MYD88_BOVIN
ID MYD88_BOVIN Reviewed; 296 AA.
AC Q599T9; Q49BZ6; Q49CF6; Q6GV22;
DT 23-MAR-2010, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2005, sequence version 1.
DT 03-AUG-2022, entry version 123.
DE RecName: Full=Myeloid differentiation primary response protein MyD88;
GN Name=MYD88;
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] (ISOFORM 1), AND FUNCTION.
RC TISSUE=Mammary gland;
RX PubMed=17936907; DOI=10.1016/j.molimm.2007.09.004;
RA Yang W., Zerbe H., Petzl W., Brunner R.M., Gunther J., Draing C.,
RA von Aulock S., Schuberth H.J., Seyfert H.M.;
RT "Bovine TLR2 and TLR4 properly transduce signals from Staphylococcus aureus
RT and E. coli, but S. aureus fails to both activate NF-kappaB in mammary
RT epithelial cells and to quickly induce TNFalpha and interleukin-8 (CXCL8)
RT expression in the udder.";
RL Mol. Immunol. 45:1385-1397(2008).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3).
RA Bailey R., Yamakawa Y., Stalker A., Willcocks S., Werling D.;
RT "Regulation of TLR-mediated NFkB activation by alternative splicing of
RT bovine MyD88.";
RL Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=Crossbred X Angus; TISSUE=Ileum;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 206-296 (ISOFORMS 1/2).
RX PubMed=16701904; DOI=10.1016/j.vetimm.2006.03.007;
RA Werling D., Piercy J., Coffey T.J.;
RT "Expression of TOLL-like receptors (TLR) by bovine antigen-presenting
RT cells-potential role in pathogen discrimination?";
RL Vet. Immunol. Immunopathol. 112:2-11(2006).
RN [5]
RP FUNCTION.
RX PubMed=18760477; DOI=10.1016/j.cimid.2008.06.001;
RA Cates E.A., Connor E.E., Mosser D.M., Bannerman D.D.;
RT "Functional characterization of bovine TIRAP and MyD88 in mediating
RT bacterial lipopolysaccharide-induced endothelial NF-kappaB activation and
RT apoptosis.";
RL Comp. Immunol. Microbiol. Infect. Dis. 32:477-490(2009).
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 and TRAF6, leading to NF-kappa-B activation, cytokine
CC secretion and the inflammatory response. Increases IL-8 transcription.
CC Involved in IL-18-mediated signaling pathway. Activates IRF1 resulting
CC in its rapid migration into the nucleus to mediate an efficient
CC induction of IFN-beta, NOS2/INOS, and IL12A genes (PubMed:17936907,
CC PubMed:18760477). Upon TLR8 activation by GU-rich single-stranded RNA
CC (GU-rich RNA) derived from viruses, induces IL1B release through NLRP3
CC inflammasome activation (By similarity). MyD88-mediated signaling in
CC intestinal epithelial cells is crucial for maintenance of gut
CC homeostasis and controls the expression of the antimicrobial lectin
CC REG3G in the small intestine (By similarity).
CC {ECO:0000250|UniProtKB:P22366, ECO:0000250|UniProtKB:Q99836,
CC ECO:0000269|PubMed:17936907, ECO:0000269|PubMed:18760477}.
CC -!- SUBUNIT: Homodimer. Also forms heterodimers with TIRAP. Binds to TLR2,
CC TLR4, TLR5, 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 -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q599T9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q599T9-2; Sequence=VSP_038889;
CC Name=3;
CC IsoId=Q599T9-3; Sequence=VSP_038889, VSP_038890, VSP_038891;
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; AJ853453; CAH68521.1; -; mRNA.
DR EMBL; AY934808; AAY16578.1; -; mRNA.
DR EMBL; AY937381; AAY22119.1; -; mRNA.
DR EMBL; BC102851; AAI02852.1; -; mRNA.
DR EMBL; AY634627; AAT48485.1; -; mRNA.
DR RefSeq; NP_001014404.1; NM_001014382.2. [Q599T9-1]
DR AlphaFoldDB; Q599T9; -.
DR SMR; Q599T9; -.
DR STRING; 9913.ENSBTAP00000000735; -.
DR PaxDb; Q599T9; -.
DR PRIDE; Q599T9; -.
DR GeneID; 444881; -.
DR KEGG; bta:444881; -.
DR CTD; 4615; -.
DR eggNOG; ENOG502QWKI; Eukaryota.
DR InParanoid; Q599T9; -.
DR TreeFam; TF326264; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0070976; F:TIR domain binding; IEA:InterPro.
DR GO; GO:0035325; F:Toll-like receptor binding; IBA:GO_Central.
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:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IBA:GO_Central.
DR GO; GO:0002755; P:MyD88-dependent toll-like receptor signaling pathway; IEA:InterPro.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IEA:InterPro.
DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; ISS:UniProtKB.
DR GO; GO:1900227; P:positive regulation of NLRP3 inflammasome complex assembly; ISS:UniProtKB.
DR GO; GO:0008063; P:Toll signaling pathway; IBA:GO_Central.
DR GO; GO:0034158; P:toll-like receptor 8 signaling pathway; ISS:UniProtKB.
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 Alternative splicing; Cytoplasm; Immunity; Inflammatory response;
KW Innate immunity; Nucleus; Phosphoprotein; Reference proteome;
KW Ubl conjugation.
FT CHAIN 1..296
FT /note="Myeloid differentiation primary response protein
FT MyD88"
FT /id="PRO_0000393129"
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 VAR_SEQ 111..155
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_038889"
FT VAR_SEQ 216..264
FT /note="CRRMVVVVSDEYLQSKECDFQTKFALSLSPGAHQKRLIPIKYKPMKKEF ->
FT LATWPQGKWVGVQSPARDPHAGVLPAGPCLAWHSGILPRLSPGGSPRCL (in
FT isoform 3)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_038890"
FT VAR_SEQ 265..296
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_038891"
SQ SEQUENCE 296 AA; 33709 MW; CA644B4AE7B1D9AA CRC64;
MAEGVPRAGS ALPAASLSSL PLAALNVRVR RRLSLFLNVR APVAADWTVL AEAMDFEYLE
IQQLEKYADP TSRLLDDWQR RPGASVGRLL ELLAKLGRDD VLMELGPSIE EDCQKYILKQ
QQEASEKPLQ VDSIDSSITR INDMAGITIR DDPLGQKPEC FDAFICYCPS DIEFVHEMIR
QLEQTNYRLK LCVSDRDVLP GTCVWSIASE LIEKRCRRMV VVVSDEYLQS KECDFQTKFA
LSLSPGAHQK RLIPIKYKPM KKEFPSILRF ITVCDYTNPC TQNWFWTRLA KALSMP
