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Protein

TIR domain-containing adapter molecule 1

Gene

TICAM1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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.3 Publications

GO - Molecular functioni

  • protein kinase binding Source: UniProtKB
  • signal transducer activity Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Antiviral defense, Apoptosis, Immunity, Inflammatory response, Innate immunity

Enzyme and pathway databases

ReactomeiR-HSA-140534. Ligand-dependent caspase activation.
R-HSA-166166. MyD88-independent TLR3/TLR4 cascade.
R-HSA-1810476. RIP-mediated NFkB activation via ZBP1.
R-HSA-2562578. TRIF-mediated programmed cell death.
R-HSA-5602566. TICAM1 deficiency - HSE.
R-HSA-5602571. TRAF3 deficiency - HSE.
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.
SignaLinkiQ8IUC6.
SIGNORiQ8IUC6.

Names & Taxonomyi

Protein namesi
Recommended name:
TIR domain-containing adapter molecule 1
Short name:
TICAM-1
Alternative name(s):
Proline-rich, vinculin and TIR domain-containing protein B
Putative NF-kappa-B-activating protein 502H
Toll-interleukin-1 receptor domain-containing adapter protein inducing interferon beta
Short name:
MyD88-3
Short name:
TIR domain-containing adapter protein inducing IFN-beta
Gene namesi
Name:TICAM1
Synonyms:PRVTIRB, TRIF
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:18348. TICAM1.

Subcellular locationi

GO - Cellular componenti

  • autophagosome Source: UniProtKB-SubCell
  • cytoplasmic vesicle Source: UniProtKB-KW
  • cytosol Source: Reactome
  • endosome membrane Source: Reactome
  • ripoptosome Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasmic vesicle

Pathology & Biotechi

Involvement in diseasei

Herpes simplex encephalitis 4 (HSE4)1 Publication
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA rare complication of human herpesvirus 1 (HHV-1) infection, occurring in only a small minority of HHV-1 infected individuals. HSE is characterized by hemorrhagic necrosis of parts of the temporal and frontal lobes. Onset is over several days and involves fever, headache, seizures, stupor, and often coma, frequently with a fatal outcome.
See also OMIM:614850
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_069082186S → L in HSE4. 1 PublicationCorresponds to variant rs146550489dbSNPEnsembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi88E → A: Reduces binding to TRAF6 and activation of NFKB signaling pathway; when associated with A-252 and A-303. 1 Publication1
Mutagenesisi252E → A: Loss of TCAM1-induced NF-kappa-B activation. Reduces interaction with TRAF6 and activation of NF-kappa-B signaling pathway; when associated with A-88 and A-303. 2 Publications1
Mutagenesisi281D → E: Resistant to caspase cleavage, no effect on TRIM38-mediated degradation; when associated with E-289. 1 Publication1
Mutagenesisi289D → E: Resistant to caspase cleavage, no effect on TRIM38-mediated degradation; when associated with E-281. 1 Publication1
Mutagenesisi303E → A: Reduces binding to TRAF6 and activation of NFKB signaling pathway; when associated with A-88 and A-252. 1 Publication1
Mutagenesisi434P → H: Abolishes interaction with TLR3. 1 Publication1
Mutagenesisi493E → A: Loss of TCAM1-induced NF-kappa-B and IRF3 activation. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi148022.
MalaCardsiTICAM1.
MIMi614850. phenotype.
OpenTargetsiENSG00000127666.
Orphaneti1930. Herpetic encephalitis.
PharmGKBiPA142670812.

Polymorphism and mutation databases

BioMutaiTICAM1.
DMDMi74727957.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003176631 – 712TIR domain-containing adapter molecule 1Add BLAST712

Post-translational modificationi

Phosphorylated by TBK1.1 Publication
Polyubiquitinated by TRIM38 with 'Lys-48'-linked chains, leading to proteasomal degradation.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiQ8IUC6.
PaxDbiQ8IUC6.
PeptideAtlasiQ8IUC6.
PRIDEiQ8IUC6.

PTM databases

iPTMnetiQ8IUC6.
PhosphoSitePlusiQ8IUC6.

Expressioni

Tissue specificityi

Ubiquitously expressed but with higher levels in liver.2 Publications

Gene expression databases

BgeeiENSG00000127666.
CleanExiHS_TICAM1.
ExpressionAtlasiQ8IUC6. baseline and differential.
GenevisibleiQ8IUC6. HS.

Organism-specific databases

HPAiHPA042460.

Interactioni

Subunit structurei

Homodimer (Probable). Interacts with AZI2, IRF3 and IRF7. Interacts with TICAM2 in TLR4 recruitment. Interaction with PIAS4 inhibits the TICAM1-induced NF-kappa-B, IRF and IFNB1 activation. Interacts with IKBKB and IKBKE. Interaction with SARM1 blocks TICAM1-dependent transcription factor activation. Interacts with TRAF3 (By similarity). Interacts with TBK1, TRAF6 and RIPK1 and these interactions are enhanced in the presence of WDFY1 (PubMed:25736436). Interacts with TRAFD1 (By similarity). Interacts with UBQLN1 (via UBA domain). Interacts with TLR4 in response to LPS in a WDFY1-dependent manner (By similarity). Interacts with WDFY1 in response to poly(I:C) (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 TRIM56 (PubMed:22948160).By similarityCurated3 Publications

GO - Molecular functioni

  • protein kinase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi127114. 34 interactors.
DIPiDIP-33490N.
IntActiQ8IUC6. 11 interactors.
MINTiMINT-1202912.
STRINGi9606.ENSP00000248244.

Structurei

Secondary structure

1712
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi8 – 16Combined sources9
Helixi20 – 30Combined sources11
Helixi40 – 50Combined sources11
Helixi54 – 62Combined sources9
Turni63 – 66Combined sources4
Helixi68 – 76Combined sources9
Beta strandi83 – 85Combined sources3
Helixi93 – 105Combined sources13
Helixi111 – 127Combined sources17
Helixi133 – 144Combined sources12
Helixi200 – 206Combined sources7
Beta strandi369 – 371Combined sources3
Helixi406 – 417Combined sources12
Beta strandi431 – 433Combined sources3
Helixi444 – 447Combined sources4
Beta strandi448 – 455Combined sources8
Helixi462 – 475Combined sources14
Turni477 – 480Combined sources4
Beta strandi486 – 490Combined sources5
Beta strandi492 – 494Combined sources3
Helixi503 – 506Combined sources4
Beta strandi508 – 510Combined sources3
Beta strandi513 – 516Combined sources4
Helixi520 – 527Combined sources8
Helixi530 – 535Combined sources6
Turni536 – 540Combined sources5
Helixi541 – 543Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2M1XNMR-A387-545[»]
2M63NMR-A1-156[»]
3RC4X-ray1.50B360-372[»]
4BSXX-ray2.23A/B/C/D1-153[»]
4C0MX-ray2.80A/B/C/D1-153[»]
5JELX-ray1.60B199-217[»]
ProteinModelPortaliQ8IUC6.
SMRiQ8IUC6.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ8IUC6.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini390 – 460TIRAdd BLAST71

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 153TRIF-NTD1 PublicationAdd BLAST153
Regioni512 – 712Sufficient to induce apoptosisAdd BLAST201

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi84 – 91TRAF6-binding8
Motifi248 – 255TRAF6-binding8
Motifi299 – 309TRAF6-bindingAdd BLAST11

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi213 – 371Pro-richAdd BLAST159
Compositional biasi614 – 678Pro-richAdd BLAST65

Domaini

The N-terminal region is essential for activation of the IFNB promoter activity.3 Publications
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.1 Publication

Sequence similaritiesi

Contains 1 TIR domain.Curated

Phylogenomic databases

eggNOGiENOG410IJUV. Eukaryota.
ENOG410Y8DE. LUCA.
GeneTreeiENSGT00510000049574.
HOGENOMiHOG000068973.
HOVERGENiHBG108551.
InParanoidiQ8IUC6.
KOiK05842.
OMAiEEKLCPA.
OrthoDBiEOG091G07G7.
PhylomeDBiQ8IUC6.
TreeFamiTF336953.

Family and domain databases

InterProiIPR025735. RHIM_dom.
IPR017278. TICAM1.
IPR000157. TIR_dom.
[Graphical view]
PfamiPF12721. RHIM. 1 hit.
[Graphical view]
PIRSFiPIRSF037744. TIR_Ticam. 1 hit.
SUPFAMiSSF52200. SSF52200. 1 hit.

Sequencei

Sequence statusi: Complete.

Q8IUC6-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MACTGPSLPS AFDILGAAGQ DKLLYLKHKL KTPRPGCQGQ DLLHAMVLLK
60 70 80 90 100
LGQETEARIS LEALKADAVA RLVARQWAGV DSTEDPEEPP DVSWAVARLY
110 120 130 140 150
HLLAEEKLCP ASLRDVAYQE AVRTLSSRDD HRLGELQDEA RNRCGWDIAG
160 170 180 190 200
DPGSIRTLQS NLGCLPPSSA LPSGTRSLPR PIDGVSDWSQ GCSLRSTGSP
210 220 230 240 250
ASLASNLEIS QSPTMPFLSL HRSPHGPSKL CDDPQASLVP EPVPGGCQEP
260 270 280 290 300
EEMSWPPSGE IASPPELPSS PPPGLPEVAP DATSTGLPDT PAAPETSTNY
310 320 330 340 350
PVECTEGSAG PQSLPLPILE PVKNPCSVKD QTPLQLSVED TTSPNTKPCP
360 370 380 390 400
PTPTTPETSP PPPPPPPSST PCSAHLTPSS LFPSSLESSS EQKFYNFVIL
410 420 430 440 450
HARADEHIAL RVREKLEALG VPDGATFCED FQVPGRGELS CLQDAIDHSA
460 470 480 490 500
FIILLLTSNF DCRLSLHQVN QAMMSNLTRQ GSPDCVIPFL PLESSPAQLS
510 520 530 540 550
SDTASLLSGL VRLDEHSQIF ARKVANTFKP HRLQARKAMW RKEQDTRALR
560 570 580 590 600
EQSQHLDGER MQAAALNAAY SAYLQSYLSY QAQMEQLQVA FGSHMSFGTG
610 620 630 640 650
APYGARMPFG GQVPLGAPPP FPTWPGCPQP PPLHAWQAGT PPPPSPQPAA
660 670 680 690 700
FPQSLPFPQS PAFPTASPAP PQSPGLQPLI IHHAQMVQLG LNNHMWNQRG
710
SQAPEDKTQE AE
Length:712
Mass (Da):76,422
Last modified:March 1, 2003 - v1
Checksum:i5D071E3BE9240D9A
GO

Sequence cautioni

The sequence AAO85488 differs from that shown. Reason: Frameshift at positions 141, 148 and 161.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti147D → T in AAO85488 (Ref. 6) Curated1
Sequence conflicti150G → W in AAO85488 (Ref. 6) Curated1
Sequence conflicti162L → S in AAO85488 (Ref. 6) Curated1
Sequence conflicti633 – 659Missing in AAO85488 (Ref. 6) CuratedAdd BLAST27
Sequence conflicti660S → P in AAO85488 (Ref. 6) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03878946M → I in a breast cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_05141675R → C.Corresponds to variant rs11466719dbSNPEnsembl.1
Natural variantiVAR_069082186S → L in HSE4. 1 PublicationCorresponds to variant rs146550489dbSNPEnsembl.1
Natural variantiVAR_051417275L → V.Corresponds to variant rs11466721dbSNPEnsembl.1
Natural variantiVAR_051418666A → T.Corresponds to variant rs11466724dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB093555 mRNA. Translation: BAC44839.1.
AB086380 mRNA. Translation: BAC55579.1.
AB446484 mRNA. Translation: BAG55261.1.
AB097023 mRNA. Translation: BAC77376.1.
BC009860 mRNA. Translation: AAH09860.2.
BC136556 mRNA. Translation: AAI36557.1.
BC136557 mRNA. Translation: AAI36558.1.
AF492646 mRNA. Translation: AAO85488.1. Frameshift.
AF070530 mRNA. Translation: AAC28630.1.
CCDSiCCDS12136.1.
RefSeqiNP_891549.1. NM_182919.3.
UniGeneiHs.29344.

Genome annotation databases

EnsembliENST00000248244; ENSP00000248244; ENSG00000127666.
GeneIDi148022.
KEGGihsa:148022.
UCSCiuc002mbi.5. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB093555 mRNA. Translation: BAC44839.1.
AB086380 mRNA. Translation: BAC55579.1.
AB446484 mRNA. Translation: BAG55261.1.
AB097023 mRNA. Translation: BAC77376.1.
BC009860 mRNA. Translation: AAH09860.2.
BC136556 mRNA. Translation: AAI36557.1.
BC136557 mRNA. Translation: AAI36558.1.
AF492646 mRNA. Translation: AAO85488.1. Frameshift.
AF070530 mRNA. Translation: AAC28630.1.
CCDSiCCDS12136.1.
RefSeqiNP_891549.1. NM_182919.3.
UniGeneiHs.29344.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2M1XNMR-A387-545[»]
2M63NMR-A1-156[»]
3RC4X-ray1.50B360-372[»]
4BSXX-ray2.23A/B/C/D1-153[»]
4C0MX-ray2.80A/B/C/D1-153[»]
5JELX-ray1.60B199-217[»]
ProteinModelPortaliQ8IUC6.
SMRiQ8IUC6.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi127114. 34 interactors.
DIPiDIP-33490N.
IntActiQ8IUC6. 11 interactors.
MINTiMINT-1202912.
STRINGi9606.ENSP00000248244.

PTM databases

iPTMnetiQ8IUC6.
PhosphoSitePlusiQ8IUC6.

Polymorphism and mutation databases

BioMutaiTICAM1.
DMDMi74727957.

Proteomic databases

MaxQBiQ8IUC6.
PaxDbiQ8IUC6.
PeptideAtlasiQ8IUC6.
PRIDEiQ8IUC6.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000248244; ENSP00000248244; ENSG00000127666.
GeneIDi148022.
KEGGihsa:148022.
UCSCiuc002mbi.5. human.

Organism-specific databases

CTDi148022.
DisGeNETi148022.
GeneCardsiTICAM1.
HGNCiHGNC:18348. TICAM1.
HPAiHPA042460.
MalaCardsiTICAM1.
MIMi607601. gene.
614850. phenotype.
neXtProtiNX_Q8IUC6.
OpenTargetsiENSG00000127666.
Orphaneti1930. Herpetic encephalitis.
PharmGKBiPA142670812.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IJUV. Eukaryota.
ENOG410Y8DE. LUCA.
GeneTreeiENSGT00510000049574.
HOGENOMiHOG000068973.
HOVERGENiHBG108551.
InParanoidiQ8IUC6.
KOiK05842.
OMAiEEKLCPA.
OrthoDBiEOG091G07G7.
PhylomeDBiQ8IUC6.
TreeFamiTF336953.

Enzyme and pathway databases

ReactomeiR-HSA-140534. Ligand-dependent caspase activation.
R-HSA-166166. MyD88-independent TLR3/TLR4 cascade.
R-HSA-1810476. RIP-mediated NFkB activation via ZBP1.
R-HSA-2562578. TRIF-mediated programmed cell death.
R-HSA-5602566. TICAM1 deficiency - HSE.
R-HSA-5602571. TRAF3 deficiency - HSE.
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.
SignaLinkiQ8IUC6.
SIGNORiQ8IUC6.

Miscellaneous databases

ChiTaRSiTICAM1. human.
EvolutionaryTraceiQ8IUC6.
GenomeRNAii148022.
PROiQ8IUC6.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000127666.
CleanExiHS_TICAM1.
ExpressionAtlasiQ8IUC6. baseline and differential.
GenevisibleiQ8IUC6. HS.

Family and domain databases

InterProiIPR025735. RHIM_dom.
IPR017278. TICAM1.
IPR000157. TIR_dom.
[Graphical view]
PfamiPF12721. RHIM. 1 hit.
[Graphical view]
PIRSFiPIRSF037744. TIR_Ticam. 1 hit.
SUPFAMiSSF52200. SSF52200. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiTCAM1_HUMAN
AccessioniPrimary (citable) accession number: Q8IUC6
Secondary accession number(s): B3Y691
, O75532, Q86XP8, Q96GA0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 5, 2008
Last sequence update: March 1, 2003
Last modified: November 2, 2016
This is version 127 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 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. 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.