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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q99836: Variant p.Arg196Cys

Myeloid differentiation primary response protein MyD88
Gene: MYD88
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Variant information Variant position: help 196
Type of variant: help LP/P [Disclaimer]
Residue change: help From Arginine (R) to Cysteine (C) at position 196 (R196C, p.Arg196Cys).
Physico-chemical properties: help Change from large size and basic (R) to medium size and polar (C)
BLOSUM score: help -3
Variant description: help In IMD68; results in a loss of function; decreases NF-kappa-B complex activation.
Other resources: help


Sequence information Variant position: help 196
Protein sequence length: help 296
Location on the sequence: help QEMIRQLEQTNYRLKLCVSD R DVLPGTCVWSIASELIEKRC
Residue conservation: help
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: help
TypePositionsDescription
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.