Human Gene TICAM2 (ENST00000427199.3_7) from GENCODE V47lift37
  Description: toll like receptor adaptor molecule 2 (from RefSeq NM_021649.7)
Gencode Transcript: ENST00000427199.3_7
Gencode Gene: ENSG00000243414.6_9
Transcript (Including UTRs)
   Position: hg19 chr5:114,914,193-114,938,176 Size: 23,984 Total Exon Count: 2 Strand: -
Coding Region
   Position: hg19 chr5:114,916,246-114,916,953 Size: 708 Coding Exon Count: 1 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
Gene AllelesRNA-Seq ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated at UCSC: 2024-08-22 23:36:26

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr5:114,914,193-114,938,176)mRNA (may differ from genome)Protein (235 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
AlphaFoldBioGPSEnsemblEntrez GeneExonPrimerGeneCards
HGNCMalacardsMGIOMIMPubMedReactome
UniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: TCAM2_HUMAN
DESCRIPTION: RecName: Full=TIR domain-containing adapter molecule 2; Short=TICAM-2; AltName: Full=Putative NF-kappa-B-activating protein 502; AltName: Full=TRIF-related adapter molecule; AltName: Full=Toll-like receptor adaptor protein 3; AltName: Full=Toll/interleukin-1 receptor domain-containing protein;
FUNCTION: Functions in LPS-TLR4 signaling to regulate the MYD88- independent pathway during the innate immune response to LPS. Also involved in IL1-triggered NF-kappa-B activation, functioning upstream of IRAK1, IRAK2, TRAF6, and IKBKB. Physically bridges TLR4 and TICAM1 and functionally transmits LPS-TRL4 signal to TICAM1.
SUBUNIT: Homodimer. Interacts with TLR4, TICAM1, IRF3 and IRF7 in response to LPS. Interacts with IL1R1, IL1RAP, IRAK2, IRAK3 and TRAF6. Interacts with protein kinase-inactive mutants of IRAK1 and IRAK4.
SUBCELLULAR LOCATION: Cytoplasm. Golgi apparatus. Cell membrane. Note=Localized to the plasma membrane as a result of myristoylation. Phosphorylation on Ser-16 leads to its depletion from the membrane.
TISSUE SPECIFICITY: Expressed in spleen, prostate, testis, uterus, small intestine, colon, peripheral blood leukocytes, heart, placenta, lung, liver, skeletal muscle, and pancreas.
DOMAIN: The TIR domain mediates the interaction with TRAF6.
PTM: Phosphorylated by PRKCE in response to LPS. Phosphorylation is essential for its function. It is depleted from the membrane upon phosphorylation.
PTM: Myristoylated. Required for membrane association which is critical for its ability to initiate efficient signaling.
SIMILARITY: Contains 1 TIR domain.

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: TICAM2
Diseases sorted by gene-association score: primary bacterial infectious disease (2), parasitic protozoa infectious disease (1)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 2.67 RPKM in Cells - EBV-transformed lymphocytes
Total median expression: 61.88 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -197.70442-0.447 Picture PostScript Text
3' UTR -513.302053-0.250 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR000157 - TIR_dom

Pfam Domains:
PF13676 - TIR domain

SCOP Domains:
52200 - Toll/Interleukin receptor TIR domain

ModBase Predicted Comparative 3D Structure on Q86XR7
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
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-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005515 protein binding
GO:0005543 phospholipid binding

Biological Process:
GO:0001817 regulation of cytokine production
GO:0002376 immune system process
GO:0002756 MyD88-independent toll-like receptor signaling pathway
GO:0006954 inflammatory response
GO:0007165 signal transduction
GO:0007249 I-kappaB kinase/NF-kappaB signaling
GO:0032729 positive regulation of interferon-gamma production
GO:0032755 positive regulation of interleukin-6 production
GO:0034128 negative regulation of MyD88-independent toll-like receptor signaling pathway
GO:0034142 toll-like receptor 4 signaling pathway
GO:0034144 negative regulation of toll-like receptor 4 signaling pathway
GO:0034145 positive regulation of toll-like receptor 4 signaling pathway
GO:0035666 TRIF-dependent toll-like receptor signaling pathway
GO:0035669 TRAM-dependent toll-like receptor 4 signaling pathway
GO:0043123 positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:0043312 neutrophil degranulation
GO:0045087 innate immune response
GO:0051607 defense response to virus
GO:0070266 necroptotic process
GO:0070671 response to interleukin-12
GO:0071222 cellular response to lipopolysaccharide
GO:0071650 negative regulation of chemokine (C-C motif) ligand 5 production
GO:0071651 positive regulation of chemokine (C-C motif) ligand 5 production
GO:0097190 apoptotic signaling pathway
GO:2000494 positive regulation of interleukin-18-mediated signaling pathway

Cellular Component:
GO:0005737 cytoplasm
GO:0005768 endosome
GO:0005769 early endosome
GO:0005770 late endosome
GO:0005783 endoplasmic reticulum
GO:0005794 Golgi apparatus
GO:0005886 plasma membrane
GO:0010008 endosome membrane
GO:0016020 membrane
GO:0030667 secretory granule membrane
GO:0031901 early endosome membrane
GO:0031902 late endosome membrane


-  Descriptions from all associated GenBank mRNAs
  BC064944 - Homo sapiens cDNA clone IMAGE:6018003, **** WARNING: chimeric clone ****.
AY304583 - Homo sapiens TIRAP3a (TIRAP3) mRNA, complete cds.
AY304584 - Homo sapiens TIRAP3b (TIRAP3) mRNA, complete cds.
AY275836 - Homo sapiens TIR domain-containing adapter protein mRNA, complete cds.
AK075218 - Homo sapiens cDNA FLJ90737 fis, clone PLACE1010827, moderately similar to Membrane protein p24B precursor.
AY304581 - Homo sapiens TIRAP3b long form (TIRAP3) mRNA, complete cds.
AB097022 - Homo sapiens mRNA for putative NFkB activating protein, complete cds, clone: 502.
AB002444 - Homo sapiens mRNA, clone: P11-C, from chromosome 5q21-q22.
BC109265 - Homo sapiens toll-like receptor adaptor molecule 2, mRNA (cDNA clone MGC:129876 IMAGE:40025951), complete cds.
BC109266 - Homo sapiens toll-like receptor adaptor molecule 2, mRNA (cDNA clone MGC:129877 IMAGE:40025952), complete cds.
AB091054 - Homo sapiens mRNA for TICAM-2, complete cds.
AB109098 - Homo sapiens TICAM-2 mRNA for TIR-containing adapter molecule-2, complete cds.
AB446491 - Homo sapiens TICAM2 mRNA for TIR domain-containing adaptor molecule 2, complete cds.
AY232653 - Homo sapiens TRIF-related adapter molecule (TRAM) mRNA, complete cds.
AY304582 - Homo sapiens TIRAP3a short form (TIRAP3) mRNA, complete cds.
KJ896134 - Synthetic construct Homo sapiens clone ccsbBroadEn_05528 TICAM2 gene, encodes complete protein.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein Q86XR7 (Reactome details) participates in the following event(s):

R-HSA-2201341 Endocytosis of TRAM (TICAM2)
R-HSA-166168 TLR4:LY96:LPS:CD14 recruits TRAM (TICAM2)
R-HSA-6798743 Exocytosis of secretory granule membrane proteins
R-HSA-166175 TRAM:TLR4:LY96:LPS:CD14 recruits TRIF (TICAM1)
R-HSA-168921 TRIF:activated TLR3/TLR4 complex recruits RIP1
R-HSA-936985 Activated TLR4:TICAM1 recruits TRAF6
R-HSA-2201338 TRAF3 binds TICAM1:activated TLR4 complex
R-HSA-2559568 SARM binds TICAM1:TRAM:TLR4:LY96:LPS:CD14
R-HSA-937075 Phosphorylated TAK1 leaves activated TLR receptor complex
R-HSA-168915 K63-linked ubiquitination of RIP1 bound to the activated TLR complex
R-HSA-2562541 TLR4-induced ripoptosome assembly
R-HSA-936947 Activated TLR4:TICAM1:K63pUb-TRAF6 recruits TAK1complex
R-HSA-937029 IKBKG subunit of IKK complex binds polyubiquinated RIP1
R-HSA-5362486 TANK binds K63-poly-Ub-TRAF3:TICAM1:activated TLR4
R-HSA-2562564 Caspase-8 processing within TLR4 complex
R-HSA-2569057 RIP3 binds TRIF to mediate necroptosis
R-HSA-936951 Activation of TAK1 complex bound to activated TLR4 complex
R-HSA-936941 Recruitment of TBK1/IKK epsilon to K63-pUb-TANK:K63-pUb-TRAF3:TRIF:activated TLR4 followed by their phosphorylation
R-HSA-166271 IRF3/IRF7 recruitment to p-TBK1/p-IKK epsilon bound to the activated TLR4
R-HSA-166245 Phosphorylation of IRF-3/IRF7 and their release from the activated TLR complex
R-HSA-166016 Toll Like Receptor 4 (TLR4) Cascade
R-HSA-6798695 Neutrophil degranulation
R-HSA-168898 Toll-Like Receptors Cascades
R-HSA-166166 MyD88-independent TLR4 cascade
R-HSA-168249 Innate Immune System
R-HSA-937041 IKK complex recruitment mediated by RIP1
R-HSA-937072 TRAF6-mediated induction of TAK1 complex within TLR4 complex
R-HSA-936964 Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon
R-HSA-168256 Immune System
R-HSA-2562578 TRIF-mediated programmed cell death
R-HSA-140534 Ligand-dependent caspase activation
R-HSA-937061 TRIF(TICAM1)-mediated TLR4 signaling
R-HSA-5357769 Caspase activation via extrinsic apoptotic signalling pathway
R-HSA-975163 IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation
R-HSA-9014325 TICAM1,TRAF6-dependent induction of TAK1 complex
R-HSA-109581 Apoptosis
R-HSA-975138 TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation
R-HSA-168164 Toll Like Receptor 3 (TLR3) Cascade
R-HSA-5357801 Programmed Cell Death
R-HSA-975155 MyD88 dependent cascade initiated on endosome
R-HSA-168138 Toll Like Receptor 9 (TLR9) Cascade
R-HSA-168181 Toll Like Receptor 7/8 (TLR7/8) Cascade

-  Other Names for This Gene
  Alternate Gene Symbols: B3Y698, ENST00000427199.1, ENST00000427199.2, NM_021649, Q6JUT2, Q86XR7, TCAM2_HUMAN, TIRAP3, TIRP, TRAM, uc319wgs.1, uc319wgs.2
UCSC ID: ENST00000427199.3_7
RefSeq Accession: NM_021649.7
Protein: Q86XR7 (aka TCAM2_HUMAN)

-  Gene Model Information
  Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.