465	30867549
ENSE00001479306	30871699	30871801
ENSE00001479307	30827442	30831575
ENSE00001720328	30852778	30852938
ENSE00002184624	30859487	30859678
ENSE00003714748	30889114	30889254
ENSE00003719691	30846551	30846644

Expression profiles

Bgee: expression breadth ubiquitous, 257 present calls, max score 98.81.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.4577 / max 249.4806, expressed in 1661 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
198789	6.5015	1619
198790	0.4031	199
198792	0.3811	186
198791	0.1720	66

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
epithelial cell of pancreas	CL:0000083	98.81	gold quality
pancreatic ductal cell	CL:0002079	98.12	gold quality
germinal epithelium of ovary	UBERON:0001304	96.50	gold quality
esophagus squamous epithelium	UBERON:0006920	96.22	gold quality
amniotic fluid	UBERON:0000173	94.42	gold quality
kidney epithelium	UBERON:0004819	93.36	gold quality
epithelium of nasopharynx	UBERON:0001951	93.32	gold quality
buccal mucosa cell	CL:0002336	93.30	gold quality
gingival epithelium	UBERON:0001949	93.28	gold quality
gingiva	UBERON:0001828	92.24	gold quality
cauda epididymis	UBERON:0004360	92.20	gold quality
palpebral conjunctiva	UBERON:0001812	91.68	gold quality
visceral pleura	UBERON:0002401	91.60	gold quality
oral cavity	UBERON:0000167	91.52	gold quality
sperm	CL:0000019	91.40	gold quality
parietal pleura	UBERON:0002400	91.26	gold quality
placenta	UBERON:0001987	91.10	gold quality
trabecular bone tissue	UBERON:0002483	91.00	gold quality
ileal mucosa	UBERON:0000331	90.79	gold quality
caput epididymis	UBERON:0004358	90.52	gold quality
corpus epididymis	UBERON:0004359	90.51	gold quality
cardiac muscle of right atrium	UBERON:0003379	90.50	gold quality
seminal vesicle	UBERON:0000998	90.46	gold quality
deltoid	UBERON:0001476	90.16	gold quality
tibia	UBERON:0000979	89.95	gold quality
left ventricle myocardium	UBERON:0006566	89.95	gold quality
cortical plate	UBERON:0005343	89.93	gold quality
Brodmann (1909) area 23	UBERON:0013554	89.62	gold quality
tibialis anterior	UBERON:0001385	89.61	gold quality
upper leg skin	UBERON:0004262	88.61	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	4.79

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HR

miRNA regulators (miRDB)

365 targeting TAB3, 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-5011-5P	100.00	83.46	5820
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4262	100.00	73.26	3931
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-4533	100.00	69.48	2758
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997

Literature-anchored findings (GeneRIF, showing 24)

• TAB3 is involved in IL-1-induced NF-kappaB activation by physically linking TAK1 to TRAF6. (PMID:14633987)
• Identification of TAB3 as a binding partner of the protein kinase TAK1. (PMID:14670075)
• TAB3 transforming growth factor is a constituent of the NF-kappaB pathway functioning upstream of tumor necrosis factor alpha-associated factor 6/transforming growth factor beta-activated kinase (PMID:14766965)
• Data show that TAB2 and TAB3 are receptors that bind preferentially to polyubiquitin chains through a highly conserved zinc finger (ZnF) domain, and activate NF-kappa B and IKK. (PMID:15327770)
• The TAB2/TAB3 interaction with TAK1 is crucial for the activation of signaling cascades mediated by interleukin-1, tumor necrosis factor, and receptor activator of nuclear factor-kappa B ligand (RANKL). (PMID:17158449)
• These results point to the existence of an autophagy-stimulatory ‘switch’ whereby TAB2 and TAB3 abandon inhibitory interactions with Beclin 1 to engage in a stimulatory liaison with TAK1. (PMID:22081109)
• human TAB2 and TAB3, ubiquitin-chain sensory proteins involved in NF-kappaB signalling, are directly inactivated by enteropathogenic Escherichia coli NleE, a conserved bacterial type-III-secreted effector responsible for blocking host NF-kappaB signalling (PMID:22158122)
• MiR-23b suppresses IL-17-, tumor necrosis factor alpha (TNF-alpha)- or IL-1beta-induced NF-kappaB activation and inflammatory cytokine expression by targeting TAB2, TAB3 and IKK-alpha. (PMID:22660635)
• Studies show that three proteins expressed in HEK-293T cells (NAP1, TANK and TBKBP1) interact with TBK1. (PMID:23286385)
• conclude that TRIM38 negatively regulates TNFalpha- and IL-1beta-induced signaling by mediating lysosome-dependent degradation of TAB2/3, two critical components in TNFalpha- and IL-1beta-induced signaling pathways (PMID:24434549)
• miR-26b suppresses NF-kappaB signaling and sensitizes hepatocellular carcinoma cells to doxorubicin-induced apoptosis by inhibiting the expression of TAK1 and TAB3. (PMID:24565101)
• Data show that knockdown of transforming growth factor-activated kinase 1 (TAK1)-binding protein 3 (TAB3) inhibited proliferation of non-small cell lung cancer (NSCLC) cells. (PMID:26476534)
• miR-30a in MSCs may participate in the immune dysregulation of the maternal-fetal interface during PE (PMID:26555189)
• Upregulation of miR-532-5p and subsequent suppression of the SESTD1 and TAB3 genes represent an antiviral response aimed at limiting West Nile virus infection. (PMID:26676784)
• Our study provides insights into the mechanism of TAB3 regulating activity and suggests its important implications in triple negative breast cancer metastasis. (PMID:27009840)
• The combination of WES, genomic triangulation, and systems biology has uncovered perturbations in TGF-beta activated kinase 1 signaling as a novel pathogenic substrate for polyvalvular syndrome. (PMID:27452334)
• TAB3 regulated ovarian cancer cell bioactivity and chemotherapy performance via the NF-kappaB pathway. (PMID:27651027)
• these results demonstrated that TAB3 may be a promising therapeutic target for the treatment of Esophageal squamous cell carcinoma. (PMID:30226617)
• multiple GPCR agonists utilize non-canonical TAB1-TAB2 and TAB1-TAB3-dependent p38 activation to promote endothelial inflammatory responses. (PMID:30760523)
• TAB3 may play a significant role at the level of T-cell activation and may also be a candidate biomarker for peanut allergy. (PMID:30893695)
• TAB3 upregulates PIM1 expression by directly activating the TAK1-STAT3 complex to promote colorectal cancer growth. (PMID:32229191)
• ZEB2-AS1 regulates the expression of TAB3 and promotes the development of colon cancer by adsorbing microRNA-188. (PMID:32373954)
• Neddylation promotes protein translocation between the cytoplasm and nucleus. (PMID:32819610)
• miR-27a-3p upregulation by p65 facilitates cervical tumorigenesis by increasing TAB3 expression and is involved in the positive feedback loop of NF-kappaB signaling. (PMID:37203408)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tab3	ENSDARG00000062063
mus_musculus	Tab3	ENSMUSG00000035476
rattus_norvegicus	Tab3	ENSRNOG00000003643

Paralogs (3): TAB2 (ENSG00000055208), BTF3L4 (ENSG00000134717), BTF3 (ENSG00000145741)

Protein

Protein identifiers

TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 — Q8N5C8 (reviewed: Q8N5C8)

Alternative names: Mitogen-activated protein kinase kinase kinase 7-interacting protein 3, NF-kappa-B-activating protein 1, TAK1-binding protein 3, TGF-beta-activated kinase 1-binding protein 3

All UniProt accessions (3): Q8N5C8, A0A0A0MQY2, F6SS63

UniProt curated annotations — full annotation on UniProt →

Function. Adapter required to activate the JNK and NF-kappa-B signaling pathways through the specific recognition of ‘Lys-63’-linked polyubiquitin chains by its RanBP2-type zinc finger (NZF). Acts as an adapter linking MAP3K7/TAK1 and TRAF6 to ‘Lys-63’-linked polyubiquitin chains. The RanBP2-type zinc finger (NZF) specifically recognizes Lys-63’-linked polyubiquitin chains unanchored or anchored to the substrate proteins such as RIPK1/RIP1 and RIPK2: this acts as a scaffold to organize a large signaling complex to promote autophosphorylation of MAP3K7/TAK1, and subsequent activation of I-kappa-B-kinase (IKK) core complex by MAP3K7/TAK1. May be an oncogenic factor.

Subunit / interactions. Interacts with TAB1, TAB2, MAP3K7, TRAF2 and TRAF6. The minimal TAB3-containing complex (TAB1-MAP3K7-TAB3) appears not to contain TAB2. However, it seems sensible to consider that TAB2 may also join this complex and may act in a cooperative manner with TAB3. Interacts with DYNC2I2 (via the WD domains). Interacts with RBCK1. Binds ‘Lys-63’-linked polyubiquitin chains. Interacts with TRIM5. Interacts with TRIM38 (via B30.2/SPRY domain), leading to its translocation to lysosomes and degradation. Interacts with ASB1. (Microbial infection) Interacts with M.tuberculosis PtpA, which blocks the NF-kappa-B signaling pathway.

Tissue specificity. Widely expressed. Constitutively overexpressed in certain tumor tissues. Major transcript. Minor transcript.

Post-translational modifications. Ubiquitinated; following IL1 stimulation or TRAF6 overexpression. Ubiquitinated by AMFR via ‘Lys-27’-linked polyubiquitination; leading to TAK1/MAP3K7 activation. Degraded in a lysosome-dependent manner following interaction with TRIM38. Phosphorylated at Ser-506 by MAPKAPK2 and MAPKAPK3 following IL1 treatment. (Microbial infection) Methylated at Cys-692 by enteropathogenic E.coli protein NleE or S.flexneri protein OspZ: methylation disrupts zinc-binding and ability to bind ‘Lys-63’-linked ubiquitin, leading to NF-kappa-B inactivation.

Domain organisation. The RanBP2-type zinc finger (NZF) mediates binding to two consecutive ‘Lys-63’-linked ubiquitins.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8N5C8-1	1, Tab3a	yes
Q8N5C8-2	2, Tab3b

RefSeq proteins (4): NP_001386799, NP_001386801, NP_001386802, NP_690000* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001876	Znf_RanBP2	Domain
IPR003892	CUE	Domain
IPR036443	Znf_RanBP2_sf	Homologous_superfamily
IPR041911	TAB2/3_CUE	Domain

Pfam: PF02845

UniProt features (38 total): modified residue 10, compositionally biased region 9, region of interest 6, mutagenesis site 5, initiator methionine 1, chain 1, coiled-coil region 1, domain 1, zinc finger region 1, cross-link 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N5C8-F1	53.89	0.14

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 (11): 2, 60, 101, 103, 385, 404, 409, 492, 506, 692, 649

Mutagenesis-validated functional residues (5):

Position	Phenotype
649	almost complete loss of amfr-induced ’lys-27’-linked ubiquitination.
689	disrupted zinc-finger; abolished methylation at c-692.
692	abolished cys methylation and ability to bind ’lys-63’-linked ubiquitin.
703	disrupted zinc-finger; abolished methylation at c-692.
706	disrupted zinc-finger; abolished methylation at c-692.

Function

Pathways and Gene Ontology

Reactome pathways

49 pathways

ID	Pathway
R-HSA-168638	NOD1/2 Signaling Pathway
R-HSA-2871837	FCERI mediated NF-kB activation
R-HSA-445989	TAK1-dependent IKK and NF-kappa-B activation
R-HSA-450302	activated TAK1 mediates p38 MAPK activation
R-HSA-450321	JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1
R-HSA-5357956	TNFR1-induced NF-kappa-B signaling pathway
R-HSA-5607764	CLEC7A (Dectin-1) signaling
R-HSA-9014325	TICAM1,TRAF6-dependent induction of TAK1 complex
R-HSA-9020702	Interleukin-1 signaling
R-HSA-937042	IRAK2 mediated activation of TAK1 complex
R-HSA-937072	TRAF6-mediated induction of TAK1 complex within TLR4 complex
R-HSA-9645460	Alpha-protein kinase 1 signaling pathway
R-HSA-9705671	SARS-CoV-2 activates/modulates innate and adaptive immune responses
R-HSA-975163	IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-162582	Signal Transduction
R-HSA-1643685	Disease
R-HSA-166016	Toll Like Receptor 4 (TLR4) Cascade
R-HSA-166058	MyD88:MAL(TIRAP) cascade initiated on plasma membrane
R-HSA-166166	MyD88-independent TLR4 cascade
R-HSA-168138	Toll Like Receptor 9 (TLR9) Cascade
R-HSA-168142	Toll Like Receptor 10 (TLR10) Cascade
R-HSA-168164	Toll Like Receptor 3 (TLR3) Cascade
R-HSA-168176	Toll Like Receptor 5 (TLR5) Cascade
R-HSA-168179	Toll Like Receptor TLR1:TLR2 Cascade
R-HSA-168181	Toll Like Receptor 7/8 (TLR7/8) Cascade
R-HSA-168188	Toll Like Receptor TLR6:TLR2 Cascade
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-168643	Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways

MSigDB gene sets: 225 (showing top): REACTOME_TRAF6_MEDIATED_INDUCTION_OF_TAK1_COMPLEX_WITHIN_TLR4_COMPLEX, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_REGULATION_OF_AUTOPHAGY, REACTOME_INNATE_IMMUNE_SYSTEM, REACTOME_NOD1_2_SIGNALING_PATHWAY, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, RORA1_01, REACTOME_NUCLEOTIDE_BINDING_DOMAIN_LEUCINE_RICH_REPEAT_CONTAINING_RECEPTOR_NLR_SIGNALING_PATHWAYS, TTTGTAG_MIR520D, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, TGACCTY_ERR1_Q2, TACAATC_MIR508, GOBP_NEGATIVE_REGULATION_OF_AUTOPHAGY, GOBP_REGULATION_OF_CATABOLIC_PROCESS

GO Biological Process (8): negative regulation of autophagy (GO:0010507), non-canonical NF-kappaB signal transduction (GO:0038061), defense response to bacterium (GO:0042742), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), canonical NF-kappaB signal transduction (GO:0007249), response to bacterium (GO:0009617), p38MAPK cascade (GO:0038066), negative regulation of canonical NF-kappaB signal transduction (GO:0043124)

GO Molecular Function (6): zinc ion binding (GO:0008270), ubiquitin binding (GO:0043130), molecular adaptor activity (GO:0060090), K63-linked polyubiquitin modification-dependent protein binding (GO:0070530), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (5): endoplasmic reticulum (GO:0005783), cytosol (GO:0005829), plasma membrane (GO:0005886), endosome membrane (GO:0010008), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-19 pathways:

Category	Pathways
MyD88:MAL(TIRAP) cascade initiated on plasma membrane	2
Toll Like Receptor 3 (TLR3) Cascade	2
TRIF (TICAM1)-mediated TLR4 signaling	2
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation	2
MyD88 cascade initiated on plasma membrane	2
MAP kinase activation	2
Toll Like Receptor 4 (TLR4) Cascade	2
Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways	1
Fc epsilon receptor (FCERI) signaling	1
Interleukin-1 signaling	1
TNF signaling	1
C-type lectin receptors (CLRs)	1
Interleukin-1 family signaling	1
Innate Immune System	1
SARS-CoV-2-host interactions	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular signaling cassette	2
canonical NF-kappaB signal transduction	2
regulation of canonical NF-kappaB signal transduction	2
binding	2
cytoplasm	2
autophagy	1
negative regulation of catabolic process	1
regulation of autophagy	1
defense response	1
response to bacterium	1
positive regulation of intracellular signal transduction	1
response to other organism	1
MAPK cascade	1
negative regulation of intracellular signal transduction	1
transition metal ion binding	1
ubiquitin-like protein binding	1
molecular_function	1
polyubiquitin modification-dependent protein binding	1
cation binding	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1
membrane	1
cell periphery	1
endosome	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
extracellular vesicle	1

Protein interactions and networks

STRING

1643 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TAB3	TAB1	Q15750	998
TAB3	TRAF6	Q9Y4K3	996
TAB3	MAP3K7	O43318	995
TAB3	TAB2	Q9NYJ8	986
TAB3	IKBKG	Q9Y6K9	894
TAB3	RIPK1	Q13546	865
TAB3	SMAD7	O15105	863
TAB3	IKBKB	O14920	808
TAB3	PHF20	Q9BVI0	799
TAB3	G3V2F7	G3V2F7	782
TAB3	DYNC2I2	Q96EX3	778
TAB3	UBE2N	P61088	770
TAB3	MYD88	P78397	761
TAB3	TRAF3	Q13114	749
TAB3	RIPK2	O43353	738

IntAct

69 interactions, top by confidence:

A	B	Type	Score
TAB2	MAP3K7	psi-mi:“MI:0914”(association)	0.920
TAB1	MAP3K7	psi-mi:“MI:0914”(association)	0.900
MAP3K7	TAB1	psi-mi:“MI:0914”(association)	0.900
TAB3	MAP3K7	psi-mi:“MI:0914”(association)	0.830
TAB3	MAP3K7	psi-mi:“MI:0915”(physical association)	0.830
YBX1	HNRNPR	psi-mi:“MI:0915”(physical association)	0.770
MAP3K7	UBC	psi-mi:“MI:0915”(physical association)	0.740
TAB1	HSPA8	psi-mi:“MI:0914”(association)	0.740
TAB3	MAP3K7CL	psi-mi:“MI:0915”(physical association)	0.720
MAP3K7CL	TAB3	psi-mi:“MI:0915”(physical association)	0.720
TRAF6	MAP3K7	psi-mi:“MI:0914”(association)	0.670
BECN1	TAB3	psi-mi:“MI:0915”(physical association)	0.650
TAB3	BECN1	psi-mi:“MI:0915”(physical association)	0.650
BECN1	TAB3	psi-mi:“MI:0407”(direct interaction)	0.650
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570

BioGRID (141): TAB3 (Two-hybrid), TAB3 (Two-hybrid), CEP57L1 (Two-hybrid), TAB3 (Reconstituted Complex), TAB3 (Two-hybrid), TAB3 (Affinity Capture-Western), TAB3 (Affinity Capture-Western), ptpA (Affinity Capture-Western), ptpA (Reconstituted Complex), UBC (Reconstituted Complex), TAB3 (Affinity Capture-MS), RNF4 (Affinity Capture-Western), PBXIP1 (Affinity Capture-Western), MAP3K7 (Affinity Capture-Western), IKBKB (Affinity Capture-Western)

ESM2 similar proteins: A0A8C0NGY6, A0A8I3PQN6, A1L1N5, A2BEA6, A2ICN5, A2VDZ3, A4QNP0, D6C652, F1LYL9, H2LBU8, O18896, O94842, P19484, P23899, P27889, P35680, P46936, P46937, P46938, P48436, P61753, P61754, Q02078, Q03365, Q04887, Q0P5K4, Q1L8J7, Q2EJA0, Q2LE08, Q2MJT0, Q32NJ6, Q4VYR7, Q571K4, Q5R6A9, Q5RER5, Q5XGD9, Q62431, Q6GQD7, Q7YRJ7, Q7ZXH3

Diamond homologs: Q571K4, Q5RFW2, Q5U303, Q7ZXH3, Q8N5C8, Q99K90, Q9NYJ8

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
TAB3	“up-regulates activity”	MAP3K7	binding
SMAD7	up-regulates	TAB3	binding
RIPK1	“up-regulates activity”	TAB3	binding
TAB3	up-regulates	JNK	binding
TAB3	up-regulates	p38	binding
TRAF6	“up-regulates activity”	TAB3	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 40 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation	5	119.0×	3e-08
TRAF6-mediated induction of TAK1 complex within TLR4 complex	5	111.5×	3e-08
JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1	5	81.1×	1e-07
activated TAK1 mediates p38 MAPK activation	5	77.6×	1e-07
TNFR1-induced NF-kappa-B signaling pathway	6	63.0×	3e-08
NOD1/2 Signaling Pathway	6	59.5×	3e-08
TAK1-dependent IKK and NF-kappa-B activation	6	56.4×	4e-08
SARS-CoV-2-host interactions	8	29.7×	2e-08

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of canonical NF-kappaB signal transduction	5	10.1×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	53
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2424847	NC_000023.10:g.(?28807451)(31201031_?)del	Likely pathogenic

SpliceAI

3327 predictions. Top by Δscore:

Variant	Effect	Δscore
X:30842962:TCA:T	donor_loss	1.0000
X:30842963:CA:C	donor_loss	1.0000
X:30842964:A:AC	donor_gain	1.0000
X:30842964:AC:A	donor_gain	1.0000
X:30842965:C:CC	donor_gain	1.0000
X:30842965:CC:C	donor_gain	1.0000
X:30842965:CCT:C	donor_gain	1.0000
X:30843045:GTTTC:G	acceptor_gain	1.0000
X:30843046:TTTC:T	acceptor_gain	1.0000
X:30843047:TTC:T	acceptor_gain	1.0000
X:30843047:TTCCT:T	acceptor_loss	1.0000
X:30843048:TC:T	acceptor_gain	1.0000
X:30843048:TCC:T	acceptor_loss	1.0000
X:30843049:CC:C	acceptor_gain	1.0000
X:30843049:CCTAT:C	acceptor_loss	1.0000
X:30843050:C:CC	acceptor_gain	1.0000
X:30843051:T:A	acceptor_loss	1.0000
X:30852934:CAAGG:C	acceptor_gain	1.0000
X:30859482:CTTA:C	donor_loss	1.0000
X:30859483:TTAC:T	donor_loss	1.0000
X:30859484:TA:T	donor_loss	1.0000
X:30859485:ACC:A	donor_loss	1.0000
X:30859486:C:CT	donor_loss	1.0000
X:30859674:ATTTT:A	acceptor_gain	1.0000
X:30859675:TTTT:T	acceptor_gain	1.0000
X:30859676:TTT:T	acceptor_gain	1.0000
X:30859676:TTTC:T	acceptor_loss	1.0000
X:30859677:TT:T	acceptor_gain	1.0000
X:30859678:TC:T	acceptor_loss	1.0000
X:30859679:C:CC	acceptor_gain	1.0000

AlphaMissense

302 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:30855528:A:G	L46P	1.000
X:30855528:A:T	L46H	1.000
X:30859529:G:C	F20L	1.000
X:30859529:G:T	F20L	1.000
X:30859530:A:G	F20S	1.000
X:30859531:A:G	F20L	1.000
X:30859542:A:G	L16P	1.000
X:30855539:A:C	C42W	0.999
X:30855541:A:G	C42R	0.999
X:30859521:A:C	I23S	0.999
X:30859542:A:T	L16H	0.999
X:30855528:A:C	L46R	0.998
X:30855540:C:T	C42Y	0.998
X:30859521:A:G	I23T	0.998
X:30859521:A:T	I23N	0.998
X:30859531:A:C	F20V	0.997
X:30859542:A:C	L16R	0.997
X:30859506:A:T	V28E	0.996
X:30859530:A:C	F20C	0.996
X:30859531:A:T	F20I	0.996
X:30859533:C:G	R19P	0.996
X:30859551:A:G	L13P	0.993
X:30855540:C:A	C42F	0.991
X:30859525:C:T	E22K	0.990
X:30859504:A:G	S29P	0.989
X:30859539:C:G	R17P	0.989
X:30859498:A:G	C31R	0.988
X:30859494:A:T	M32K	0.987
X:30859522:T:A	I23F	0.987
X:30855540:C:G	C42S	0.986

dbSNP variants (sampled 300 via entrez): RS1000032598 (X:30871328 G>T), RS1000082522 (X:30883503 G>A), RS1000093633 (X:30867269 T>A,G), RS1000129516 (X:30843837 G>A), RS1000150902 (X:30866731 G>A), RS1000184896 (X:30842099 T>A), RS1000216063 (X:30842702 C>T), RS1000323480 (X:30880787 T>G), RS1000333271 (X:30873233 T>C), RS1000356115 (X:30832424 C>T), RS1000378781 (X:30851834 T>G), RS1000395790 (X:30853976 C>T), RS1000413907 (X:30844371 A>G), RS1000512798 (X:30844657 A>G,T), RS1000683960 (X:30853513 T>A)

Disease associations

OMIM: gene MIM:300480 | disease phenotypes: MIM:310200

GenCC curated gene-disease

Mondo (1): Duchenne muscular dystrophy (MONDO:0010679)

Orphanet (1): Duchenne muscular dystrophy (Orphanet:98896)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D020388	Muscular Dystrophy, Duchenne	C05.651.534.500.300; C10.668.491.175.500.300; C16.320.322.562; C16.320.577.300

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295902 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases expression, increases methylation	5
Quercetin	decreases phosphorylation, increases expression	3
Tetrachlorodibenzodioxin	increases expression	3
Formaldehyde	decreases expression, increases expression	2
Aflatoxin B1	increases expression, decreases methylation	2
Cadmium Chloride	increases expression, decreases expression, increases abundance	2
FR900359	increases phosphorylation	1
dimethylselenide	increases expression, increases oxidation	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
PCI 5002	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Leflunomide	increases expression	1
Acetaminophen	decreases expression	1
Cadmium	decreases expression, increases abundance	1
Carbamazepine	affects expression	1
Chelating Agents	affects binding, increases expression	1
Cisplatin	increases expression	1
Copper	affects binding, increases expression	1
Doxorubicin	decreases expression	1
Endosulfan	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Fatty Acids, Nonesterified	affects expression, decreases reaction	1
Methapyrilene	decreases methylation	1
Methyl Methanesulfonate	increases expression	1
Ozone	increases oxidation, increases expression	1
Dronabinol	increases expression	1
Thiram	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4118640	Binding	Binding affinity to TAB3 in human NCI-H23 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D8BZ	Ubigene A-549 TAB3 KO	Cancer cell line	Male
CVCL_D9TU	Ubigene HEK293 TAB3 KO	Transformed cell line	Female
CVCL_TR45	HAP1 TAB3 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00606775	PHASE4	UNKNOWN	The Preventive Efficacy of Carvedilol on Cardiac Dysfunction in Duchenne Muscular Dystrophy
NCT00819845	PHASE4	UNKNOWN	Ramipril Versus Carvedilol in Duchenne and Becker Patients
NCT01422200	PHASE4	COMPLETED	Flu Vaccine Study in Neuromuscular Patients 2011
NCT01999075	PHASE4	COMPLETED	Stacking Exercises Aid the Decline in FVC and Sick Time
NCT04687020	PHASE4	ACTIVE_NOT_RECRUITING	Long-term Use of Viltolarsen in Boys With Duchenne Muscular Dystrophy in Clinical Practice (VILT-502)
NCT04708314	PHASE4	TERMINATED	An Open-Label Study of Golodirsen in Non-Ambulant Patients With Duchenne Muscular Dystrophy
NCT05412394	PHASE4	RECRUITING	Once Weekly Infant Corticosteroid Trial for DMD
NCT06713135	PHASE4	ACTIVE_NOT_RECRUITING	A Study on Safety and Effectiveness of Long-term Treatment With Vamorolone in Boys With Duchenne Muscular Dystrophy
NCT07542314	PHASE4	NOT_YET_RECRUITING	Study to Evaluate the Safety and Effectiveness of ELEVIDYS in Participants With Duchenne Muscular Dystrophy Treated in a Post-Marketing Setting
NCT00004646	PHASE3	COMPLETED	Phase III Randomized, Double-Blind Study of Prednisone for Duchenne Muscular Dystrophy
NCT00110669	PHASE3	COMPLETED	High-dose Prednisone in Duchenne Muscular Dystrophy
NCT00308113	PHASE3	TERMINATED	CoQ10 and Prednisone in Non-Ambulatory DMD
NCT00839033	PHASE3	TERMINATED	Evaluation of a Mechanical Device During Acute Respiratory Failure in Patients With Neuromuscular Disorders
NCT01247207	PHASE3	COMPLETED	Study of Ataluren in Previously Treated Participants With Nonsense Mutation Dystrophinopathy (nmDBMD)
NCT01557400	PHASE3	COMPLETED	Study of Ataluren for Previously Treated Participants With Nonsense Mutation Duchenne/Becker Muscular Dystrophy (nmDBMD) in Europe, Israel, Australia, and Canada
NCT01603407	PHASE3	COMPLETED	Finding the Optimum Regimen for Duchenne Muscular Dystrophy
NCT01648634	PHASE3	COMPLETED	Nebivolol for the Prevention of Left Ventricular Systolic Dysfunction in Patients With Duchenne Muscular Dystrophy
NCT02255552	PHASE3	COMPLETED	Study of Eteplirsen in DMD Patients
NCT02354352	PHASE3	COMPLETED	Therapeutic Potential for Aldosterone Inhibition in Duchenne Muscular Dystrophy
NCT02500381	PHASE3	COMPLETED	Study of SRP-4045 (Casimersen) and SRP-4053 (Golodirsen) in Participants With Duchenne Muscular Dystrophy (DMD)
NCT02814019	PHASE3	TERMINATED	A Phase III Double-blind Study With Idebenone in Patients With Duchenne Muscular Dystrophy (DMD) Taking Glucocorticoid Steroids
NCT02851797	PHASE3	COMPLETED	Clinical Study to Evaluate the Efficacy and Safety of Givinostat in Ambulant Patients With Duchenne Muscular Dystrophy
NCT03354039	PHASE3	COMPLETED	Tamoxifen in Duchenne Muscular Dystrophy
NCT03532542	PHASE3	TERMINATED	An Extension Study to Evaluate Casimersen or Golodirsen in Patients With Duchenne Muscular Dystrophy
NCT03603288	PHASE3	TERMINATED	Phase III Study With Idebenone in Patients With Duchenne Muscular Dystrophy (SIDEROS-E)
NCT03642145	PHASE3	WITHDRAWN	A Study of Deflazacort (Emflaza®) in Participants With Duchenne Muscular Dystrophy (DMD)
NCT03917719	PHASE3	TERMINATED	An Open-Label Extension Study of Edasalonexent in Boys With Duchenne Muscular Dystrophy
NCT04060199	PHASE3	COMPLETED	Study to Assess the Efficacy and Safety of Viltolarsen in Ambulant Boys With DMD (RACER53)
NCT04281485	PHASE3	ACTIVE_NOT_RECRUITING	Study to Evaluate the Safety and Efficacy of PF-06939926 for the Treatment of Duchenne Muscular Dystrophy
NCT04371666	PHASE3	TERMINATED	Phase 3 Trial of Pamrevlumab or Placebo With Systemic Corticosteroids in Participants With Non-ambulatory Duchenne Muscular Dystrophy (DMD)
NCT04587908	PHASE3	ACTIVE_NOT_RECRUITING	A Phase 3 Study of TAS-205 in Patients With Duchenne Muscular Dystrophy（REACH-DMD）
NCT04632940	PHASE3	TERMINATED	Phase 3 Trial of Pamrevlumab or Placebo in Combination With Systemic Corticosteroids in Participants With Ambulatory DMD
NCT04768062	PHASE3	UNKNOWN	Study to Assess the Safety and Efficacy of Viltolarsen in Ambulant Boys With DMD (RACER53-X)
NCT05096221	PHASE3	COMPLETED	A Gene Transfer Therapy Study to Evaluate the Safety and Efficacy of Delandistrogene Moxeparvovec (SRP-9001) in Participants With Duchenne Muscular Dystrophy (DMD)
NCT05689164	PHASE3	TERMINATED	A Study to Understand the Long-term Safety and Effects of an Experimental Gene Therapy for Duchenne Muscular Dystrophy.
NCT05881408	PHASE3	ACTIVE_NOT_RECRUITING	A Gene Transfer Therapy Study to Evaluate the Safety and Efficacy of Delandistrogene Moxeparvovec (SRP-9001) in Non-Ambulatory and Ambulatory Participants With Duchenne Muscular Dystrophy (DMD)
NCT05933057	PHASE3	RECRUITING	Efficacy, Safety and Tolerability of Givinostat in Non-ambulant Patients With Duchenne Muscular Dystrophy
NCT05967351	PHASE3	ENROLLING_BY_INVITATION	A Long-term Follow-up Study of Participants Who Received Delandistrogene Moxeparvovec (SRP-9001) in a Previous Clinical Study
NCT07160634	PHASE3	RECRUITING	A Study of SGT-003 Gene Therapy in Ambulant Males With Duchenne Muscular Dystrophy (IMPACT DUCHENNE)
NCT07587242	PHASE3	NOT_YET_RECRUITING	A Phase 3 Study to Evaluate the Safety and Efficacy of AOC 1044 (Also Referred to as Delpacibart Zotadirsen) in Participants With DMD With Gene Mutations Amenable to Exon 44 Skipping