Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

TIR domain-containing adapter molecule 1

Gene

Ticam1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Involved in innate immunity against invading pathogens. Adapter used by TLR3 and TLR4 (through TICAM2) to mediate NF-kappa-B and interferon-regulatory factor (IRF) activation, and to induce apoptosis. Ligand binding to these receptors results in TRIF recruitment through its TIR domain. Distinct protein-interaction motifs allow recruitment of the effector proteins TBK1, TRAF6 and RIPK1, which in turn, lead to the activation of transcription factors IRF3 and IRF7, NF-kappa-B and FADD respectively.2 Publications

GO - Molecular functioni

GO - Biological processi

  • apoptotic signaling pathway Source: MGI
  • defense response to virus Source: MGI
  • inflammatory response Source: UniProtKB-KW
  • innate immune response Source: UniProtKB-KW
  • lipopolysaccharide-mediated signaling pathway Source: MGI
  • macrophage activation involved in immune response Source: MGI
  • MyD88-independent toll-like receptor signaling pathway Source: MGI
  • positive regulation of B cell activation Source: MGI
  • positive regulation of B cell proliferation Source: MGI
  • positive regulation of chemokine biosynthetic process Source: MGI
  • positive regulation of I-kappaB kinase/NF-kappaB signaling Source: MGI
  • positive regulation of interferon-beta biosynthetic process Source: MGI
  • positive regulation of interleukin-6 production Source: MGI
  • positive regulation of natural killer cell activation Source: MGI
  • positive regulation of NF-kappaB transcription factor activity Source: MGI
  • positive regulation of nitric oxide biosynthetic process Source: MGI
  • positive regulation of protein binding Source: MGI
  • positive regulation of protein ubiquitination Source: MGI
  • positive regulation of tumor necrosis factor production Source: MGI
  • positive regulation of type I interferon production Source: MGI
  • regulation of protein homodimerization activity Source: MGI
  • response to exogenous dsRNA Source: MGI
  • response to lipopolysaccharide Source: MGI
Complete GO annotation...

Keywords - Biological processi

Antiviral defense, Apoptosis, Immunity, Inflammatory response, Innate immunity

Enzyme and pathway databases

ReactomeiR-MMU-166166. MyD88-independent TLR3/TLR4 cascade.
R-MMU-1810476. RIP-mediated NFkB activation via ZBP1.

Names & Taxonomyi

Protein namesi
Recommended name:
TIR domain-containing adapter molecule 1
Short name:
TICAM-1
Alternative name(s):
Toll-interleukin-1 receptor domain-containing adapter protein inducing interferon beta
Short name:
TIR domain-containing adapter protein inducing IFN-beta
Gene namesi
Name:Ticam1
Synonyms:Trif
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 17

Organism-specific databases

MGIiMGI:2147032. Ticam1.

Subcellular locationi

  • Cytoplasmic vesicleautophagosome By similarity

  • Note: Colocalizes with UBQLN1 in the autophagosome.By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasmic vesicle

Pathology & Biotechi

Disruption phenotypei

Mice are viable but exhibit abnormalities of the innate immune system.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 732732TIR domain-containing adapter molecule 1PRO_0000317664Add
BLAST

Post-translational modificationi

Phosphorylated by TBK1.By similarity
Polyubiquitinated by TRIM38 with 'Lys-48'-linked chains, leading to proteasomal degradation.By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiQ80UF7.
PaxDbiQ80UF7.
PRIDEiQ80UF7.

PTM databases

PhosphoSiteiQ80UF7.

Expressioni

Gene expression databases

BgeeiQ80UF7.
CleanExiMM_TICAM1.
GenevisibleiQ80UF7. MM.

Interactioni

Subunit structurei

Homodimer (By similarity). Interacts with AZI2, IRF3 and IRF7 (By similarity). Interacts with TICAM2 in TLR4 recruitment (By similarity). Interaction with PIAS4 inhibits the TICAM1-induced NF-kappa-B, IRF and IFNB1 activation (By similarity). Interacts with IKBKB and IKBKE (By similarity). Interaction with SARM1 blocks TICAM1-dependent transcription factor activation (By similarity). Interacts with TRAF3. Interacts with TRAFD1. Interacts with UBQLN1 (via UBA domain). Interacts with TBK1, TRAF6 and RIPK1 and these interactions are enhanced in the presence of WDFY1 (By similarity). Interacts (via the TIR domain) with TLR3 in response to poly(I:C) and this interaction is enhanced in the presence of WDFY1 (PubMed:25736436). Interacts with TLR4 in response to poly(I:C) in a WDFY1-dependent manner (PubMed:25736436). Interacts with WDFY1 in response to poly(I:C) (PubMed:25736436).By similarity3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
BtkP359912EBI-3649271,EBI-625119
CblbQ3TTA72EBI-3649271,EBI-3649276

GO - Molecular functioni

Protein-protein interaction databases

BioGridi223122. 8 interactions.
DIPiDIP-60033N.
IntActiQ80UF7. 4 interactions.
STRINGi10090.ENSMUSP00000055104.

Structurei

3D structure databases

ProteinModelPortaliQ80UF7.
SMRiQ80UF7. Positions 5-148, 391-547.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini392 – 46574TIRAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 153153TRIF-NTDBy similarityAdd
BLAST
Regioni514 – 713200Sufficient to induce apoptosisBy similarityAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi84 – 918TRAF6-bindingBy similarity
Motifi247 – 2548TRAF6-bindingBy similarity
Motifi296 – 30611TRAF6-bindingBy similarityAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi348 – 38437Pro-richAdd
BLAST
Compositional biasi602 – 67978Pro-richAdd
BLAST

Domaini

The N-terminal region is essential for activation of the IFNB promoter activity.By similarity
The N-terminal domain (TRIF-NTD) is globular and consists of two alpha-helical subdomains connected by a 14-residue linker. It shares structural similarity with IFIT family members N-terminal regions.By similarity

Sequence similaritiesi

Contains 1 TIR domain.Curated

Phylogenomic databases

eggNOGiENOG410IJUV. Eukaryota.
ENOG410Y8DE. LUCA.
GeneTreeiENSGT00510000049574.
HOGENOMiHOG000068973.
HOVERGENiHBG108551.
InParanoidiQ80UF7.
KOiK05842.
OMAiEEKLCPA.
OrthoDBiEOG7GFB4H.
PhylomeDBiQ80UF7.
TreeFamiTF336953.

Family and domain databases

InterProiIPR025735. RHIM_dom.
IPR017278. TICAM1.
IPR000157. TIR_dom.
[Graphical view]
PfamiPF12721. RHIM. 1 hit.
[Graphical view]
PIRSFiPIRSF037744. TIR_Ticam. 1 hit.
SUPFAMiSSF52200. SSF52200. 1 hit.

Sequencei

Sequence statusi: Complete.

Q80UF7-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDNPGPSLRG AFGILGALER DRLTHLKHKL GSLCSGSQES KLLHAMVLLA
60 70 80 90 100
LGQDTEARVS LESLKMNTVA QLVAHQWADM ETTEGPEEPP DLSWTVARLY
110 120 130 140 150
HLLAEENLCP ASTRDMAYQV ALRDFASQGD HQLGQLQNEA WDRCSSDIKG
160 170 180 190 200
DPSGFQPLHS HQGSLQPPSA SPAVTRSQPR PIDTPDWSWG HTLHSTNSTA
210 220 230 240 250
SLASHLEISQ SPTLAFLSSH HGTHGPSKLC NTPLDTQEPQ LVPEGCQEPE
260 270 280 290 300
EISWPPSVET SVSLGLPHEI SVPEVSPEEA SPILPDALAA PDTSVHCPIE
310 320 330 340 350
CTELSTNSRS PLTSTTESVG KQWPITSQRS PQVPVGDDSL QNTTSSSPPA
360 370 380 390 400
QPPSLQASPK LPPSPLSSAS SPSSYPAPPT STSPVLDHSE TSDQKFYNFV
410 420 430 440 450
VIHARADEQV ALRIREKLET LGVPDGATFC EEFQVPGRGE LHCLQDAIDH
460 470 480 490 500
SGFTILLLTA SFDCSLSLHQ INHALMNSLT QSGRQDCVIP LLPLECSQAQ
510 520 530 540 550
LSPDTTRLLH SIVWLDEHSP IFARKVANTF KTQKLQAQRV RWKKAQEART
560 570 580 590 600
LKEQSIQLEA ERQNVAAISA AYTAYVHSYR AWQAEMNKLG VAFGKNLSLG
610 620 630 640 650
TPTPSWPGCP QPIPSHPQGG TPVFPYSPQP PSFPQPPCFP QPPSFPQPPS
660 670 680 690 700
FPLPPVSSPQ SQSFPSASSP APQTPGPQPL IIHHAQMVQL GVNNHMWGHT
710 720 730
GAQSSDDKTE CSENPCMGPL TDQGEPLLET PE
Length:732
Mass (Da):79,230
Last modified:June 1, 2003 - v1
Checksum:i2EAC87F1936B7C83
GO

Sequence cautioni

The sequence AAH33406.1 differs from that shown.Curated
The sequence AAH37048.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence AAH62191.1 differs from that shown. Reason: Frameshift at position 350. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti227 – 2271S → G in BAE29344 (PubMed:16141072).Curated
Sequence conflicti351 – 43585Missing in AAH62191 (PubMed:15489334).CuratedAdd
BLAST
Sequence conflicti435 – 4351V → A in BAE25531 (PubMed:16141072).Curated
Sequence conflicti513 – 5131V → A in BAE29344 (PubMed:16141072).Curated
Sequence conflicti628 – 63912Missing in AAH33406 (PubMed:15489334).CuratedAdd
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB091053 mRNA. Translation: BAC55581.1.
AK143766 mRNA. Translation: BAE25531.1.
AK150150 mRNA. Translation: BAE29344.1.
AK155245 mRNA. Translation: BAE33144.1.
BC033406 mRNA. Translation: AAH33406.1. Sequence problems.
BC037048 mRNA. Translation: AAH37048.1. Different initiation.
BC062191 mRNA. Translation: AAH62191.1. Frameshift.
BC094338 mRNA. Translation: AAH94338.1.
CCDSiCCDS28900.1.
RefSeqiNP_778154.1. NM_174989.4.
UniGeneiMm.203952.

Genome annotation databases

EnsembliENSMUST00000058136; ENSMUSP00000055104; ENSMUSG00000047123.
GeneIDi106759.
KEGGimmu:106759.
UCSCiuc008dbm.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB091053 mRNA. Translation: BAC55581.1.
AK143766 mRNA. Translation: BAE25531.1.
AK150150 mRNA. Translation: BAE29344.1.
AK155245 mRNA. Translation: BAE33144.1.
BC033406 mRNA. Translation: AAH33406.1. Sequence problems.
BC037048 mRNA. Translation: AAH37048.1. Different initiation.
BC062191 mRNA. Translation: AAH62191.1. Frameshift.
BC094338 mRNA. Translation: AAH94338.1.
CCDSiCCDS28900.1.
RefSeqiNP_778154.1. NM_174989.4.
UniGeneiMm.203952.

3D structure databases

ProteinModelPortaliQ80UF7.
SMRiQ80UF7. Positions 5-148, 391-547.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi223122. 8 interactions.
DIPiDIP-60033N.
IntActiQ80UF7. 4 interactions.
STRINGi10090.ENSMUSP00000055104.

PTM databases

PhosphoSiteiQ80UF7.

Proteomic databases

MaxQBiQ80UF7.
PaxDbiQ80UF7.
PRIDEiQ80UF7.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000058136; ENSMUSP00000055104; ENSMUSG00000047123.
GeneIDi106759.
KEGGimmu:106759.
UCSCiuc008dbm.2. mouse.

Organism-specific databases

CTDi148022.
MGIiMGI:2147032. Ticam1.

Phylogenomic databases

eggNOGiENOG410IJUV. Eukaryota.
ENOG410Y8DE. LUCA.
GeneTreeiENSGT00510000049574.
HOGENOMiHOG000068973.
HOVERGENiHBG108551.
InParanoidiQ80UF7.
KOiK05842.
OMAiEEKLCPA.
OrthoDBiEOG7GFB4H.
PhylomeDBiQ80UF7.
TreeFamiTF336953.

Enzyme and pathway databases

ReactomeiR-MMU-166166. MyD88-independent TLR3/TLR4 cascade.
R-MMU-1810476. RIP-mediated NFkB activation via ZBP1.

Miscellaneous databases

NextBioi358372.
PROiQ80UF7.
SOURCEiSearch...

Gene expression databases

BgeeiQ80UF7.
CleanExiMM_TICAM1.
GenevisibleiQ80UF7. MM.

Family and domain databases

InterProiIPR025735. RHIM_dom.
IPR017278. TICAM1.
IPR000157. TIR_dom.
[Graphical view]
PfamiPF12721. RHIM. 1 hit.
[Graphical view]
PIRSFiPIRSF037744. TIR_Ticam. 1 hit.
SUPFAMiSSF52200. SSF52200. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "TICAM-1, an adapter molecule that participates in Toll-like receptor 3 mediated interferon-beta induction."
    Oshiumi H., Matsumoto M., Funami K., Akazawa T., Seya T.
    Nat. Immunol. 4:161-167(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J and NOD.
    Tissue: Bone marrow and Spleen.
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J, FVB/N and FVB/N-3.
    Tissue: Eye, Jaw, Limb, Mammary tumor and Salivary gland.
  4. "Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway."
    Yamamoto M., Sato S., Hemmi H., Hoshino K., Kaisho T., Sanjo H., Takeuchi O., Sugiyama M., Okabe M., Takeda K., Akira S.
    Science 301:640-643(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE.
  5. "TLR4 and Toll-IL-1 receptor domain-containing adapter-inducing IFN-beta, but not MyD88, regulate Escherichia coli-induced dendritic cell maturation and apoptosis in vivo."
    De Trez C., Pajak B., Brait M., Glaichenhaus N., Urbain J., Moser M., Lauvau G., Muraille E.
    J. Immunol. 175:839-846(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  6. "Critical role of TRAF3 in the Toll-like receptor-dependent and -independent antiviral response."
    Oganesyan G., Saha S.K., Guo B., He J.Q., Shahangian A., Zarnegar B., Perry A., Cheng G.
    Nature 439:208-211(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH TRAF3.
  7. "The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling."
    O'Neill L.A., Bowie A.G.
    Nat. Rev. Immunol. 7:353-364(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  8. "FLN29 deficiency reveals its negative regulatory role in the Toll-like receptor (TLR) and retinoic acid-inducible gene I (RIG-I)-like helicase signaling pathway."
    Sanada T., Takaesu G., Mashima R., Yoshida R., Kobayashi T., Yoshimura A.
    J. Biol. Chem. 283:33858-33864(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH TRAFD1.
  9. "WDFY1 mediates TLR3/4 signaling by recruiting TRIF."
    Hu Y.H., Zhang Y., Jiang L.Q., Wang S., Lei C.Q., Sun M.S., Shu H.B., Liu Y.
    EMBO Rep. 16:447-455(2015) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH WDFY1; TLR3 AND TLR4.

Entry informationi

Entry nameiTCAM1_MOUSE
AccessioniPrimary (citable) accession number: Q80UF7
Secondary accession number(s): Q3UDB7
, Q3UP66, Q6P6J2, Q8CIB7, Q8JZV0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 5, 2008
Last sequence update: June 1, 2003
Last modified: December 9, 2015
This is version 103 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.