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Protein

Myeloid differentiation primary response protein MyD88

Gene

Myd88

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -Experimental evidence at transcript leveli

Functioni

Adapter protein involved in the Toll-like receptor and IL-1 receptor signaling pathway in the innate immune response. Acts via IRAK1, IRAK2, IRF7 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. Increases IL-8 transcription. Involved in IL-18-mediated signaling pathway. Activates IRF1 resulting in its rapid migration into the nucleus to mediate an efficient induction of IFN-beta, NOS2/INOS, and IL12A genes (By similarity). MyD88-mediated signaling in intestinal epithelial cells is crucial for maintenance of gut homeostasis and controls the expression of the antimicrobial lectin REG3G in the small intestine (By similarity).By similarity

GO - Molecular functioni

  • interleukin-1 receptor binding Source: RGD
  • signaling receptor binding Source: RGD
  • TIR domain binding Source: InterPro
  • Toll binding Source: RGD
  • Toll-like receptor binding Source: Ensembl

GO - Biological processi

Keywordsi

Biological processImmunity, Inflammatory response, Innate immunity

Enzyme and pathway databases

ReactomeiR-RNO-1257604 PIP3 activates AKT signaling
R-RNO-1810476 RIP-mediated NFkB activation via ZBP1
R-RNO-209543 p75NTR recruits signalling complexes
R-RNO-3134963 DEx/H-box helicases activate type I IFN and inflammatory cytokines production
R-RNO-445989 TAK1 activates NFkB by phosphorylation and activation of IKKs complex
R-RNO-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-RNO-9020702 Interleukin-1 signaling
R-RNO-933541 TRAF6 mediated IRF7 activation
R-RNO-933542 TRAF6 mediated NF-kB activation
R-RNO-975110 TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling
R-RNO-975138 TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation
R-RNO-975155 MyD88 dependent cascade initiated on endosome

Names & Taxonomyi

Protein namesi
Recommended name:
Myeloid differentiation primary response protein MyD88
Gene namesi
Name:Myd88
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 8

Organism-specific databases

RGDi735043 Myd88

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003931381 – 296Myeloid differentiation primary response protein MyD88Add BLAST296

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei244PhosphoserineBy similarity1

Post-translational modificationi

Ubiquitinated; undergoes 'Lys-63'-linked polyubiquitination. OTUD4 specifically hydrolyzes 'Lys-63'-linked polyubiquitinated MYD88.By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ6Y1S1

Expressioni

Gene expression databases

BgeeiENSRNOG00000013634
GenevisibleiQ6Y1S1 RN

Interactioni

Subunit structurei

Homodimer. Also forms heterodimers with TIRAP. Binds to TLR2, TLR4, IRAK1, IRAK2 and IRAK4 via their respective TIR domains. Interacts with IL18R1. Interacts with BMX, IL1RL1, IKBKE and IRF7. Interacts with LRRFIP1 and LRRFIP2; this interaction positively regulates Toll-like receptor (TLR) signaling in response to agonist. Interacts with FLII. LRRFIP1 and LRRFIP2 compete with FLII for MYD88-binding. Interacts with IRF1. Upon IL1B treatment, forms a complex with PELI1, IRAK1, IRAK4 and TRAF6; this complex recruits MAP3K7/TAK1, TAB1 and TAB2 to mediate NF-kappa-B activation. Direct binding of SMAD6 to PELI1 prevents the complex formation and hence negatively regulates IL1R-TLR signaling and eventually NF-kappa-B-mediated gene expression. May interact with PIK3AP1. Interacts (via TIR domain) with DHX9 (via H2A and OB-fold regions); this interaction is direct. Interacts with OTUD4 deubiquitinase; the interaction is direct.By similarity

GO - Molecular functioni

  • interleukin-1 receptor binding Source: RGD
  • signaling receptor binding Source: RGD
  • TIR domain binding Source: InterPro
  • Toll binding Source: RGD
  • Toll-like receptor binding Source: Ensembl

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000018341

Structurei

3D structure databases

ProteinModelPortaliQ6Y1S1
SMRiQ6Y1S1
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini32 – 109DeathPROSITE-ProRule annotationAdd BLAST78
Domaini159 – 296TIRPROSITE-ProRule annotationAdd BLAST138

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni110 – 155Intermediate domainBy similarityAdd BLAST46

Domaini

The intermediate domain (ID) is required for the phosphorylation and activation of IRAK.By similarity

Phylogenomic databases

eggNOGiENOG410IIN8 Eukaryota
ENOG410ZIY0 LUCA
GeneTreeiENSGT00510000048324
HOGENOMiHOG000068971
HOVERGENiHBG052547
InParanoidiQ6Y1S1
KOiK04729
OMAiRCKRMVV
OrthoDBiEOG091G0NDI
PhylomeDBiQ6Y1S1
TreeFamiTF326264

Family and domain databases

CDDicd08312 Death_MyD88, 1 hit
Gene3Di3.40.50.10140, 1 hit
InterProiView protein in InterPro
IPR011029 DEATH-like_dom_sf
IPR000488 Death_domain
IPR034249 MyD88_Death
IPR017281 Myelin_different_resp_MyD88
IPR000157 TIR_dom
IPR035897 Toll_tir_struct_dom_sf
PANTHERiPTHR15079 PTHR15079, 1 hit
PfamiView protein in Pfam
PF00531 Death, 1 hit
PF01582 TIR, 1 hit
PIRSFiPIRSF037756 MyD88, 1 hit
SMARTiView protein in SMART
SM00005 DEATH, 1 hit
SM00255 TIR, 1 hit
SUPFAMiSSF47986 SSF47986, 1 hit
SSF52200 SSF52200, 1 hit
PROSITEiView protein in PROSITE
PS50017 DEATH_DOMAIN, 1 hit
PS50104 TIR, 1 hit

Sequencei

Sequence statusi: Complete.

Q6Y1S1-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSAGGPRVGS VSVDSYLFSL PLVALNVGVR RRLSLFLNPR TTAAADWTSL
60 70 80 90 100
AEEMGFEYLE IREFETRPDP TRSLLDAWQG RSGSSVGRLL ELLALLDRED
110 120 130 140 150
ILYELKDRIE EDCQKYIRNQ QKQESEKPLQ VARVESSVPQ TKELGGITTL
160 170 180 190 200
DDPLGQTPEL FDAFICYCPS DIEFVQEMIR QLEQTDYRLK LCVSDRDVLP
210 220 230 240 250
GTCVWSIASE LIEKRCRRMV VVVSDDYLQS KECDFQTKFA LSLSPGVQQK
260 270 280 290
RLIPIKYKAM KKDFPSILRF ITICDYTNPC TKSWFWTRLA KALSLP
Length:296
Mass (Da):33,856
Last modified:March 23, 2010 - v2
Checksum:i6B84304BF7EDB010
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti170S → N in AAO91937 (Ref. 1) Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY191270 mRNA Translation: AAO91937.1
BC097266 mRNA Translation: AAH97266.1
RefSeqiNP_937763.1, NM_198130.1
XP_006244149.1, XM_006244087.3
UniGeneiRn.37341

Genome annotation databases

EnsembliENSRNOT00000018341; ENSRNOP00000018341; ENSRNOG00000013634
GeneIDi301059
KEGGirno:301059
UCSCiRGD:735043 rat

Similar proteinsi

Entry informationi

Entry nameiMYD88_RAT
AccessioniPrimary (citable) accession number: Q6Y1S1
Secondary accession number(s): Q4QRC0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 23, 2010
Last sequence update: March 23, 2010
Last modified: June 20, 2018
This is version 107 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

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