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Protein

Myeloid differentiation primary response protein MyD88

Gene

MYD88

Organism
Bos taurus (Bovine)
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 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.2 Publications

GO - Biological processi

  1. defense response to Gram-positive bacterium Source: UniProtKB
  2. establishment of endothelial intestinal barrier Source: Ensembl
  3. immunoglobulin mediated immune response Source: Ensembl
  4. inflammatory response Source: UniProtKB-KW
  5. innate immune response Source: UniProtKB-KW
  6. lipopolysaccharide-mediated signaling pathway Source: Ensembl
  7. MyD88-dependent toll-like receptor signaling pathway Source: Ensembl
  8. negative regulation of growth of symbiont in host Source: Ensembl
  9. positive regulation of chemokine biosynthetic process Source: Ensembl
  10. positive regulation of I-kappaB kinase/NF-kappaB signaling Source: Ensembl
  11. positive regulation of interleukin-17 production Source: Ensembl
  12. positive regulation of interleukin-23 production Source: Ensembl
  13. positive regulation of interleukin-6 production Source: Ensembl
  14. positive regulation of JNK cascade Source: Ensembl
  15. positive regulation of lymphocyte proliferation Source: Ensembl
  16. positive regulation of NF-kappaB transcription factor activity Source: Ensembl
  17. positive regulation of tumor necrosis factor production Source: Ensembl
  18. regulation of inflammatory response Source: Ensembl
  19. response to molecule of fungal origin Source: Ensembl
  20. response to peptidoglycan Source: Ensembl
  21. response to virus Source: Ensembl
  22. type I interferon biosynthetic process Source: Ensembl
Complete GO annotation...

Keywords - Biological processi

Immunity, Inflammatory response, Innate immunity

Enzyme and pathway databases

ReactomeiREACT_275029. TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation.
REACT_276127. DEx/H-box helicases activate type I IFN and inflammatory cytokines production.
REACT_286248. TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling.
REACT_291180. MyD88 dependent cascade initiated on endosome.
REACT_294285. TAK1 activates NFkB by phosphorylation and activation of IKKs complex.
REACT_297578. p75NTR recruits signalling complexes.
REACT_305366. MyD88:Mal cascade initiated on plasma membrane.
REACT_313765. TRAF6 mediated NF-kB activation.
REACT_321905. Interleukin-1 signaling.
REACT_328076. RIP-mediated NFkB activation via ZBP1.
REACT_341758. TRAF6 mediated IRF7 activation.
REACT_351415. MyD88 cascade initiated on plasma membrane.

Names & Taxonomyi

Protein namesi
Recommended name:
Myeloid differentiation primary response protein MyD88
Gene namesi
Name:MYD88
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
ProteomesiUP000009136 Componenti: Chromosome 22

Subcellular locationi

  1. Cytoplasm By similarity

GO - Cellular componenti

  1. cytosol Source: Ensembl
  2. plasma membrane Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 296296Myeloid differentiation primary response protein MyD88PRO_0000393129Add
BLAST

Proteomic databases

PRIDEiQ599T9.

Expressioni

Gene expression databases

ExpressionAtlasiQ599T9. baseline.

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

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000000735.

Structurei

3D structure databases

ProteinModelPortaliQ599T9.
SMRiQ599T9. 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

eggNOGiNOG70664.
GeneTreeiENSGT00510000048324.
HOGENOMiHOG000068971.
HOVERGENiHBG052547.
InParanoidiQ599T9.
KOiK04729.
OMAiRCKRMVV.
OrthoDBiEOG7H792K.
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]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q599T9-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MAEGVPRAGS ALPAASLSSL PLAALNVRVR RRLSLFLNVR APVAADWTVL
60 70 80 90 100
AEAMDFEYLE IQQLEKYADP TSRLLDDWQR RPGASVGRLL ELLAKLGRDD
110 120 130 140 150
VLMELGPSIE EDCQKYILKQ QQEASEKPLQ VDSIDSSITR INDMAGITIR
160 170 180 190 200
DDPLGQKPEC FDAFICYCPS DIEFVHEMIR QLEQTNYRLK LCVSDRDVLP
210 220 230 240 250
GTCVWSIASE LIEKRCRRMV VVVSDEYLQS KECDFQTKFA LSLSPGAHQK
260 270 280 290
RLIPIKYKPM KKEFPSILRF ITVCDYTNPC TQNWFWTRLA KALSMP
Length:296
Mass (Da):33,709
Last modified:April 26, 2005 - v1
Checksum:iCA644B4AE7B1D9AA
GO
Isoform 2 (identifier: Q599T9-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     111-155: Missing.

Show »
Length:251
Mass (Da):28,663
Checksum:i1398D566C39E81F8
GO
Isoform 3 (identifier: Q599T9-3) [UniParc]FASTAAdd to basket

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

Show »
Length:219
Mass (Da):24,228
Checksum:i3ED4B61A6B28242B
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei111 – 15545Missing in isoform 2 and isoform 3. 1 PublicationVSP_038889Add
BLAST
Alternative sequencei216 – 26449CRRMV…MKKEF → LATWPQGKWVGVQSPARDPH AGVLPAGPCLAWHSGILPRL SPGGSPRCL in isoform 3. 1 PublicationVSP_038890Add
BLAST
Alternative sequencei265 – 29632Missing in isoform 3. 1 PublicationVSP_038891Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
RefSeqiNP_001014404.1. NM_001014382.2. [Q599T9-1]
UniGeneiBt.48995.

Genome annotation databases

EnsembliENSBTAT00000000735; ENSBTAP00000000735; ENSBTAG00000000563. [Q599T9-1]
GeneIDi444881.
KEGGibta:444881.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
RefSeqiNP_001014404.1. NM_001014382.2. [Q599T9-1]
UniGeneiBt.48995.

3D structure databases

ProteinModelPortaliQ599T9.
SMRiQ599T9. Positions 146-296.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000000735.

Proteomic databases

PRIDEiQ599T9.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSBTAT00000000735; ENSBTAP00000000735; ENSBTAG00000000563. [Q599T9-1]
GeneIDi444881.
KEGGibta:444881.

Organism-specific databases

CTDi4615.

Phylogenomic databases

eggNOGiNOG70664.
GeneTreeiENSGT00510000048324.
HOGENOMiHOG000068971.
HOVERGENiHBG052547.
InParanoidiQ599T9.
KOiK04729.
OMAiRCKRMVV.
OrthoDBiEOG7H792K.
TreeFamiTF326264.

Enzyme and pathway databases

ReactomeiREACT_275029. TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation.
REACT_276127. DEx/H-box helicases activate type I IFN and inflammatory cytokines production.
REACT_286248. TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling.
REACT_291180. MyD88 dependent cascade initiated on endosome.
REACT_294285. TAK1 activates NFkB by phosphorylation and activation of IKKs complex.
REACT_297578. p75NTR recruits signalling complexes.
REACT_305366. MyD88:Mal cascade initiated on plasma membrane.
REACT_313765. TRAF6 mediated NF-kB activation.
REACT_321905. Interleukin-1 signaling.
REACT_328076. RIP-mediated NFkB activation via ZBP1.
REACT_341758. TRAF6 mediated IRF7 activation.
REACT_351415. MyD88 cascade initiated on plasma membrane.

Miscellaneous databases

NextBioi20831769.

Gene expression databases

ExpressionAtlasiQ599T9. baseline.

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. "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.

Entry informationi

Entry nameiMYD88_BOVIN
AccessioniPrimary (citable) accession number: Q599T9
Secondary accession number(s): Q49BZ6, Q49CF6, Q6GV22
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 23, 2010
Last sequence update: April 26, 2005
Last modified: April 1, 2015
This is version 80 of the entry and version 1 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

External Data

Dasty 3

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 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.