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Protein

TIR domain-containing adapter molecule 2

Gene

Ticam2

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

Functioni

Functions as sorting adapter in LPS-TLR4 signaling to regulate the MYD88-independent pathway during the innate immune response to LPS. Physically bridges TLR4 and TICAM1 and functionally transmits LPS-TRL4 signal to TICAM1; signaling is proposed to occur in early endosomes after endocytosis of TLR4. May also be involved in IL1-triggered NF-kappa-B activation, functioning upstream of IRAK1, IRAK2, TRAF6, and IKBKB; however, reports are controversial. Involved in IL-18 signaling and is proposed to function as a sorting adaptor for MYD88 in IL-18 signaling during adaptive immune response.3 Publications

GO - Molecular functioni

GO - Biological processi

  • cellular response to lipopolysaccharide Source: UniProtKB
  • defense response to virus Source: MGI
  • inflammatory response Source: UniProtKB-KW
  • innate immune response Source: UniProtKB-KW
  • negative regulation of chemokine (C-C motif) ligand 5 production Source: MGI
  • negative regulation of toll-like receptor 4 signaling pathway Source: MGI
  • positive regulation of chemokine (C-C motif) ligand 5 production Source: UniProtKB
  • positive regulation of interferon-gamma production Source: UniProtKB
  • positive regulation of interleukin-18-mediated signaling pathway Source: UniProtKB
  • positive regulation of interleukin-6 production Source: UniProtKB
  • positive regulation of toll-like receptor 4 signaling pathway Source: UniProtKB
  • regulation of cytokine production Source: MGI
  • regulation of I-kappaB kinase/NF-kappaB signaling Source: MGI
  • response to interleukin-12 Source: UniProtKB
  • TRAM-dependent toll-like receptor 4 signaling pathway Source: UniProtKB

Keywordsi

Biological processImmunity, Inflammatory response, Innate immunity

Enzyme and pathway databases

ReactomeiR-MMU-140534 Ligand-dependent caspase activation
R-MMU-166016 Toll Like Receptor 4 (TLR4) Cascade
R-MMU-166166 MyD88-independent TLR4 cascade
R-MMU-2562578 TRIF-mediated programmed cell death
R-MMU-6798695 Neutrophil degranulation
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 2
Short name:
TICAM-2
Alternative name(s):
TRIF-related adapter molecule
Toll/interleukin-1 receptor domain-containing protein
Gene namesi
Name:Ticam2
Synonyms:Tirp, Tram
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 18

Organism-specific databases

MGIiMGI:3040056 Ticam2

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

Cell membrane, Cytoplasm, Endoplasmic reticulum, Endosome, Golgi apparatus, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi2G → A: Results in relocalization from membrane to cytosol; impairs ability to promote LPS-induced IL6 and CCL5 production. 1 Publication1
Mutagenesisi7K → E: Results in exclusive localization to early endosomes and no effect on ability to promote LPS-induced IL6 and CCL5 production; when associated with E-15 and E-17. 1 Publication1
Mutagenesisi15W → E: Results in exclusive localization to early endosomes and no effect on ability to promote LPS-induced IL6 and CCL5 production; when associated with E-7 and E-17. 1 Publication1
Mutagenesisi17K → E: Results in exclusive localization to early endosomes and no effect on ability to promote LPS-induced IL6 and CCL5 production; when associated with E-7 and E-15. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00003176902 – 232TIR domain-containing adapter molecule 2Add BLAST231

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi2N-myristoyl glycineBy similarity1

Post-translational modificationi

Myristoylated. Required for membrane association which is critical for its ability to initiate efficient signaling (By similarity).By similarity

Keywords - PTMi

Lipoprotein, Myristate

Proteomic databases

MaxQBiQ8BJQ4
PaxDbiQ8BJQ4
PRIDEiQ8BJQ4

PTM databases

iPTMnetiQ8BJQ4
PhosphoSitePlusiQ8BJQ4

Expressioni

Gene expression databases

BgeeiENSMUSG00000056130
CleanExiMM_TICAM2

Interactioni

Subunit structurei

Homodimer. Interacts with TLR4, TICAM1, IRF3 and IRF7 in response to LPS. Interacts with IL1R1, IL1RAP, IRAK2, IRAK3 and TRAF6. Interacts with kinase-inactive mutants of IRAK1 and IRAK4. Interacts with MYD88; the interaction decreases after IL-18 stimulation in a time-dependent manner. Interacts with IL18R1 and IL18RAP (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

BioGridi230399, 6 interactors
IntActiQ8BJQ4, 1 interactor
STRINGi10090.ENSMUSP00000066239

Structurei

3D structure databases

ProteinModelPortaliQ8BJQ4
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini70 – 214TIR; atypicalAdd BLAST145

Domaini

The TIR domain mediates the interaction with TRAF6 and MYD88.By similarity

Phylogenomic databases

eggNOGiENOG410IKI2 Eukaryota
ENOG410Y8DE LUCA
GeneTreeiENSGT00900000141066
HOGENOMiHOG000068974
HOVERGENiHBG102133
InParanoidiQ8BJQ4
KOiK05409
OMAiIWRETRN
OrthoDBiEOG091G0LX8
PhylomeDBiQ8BJQ4
TreeFamiTF336953

Family and domain databases

Gene3Di3.40.50.10140, 1 hit
InterProiView protein in InterPro
IPR000157 TIR_dom
IPR015720 TMP21-related
IPR035897 Toll_tir_struct_dom_sf
PANTHERiPTHR22811 PTHR22811, 1 hit
PfamiView protein in Pfam
PF13676 TIR_2, 1 hit
SUPFAMiSSF52200 SSF52200, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q8BJQ4-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGVGKSKLDK CPLSWHKKDS VDADQDGHES DSKNSEEACL RGFVEQSSGS
60 70 80 90 100
EPPTGEQDQP EAKGAGPEEQ DEEEFLKFVI LHAEDDTDEA LRVQDLLQND
110 120 130 140 150
FGIRPGIVFA EMPCGRLHLQ NLDDAVNGSA WTILLLTENF LRDTWCNFQF
160 170 180 190 200
YTSLMNSVSR QHKYNSVIPM RPLNSPLPRE RTPLALQTIN ALEEESQGFS
210 220 230
TQVERIFRES VFERQQSIWK ETRSVSQKQF IA
Length:232
Mass (Da):26,362
Last modified:March 1, 2003 - v1
Checksum:iB41B3B826365D569
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti185A → T in BAE30771 (PubMed:16141072).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB100441 mRNA Translation: BAC98398.1
AY275837 mRNA Translation: AAP81749.1
AY268050 mRNA Translation: AAP29979.1
AK080873 mRNA Translation: BAC38055.1
AK151885 mRNA Translation: BAE30771.1
AK134103 mRNA Translation: BAE22014.1
BC099933 mRNA Translation: AAH99933.1
CCDSiCCDS29232.1
RefSeqiNP_775570.1, NM_173394.3
UniGeneiMm.149280

Genome annotation databases

EnsembliENSMUST00000070084; ENSMUSP00000066239; ENSMUSG00000056130
GeneIDi225471
KEGGimmu:225471
UCSCiuc008evp.2 mouse

Similar proteinsi

Entry informationi

Entry nameiTCAM2_MOUSE
AccessioniPrimary (citable) accession number: Q8BJQ4
Secondary accession number(s): Q3U996
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 5, 2008
Last sequence update: March 1, 2003
Last modified: April 25, 2018
This is version 122 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

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