Reviewed, UniProtKB/Swiss-Prot Q99836 (MYD88_HUMAN)

Names and origin

Protein names

Recommended name:
    Myeloid differentiation primary response protein MyD88

Gene names

Name:

MYD88

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

Keywords
Biological process	Immune response Inflammatory response
Cellular component	Cytoplasm
Disease	Disease mutation
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	I-kappaB kinase/NF-kappaB cascade Inferred from Experiment. Source: Reactome anti-apoptosis Inferred from Experiment. Source: Reactome cell surface receptor linked signal transduction Traceable author statement. Source: ProtInc inflammatory response Inferred from electronic annotation. Source: UniProtKB-KW innate immune response Inferred from electronic annotation. Source: InterPro positive regulation of I-kappaB kinase/NF-kappaB cascade Inferred from expression pattern. Source: UniProtKB response to interleukin-1 Inferred from mutant phenotype. Source: UniProtKB
Cellular component	cytosol Inferred from Experiment. Source: Reactome intrinsic to membrane Inferred from electronic annotation. Source: InterPro
Molecular function	death receptor binding Traceable author statement. Source: ProtInc transmembrane receptor activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

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

1

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296

Helix Strand Turn

Details...

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

	Sequence		Length	Mass (Da)
	Q99836-1 [UniParc]. Last modified May 1, 1997. Version 1. Checksum: CEAE3F6B99524333	FASTA	296	33,233
	10 20 30 40 50 60 MAAGGPGAGS AAPVSSTSSL PLAALNMRVR RRLSLFLNVR TQVAADWTAL AEEMDFEYLE 70 80 90 100 110 120 IRQLETQADP TGRLLDAWQG RPGASVGRLL ELLTKLGRDD VLLELGPSIE EDCQKYILKQ 130 140 150 160 170 180 QQEEAEKPLQ VAAVDSSVPR TAELAGITTL DDPLGHMPER FDAFICYCPS DIQFVQEMIR 190 200 210 220 230 240 QLEQTNYRLK LCVSDRDVLP GTCVWSIASE LIEKRCRRMV VVVSDDYLQS KECDFQTKFA 250 260 270 280 290 LSLSPGAHQK RLIPIKYKAM KKEFPSILRF ITVCDYTNPC TKSWFWTRLA KALSLP

References

	« Hide 'large scale' referencesShow '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. , Ruiz-Ortiz E., Juan M., Fortuny C., Yaguee J., Anton J., Pascal M., Chang H.-H., Janniere L., Rose Y., Garty B.-Z., Chapel H., Issekutz A., Marodi L., Rodriguez-Gallego C., Banchereau J., Abel L., Li X., Chaussabel D., Puel A., 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

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2JS7	NMR	-	A	146-296	[»]
2Z5V	NMR	-	A	148-296	[»]

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

Integrated into UniProtKB/Swiss-Prot:	October 18, 2001
Last sequence update:	May 1, 1997
Last modified:	February 9, 2010
This is version 96 of the entry and version 1 of the sequence. [Complete 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.