TCAM1_BOVIN
ID TCAM1_BOVIN Reviewed; 759 AA.
AC Q4JF29; A7E2Y9;
DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 05-FEB-2008, sequence version 2.
DT 03-AUG-2022, entry version 78.
DE RecName: Full=TIR domain-containing adapter molecule 1;
DE Short=TICAM-1;
DE AltName: Full=Toll-interleukin-1 receptor domain-containing adapter protein inducing interferon beta;
DE Short=TIR domain-containing adapter protein inducing IFN-beta;
GN Name=TICAM1; Synonyms=TRIF;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Mammary gland;
RA Yang W., Seyfert H.M.;
RT "Dissection of MyD88 dependent and independent TLR-mediated signal
RT transduction in mammary epithelial cells of the cow.";
RL Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Fetal pons;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (AUG-2007) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Involved in innate immunity against invading pathogens.
CC Adapter used by TLR3, TLR4 (through TICAM2) and TLR5 to mediate NF-
CC kappa-B and interferon-regulatory factor (IRF) activation, and to
CC induce apoptosis. Ligand binding to these receptors results in TRIF
CC recruitment through its TIR domain. Distinct protein-interaction motifs
CC allow recruitment of the effector proteins TBK1, TRAF6 and RIPK1, which
CC in turn, lead to the activation of transcription factors IRF3 and IRF7,
CC NF-kappa-B and FADD respectively. Phosphorylation by TBK1 on the pLxIS
CC motif leads to recruitment and subsequent activation of the
CC transcription factor IRF3 to induce expression of type I interferon and
CC exert a potent immunity against invading pathogens (By similarity).
CC Component of a multi-helicase-TICAM1 complex that acts as a cytoplasmic
CC sensor of viral double-stranded RNA (dsRNA) and plays a role in the
CC activation of a cascade of antiviral responses including the induction
CC of pro-inflammatory cytokines (By similarity).
CC {ECO:0000250|UniProtKB:Q80UF7, ECO:0000250|UniProtKB:Q8IUC6}.
CC -!- SUBUNIT: Homodimer (By similarity). Found in a multi-helicase-TICAM1
CC complex at least composed of DHX36, DDX1, DDX21 and TICAM1; this
CC complex exists in resting cells with or without poly(I:C) RNA ligand
CC stimulation. Interacts (via TIR domain) with DDX21 (via C-terminus).
CC Interacts (via TIR domain) with DHX36 (via C-terminus) (By similarity).
CC Interacts with AZI2 and IRF7. Interacts with TICAM2 in TLR4
CC recruitment. Interaction with PIAS4 inhibits the TICAM1-induced NF-
CC kappa-B, IRF and IFNB1 activation. Interacts with IKBKB and IKBKE.
CC Interaction with SARM1 blocks TICAM1-dependent transcription factor
CC activation (By similarity). Interacts with TRAF3 (By similarity).
CC Interacts (when phosphorylated) with IRF3; following activation and
CC phosphorylation on the pLxIS motif by TBK1, recruits IRF3. Interacts
CC with TBK1, TRAF6 and RIPK1 and these interactions are enhanced in the
CC presence of WDFY1 (By similarity). Interacts with TRAFD1 (By
CC similarity). Interacts with UBQLN1 (via UBA domain) (By similarity).
CC Interacts with TLR4 in response to LPS in a WDFY1-dependent manner.
CC Interacts with WDFY1 in response to poly(I:C) (By similarity).
CC Interacts (via the TIR domain) with TLR3 in response to poly(I:C) and
CC this interaction is enhanced in the presence of WDFY1. Interacts with
CC TRIM56 (By similarity). Component of a multi-helicase-TICAM1 complex
CC that acts as a cytoplasmic sensor of viral double-stranded RNA (dsRNA)
CC and plays a role in the activation of a cascade of antiviral responses
CC including the induction of pro-inflammatory cytokines (By similarity).
CC Interacts (via the TIR domain) with TLR5 (By similarity). Interacts
CC with TRIM8 (By similarity). {ECO:0000250|UniProtKB:Q80UF7,
CC ECO:0000250|UniProtKB:Q8IUC6}.
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, autophagosome
CC {ECO:0000250|UniProtKB:Q8IUC6}. Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q80UF7}. Mitochondrion
CC {ECO:0000250|UniProtKB:Q80UF7}. Note=Colocalizes with UBQLN1 in the
CC autophagosome (By similarity). Colocalizes in the cytosol with DDX1,
CC DDX21 and DHX36. Colocalizes in the mitochondria with DDX1 and
CC poly(I:C) RNA ligand. The multi-helicase-TICAM1 complex may translocate
CC to the mitochondria upon poly(I:C) RNA ligand stimulation (By
CC similarity). {ECO:0000250|UniProtKB:Q80UF7,
CC ECO:0000250|UniProtKB:Q8IUC6}.
CC -!- DOMAIN: The pLxIS motif constitutes an IRF3-binding motif: following
CC phosphorylation by TBK1, the phosphorylated pLxIS motif of TICAM1
CC recruits IRF3. IRF3 is then phosphorylated and activated by TBK1 to
CC induce type-I interferons and other cytokines.
CC {ECO:0000250|UniProtKB:Q8IUC6}.
CC -!- DOMAIN: The N-terminal region is essential for activation of the IFNB
CC promoter activity. {ECO:0000250|UniProtKB:Q8IUC6}.
CC -!- DOMAIN: The N-terminal domain (TRIF-NTD) is globular and consists of
CC two alpha-helical subdomains connected by a 14-residue linker. It
CC shares structural similarity with IFIT family members N-terminal
CC regions. {ECO:0000250|UniProtKB:Q8IUC6}.
CC -!- PTM: Phosphorylated by TBK1. Following activation, phosphorylated by
CC TBK1 at Ser-210 in the pLxIS motif. The phosphorylated pLxIS motif
CC constitutes an IRF3-binding motif, leading to recruitment of the
CC transcription factor IRF3 to induce type-I interferons and other
CC cytokines. {ECO:0000250|UniProtKB:Q8IUC6}.
CC -!- PTM: Polyubiquitinated at Lys-229 by TRIM38 with 'Lys-48'-linked
CC chains, leading to proteasomal degradation. Polyubiquitinated with
CC 'Lys-6' and 'Lys-33'-linked chains in a TRIM8-dependent manner.
CC {ECO:0000250|UniProtKB:Q8IUC6}.
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DR EMBL; AJ879588; CAI53671.1; -; mRNA.
DR EMBL; BC151622; AAI51623.1; -; mRNA.
DR RefSeq; NP_001025472.1; NM_001030301.1.
DR AlphaFoldDB; Q4JF29; -.
DR SMR; Q4JF29; -.
DR STRING; 9913.ENSBTAP00000026593; -.
DR PaxDb; Q4JF29; -.
DR PRIDE; Q4JF29; -.
DR GeneID; 510427; -.
DR KEGG; bta:510427; -.
DR CTD; 148022; -.
DR eggNOG; ENOG502RXF3; Eukaryota.
DR InParanoid; Q4JF29; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0005776; C:autophagosome; IEA:UniProtKB-SubCell.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; IBA:GO_Central.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0051607; P:defense response to virus; IEA:UniProtKB-KW.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; IBA:GO_Central.
DR GO; GO:1900017; P:positive regulation of cytokine production involved in inflammatory response; IBA:GO_Central.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; ISS:UniProtKB.
DR GO; GO:0002735; P:positive regulation of myeloid dendritic cell cytokine production; ISS:UniProtKB.
DR GO; GO:0032816; P:positive regulation of natural killer cell activation; IBA:GO_Central.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IBA:GO_Central.
DR GO; GO:0043330; P:response to exogenous dsRNA; ISS:UniProtKB.
DR GO; GO:0035666; P:TRIF-dependent toll-like receptor signaling pathway; IBA:GO_Central.
DR Gene3D; 3.40.50.10140; -; 1.
DR InterPro; IPR025735; RHIM_dom.
DR InterPro; IPR017278; TICAM1.
DR InterPro; IPR000157; TIR_dom.
DR InterPro; IPR035897; Toll_tir_struct_dom_sf.
DR InterPro; IPR040886; TRIF_N.
DR PANTHER; PTHR47230; PTHR47230; 2.
DR Pfam; PF12721; RHIM; 1.
DR Pfam; PF17798; TRIF-NTD; 1.
DR PIRSF; PIRSF037744; TIR_Ticam; 1.
DR PROSITE; PS50104; TIR; 1.
PE 2: Evidence at transcript level;
KW Antiviral defense; Apoptosis; Cytoplasm; Cytoplasmic vesicle; Immunity;
KW Inflammatory response; Innate immunity; Isopeptide bond; Mitochondrion;
KW Phosphoprotein; Reference proteome; Ubl conjugation.
FT CHAIN 1..759
FT /note="TIR domain-containing adapter molecule 1"
FT /id="PRO_0000317662"
FT DOMAIN 430..590
FT /note="TIR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00204"
FT REGION 1..153
FT /note="TRIF-NTD"
FT /evidence="ECO:0000250|UniProtKB:Q8IUC6"
FT REGION 241..296
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 340..426
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 549..759
FT /note="Sufficient to induce apoptosis"
FT /evidence="ECO:0000250|UniProtKB:Q8IUC6"
FT REGION 642..723
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 84..91
FT /note="TRAF6-binding"
FT /evidence="ECO:0000250|UniProtKB:Q8IUC6"
FT MOTIF 207..210
FT /note="pLxIS motif"
FT /evidence="ECO:0000250|UniProtKB:Q8IUC6"
FT MOTIF 248..255
FT /note="TRAF6-binding"
FT /evidence="ECO:0000250|UniProtKB:Q8IUC6"
FT MOTIF 299..309
FT /note="TRAF6-binding"
FT /evidence="ECO:0000250|UniProtKB:Q8IUC6"
FT COMPBIAS 362..401
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 654..721
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 210
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8IUC6"
FT CROSSLNK 229
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q80UF7"
FT CONFLICT 4
FT /note="T -> P (in Ref. 1; CAI53671)"
FT /evidence="ECO:0000305"
FT CONFLICT 285
FT /note="A -> T (in Ref. 2; AAI51623)"
FT /evidence="ECO:0000305"
FT CONFLICT 288
FT /note="H -> Q (in Ref. 2; AAI51623)"
FT /evidence="ECO:0000305"
FT CONFLICT 294
FT /note="P -> L (in Ref. 2; AAI51623)"
FT /evidence="ECO:0000305"
FT CONFLICT 321
FT /note="T -> A (in Ref. 2; AAI51623)"
FT /evidence="ECO:0000305"
FT CONFLICT 407
FT /note="S -> F (in Ref. 1; CAI53671)"
FT /evidence="ECO:0000305"
FT CONFLICT 589
FT /note="Q -> K (in Ref. 2; AAI51623)"
FT /evidence="ECO:0000305"
FT CONFLICT 652
FT /note="S -> P (in Ref. 2; AAI51623)"
FT /evidence="ECO:0000305"
FT CONFLICT 681
FT /note="Q -> P (in Ref. 2; AAI51623)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 759 AA; 82359 MW; A0132ABC67D99282 CRC64;
MACTGPSLSG AFDILGAAGQ DKLLYLKHKL KTLRPGCRGA YLLHAMVLLK LGQETEARIS
LEALKADAVA QLVARQWAGV DSTETPEEPP DLSWAVARVY HLLTEEKLCP ATMREEAYRA
ALRAFRSRDD LQLGELQEEA RDRCGWDVLG DLGGVQTLRS DLGCLPPSSA SLSRTRSDPR
PIEHLSGWST ACSLRSTGSP ASLGSNLEIS QSPTMALLSV HHSHHGPSKL CDHPQASVVP
EPAPMGCQEP EEMSWPPSVE AADSPVRPSS PGPGLPEVTT DACPASPHDP PEVPEISAHY
PVECTDVPAA PKSLPSPSKN TCLVTDQTPV QLSEEDTAYL SAQPRPPTPS VPQTSPSFPS
ASTSPFPSPS TPPEAHPTPS KAHPTPPKAH STPPKAHPTS PKAHPTSPKA HPTVWNPEPP
PPELESSEQK FYNFVVLHAS ADEHIALRVR ERLEALGVHD GATFCEDFQV PGRGELHCLQ
DALDHSAFII LLLTSNFDCR LSQHQTNQSL MSSLTRHGWQ DCVIPFLPLE SSLAQLSPST
SSLLTGLVLL DEHSKIFARK VTNTFKPQML RARKAKWRKE QDARALREQS QQLESERQHA
AAWGAAYSAY VHSYLAYQTQ VEKLQVALAN YMPFGTQLPF GGQGSLGTPP SSFPTLPGHQ
PPPLPPWLGG TPPPIFPQPP QTFPQPPPTF PQPPPTFQQP PPACPQPLDF SQAPPARPQS
PGLQPLIIHH AQMVQLGVNN HMWNQRGTQA PEDNTRETE
