MYD88_MACFA
ID MYD88_MACFA Reviewed; 296 AA.
AC B3Y682;
DT 23-MAR-2010, integrated into UniProtKB/Swiss-Prot.
DT 23-SEP-2008, sequence version 1.
DT 03-AUG-2022, entry version 53.
DE RecName: Full=Myeloid differentiation primary response protein MyD88;
GN Name=MYD88;
OS Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9541;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=18810425; DOI=10.1007/s00251-008-0332-0;
RA Nakajima T., Ohtani H., Satta Y., Uno Y., Akari H., Ishida T., Kimura A.;
RT "Natural selection in the TLR-related genes in the course of primate
RT evolution.";
RL Immunogenetics 60:727-735(2008).
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; AB446475; BAG55252.1; -; mRNA.
DR AlphaFoldDB; B3Y682; -.
DR BMRB; B3Y682; -.
DR SMR; B3Y682; -.
DR STRING; 9541.XP_005546717.1; -.
DR eggNOG; ENOG502QWKI; Eukaryota.
DR Proteomes; UP000233100; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0070976; F:TIR domain binding; IEA:InterPro.
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; IEA:UniProtKB-KW.
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: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 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_0000393132"
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"
SQ SEQUENCE 296 AA; 33354 MW; B8481293C66E756E CRC64;
MAAGGPGTEP AAPVSSTSSL PLAALNMRVR RRLSLFLNVR TQVAADWTAL AEEMDFEYLE
IRQLETHADP TGRLLDAWQG RPGASVGRLL ELLTKLGRDD VLLELGPSIE EDCQKYILKQ
QQEEAEKPLQ VAAVDSSVPR TAELAGITTL DDPLGHMPER FDAFICYCPS DIQFVQEMIR
QLEQTNYRLK LCVSDRDVLP GTCVWSIASE LIEKRCRRMV VVVSDDYLQS KECDFQTKFA
LSLSPGAHQK RLIPIKYKAM KKEFPSILRF ITVCDYTNPC TKSWFWTRLA KALSLP
