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Toll-like receptor 4 (Toll4) (CD antigen CD284)

 TLR4_RAT                Reviewed;         835 AA.
Q9QX05;
11-FEB-2002, integrated into UniProtKB/Swiss-Prot.
01-MAY-2000, sequence version 1.
13-NOV-2019, entry version 147.
RecName: Full=Toll-like receptor 4;
Short=Toll4;
AltName: CD_antigen=CD284;
Flags: Precursor;
Name=Tlr4;
Rattus norvegicus (Rat).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Rattus.
NCBI_TaxID=10116;
[1]
NUCLEOTIDE SEQUENCE [MRNA].
STRAIN=Sprague-Dawley; TISSUE=Heart;
PubMed=10430608; DOI=10.1172/jci6709;
Frantz S., Kobzik L., Kim Y.-D., Fukazawa R., Medzhitov R., Lee R.T.,
Kelly R.A.;
"Toll4 (TLR4) expression in cardiac myocytes in normal and failing
myocardium.";
J. Clin. Invest. 104:271-280(1999).
-!- FUNCTION: Cooperates with LY96 and CD14 to mediate the innate
immune response to bacterial lipopolysaccharide (LPS). Acts via
MYD88, TIRAP and TRAF6, leading to NF-kappa-B activation, cytokine
secretion and the inflammatory response. Also involved in LPS-
independent inflammatory responses triggered by free fatty acids,
such as palmitate. In complex with TLR6, promotes sterile
inflammation in monocytes/macrophages in response to oxidized low-
density lipoprotein (oxLDL) or amyloid-beta 42. In this context,
the initial signal is provided by oxLDL- or amyloid-beta 42-
binding to CD36. This event induces the formation of a heterodimer
of TLR4 and TLR6, which is rapidly internalized and triggers
inflammatory response, leading to the NF-kappa-B-dependent
production of CXCL1, CXCL2 and CCL9 cytokines, via MYD88 signaling
pathway, and CCL5 cytokine, via TICAM1 signaling pathway, as well
as IL1B secretion. Binds electronegative LDL (LDL(-)) and mediates
the cytokine release induced by LDL(-) (By similarity).
{ECO:0000250|UniProtKB:O00206}.
-!- SUBUNIT: Belongs to the lipopolysaccharide (LPS) receptor, a
multi-protein complex containing at least CD14, LY96 and TLR4.
Binding to bacterial LPS leads to homodimerization. Interacts with
LY96 via the extracellular domain. Interacts with MYD88 and TIRAP
via their respective TIR domains. Interacts with TICAM2. Interacts
with NOX4. Interacts with CNPY3 and HSP90B1; this interaction is
required for proper folding in the endoplasmic reticulum.
Interacts with MAP3K21; this interaction leads to negative
regulation of TLR4 signaling. Interacts with CD36, following CD36
stimulation by oxLDL or amyloid-beta 42, and forms a heterodimer
with TLR6. The trimeric complex is internalized and triggers
inflammatory response. LYN kinase activity facilitates TLR4-TLR6
heterodimerization and signal initiation. Interacts with TICAM1 in
response to LPS in a WDFY1-dependent manner. Interacts with WDFY1
in response to LPS. Interacts with SMPDL3B. Interacts with
CEACAM1; upon lipopolysaccharide stimulation, forms a complex
including TLR4 and the phosphorylated form of SYK and CEACAM1,
which in turn, recruits PTPN6 that dephosphorylates SYK, reducing
the production of reactive oxygen species (ROS) and lysosome
disruption, which in turn, reduces the activity of the
inflammasome. Interacts with RFTN1; the interaction occurs in
response to lipopolysaccharide stimulation. Interacts with SCIMP;
the interaction occurs in response to lipopolysaccharide
stimulation and is enhanced by phosphorylation of SCIMP by LYN (By
similarity). This interaction facilitates the phosphorylation of
TLR4 by LYN which elicits a selective cytokine response in
macrophages (By similarity). {ECO:0000250|UniProtKB:O00206,
ECO:0000250|UniProtKB:Q9QUK6}.
-!- SUBCELLULAR LOCATION: Cell membrane
{ECO:0000250|UniProtKB:O00206}; Single-pass type I membrane
protein {ECO:0000250|UniProtKB:O00206}. Early endosome
{ECO:0000250|UniProtKB:O00206}. Cell projection, ruffle
{ECO:0000250|UniProtKB:Q9QUK6}. Note=Upon complex formation with
CD36 and TLR6, internalized through dynamin-dependent endocytosis.
Colocalizes with RFTN1 at cell membrane and then together with
RFTN1 moves to endosomes, upon lipopolysaccharide stimulation.
{ECO:0000250|UniProtKB:O00206}.
-!- DOMAIN: The TIR domain mediates interaction with NOX4.
{ECO:0000250|UniProtKB:O00206}.
-!- PTM: Phosphorylated on tyrosine residues by LYN after binding
lipopolysaccharide. {ECO:0000250|UniProtKB:Q9QUK6}.
-!- SIMILARITY: Belongs to the Toll-like receptor family.
{ECO:0000305}.
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EMBL; AF057025; AAC13313.1; -; mRNA.
RefSeq; NP_062051.1; NM_019178.1.
SMR; Q9QX05; -.
STRING; 10116.ENSRNOP00000014020; -.
PaxDb; Q9QX05; -.
PRIDE; Q9QX05; -.
GeneID; 29260; -.
KEGG; rno:29260; -.
UCSC; RGD:3870; rat.
CTD; 7099; -.
RGD; 3870; Tlr4.
eggNOG; KOG4641; Eukaryota.
eggNOG; COG4886; LUCA.
HOGENOM; HOG000037951; -.
InParanoid; Q9QX05; -.
KO; K10160; -.
OrthoDB; 282372at2759; -.
PhylomeDB; Q9QX05; -.
Reactome; R-RNO-5686938; Regulation of TLR by endogenous ligand.
Reactome; R-RNO-936964; Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon.
Reactome; R-RNO-937072; TRAF6-mediated induction of TAK1 complex within TLR4 complex.
PRO; PR:Q9QX05; -.
Proteomes; UP000002494; Unplaced.
GO; GO:0009986; C:cell surface; IDA:RGD.
GO; GO:0005737; C:cytoplasm; IDA:RGD.
GO; GO:0005769; C:early endosome; IEA:UniProtKB-SubCell.
GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
GO; GO:0046696; C:lipopolysaccharide receptor complex; ISS:UniProtKB.
GO; GO:0001726; C:ruffle; IEA:UniProtKB-SubCell.
GO; GO:0001530; F:lipopolysaccharide binding; IDA:RGD.
GO; GO:0001875; F:lipopolysaccharide receptor activity; ISS:UniProtKB.
GO; GO:0043548; F:phosphatidylinositol 3-kinase binding; IPI:RGD.
GO; GO:0038023; F:signaling receptor activity; TAS:RGD.
GO; GO:0071222; P:cellular response to lipopolysaccharide; IEP:RGD.
GO; GO:0071260; P:cellular response to mechanical stimulus; IEP:RGD.
GO; GO:0071300; P:cellular response to retinoic acid; IEP:RGD.
GO; GO:0050829; P:defense response to Gram-negative bacterium; IBA:GO_Central.
GO; GO:0032497; P:detection of lipopolysaccharide; ISS:UniProtKB.
GO; GO:0050966; P:detection of mechanical stimulus involved in sensory perception of pain; IMP:RGD.
GO; GO:0050965; P:detection of temperature stimulus involved in sensory perception of pain; IMP:RGD.
GO; GO:0016064; P:immunoglobulin mediated immune response; IEP:RGD.
GO; GO:0006954; P:inflammatory response; IEP:RGD.
GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
GO; GO:0002758; P:innate immune response-activating signal transduction; IMP:RGD.
GO; GO:0050702; P:interleukin-1 beta secretion; ISS:UniProtKB.
GO; GO:0006691; P:leukotriene metabolic process; IDA:RGD.
GO; GO:0001774; P:microglial cell activation; IDA:RGD.
GO; GO:0120163; P:negative regulation of cold-induced thermogenesis; ISS:YuBioLab.
GO; GO:0043065; P:positive regulation of apoptotic process; IMP:RGD.
GO; GO:0043388; P:positive regulation of DNA binding; IMP:RGD.
GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IMP:RGD.
GO; GO:0050729; P:positive regulation of inflammatory response; IMP:RGD.
GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IMP:RGD.
GO; GO:1900227; P:positive regulation of NLRP3 inflammasome complex assembly; ISS:UniProtKB.
GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IDA:RGD.
GO; GO:0051930; P:regulation of sensory perception of pain; IMP:RGD.
GO; GO:1904467; P:regulation of tumor necrosis factor secretion; IMP:RGD.
GO; GO:0014823; P:response to activity; IEP:RGD.
GO; GO:0045471; P:response to ethanol; IMP:RGD.
GO; GO:0070542; P:response to fatty acid; IDA:RGD.
GO; GO:0051384; P:response to glucocorticoid; IEP:RGD.
GO; GO:1990268; P:response to gold nanoparticle; IEP:RGD.
GO; GO:0001666; P:response to hypoxia; IEP:RGD.
GO; GO:0032868; P:response to insulin; IEP:RGD.
GO; GO:0032496; P:response to lipopolysaccharide; IDA:RGD.
GO; GO:0043278; P:response to morphine; IEP:RGD.
GO; GO:0006979; P:response to oxidative stress; IMP:RGD.
GO; GO:0032570; P:response to progesterone; IEP:RGD.
GO; GO:0032526; P:response to retinoic acid; IEP:RGD.
GO; GO:0009636; P:response to toxic substance; IEP:RGD.
GO; GO:0003009; P:skeletal muscle contraction; IEP:RGD.
GO; GO:0002224; P:toll-like receptor signaling pathway; IDA:RGD.
Gene3D; 3.40.50.10140; -; 1.
Gene3D; 3.80.10.10; -; 1.
InterPro; IPR001611; Leu-rich_rpt.
InterPro; IPR003591; Leu-rich_rpt_typical-subtyp.
InterPro; IPR032675; LRR_dom_sf.
InterPro; IPR000157; TIR_dom.
InterPro; IPR035897; Toll_tir_struct_dom_sf.
Pfam; PF13855; LRR_8; 3.
Pfam; PF01582; TIR; 1.
SMART; SM00369; LRR_TYP; 9.
SMART; SM00255; TIR; 1.
SUPFAM; SSF52200; SSF52200; 1.
PROSITE; PS51450; LRR; 13.
PROSITE; PS50104; TIR; 1.
2: Evidence at transcript level;
Cell membrane; Cell projection; Complete proteome; Disulfide bond;
Endosome; Glycoprotein; Immunity; Inflammatory response;
Innate immunity; Leucine-rich repeat; Membrane; Receptor;
Reference proteome; Repeat; Signal; Transmembrane;
Transmembrane helix.
SIGNAL 1 25 {ECO:0000255}.
CHAIN 26 835 Toll-like receptor 4.
/FTId=PRO_0000034728.
TOPO_DOM 26 638 Extracellular. {ECO:0000255}.
TRANSMEM 639 659 Helical. {ECO:0000255}.
TOPO_DOM 660 835 Cytoplasmic. {ECO:0000255}.
REPEAT 54 75 LRR 1.
REPEAT 78 99 LRR 2.
REPEAT 102 123 LRR 3.
REPEAT 126 147 LRR 4.
REPEAT 150 171 LRR 5.
REPEAT 175 198 LRR 6.
REPEAT 204 224 LRR 7.
REPEAT 226 247 LRR 8.
REPEAT 372 381 LRR 9.
REPEAT 398 420 LRR 10.
REPEAT 421 442 LRR 11.
REPEAT 446 467 LRR 12.
REPEAT 470 491 LRR 13.
REPEAT 495 516 LRR 14.
REPEAT 519 540 LRR 15.
REPEAT 543 564 LRR 16.
DOMAIN 576 627 LRRCT.
DOMAIN 670 816 TIR. {ECO:0000255|PROSITE-
ProRule:PRU00204}.
CARBOHYD 34 34 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 43 43 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 75 75 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 172 172 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 204 204 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 237 237 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 248 248 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 281 281 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 307 307 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 492 492 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 495 495 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 524 524 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 572 572 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 575 575 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 622 622 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
DISULFID 28 39 {ECO:0000250|UniProtKB:O00206}.
DISULFID 280 304 {ECO:0000250|UniProtKB:O00206}.
DISULFID 388 389 {ECO:0000250|UniProtKB:O00206}.
DISULFID 580 606 {ECO:0000250|UniProtKB:O00206}.
DISULFID 582 625 {ECO:0000250|UniProtKB:O00206}.
SEQUENCE 835 AA; 96072 MW; DF5E16A30851E3A0 CRC64;
MMPLLHLAGT LIMALFLSCL RPGSLNPCIE VLPNITYQCM DQNLSKIPHD IPYSTKNLDL
SFNPLKILRS YSFTNFSQLQ WLDLSRCEIE TIEDKAWHGL NQLSTLVLTG NPIKSFSPGS
FSGLTNLENL VAVETKMTSL EGFHIGQLIS LKKLNVAHNL IHSFKLPEYF SNLTNLEHVD
LSYNYIQTIS VKDLQFLREN PQVNLSLDLS LNPIDSIQAQ AFQGIRLHEL TLRSNFNSSN
VLKMCLQNMT GLHVHRLILG EFKNERNLES FDRSVMEGLC NVSIDEFRLT YINHFSDDIY
NLNCLANISA MSFTGVHIKH IADVPRHFKW QSLSIIRCHL KPFPKLSLPF LKSWTLTTNR
EDISFGQLAL PSLRYLDLSR NAMSFRGCCS YSDFGTNNLK YLDLSFNGVI LMSANFMGLE
ELEYLDFQHS TLKKVTEFSV FLSLEKLLYL DISYTNTKID FDGIFLGLIS LNTLKMAGNS
FKDNTLSNVF TNTTNLTFLD LSKCQLEQIS RGVFDTLYRL QLLNMSHNNL LFLDPSHYKQ
LYSLRTLDCS FNRIETSKGI LQHFPKSLAV FNLTNNSVAC ICEYQNFLQW VKDQKMFLVN
VEQMKCASPI DMKASLVLDF TNSTCYIYKT IISVSVVSVL VVATVAFLIY HFYFHLILIA
GCKKYSRGES IYDAFVIYSS QNEDWVRNEL VKNLEEGVPR FQLCLHYRDF IPGVAIAANI
IQEGFHKSRK VIVVVSRHFI QSRWCIFEYE IAQTWQFLSS RSGIIFIVLE KVEKSLLRQQ
VELYRLLSRN TYLEWEDNAL GRHIFWRRLK KALLDGKALN PDETSEEEQE ATTLT


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[Tlr4] Toll-like receptor 4 (Toll4) (CD antigen CD284)
[Tlr4 Lps] Toll-like receptor 4 (CD antigen CD284)
[TLR4] Toll-like receptor 4 (hToll) (CD antigen CD284)
[TLR4] Toll-like receptor 4 (CD antigen CD284)
[TLR4] Toll-like receptor 4 (CD antigen CD284)
[TLR4] Toll-like receptor 4 (CD antigen CD284)
[TLR4] Toll-like receptor 4 (CD antigen CD284)
[TLR4] Toll-like receptor 4 (CD antigen CD284)
[TLR4] Toll-like receptor 4 (CD antigen CD284)
[TLR4] Toll-like receptor 4 (CD antigen CD284)
[TLR4] Toll-like receptor 4 (CD antigen CD284)
[TLR4] Toll-like receptor 4 (CD antigen CD284)
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[TLR2 TIL4] Toll-like receptor 2 (Toll/interleukin-1 receptor-like protein 4) (CD antigen CD282)
[Ceacam1 Bgp Bgp1] Carcinoembryonic antigen-related cell adhesion molecule 1 (Biliary glycoprotein 1) (BGP-1) (Biliary glycoprotein D) (MHVR1) (Murine hepatitis virus receptor) (MHV-R) (CD antigen CD66a)
[CD36 GP3B GP4] Platelet glycoprotein 4 (Fatty acid translocase) (FAT) (Glycoprotein IIIb) (GPIIIB) (Leukocyte differentiation antigen CD36) (PAS IV) (PAS-4) (Platelet collagen receptor) (Platelet glycoprotein IV) (GPIV) (Thrombospondin receptor) (CD antigen CD36)
[Tlr1] Toll-like receptor 1 (Toll/interleukin-1 receptor-like protein) (TIL) (CD antigen CD281)
[Tlr2] Toll-like receptor 2 (CD antigen CD282)
[LILRA4 ILT7] Leukocyte immunoglobulin-like receptor subfamily A member 4 (CD85 antigen-like family member G) (Immunoglobulin-like transcript 7) (ILT-7) (CD antigen CD85g)
[TLR6] Toll-like receptor 6 (CD antigen CD286)
[TLR1 KIAA0012] Toll-like receptor 1 (Toll/interleukin-1 receptor-like protein) (TIL) (CD antigen CD281)
[CD44 LHR MDU2 MDU3 MIC4] CD44 antigen (CDw44) (Epican) (Extracellular matrix receptor III) (ECMR-III) (GP90 lymphocyte homing/adhesion receptor) (HUTCH-I) (Heparan sulfate proteoglycan) (Hermes antigen) (Hyaluronate receptor) (Phagocytic glycoprotein 1) (PGP-1) (Phagocytic glycoprotein I) (PGP-I) (CD antigen CD44)
[CD80 CD28LG CD28LG1 LAB7] T-lymphocyte activation antigen CD80 (Activation B7-1 antigen) (BB1) (CTLA-4 counter-receptor B7.1) (B7) (CD antigen CD80)
[CD86 CD28LG2] T-lymphocyte activation antigen CD86 (Activation B7-2 antigen) (B70) (BU63) (CTLA-4 counter-receptor B7.2) (FUN-1) (CD antigen CD86)
[TLR6] Toll-like receptor 6 (CD antigen CD286)
[Tlr6] Toll-like receptor 6 (CD antigen CD286)
[LILRB2 ILT4 LIR2 MIR10] Leukocyte immunoglobulin-like receptor subfamily B member 2 (LIR-2) (Leukocyte immunoglobulin-like receptor 2) (CD85 antigen-like family member D) (Immunoglobulin-like transcript 4) (ILT-4) (Monocyte/macrophage immunoglobulin-like receptor 10) (MIR-10) (CD antigen CD85d)
[Tlr9] Toll-like receptor 9 (CD antigen CD289)
[TLR9 UNQ5798/PRO19605] Toll-like receptor 9 (CD antigen CD289)
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Bibliography :
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