UniProtKB/SwissProt variant VAR

Myeloid differentiation primary response protein MyD88
Gene: MYD88
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Variant information Variant position:

196
Type of variant:

LP/P [Disclaimer]
Residue change:

From Arginine (R) to Cysteine (C) at position 196 (R196C, p.Arg196Cys).
Physico-chemical properties:

Change from large size and basic (R) to medium size and polar (C)
BLOSUM score:

-3
Variant description:

In IMD68; results in a loss of function; decreases NF-kappa-B complex activation.
Other resources:

Variant rs137853064 [ dbSNP | Ensembl ]

Sequence information Variant position:

196
Protein sequence length:

296
Location on the sequence:

QEMIRQLEQTNYRLKLCVSD R DVLPGTCVWSIASELIEKRC
Residue conservation:

Human                         QEMIRQLEQTNYRLKLCVSDRDVLPGTCVWSIASELIEKRC

Gorilla                       QEMIRQLEQTNYRLKLCVSDRDVLPGTCVWSIASELIEKRC

Rhesus macaque                QEMIRQLEQTNYRLKLCVSDRDVLPGTCVWSIASELIEKRC

Chimpanzee                    QEMIRQLEQTNYRLKLCVSDRDVLPGTCVWSIASELIEKRC

Mouse                         QEMIRQLEQTDYRLKLCVSDRDVLPGTCVWSIASELIEKRC

Rat                           QEMIRQLEQTDYRLKLCVSDRDVLPGTCVWSIASELIEKRC

Pig                           QEMIRQLEQTNYRLKLCVSDRDVLPGTCVWSIASELIEKRC

Bovine                        HEMIRQLEQTNYRLKLCVSDRDVLPGTCVWSIASELIEKRC

Sheep                         HEMIRQLEQTNYRLKLCVSDRDVLPGTCVWSIASELIEKRC

Chicken                       QEMIRELEQTEFKLKLCVFDRDVLPGTCVWSISGELIERRC

Xenopus tropicalis            QEMISRLEQTDYKLKLCVFDRDVLPGTCLWSITSELIEHRC

Zebrafish                     HEMIKQLEHTEYNLKLCVFDRDVLPGTCVWTIASELIEKRC

Sequence annotation in neighborhood:

Type	Positions	Description
Chain	1 – 296	Myeloid differentiation primary response protein MyD88
Domain	159 – 293	TIR
Alternative sequence	156 – 296	HMPERFDAFICYCPSDIQFVQEMIRQLEQTNYRLKLCVSDRDVLPGTCVWSIASELIEKRCRRMVVVVSDDYLQSKECDFQTKFALSLSPGAHQKRLIPIKYKAMKKEFPSILRFITVCDYTNPCTKSWFWTRLAKALSLP -> AAGWWWLSLMITCRARNVTSRPNLHSASLQVPIRSD. In isoform 3 and isoform 4.
Alternative sequence	215 – 215	R -> RLARRPRGG. In isoform 6.
Mutagenesis	179 – 179	I -> N. In Pococurante (Poc); abolished MYD88-dependent sensing of most Toll-like receptor (TLR) ligands.
Mutagenesis	196 – 196	R -> A. Reduced interaction with TIRAP, and strongly reduced activity. Strongly reduced interaction with TIRAP; when associated with A-288.
Mutagenesis	197 – 197	D -> A. Slightly reduced activity.
Mutagenesis	203 – 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.
Helix	196 – 198

Literature citations
Functional assessment of the mutational effects of human IRAK4 and MyD88 genes.
Yamamoto T.; Tsutsumi N.; Tochio H.; Ohnishi H.; Kubota K.; Kato Z.; Shirakawa M.; Kondo N.;
Mol. Immunol. 58:66-76(2014)
Cited for: FUNCTION; INTERACTION WITH IRAK4; CHARACTERIZATION OF VARIANTS TYR-34; CYS-98 AND ILE-178; CHARACTERIZATION OF VARIANTS IMD68 GLU-52 DEL; PRO-93 AND CYS-196; Structural basis for the multiple interactions of the MyD88 TIR domain in TLR4 signaling.
Ohnishi H.; Tochio H.; Kato Z.; Orii K.E.; Li A.; Kimura T.; Hiroaki H.; Kondo N.; Shirakawa M.;
Proc. Natl. Acad. Sci. U.S.A. 106:10260-10265(2009)
Cited for: STRUCTURE BY NMR OF 148-296; FUNCTION; INTERACTION WITH TIRAP AND IRAK4; MUTAGENESIS OF ARG-196; ASP-197; ARG-217; LYS-282 AND ARG-288; CHARACTERIZATION OF VARIANT IMD68 CYS-196; 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)
Cited for: VARIANTS IMD68 PRO-93 AND CYS-196; CHARACTERIZATION OF VARIANTS IMD68 PRO-93 AND CYS-196; Clinical features and outcome of patients with IRAK-4 and MyD88 deficiency.
Picard C.; von Bernuth H.; Ghandil P.; Chrabieh M.; Levy O.; Arkwright P.D.; McDonald D.; Geha R.S.; Takada H.; Krause J.C.; Creech C.B.; Ku C.L.; Ehl S.; Marodi L.; Al-Muhsen S.; Al-Hajjar S.; Al-Ghonaium A.; Day-Good N.K.; Holland S.M.; Gallin J.I.; Chapel H.; Speert D.P.; Rodriguez-Gallego C.; Colino E.; Garty B.Z.; Roifman C.; Hara T.; Yoshikawa H.; Nonoyama S.; Domachowske J.; Issekutz A.C.; Tang M.; Smart J.; Zitnik S.E.; Hoarau C.; Kumararatne D.S.; Thrasher A.J.; Davies E.G.; Bethune C.; Sirvent N.; de Ricaud D.; Camcioglu Y.; Vasconcelos J.; Guedes M.; Vitor A.B.; Rodrigo C.; Almazan F.; Mendez M.; Arostegui J.I.; Alsina L.; Fortuny C.; Reichenbach J.; Verbsky J.W.; Bossuyt X.; Doffinger R.; Abel L.; Puel A.; Casanova J.L.;
Medicine (Baltimore) 89:403-425(2010)
Cited for: INVOLVEMENT IN IMD68; VARIANTS IMD68 GLU-52 DEL; PRO-93 AND CYS-196;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q99836: Variant p.Arg196Cys