TICAM1 (TIR domain containing adaptor molecule 1)

Gene

• Entrez ID: 148022
• Gene name: TIR domain containing adaptor molecule 1
• Gene symbol: TICAM1
• Synonyms: IIAE6, MyD88-3, PRVTIRB, TICAM-1, TRIF
• Chromosome: 19
• Chromosome location: 19p13.3
• Summary: This gene encodes an adaptor protein containing a Toll/interleukin-1 receptor (TIR) homology domain, which is an intracellular signaling domain that mediates protein-protein interactions between the Toll-like receptors (TLRs) and signal-transduction compo

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs143679494	C>A,T	Likely-benign, risk-factor	Missense variant, coding sequence variant
rs387907307	G>A,C	Risk-factor	Stop gained, coding sequence variant, missense variant
rs1555730283	G>A	Risk-factor	Coding sequence variant, missense variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT005475	hsa-miR-221-3p	Luciferase reporter assay, Northern blot, qRT-PCR, Western blot	21236259
MIRT041391	hsa-miR-193b-3p	CLASH	23622248

Transcription factors

Transcription factor	Regulation	Reference
SP1	Repression	14960149
TRAF6	Unknown	14530355;20047764

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0002281	Process	Macrophage activation involved in immune response	IEA
GO:0002735	Process	Positive regulation of myeloid dendritic cell cytokine production	IBA	21873635
GO:0002735	Process	Positive regulation of myeloid dendritic cell cytokine production	ISS
GO:0002756	Process	MyD88-independent toll-like receptor signaling pathway	TAS
GO:0005515	Function	Protein binding	IPI	14982987, 15142865, 15841462, 19416887, 21903422, 22948160, 25736436
GO:0005739	Component	Mitochondrion	ISS
GO:0005776	Component	Autophagosome	IEA
GO:0005829	Component	Cytosol	TAS
GO:0006954	Process	Inflammatory response	IEA
GO:0007249	Process	I-kappaB kinase/NF-kappaB signaling	TAS
GO:0010008	Component	Endosome membrane	TAS
GO:0010508	Process	Positive regulation of autophagy	ISS
GO:0010628	Process	Positive regulation of gene expression	ISS
GO:0016032	Process	Viral process	IEA
GO:0019901	Function	Protein kinase binding	IBA	21873635
GO:0019901	Function	Protein kinase binding	IPI	14530355
GO:0030890	Process	Positive regulation of B cell proliferation	IEA
GO:0031398	Process	Positive regulation of protein ubiquitination	IEA
GO:0031663	Process	Lipopolysaccharide-mediated signaling pathway	IBA	21873635
GO:0032092	Process	Positive regulation of protein binding	IEA
GO:0032722	Process	Positive regulation of chemokine production	IEA
GO:0032728	Process	Positive regulation of interferon-beta production	IEA
GO:0032755	Process	Positive regulation of interleukin-6 production	IEA
GO:0032760	Process	Positive regulation of tumor necrosis factor production	IEA
GO:0032816	Process	Positive regulation of natural killer cell activation	IBA	21873635
GO:0034128	Process	Negative regulation of MyD88-independent toll-like receptor signaling pathway	TAS
GO:0034138	Process	Toll-like receptor 3 signaling pathway	TAS
GO:0035666	Process	TRIF-dependent toll-like receptor signaling pathway	IBA	21873635
GO:0035666	Process	TRIF-dependent toll-like receptor signaling pathway	IMP	25636800
GO:0035666	Process	TRIF-dependent toll-like receptor signaling pathway	ISS
GO:0035666	Process	TRIF-dependent toll-like receptor signaling pathway	TAS
GO:0043123	Process	Positive regulation of I-kappaB kinase/NF-kappaB signaling	HMP	12761501
GO:0043123	Process	Positive regulation of I-kappaB kinase/NF-kappaB signaling	IBA	21873635
GO:0043123	Process	Positive regulation of I-kappaB kinase/NF-kappaB signaling	IMP	14982987
GO:0043123	Process	Positive regulation of I-kappaB kinase/NF-kappaB signaling	ISS
GO:0043254	Process	Regulation of protein-containing complex assembly	IEA
GO:0043330	Process	Response to exogenous dsRNA	IBA	21873635
GO:0043330	Process	Response to exogenous dsRNA	IMP	21266579
GO:0043330	Process	Response to exogenous dsRNA	ISS
GO:0045087	Process	Innate immune response	IEA
GO:0045429	Process	Positive regulation of nitric oxide biosynthetic process	IEA
GO:0051092	Process	Positive regulation of NF-kappaB transcription factor activity	IBA	21873635
GO:0051607	Process	Defense response to virus	IEA
GO:0070266	Process	Necroptotic process	TAS
GO:0071222	Process	Cellular response to lipopolysaccharide	ISS
GO:0097190	Process	Apoptotic signaling pathway	TAS
GO:0097342	Component	Ripoptosome	IDA	21737330
GO:0140052	Process	Cellular response to oxidised low-density lipoprotein particle stimulus	ISS
GO:1900017	Process	Positive regulation of cytokine production involved in inflammatory response	IBA	21873635
GO:1900017	Process	Positive regulation of cytokine production involved in inflammatory response	ISS

Other IDs

• MIM: 607601
• HGNC: 18348
• e!Ensembl: ENSG00000127666

Protein

• UniProt ID: Q8IUC6
• Protein name: TIR domain-containing adapter molecule 1 (TICAM-1) (Proline-rich, vinculin and TIR domain-containing protein B) (Putative NF-kappa-B-activating protein 502H) (Toll-interleukin-1 receptor domain-containing adapter protein inducing interferon beta) (MyD88-3
• Protein function: Involved in innate immunity against invading pathogens. Adapter used by TLR3, TLR4 (through TICAM2) and TLR5 to mediate NF-kappa-B and interferon-regulatory factor (IRF) activation, and to induce apoptosis (PubMed:12471095, PubMed:12539043, PubM
• PDB: 2M1X, 2M63, 3RC4, 4BSX, 4C0M, 5JEL, 9DK8
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF17798	TRIF-NTD	1 → 148	TRIF N-terminal domain	Domain
  PF12721	RHIM	642 → 697	RIP homotypic interaction motif	Family

• Sequence:

  MACTGPSLPSAFDILGAAGQDKLLYLKHKLKTPRPGCQGQDLLHAMVLLKLGQETEARIS
  LEALKADAVARLVARQWAGVDSTEDPEEPPDVSWAVARLYHLLAEEKLCPASLRDVAYQE
  AVRTLSSRDDHRLGELQDEARNRCGWDIAGDPGSIRTLQSNLGCLPPSSALPSGTRSLPR
  PIDGVSDWSQGCSLRSTGSPASLASNLEISQSPTMPFLSLHRSPHGPSKLCDDPQASLVP
  EPVPGGCQEPEEMSWPPSGEIASPPELPSSPPPGLPEVAPDATSTGLPDTPAAPETSTNY
  PVECTEGSAGPQSLPLPILEPVKNPCSVKDQTPLQLSVEDTTSPNTKPCPPTPTTPETSP
  PPPPPPPSSTPCSAHLTPSSLFPSSLESSSEQKFYNFVILHARADEHIALRVREKLEALG
  VPDGATFCEDFQVPGRGELSCLQDAIDHSAFIILLLTSNFDCRLSLHQVNQAMMSNLTRQ
  GSPDCVIPFLPLESSPAQLSSDTASLLSGLVRLDEHSQIFARKVANTFKPHRLQARKAMW
  RKEQDTRALREQSQHLDGERMQAAALNAAYSAYLQSYLSYQAQMEQLQVAFGSHMSFGTG
  APYGARMPFGGQVPLGAPPPFPTWPGCPQPPPLHAWQAGTPPPPSPQPAAFPQSLPFPQS
  PAFPTASPAPPQSPGLQPLIIHHAQMVQLGLNNHMWNQRGSQAPEDKTQEAE

• Sequence length: 712

Pathways

KEGG:

NF-kappa B signaling pathway
Necroptosis
Toll-like receptor signaling pathway
NOD-like receptor signaling pathway
Alcoholic liver disease
Pertussis
Yersinia infection
Chagas disease
Hepatitis C
Hepatitis B
Influenza A
Human papillomavirus infection
Kaposi sarcoma-associated herpesvirus infection
Herpes simplex virus 1 infection
PD-L1 expression and PD-1 checkpoint pathway in cancer
Lipid and atherosclerosis

Reactome:

Caspase activation via Death Receptors in the presence of ligand
MyD88-independent TLR4 cascade
Toll Like Receptor 3 (TLR3) Cascade
TICAM1, RIP1-mediated IKK complex recruitment
RIP-mediated NFkB activation via ZBP1
TRIF-mediated programmed cell death
TICAM1 deficiency - HSE
TRAF3 deficiency - HSE
TLR3-mediated TICAM1-dependent programmed cell death
TICAM1-dependent activation of IRF3/IRF7
TICAM1,TRAF6-dependent induction of TAK1 complex
Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon
IKK complex recruitment mediated by RIP1
TRAF6-mediated induction of TAK1 complex within TLR4 complex
IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Breast cancer	Malignant neoplasm of breast	rs587776547, rs1137887, rs137853007, rs587776650, rs80359351, rs80359714, rs121917783, rs104886456, rs121964878, rs80359874, rs80357868, rs80357508, rs387906843, rs80357569, rs80358158, rs80357524, rs80357115, rs80357945, rs80357729, rs80357609, rs80357259, rs80357981, rs80358063, rs80357389, rs80356862, rs80359876, rs80357580, rs80358053, rs80358089, rs80187739, rs397507241, rs80358069, rs80357590, rs80357284, rs80357941, rs80359261, rs80359272, rs80359276, rs276174813, rs80358474, rs80359316, rs1555282969, rs80359388, rs80359499, rs80359505, rs80359520, rs80359526, rs80359533, rs56253082, rs80358824, rs80359554, rs80359636, rs80359651, rs80359659, rs80359011, rs80359012, rs80359013, rs80359718, rs397507410, rs81002812, rs80359730, rs80359152, rs80359159, rs397507419, rs28897759, rs80359211, rs80359775, rs397514577, rs397507584, rs80358435, rs80358456, rs80359340, rs80359343, rs80359365, rs80358579, rs397507670, rs80358593, rs80359406, rs80359444, rs80359454, rs276174853, rs276174854, rs80359483, rs80359537, rs80358815, rs80358843, rs80359558, rs80359560, rs80359594, rs80358893, rs28897743, rs397507900, rs397507906, rs397507918, rs80358971, rs80358981, rs397507941, rs80359030, rs80359035, rs41293511, rs397507396, rs81002806, rs80359112, rs397508006, rs81002893, rs45580035, rs80359760, rs397508051, rs80359772, rs4987049, rs80359777, rs80357770, rs397508867, rs62625303, rs397508874, rs80357506, rs80357287, rs273898674, rs80358042, rs80358083, rs80357058, rs41286296, rs80357960, rs80356945, rs80357223, rs386134270, rs80358116, rs80357856, rs80357424, rs397509050, rs80357485, rs80357966, rs397509067, rs80357310, rs80356866, rs80357260, rs80357437, rs80358023, rs80358086, rs80357133, rs80356993, rs80357997, rs80357239, rs80357227, rs397509243, rs80356969, rs80356959, rs63750617, rs63751319, rs587779315, rs200640585, rs398122546, rs80357543, rs398122687, rs80359328, rs398122779, rs398122783, rs62517194, rs80358029, rs515726060, rs180177103, rs180177111, rs180177133, rs587776527, rs180177135, rs180177136, rs515726117, rs587779813, rs587779909, rs587780024, rs587780100, rs28909982, rs121908698, rs180177100, rs587780210, rs587780240, rs587780639, rs587781269, rs587781353, rs587781471, rs587781658, rs587781697, rs587781730, rs587781894, rs587781948, rs587782005, rs587782011, rs200928781, rs587781558, rs370228071, rs587782245, rs587782401, rs180177110, rs587782504, rs72552322, rs587782531, rs587782620, rs587782680, rs587782774, rs587782818, rs730881411, rs730881389, rs564652222, rs397507768, rs587776419, rs730881868, rs730881940, rs56383036, rs758972589, rs201089102, rs730881348, rs786202608, rs786201886, rs786203318, rs786203775, rs786203714, rs786202033, rs750621215, rs786203884, rs786203650, rs772821016, rs863224521, rs864622223, rs864622655, rs375699023, rs876659572, rs768362387, rs876659535, rs876658957, rs483353072, rs876659435, rs267608041, rs876661113, rs730881369, rs878853535, rs772228129, rs878855122, rs760551339, rs80359596, rs397509222, rs886039630, rs886039683, rs886040828, rs587781799, rs886040374, rs886040649, rs397507967, rs878854957, rs886040043, rs1057517589, rs1060502769, rs866380588, rs863224765, rs1064793243, rs747563556, rs1555074976, rs1064795885, rs753961188, rs1064794708, rs869312772, rs1064793887, rs1131690820, rs1135401928, rs1135401868, rs1135401859, rs1553370324, rs397507630, rs1555283160, rs1555283251, rs1555283262, rs1555283361, rs1555286298, rs1555288462, rs886040950, rs1555289566, rs776323117, rs80357123, rs1555579627, rs1555580697, rs80358054, rs1555593302, rs1328985852, rs763470424, rs1555139694, rs878854697, rs1555461217, rs1555461765, rs774684620, rs766416564, rs1554558613, rs1305740166, rs1555461460, rs1555461407, rs1555461586, rs1555567202, rs1555607022, rs1555069815, rs1442299125, rs1474786480, rs1555084947, rs1555457867, rs141087784, rs1482641121, rs1564830522, rs1565469955, rs1565503137, rs864622613, rs755263466, rs757679199, rs1593903166, rs1597801649, rs1603293306, rs879253880, rs80358754, rs1597062038, rs45494092, rs1603275367, rs887358871, rs1597091518, rs1966967065, rs1064793049, rs2082872908, rs2085078278, rs2072475243

Unknown
Disease name	Disease term	dbSNP ID	References
Vitiligo	Vitiligo		22561518