Protein: TLR4_HUMAN
Sequence: MMSASRLAGTLIPAMAFLSCVRPESWEPCVEVVPNITYQCMELNFYKIPDNLPFSTKNLDLSFNPLRHLGSYSFFSFPELQVLDLSRCEIQTIEDGAYQSLSHLSTLILTGNPIQSLALGAFSGLSSLQKLVAVETNLASLENFPIGHLKTLKELNVAHNLIQSFKLPEYFSNLTNLEHLDLSSNKIQSIYCTDLRVLHQMPLLNLSLDLSLNPMNFIQPGAFKEIRLHKLTLRNNFDSLNVMKTCIQGLAGLEVHRLVLGEFRNEGNLEKFDKSALEGLCNLTIEEFRLAYLDYYLDDIIDLFNCLTNVSSFSLVSVTIERVKDFSYNFGWQHLELVNCKFGQFPTLKLKSLKRLTFTSNKGGNAFSEVDLPSLEFLDLSRNGLSFKGCCSQSDFGTTSLKYLDLSFNGVITMSSNFLGLEQLEHLDFQHSNLKQMSEFSVFLSLRNLIYLDISHTHTRVAFNGIFNGLSSLEVLKMAGNSFQENFLPDIFTELRNLTFLDLSQCQLEQLSPTAFNSLSSLQVLNMSHNNFFSLDTFPYKCLNSLQVLDYSLNHIMTSKKQELQHFPSSLAFLNLTQNDFACTCEHQSFLQWIKDQRQLLVEVERMECATPSDKQGMPVLSLNITCQMNKTIIGVSVLSVLVVSVVAVLVYKFYFHLMLLAGCIKYGRGENIYDAFVIYSSQDEDWVRNELVKNLEEGVPPFQLCLHYRDFIPGVAIAANIIHEGFHKSRKVIVVVSQHFIQSRWCIFEYEIAQTWQFLSSRAGIIFIVLQKVEKTLLRQQVELYRLLSRNTYLEWEDSVLGRHIFWRRLRKALLDGKSWNPEGTVGTGCNWQEATSI
What is the function of this protein?
Cooperates with LY96 and CD14 to mediate the innate immune response to bacterial lipopolysaccharide (LPS) (PubMed:27022195).  Acts via MYD88, TIRAP and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response (PubMed:9237759, PubMed:10835634, PubMed:27022195, PubMed:21393102).  Also involved in LPS-independent inflammatory responses triggered by free fatty acids, such as palmitate, and Ni(2+).  Responses triggered by Ni(2+) require non-conserved histidines and are, therefore, species-specific (PubMed:20711192).  Both M. tuberculosis HSP70 (dnaK) and HSP65 (groEL-2) act via this protein to stimulate NF-kappa-B expression (PubMed:15809303).  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(-) (PubMed:23880187).  Stimulation of monocytes in vitro with M. tuberculosis PstS1 induces p38 MAPK and ERK1/2 activation primarily via TLR2, but also partially via this receptor (PubMed:16622205, PubMed:10835634, PubMed:15809303, PubMed:17478729, PubMed:20037584, PubMed:20711192, PubMed:23880187, PubMed:27022195, PubMed:9237759).  Activated by the signaling pathway regulator NMI which acts as damage-associated molecular patterns (DAMPs) in response to cell injury or pathogen invasion, therefore promoting nuclear factor NF-kappa-B activation (PubMed:29038465).
What are the official names of this protein?
Toll-like receptor 4, hToll.
What is the protein family that this protein belongs to?
Belongs to the Toll-like receptor family.
What are the subcellular locations of this protein?
Cell membrane; Single-pass type I membrane protein. Early endosome. Cell projection, ruffle. Note=Upon complex formation with CD36 and TLR6, internalized through dynamin-dependent endocytosis (PubMed:20037584). Colocalizes with RFTN1 at cell membrane and then together with RFTN1 moves to endosomes, upon lipopolysaccharide stimulation.