TICAM2

Summary

TICAM2 (TIR domain containing adaptor molecule 2, HGNC:21354) is a protein-coding gene on chromosome 5q22.3, encoding TIR domain-containing adapter molecule 2 (Q86XR7). Functions as a sorting adapter in different signaling pathways to facilitate downstream signaling leading to type I interferon induction.

Enables molecular adaptor activity. Involved in several processes, including positive regulation of interleukin-18-mediated signaling pathway; regulation of cytokine production; and regulation of innate immune response. Located in endoplasmic reticulum; endosome; and phagocytic cup. Is active in endosome membrane.

Source: NCBI Gene 353376 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 8 total
• MANE Select transcript: NM_021649

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21354
Approved symbol	TICAM2
Name	TIR domain containing adaptor molecule 2
Location	5q22.3
Locus type	gene with protein product
Status	Approved
Aliases	TRAM, TICAM-2, TIRP
Ensembl gene	ENSG00000243414
Ensembl biotype	protein_coding
OMIM	608321
Entrez	353376

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000427199, ENST00000513729, ENST00000957908

RefSeq mRNA: 1 — MANE Select: NM_021649 NM_021649

CCDS: CCDS4119

Canonical transcript exons

ENST00000427199 — 2 exons

Exon	Start	End
ENSE00001610185	115602097	115602479
ENSE00001741902	115578496	115581315

Expression profiles

Bgee: expression breadth ubiquitous, 131 present calls, max score 86.29.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.4130 / max 111.5175, expressed in 1196 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
63016	4.4130	1196

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	86.29	gold quality
leukocyte	CL:0000738	85.91	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.57	gold quality
granulocyte	CL:0000094	79.29	gold quality
calcaneal tendon	UBERON:0003701	77.92	gold quality
endometrium	UBERON:0001295	74.57	gold quality
lower esophagus mucosa	UBERON:0035834	74.27	gold quality
descending thoracic aorta	UBERON:0002345	73.93	gold quality
right adrenal gland cortex	UBERON:0035827	73.59	gold quality
stromal cell of endometrium	CL:0002255	73.44	gold quality
spleen	UBERON:0002106	72.86	gold quality
right adrenal gland	UBERON:0001233	72.75	gold quality
lymph node	UBERON:0000029	72.61	gold quality
right coronary artery	UBERON:0001625	72.52	gold quality
left adrenal gland	UBERON:0001234	72.20	gold quality
left adrenal gland cortex	UBERON:0035825	72.05	gold quality
vermiform appendix	UBERON:0001154	71.93	gold quality
body of pancreas	UBERON:0001150	71.60	gold quality
thoracic aorta	UBERON:0001515	71.22	gold quality
ascending aorta	UBERON:0001496	71.05	gold quality
smooth muscle tissue	UBERON:0001135	71.04	gold quality
left coronary artery	UBERON:0001626	70.92	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	70.77	gold quality
subcutaneous adipose tissue	UBERON:0002190	70.61	gold quality
adipose tissue	UBERON:0001013	70.39	gold quality
omental fat pad	UBERON:0010414	70.19	gold quality
right lobe of liver	UBERON:0001114	70.02	gold quality
lower esophagus	UBERON:0013473	69.98	gold quality
lower esophagus muscularis layer	UBERON:0035833	69.94	gold quality
body of uterus	UBERON:0009853	69.75	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.13

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP53, ZNF79

miRNA regulators (miRDB)

92 targeting TICAM2, 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-4283	100.00	66.42	2097
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-8076	99.78	68.52	1170
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-1296-3P	99.72	64.04	636

Literature-anchored findings (GeneRIF, showing 17)

• Overexpression of TIRP activates NF-kappaB and potentiates IL-1 receptor-mediated NF-kappaB activation (PMID:12721283)
• the adapter complex of TICAM-2 and TICAM-1 plays a crucial role in lipopolysaccharide-TLR4-mediated activation of IFN-beta (PMID:14519765)
• The myristoylation of TRAM targets it to the plasma membrane, where it is essential for LPS responses through the TLR4 signal transduction pathway. (PMID:16603631)
• TRAM functions as a sorting adaptor that controls the initiation of TRIF/TICAM1-dependent signaling from an endosomal compartment; TRAM seems to be required for Toll-like receptor-4 coupling on the cell surface to the endosomal activation of TRIF-TRAF3. (PMID:18297073)
• TAG is a splice variant of TRAM. TAG inhibits TRAM by displacing TRIF, and TAG overexpression specifically inhibits TLR4 signaling. (PMID:19412184)
• viral inhibitor peptide of TLR4 possibly represents a surface domain of A46 that specifically inhibits TLR4 by masking critical binding sites on MyD88 adaptor-like and TRIF-related adaptor molecule (PMID:20802145)
• Data indicate that MyD88 works together with the IL-1/IL-18 receptors, can interact with two distinct sorting adaptors, TRAM and Mal, in a conserved manner. (PMID:22685567)
• induction of both IL-6 and IL-8 is associated with elevated TIRAP and reduced TRAM mRNA expression (PMID:22970235)
• results suggest TLR adaptor molecules knockdown, such as MyD88 or TRAM, can decrease IL-6 and IL-8 mRNA and increase CXCL12 mRNA expression in HGF and HPDLF. (PMID:23136947)
• The homotypic interaction between TICAM-2 TIR is indispensable to present a scaffold for recruiting the monomeric moiety of the TICAM-1 TIR dimer. (PMID:24255114)
• A putative TRAF6-binding motif in TRAM may mediate a new TRAM function in TLR4 signaling in regulating inflammatory responses, distinct from its bridging TLR4 and TRIF. A TRAM E183A mutation abolished this. (PMID:24812060)
• TRAM plays a role in TLR7 signaling through a novel signaling axis towards the activation of anti-viral immunity. (PMID:25211222)
• TRAM acts as a sorting adaptor not only for TLR4, but also for TLR2, to facilitate signaling to IRF7 at the endosome, which explains how TLR2 is capable of causing type I IFN induction. (PMID:25385819)
• Findings were SNPs in TICAM2 (P = 3.6 x 10(-6)) and IL1B (P = 4.3 x 10(-5)) associated with TB. (PMID:25521228)
• Data show that Toll/IL-1R domain-containing adaptor molecule (TICAM)-2 possesses two conserved acidic amino acids, D91 and E92, which regulate TICAM-2 self-activation and signaling. (PMID:26408662)
• Data suggest that endosomal localization of TICAM2 is essential for TLR4-mediated type I interferon-inducing signaling from endosomes; TICAM2 acts as scaffold protein and activates TICAM1; N-terminal myristoylation allows TICAM2 to anchor to endosomal membrane. (TICAM2 = toll like receptor adaptor molecule-2; TICAM1 = toll like receptor adaptor molecule-1; TLR4 = toll-like receptor 4) [REVIEW] (PMID:28630139)
• SLAMF1 is required for TLR4-mediated TRAM-TRIF-dependent signaling in human macrophages. (PMID:29440514)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
danio_rerio	ticam1	ENSDARG00000102493
rattus_norvegicus	Ticam2	ENSRNOG00000042070

Protein

Protein identifiers

TIR domain-containing adapter molecule 2 — Q86XR7 (reviewed: Q86XR7)

Alternative names: Putative NF-kappa-B-activating protein 502, TRIF-related adapter molecule, Toll-like receptor adaptor protein 3, Toll/interleukin-1 receptor domain-containing protein

All UniProt accessions (1): Q86XR7

UniProt curated annotations — full annotation on UniProt →

Function. Functions as a sorting adapter in different signaling pathways to facilitate downstream signaling leading to type I interferon induction. In TLR4 signaling, physically bridges TLR4 and TICAM1 and functionally transmits signal to TICAM1 in early endosomes after endocytosis of TLR4. In TLR2 signaling, physically bridges TLR2 and MYD88 and is required for the TLR2-dependent movement of MYD88 to endosomes following ligand engagement. Involved in IL-18 signaling and is proposed to function as a sorting adapter for MYD88 in IL-18 signaling during adaptive immune response. Forms a complex with RAB11FIP2 that is recruited to the phagosomes to promote the activation of the actin-regulatory GTPases RAC1 and CDC42 and subsequent phagocytosis of Gram-negative bacteria. Proposed to inhibit LPS-TLR4 signaling at the late endosome by interaction with isoform 1 thereby disrupting the association of isoform 1 with TICAM1. May be involved in TLR4 degradation in late endosomes.

Subunit / interactions. Homodimer. Interacts with TLR4, TICAM1, IRF3 and IRF7 in response to LPS. Interacts with IL1R1, IL1RAP, IRAK2, IRAK3 and TRAF6. Interacts with protein kinase-inactive mutants of IRAK1 and IRAK4. Isoform 1 interacts with isoform 2; the interaction occurs in late endosomes and disrupts the interaction between isoform 1 and TICAM1. Interacts with MYD88; the interaction decreases after IL-18 stimulation in a time-dependent manner. Interacts with IL18R1 and IL18RAP. Interacts with TLR2. Interacts with RAB11FIP2.

Subcellular location. Cytoplasm. Golgi apparatus. Cell membrane. Endoplasmic reticulum. Early endosome membrane. Late endosome membrane. Cell projection. Phagocytic cup Endoplasmic reticulum.

Tissue specificity. Expressed in spleen, prostate, testis, uterus, small intestine, colon, peripheral blood leukocytes, heart, placenta, lung, liver, skeletal muscle, and pancreas Isoform 2 is ubiquitously expressed (at lower levels than isoform 1).

Post-translational modifications. Phosphorylated by PRKCE in response to LPS. Phosphorylation is essential for its function. It is depleted from the membrane upon phosphorylation. Tyrosine phosphorylation is inhibited by phosphatase PTPN4. Isoform 1 is myristoylated. Required for membrane association which is critical for its ability to initiate efficient signaling.

Domain organisation. The TIR domain mediates the interaction with TRAF6 and MYD88.

Isoforms (2)

UniProt ID	Names	Canonical?
Q86XR7-1	1, TRAM	yes
Q86XR7-2	2, TAG, TRAM adaptor with GOLD domain

RefSeq proteins (1): NP_067681* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000157	TIR_dom	Domain
IPR035897	Toll_tir_struct_dom_sf	Homologous_superfamily
IPR046946	TCAM1/2	Family

Pfam: PF13676

UniProt features (38 total): mutagenesis site 10, strand 9, helix 7, turn 3, modified residue 2, initiator methionine 1, chain 1, domain 1, region of interest 1, compositionally biased region 1, lipid moiety-binding region 1, splice variant 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
9DKI	X-RAY DIFFRACTION	3
9DLG	ELECTRON MICROSCOPY	5.6
2M1W	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86XR7-F1	75.40	0.53

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 (3): 16, 167, 2

Mutagenesis-validated functional residues (10):

Position	Phenotype
6	loss of phosphorylation. significant reduction in the ability to activate irf3 or nf-kappa-b.
10	no effect on phosphorylation and on the ability to activate irf3 or nf-kappa-b.
14	no effect on phosphorylation and on the ability to activate irf3 or nf-kappa-b.
16	loss of phosphorylation. abolishes ability to activate irf3 or nf-kappa-b and to transduce tlr4 signal.
16	significant decrease of localization in the membrane.
116	loss of ability to dimerize. significant loss of rantes-inducing activity. loss of ability to induce nf-kappa-b activati
117	loss of ability to dimerize. loss of rantes-inducing activity and ability to induce nf-kappa-b activation. inhibition of
154	no effect on phosphorylation.
167	complete loss of phosphorylation in response to lps.
2	results in relocalization from membrane to cytosol; loss of ability to transduce tlr4-signal. loss of tlr2-mediated acti

Function

Pathways and Gene Ontology

Reactome pathways

21 pathways

ID	Pathway
R-HSA-140534	Caspase activation via Death Receptors in the presence of ligand
R-HSA-166016	Toll Like Receptor 4 (TLR4) Cascade
R-HSA-166166	MyD88-independent TLR4 cascade
R-HSA-2562578	TRIF-mediated programmed cell death
R-HSA-6798695	Neutrophil degranulation
R-HSA-936964	Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE)
R-HSA-937041	IKK complex recruitment mediated by RIP1
R-HSA-937072	TRAF6-mediated induction of TAK1 complex within TLR4 complex
R-HSA-975163	IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation
R-HSA-9824878	Regulation of TBK1, IKKε (IKBKE)-mediated activation of IRF3, IRF7
R-HSA-109581	Apoptosis
R-HSA-168138	Toll Like Receptor 9 (TLR9) Cascade
R-HSA-168181	Toll Like Receptor 7/8 (TLR7/8) Cascade
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-168898	Toll-like Receptor Cascades
R-HSA-5357769	Caspase activation via extrinsic apoptotic signalling pathway
R-HSA-5357801	Programmed Cell Death
R-HSA-937061	TRIF (TICAM1)-mediated TLR4 signaling
R-HSA-975138	TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation
R-HSA-975155	MyD88 dependent cascade initiated on endosome

MSigDB gene sets: 162 (showing top): REACTOME_TRAF6_MEDIATED_INDUCTION_OF_TAK1_COMPLEX_WITHIN_TLR4_COMPLEX, GSE45365_NK_CELL_VS_CD8_TCELL_UP, REACTOME_IKK_COMPLEX_RECRUITMENT_MEDIATED_BY_RIP1, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_POSITIVE_REGULATION_OF_TYPE_I_INTERFERON_PRODUCTION, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOCC_SECRETORY_GRANULE, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, PID_IL1_PATHWAY, GOBP_REGULATION_OF_TOLL_LIKE_RECEPTOR_4_SIGNALING_PATHWAY, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, GOBP_VESICLE_MEDIATED_TRANSPORT

GO Biological Process (17): phagocytosis (GO:0006909), inflammatory response (GO:0006954), positive regulation of type I interferon production (GO:0032481), toll-like receptor 4 signaling pathway (GO:0034142), negative regulation of toll-like receptor 4 signaling pathway (GO:0034144), positive regulation of toll-like receptor 4 signaling pathway (GO:0034145), TRIF-dependent toll-like receptor signaling pathway (GO:0035666), TRAM-dependent toll-like receptor 4 signaling pathway (GO:0035669), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), innate immune response (GO:0045087), cellular response to lipopolysaccharide (GO:0071222), negative regulation of chemokine (C-C motif) ligand 5 production (GO:0071650), positive regulation of chemokine (C-C motif) ligand 5 production (GO:0071651), positive regulation of interleukin-18-mediated signaling pathway (GO:2000494), immune system process (GO:0002376), signal transduction (GO:0007165), response to other organism (GO:0051707)

GO Molecular Function (3): signaling adaptor activity (GO:0035591), molecular adaptor activity (GO:0060090), protein binding (GO:0005515)

GO Cellular Component (14): phagocytic cup (GO:0001891), endosome (GO:0005768), early endosome (GO:0005769), late endosome (GO:0005770), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), endosome membrane (GO:0010008), secretory granule membrane (GO:0030667), early endosome membrane (GO:0031901), late endosome membrane (GO:0031902), cytoplasm (GO:0005737), membrane (GO:0016020), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
TRIF (TICAM1)-mediated TLR4 signaling	4
Toll-like Receptor Cascades	3
Innate Immune System	2
Caspase activation via extrinsic apoptotic signalling pathway	1
Toll Like Receptor 4 (TLR4) Cascade	1
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation	1
Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE)	1
Programmed Cell Death	1
Immune System	1
Apoptosis	1
MyD88-independent TLR4 cascade	1
MyD88 dependent cascade initiated on endosome	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
toll-like receptor 4 signaling pathway	3
endomembrane system	3
endosome	3
regulation of toll-like receptor 4 signaling pathway	2
chemokine (C-C motif) ligand 5 production	2
regulation of chemokine (C-C motif) ligand 5 production	2
binding	2
cytoplasm	2
intracellular membrane-bounded organelle	2
cytoplasmic vesicle membrane	2
bounding membrane of organelle	2
endosome membrane	2
endocytosis	1
defense response	1
positive regulation of cytokine production	1
regulation of type I interferon production	1
type I interferon production	1
cell surface toll-like receptor signaling pathway	1
negative regulation of immune system process	1
negative regulation of signal transduction	1
positive regulation of pattern recognition receptor signaling pathway	1
MyD88-independent toll-like receptor signaling pathway	1
TRAM-dependent toll-like receptor signaling pathway	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
positive regulation of intracellular signal transduction	1
immune response	1
defense response to symbiont	1
response to lipopolysaccharide	1
cellular response to molecule of bacterial origin	1
cellular response to lipid	1
cellular response to oxygen-containing compound	1
negative regulation of chemokine production	1
positive regulation of chemokine production	1
positive regulation of cytokine-mediated signaling pathway	1
interleukin-18-mediated signaling pathway	1
regulation of interleukin-18-mediated signaling pathway	1
biological_process	1
cell communication	1

Protein interactions and networks

STRING

1185 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TICAM2	TLR4	O00206	988
TICAM2	TIRAP	P58753	923
TICAM2	TLR2	O60603	887
TICAM2	MYD88	P78397	872
TICAM2	IFNB1	P01574	825
TICAM2	TLR3	O15455	798
TICAM2	IRAK1	P51617	793
TICAM2	LY96	Q9Y6Y9	724
TICAM2	IL1R1	P14778	720
TICAM2	IRAK4	Q9NWZ3	676
TICAM2	TICAM1	Q8IUC6	667
TICAM2	TBK1	Q9UHD2	664
TICAM2	TRAF3	Q13114	657
TICAM2	IRF3	Q14653	651
TICAM2	IRAK2	O43187	645

IntAct

34 interactions, top by confidence:

A	B	Type	Score
TLR4	TIRAP	psi-mi:“MI:0914”(association)	0.810
TLR4	TICAM2	psi-mi:“MI:0915”(physical association)	0.680
SARM1	TICAM2	psi-mi:“MI:0407”(direct interaction)	0.590
TICAM2	SARM1	psi-mi:“MI:0915”(physical association)	0.590
MEOX2	TICAM2	psi-mi:“MI:0915”(physical association)	0.560
TICAM2	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
AGER	TIRAP	psi-mi:“MI:0914”(association)	0.560
TICAM2	NTAQ1	psi-mi:“MI:0915”(physical association)	0.560
C	TICAM2	psi-mi:“MI:0403”(colocalization)	0.460
TICAM2	C	psi-mi:“MI:0915”(physical association)	0.460
IL1R1	TICAM2	psi-mi:“MI:0915”(physical association)	0.400
IL1RAP	TICAM2	psi-mi:“MI:0915”(physical association)	0.400
TICAM2	TIRAP	psi-mi:“MI:0915”(physical association)	0.400
TICAM2	TICAM1	psi-mi:“MI:0915”(physical association)	0.400
TRAF6	TICAM2	psi-mi:“MI:0915”(physical association)	0.400
TICAM2	IRAK2	psi-mi:“MI:0915”(physical association)	0.400
TICAM2	IRAK3	psi-mi:“MI:0915”(physical association)	0.400
TICAM2	TICAM2	psi-mi:“MI:0915”(physical association)	0.370
TICAM2	PIAS2	psi-mi:“MI:0915”(physical association)	0.370
TICAM2	FTH1	psi-mi:“MI:0915”(physical association)	0.370
CANX	HLA-A	psi-mi:“MI:0914”(association)	0.350
PGRMC1	NBAS	psi-mi:“MI:0914”(association)	0.350
RAB1B	TOMM40	psi-mi:“MI:0914”(association)	0.350
TMED10	PGRMC1	psi-mi:“MI:0914”(association)	0.350
TMED2	PGRMC1	psi-mi:“MI:0914”(association)	0.350
YIPF5	EI24	psi-mi:“MI:0914”(association)	0.350
CD79A	TMEM131L	psi-mi:“MI:0914”(association)	0.350
TICAM2	ERBB2	psi-mi:“MI:0914”(association)	0.350

BioGRID (42): TICAM2 (Two-hybrid), TICAM2 (Affinity Capture-Western), TRAF6 (Reconstituted Complex), TICAM2 (Affinity Capture-Western), TICAM2 (Affinity Capture-Western), TMED7-TICAM2 (Affinity Capture-RNA), TMED7-TICAM2 (Affinity Capture-RNA), TICAM2 (Two-hybrid), TICAM2 (Affinity Capture-Western), TICAM2 (Affinity Capture-Western), TMED7-TICAM2 (Affinity Capture-MS), TMED7-TICAM2 (Affinity Capture-MS), TICAM2 (Affinity Capture-MS), ACVR2A (Affinity Capture-MS), AXL (Affinity Capture-MS)

ESM2 similar proteins: O08736, O35368, O35732, O75601, O89110, P0C7P3, P0DOV1, P0DOV2, P13504, P14778, P29452, P29466, P29594, P43527, P49662, P51878, P55215, P70343, Q02955, Q075B4, Q14790, Q153Z0, Q2LGB7, Q3UX83, Q4AC99, Q4R7Q1, Q504J1, Q504N7, Q5E9C1, Q5RAV7, Q62929, Q6UXS9, Q7TPQ3, Q86XR7, Q8BJQ4, Q8BV49, Q8CEL2, Q8NE18, Q920D5, Q92851

Diamond homologs: Q2LGB7, Q4JF29, Q80UF7, Q86XR7, Q8BJQ4, Q8IUC6

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
TICAM2	“up-regulates activity”	TICAM1	binding
PRKCE	up-regulates	TICAM2	phosphorylation
TLR4	up-regulates	TICAM2	binding
TLRs	“up-regulates activity”	TICAM2	binding
TLR2	“up-regulates activity”	TICAM2	binding
TLR9	“up-regulates activity”	TICAM2	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 30 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
TRAF6-mediated induction of TAK1 complex within TLR4 complex	5	155.2×	2e-08
MyD88:MAL(TIRAP) cascade initiated on plasma membrane	5	33.1×	1e-05
Interleukin-1 signaling	5	27.0×	3e-05

GO biological processes:

GO term	Partners	Fold	FDR
MyD88-dependent toll-like receptor signaling pathway	5	167.2×	3e-08
interleukin-1-mediated signaling pathway	5	143.3×	3e-08
lipopolysaccharide-mediated signaling pathway	5	94.0×	2e-07
toll-like receptor 4 signaling pathway	5	94.0×	2e-07
positive regulation of interleukin-6 production	6	35.8×	9e-07
positive regulation of canonical NF-kappaB signal transduction	8	20.8×	2e-07
inflammatory response	8	10.8×	2e-05
immune response	5	8.4×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	4
Likely benign	0
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

393 predictions. Top by Δscore:

Variant	Effect	Δscore
5:115581207:C:CT	acceptor_gain	1.0000
5:115581207:C:T	acceptor_gain	1.0000
5:115581208:A:T	acceptor_gain	1.0000
5:115600032:G:C	donor_gain	0.9800
5:115581316:C:CC	acceptor_gain	0.9700
5:115602089:GTACT:G	donor_loss	0.9700
5:115602090:TACTT:T	donor_loss	0.9700
5:115602091:A:AC	donor_gain	0.9700
5:115602091:ACTT:A	donor_loss	0.9700
5:115602092:C:CC	donor_gain	0.9700
5:115602093:TTG:T	donor_loss	0.9700
5:115602094:TG:T	donor_loss	0.9700
5:115602096:C:CG	donor_loss	0.9700
5:115602141:T:TA	donor_gain	0.9700
5:115581206:C:T	acceptor_gain	0.9500
5:115581816:G:T	donor_gain	0.9500
5:115602088:GGTAC:G	donor_loss	0.9500
5:115602093:T:C	donor_gain	0.9300
5:115581313:AATC:A	acceptor_loss	0.9200
5:115581313:AATCT:A	acceptor_loss	0.9200
5:115581314:ATCT:A	acceptor_loss	0.9200
5:115581314:ATCTA:A	acceptor_loss	0.9200
5:115581315:TCT:T	acceptor_loss	0.9200
5:115581315:TCTA:T	acceptor_loss	0.9200
5:115581316:CT:C	acceptor_loss	0.9200
5:115581317:T:G	acceptor_loss	0.9200
5:115581312:CAAT:C	acceptor_gain	0.9100
5:115581330:A:T	acceptor_loss	0.9100
5:115581792:A:C	donor_gain	0.9100
5:115581868:A:AC	donor_gain	0.9000

AlphaMissense

1568 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:115580857:A:G	W134R	0.998
5:115580857:A:T	W134R	0.998
5:115581014:A:C	F81L	0.998
5:115581014:A:T	F81L	0.998
5:115581016:A:G	F81L	0.998
5:115580673:A:G	L195S	0.997
5:115580748:A:T	V170D	0.997
5:115580752:A:G	S169P	0.997
5:115580759:T:A	K166N	0.997
5:115580759:T:G	K166N	0.997
5:115580828:A:C	F143L	0.997
5:115580828:A:T	F143L	0.997
5:115580830:A:G	F143L	0.997
5:115580838:G:A	T140I	0.997
5:115581009:A:T	I83K	0.997
5:115580742:G:T	P172H	0.996
5:115580743:G:A	P172S	0.996
5:115580745:A:T	I171K	0.996
5:115580844:A:G	L138S	0.996
5:115580651:A:C	F202L	0.995
5:115580651:A:T	F202L	0.995
5:115580653:A:G	F202L	0.995
5:115580691:A:T	L189H	0.995
5:115580761:T:C	K166E	0.995
5:115580855:C:A	W134C	0.995
5:115580855:C:G	W134C	0.995
5:115581009:A:C	I83R	0.995
5:115580760:T:A	K166I	0.994
5:115580775:A:T	V161D	0.994
5:115580859:G:T	A133E	0.994

dbSNP variants (sampled 300 via entrez): RS1000189939 (5:115597986 T>C), RS1000373144 (5:115600878 G>A,T), RS1000455695 (5:115597764 A>G), RS1000531891 (5:115599370 T>C), RS1000591363 (5:115593545 A>G), RS1000754804 (5:115603455 T>C), RS1000943923 (5:115582465 G>A), RS1001005293 (5:115595721 T>C,G), RS1001111931 (5:115587830 T>A), RS1001197516 (5:115599121 G>A,T), RS1001230863 (5:115591498 T>C), RS1001351101 (5:115579117 T>A,C), RS1001481256 (5:115587639 T>C), RS1001488001 (5:115578924 T>C), RS1001573951 (5:115597423 T>C,G)

Disease associations

OMIM: gene MIM:608321 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST007059_14	Response to antidepressants (symptom improvement)	5.000000e-06
GCST007732_4	Allergic disease (asthma, hay fever or eczema)	3.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, increases expression	2
Benzo(a)pyrene	increases expression	2
Plant Extracts	affects cotreatment, increases expression, decreases reaction	2
aristolochic acid I	increases expression	1
bisphenol F	affects cotreatment, increases expression	1
sodium arsenate	increases abundance, increases expression	1
salinomycin	decreases expression	1
gossypol acetic acid	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
pentabromodiphenyl ether	increases expression	1
ICG 001	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
3,5-bis(2-fluorobenzylidene)piperidin-4-one	decreases reaction, increases expression	1
jinfukang	affects cotreatment, decreases expression	1
PCI 5002	affects cotreatment, increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Bortezomib	increases expression, increases reaction	1
Resveratrol	affects cotreatment, increases expression	1
Arsenic Trioxide	increases reaction, increases expression	1
Antigens, Viral	increases expression	1
Arsenic	increases abundance, increases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Copper	affects binding, decreases expression	1
Curcumin	decreases reaction, increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Dinitrofluorobenzene	increases expression	1
Disulfiram	affects binding, decreases expression	1
Estradiol	increases expression, affects cotreatment	1
Herbicides	decreases expression	1
Indomethacin	affects cotreatment, increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TS34	HAP1 TICAM2 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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