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Protein

TIR domain-containing adapter molecule 2

Gene

Ticam2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

Complete GO annotation...

Keywords - Biological processi

Immunity, Inflammatory response, Innate immunity

Enzyme and pathway databases

ReactomeiR-MMU-166016. Toll Like Receptor 4 (TLR4) Cascade.
R-MMU-166166. MyD88-independent TLR3/TLR4 cascade.

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 18

Organism-specific databases

MGIiMGI:3040056. Ticam2.

Subcellular locationi

GO - Cellular componenti

  • early endosome Source: UniProtKB
  • endoplasmic reticulum Source: UniProtKB
  • endosome Source: UniProtKB
  • Golgi apparatus Source: UniProtKB-SubCell
  • interleukin-1 receptor complex Source: MGI
  • late endosome Source: UniProtKB
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

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

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi2 – 21G → A: Results in relocalization from membrane to cytosol; impairs ability to promote LPS-induced IL6 and CCL5 production. 1 Publication
Mutagenesisi7 – 71K → 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 Publication
Mutagenesisi15 – 151W → 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 Publication
Mutagenesisi17 – 171K → 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 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedBy similarity
Chaini2 – 232231TIR domain-containing adapter molecule 2PRO_0000317690Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi2 – 21N-myristoyl glycineBy similarity

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.
PhosphoSiteiQ8BJQ4.

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 interactions.
IntActiQ8BJQ4. 1 interaction.
STRINGi10090.ENSMUSP00000066239.

Structurei

3D structure databases

ProteinModelPortaliQ8BJQ4.
SMRiQ8BJQ4. Positions 72-232.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini70 – 214145TIR; atypicalAdd
BLAST

Domaini

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

Sequence similaritiesi

Contains 1 TIR domain.Curated

Phylogenomic databases

eggNOGiENOG410IKI2. Eukaryota.
ENOG410Y8DE. LUCA.
GeneTreeiENSGT00670000097656.
HOGENOMiHOG000068974.
HOVERGENiHBG102133.
InParanoidiQ8BJQ4.
KOiK05409.
OMAiIWRETRN.
OrthoDBiEOG091G0LX8.
PhylomeDBiQ8BJQ4.
TreeFamiTF336953.

Family and domain databases

Gene3Di3.40.50.10140. 1 hit.
InterProiIPR000157. TIR_dom.
IPR015720. TMP21-related.
[Graphical view]
PANTHERiPTHR22811. PTHR22811. 1 hit.
PfamiPF13676. TIR_2. 1 hit.
[Graphical view]
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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti185 – 1851A → T in BAE30771 (PubMed:16141072).Curated

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.

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliQ8BJQ4.
SMRiQ8BJQ4. Positions 72-232.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi230399. 6 interactions.
IntActiQ8BJQ4. 1 interaction.
STRINGi10090.ENSMUSP00000066239.

PTM databases

iPTMnetiQ8BJQ4.
PhosphoSiteiQ8BJQ4.

Proteomic databases

MaxQBiQ8BJQ4.
PaxDbiQ8BJQ4.
PRIDEiQ8BJQ4.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi353376.
MGIiMGI:3040056. Ticam2.

Phylogenomic databases

eggNOGiENOG410IKI2. Eukaryota.
ENOG410Y8DE. LUCA.
GeneTreeiENSGT00670000097656.
HOGENOMiHOG000068974.
HOVERGENiHBG102133.
InParanoidiQ8BJQ4.
KOiK05409.
OMAiIWRETRN.
OrthoDBiEOG091G0LX8.
PhylomeDBiQ8BJQ4.
TreeFamiTF336953.

Enzyme and pathway databases

ReactomeiR-MMU-166016. Toll Like Receptor 4 (TLR4) Cascade.
R-MMU-166166. MyD88-independent TLR3/TLR4 cascade.

Miscellaneous databases

PROiQ8BJQ4.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000056130.
CleanExiMM_TICAM2.

Family and domain databases

Gene3Di3.40.50.10140. 1 hit.
InterProiIPR000157. TIR_dom.
IPR015720. TMP21-related.
[Graphical view]
PANTHERiPTHR22811. PTHR22811. 1 hit.
PfamiPF13676. TIR_2. 1 hit.
[Graphical view]
SUPFAMiSSF52200. SSF52200. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiTCAM2_MOUSE
AccessioniPrimary (citable) accession number: Q8BJQ4
Secondary accession number(s): Q3U996
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 5, 2008
Last sequence update: March 1, 2003
Last modified: September 7, 2016
This is version 110 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.