Q599T9 (MYD88_BOVIN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Myeloid differentiation primary response protein MyD88

Gene names

Name:

MYD88

Organism

Bos taurus (Bovine) [Reference proteome]

Taxonomic identifier

9913 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Laurasiatheria › Cetartiodactyla › Ruminantia › Pecora › Bovidae › Bovinae › Bos

Protein attributes

Sequence length	296 AA.
Sequence status	Complete.
Protein existence	Evidence 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 By similarity. 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 IL1RL1. Interacts with IL18R1. Interacts with BMX and IRF7 By similarity. Interacts with LRRFIP1 and LRRFIP2; this interaction positively regulates Toll-like receptor (TLR) signaling in response to agonist By similarity. Interacts with FLII By similarity. LRRFIP1 and LRRFIP2 compete with FLII for MYD88-binding By similarity. Interacts with IRF1 By similarity. 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 By similarity. 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 process	Immunity Inflammatory response Innate immunity
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	MyD88-dependent toll-like receptor signaling pathway Inferred from electronic annotation. Source: Compara defense response to Gram-positive bacterium Inferred from electronic annotation. Source: Compara immunoglobulin mediated immune response Inferred from electronic annotation. Source: Compara 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: Compara negative regulation of growth of symbiont in host Inferred from electronic annotation. Source: Compara positive regulation of I-kappaB kinase/NF-kappaB cascade Inferred from electronic annotation. Source: Compara positive regulation of JNK cascade Inferred from electronic annotation. Source: Compara positive regulation of NF-kappaB transcription factor activity Inferred from electronic annotation. Source: Compara positive regulation of chemokine biosynthetic process Inferred from electronic annotation. Source: Compara positive regulation of interleukin-17 production Inferred from electronic annotation. Source: Compara positive regulation of interleukin-23 production Inferred from electronic annotation. Source: Compara positive regulation of interleukin-6 production Inferred from electronic annotation. Source: Compara positive regulation of lymphocyte proliferation Inferred from electronic annotation. Source: Compara positive regulation of tumor necrosis factor production Inferred from electronic annotation. Source: Compara regulation of inflammatory response Inferred from electronic annotation. Source: Compara response to molecule of fungal origin Inferred from electronic annotation. Source: Compara response to peptidoglycan Inferred from electronic annotation. Source: Compara response to virus Inferred from electronic annotation. Source: Compara type I interferon biosynthetic process Inferred from electronic annotation. Source: Compara
Cellular_component	cytosol Inferred from electronic annotation. Source: Compara plasma membrane Inferred from electronic annotation. Source: Compara
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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 296	296	Myeloid differentiation primary response protein MyD88		PRO_0000393129
Regions
	Domain	32 – 109	78	Death
	Domain	159 – 296	138	TIR
	Region	110 – 155	46	Intermediate domain By similarity
Natural variations
	Alternative sequence	111 – 155	45	Missing in isoform 2 and isoform 3.		VSP_038889
	Alternative sequence	216 – 264	49	CRRMV…MKKEF → LATWPQGKWVGVQSPARDPH AGVLPAGPCLAWHSGILPRL SPGGSPRCL in isoform 3.		VSP_038890
	Alternative sequence	265 – 296	32	Missing in isoform 3.		VSP_038891

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified April 26, 2005. Version 1. Checksum: CA644B4AE7B1D9AA	FASTA	296	33,709
	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
	Isoform 2 [UniParc]. Checksum: 1398D566C39E81F8	FASTA	251	28,663
	10 20 30 40 50 60 MAEGVPRAGS ALPAASLSSL PLAALNVRVR RRLSLFLNVR APVAADWTVL AEAMDFEYLE 70 80 90 100 110 120 IQQLEKYADP TSRLLDDWQR RPGASVGRLL ELLAKLGRDD VLMELGPSIE QKPECFDAFI 130 140 150 160 170 180 CYCPSDIEFV HEMIRQLEQT NYRLKLCVSD RDVLPGTCVW SIASELIEKR CRRMVVVVSD 190 200 210 220 230 240 EYLQSKECDF QTKFALSLSP GAHQKRLIPI KYKPMKKEFP SILRFITVCD YTNPCTQNWF 250 WTRLAKALSM P
	Isoform 3 [UniParc]. Checksum: 3ED4B61A6B28242B	FASTA	219	24,228
	10 20 30 40 50 60 MAEGVPRAGS ALPAASLSSL PLAALNVRVR RRLSLFLNVR APVAADWTVL AEAMDFEYLE 70 80 90 100 110 120 IQQLEKYADP TSRLLDDWQR RPGASVGRLL ELLAKLGRDD VLMELGPSIE QKPECFDAFI 130 140 150 160 170 180 CYCPSDIEFV HEMIRQLEQT NYRLKLCVSD RDVLPGTCVW SIASELIEKR LATWPQGKWV 190 200 210 GVQSPARDPH AGVLPAGPCL AWHSGILPRL SPGGSPRCL

References

	« Hide 'large scale' referencesShow '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.
IPI	IPI00687923. IPI00692293. IPI00837619.
RefSeq	NP_001014404.1. NM_001014382.2.
UniGene	Bt.48995.
3D structure databases
ProteinModelPortal	Q599T9.
SMR	Q599T9. Positions 146-296.
ModBase	Search...
Protein-protein interaction databases
STRING	9913.ENSBTAP00000000735.
Proteomic databases
PRIDE	Q599T9.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSBTAT00000000735; ENSBTAP00000000735; ENSBTAG00000000563.
GeneID	444881.
KEGG	bta:444881.
Organism-specific databases
CTD	4615.
Phylogenomic databases
eggNOG	NOG70664.
GeneTree	ENSGT00510000048324.
HOGENOM	HOG000068971.
HOVERGEN	HBG052547.
InParanoid	Q599T9.
KO	K04729.
OMA	RCKRMVV.
OrthoDB	EOG4GXFNH.
Gene expression databases
ArrayExpress	Q599T9.
Family and domain databases
Gene3D	1.10.533.10. 1 hit.
InterPro	IPR011029. DEATH-like_dom. IPR000488. Death_domain. IPR017281. Myelin_different_resp_MyD88. IPR000157. TIR_dom. [Graphical view]
Pfam	PF00531. Death. 1 hit. PF01582. TIR. 1 hit. [Graphical view]
PIRSF	PIRSF037756. MyD88. 1 hit.
SMART	SM00005. DEATH. 1 hit. SM00255. TIR. 1 hit. [Graphical view]
SUPFAM	SSF47986. DEATH_like. 1 hit. SSF52200. TIR. 1 hit.
PROSITE	PS50017. DEATH_DOMAIN. 1 hit. PS50104. TIR. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	20831769.

Entry information

Entry name

MYD88_BOVIN

Accession

Primary (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 29, 2013
This is version 64 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program