TICAM1 (TIR domain containing adaptor molecule 1)

Gene

• Entrez ID: 148022
• Gene name: TIR domain containing adaptor molecule 1
• Gene symbol: TICAM1
• Synonyms (NCBI Gene): 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:0002224	Process	Toll-like receptor signaling pathway	IDA	12471095
GO:0002281	Process	Macrophage activation involved in immune response	IEA
GO:0002376	Process	Immune system process	IEA
GO:0002735	Process	Positive regulation of myeloid dendritic cell cytokine production	IEA
GO:0002735	Process	Positive regulation of myeloid dendritic cell cytokine production	ISS
GO:0002756	Process	MyD88-independent toll-like receptor signaling pathway	IEA
GO:0005515	Function	Protein binding	IPI	14982987, 15142865, 15841462, 19416887, 21903422, 22948160, 25736436, 33961781, 36232715
GO:0005737	Component	Cytoplasm	IEA
GO:0005739	Component	Mitochondrion	IEA
GO:0005739	Component	Mitochondrion	ISS
GO:0005768	Component	Endosome	IBA
GO:0005768	Component	Endosome	IDA	18222170
GO:0005769	Component	Early endosome	IDA	17982077
GO:0005776	Component	Autophagosome	IEA
GO:0005829	Component	Cytosol	IEA
GO:0005829	Component	Cytosol	TAS
GO:0006809	Process	Nitric oxide biosynthetic process	IEA
GO:0006915	Process	Apoptotic process	IEA
GO:0006954	Process	Inflammatory response	IEA
GO:0007165	Process	Signal transduction	IEA
GO:0007166	Process	Cell surface receptor signaling pathway	IEA
GO:0010008	Component	Endosome membrane	IDA	18222170
GO:0010008	Component	Endosome membrane	TAS
GO:0010508	Process	Positive regulation of autophagy	IEA
GO:0010508	Process	Positive regulation of autophagy	ISS
GO:0010628	Process	Positive regulation of gene expression	IEA
GO:0010628	Process	Positive regulation of gene expression	ISS
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:0031410	Component	Cytoplasmic vesicle	IEA
GO:0031663	Process	Lipopolysaccharide-mediated signaling pathway	IEA
GO:0032481	Process	Positive regulation of type I interferon production	IBA
GO:0032481	Process	Positive regulation of type I interferon production	IDA	14703513, 19898473
GO:0032481	Process	Positive regulation of type I interferon production	IDA	28049150
GO:0032481	Process	Positive regulation of type I interferon production	IEA
GO:0032481	Process	Positive regulation of type I interferon production	IEA
GO:0032496	Process	Response to lipopolysaccharide	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	IEA
GO:0034138	Process	Toll-like receptor 3 signaling pathway	IDA	12471095
GO:0034142	Process	Toll-like receptor 4 signaling pathway	IDA	18222170, 25636800, 28747347
GO:0034142	Process	Toll-like receptor 4 signaling pathway	IDA	12471095
GO:0035591	Function	Signaling adaptor activity	IBA
GO:0035591	Function	Signaling adaptor activity	IEA
GO:0035666	Process	TRIF-dependent toll-like receptor signaling pathway	IBA
GO:0035666	Process	TRIF-dependent toll-like receptor signaling pathway	IEA
GO:0035666	Process	TRIF-dependent toll-like receptor signaling pathway	IMP	25636800
GO:0035666	Process	TRIF-dependent toll-like receptor signaling pathway	ISS
GO:0042100	Process	B cell proliferation	IEA
GO:0042113	Process	B cell activation	IEA
GO:0043123	Process	Positive regulation of canonical NF-kappaB signal transduction	HMP	12761501
GO:0043123	Process	Positive regulation of canonical NF-kappaB signal transduction	IBA
GO:0043123	Process	Positive regulation of canonical NF-kappaB signal transduction	IEA
GO:0043123	Process	Positive regulation of canonical NF-kappaB signal transduction	IMP	14982987
GO:0043123	Process	Positive regulation of canonical NF-kappaB signal transduction	ISS
GO:0043254	Process	Regulation of protein-containing complex assembly	IEA
GO:0043330	Process	Response to exogenous dsRNA	IEA
GO:0043330	Process	Response to exogenous dsRNA	IEA
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:0050871	Process	Positive regulation of B cell activation	IEA
GO:0051607	Process	Defense response to virus	IEA
GO:0051607	Process	Defense response to virus	IEA
GO:0060090	Function	Molecular adaptor activity	IDA	12471095
GO:0060090	Function	Molecular adaptor activity	IEA
GO:0060907	Process	Positive regulation of macrophage cytokine production	IEA
GO:0071222	Process	Cellular response to lipopolysaccharide	IEA
GO:0071222	Process	Cellular response to lipopolysaccharide	ISS
GO:0097190	Process	Apoptotic signaling pathway	IEA
GO:0097342	Component	Ripoptosome	IDA	21737330
GO:0140052	Process	Cellular response to oxidised low-density lipoprotein particle stimulus	IEA
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	IEA
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

• Tissue specificity: TISSUE SPECIFICITY: Ubiquitously expressed but with higher levels in liver. {ECO:0000269|PubMed:12471095, ECO:0000269|PubMed:12539043}.
• 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

Unknown
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Herpes simplex encephalitis, susceptibility to, 4	Uncertain significance; Likely benign; Benign; Conflicting classifications of pathogenicity; risk factor	rs148396522, rs2093587726, rs757786083, rs760097887, rs767397394, rs762670581, rs2093585998, rs770034965, rs749928559, rs765301499, rs758634091, rs760290741, rs1427361110, rs567288271, rs2146168208, rs1256701940, rs147816959, rs200885543, rs779115581, rs775404991, rs201230476, rs1321096386, rs766695629, rs1344974408, rs375880539, rs1439343592, rs201782115, rs2146167795, rs1382708516, rs544182648, rs2093587423, rs781668575, rs113493978, rs201239888, rs1309063391, rs761547868, rs1257125762, rs2146168812, rs142635281, rs765570758, rs140524280, rs369799199, rs2093591181, rs376605000, rs201978370, rs11466722, rs1300806411, rs765752632, rs2093587484, rs767013628, rs373468408, rs2146169940, rs765491561, rs2093589455, rs779772992, rs1271210390, rs765891838, rs2093591387, rs1261663079, rs1467248135, rs780201394, rs768611254, rs746169578, rs2093587189, rs781426719, rs146110283, rs1222745582, rs2146168352, rs375230364, rs754776028, rs370345154, rs766504909, rs749133560, rs543684306, rs779250040, rs370301428, rs376421303, rs142171170, rs2146169294, rs1294358833, rs375571285, rs752524876, rs545638589, rs751977492, rs2093585647, rs769041568, rs758048210, rs995707106, rs2146171028, rs1242807777, rs776276419, rs765489270, rs374044969, rs747280830, rs146025102, rs775931722, rs1257504893, rs776306470, rs748521173, rs1184776744, rs777706412, rs1264864660, rs891068141, rs565171871, rs1003883000, rs912548534, rs747628325, rs764485662, rs200795596, rs772969793, rs199935588, rs751395479, rs762939077, rs774006618, rs1204752747, rs538901003, rs566243001, rs766416767, rs747059000, rs562147335, rs777980938, rs2146169253, rs780241594, rs763771528, rs762032500, rs1317469292, rs772462289, rs2093586206, rs560174200, rs1360285784, rs764694460, rs1280853552, rs761271093, rs776106254, rs770414344, rs753498364, rs778249694, rs201821648, rs749264598, rs377509189, rs779499603, rs376914657, rs2093586143, rs1221705597, rs2512399436, rs906910043, rs754654920, rs765583204, rs1322959750, rs2512399287, rs2093587809, rs370342886, rs2093591175, rs200773818, rs750634396, rs773993340, rs371551573, rs2512400082, rs2512399424, rs2512399609, rs2093591408, rs1249073197, rs2512398787, rs2512400289, rs2512399719, rs2093588565, rs925405032, rs748477430, rs2093586082, rs772973812, rs143873813, rs370748549, rs2512399562, rs774037288, rs2512398252, rs2512397922, rs757039942, rs200318863, rs2512400172, rs761523820, rs1568365385, rs2512398577, rs201008382, rs769060173, rs2512397316, rs779591355, rs2512398155, rs7255265, rs758423248, rs199519963, rs760042063, rs1335525540, rs1424286300, rs763998229, rs758372052, rs2512400243, rs1005476424, rs768957889, rs2093587154, rs748972207, rs752174873, rs756715938, rs751804319, rs139033075, rs775069081, rs2512398601, rs943790887, rs2512398607, rs766706840, rs760378603, rs2512399849, rs747970026, rs746548359, rs2512399410, rs2292151, rs387907307, rs146550489, rs151272128, rs141687483, rs143679494, rs574449966, rs373242041, rs145148929, rs1555730283, rs199784356, rs143066432, rs1555730200, rs11466723, rs140568066, rs144531955, rs1555730261, rs754876060, rs759330259, rs11466719, rs772590478, rs141394423, rs199816697, rs1332617784, rs11466720, rs79591246, rs755557071, rs143789239, rs201291933, rs777499533, rs148925210, rs763590950, rs770166865, rs753365777, rs200326236, rs370487475, rs141739488, rs199683447, rs1437926927, rs1202936308, rs372838204, rs3177471, rs74359855, rs1284363590, rs751265594, rs772349684, rs1032622935, rs201853120, rs1599143486, rs372818181, rs150740529, rs150390826, rs149930656, rs374044654, rs200096641, rs754441119, rs200697470, rs150224968, rs758914983, rs1600053874, rs758835511, rs756453374, rs751074807, rs751674787, rs139939816, rs765090691, rs371101914, rs139810575, rs749898071, rs1292695561, rs762126373, rs749105540, rs759573569, rs373671679, rs763237315, rs769618186, rs2093588326, rs773920190, rs767551524, rs2093589331, rs747441149, rs768828649, rs940970222, rs753273529, rs780257437, rs935231020, rs142880589, rs945545750, rs867839844, rs2093590230, rs2093585623, rs2093586437, rs749950910, rs1176341029, rs775445910, rs1224448097, rs2093591434, rs752723765, rs199751361, rs2093590817, rs2093590771, rs536690750, rs561021962, rs752768415, rs780460725, rs1028603882, rs373241772, rs369953609	RCV001321805 RCV001316774 RCV001315746 RCV001318542 RCV001318605 RCV001344707 RCV001350075 RCV001347067 RCV001340941 RCV001339969 RCV001351499 RCV001370614 RCV001367609 RCV001364485 RCV001369063 RCV001372735 RCV001370846 RCV001362544 RCV001366029 RCV001404404 RCV001416610 RCV001401751 RCV001400860 RCV001411852 RCV001407784 RCV001416773 RCV001404179 RCV001422641 RCV001435172 RCV001427812 RCV001426208 RCV001443535 RCV001423667 RCV001445597 RCV001474332 RCV001464428 RCV001464684 RCV001469906 RCV001476699 RCV001476051 RCV001452934 RCV001460400 RCV001476629 RCV001505389 RCV001511328 RCV001997382 RCV001920582 RCV001989439 RCV001974927 RCV001892657 RCV001965173 RCV001872109 RCV001968845 RCV001993620 RCV001949789 RCV002034363 RCV001945309 RCV001953314 RCV001901834 RCV001938229 RCV002019307 RCV002019739 RCV001956035 RCV001992532 RCV002017510 RCV001912473 RCV001898223 RCV001973877 RCV001989840 RCV001998303 RCV001929050 RCV001869912 RCV001926518 RCV002038249 RCV001915041 RCV001924404 RCV002024519 RCV001990080 RCV001933858 RCV001949044 RCV002037344 RCV002016862 RCV002031840 RCV001964706 RCV001973066 RCV002047355 RCV001937749 RCV001918243 RCV001981610 RCV001966622 RCV002051446 RCV001874001 RCV001910051 RCV002011828 RCV001968348 RCV002172969 RCV002131100 RCV002131272 RCV002089234 RCV002201845 RCV002175164 RCV002195249 RCV002211881 RCV002105456 RCV002207464 RCV002149905 RCV002149910 RCV002132524 RCV002101372 RCV002213718 RCV002077734 RCV002088668 RCV002076767 RCV002076901 RCV002186838 RCV002205986 RCV002108635 RCV002106188 RCV002142843 RCV002150218 RCV002122218 RCV002092720 RCV002083675 RCV002296401 RCV003075908 RCV003075431 RCV003074924 RCV003080249 RCV003080010 RCV002628229 RCV002619216 RCV002611379 RCV002619949 RCV002625023 RCV002625024 RCV002612440 RCV002629344 RCV002647775 RCV003108556 RCV002575798 RCV002589045 RCV002594328 RCV002598348 RCV002600673 RCV002601952 RCV002591101 RCV002617801 RCV002635788 RCV002635680 RCV002605368 RCV002667055 RCV002663695 RCV002706402 RCV002672115 RCV002700599 RCV002730619 RCV002790744 RCV002761516 RCV002761561 RCV002780816 RCV002775965 RCV002790487 RCV002815760 RCV002820888 RCV002820889 RCV002825044 RCV002814428 RCV002815063 RCV002828605 RCV002833729 RCV002861598 RCV002863032 RCV002885220 RCV002886287 RCV002908721 RCV002932315 RCV002953749 RCV002966133 RCV002970960 RCV002957858 RCV002949629 RCV002982587 RCV002999324 RCV002999341 RCV003002693 RCV003016640 RCV003027348 RCV003017537 RCV003014874 RCV003046600 RCV003043099 RCV003048300 RCV003063897 RCV003534028 RCV003534101 RCV003534062 RCV003531624 RCV003531811 RCV003531835 RCV003532424 RCV003532461 RCV003647286 RCV003648228 RCV003648424 RCV003648389 RCV003648479 RCV003648560 RCV003648647 RCV003648622 RCV003648642 RCV003648759 RCV003648939 RCV003648934 RCV003649129 RCV003649029 RCV003811640 RCV003835989 RCV003848316 RCV003843009 RCV003855363 RCV003855637 RCV003870679 RCV003870024 RCV003880511 RCV005101602 RCV001516629 RCV001516627 RCV001516628 RCV000030823 RCV000030824 RCV000550916 RCV000558222 RCV000543404 RCV001088836 RCV000537526 RCV000547869 RCV000585896 RCV000650568 RCV000650562 RCV000650561 RCV000650571 RCV000650564 RCV000650567 RCV001440834 RCV000650563 RCV001485149 RCV000650566 RCV000650559 RCV000650560 RCV000650558 RCV000650565 RCV000650572 RCV000650573 RCV000693305 RCV000705831 RCV000693219 RCV000707570 RCV000706813 RCV000686317 RCV000703758 RCV000700411 RCV000704121 RCV000704138 RCV000700624 RCV000693075 RCV000707447 RCV000698021 RCV000685374 RCV003224460 RCV000802786 RCV000807139 RCV000817413 RCV000813760 RCV000822399 RCV000793916 RCV000809118 RCV000802607 RCV000802529 RCV000792698 RCV000808431 RCV000957842 RCV000966471 RCV000961580 RCV000884994 RCV000884987 RCV000886936 RCV001432775 RCV000909819 RCV001490535 RCV000898844 RCV000915616 RCV000919003 RCV000913797 RCV001500119 RCV000915508 RCV000927815 RCV000938059 RCV003532333 RCV000932961 RCV001466734 RCV001414911 RCV001418442 RCV000929697 RCV000979433 RCV000981364 RCV001484309 RCV001410963 RCV001043228 RCV001071107 RCV001044506 RCV001059478 RCV001056306 RCV001055509 RCV001068789 RCV001035453 RCV001041974 RCV001056200 RCV001068489 RCV001045012 RCV001048367 RCV001047631 RCV001039077 RCV001037831 RCV001046218 RCV001047750 RCV001055148 RCV001214734 RCV001220013 RCV001221974 RCV001206639 RCV001203328 RCV001202156 RCV001203037 RCV001209590 RCV001213185 RCV001208242 RCV001204826 RCV001228502 RCV001226353 RCV001228817 RCV001240964 RCV001247820 RCV001306744 RCV001309641 RCV001297301 RCV001294575 RCV001307871 RCV001304471 RCV001308604 RCV001302149 RCV001309886
Susceptibility to severe COVID-19	Likely risk allele; Uncertain significance	rs752908663, rs74359855	RCV003120373 RCV003117596
TICAM1-related disorder	Likely benign; Benign; Conflicting classifications of pathogenicity	rs375880539, rs781668575, rs201978370, rs772973812, rs2512399410, rs143679494, rs11466723, rs11466720, rs150740529, rs150224968, rs139810575	RCV003930871 RCV003965863 RCV003948497 RCV003943566 RCV003901944 RCV004757247 RCV003937966 RCV003937967 RCV003962829 RCV004757328 RCV003895659

Associations from Text Mining
Disease Name	Relationship Type	References
Autism Spectrum Disorder	Associate	37168851
Breast Neoplasms	Associate	31287789
Carcinoma Basal Cell	Associate	34278484
Carcinoma Squamous Cell	Associate	22808251
Colorectal Neoplasms	Associate	34689394
Diabetes Mellitus Type 2	Associate	20067962
Down Syndrome	Associate	31611734
Encephalitis	Stimulate	29116594
Encephalitis Herpes Simplex	Associate	22105173
Esophageal Neoplasms	Associate	36588538
Hepatitis Alcoholic	Associate	24997224
Immunologic Deficiency Syndromes	Inhibit	22105173
Infections	Associate	37071125
Inflammation	Associate	20360984, 28052863, 35933370
Mitochondrial Diseases	Associate	34278484
Mucocutaneous Lymph Node Syndrome	Associate	25780885
Multiple Myeloma	Associate	29214775
Myelodysplastic Syndromes	Associate	37071125
Neoplasms	Associate	36588538
Papillomavirus Infections	Associate	33164635
Pre Eclampsia	Associate	31477211
Pulmonary Disease Chronic Obstructive	Inhibit	26498252
Thromboangiitis Obliterans	Associate	38640750
Thyroid Cancer Papillary	Associate	27207655
Thyroid Neoplasms	Associate	35546566
Wilms Tumor	Associate	35933370