MYD88

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 similarity6 Publications

GO - Molecular functionⁱ

Complete GO annotation on QuickGO ...

GO - Biological processⁱ

Complete GO annotation on QuickGO ...

Keywordsⁱ

Biological process	Immunity, Inflammatory response, Innate immunity

Biological process

Immunity, Inflammatory response, Innate immunity

Enzyme and pathway databases

PathwayCommonsⁱ	Q99836
Reactomeⁱ	R-HSA-1236974, ER-Phagosome pathway R-HSA-1257604, PIP3 activates AKT signaling R-HSA-166058, MyD88:MAL(TIRAP) 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-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-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
SignaLinkⁱ	Q99836
SIGNORⁱ	Q99836

Names & Taxonomyⁱ

Protein namesⁱ	Recommended name: Myeloid differentiation primary response protein MyD88
Gene namesⁱ	Name:MYD88Imported
Organismⁱ	Homo sapiens (Human)
Taxonomic identifierⁱ	9606 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo
Proteomesⁱ	UP000005640 Componentⁱ: Chromosome 3

Organism-specific databases

Human Gene Nomenclature Database More...HGNCⁱ	HGNC:7562, MYD88
MIMⁱ	602170, gene
neXtProtⁱ	NX_Q99836
VEuPathDBⁱ	HostDB:ENSG00000172936.12

Keywords - Cellular componentⁱ

Cytoplasm, Nucleus

Pathology & Biotechⁱ

Involvement in diseaseⁱ

Immunodeficiency 68 (IMD68)4 Publications

The disease is caused by variants affecting the gene represented in this entry.

Disease descriptionAn autosomal recessive primary immunodeficiency characterized by life-threatening, often recurrent, pyogenic bacterial infections, including invasive pneumococcal disease, beginning in infancy or early childhood.

Related information in OMIM

Feature key	Position(s)	DescriptionActions	Length
Natural variantⁱVAR_072894	52	Missing in IMD68; loss of NF-kappa-B complex activation. 2 Publications	1
Natural variantⁱVAR_047953	93	L → P in IMD68; results in a loss of function; loss of NF-kappa-B complex activation. 3 PublicationsCorresponds to variant dbSNP:rs137853065EnsemblClinVar.	1
Natural variantⁱVAR_047954	196	R → C in IMD68; results in a loss of function; decreases NF-kappa-B complex activation. 4 PublicationsCorresponds to variant dbSNP:rs137853064EnsemblClinVar.	1

Defects in MYD88 are frequently found in many hematological malignancies, such as activated B-cell type diffuse large B-cell lymphoma (ABC-DLBCL), Waldenstroem macroglobulinemia, cutaneous diffuse large B cell lymphoma (CBCL) and primary central nervous system lymphoma (PCNSL).2 Publications

Mutagenesis

Feature key	Position(s)	DescriptionActions	Length
Mutagenesisⁱ	179	I → N in Pococurante (Poc); abolished MYD88-dependent sensing of most Toll-like receptor (TLR) ligands. 1 Publication	1
Mutagenesisⁱ	196	R → A: Reduced interaction with TIRAP, and strongly reduced activity. Strongly reduced interaction with TIRAP; when associated with A-288. 1 Publication	1
Mutagenesisⁱ	197	D → A: Slightly reduced activity. 1 Publication	1
Mutagenesisⁱ	203	C → S: Abolished interaction with E.coli TcpC without affecting ability to promote Toll-like receptor (TLR)-mediated cytokine production; when associated with S-280. 1 Publication	1
Mutagenesisⁱ	217	R → A: Strongly reduced activity. 1 Publication	1
Mutagenesisⁱ	280	C → S: Abolished interaction with E.coli TcpC without affecting ability to promote Toll-like receptor (TLR)-mediated cytokine production; when associated with S-203. 1 Publication	1
Mutagenesisⁱ	282	K → A: Slightly reduced activity. 1 Publication	1
Mutagenesisⁱ	288	R → A: Slightly reduced activity, and reduced interaction with TIRAP. Strongly reduced interaction with TIRAP; when associated with A-196. 1 Publication	1

Keywords - Diseaseⁱ

Disease variant

Organism-specific databases

DisGeNET More...DisGeNETⁱ	4615
MalaCards human disease database More...MalaCardsⁱ	MYD88
MIMⁱ	612260, phenotype
Open Targets More...OpenTargetsⁱ	ENSG00000172936
Orphanetⁱ	183713, Bacterial susceptibility due to TLR signaling pathway deficiency 33226, Waldenstroem macroglobulinemia
PharmGKBⁱ	PA31361

Miscellaneous databases

Pharosⁱ	Q99836, Tbio

Pharosⁱ

Q99836, Tbio

Chemistry databases

ChEMBLⁱ	CHEMBL5919

ChEMBLⁱ

CHEMBL5919

Genetic variation databases

BioMutaⁱ	MYD88
DMDMⁱ	18202671

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
ChainⁱPRO_0000096666	1 – 296	Myeloid differentiation primary response protein MyD88Add BLAST		296

Amino acid modifications

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Modified residueⁱ	244	PhosphoserineCombined sources		1

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

EPDⁱ	Q99836
jPOSTⁱ	Q99836
MassIVEⁱ	Q99836
MaxQB - The MaxQuant DataBase More...MaxQBⁱ	Q99836
PaxDbⁱ	Q99836
PeptideAtlas More...PeptideAtlasⁱ	Q99836
PRIDEⁱ	Q99836
ProteomicsDBⁱ	78500 [Q99836-1] 78501 [Q99836-2] 78502 [Q99836-3] 78503 [Q99836-4]
TopDownProteomicsⁱ	Q99836-4 [Q99836-4]

PTM databases

iPTMnetⁱ	Q99836
PhosphoSitePlusⁱ	Q99836
SwissPalmⁱ	Q99836

Expressionⁱ

Tissue specificityⁱ

Ubiquitous.1 Publication

Gene expression databases

Bgeeⁱ	ENSG00000172936, Expressed in blood and 233 other tissues
ExpressionAtlasⁱ	Q99836, baseline and differential

Organism-specific databases

Human Protein Atlas More...HPAⁱ	ENSG00000172936, Tissue enhanced (blood)

HPAⁱ

ENSG00000172936, Tissue enhanced (blood)

Interactionⁱ

Subunit structureⁱ

Homodimer. Also forms heterodimers with TIRAP. Binds to TLR2, TLR4, TLR5, 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).

15 Publications

(Microbial infection) In case of infection, interacts with uropathogenic E.coli protein TcpC; suppressing Toll-like receptor (TLR)-mediated cytokine production.

1 Publication

(Microbial infection) In case of infection, interacts with uropathogenic E.faecalis protein TcpF; suppressing Toll-like receptor (TLR)-mediated cytokine production.

1 Publication

Binary interactionsⁱ

Hide details

Q99836

With	#Exp.	IntAct
DOCK8 [Q8NF50]	3	EBI-447677,EBI-2548605
FADD [Q13158]	3	EBI-447677,EBI-494804
HDAC6 [Q9UBN7]	6	EBI-447677,EBI-301697
IRAK1 [P51617]	2	EBI-447677,EBI-358664
IRAK4 [Q69FE3]	5	EBI-447677,EBI-10249217
IRAK4 [Q9NWZ3]	15	EBI-447677,EBI-448378
itself	40	EBI-447677,EBI-447677
NTAQ1 [Q96HA8]	3	EBI-447677,EBI-741158
RNF4 [P78317]	3	EBI-447677,EBI-2340927
SARM1 [Q6SZW1]	5	EBI-447677,EBI-11693532
SIAH1 [Q8IUQ4]	3	EBI-447677,EBI-747107
SMAD3 [P84022]	3	EBI-447677,EBI-347161
SPOP [O43791]	7	EBI-447677,EBI-743549
SPOPL [Q6IQ16]	3	EBI-447677,EBI-2822161
STAP2 [Q9UGK3]	3	EBI-447677,EBI-1553984
TIRAP [P58753]	8	EBI-447677,EBI-528644
TLR2 [O60603]	4	EBI-447677,EBI-973722
TLR4 [O00206]	4	EBI-447677,EBI-528701
TNFRSF13B [O14836]	12	EBI-447677,EBI-519160
TXN [P10599]	4	EBI-447677,EBI-594644
USP7 [Q93009]	3	EBI-447677,EBI-302474
ZNF35 [P13682]	3	EBI-447677,EBI-11041653
BMEI1694 [Q8YF33] from Brucella melitensis biotype 1 (strain 16M / ATCC 23456 / NCTC 10094).	4	EBI-447677,EBI-11616155
Non-structural protein 5A (PRO_0000278740) from Hepatitis C virus genotype 1b (isolate HC-J1).	3	EBI-447677,EBI-8803426

Isoform 1 [Q99836-1]

With	#Exp.	IntAct
CYTH2 [Q99418]	3	EBI-15855480,EBI-448974
IRAK4 [Q9NWZ3]	9	EBI-15855480,EBI-448378

GO - Molecular functionⁱ

Complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGRIDⁱ	110700, 73 interactors
Database of interacting proteins More...DIPⁱ	DIP-31349N
IntActⁱ	Q99836, 46 interactors
Molecular INTeraction database More...MINTⁱ	Q99836
STRINGⁱ	9606.ENSP00000401399

Miscellaneous databases

RNActⁱ	Q99836, protein

RNActⁱ

Q99836, protein

Structureⁱ

Secondary structure

Legend: HelixTurnBeta strandPDB Structure known for this area

Feature key	Position(s)	DescriptionActions	Length
Helixⁱ	22 – 24	Combined sources	3
Helixⁱ	27 – 37	Combined sources	11
Beta strandⁱ	42 – 44	Combined sources	3
Helixⁱ	47 – 53	Combined sources	7
Helixⁱ	58 – 64	Combined sources	7
Beta strandⁱ	66 – 69	Combined sources	4
Helixⁱ	70 – 77	Combined sources	8
Beta strandⁱ	79 – 81	Combined sources	3
Helixⁱ	86 – 95	Combined sources	10
Helixⁱ	100 – 104	Combined sources	5
Helixⁱ	106 – 120	Combined sources	15
Beta strandⁱ	159 – 166	Combined sources	8
Helixⁱ	169 – 171	Combined sources	3
Helixⁱ	172 – 183	Combined sources	12
Beta strandⁱ	185 – 187	Combined sources	3
Beta strandⁱ	191 – 194	Combined sources	4
Helixⁱ	196 – 198	Combined sources	3
Helixⁱ	209 – 211	Combined sources	3
Helixⁱ	212 – 215	Combined sources	4
Beta strandⁱ	216 – 223	Combined sources	8
Helixⁱ	227 – 229	Combined sources	3
Helixⁱ	231 – 242	Combined sources	12
Helixⁱ	247 – 251	Combined sources	5
Beta strandⁱ	252 – 256	Combined sources	5
Helixⁱ	266 – 268	Combined sources	3
Beta strandⁱ	269 – 271	Combined sources	3
Helixⁱ	279 – 281	Combined sources	3
Helixⁱ	285 – 294	Combined sources	10

Show more details

3D structure databases

SMRⁱ	Q99836
ModBaseⁱ	Search...
PDBe-KBⁱ	Search...

Miscellaneous databases

EvolutionaryTraceⁱ	Q99836

EvolutionaryTraceⁱ

Q99836

Family & Domainsⁱ

Domains and Repeats

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Domainⁱ	54 – 109	DeathPROSITE-ProRule annotationAdd BLAST		56
Domainⁱ	159 – 293	TIRPROSITE-ProRule annotationAdd BLAST		135

Region

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Regionⁱ	110 – 155	Intermediate domainBy similarityAdd BLAST		46

Domainⁱ

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

Phylogenomic databases

eggNOGⁱ	ENOG502QWKI, Eukaryota
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00510000048324
HOGENOMⁱ	CLU_116540_0_0_1
InParanoidⁱ	Q99836
PhylomeDBⁱ	Q99836
TreeFamⁱ	TF326264

Family and domain databases

Conserved Domains Database More...CDDⁱ	cd08312, Death_MyD88, 1 hit
Gene3Dⁱ	3.40.50.10140, 1 hit
InterProⁱ	View 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
PANTHERⁱ	PTHR15079, PTHR15079, 1 hit
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF00531, Death, 1 hit PF01582, TIR, 1 hit
PIRSFⁱ	PIRSF037756, MyD88, 1 hit
SMARTⁱ	View protein in SMART SM00005, DEATH, 1 hit SM00255, TIR, 1 hit
SUPFAMⁱ	SSF47986, SSF47986, 1 hit SSF52200, SSF52200, 1 hit
PROSITEⁱ	View 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. Align Add to basket

This entry has 6 described isoforms and 4 potential isoforms that are computationally mapped.Show all Align All

Isoform 1 (identifier: Q99836-1) [UniParc]FASTA Add to basket

This isoform has been chosen as the canonicalⁱ 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]FASTA Add to basket

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

« 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
VLLELGPSIG HMPERFDAFI CYCPSDIQFV QEMIRQLEQT NYRLKLCVSD 
       160        170        180        190        200
RDVLPGTCVW SIASELIEKR CRRMVVVVSD DYLQSKECDF QTKFALSLSP 
       210        220        230        240        250
GAHQKRLIPI KYKAMKKEFP SILRFITVCD YTNPCTKSWF WTRLAKALSL 

P

Show »

Length:251

Mass (Da):28,280

Checksum:ⁱ1841504370960C90

GO

Isoform 3 (identifier: Q99836-3) [UniParc]FASTA Add to basket

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

« 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 
DDPLGAAGWW WLSLMITCRA RNVTSRPNLH SASLQVPIRS D

Show »

Length:191

Mass (Da):20,777

Checksum:ⁱ5995DBBBA11780B8

GO

Isoform 4 (identifier: Q99836-4) [UniParc]FASTA Add 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

« 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 
VLLELGPSIG AAGWWWLSLM ITCRARNVTS RPNLHSASLQ VPIRSD

Show »

Length:146

Mass (Da):15,823

Checksum:ⁱ6791101414C872CA

GO

Isoform 5 (identifier: Q99836-5) [UniParc]FASTA Add to basket

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

« Hide

        10         20         30         40         50
MAALNMRVRR RLSLFLNVRT QVAADWTALA EEMDFEYLEI RQLETQADPT 
        60         70         80         90        100
GRLLDAWQGR PGASVGRLLE LLTKLGRDDV LLELGPSIEE DCQKYILKQQ 
       110        120        130        140        150
QEEAEKPLQV AAVDSSVPRT AELAGITTLD DPLGHMPERF DAFICYCPSD 
       160        170        180        190        200
IQFVQEMIRQ LEQTNYRLKL CVSDRDVLPG TCVWSIASEL IEKRCRRMVV 
       210        220        230        240        250
VVSDDYLQSK ECDFQTKFAL SLSPGAHQKR LIPIKYKAMK KEFPSILRFI 
       260        270 
TVCDYTNPCT KSWFWTRLAK ALSLP

Show »

Length:275

Mass (Da):31,496

Checksum:ⁱ06D06EECD46F5E2F

GO

Isoform 6 (identifier: Q99836-6) [UniParc]FASTA Add to basket

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

« 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 LIEKRLARRP RGGCRRMVVV VSDDYLQSKE CDFQTKFALS 
       260        270        280        290        300
LSPGAHQKRL IPIKYKAMKK EFPSILRFIT VCDYTNPCTK SWFWTRLAKA 

LSLP

Show »

Length:304

Mass (Da):34,097

Checksum:ⁱC6CE78108FE60498

GO

Computationally mapped potential isoform sequencesⁱ

There are 4 potential isoforms mapped to this entry.BLAST Align Show all Add to basket

Entry	Entry name	Protein names	Gene names	Length	Annotation

A0A0A0MSI9	A0A0A0MSI9_HUMAN	Myeloid differentiation primary res... Myeloid differentiation primary response protein MyD88	MYD88	264	Annotation score:
A0A494C0J8	A0A494C0J8_HUMAN	Myeloid differentiation primary res... Myeloid differentiation primary response protein MyD88	MYD88	245	Annotation score:
A0A3B3ITY3	A0A3B3ITY3_HUMAN	Myeloid differentiation primary res... Myeloid differentiation primary response protein MyD88	MYD88	159	Annotation score:
A0A3F2YP85	A0A3F2YP85_HUMAN	Myeloid differentiation primary res... Myeloid differentiation primary response protein MyD88	MYD88	204	Annotation score:

Sequence cautionⁱ

The sequence BAG60822 differs from that shown. Reason: Erroneous initiation. Extended N-terminus.Curated

The sequence BAG60834 differs from that shown. Reason: Erroneous initiation. Extended N-terminus.Curated

The sequence EAW64521 differs from that shown. Reason: Erroneous gene model prediction.Curated

Experimental Info

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Sequence conflictⁱ	190	K → T in BI524129 (PubMed:15489334).Curated		1
Sequence conflictⁱ	223 – 224	VS → WL in BI524129 (PubMed:15489334).Curated		2

Natural variant

Feature key	Position(s)	DescriptionActions	Length
Natural variantⁱVAR_072893	34	S → Y Rare variant; unknown pathological significance; loss of NF-kappa-B complex activation; loss of interaction with IRAK4; reduces homooligomerization. 2 PublicationsCorresponds to variant dbSNP:rs1319438Ensembl.	1
Natural variantⁱVAR_073252	39	V → M Found in hematological malignancies; somatic mutation; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs770387646Ensembl.	1
Natural variantⁱVAR_072894	52	Missing in IMD68; loss of NF-kappa-B complex activation. 2 Publications	1
Natural variantⁱVAR_047953	93	L → P in IMD68; results in a loss of function; loss of NF-kappa-B complex activation. 3 PublicationsCorresponds to variant dbSNP:rs137853065EnsemblClinVar.	1
Natural variantⁱVAR_072895	98	R → 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 PublicationsCorresponds to variant dbSNP:rs199396Ensembl.	1
Natural variantⁱVAR_073253	136	S → G Found in hematological malignancies; somatic mutation; unknown pathological significance. 1 Publication	1
Natural variantⁱVAR_073254	136	S → I Found in hematological malignancies; somatic mutation; unknown pathological significance. 1 Publication	1
Natural variantⁱVAR_072896	178	M → I Found in hematological malignancies; somatic mutation; unknown pathological significance; no effect on NF-kappaB complex activation. 2 PublicationsCorresponds to variant dbSNP:rs41285117Ensembl.	1
Natural variantⁱVAR_047954	196	R → C in IMD68; results in a loss of function; decreases NF-kappa-B complex activation. 4 PublicationsCorresponds to variant dbSNP:rs137853064EnsemblClinVar.	1
Natural variantⁱVAR_073255	204	V → F Found in hematological malignancies; somatic mutation; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs776995408Ensembl.	1
Natural variantⁱVAR_073256	205	W → R Found in hematological malignancies; somatic mutation; unknown pathological significance. 1 Publication	1
Natural variantⁱVAR_073257	206	S → C Found in hematological malignancies; somatic mutation; unknown pathological significance. 1 Publication	1
Natural variantⁱVAR_073258	207	I → T Found in hematological malignancies; somatic mutation; unknown pathological significance. 1 Publication	1
Natural variantⁱVAR_073259	209	S → R Found in hematological malignancies; somatic mutation; unknown pathological significance; constitutively activates NF-kappaB complex activation. 1 Publication	1
Natural variantⁱVAR_073260	219	M → T Found in hematological malignancies; somatic mutation; unknown pathological significance; constitutively activates NF-kappaB complex activation. 1 Publication	1
Natural variantⁱVAR_073261	230	S → N Found in hematological malignancies; somatic mutation; unknown pathological significance; constitutively activates NF-kappaB complex activation. 1 PublicationCorresponds to variant dbSNP:rs1353791431Ensembl.	1
Natural variantⁱVAR_073262	252	L → P Found in hematological malignancies; common mutation in Waldenstroem macroglobulinemia; somatic mutation; unknown pathological significance; constitutively activates NF-kappaB complex activation; gain-of-function mutation; does not affect interaction with IRAK4. 3 PublicationsCorresponds to variant dbSNP:rs387907272EnsemblClinVar.	1
Natural variantⁱVAR_073263	281	T → P Found in hematological malignancies; somatic mutation; unknown pathological significance; no effect on NF-kappaB complex activation. 1 Publication	1

Alternative sequence

Feature key	Position(s)	DescriptionActions	Length
Alternative sequenceⁱVSP_053764	1 – 22	MAAGG…SSLPL → M in isoform 5. 1 PublicationAdd BLAST	22
Alternative sequenceⁱVSP_038887	110 – 154	Missing in isoform 2. 1 PublicationAdd BLAST	45
Alternative sequenceⁱVSP_043498	110	E → G in isoform 4. 1 Publication	1
Alternative sequenceⁱVSP_043499	111 – 155	Missing in isoform 4. 1 PublicationAdd BLAST	45
Alternative sequenceⁱVSP_043500	156 – 296	HMPER…ALSLP → AAGWWWLSLMITCRARNVTS RPNLHSASLQVPIRSD in isoform 3 and isoform 4. 1 PublicationAdd BLAST	141
Alternative sequenceⁱVSP_053765	215	R → RLARRPRGG in isoform 6. 1 Publication	1

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.
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS2674.2 [Q99836-1] CCDS54565.1 [Q99836-6] CCDS54566.1 [Q99836-3] CCDS54567.1 [Q99836-2] CCDS54568.1 [Q99836-4]
NCBI Reference Sequences More...RefSeqⁱ	NP_001166037.1, NM_001172566.1 [Q99836-4] NP_001166039.1, NM_001172568.1 [Q99836-2] NP_001166040.1, NM_001172569.1 [Q99836-3] NP_002459.2, NM_002468.4 [Q99836-1]

Genome annotation databases

Ensemblⁱ	ENST00000396334; ENSP00000379625; ENSG00000172936 [Q99836-1] ENST00000417037; ENSP00000401399; ENSG00000172936 [Q99836-2] ENST00000421516; ENSP00000391753; ENSG00000172936 [Q99836-6] ENST00000650112; ENSP00000497991; ENSG00000172936 [Q99836-4] ENST00000650905; ENSP00000498360; ENSG00000172936 [Q99836-1] ENST00000651800; ENSP00000499012; ENSG00000172936 [Q99836-3]
GeneIDⁱ	4615
KEGGⁱ	hsa:4615
UCSC genome browser More...UCSCⁱ	uc011ayj.3, human [Q99836-1]

Keywords - Coding sequence diversityⁱ

Alternative splicing

Similar proteinsⁱ

100% Identity
90% Identity
50% Identity

Protein	Similar proteins	Species	Length	Source
Q99836-2	Myeloid differentiation primary response protein MyD88	HUMAN	264	UniRef100_A0A0A0MSI9
Q99836-3	Myeloid differentiation primary response protein MyD88	HUMAN	204	UniRef100_A0A3F2YP85
Q99836-4	Myeloid differentiation primary response protein MyD88	HUMAN	159	UniRef100_A0A3B3ITY3

Protein	Similar proteins		Species	Score	Length	Source
Q99836	Myeloid differentiation primary response protein MyD88		PANPA		296	UniRef90_Q99836
Myeloid differentiation primary response protein MyD88		RABIT		303
Myeloid differentiation primary response protein MyD88		CARSF		296
Isoform 5 of Myeloid differentiation primary response protein MyD88		HUMAN		275
+8
Q99836-2	Myeloid differentiation primary response protein MyD88		PANTR		264	UniRef90_K7CCX1
Myeloid differentiation primary response protein MyD88		HUMAN		264
Myeloid differentiation primary response protein MyD88		GORGO		264
Myeloid differentiation primary response protein MyD88		PROCO		264
Myeloid differentiation primary response protein MyD88		PANPA		264
+4
Q99836-3	Death domain-containing protein		NOMLE		204	UniRef90_A0A2I3HVI7
Myeloid differentiation primary response protein MyD88		HUMAN		204
Death domain-containing protein		AOTNA		204
Death domain-containing protein		COLAP		204
Death domain-containing protein		PANPA		204
+16
Q99836-4	Death domain-containing protein		NOMLE		159	UniRef90_A0A2I3GWM4
Myeloid differentiation primary response protein MyD88		HUMAN		159
Death domain-containing protein		AOTNA		159
Death domain-containing protein		PAPAN		159
Myeloid differentiation primary response protein MyD88		PANTR		159
+13
Q99836-6	Myeloid differentiation primary response protein MyD88		MACFA		296	UniRef90_Q99836-6
Myeloid differentiation primary response protein MyD88		CERAT		296
Myeloid differentiation primary response protein MyD88		MACMU		296
Myeloid differentiation primary response protein MyD88		PANTR		296
Myeloid differentiation primary response protein MyD88		GORGO		296
+61

Protein	Similar proteins		Species	Score	Length	Source
Q99836	Myeloid differentiation primary response protein MyD88		PANPA		296	UniRef50_Q99836
Myeloid differentiation primary response protein MyD88		GORGO		296
Myeloid differentiation primary response protein MyD88		PONPY		296
Myeloid differentiation primary response protein MyD88		MACFA		296
Myeloid differentiation primary response protein MyD88		CERAT		296
+207
Q99836-2	Myeloid differentiation primary response protein MyD88		MOUSE		296	UniRef50_P22366
Myeloid differentiation primary response protein MyD88		RAT		296
Myeloid differentiation primary response protein MyD88		XENTR		283
Myeloid differentiation primary response protein MyD88		MUSCR		296
Myeloid differentiation primary response protein MyD88		NEOLE		296
+125
Q99836-3	Isoform 3 of Myeloid differentiation primary response protein MyD88		BOVIN		219	UniRef50_Q599T9-3
TIR domain-containing protein (Fragment)		BALPH		221
MYD88 innate immune signal transduction adaptor		ROUAE		191
MYD88 innate immune signal transduction adaptor		RHIFE		204
Myeloid differentiation primary response protein MyD88		PANTR		204
+41
Q99836-4	Death domain-containing protein		NOMLE		159	UniRef50_A0A2I3GWM4
Death domain-containing protein		AOTNA		159
Myeloid differentiation primary response protein MyD88		PANTR		159
Death domain-containing protein		COLAP		159
MYD88 innate immune signal transduction adaptor		CALJA		159
+27

Cross-referencesⁱ

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.
CCDSⁱ	CCDS2674.2 [Q99836-1] CCDS54565.1 [Q99836-6] CCDS54566.1 [Q99836-3] CCDS54567.1 [Q99836-2] CCDS54568.1 [Q99836-4]
RefSeqⁱ	NP_001166037.1, NM_001172566.1 [Q99836-4] NP_001166039.1, NM_001172568.1 [Q99836-2] NP_001166040.1, NM_001172569.1 [Q99836-3] NP_002459.2, NM_002468.4 [Q99836-1]

3D structure databases

Select the link destinations: Protein Data Bank Europe More...PDBeⁱ Protein Data Bank RCSB More...RCSB PDBⁱ Protein Data Bank Japan More...PDBjⁱ Links Updated	PDB entry	Method	Resolution (Å)	Chain	Positions	PDBsum
	2JS7	NMR	-	A	146-296	[»]
	2Z5V	NMR	-	A	148-296	[»]
	3MOP	X-ray	3.40	A/B/C/D/E/F	20-117	[»]
	4DOM	X-ray	1.80	A	157-296	[»]
	4EO7	X-ray	1.45	A	157-296	[»]
	6I3N	electron microscopy	3.10	A/B/C/D/E/F/G/H/I/J/K/L/M	1-151	[»]
SMRⁱ	Q99836
ModBaseⁱ	Search...
PDBe-KBⁱ	Search...

Protein-protein interaction databases

BioGRIDⁱ	110700, 73 interactors
DIPⁱ	DIP-31349N
IntActⁱ	Q99836, 46 interactors
MINTⁱ	Q99836
STRINGⁱ	9606.ENSP00000401399

Chemistry databases

ChEMBLⁱ	CHEMBL5919

ChEMBLⁱ

CHEMBL5919

PTM databases

iPTMnetⁱ	Q99836
PhosphoSitePlusⁱ	Q99836
SwissPalmⁱ	Q99836

Genetic variation databases

BioMutaⁱ	MYD88
DMDMⁱ	18202671

Proteomic databases

EPDⁱ	Q99836
jPOSTⁱ	Q99836
MassIVEⁱ	Q99836
MaxQBⁱ	Q99836
PaxDbⁱ	Q99836
PeptideAtlasⁱ	Q99836
PRIDEⁱ	Q99836
ProteomicsDBⁱ	78500 [Q99836-1] 78501 [Q99836-2] 78502 [Q99836-3] 78503 [Q99836-4]
TopDownProteomicsⁱ	Q99836-4 [Q99836-4]

Protocols and materials databases

Antibodypediaⁱ	3965, 943 antibodies
The DNASU plasmid repository More...DNASUⁱ	4615

Genome annotation databases

Ensemblⁱ	ENST00000396334; ENSP00000379625; ENSG00000172936 [Q99836-1] ENST00000417037; ENSP00000401399; ENSG00000172936 [Q99836-2] ENST00000421516; ENSP00000391753; ENSG00000172936 [Q99836-6] ENST00000650112; ENSP00000497991; ENSG00000172936 [Q99836-4] ENST00000650905; ENSP00000498360; ENSG00000172936 [Q99836-1] ENST00000651800; ENSP00000499012; ENSG00000172936 [Q99836-3]
GeneIDⁱ	4615
KEGGⁱ	hsa:4615
UCSCⁱ	uc011ayj.3, human [Q99836-1]

Organism-specific databases

CTDⁱ	4615
DisGeNETⁱ	4615
GeneCardsⁱ	MYD88
HGNCⁱ	HGNC:7562, MYD88
HPAⁱ	ENSG00000172936, Tissue enhanced (blood)
MalaCardsⁱ	MYD88
MIMⁱ	602170, gene 612260, phenotype
neXtProtⁱ	NX_Q99836
OpenTargetsⁱ	ENSG00000172936
Orphanetⁱ	183713, Bacterial susceptibility due to TLR signaling pathway deficiency 33226, Waldenstroem macroglobulinemia
PharmGKBⁱ	PA31361
VEuPathDBⁱ	HostDB:ENSG00000172936.12
GenAtlas: human gene database More...GenAtlasⁱ	Search...

Phylogenomic databases

eggNOGⁱ	ENOG502QWKI, Eukaryota
GeneTreeⁱ	ENSGT00510000048324
HOGENOMⁱ	CLU_116540_0_0_1
InParanoidⁱ	Q99836
PhylomeDBⁱ	Q99836
TreeFamⁱ	TF326264

Enzyme and pathway databases

PathwayCommonsⁱ	Q99836
Reactomeⁱ	R-HSA-1236974, ER-Phagosome pathway R-HSA-1257604, PIP3 activates AKT signaling R-HSA-166058, MyD88:MAL(TIRAP) 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-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-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
SignaLinkⁱ	Q99836
SIGNORⁱ	Q99836

Miscellaneous databases

BioGRID-ORCSⁱ	4615, 18 hits in 995 CRISPR screens
ChiTaRSⁱ	MYD88, human
EvolutionaryTraceⁱ	Q99836
GeneWikiⁱ	MYD88
GenomeRNAiⁱ	4615
Pharosⁱ	Q99836, Tbio
Protein Ontology More...PROⁱ	PR:Q99836
RNActⁱ	Q99836, protein
SOURCEⁱ	Search...

Gene expression databases

Bgeeⁱ	ENSG00000172936, Expressed in blood and 233 other tissues
ExpressionAtlasⁱ	Q99836, baseline and differential

Family and domain databases

CDDⁱ	cd08312, Death_MyD88, 1 hit
Gene3Dⁱ	3.40.50.10140, 1 hit
InterProⁱ	View 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
PANTHERⁱ	PTHR15079, PTHR15079, 1 hit
Pfamⁱ	View protein in Pfam PF00531, Death, 1 hit PF01582, TIR, 1 hit
PIRSFⁱ	PIRSF037756, MyD88, 1 hit
SMARTⁱ	View protein in SMART SM00005, DEATH, 1 hit SM00255, TIR, 1 hit
SUPFAMⁱ	SSF47986, SSF47986, 1 hit SSF52200, SSF52200, 1 hit
PROSITEⁱ	View protein in PROSITE PS50017, DEATH_DOMAIN, 1 hit PS50104, TIR, 1 hit
ProtoNetⁱ	Search...
MobiDBⁱ	Search...

Entry informationⁱ

Entry nameⁱ	MYD88_HUMAN
Accessionⁱ	Q99836Primary (citable) accession number: Q99836 Secondary accession number(s): B4DKH8 Q53XS7
Entry historyⁱ	Integrated into UniProtKB/Swiss-Prot:	October 18, 2001
	Last sequence update:	May 1, 1997
	Last modified:	April 7, 2021
	This is version 207 of the entry and version 1 of the sequence. See complete history.
Entry statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Chordata Protein Annotation Program
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.

Miscellaneousⁱ

Keywords - Technical termⁱ

3D-structure, Reference proteome

Documents

Human chromosome 3
Human chromosome 3: entries, gene names and cross-references to MIM
Human entries with genetic variants
List of human entries with genetic variants
Human variants curated from literature reports
Index of human variants curated from literature reports
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

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UniProtKB - Q99836 (MYD88_HUMAN)

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Myeloid differentiation primary response protein MyD88

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<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

Enzyme and pathway databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Cytoplasm and Cytosol

Nucleus

Cytosol

Endosome

Nucleus

Plasma Membrane

Other locations

Keywords - Cellular componenti

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Mutagenesis

Keywords - Diseasei

Organism-specific databases

Miscellaneous databases

Chemistry databases

Genetic variation databases

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Amino acid modifications

Keywords - PTMi

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

Organism-specific databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

Q99836

Isoform 1 [Q99836-1]

GO - Molecular functioni

Protein-protein interaction databases

Miscellaneous databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

3D structure databases

Miscellaneous databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Region

Phylogenomic databases

Family and domain databases

<p>This subsection of the 'Sequence' section reports difference(s) between the protein sequence shown in the UniProtKB entry and other available protein sequences derived from the same gene.<p><a href='/help/sequence_caution' target='_top'>More...</a></p>Sequence cautioni

Experimental Info

Natural variant

Alternative sequence

Sequence databases

Genome annotation databases

Keywords - Coding sequence diversityi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

3D structure databases

Protein-protein interaction databases

Chemistry databases

PTM databases

Genetic variation databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Miscellaneous databases

Gene expression databases

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Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

Keywords - Diseaseⁱ

PTM / Processingⁱ

Keywords - PTMⁱ

Expressionⁱ

Interactionⁱ

GO - Molecular functionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence cautionⁱ

Keywords - Coding sequence diversityⁱ

Cross-referencesⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ