Reviewed,
UniProtKB/Swiss-Prot Q99836 (MYD88_HUMAN)
Last modified
February 9, 2010.
Version 96.
History...
Clusters with 100%,
90%,
50% identity |
Documents (6) |
Third-party data |
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Names and origin
| Protein names | Recommended name: Myeloid differentiation primary response protein MyD88 | ||
| Gene names |
| ||
| Organism | Homo sapiens (Human) [Complete proteome] | ||
| Taxonomic identifier | 9606 [NCBI] | ||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 296 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence 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 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. Increases IL-8 transcription. May be involved in myeloid differentiation. |
| Subunit structure | Homodimer. Also forms heterodimers with TIRAP. Binds to TLR2, TLR4, IRAK1 and IRAK2 via their respective TIR domains. Interacts with IL1RL1. Ref.6 |
| Subcellular location | Cytoplasm Probable. |
| Tissue specificity | Ubiquitous. |
| Involvement in disease | Defects in MYD88 are the cause of MYD88 deficiency (MYD88D) [MIM:612260]; also known as recurrent pyogenic bacterial infections due to MYD88 deficiency. Patients suffer from autosomal recessive, life-threatening, often recurrent pyogenic bacterial infections, including invasive pneumococcal disease, and die between 1 and 11 months of age. Surviving patients are otherwise healthy, with normal resistance to other microbes, and their clinical status improved with age. Ref.7 |
| Sequence similarities | Contains 1 death domain. Contains 1 TIR domain. |
Ontologies
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| FADD | Q13158 | 1 | EBI-447677,EBI-494804 | |
| IL1RL1 | Q01638 | 1 | EBI-447677,EBI-993762 | |
| IRAK1 | P51617 | 1 | EBI-447677,EBI-358664 | |
| IRAK2 | O43187 | 1 | EBI-447677,EBI-447733 | |
| IRAK3 | Q9Y616 | 1 | EBI-447677,EBI-447690 | |
| STAP2 | Q9UGK3 | 2 | EBI-447677,EBI-1553984 | |
| TIRAP | P58753 | 1 | EBI-447677,EBI-528644 |
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_0000096666 | ||||||||||||||||||||||||||||||||||
Regions | ||||||||||||||||||||||||||||||||||||||
| Domain | 54 – 109 | 56 | Death | |||||||||||||||||||||||||||||||||||
| Domain | 159 – 296 | 138 | TIR | |||||||||||||||||||||||||||||||||||
Natural variations | ||||||||||||||||||||||||||||||||||||||
| Natural variant | 93 | 1 | L → P in MYD88D; results in a loss of function. Ref.7 | VAR_047953 | ||||||||||||||||||||||||||||||||||
| Natural variant | 196 | 1 | R → C in MYD88D; results in a loss of function. Ref.7 | VAR_047954 | ||||||||||||||||||||||||||||||||||
Experimental info | ||||||||||||||||||||||||||||||||||||||
| Sequence conflict | 98 | 1 | R → C in AAB49967. Ref.1 | |||||||||||||||||||||||||||||||||||
Secondary structure | ||||||||||||||||||||||||||||||||||||||
Helix Strand Turn | ||||||||||||||||||||||||||||||||||||||
| Beta strand | 161 – 166 | 6 | ||||||||||||||||||||||||||||||||||||
| Helix | 169 – 171 | 3 | ||||||||||||||||||||||||||||||||||||
| Helix | 172 – 183 | 12 | ||||||||||||||||||||||||||||||||||||
| Beta strand | 185 – 187 | 3 | ||||||||||||||||||||||||||||||||||||
| Beta strand | 192 – 194 | 3 | ||||||||||||||||||||||||||||||||||||
| Beta strand | 197 – 201 | 5 | ||||||||||||||||||||||||||||||||||||
| Helix | 209 – 211 | 3 | ||||||||||||||||||||||||||||||||||||
| Helix | 212 – 215 | 4 | ||||||||||||||||||||||||||||||||||||
| Beta strand | 216 – 222 | 7 | ||||||||||||||||||||||||||||||||||||
| Helix | 225 – 229 | 5 | ||||||||||||||||||||||||||||||||||||
| Helix | 231 – 243 | 13 | ||||||||||||||||||||||||||||||||||||
| Helix | 247 – 250 | 4 | ||||||||||||||||||||||||||||||||||||
| Beta strand | 252 – 258 | 7 | ||||||||||||||||||||||||||||||||||||
| Turn | 266 – 268 | 3 | ||||||||||||||||||||||||||||||||||||
| Turn | 279 – 281 | 3 | ||||||||||||||||||||||||||||||||||||
| Helix | 285 – 294 | 10 | ||||||||||||||||||||||||||||||||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Molecular characterization and modular analysis of human MyD88." Hardiman G., Rock F.L., Balasubramanian S., Kastelein R.A., Bazan J.F. Oncogene 13:2467-2475(1996) [PubMed: 8957090] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Dendritic cell. |
| [2] | "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: 9013863] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Epidermal carcinoma. |
| [3] | "Natural selection in the TLR-related genes in the course of primate evolution." Nakajima T., Ohtani H., Satta Y., Uno Y., Akari H., Ishida T., Kimura A. Immunogenetics 60:727-735(2008) [PubMed: 18810425] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. |
| [4] | "Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. |
| [5] | "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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Pancreas. |
| [6] | "IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST 2 and induces T helper type 2-associated cytokines." Schmitz J., Owyang A., Oldham E., Song Y., Murphy E., McClanahan T.K., Zurawski G., Moshrefi M., Qin J., Li X., Gorman D.M., Bazan J.F., Kastelein R.A. Immunity 23:479-490(2005) [PubMed: 16286016] [Abstract] Cited for: INTERACTION WITH IL1RL1. |
| [7] | "Pyogenic bacterial infections in humans with MyD88 deficiency." von Bernuth H., Picard C., Jin Z., Pankla R., Xiao H., Ku C.-L., Chrabieh M., Mustapha I.B., Ghandil P., Camcioglu Y., Vasconcelos J., Sirvent N., Guedes M., Vitor A.B., Herrero-Mata M.J., Arostegui J.I., Rodrigo C., Alsina L. Casanova J.-L.Science 321:691-696(2008) [PubMed: 18669862] [Abstract] Cited for: VARIANTS MYD88D PRO-93 AND CYS-196, CHARACTERIZATION OF VARIANTS MYD88D PRO-93 AND CYS-196. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| EMBL GenBank DDBJ | U70451 mRNA. Translation: AAB49967.1. U84408 mRNA. Translation: AAC50954.1. AB446470 mRNA. Translation: BAG55247.1. BT007376 mRNA. Translation: AAP36040.1. BC013589 mRNA. Translation: AAH13589.1. | ||||||||||||||||||
| IPI | IPI00796856. | ||||||||||||||||||
| RefSeq | NP_002459.2. | ||||||||||||||||||
| UniGene | Hs.82116 | ||||||||||||||||||
3D structure databases | |||||||||||||||||||
| PDBe RCSB PDB PDBj |
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| SMR | Q99836. Positions 18-117. | ||||||||||||||||||
| ModBase | Search... | ||||||||||||||||||
Protein-protein interaction databases | |||||||||||||||||||
| IntAct | Q99836. 12 interactions. | ||||||||||||||||||
| STRING | Q99836. | ||||||||||||||||||
PTM databases | |||||||||||||||||||
| PhosphoSite | Q99836. | ||||||||||||||||||
Proteomic databases | |||||||||||||||||||
| PRIDE | Q99836. | ||||||||||||||||||
Genome annotation databases | |||||||||||||||||||
| Ensembl | ENST00000396334; ENSP00000379625; ENSG00000172936; Homo sapiens. [Genome view] ENST00000417037; ENSP00000401399; ENSG00000172936; Homo sapiens. [Genome view] | ||||||||||||||||||
| GeneID | 4615. | ||||||||||||||||||
| KEGG | hsa:4615. | ||||||||||||||||||
| UCSC | uc003chw.1. human. | ||||||||||||||||||
Organism-specific databases | |||||||||||||||||||
| CTD | 4615. | ||||||||||||||||||
| GeneCards | GC03P038155. | ||||||||||||||||||
| H-InvDB | HIX0003178. | ||||||||||||||||||
| HGNC | HGNC:7562. MYD88. | ||||||||||||||||||
| HPA | CAB009104. | ||||||||||||||||||
| MIM | 602170. gene. 612260. phenotype. | ||||||||||||||||||
| Orphanet | 183713. Pyogenic bacterial infections due to MyD88 deficiency. | ||||||||||||||||||
| PharmGKB | PA31361. | ||||||||||||||||||
| GenAtlas | Search... | ||||||||||||||||||
Phylogenomic databases | |||||||||||||||||||
| eggNOG | prNOG08701. | ||||||||||||||||||
| HOVERGEN | Q99836. | ||||||||||||||||||
| InParanoid | Q99836. | ||||||||||||||||||
| PhylomeDB | Q99836. | ||||||||||||||||||
Enzyme and pathway databases | |||||||||||||||||||
| Pathway_Interaction_DB | il1pathway. IL1-mediated signaling events. p75ntrpathway. p75(NTR)-mediated signaling. | ||||||||||||||||||
| Reactome | REACT_11061. Signalling by NGF. REACT_6900. Signaling in Immune system. | ||||||||||||||||||
Gene expression databases | |||||||||||||||||||
| ArrayExpress | Q99836. | ||||||||||||||||||
| Bgee | Q99836. | ||||||||||||||||||
| CleanEx | HS_MYD88. | ||||||||||||||||||
| Genevestigator | Q99836. | ||||||||||||||||||
| GermOnline | ENSG00000172936. Homo sapiens. | ||||||||||||||||||
Family and domain databases | |||||||||||||||||||
| InterPro | IPR000488. Death. IPR011029. DEATH-like. IPR017281. Myelin_different_resp_MyD88. IPR000157. Toll-Interleukin_rcpt. [Graphical view] | ||||||||||||||||||
| Gene3D | G3DSA:1.10.533.10. DEATH_like. 1 hit. | ||||||||||||||||||
| 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] | ||||||||||||||||||
| PROSITE | PS50017. DEATH_DOMAIN. 1 hit. PS50104. TIR. 1 hit. [Graphical view] | ||||||||||||||||||
| ProtoNet | Search... | ||||||||||||||||||
Other Resources | |||||||||||||||||||
| NextBio | 17764. | ||||||||||||||||||
| SOURCE | Search... | ||||||||||||||||||
Entry information
| Entry name | MYD88_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q99836 Secondary accession number(s): P78397, Q53XS7 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
| Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. | ||||||||
Relevant documents
| Human chromosome 3 Human chromosome 3: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| PDB cross-references Index of Protein Data Bank (PDB) cross-references |
| SIMILARITY comments Index of protein domains and families |

Clusters with


