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Protein

TIR domain-containing adapter molecule 1

Gene

Ticam1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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. Component of a multi-helicase-TICAM1 complex that acts as a cytoplasmic sensor of viral double-stranded RNA (dsRNA) and plays a role in the activation of a cascade of antiviral responses including the induction of proinflammatory cytokines (PubMed:21703541).3 Publications

GO - Molecular functioni

GO - Biological processi

Keywordsi

Biological processAntiviral defense, Apoptosis, Immunity, Inflammatory response, Innate immunity

Enzyme and pathway databases

ReactomeiR-MMU-140534 via Death Receptors in the presence of ligand
R-MMU-166166 MyD88-independent TLR4 cascade
R-MMU-2562578 TRIF-mediated programmed cell death
R-MMU-936964 Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon
R-MMU-937041 IKK complex recruitment mediated by RIP1
R-MMU-937072 TRAF6-mediated induction of TAK1 complex within TLR4 complex

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 17

Organism-specific databases

MGIiMGI:2147032 Ticam1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Cytoplasmic vesicle, Mitochondrion

Pathology & Biotechi

Disruption phenotypei

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003176641 – 732TIR domain-containing adapter molecule 1Add BLAST732

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

PaxDbiQ80UF7
PRIDEiQ80UF7

PTM databases

PhosphoSitePlusiQ80UF7

Expressioni

Gene expression databases

BgeeiENSMUSG00000047123 Expressed in 153 organ(s), highest expression level in intestine
CleanExiMM_TICAM1
GenevisibleiQ80UF7 MM

Interactioni

Subunit structurei

Homodimer (By similarity). Found in a multi-helicase-TICAM1 complex at least composed of DHX36, DDX1, DDX21 and TICAM1; this complex exists in resting cells with or without poly(I:C) RNA ligand stimulation (PubMed:21703541). Interacts (via TIR domain) with DDX21 (via C-terminus) (PubMed:21703541). Interacts (via TIR domain) with DHX36 (via C-terminus) (PubMed:21703541). 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). Interacts with TRIM56 (By similarity).By similarity4 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi223122, 9 interactors
DIPiDIP-60033N
IntActiQ80UF7, 6 interactors
STRINGi10090.ENSMUSP00000055104

Structurei

3D structure databases

ProteinModelPortaliQ80UF7
SMRiQ80UF7
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini392 – 465TIRAdd BLAST74

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 153TRIF-NTDBy similarityAdd BLAST153
Regioni514 – 713Sufficient to induce apoptosisBy similarityAdd BLAST200

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi84 – 91TRAF6-bindingBy similarity8
Motifi247 – 254TRAF6-bindingBy similarity8
Motifi296 – 306TRAF6-bindingBy similarityAdd BLAST11

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi348 – 384Pro-richAdd BLAST37
Compositional biasi602 – 679Pro-richAdd BLAST78

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

Phylogenomic databases

eggNOGiENOG410IJUV Eukaryota
ENOG410Y8DE LUCA
GeneTreeiENSGT00900000141066
HOGENOMiHOG000068973
HOVERGENiHBG108551
InParanoidiQ80UF7
KOiK05842
OMAiEEKLCPA
OrthoDBiEOG091G07G7
PhylomeDBiQ80UF7
TreeFamiTF336953

Family and domain databases

Gene3Di3.40.50.10140, 1 hit
InterProiView protein in InterPro
IPR025735 RHIM_dom
IPR017278 TICAM1
IPR035897 Toll_tir_struct_dom_sf
PANTHERiPTHR23213:SF331 PTHR23213:SF331, 1 hit
PfamiView protein in Pfam
PF12721 RHIM, 1 hit
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 differs from that shown.Curated
The sequence AAH37048 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence AAH62191 differs from that shown. Reason: Frameshift at position 350.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti227S → G in BAE29344 (PubMed:16141072).Curated1
Sequence conflicti351 – 435Missing in AAH62191 (PubMed:15489334).CuratedAdd BLAST85
Sequence conflicti435V → A in BAE25531 (PubMed:16141072).Curated1
Sequence conflicti513V → A in BAE29344 (PubMed:16141072).Curated1
Sequence conflicti628 – 639Missing in AAH33406 (PubMed:15489334).CuratedAdd BLAST12

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

Similar proteinsi

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
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi223122, 9 interactors
DIPiDIP-60033N
IntActiQ80UF7, 6 interactors
STRINGi10090.ENSMUSP00000055104

PTM databases

PhosphoSitePlusiQ80UF7

Proteomic databases

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
GeneTreeiENSGT00900000141066
HOGENOMiHOG000068973
HOVERGENiHBG108551
InParanoidiQ80UF7
KOiK05842
OMAiEEKLCPA
OrthoDBiEOG091G07G7
PhylomeDBiQ80UF7
TreeFamiTF336953

Enzyme and pathway databases

ReactomeiR-MMU-140534 via Death Receptors in the presence of ligand
R-MMU-166166 MyD88-independent TLR4 cascade
R-MMU-2562578 TRIF-mediated programmed cell death
R-MMU-936964 Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon
R-MMU-937041 IKK complex recruitment mediated by RIP1
R-MMU-937072 TRAF6-mediated induction of TAK1 complex within TLR4 complex

Miscellaneous databases

PROiPR:Q80UF7
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000047123 Expressed in 153 organ(s), highest expression level in intestine
CleanExiMM_TICAM1
GenevisibleiQ80UF7 MM

Family and domain databases

Gene3Di3.40.50.10140, 1 hit
InterProiView protein in InterPro
IPR025735 RHIM_dom
IPR017278 TICAM1
IPR035897 Toll_tir_struct_dom_sf
PANTHERiPTHR23213:SF331 PTHR23213:SF331, 1 hit
PfamiView protein in Pfam
PF12721 RHIM, 1 hit
PIRSFiPIRSF037744 TIR_Ticam, 1 hit
SUPFAMiSSF52200 SSF52200, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiTCAM1_MOUSE
AccessioniPrimary (citable) accession number: Q80UF7
Secondary accession number(s): Q3UDB7
, Q3UP66, Q6P6J2, Q8CIB7, Q8JZV0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 5, 2008
Last sequence update: June 1, 2003
Last modified: October 10, 2018
This is version 119 of the entry and version 1 of the sequence. See 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
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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