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Q8IUC6 (TCAM1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 102. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:TICAM1
Synonyms:PRVTIRB, TRIF
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length712 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.1 Ref.2 Ref.11

Subunit structure

Homodimer Probable. Interacts (via the TIR domain) with TLR3; mediates TLR3 signaling. Interacts with AZI2, TBK1, 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 TRAF6. Interacts with TRAFD1 By similarity. Ref.1 Ref.2 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14

Tissue specificity

Ubiquitously expressed but with higher levels in liver. Ref.1 Ref.2

Domain

The N-terminal region is essential for activation of the IFNB promoter activity. Ref.1 Ref.2 Ref.11

Post-translational modification

Phosphorylated by TBK1. Ref.9

Involvement in disease

Herpes simplex encephalitis 4 (HSE4) [MIM:614850]: A 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.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.18

Sequence similarities

Contains 1 TIR domain.

Sequence caution

The sequence AAO85488.1 differs from that shown. Reason: Frameshift at positions 141, 148 and 161.

Ontologies

Keywords
   Biological processAntiviral defense
Apoptosis
Immunity
Inflammatory response
Innate immunity
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processI-kappaB kinase/NF-kappaB signaling

Traceable author statement. Source: Reactome

MyD88-independent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

TRIF-dependent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

apoptotic signaling pathway

Inferred from electronic annotation. Source: Ensembl

defense response to virus

Inferred from electronic annotation. Source: UniProtKB-KW

inflammatory response

Inferred from electronic annotation. Source: UniProtKB-KW

innate immune response

Traceable author statement. Source: Reactome

lipopolysaccharide-mediated signaling pathway

Inferred from electronic annotation. Source: Ensembl

macrophage activation involved in immune response

Inferred from electronic annotation. Source: Ensembl

positive regulation of B cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of I-kappaB kinase/NF-kappaB signaling

Inferred from mutant phenotype Ref.4Ref.12. Source: UniProtKB

positive regulation of NF-kappaB transcription factor activity

Inferred from electronic annotation. Source: Ensembl

positive regulation of chemokine biosynthetic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of interferon-beta biosynthetic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of interleukin-6 production

Inferred from electronic annotation. Source: Ensembl

positive regulation of nitric oxide biosynthetic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of protein binding

Inferred from electronic annotation. Source: Ensembl

positive regulation of protein ubiquitination

Inferred from electronic annotation. Source: Ensembl

positive regulation of tumor necrosis factor production

Inferred from electronic annotation. Source: Ensembl

positive regulation of type I interferon production

Inferred from electronic annotation. Source: Ensembl

regulation of protein homodimerization activity

Inferred from electronic annotation. Source: Ensembl

response to exogenous dsRNA

Inferred from mutant phenotype PubMed 21266579. Source: MGI

toll-like receptor 3 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 4 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

   Cellular_componentcytosol

Traceable author statement. Source: Reactome

endosome membrane

Traceable author statement. Source: Reactome

ripoptosome

Inferred from direct assay PubMed 21737330. Source: UniProtKB

   Molecular_functionprotein binding

Inferred from physical interaction Ref.12. Source: UniProtKB

protein kinase binding

Inferred from physical interaction Ref.9. Source: UniProtKB

signal transducer activity

Inferred from mutant phenotype Ref.4. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 712712TIR domain-containing adapter molecule 1
PRO_0000317663

Regions

Domain390 – 46071TIR
Region512 – 712201Sufficient to induce apoptosis
Motif84 – 918TRAF6-binding
Motif248 – 2558TRAF6-binding
Motif299 – 30911TRAF6-binding
Compositional bias213 – 371159Pro-rich
Compositional bias614 – 67865Pro-rich

Natural variations

Natural variant461M → I in a breast cancer sample; somatic mutation. Ref.17
VAR_038789
Natural variant751R → C.
Corresponds to variant rs11466719 [ dbSNP | Ensembl ].
VAR_051416
Natural variant1861S → L in HSE4. Ref.18
Corresponds to variant rs146550489 [ dbSNP | Ensembl ].
VAR_069082
Natural variant2751L → V.
Corresponds to variant rs11466721 [ dbSNP | Ensembl ].
VAR_051417
Natural variant6661A → T.
Corresponds to variant rs11466724 [ dbSNP | Ensembl ].
VAR_051418

Experimental info

Mutagenesis881E → A: Reduces binding to TRAF6 and activation of NFKB signaling pathway; when associated with A-252 and A-303. Ref.9
Mutagenesis2521E → 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. Ref.9 Ref.12
Mutagenesis3031E → A: Reduces binding to TRAF6 and activation of NFKB signaling pathway; when associated with A-88 and A-252. Ref.9
Mutagenesis4341P → H: Abolishes interaction with TLR3. Ref.2
Mutagenesis4931E → A: Loss of TCAM1-induced NF-kappa-B and IRF3 activation. Ref.12
Sequence conflict1471D → T in AAO85488. Ref.6
Sequence conflict1501G → W in AAO85488. Ref.6
Sequence conflict1621L → S in AAO85488. Ref.6
Sequence conflict633 – 65927Missing in AAO85488. Ref.6
Sequence conflict6601S → P in AAO85488. Ref.6

Secondary structure

................................................. 712
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q8IUC6 [UniParc].

Last modified March 1, 2003. Version 1.
Checksum: 5D071E3BE9240D9A

FASTA71276,422
        10         20         30         40         50         60 
MACTGPSLPS AFDILGAAGQ DKLLYLKHKL KTPRPGCQGQ DLLHAMVLLK LGQETEARIS 

        70         80         90        100        110        120 
LEALKADAVA RLVARQWAGV DSTEDPEEPP DVSWAVARLY HLLAEEKLCP ASLRDVAYQE 

       130        140        150        160        170        180 
AVRTLSSRDD HRLGELQDEA RNRCGWDIAG DPGSIRTLQS NLGCLPPSSA LPSGTRSLPR 

       190        200        210        220        230        240 
PIDGVSDWSQ GCSLRSTGSP ASLASNLEIS QSPTMPFLSL HRSPHGPSKL CDDPQASLVP 

       250        260        270        280        290        300 
EPVPGGCQEP EEMSWPPSGE IASPPELPSS PPPGLPEVAP DATSTGLPDT PAAPETSTNY 

       310        320        330        340        350        360 
PVECTEGSAG PQSLPLPILE PVKNPCSVKD QTPLQLSVED TTSPNTKPCP PTPTTPETSP 

       370        380        390        400        410        420 
PPPPPPPSST PCSAHLTPSS LFPSSLESSS EQKFYNFVIL HARADEHIAL RVREKLEALG 

       430        440        450        460        470        480 
VPDGATFCED FQVPGRGELS CLQDAIDHSA FIILLLTSNF DCRLSLHQVN QAMMSNLTRQ 

       490        500        510        520        530        540 
GSPDCVIPFL PLESSPAQLS SDTASLLSGL VRLDEHSQIF ARKVANTFKP HRLQARKAMW 

       550        560        570        580        590        600 
RKEQDTRALR EQSQHLDGER MQAAALNAAY SAYLQSYLSY QAQMEQLQVA FGSHMSFGTG 

       610        620        630        640        650        660 
APYGARMPFG GQVPLGAPPP FPTWPGCPQP PPLHAWQAGT PPPPSPQPAA FPQSLPFPQS 

       670        680        690        700        710 
PAFPTASPAP PQSPGLQPLI IHHAQMVQLG LNNHMWNQRG SQAPEDKTQE AE 

« Hide

References

« Hide 'large scale' references
[1]"A novel Toll/IL-1 receptor domain-containing adapter that preferentially activates the IFN-beta promoter in the Toll-like receptor signaling."
Yamamoto M., Sato S., Mori K., Hoshino K., Takeuchi O., Takeda K., Akira S.
J. Immunol. 169:6668-6672(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, DOMAIN, INTERACTION WITH IRF3; TLR2 AND TLR3.
[2]"TICAM-1, an adapter molecule that participates in Toll-like receptor 3 mediated interferon-beta induction."
Oshiumi H., Matsumoto M., Funami K., Akazawa T., Seya T.
Nat. Immunol. 4:161-167(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH TLR3, SUBUNIT, TISSUE SPECIFICITY, DOMAIN, MUTAGENESIS OF PRO-434.
Tissue: Lung.
[3]"Natural selection in the TLR-related genes in the course of primate evolution."
Nakajima T., Ohtani H., Satta Y., Uno Y., Akari H., Ishida T., Kimura A.
Immunogenetics 60:727-735(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]"Large-scale identification and characterization of human genes that activate NF-kappaB and MAPK signaling pathways."
Matsuda A., Suzuki Y., Honda G., Muramatsu S., Matsuzaki O., Nagano Y., Doi T., Shimotohno K., Harada T., Nishida E., Hayashi H., Sugano S.
Oncogene 22:3307-3318(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Lung.
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Ovary and Testis.
[6]"PRVTIRB is a differentially expressed gene."
Begum N.A.
Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 137-712.
[7]Yu W., Gibbs R.A.
Submitted (JUN-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 297-712.
Tissue: Brain.
[8]"TIRP, a novel Toll/interleukin-1 receptor (TIR) domain-containing adapter protein involved in TIR signaling."
Bin L.-H., Xu L.-G., Shu H.-B.
J. Biol. Chem. 278:24526-24532(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TICAM2.
[9]"Toll/IL-1 receptor domain-containing adaptor inducing IFN-beta (TRIF) associates with TNF receptor-associated factor 6 and TANK-binding kinase 1, and activates two distinct transcription factors, NF-kappa B and IFN-regulatory factor-3, in the Toll-like receptor signaling."
Sato S., Sugiyama M., Yamamoto M., Watanabe Y., Kawai T., Takeda K., Akira S.
J. Immunol. 171:4304-4310(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TRAF6 AND TBK1, PHOSPHORYLATION BY TBK1, MOTIF, MUTAGENESIS OF GLU-88; GLU-252 AND GLU-303.
[10]"PIASy represses TRIF-induced ISRE and NF-kappaB activation but not apoptosis."
Zhang J., Xu L.G., Han K.J., Wei X., Shu H.B.
FEBS Lett. 570:97-101(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PIAS4.
[11]"Mechanisms of the TRIF-induced interferon-stimulated response element and NF-kappaB activation and apoptosis pathways."
Han K.J., Su X., Xu L.-G., Bin L.H., Zhang J., Shu H.-B.
J. Biol. Chem. 279:15652-15661(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH IKBKB; IKBKE; IRF3; IRF7; TBK1 AND TRAF6, DOMAIN.
[12]"Toll-like receptor 3-mediated activation of NF-kappaB and IRF3 diverges at Toll-IL-1 receptor domain-containing adapter inducing IFN-beta."
Jiang Z., Mak T.W., Sen G., Li X.
Proc. Natl. Acad. Sci. U.S.A. 101:3533-3538(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TRAF6, MUTAGENESIS OF GLU-252 AND GLU-493.
[13]"NF-kappaB-activating kinase-associated protein 1 participates in TLR3/Toll-IL-1 homology domain-containing adapter molecule-1-mediated IFN regulatory factor 3 activation."
Sasai M., Oshiumi H., Matsumoto M., Inoue N., Fujita F., Nakanishi M., Seya T.
J. Immunol. 174:27-30(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH AZI2.
[14]"The human adaptor SARM negatively regulates adaptor protein TRIF-dependent Toll-like receptor signaling."
Carty M., Goodbody R., Schroeder M., Stack J., Moynagh P.N., Bowie A.G.
Nat. Immunol. 7:1074-1081(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SARM1.
[15]"The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling."
O'Neill L.A., Bowie A.G.
Nat. Rev. Immunol. 7:353-364(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[16]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[17]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] ILE-46.
[18]"Herpes simplex encephalitis in children with autosomal recessive and dominant TRIF deficiency."
Sancho-Shimizu V., Perez de Diego R., Lorenzo L., Halwani R., Alangari A., Israelsson E., Fabrega S., Cardon A., Maluenda J., Tatematsu M., Mahvelati F., Herman M., Ciancanelli M., Guo Y., AlSum Z., Alkhamis N., Al-Makadma A.S., Ghadiri A. expand/collapse author list , Boucherit S., Plancoulaine S., Picard C., Rozenberg F., Tardieu M., Lebon P., Jouanguy E., Rezaei N., Seya T., Matsumoto M., Chaussabel D., Puel A., Zhang S.Y., Abel L., Al-Muhsen S., Casanova J.L.
J. Clin. Invest. 121:4889-4902(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HSE4 LEU-186.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS12136.1.
RefSeqNP_891549.1. NM_182919.3.
UniGeneHs.29344.

3D structure databases

PDBe
RCSB-PDB
PDBj
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[»]
ProteinModelPortalQ8IUC6.
SMRQ8IUC6. Positions 1-156, 386-545.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid127114. 24 interactions.
DIPDIP-33490N.
IntActQ8IUC6. 4 interactions.
MINTMINT-1202912.
STRING9606.ENSP00000248244.

PTM databases

PhosphoSiteQ8IUC6.

Polymorphism databases

DMDM74727957.

Proteomic databases

MaxQBQ8IUC6.
PaxDbQ8IUC6.
PRIDEQ8IUC6.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000248244; ENSP00000248244; ENSG00000127666.
GeneID148022.
KEGGhsa:148022.
UCSCuc002mbi.4. human.

Organism-specific databases

CTD148022.
GeneCardsGC19M004815.
HGNCHGNC:18348. TICAM1.
HPAHPA042460.
MIM607601. gene.
614850. phenotype.
neXtProtNX_Q8IUC6.
Orphanet1930. Herpetic encephalitis.
PharmGKBPA142670812.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG67739.
HOGENOMHOG000068973.
HOVERGENHBG108551.
InParanoidQ8IUC6.
KOK05842.
OMAEQKFYNF.
OrthoDBEOG7GFB4H.
PhylomeDBQ8IUC6.
TreeFamTF336953.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.
SignaLinkQ8IUC6.

Gene expression databases

BgeeQ8IUC6.
CleanExHS_TICAM1.
GenevestigatorQ8IUC6.

Family and domain databases

InterProIPR025735. RHIM_dom.
IPR017278. TICAM1.
IPR000157. TIR_dom.
[Graphical view]
PfamPF12721. RHIM. 1 hit.
[Graphical view]
PIRSFPIRSF037744. TIR_Ticam. 1 hit.
SUPFAMSSF52200. SSF52200. 1 hit.
ProtoNetSearch...

Other

EvolutionaryTraceQ8IUC6.
GenomeRNAi148022.
NextBio85815.
PROQ8IUC6.
SOURCESearch...

Entry information

Entry nameTCAM1_HUMAN
AccessionPrimary (citable) accession number: Q8IUC6
Secondary accession number(s): B3Y691 expand/collapse secondary AC list , O75532, Q86XP8, Q96GA0
Entry history
Integrated into UniProtKB/Swiss-Prot: February 5, 2008
Last sequence update: March 1, 2003
Last modified: July 9, 2014
This is version 102 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM