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P22366 (MYD88_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 136. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Myeloid differentiation primary response protein MyD88
Gene names
Name:Myd88
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length296 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Isoform 2 is defective in its ability to induce IRAK phosphorylation and NF-kappa-B activation and can function as a negative regulator of activation by IL-1 or lipopolysaccharide (LPS). Activates IRF1 resulting in its rapid migration into the nucleus to mediate an efficient induction of IFN-beta, NOS2/INOS, and IL12A genes. 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. Ref.4 Ref.5 Ref.6 Ref.7 Ref.9 Ref.10 Ref.11 Ref.12

Subunit structure

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. Ref.5 Ref.6 Ref.7 Ref.8 Ref.9 Ref.13

Subcellular location

Cytoplasm Ref.9.

Tissue specificity

Detected in bone marrow. Isoform 1 is expressed in testis, kidney, lung, ovary, adrenal gland, prostate, thymus and heart, and weakly in skeletal muscle, liver, spleen and brain. Isoform 2 is mainly expressed in the spleen and weakly in brain. Ref.1 Ref.4 Ref.5 Ref.7 Ref.12

Induction

By interleukin-6. Ref.4

Domain

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

Disruption phenotype

Mice appear normal, but display loss of activation of NF-kappa-B in response to IL-1 or IL-18. They show no increase in interferon gamma production or in stimulation of natural killer cell activity in response to IL-18. They are impaired in production of cytokines in response to IL-1. They have defects in proinflammatory gene expression and leukocyte recruitment after brain injury. Mice have a diminished capacity to kill L.monocytogenes in the lumen of the distal small intestine and express markedly diminished levels of REG3G. Ref.6 Ref.11 Ref.12

Sequence similarities

Contains 1 death domain.

Contains 1 TIR domain.

Sequence caution

The sequence CAA35762.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
   Biological processImmunity
Inflammatory response
Innate immunity
   Cellular componentCytoplasm
   Coding sequence diversityAlternative splicing
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processJNK cascade

Inferred from electronic annotation. Source: Ensembl

MyD88-dependent toll-like receptor signaling pathway

Inferred from mutant phenotype PubMed 12872135PubMed 14764662. Source: MGI

Toll signaling pathway

Inferred from electronic annotation. Source: Ensembl

cell surface receptor signaling pathway

Inferred from mutant phenotype PubMed 12719478. Source: MGI

cytokine-mediated signaling pathway

Inferred from electronic annotation. Source: Ensembl

defense response to Gram-positive bacterium

Inferred from mutant phenotype Ref.10. Source: UniProtKB

establishment of endothelial intestinal barrier

Inferred from mutant phenotype PubMed 22155109. Source: MGI

immune response

Traceable author statement PubMed 11526399. Source: MGI

immunoglobulin mediated immune response

Inferred from mutant phenotype PubMed 15800576. Source: MGI

inflammatory response

Inferred from electronic annotation. Source: UniProtKB-KW

innate immune response

Inferred from electronic annotation. Source: UniProtKB-KW

lipopolysaccharide-mediated signaling pathway

Inferred from mutant phenotype PubMed 12855817. Source: MGI

negative regulation of growth of symbiont in host

Inferred from mutant phenotype PubMed 11067888. Source: MGI

positive regulation of I-kappaB kinase/NF-kappaB signaling

Inferred from mutant phenotype PubMed 12855817. Source: MGI

positive regulation of JNK cascade

Inferred from mutant phenotype PubMed 12855817. Source: MGI

positive regulation of NF-kappaB transcription factor activity

Inferred from mutant phenotype PubMed 12855817. Source: MGI

positive regulation of chemokine biosynthetic process

Inferred from genetic interaction PubMed 12855817. Source: MGI

positive regulation of interleukin-17 production

Inferred from mutant phenotype PubMed 18203139. Source: BHF-UCL

positive regulation of interleukin-23 production

Inferred from mutant phenotype PubMed 18203139. Source: BHF-UCL

positive regulation of interleukin-6 production

Inferred from mutant phenotype PubMed 18203139. Source: BHF-UCL

positive regulation of lymphocyte proliferation

Inferred from mutant phenotype PubMed 10607756. Source: MGI

positive regulation of smooth muscle cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

positive regulation of tumor necrosis factor production

Inferred from mutant phenotype PubMed 10607756PubMed 11067888PubMed 12719478PubMed 12872135. Source: MGI

regulation of cell proliferation

Inferred from genetic interaction PubMed 17615359. Source: MGI

regulation of inflammatory response

Inferred from mutant phenotype PubMed 18203139. Source: BHF-UCL

response to lipopolysaccharide

Inferred from mutant phenotype PubMed 10607756PubMed 12719478PubMed 12855817PubMed 12872135. Source: MGI

response to molecule of fungal origin

Inferred from mutant phenotype PubMed 12719478. Source: MGI

response to peptidoglycan

Inferred from mutant phenotype PubMed 10607756. Source: MGI

response to virus

Inferred from mutant phenotype PubMed 14993594PubMed 15800576. Source: MGI

transmembrane receptor protein serine/threonine kinase signaling pathway

Traceable author statement PubMed 10465784. Source: MGI

type I interferon biosynthetic process

Inferred from mutant phenotype PubMed 15800576. Source: MGI

   Cellular_componentcytoplasm

Traceable author statement PubMed 10465784. Source: MGI

cytosol

Inferred from direct assay PubMed 16751103. Source: BHF-UCL

plasma membrane

Inferred from direct assay PubMed 16751103. Source: BHF-UCL

postsynaptic density

Inferred from electronic annotation. Source: Ensembl

protein complex

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P22366-1)

Also known as: MyD88L;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Note: Major isoform.
Isoform 2 (identifier: P22366-2)

Also known as: MyD88S;

The sequence of this isoform differs from the canonical sequence as follows:
     110-155: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 296296Myeloid differentiation primary response protein MyD88
PRO_0000096667

Regions

Domain54 – 10956Death
Domain159 – 296138TIR
Region110 – 15546Intermediate domain

Natural variations

Alternative sequence110 – 15546Missing in isoform 2.
VSP_038888

Experimental info

Mutagenesis561F → N: Prevents dimerization of death domains and activation of JNK and NF-kappa-B. Ref.5
Sequence conflict511A → P in AAC53013. Ref.1
Sequence conflict511A → P in CAA35762. Ref.4

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (MyD88L) [UniParc].

Last modified March 27, 2002. Version 3.
Checksum: 393A75C3723FFE69

FASTA29633,753
        10         20         30         40         50         60 
MSAGDPRVGS GSLDSFMFSI PLVALNVGVR RRLSLFLNPR TPVAADWTLL AEEMGFEYLE 

        70         80         90        100        110        120 
IRELETRPDP TRSLLDAWQG RSGASVGRLL ELLALLDRED ILKELKSRIE EDCQKYLGKQ 

       130        140        150        160        170        180 
QNQESEKPLQ VARVESSVPQ TKELGGITTL DDPLGQTPEL FDAFICYCPN DIEFVQEMIR 

       190        200        210        220        230        240 
QLEQTDYRLK LCVSDRDVLP GTCVWSIASE LIEKRCRRMV VVVSDDYLQS KECDFQTKFA 

       250        260        270        280        290 
LSLSPGVQQK RLIPIKYKAM KKDFPSILRF ITICDYTNPC TKSWFWTRLA KALSLP 

« Hide

Isoform 2 (MyD88S) [UniParc].

Checksum: B8A0F358402EBC1E
Show »

FASTA25028,683

References

« Hide 'large scale' references
[1]"The cloning and characterization of human MyD88: a member of an IL-1 receptor related family."
Bonnert T.P., Garka K.E., Parnet P., Sonoda G., Testa J.R., Sims J.E.
FEBS Lett. 402:81-84(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
[2]"Genetic structure and chromosomal mapping of MyD88."
Hardiman G., Jenkins N.A., Copeland N.G., Gilbert D.J., Garcia D.K., Naylor S.L., Kastelein R.A., Bazan J.F.
Genomics 45:332-339(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Tissue: Myeloid leukemia cell.
[3]"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] (ISOFORM 1).
Strain: C57BL/6J.
Tissue: Mammary gland and Olfactory epithelium.
[4]"Nucleotide sequence and expression of a cDNA encoding MyD88, a novel myeloid differentiation primary response gene induced by IL6."
Lord K.A., Hoffman-Liebermann B., Liebermann D.A.
Oncogene 5:1095-1097(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 18-296 (ISOFORM 1), FUNCTION, INDUCTION, TISSUE SPECIFICITY.
[5]"MyD88, an adapter protein involved in interleukin-1 signaling."
Burns K., Martinon F., Esslinger C., Pahl H., Schneider P., Bodmer J.-L., Di Marco F., French L., Tschopp J.
J. Biol. Chem. 273:12203-12209(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBUNIT, TISSUE SPECIFICITY, MUTAGENESIS OF PHE-56.
Tissue: Bone marrow.
[6]"Targeted disruption of the MyD88 gene results in loss of IL-1- and IL-18-mediated function."
Adachi O., Kawai T., Takeda K., Matsumoto M., Tsutsui H., Sakagami M., Nakanishi K., Akira S.
Immunity 9:143-150(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH IL18R1, DISRUPTION PHENOTYPE.
[7]"Regulation of interleukin-1- and lipopolysaccharide-induced NF-kappaB activation by alternative splicing of MyD88."
Janssens S., Burns K., Tschopp J., Beyaert R.
Curr. Biol. 12:467-471(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: ALTERNATIVE SPLICING, IDENTIFICATION OF ISOFORM 2, FUNCTION, SUBUNIT, TISSUE SPECIFICITY.
[8]"Smad6 negatively regulates interleukin 1-receptor-Toll-like receptor signaling through direct interaction with the adaptor Pellino-1."
Choi K.C., Lee Y.S., Lim S., Choi H.K., Lee C.H., Lee E.K., Hong S., Kim I.H., Kim S.J., Park S.H.
Nat. Immunol. 7:1057-1065(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN COMPLEX WITH IRAK1; IRAK4; TRAF6 AND PELI1.
[9]"Evidence for licensing of IFN-gamma-induced IFN regulatory factor 1 transcription factor by MyD88 in Toll-like receptor-dependent gene induction program."
Negishi H., Fujita Y., Yanai H., Sakaguchi S., Ouyang X., Shinohara M., Takayanagi H., Ohba Y., Taniguchi T., Honda K.
Proc. Natl. Acad. Sci. U.S.A. 103:15136-15141(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH IRF1.
[10]"MyD88-mediated signals induce the bactericidal lectin RegIII gamma and protect mice against intestinal Listeria monocytogenes infection."
Brandl K., Plitas G., Schnabl B., DeMatteo R.P., Pamer E.G.
J. Exp. Med. 204:1891-1900(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[11]"Signaling through MyD88 regulates leukocyte recruitment after brain injury."
Babcock A.A., Toft-Hansen H., Owens T.
J. Immunol. 181:6481-6490(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[12]"The antibacterial lectin RegIIIgamma promotes the spatial segregation of microbiota and host in the intestine."
Vaishnava S., Yamamoto M., Severson K.M., Ruhn K.A., Yu X., Koren O., Ley R., Wakeland E.K., Hooper L.V.
Science 334:255-258(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE.
[13]"Role for B-cell adapter for PI3K (BCAP) as a signaling adapter linking Toll-like receptors (TLRs) to serine/threonine kinases PI3K/Akt."
Troutman T.D., Hu W., Fulenchek S., Yamazaki T., Kurosaki T., Bazan J.F., Pasare C.
Proc. Natl. Acad. Sci. U.S.A. 109:273-278(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PIK3AP1.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U84409 mRNA. Translation: AAC53013.1.
U89023 Genomic DNA. Translation: AAB83958.1.
BC005591 mRNA. Translation: AAH05591.1.
BC058787 mRNA. Translation: AAH58787.1.
X51397 mRNA. Translation: CAA35762.1. Different initiation.
PIRS11226.
RefSeqNP_034981.1. NM_010851.2.
UniGeneMm.213003.

3D structure databases

ProteinModelPortalP22366.
SMRP22366. Positions 20-118, 158-296.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid201639. 29 interactions.
DIPDIP-34957N.
IntActP22366. 16 interactions.

PTM databases

PhosphoSiteP22366.

Proteomic databases

PaxDbP22366.
PRIDEP22366.

Protocols and materials databases

DNASU17874.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000035092; ENSMUSP00000035092; ENSMUSG00000032508. [P22366-1]
GeneID17874.
KEGGmmu:17874.
UCSCuc009sar.1. mouse. [P22366-1]

Organism-specific databases

CTD4615.
MGIMGI:108005. Myd88.

Phylogenomic databases

eggNOGNOG70664.
HOGENOMHOG000068971.
HOVERGENHBG052547.
InParanoidP22366.
KOK04729.
OMARCKRMVV.
OrthoDBEOG7H792K.
PhylomeDBP22366.
TreeFamTF326264.

Gene expression databases

ArrayExpressP22366.
BgeeP22366.
CleanExMM_MYD88.
GenevestigatorP22366.

Family and domain databases

Gene3D1.10.533.10. 1 hit.
3.40.50.10140. 1 hit.
InterProIPR011029. DEATH-like_dom.
IPR000488. Death_domain.
IPR017281. Myelin_different_resp_MyD88.
IPR000157. TIR_dom.
[Graphical view]
PfamPF00531. Death. 1 hit.
PF01582. TIR. 1 hit.
[Graphical view]
PIRSFPIRSF037756. MyD88. 1 hit.
SMARTSM00005. DEATH. 1 hit.
SM00255. TIR. 1 hit.
[Graphical view]
SUPFAMSSF47986. SSF47986. 1 hit.
SSF52200. SSF52200. 1 hit.
PROSITEPS50017. DEATH_DOMAIN. 1 hit.
PS50104. TIR. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio292657.
PROP22366.
SOURCESearch...

Entry information

Entry nameMYD88_MOUSE
AccessionPrimary (citable) accession number: P22366
Secondary accession number(s): O35916
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: March 27, 2002
Last modified: April 16, 2014
This is version 136 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot