MYD88_RAT
ID MYD88_RAT Reviewed; 296 AA.
AC Q6Y1S1; Q4QRC0;
DT 23-MAR-2010, integrated into UniProtKB/Swiss-Prot.
DT 23-MAR-2010, sequence version 2.
DT 03-AUG-2022, entry version 127.
DE RecName: Full=Myeloid differentiation primary response protein MyD88;
GN Name=Myd88;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Wistar; TISSUE=Spleen;
RA Li Y., Ji A., Schafer M.K.;
RT "Molecular cloning and regulation of MyD88 mRNA in rat spleen.";
RL Submitted (DEC-2002) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
CC -!- FUNCTION: Adapter protein involved in the Toll-like receptor and IL-1
CC receptor signaling pathway in the innate immune response. Acts via
CC IRAK1, IRAK2, IRF7 and TRAF6, leading to NF-kappa-B activation,
CC cytokine secretion and the inflammatory response. Increases IL-8
CC transcription. Involved in IL-18-mediated signaling pathway. Activates
CC IRF1 resulting in its rapid migration into the nucleus to mediate an
CC efficient induction of IFN-beta, NOS2/INOS, and IL12A genes. Upon TLR8
CC activation by GU-rich single-stranded RNA (GU-rich RNA) derived from
CC viruses, induces IL1B release through NLRP3 inflammasome activation (By
CC similarity). MyD88-mediated signaling in intestinal epithelial cells is
CC crucial for maintenance of gut homeostasis and controls the expression
CC of the antimicrobial lectin REG3G in the small intestine (By
CC similarity). {ECO:0000250|UniProtKB:P22366,
CC ECO:0000250|UniProtKB:Q99836}.
CC -!- SUBUNIT: Homodimer. Also forms heterodimers with TIRAP. Binds to TLR2,
CC TLR4, IRAK1, IRAK2 and IRAK4 via their respective TIR domains.
CC Interacts with IL18R1. Interacts with BMX, IL1RL1, IKBKE and IRF7.
CC Interacts with LRRFIP1 and LRRFIP2; this interaction positively
CC regulates Toll-like receptor (TLR) signaling in response to agonist.
CC Interacts with FLII. LRRFIP1 and LRRFIP2 compete with FLII for MYD88-
CC binding. Interacts with IRF1. Upon IL1B treatment, forms a complex with
CC PELI1, IRAK1, IRAK4 and TRAF6; this complex recruits MAP3K7/TAK1, TAB1
CC and TAB2 to mediate NF-kappa-B activation. Direct binding of SMAD6 to
CC PELI1 prevents the complex formation and hence negatively regulates
CC IL1R-TLR signaling and eventually NF-kappa-B-mediated gene expression.
CC May interact with PIK3AP1. Interacts (via TIR domain) with DHX9 (via
CC H2A and OB-fold regions); this interaction is direct. Interacts with
CC OTUD4 deubiquitinase; the interaction is direct.
CC {ECO:0000250|UniProtKB:Q99836}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q99836}. Nucleus
CC {ECO:0000250|UniProtKB:Q99836}.
CC -!- DOMAIN: The intermediate domain (ID) is required for the
CC phosphorylation and activation of IRAK. {ECO:0000250|UniProtKB:P22366}.
CC -!- PTM: Ubiquitinated; undergoes 'Lys-63'-linked polyubiquitination. OTUD4
CC specifically hydrolyzes 'Lys-63'-linked polyubiquitinated MYD88.
CC {ECO:0000250|UniProtKB:Q99836}.
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DR EMBL; AY191270; AAO91937.1; -; mRNA.
DR EMBL; BC097266; AAH97266.1; -; mRNA.
DR RefSeq; NP_937763.1; NM_198130.1.
DR RefSeq; XP_006244149.1; XM_006244087.3.
DR AlphaFoldDB; Q6Y1S1; -.
DR SMR; Q6Y1S1; -.
DR STRING; 10116.ENSRNOP00000018341; -.
DR PaxDb; Q6Y1S1; -.
DR Ensembl; ENSRNOT00000018341; ENSRNOP00000018341; ENSRNOG00000013634.
DR GeneID; 301059; -.
DR KEGG; rno:301059; -.
DR UCSC; RGD:735043; rat.
DR CTD; 4615; -.
DR RGD; 735043; Myd88.
DR eggNOG; ENOG502QWKI; Eukaryota.
DR GeneTree; ENSGT00510000048324; -.
DR HOGENOM; CLU_045884_0_0_1; -.
DR InParanoid; Q6Y1S1; -.
DR OMA; CTQSWFW; -.
DR OrthoDB; 890418at2759; -.
DR PhylomeDB; Q6Y1S1; -.
DR TreeFam; TF326264; -.
DR Reactome; R-RNO-1257604; PIP3 activates AKT signaling.
DR Reactome; R-RNO-1810476; RIP-mediated NFkB activation via ZBP1.
DR Reactome; R-RNO-209543; p75NTR recruits signalling complexes.
DR Reactome; R-RNO-3134963; DEx/H-box helicases activate type I IFN and inflammatory cytokines production.
DR Reactome; R-RNO-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR Reactome; R-RNO-9020702; Interleukin-1 signaling.
DR PRO; PR:Q6Y1S1; -.
DR Proteomes; UP000002494; Chromosome 8.
DR Bgee; ENSRNOG00000013634; Expressed in spleen and 19 other tissues.
DR Genevisible; Q6Y1S1; RN.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005829; C:cytosol; ISO:RGD.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0014069; C:postsynaptic density; IDA:RGD.
DR GO; GO:0032991; C:protein-containing complex; IDA:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0005149; F:interleukin-1 receptor binding; IPI:RGD.
DR GO; GO:0043621; F:protein self-association; ISO:RGD.
DR GO; GO:0005102; F:signaling receptor binding; IPI:RGD.
DR GO; GO:0070976; F:TIR domain binding; ISO:RGD.
DR GO; GO:0005121; F:Toll binding; IDA:RGD.
DR GO; GO:0035325; F:Toll-like receptor binding; ISO:RGD.
DR GO; GO:0070935; P:3'-UTR-mediated mRNA stabilization; ISO:RGD.
DR GO; GO:0006915; P:apoptotic process; ISO:RGD.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; ISO:RGD.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; ISO:RGD.
DR GO; GO:0140052; P:cellular response to oxidised low-density lipoprotein particle stimulus; ISO:RGD.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IMP:RGD.
DR GO; GO:0042742; P:defense response to bacterium; ISO:RGD.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; ISS:UniProtKB.
DR GO; GO:0051607; P:defense response to virus; ISS:UniProtKB.
DR GO; GO:0090557; P:establishment of endothelial intestinal barrier; ISO:RGD.
DR GO; GO:0007249; P:I-kappaB kinase/NF-kappaB signaling; IEA:Ensembl.
DR GO; GO:0016064; P:immunoglobulin mediated immune response; ISO:RGD.
DR GO; GO:0009682; P:induced systemic resistance; ISO:RGD.
DR GO; GO:0006954; P:inflammatory response; ISO:RGD.
DR GO; GO:0045087; P:innate immune response; IBA:GO_Central.
DR GO; GO:0070498; P:interleukin-1-mediated signaling pathway; ISO:RGD.
DR GO; GO:0007254; P:JNK cascade; IMP:RGD.
DR GO; GO:0002269; P:leukocyte activation involved in inflammatory response; ISO:RGD.
DR GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; ISO:RGD.
DR GO; GO:0002755; P:MyD88-dependent toll-like receptor signaling pathway; ISO:RGD.
DR GO; GO:0002283; P:neutrophil activation involved in immune response; ISO:RGD.
DR GO; GO:0070944; P:neutrophil-mediated killing of bacterium; ISO:RGD.
DR GO; GO:0006909; P:phagocytosis; ISO:RGD.
DR GO; GO:0032722; P:positive regulation of chemokine production; ISO:RGD.
DR GO; GO:1900017; P:positive regulation of cytokine production involved in inflammatory response; ISO:RGD.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; ISO:RGD.
DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; ISS:UniProtKB.
DR GO; GO:0032740; P:positive regulation of interleukin-17 production; ISO:RGD.
DR GO; GO:0032747; P:positive regulation of interleukin-23 production; ISO:RGD.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; ISO:RGD.
DR GO; GO:0032757; P:positive regulation of interleukin-8 production; ISO:RGD.
DR GO; GO:0046330; P:positive regulation of JNK cascade; ISO:RGD.
DR GO; GO:0050671; P:positive regulation of lymphocyte proliferation; ISO:RGD.
DR GO; GO:0060907; P:positive regulation of macrophage cytokine production; IEA:Ensembl.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISO:RGD.
DR GO; GO:1900227; P:positive regulation of NLRP3 inflammasome complex assembly; ISS:UniProtKB.
DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; IMP:RGD.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; ISO:RGD.
DR GO; GO:0032481; P:positive regulation of type I interferon production; ISO:RGD.
DR GO; GO:0042127; P:regulation of cell population proliferation; ISO:RGD.
DR GO; GO:2000338; P:regulation of chemokine (C-X-C motif) ligand 1 production; ISO:RGD.
DR GO; GO:2000341; P:regulation of chemokine (C-X-C motif) ligand 2 production; ISO:RGD.
DR GO; GO:0010468; P:regulation of gene expression; ISO:RGD.
DR GO; GO:0050727; P:regulation of inflammatory response; ISO:RGD.
DR GO; GO:0032675; P:regulation of interleukin-6 production; ISO:RGD.
DR GO; GO:1902622; P:regulation of neutrophil migration; ISO:RGD.
DR GO; GO:0032680; P:regulation of tumor necrosis factor production; ISO:RGD.
DR GO; GO:0014075; P:response to amine; IEP:RGD.
DR GO; GO:0043200; P:response to amino acid; IEP:RGD.
DR GO; GO:0045471; P:response to ethanol; IEP:RGD.
DR GO; GO:0070555; P:response to interleukin-1; ISO:RGD.
DR GO; GO:0032496; P:response to lipopolysaccharide; ISO:RGD.
DR GO; GO:0002238; P:response to molecule of fungal origin; ISO:RGD.
DR GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
DR GO; GO:0010243; P:response to organonitrogen compound; IEP:RGD.
DR GO; GO:0032494; P:response to peptidoglycan; ISO:RGD.
DR GO; GO:0009615; P:response to virus; ISO:RGD.
DR GO; GO:0008063; P:Toll signaling pathway; IDA:RGD.
DR GO; GO:0034158; P:toll-like receptor 8 signaling pathway; ISS:UniProtKB.
DR GO; GO:0060337; P:type I interferon signaling pathway; ISO:RGD.
DR CDD; cd08312; Death_MyD88; 1.
DR Gene3D; 1.10.533.10; -; 1.
DR Gene3D; 3.40.50.10140; -; 1.
DR InterPro; IPR011029; DEATH-like_dom_sf.
DR InterPro; IPR000488; Death_domain.
DR InterPro; IPR034249; MyD88_Death.
DR InterPro; IPR017281; Myelin_different_resp_MyD88.
DR InterPro; IPR000157; TIR_dom.
DR InterPro; IPR035897; Toll_tir_struct_dom_sf.
DR PANTHER; PTHR15079; PTHR15079; 1.
DR Pfam; PF00531; Death; 1.
DR Pfam; PF01582; TIR; 1.
DR PIRSF; PIRSF037756; MyD88; 1.
DR SMART; SM00005; DEATH; 1.
DR SMART; SM00255; TIR; 1.
DR SUPFAM; SSF47986; SSF47986; 1.
DR SUPFAM; SSF52200; SSF52200; 1.
DR PROSITE; PS50017; DEATH_DOMAIN; 1.
DR PROSITE; PS50104; TIR; 1.
PE 2: Evidence at transcript level;
KW Cytoplasm; Immunity; Inflammatory response; Innate immunity; Nucleus;
KW Phosphoprotein; Reference proteome; Ubl conjugation.
FT CHAIN 1..296
FT /note="Myeloid differentiation primary response protein
FT MyD88"
FT /id="PRO_0000393138"
FT DOMAIN 32..109
FT /note="Death"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00064"
FT DOMAIN 159..293
FT /note="TIR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00204"
FT REGION 110..155
FT /note="Intermediate domain"
FT /evidence="ECO:0000250"
FT MOD_RES 244
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99836"
FT CONFLICT 170
FT /note="S -> N (in Ref. 1; AAO91937)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 296 AA; 33856 MW; 6B84304BF7EDB010 CRC64;
MSAGGPRVGS VSVDSYLFSL PLVALNVGVR RRLSLFLNPR TTAAADWTSL AEEMGFEYLE
IREFETRPDP TRSLLDAWQG RSGSSVGRLL ELLALLDRED ILYELKDRIE EDCQKYIRNQ
QKQESEKPLQ VARVESSVPQ TKELGGITTL DDPLGQTPEL FDAFICYCPS DIEFVQEMIR
QLEQTDYRLK LCVSDRDVLP GTCVWSIASE LIEKRCRRMV VVVSDDYLQS KECDFQTKFA
LSLSPGVQQK RLIPIKYKAM KKDFPSILRF ITICDYTNPC TKSWFWTRLA KALSLP
