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Q599T9 (MYD88_BOVIN) Reviewed, UniProtKB/Swiss-Prot

Last modified May 14, 2014. Version 73. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·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
OrganismBos taurus (Bovine) [Reference proteome]
Taxonomic identifier9913 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos

Protein attributes

Sequence length296 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript 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 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. 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.1 Ref.5

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 By similarity.

Subcellular location

Cytoplasm By similarity.

Domain

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

Sequence similarities

Contains 1 death domain.

Contains 1 TIR domain.

Ontologies

Keywords
   Biological processImmunity
Inflammatory response
Innate immunity
   Cellular componentCytoplasm
   Coding sequence diversityAlternative splicing
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processMyD88-dependent toll-like receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

defense response to Gram-positive bacterium

Inferred from sequence or structural similarity. Source: UniProtKB

immunoglobulin mediated immune response

Inferred from electronic annotation. Source: Ensembl

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 electronic annotation. Source: Ensembl

negative regulation of growth of symbiont in host

Inferred from electronic annotation. Source: Ensembl

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

Inferred from electronic annotation. Source: Ensembl

positive regulation of JNK cascade

Inferred from electronic annotation. Source: Ensembl

positive regulation of NF-kappaB transcription factor activity

Inferred from electronic annotation. Source: Ensembl

positive regulation of chemokine biosynthetic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of interleukin-17 production

Inferred from electronic annotation. Source: Ensembl

positive regulation of interleukin-23 production

Inferred from electronic annotation. Source: Ensembl

positive regulation of interleukin-6 production

Inferred from electronic annotation. Source: Ensembl

positive regulation of lymphocyte proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of tumor necrosis factor production

Inferred from electronic annotation. Source: Ensembl

regulation of inflammatory response

Inferred from electronic annotation. Source: Ensembl

response to molecule of fungal origin

Inferred from electronic annotation. Source: Ensembl

response to peptidoglycan

Inferred from electronic annotation. Source: Ensembl

response to virus

Inferred from electronic annotation. Source: Ensembl

type I interferon biosynthetic process

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcytosol

Inferred from electronic annotation. Source: Ensembl

plasma membrane

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q599T9-1)

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.
Isoform 2 (identifier: Q599T9-2)

The sequence of this isoform differs from the canonical sequence as follows:
     111-155: Missing.
Isoform 3 (identifier: Q599T9-3)

The sequence of this isoform differs from the canonical sequence as follows:
     111-155: Missing.
     216-264: CRRMVVVVSD...IKYKPMKKEF → LATWPQGKWV...LSPGGSPRCL
     265-296: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 296296Myeloid differentiation primary response protein MyD88
PRO_0000393129

Regions

Domain32 – 10978Death
Domain159 – 296138TIR
Region110 – 15546Intermediate domain By similarity

Natural variations

Alternative sequence111 – 15545Missing in isoform 2 and isoform 3.
VSP_038889
Alternative sequence216 – 26449CRRMV…MKKEF → LATWPQGKWVGVQSPARDPH AGVLPAGPCLAWHSGILPRL SPGGSPRCL in isoform 3.
VSP_038890
Alternative sequence265 – 29632Missing in isoform 3.
VSP_038891

Sequences

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

Last modified April 26, 2005. Version 1.
Checksum: CA644B4AE7B1D9AA

FASTA29633,709
        10         20         30         40         50         60 
MAEGVPRAGS ALPAASLSSL PLAALNVRVR RRLSLFLNVR APVAADWTVL AEAMDFEYLE 

        70         80         90        100        110        120 
IQQLEKYADP TSRLLDDWQR RPGASVGRLL ELLAKLGRDD VLMELGPSIE EDCQKYILKQ 

       130        140        150        160        170        180 
QQEASEKPLQ VDSIDSSITR INDMAGITIR DDPLGQKPEC FDAFICYCPS DIEFVHEMIR 

       190        200        210        220        230        240 
QLEQTNYRLK LCVSDRDVLP GTCVWSIASE LIEKRCRRMV VVVSDEYLQS KECDFQTKFA 

       250        260        270        280        290 
LSLSPGAHQK RLIPIKYKPM KKEFPSILRF ITVCDYTNPC TQNWFWTRLA KALSMP 

« Hide

Isoform 2 [UniParc].

Checksum: 1398D566C39E81F8
Show »

FASTA25128,663
Isoform 3 [UniParc].

Checksum: 3ED4B61A6B28242B
Show »

FASTA21924,228

References

« Hide 'large scale' references
[1]"Bovine TLR2 and TLR4 properly transduce signals from Staphylococcus aureus and E. coli, but S. aureus fails to both activate NF-kappaB in mammary epithelial cells and to quickly induce TNFalpha and interleukin-8 (CXCL8) expression in the udder."
Yang W., Zerbe H., Petzl W., Brunner R.M., Gunther J., Draing C., von Aulock S., Schuberth H.J., Seyfert H.M.
Mol. Immunol. 45:1385-1397(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION.
Tissue: Mammary gland.
[2]"Regulation of TLR-mediated NFkB activation by alternative splicing of bovine MyD88."
Bailey R., Yamakawa Y., Stalker A., Willcocks S., Werling D.
Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3).
[3]NIH - Mammalian Gene Collection (MGC) project
Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Strain: Crossbred X Angus.
Tissue: Ileum.
[4]"Expression of TOLL-like receptors (TLR) by bovine antigen-presenting cells-potential role in pathogen discrimination?"
Werling D., Piercy J., Coffey T.J.
Vet. Immunol. Immunopathol. 112:2-11(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 206-296 (ISOFORMS 1/2).
[5]"Functional characterization of bovine TIRAP and MyD88 in mediating bacterial lipopolysaccharide-induced endothelial NF-kappaB activation and apoptosis."
Cates E.A., Connor E.E., Mosser D.M., Bannerman D.D.
Comp. Immunol. Microbiol. Infect. Dis. 32:477-490(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AJ853453 mRNA. Translation: CAH68521.1.
AY934808 mRNA. Translation: AAY16578.1.
AY937381 mRNA. Translation: AAY22119.1.
BC102851 mRNA. Translation: AAI02852.1.
AY634627 mRNA. Translation: AAT48485.1.
RefSeqNP_001014404.1. NM_001014382.2. [Q599T9-1]
UniGeneBt.48995.

3D structure databases

ProteinModelPortalQ599T9.
SMRQ599T9. Positions 146-296.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9913.ENSBTAP00000000735.

Proteomic databases

PRIDEQ599T9.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSBTAT00000000735; ENSBTAP00000000735; ENSBTAG00000000563. [Q599T9-1]
GeneID444881.
KEGGbta:444881.

Organism-specific databases

CTD4615.

Phylogenomic databases

eggNOGNOG70664.
GeneTreeENSGT00510000048324.
HOGENOMHOG000068971.
HOVERGENHBG052547.
InParanoidQ599T9.
KOK04729.
OMARCKRMVV.
OrthoDBEOG7H792K.
TreeFamTF326264.

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

NextBio20831769.

Entry information

Entry nameMYD88_BOVIN
AccessionPrimary (citable) accession number: Q599T9
Secondary accession number(s): Q49BZ6, Q49CF6, Q6GV22
Entry history
Integrated into UniProtKB/Swiss-Prot: March 23, 2010
Last sequence update: April 26, 2005
Last modified: May 14, 2014
This is version 73 of the entry and version 1 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