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Protein

TIR domain-containing adapter molecule 2

Gene

TICAM2

Organism
Homo sapiens (Human)
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.
Isoform 2: Proposed to inhibit LPS-TLR4 signaling at the late endosome by interaction with isoform 1 thereby disrupting the association of isoform 1 with TICAM1. May be involved in TLR4 degradation in late endosomes.

GO - Molecular functioni

  • phospholipid binding Source: Ensembl
  • signal transducer activity Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Immunity, Inflammatory response, Innate immunity

Enzyme and pathway databases

ReactomeiR-HSA-140534. Ligand-dependent caspase activation.
R-HSA-166016. Toll Like Receptor 4 (TLR4) Cascade.
R-HSA-166166. MyD88-independent TLR3/TLR4 cascade.
R-HSA-2562578. TRIF-mediated programmed cell death.
R-HSA-6798695. Neutrophil degranulation.
R-HSA-936964. Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon.
R-HSA-937041. IKK complex recruitment mediated by RIP1.
R-HSA-937072. TRAF6 mediated induction of TAK1 complex.
SignaLinkiQ86XR7.
SIGNORiQ86XR7.

Names & Taxonomyi

Protein namesi
Recommended name:
TIR domain-containing adapter molecule 2
Short name:
TICAM-2
Alternative name(s):
Putative NF-kappa-B-activating protein 502
TRIF-related adapter molecule
Toll-like receptor adaptor protein 3
Toll/interleukin-1 receptor domain-containing protein
Short name:
MyD88-4
Gene namesi
Name:TICAM2
Synonyms:TIRAP3, TIRP, TRAM
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

HGNCiHGNC:21354. TICAM2.

Subcellular locationi

Isoform 1 :
Isoform 2 :

GO - Cellular componenti

  • early endosome Source: UniProtKB
  • early endosome membrane Source: UniProtKB-SubCell
  • endoplasmic reticulum Source: UniProtKB
  • endosome membrane Source: Reactome
  • Golgi apparatus Source: UniProtKB-SubCell
  • late endosome Source: UniProtKB
  • late endosome membrane Source: UniProtKB-SubCell
  • 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)DescriptionActionsGraphical viewLength
Mutagenesisi2G → A: Results in relocalization from membrane to cytosol; Loss of ability to transduce TLR4-signal. 1 Publication1
Mutagenesisi6S → A: Loss of phosphorylation. Significant reduction in the ability to activate IRF3 or NF-kappa-B. 1 Publication1
Mutagenesisi10S → A: No effect on phosphorylation and on the ability to activate IRF3 or NF-kappa-B. 1 Publication1
Mutagenesisi14S → A: No effect on phosphorylation and on the ability to activate IRF3 or NF-kappa-B. 1 Publication1
Mutagenesisi16S → A: Loss of phosphorylation. Abolishes ability to activate IRF3 or NF-kappa-B and to transduce TLR4 signal. 1 Publication1
Mutagenesisi16S → E: Significant decrease of localization in the membrane. 1 Publication1
Mutagenesisi116P → H: Loss of ability to dimerize. Significant loss of RANTES-inducing activity. Loss of ability to induce NF-kappa-B activation. 2 Publications1
Mutagenesisi117C → H: Loss of ability to dimerize. Loss of RANTES-inducing activity and ability to induce NF-kappa-B activation. Inhibition of TLR4-dependent activation of IRF3 and IRF7. Loss of interaction with TLR4. 2 Publications1

Organism-specific databases

DisGeNETi353376.
51014.
OpenTargetsiENSG00000243414.
ENSG00000251201.
PharmGKBiPA134881157.
PA165660570.

Polymorphism and mutation databases

BioMutaiTICAM2.
DMDMi74727858.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved
ChainiPRO_00003176892 – 235TIR domain-containing adapter molecule 2Add BLAST234

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi2N-myristoyl glycine1 Publication1
Modified residuei16Phosphoserine; by PKC/PRKCE1 Publication1

Post-translational modificationi

Phosphorylated by PRKCE in response to LPS. Phosphorylation is essential for its function. It is depleted from the membrane upon phosphorylation.1 Publication
Isoform 1 is myristoylated. Required for membrane association which is critical for its ability to initiate efficient signaling.1 Publication

Keywords - PTMi

Lipoprotein, Myristate, Phosphoprotein

Proteomic databases

MaxQBiQ86XR7.
PaxDbiQ86XR7.
PeptideAtlasiQ86XR7.
PRIDEiQ86XR7.

PTM databases

iPTMnetiQ86XR7.
PhosphoSitePlusiQ86XR7.
SwissPalmiQ86XR7.

Expressioni

Tissue specificityi

Expressed in spleen, prostate, testis, uterus, small intestine, colon, peripheral blood leukocytes, heart, placenta, lung, liver, skeletal muscle, and pancreas Isoform 2 is ubiquitously expressed (at lower levels than isoform 1).3 Publications

Gene expression databases

BgeeiENSG00000243414.
CleanExiHS_TICAM2.
GenevisibleiQ86XR7. HS.

Organism-specific databases

HPAiCAB021350.
HPA008960.

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 protein kinase-inactive mutants of IRAK1 and IRAK4. Isoform 1 interacts with isoform 2; the interaction occurs in late endosomes and disrupts the interaction between isoform 1 and TICAM1. Interacts with MYD88; the interaction decreases after IL-18 stimulation in a time-dependent manner. Interacts with IL18R1 and IL18RAP.4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
MEOX2A4D1273EBI-525927,EBI-10172134
SARM1Q6SZW12EBI-525927,EBI-11693532
TLR4O002062EBI-525927,EBI-528701

Protein-protein interaction databases

BioGridi131694. 10 interactors.
DIPiDIP-33488N.
IntActiQ86XR7. 13 interactors.
STRINGi9606.ENSP00000386341.

Structurei

Secondary structure

1235
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi80 – 84Combined sources5
Beta strandi87 – 89Combined sources3
Helixi90 – 100Combined sources11
Turni101 – 104Combined sources4
Beta strandi108 – 111Combined sources4
Turni112 – 114Combined sources3
Beta strandi118 – 120Combined sources3
Helixi125 – 128Combined sources4
Beta strandi130 – 133Combined sources4
Beta strandi135 – 137Combined sources3
Helixi141 – 153Combined sources13
Helixi155 – 160Combined sources6
Beta strandi166 – 168Combined sources3
Beta strandi176 – 178Combined sources3
Helixi182 – 184Combined sources3
Turni187 – 191Combined sources5
Beta strandi196 – 199Combined sources4
Helixi202 – 209Combined sources8
Helixi212 – 232Combined sources21

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2M1WNMR-A75-235[»]
ProteinModelPortaliQ86XR7.
SMRiQ86XR7.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini73 – 232TIRPROSITE-ProRule annotationAdd BLAST160

Domaini

The TIR domain mediates the interaction with TRAF6 and MYD88.1 Publication

Sequence similaritiesi

Contains 1 TIR domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG1693. Eukaryota.
ENOG4111JPD. LUCA.
GeneTreeiENSGT00670000097656.
HOGENOMiHOG000068974.
HOVERGENiHBG102133.
InParanoidiQ86XR7.
KOiK05409.
OMAiTRVAYCH.
OrthoDBiEOG091G0LX8.
PhylomeDBiQ86XR7.
TreeFamiTF313000.

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.
PROSITEiPS50104. TIR. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q86XR7-1) [UniParc]FASTAAdd to basket
Also known as: TRAM

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MGIGKSKINS CPLSLSWGKR HSVDTSPGYH ESDSKKSEDL SLCNVAEHSN
60 70 80 90 100
TTEGPTGKQE GAQSVEEMFE EEAEEEVFLK FVILHAEDDT DEALRVQNLL
110 120 130 140 150
QDDFGIKPGI IFAEMPCGRQ HLQNLDDAVN GSAWTILLLT ENFLRDTWCN
160 170 180 190 200
FQFYTSLMNS VNRQHKYNSV IPMRPLNNPL PRERTPFALQ TINALEEESR
210 220 230
GFPTQVERIF QESVYKTQQT IWKETRNMVQ RQFIA
Length:235
Mass (Da):26,916
Last modified:June 1, 2003 - v1
Checksum:i2D1171F9B04D9C4C
GO
Isoform 2 (identifier: Q86XR7-2) [UniParc]FASTAAdd to basket
Also known as: TAG, TRAM adaptor with GOLD domain

The sequence of this isoform differs from the canonical sequence as follows:
     1-20: MGIGKSKINSCPLSLSWGKR → MPRPGSAQRW...EDLNTRVAYW

Show »
Length:404
Mass (Da):46,173
Checksum:iC539E6D9B8185764
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0474371 – 20MGIGK…SWGKR → MPRPGSAQRWAAVAGRWGCR LLALLLLVPGPGGASEITFE LPDNAKQCFYEDIAQGTKCT LEFQVITGGHYDVDCRLEDP DGKVLYKEMKKQYDSFTFTA SKNGTYKFCFSNEFSTFTHK TVYFDFQVGEDPPLFPSENR VSALTQMESACVSIHEALKS VIDYQTHFRLREAQGRSRAE DLNTRVAYW in isoform 2. 1 PublicationAdd BLAST20

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY275836 mRNA. Translation: AAP81748.1.
AB109098 mRNA. Translation: BAC98399.1.
AB091054 mRNA. Translation: BAC98397.1.
AY232653 mRNA. Translation: AAO74498.1.
AY304581 mRNA. Translation: AAQ97430.1.
AY304582 mRNA. Translation: AAQ97431.1.
AY304583 mRNA. Translation: AAQ97432.1.
AY304584 mRNA. Translation: AAQ97433.1.
AB446491 mRNA. Translation: BAG55268.1.
AB097022 mRNA. Translation: BAC77375.1.
AC010226 Genomic DNA. No translation available.
CH471086 Genomic DNA. Translation: EAW48960.1.
CH471086 Genomic DNA. Translation: EAW48961.1.
BC109265 mRNA. Translation: AAI09266.1.
BC109266 mRNA. Translation: AAI09267.1.
CCDSiCCDS4119.1. [Q86XR7-1]
RefSeqiNP_001157940.1. NM_001164468.3. [Q86XR7-2]
NP_001157941.1. NM_001164469.3.
NP_067681.1. NM_021649.7. [Q86XR7-1]
UniGeneiHs.718838.

Genome annotation databases

EnsembliENST00000427199; ENSP00000415139; ENSG00000243414. [Q86XR7-1]
GeneIDi100302736.
353376.
KEGGihsa:100302736.
hsa:353376.
UCSCiuc003krc.4. human. [Q86XR7-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY275836 mRNA. Translation: AAP81748.1.
AB109098 mRNA. Translation: BAC98399.1.
AB091054 mRNA. Translation: BAC98397.1.
AY232653 mRNA. Translation: AAO74498.1.
AY304581 mRNA. Translation: AAQ97430.1.
AY304582 mRNA. Translation: AAQ97431.1.
AY304583 mRNA. Translation: AAQ97432.1.
AY304584 mRNA. Translation: AAQ97433.1.
AB446491 mRNA. Translation: BAG55268.1.
AB097022 mRNA. Translation: BAC77375.1.
AC010226 Genomic DNA. No translation available.
CH471086 Genomic DNA. Translation: EAW48960.1.
CH471086 Genomic DNA. Translation: EAW48961.1.
BC109265 mRNA. Translation: AAI09266.1.
BC109266 mRNA. Translation: AAI09267.1.
CCDSiCCDS4119.1. [Q86XR7-1]
RefSeqiNP_001157940.1. NM_001164468.3. [Q86XR7-2]
NP_001157941.1. NM_001164469.3.
NP_067681.1. NM_021649.7. [Q86XR7-1]
UniGeneiHs.718838.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2M1WNMR-A75-235[»]
ProteinModelPortaliQ86XR7.
SMRiQ86XR7.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi131694. 10 interactors.
DIPiDIP-33488N.
IntActiQ86XR7. 13 interactors.
STRINGi9606.ENSP00000386341.

PTM databases

iPTMnetiQ86XR7.
PhosphoSitePlusiQ86XR7.
SwissPalmiQ86XR7.

Polymorphism and mutation databases

BioMutaiTICAM2.
DMDMi74727858.

Proteomic databases

MaxQBiQ86XR7.
PaxDbiQ86XR7.
PeptideAtlasiQ86XR7.
PRIDEiQ86XR7.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000427199; ENSP00000415139; ENSG00000243414. [Q86XR7-1]
GeneIDi100302736.
353376.
KEGGihsa:100302736.
hsa:353376.
UCSCiuc003krc.4. human. [Q86XR7-1]

Organism-specific databases

CTDi100302736.
353376.
DisGeNETi353376.
51014.
GeneCardsiTICAM2.
HGNCiHGNC:21354. TICAM2.
HPAiCAB021350.
HPA008960.
MIMi608321. gene.
neXtProtiNX_Q86XR7.
OpenTargetsiENSG00000243414.
ENSG00000251201.
PharmGKBiPA134881157.
PA165660570.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1693. Eukaryota.
ENOG4111JPD. LUCA.
GeneTreeiENSGT00670000097656.
HOGENOMiHOG000068974.
HOVERGENiHBG102133.
InParanoidiQ86XR7.
KOiK05409.
OMAiTRVAYCH.
OrthoDBiEOG091G0LX8.
PhylomeDBiQ86XR7.
TreeFamiTF313000.

Enzyme and pathway databases

ReactomeiR-HSA-140534. Ligand-dependent caspase activation.
R-HSA-166016. Toll Like Receptor 4 (TLR4) Cascade.
R-HSA-166166. MyD88-independent TLR3/TLR4 cascade.
R-HSA-2562578. TRIF-mediated programmed cell death.
R-HSA-6798695. Neutrophil degranulation.
R-HSA-936964. Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon.
R-HSA-937041. IKK complex recruitment mediated by RIP1.
R-HSA-937072. TRAF6 mediated induction of TAK1 complex.
SignaLinkiQ86XR7.
SIGNORiQ86XR7.

Miscellaneous databases

GeneWikiiTICAM2.
PROiQ86XR7.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000243414.
CleanExiHS_TICAM2.
GenevisibleiQ86XR7. HS.

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.
PROSITEiPS50104. TIR. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTCAM2_HUMAN
AccessioniPrimary (citable) accession number: Q86XR7
Secondary accession number(s): B3Y698, Q6JUT2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 5, 2008
Last sequence update: June 1, 2003
Last modified: November 30, 2016
This is version 140 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. 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.