Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Myeloid differentiation primary response protein MyD88

Gene

MYD88

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Adapter protein involved in the Toll-like receptor and IL-1 receptor signaling pathway in the innate immune response (PubMed:15361868, PubMed:18292575). Acts via IRAK1, IRAK2, IRF7 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response (PubMed:15361868, PubMed:24316379, PubMed:19506249). Increases IL-8 transcription (PubMed:9013863). 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 (By similarity).By similarity5 Publications

GO - Molecular functioni

  • death receptor binding Source: ProtInc
  • identical protein binding Source: IntAct
  • protein self-association Source: AgBase
  • TIR domain binding Source: BHF-UCL

GO - Biological processi

Keywordsi

Biological processImmunity, Inflammatory response, Innate immunity

Enzyme and pathway databases

ReactomeiR-HSA-1236974 ER-Phagosome pathway
R-HSA-1257604 PIP3 activates AKT signaling
R-HSA-166058 MyD88:Mal cascade initiated on plasma membrane
R-HSA-1810476 RIP-mediated NFkB activation via ZBP1
R-HSA-209543 p75NTR recruits signalling complexes
R-HSA-3134963 DEx/H-box helicases activate type I IFN and inflammatory cytokines production
R-HSA-445989 TAK1 activates NFkB by phosphorylation and activation of IKKs complex
R-HSA-5602498 MyD88 deficiency (TLR2/4)
R-HSA-5602680 MyD88 deficiency (TLR5)
R-HSA-5603037 IRAK4 deficiency (TLR5)
R-HSA-5603041 IRAK4 deficiency (TLR2/4)
R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-HSA-9020702 Interleukin-1 signaling
R-HSA-933541 TRAF6 mediated IRF7 activation
R-HSA-933542 TRAF6 mediated NF-kB activation
R-HSA-975110 TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling
R-HSA-975138 TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation
R-HSA-975155 MyD88 dependent cascade initiated on endosome
R-HSA-975871 MyD88 cascade initiated on plasma membrane
SignaLinkiQ99836
SIGNORiQ99836

Names & Taxonomyi

Protein namesi
Recommended name:
Myeloid differentiation primary response protein MyD88
Gene namesi
Name:MYD88Imported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

EuPathDBiHostDB:ENSG00000172936.12
HGNCiHGNC:7562 MYD88
MIMi602170 gene
neXtProtiNX_Q99836

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

MYD88 deficiency (MYD88D)4 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionPatients 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.
See also OMIM:612260
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07289452Missing in MYD88D; loss of NF-kappa-B complex activation. 2 Publications1
Natural variantiVAR_04795393L → P in MYD88D; results in a loss of function; loss of NF-kappa-B complex activation. 3 Publications1
Natural variantiVAR_047954196R → C in MYD88D; results in a loss of function; decreases NF-kappa-B complex activation. 4 Publications1
Defects in MYD88 are frequently found in many hematological malignancies, such as activated B-cell type diffuse large B-cell lymphoma (ABC-DLBCL), Waldenstroem's macroglobulinemia, cutaneous diffuse large B cell lymphoma (CBCL) and primary central nervous system lymphoma (PCNSL).2 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi196R → A: Reduced interaction with TIRAP, and strongly reduced activity. Strongly reduced interaction with TIRAP; when associated with A-288. 1 Publication1
Mutagenesisi197D → A: Slightly reduced activity. 1 Publication1
Mutagenesisi217R → A: Strongly reduced activity. 1 Publication1
Mutagenesisi282K → A: Slightly reduced activity. 1 Publication1
Mutagenesisi288R → A: Slightly reduced activity, and reduced interaction with TIRAP. Strongly reduced interaction with TIRAP; when associated with A-196. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi4615
MalaCardsiMYD88
MIMi612260 phenotype
Orphaneti183713 Pyogenic bacterial infections due to MyD88 deficiency
33226 Waldenstrom macroglobulinemia
PharmGKBiPA31361

Chemistry databases

ChEMBLiCHEMBL5919

Polymorphism and mutation databases

BioMutaiMYD88
DMDMi18202671

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000966661 – 296Myeloid differentiation primary response protein MyD88Add BLAST296

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei244PhosphoserineCombined sources1

Post-translational modificationi

Ubiquitinated; undergoes 'Lys-63'-linked polyubiquitination. OTUD4 specifically hydrolyzes 'Lys-63'-linked polyubiquitinated MYD88.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ99836
MaxQBiQ99836
PaxDbiQ99836
PeptideAtlasiQ99836
PRIDEiQ99836
ProteomicsDBi78500
78501 [Q99836-2]
78502 [Q99836-3]
78503 [Q99836-4]
TopDownProteomicsiQ99836-4 [Q99836-4]

PTM databases

iPTMnetiQ99836
PhosphoSitePlusiQ99836

Expressioni

Tissue specificityi

Ubiquitous.1 Publication

Gene expression databases

BgeeiENSG00000172936
CleanExiHS_MYD88
ExpressionAtlasiQ99836 baseline and differential

Organism-specific databases

HPAiCAB009104

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. Interacts (via TIR domain) with DHX9 (via H2A and OB-fold regions); this interaction is direct (PubMed:20696886). Interacts with OTUD4 deubiquitinase; the interaction is direct (PubMed:29395066).14 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • death receptor binding Source: ProtInc
  • identical protein binding Source: IntAct
  • protein self-association Source: AgBase
  • TIR domain binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi110700, 60 interactors
DIPiDIP-31349N
IntActiQ99836, 45 interactors
MINTiQ99836
STRINGi9606.ENSP00000401399

Structurei

Secondary structure

1296
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi22 – 24Combined sources3
Helixi27 – 37Combined sources11
Beta strandi42 – 44Combined sources3
Helixi47 – 51Combined sources5
Turni52 – 55Combined sources4
Helixi58 – 64Combined sources7
Beta strandi66 – 69Combined sources4
Helixi70 – 79Combined sources10
Beta strandi80 – 83Combined sources4
Helixi86 – 96Combined sources11
Helixi99 – 102Combined sources4
Helixi106 – 112Combined sources7
Turni114 – 116Combined sources3
Beta strandi159 – 166Combined sources8
Helixi169 – 171Combined sources3
Helixi172 – 183Combined sources12
Beta strandi185 – 187Combined sources3
Beta strandi191 – 194Combined sources4
Helixi196 – 198Combined sources3
Helixi209 – 211Combined sources3
Helixi212 – 215Combined sources4
Beta strandi216 – 223Combined sources8
Helixi227 – 229Combined sources3
Helixi231 – 242Combined sources12
Helixi247 – 251Combined sources5
Beta strandi252 – 256Combined sources5
Helixi266 – 268Combined sources3
Beta strandi269 – 271Combined sources3
Helixi279 – 281Combined sources3
Helixi285 – 294Combined sources10

3D structure databases

ProteinModelPortaliQ99836
SMRiQ99836
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ99836

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini54 – 109DeathPROSITE-ProRule annotationAdd BLAST56
Domaini159 – 296TIRPROSITE-ProRule annotationAdd BLAST138

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni110 – 155Intermediate domainBy similarityAdd BLAST46

Domaini

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

Phylogenomic databases

eggNOGiENOG410IIN8 Eukaryota
ENOG410ZIY0 LUCA
HOGENOMiHOG000068971
HOVERGENiHBG052547
InParanoidiQ99836
KOiK04729
PhylomeDBiQ99836

Family and domain databases

CDDicd08312 Death_MyD88, 1 hit
Gene3Di3.40.50.10140, 1 hit
InterProiView protein in InterPro
IPR011029 DEATH-like_dom_sf
IPR000488 Death_domain
IPR034249 MyD88_Death
IPR017281 Myelin_different_resp_MyD88
IPR000157 TIR_dom
IPR035897 Toll_tir_struct_dom_sf
PANTHERiPTHR15079 PTHR15079, 1 hit
PfamiView protein in Pfam
PF00531 Death, 1 hit
PF01582 TIR, 1 hit
PIRSFiPIRSF037756 MyD88, 1 hit
SMARTiView protein in SMART
SM00005 DEATH, 1 hit
SM00255 TIR, 1 hit
SUPFAMiSSF47986 SSF47986, 1 hit
SSF52200 SSF52200, 1 hit
PROSITEiView protein in PROSITE
PS50017 DEATH_DOMAIN, 1 hit
PS50104 TIR, 1 hit

Sequences (6)i

Sequence statusi: Complete.

This entry describes 6 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q99836-1) [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
MAAGGPGAGS AAPVSSTSSL PLAALNMRVR RRLSLFLNVR TQVAADWTAL
60 70 80 90 100
AEEMDFEYLE IRQLETQADP TGRLLDAWQG RPGASVGRLL ELLTKLGRDD
110 120 130 140 150
VLLELGPSIE EDCQKYILKQ QQEEAEKPLQ VAAVDSSVPR TAELAGITTL
160 170 180 190 200
DDPLGHMPER FDAFICYCPS DIQFVQEMIR QLEQTNYRLK LCVSDRDVLP
210 220 230 240 250
GTCVWSIASE LIEKRCRRMV VVVSDDYLQS KECDFQTKFA LSLSPGAHQK
260 270 280 290
RLIPIKYKAM KKEFPSILRF ITVCDYTNPC TKSWFWTRLA KALSLP
Length:296
Mass (Da):33,233
Last modified:May 1, 1997 - v1
Checksum:iCEAE3F6B99524333
GO
Isoform 2 (identifier: Q99836-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     110-154: Missing.

Note: No experimental confirmation available.
Show »
Length:251
Mass (Da):28,280
Checksum:i1841504370960C90
GO
Isoform 3 (identifier: Q99836-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     156-296: HMPERFDAFI...TRLAKALSLP → AAGWWWLSLM...ASLQVPIRSD

Note: No experimental confirmation available.
Show »
Length:191
Mass (Da):20,777
Checksum:i5995DBBBA11780B8
GO
Isoform 4 (identifier: Q99836-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     110-110: E → G
     111-155: Missing.
     156-296: HMPERFDAFI...TRLAKALSLP → AAGWWWLSLM...ASLQVPIRSD

Note: No experimental confirmation available.
Show »
Length:146
Mass (Da):15,823
Checksum:i6791101414C872CA
GO
Isoform 5 (identifier: Q99836-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-22: MAAGGPGAGSAAPVSSTSSLPL → M

Show »
Length:275
Mass (Da):31,496
Checksum:i06D06EECD46F5E2F
GO
Isoform 6 (identifier: Q99836-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     215-215: R → RLARRPRGG

Show »
Length:304
Mass (Da):34,097
Checksum:iC6CE78108FE60498
GO

Sequence cautioni

The sequence BAG60822 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence BAG60834 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence EAW64521 differs from that shown. Reason: Erroneous gene model prediction.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti190K → T in BI524129 (PubMed:15489334).Curated1
Sequence conflicti223 – 224VS → WL in BI524129 (PubMed:15489334).Curated2

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07289334S → Y Rare functional polymorphism; loss of NF-kappa-B complex activation; loss of interaction with IRAK4; reduces homooligomerization. 2 Publications1
Natural variantiVAR_07325239V → M Found in hematological malignancies; somatic mutation; unknown pathological significance. 1 Publication1
Natural variantiVAR_07289452Missing in MYD88D; loss of NF-kappa-B complex activation. 2 Publications1
Natural variantiVAR_04795393L → P in MYD88D; results in a loss of function; loss of NF-kappa-B complex activation. 3 Publications1
Natural variantiVAR_07289598R → C Found in hematological malignancies; somatic mutation; unknown pathological significance; loss of NF-kappa-B complex activation; loss of interaction with IRAK4; reduces homooligomerization. 3 Publications1
Natural variantiVAR_073253136S → G Found in hematological malignancies; somatic mutation; unknown pathological significance. 1 Publication1
Natural variantiVAR_073254136S → I Found in hematological malignancies; somatic mutation; unknown pathological significance. 1 Publication1
Natural variantiVAR_072896178M → I Found in hematological malignancies; somatic mutation; unknown pathological significance; no effect on NF-kappaB complex activation. 2 Publications1
Natural variantiVAR_047954196R → C in MYD88D; results in a loss of function; decreases NF-kappa-B complex activation. 4 Publications1
Natural variantiVAR_073255204V → F Found in hematological malignancies; somatic mutation; unknown pathological significance. 1 Publication1
Natural variantiVAR_073256205W → R Found in hematological malignancies; somatic mutation; unknown pathological significance. 1 Publication1
Natural variantiVAR_073257206S → C Found in hematological malignancies; somatic mutation; unknown pathological significance. 1 Publication1
Natural variantiVAR_073258207I → T Found in hematological malignancies; somatic mutation; unknown pathological significance. 1 Publication1
Natural variantiVAR_073259209S → R Found in hematological malignancies; somatic mutation; unknown pathological significance; constitutively activates NF-kappaB complex activation. 1 Publication1
Natural variantiVAR_073260219M → T Found in hematological malignancies; somatic mutation; unknown pathological significance; constitutively activates NF-kappaB complex activation. 1 Publication1
Natural variantiVAR_073261230S → N Found in hematological malignancies; somatic mutation; unknown pathological significance; constitutively activates NF-kappaB complex activation. 1 Publication1
Natural variantiVAR_073262252L → P Found in hematological malignancies; somatic mutation; unknown pathological significance; constitutively activates NF-kappaB complex activation; gain-of-function mutation; does not affect interaction with IRAK4. 2 Publications1
Natural variantiVAR_073263281T → P Found in hematological malignancies; somatic mutation; unknown pathological significance; no effect on NF-kappaB complex activation. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0537641 – 22MAAGG…SSLPL → M in isoform 5. 1 PublicationAdd BLAST22
Alternative sequenceiVSP_038887110 – 154Missing in isoform 2. 1 PublicationAdd BLAST45
Alternative sequenceiVSP_043498110E → G in isoform 4. 1 Publication1
Alternative sequenceiVSP_043499111 – 155Missing in isoform 4. 1 PublicationAdd BLAST45
Alternative sequenceiVSP_043500156 – 296HMPER…ALSLP → AAGWWWLSLMITCRARNVTS RPNLHSASLQVPIRSD in isoform 3 and isoform 4. 1 PublicationAdd BLAST141
Alternative sequenceiVSP_053765215R → RLARRPRGG in isoform 6. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U70451 mRNA Translation: AAB49967.1
U84408 mRNA Translation: AAC50954.1
AB446470 mRNA Translation: BAG55247.1
BT007376 mRNA Translation: AAP36040.1
AK296570 mRNA Translation: BAG59190.1
AK296716 mRNA Translation: BAG59306.1
AK298650 mRNA Translation: BAG60822.1 Different initiation.
AK298666 mRNA Translation: BAG60834.1 Different initiation.
AP006309 Genomic DNA No translation available.
CH471055 Genomic DNA Translation: EAW64521.1 Sequence problems.
BC013589 mRNA Translation: AAH13589.1
BI524129 mRNA No translation available.
RefSeqiNP_001166037.1, NM_001172566.1
NP_001166039.1, NM_001172568.1
NP_001166040.1, NM_001172569.1
NP_002459.2, NM_002468.4
UniGeneiHs.82116

Genome annotation databases

EnsembliENST00000443433; ENSP00000390565; ENSG00000172936
ENST00000495303; ENSP00000417848; ENSG00000172936
GeneIDi4615
KEGGihsa:4615
UCSCiuc011ayj.3 human [Q99836-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiMYD88_HUMAN
AccessioniPrimary (citable) accession number: Q99836
Secondary accession number(s): B4DKH8
, B4DKU4, B4DQ60, B4DQ72, J3KPU4, J3KQ87, J3KQJ6, P78397, Q53XS7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 18, 2001
Last sequence update: May 1, 1997
Last modified: July 18, 2018
This is version 187 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health