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Protein

Myeloid differentiation primary response protein MyD88

Gene

Myd88

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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
  • receptor binding Source: RGD
  • Toll binding Source: RGD

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Immunity, Inflammatory response, Innate immunity

Enzyme and pathway databases

ReactomeiR-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-446652. 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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 8

Organism-specific databases

RGDi735043. Myd88.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: Reactome
  • plasma membrane Source: Ensembl
  • postsynaptic density Source: RGD
  • protein complex Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 296296Myeloid differentiation primary response protein MyD88PRO_0000393138Add
BLAST

Proteomic databases

PaxDbiQ6Y1S1.

Expressioni

Gene expression databases

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 (By similarity).By similarity

GO - Molecular functioni

  • interleukin-1 receptor binding Source: RGD
  • receptor binding Source: RGD
  • Toll binding Source: RGD

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000018341.

Structurei

3D structure databases

ProteinModelPortaliQ6Y1S1.
SMRiQ6Y1S1. Positions 146-296.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini32 – 10978DeathPROSITE-ProRule annotationAdd
BLAST
Domaini159 – 296138TIRPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni110 – 15546Intermediate domainBy similarityAdd
BLAST

Domaini

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

Sequence similaritiesi

Contains 1 death domain.PROSITE-ProRule annotation
Contains 1 TIR domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiENOG410IIN8. Eukaryota.
ENOG410ZIY0. LUCA.
GeneTreeiENSGT00510000048324.
HOGENOMiHOG000068971.
HOVERGENiHBG052547.
InParanoidiQ6Y1S1.
KOiK04729.
OMAiRCKRMVV.
OrthoDBiEOG7H792K.
PhylomeDBiQ6Y1S1.
TreeFamiTF326264.

Family and domain databases

Gene3Di1.10.533.10. 1 hit.
3.40.50.10140. 1 hit.
InterProiIPR011029. DEATH-like_dom.
IPR000488. Death_domain.
IPR017281. Myelin_different_resp_MyD88.
IPR000157. TIR_dom.
[Graphical view]
PfamiPF00531. Death. 1 hit.
PF01582. TIR. 1 hit.
[Graphical view]
PIRSFiPIRSF037756. MyD88. 1 hit.
SMARTiSM00005. DEATH. 1 hit.
SM00255. TIR. 1 hit.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 1 hit.
SSF52200. SSF52200. 1 hit.
PROSITEiPS50017. DEATH_DOMAIN. 1 hit.
PS50104. TIR. 1 hit.
[Graphical view]

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti170 – 1701S → N in AAO91937 (Ref. 1) Curated

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_006244087.2.
UniGeneiRn.37341.

Genome annotation databases

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

Cross-referencesi

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_006244087.2.
UniGeneiRn.37341.

3D structure databases

ProteinModelPortaliQ6Y1S1.
SMRiQ6Y1S1. Positions 146-296.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000018341.

Proteomic databases

PaxDbiQ6Y1S1.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi4615.
RGDi735043. Myd88.

Phylogenomic databases

eggNOGiENOG410IIN8. Eukaryota.
ENOG410ZIY0. LUCA.
GeneTreeiENSGT00510000048324.
HOGENOMiHOG000068971.
HOVERGENiHBG052547.
InParanoidiQ6Y1S1.
KOiK04729.
OMAiRCKRMVV.
OrthoDBiEOG7H792K.
PhylomeDBiQ6Y1S1.
TreeFamiTF326264.

Enzyme and pathway databases

ReactomeiR-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-446652. 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.

Miscellaneous databases

PROiQ6Y1S1.

Gene expression databases

GenevisibleiQ6Y1S1. RN.

Family and domain databases

Gene3Di1.10.533.10. 1 hit.
3.40.50.10140. 1 hit.
InterProiIPR011029. DEATH-like_dom.
IPR000488. Death_domain.
IPR017281. Myelin_different_resp_MyD88.
IPR000157. TIR_dom.
[Graphical view]
PfamiPF00531. Death. 1 hit.
PF01582. TIR. 1 hit.
[Graphical view]
PIRSFiPIRSF037756. MyD88. 1 hit.
SMARTiSM00005. DEATH. 1 hit.
SM00255. TIR. 1 hit.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 1 hit.
SSF52200. SSF52200. 1 hit.
PROSITEiPS50017. DEATH_DOMAIN. 1 hit.
PS50104. TIR. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Molecular cloning and regulation of MyD88 mRNA in rat spleen."
    Li Y., Ji A., Schafer M.K.
    Submitted (DEC-2002) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: Wistar.
    Tissue: Spleen.
  2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Placenta.

Entry informationi

Entry nameiMYD88_RAT
AccessioniPrimary (citable) accession number: Q6Y1S1
Secondary accession number(s): Q4QRC0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 23, 2010
Last sequence update: March 23, 2010
Last modified: June 8, 2016
This is version 91 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.