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Q599T9

- MYD88_BOVIN

UniProt

Q599T9 - MYD88_BOVIN

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Protein

Myeloid differentiation primary response protein MyD88

Gene

MYD88

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

Keywords - Biological processi

Immunity, Inflammatory response, Innate immunity

Enzyme and pathway databases

ReactomeiREACT_207058. TRAF6 mediated NF-kB activation.
REACT_207826. Interleukin-1 signaling.
REACT_210227. TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling.
REACT_215391. RIP-mediated NFkB activation via ZBP1.
REACT_217214. TAK1 activates NFkB by phosphorylation and activation of IKKs complex.
REACT_217527. MyD88 cascade initiated on plasma membrane.
REACT_218091. TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation.
REACT_218986. TRAF6 mediated IRF7 activation.
REACT_219586. MyD88 dependent cascade initiated on endosome.
REACT_227345. MyD88:Mal cascade initiated on plasma membrane.
REACT_227494. p75NTR recruits signalling complexes.

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: Chromosome 22

Subcellular locationi

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. Align

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 .
RefSeqi NP_001014404.1. NM_001014382.2. [Q599T9-1 ]
UniGenei Bt.48995.

3D structure databases

ProteinModelPortali Q599T9.
SMRi Q599T9. Positions 146-296.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

STRINGi 9913.ENSBTAP00000000735.

Proteomic databases

PRIDEi Q599T9.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSBTAT00000000735 ; ENSBTAP00000000735 ; ENSBTAG00000000563 . [Q599T9-1 ]
GeneIDi 444881.
KEGGi bta:444881.

Organism-specific databases

CTDi 4615.

Phylogenomic databases

eggNOGi NOG70664.
GeneTreei ENSGT00510000048324.
HOGENOMi HOG000068971.
HOVERGENi HBG052547.
InParanoidi Q599T9.
KOi K04729.
OMAi RCKRMVV.
OrthoDBi EOG7H792K.
TreeFami TF326264.

Enzyme and pathway databases

Reactomei REACT_207058. TRAF6 mediated NF-kB activation.
REACT_207826. Interleukin-1 signaling.
REACT_210227. TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling.
REACT_215391. RIP-mediated NFkB activation via ZBP1.
REACT_217214. TAK1 activates NFkB by phosphorylation and activation of IKKs complex.
REACT_217527. MyD88 cascade initiated on plasma membrane.
REACT_218091. TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation.
REACT_218986. TRAF6 mediated IRF7 activation.
REACT_219586. MyD88 dependent cascade initiated on endosome.
REACT_227345. MyD88:Mal cascade initiated on plasma membrane.
REACT_227494. p75NTR recruits signalling complexes.

Miscellaneous databases

NextBioi 20831769.

Gene expression databases

ExpressionAtlasi Q599T9. baseline.

Family and domain databases

Gene3Di 1.10.533.10. 1 hit.
3.40.50.10140. 1 hit.
InterProi IPR011029. DEATH-like_dom.
IPR000488. Death_domain.
IPR017281. Myelin_different_resp_MyD88.
IPR000157. TIR_dom.
[Graphical view ]
Pfami PF00531. Death. 1 hit.
PF01582. TIR. 1 hit.
[Graphical view ]
PIRSFi PIRSF037756. MyD88. 1 hit.
SMARTi SM00005. DEATH. 1 hit.
SM00255. TIR. 1 hit.
[Graphical view ]
SUPFAMi SSF47986. SSF47986. 1 hit.
SSF52200. SSF52200. 1 hit.
PROSITEi PS50017. DEATH_DOMAIN. 1 hit.
PS50104. TIR. 1 hit.
[Graphical view ]
ProtoNeti Search...

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: November 26, 2014
This is version 77 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