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MYD88_HUMAN
ID   MYD88_HUMAN             Reviewed;         296 AA.
AC   Q99836; B4DKH8; B4DKU4; B4DQ60; B4DQ72; J3KPU4; J3KQ87; J3KQJ6; P78397;
AC   Q53XS7;
DT   18-OCT-2001, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-1997, sequence version 1.
DT   03-AUG-2022, entry version 212.
DE   RecName: Full=Myeloid differentiation primary response protein MyD88 {ECO:0000305};
GN   Name=MYD88 {ECO:0000312|HGNC:HGNC:7562};
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND VARIANT
RP   CYS-98.
RC   TISSUE=Dendritic cell;
RX   PubMed=8957090;
RA   Hardiman G., Rock F.L., Balasubramanian S., Kastelein R.A., Bazan J.F.;
RT   "Molecular characterization and modular analysis of human MyD88.";
RL   Oncogene 13:2467-2475(1996).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND FUNCTION.
RC   TISSUE=Epidermal carcinoma;
RX   PubMed=9013863; DOI=10.1016/s0014-5793(96)01506-2;
RA   Bonnert T.P., Garka K.E., Parnet P., Sonoda G., Testa J.R., Sims J.E.;
RT   "The cloning and characterization of human MyD88: a member of an IL-1
RT   receptor related family.";
RL   FEBS Lett. 402:81-84(1997).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX   PubMed=18810425; DOI=10.1007/s00251-008-0332-0;
RA   Nakajima T., Ohtani H., Satta Y., Uno Y., Akari H., Ishida T., Kimura A.;
RT   "Natural selection in the TLR-related genes in the course of primate
RT   evolution.";
RL   Immunogenetics 60:727-735(2008).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA   Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA   Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA   Phelan M., Farmer A.;
RT   "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL   Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2; 3; 4 AND 5).
RC   TISSUE=Umbilical cord blood;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16641997; DOI=10.1038/nature04728;
RA   Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA   Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA   Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA   Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA   Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA   Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA   Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA   Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA   Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA   Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA   Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA   Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA   Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA   Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA   Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA   Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA   Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA   Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA   Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT   "The DNA sequence, annotation and analysis of human chromosome 3.";
RL   Nature 440:1194-1198(2006).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [8]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND NUCLEOTIDE SEQUENCE
RP   [MRNA] OF 190-224 (ISOFORM 6).
RC   TISSUE=Pancreas;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [9]
RP   FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH IRF7.
RX   PubMed=15361868; DOI=10.1038/ni1118;
RA   Kawai T., Sato S., Ishii K.J., Coban C., Hemmi H., Yamamoto M., Terai K.,
RA   Matsuda M., Inoue J., Uematsu S., Takeuchi O., Akira S.;
RT   "Interferon-alpha induction through Toll-like receptors involves a direct
RT   interaction of IRF7 with MyD88 and TRAF6.";
RL   Nat. Immunol. 5:1061-1068(2004).
RN   [10]
RP   SUBCELLULAR LOCATION, AND INTERACTION WITH IRF7.
RX   PubMed=15492225; DOI=10.1073/pnas.0406933101;
RA   Honda K., Yanai H., Mizutani T., Negishi H., Shimada N., Suzuki N.,
RA   Ohba Y., Takaoka A., Yeh W.C., Taniguchi T.;
RT   "Role of a transductional-transcriptional processor complex involving MyD88
RT   and IRF-7 in Toll-like receptor signaling.";
RL   Proc. Natl. Acad. Sci. U.S.A. 101:15416-15421(2004).
RN   [11]
RP   INTERACTION WITH IL1RL1.
RX   PubMed=16286016; DOI=10.1016/j.immuni.2005.09.015;
RA   Schmitz J., Owyang A., Oldham E., Song Y., Murphy E., McClanahan T.K.,
RA   Zurawski G., Moshrefi M., Qin J., Li X., Gorman D.M., Bazan J.F.,
RA   Kastelein R.A.;
RT   "IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-
RT   related protein ST 2 and induces T helper type 2-associated cytokines.";
RL   Immunity 23:479-490(2005).
RN   [12]
RP   IDENTIFICATION IN COMPLEX WITH IRAK1; IRAK4; TRAF6 AND PELI1.
RX   PubMed=16951688; DOI=10.1038/ni1383;
RA   Choi K.C., Lee Y.S., Lim S., Choi H.K., Lee C.H., Lee E.K., Hong S.,
RA   Kim I.H., Kim S.J., Park S.H.;
RT   "Smad6 negatively regulates interleukin 1-receptor-Toll-like receptor
RT   signaling through direct interaction with the adapter Pellino-1.";
RL   Nat. Immunol. 7:1057-1065(2006).
RN   [13]
RP   FUNCTION, AND INTERACTION WITH BMX.
RX   PubMed=18292575; DOI=10.4049/jimmunol.180.5.3485;
RA   Semaan N., Alsaleh G., Gottenberg J.E., Wachsmann D., Sibilia J.;
RT   "Etk/BMX, a Btk family tyrosine kinase, and Mal contribute to the cross-
RT   talk between MyD88 and FAK pathways.";
RL   J. Immunol. 180:3485-3491(2008).
RN   [14]
RP   INTERACTION WITH FLII; LRRFIP1 AND LRRFIP2.
RX   PubMed=19265123; DOI=10.4049/jimmunol.0802260;
RA   Dai P., Jeong S.Y., Yu Y., Leng T., Wu W., Xie L., Chen X.;
RT   "Modulation of TLR signaling by multiple MyD88-interacting partners
RT   including leucine-rich repeat Fli-I-interacting proteins.";
RL   J. Immunol. 182:3450-3460(2009).
RN   [15]
RP   FUNCTION, AND INTERACTION WITH TLR5.
RX   PubMed=20855887; DOI=10.1074/jbc.m110.158394;
RA   Choi Y.J., Im E., Chung H.K., Pothoulakis C., Rhee S.H.;
RT   "TRIF mediates Toll-like receptor 5-induced signaling in intestinal
RT   epithelial cells.";
RL   J. Biol. Chem. 285:37570-37578(2010).
RN   [16]
RP   INTERACTION WITH TIRAP.
RX   PubMed=19948740; DOI=10.1074/jbc.m109.069385;
RA   Wan T., Liu T., Zhang H., Tang S., Min W.;
RT   "AIP1 functions as Arf6-GAP to negatively regulate TLR4 signaling.";
RL   J. Biol. Chem. 285:3750-3757(2010).
RN   [17]
RP   INTERACTION WITH DHX9.
RX   PubMed=20696886; DOI=10.1073/pnas.1006539107;
RA   Kim T., Pazhoor S., Bao M., Zhang Z., Hanabuchi S., Facchinetti V.,
RA   Bover L., Plumas J., Chaperot L., Qin J., Liu Y.J.;
RT   "Aspartate-glutamate-alanine-histidine box motif (DEAH)/RNA helicase A
RT   helicases sense microbial DNA in human plasmacytoid dendritic cells.";
RL   Proc. Natl. Acad. Sci. U.S.A. 107:15181-15186(2010).
RN   [18]
RP   INTERACTION WITH IRAK4, AND CHARACTERIZATION OF VARIANTS TYR-34; CYS-98 AND
RP   ILE-178.
RX   PubMed=20966070; DOI=10.1074/jbc.m110.159996;
RA   George J., Motshwene P.G., Wang H., Kubarenko A.V., Rautanen A.,
RA   Mills T.C., Hill A.V., Gay N.J., Weber A.N.;
RT   "Two human MYD88 variants, S34Y and R98C, interfere with MyD88-IRAK4-
RT   myddosome assembly.";
RL   J. Biol. Chem. 286:1341-1353(2011).
RN   [19]
RP   INTERACTION WITH IKBKE.
RX   PubMed=23453969; DOI=10.1016/j.celrep.2013.01.031;
RA   Zhou A.Y., Shen R.R., Kim E., Lock Y.J., Xu M., Chen Z.J., Hahn W.C.;
RT   "IKKepsilon-mediated tumorigenesis requires K63-linked polyubiquitination
RT   by a cIAP1/cIAP2/TRAF2 E3 ubiquitin ligase complex.";
RL   Cell Rep. 3:724-733(2013).
RN   [20]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-244, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Erythroleukemia;
RX   PubMed=23186163; DOI=10.1021/pr300630k;
RA   Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA   Mohammed S.;
RT   "Toward a comprehensive characterization of a human cancer cell
RT   phosphoproteome.";
RL   J. Proteome Res. 12:260-271(2013).
RN   [21]
RP   FUNCTION, INTERACTION WITH IRAK4, CHARACTERIZATION OF VARIANTS TYR-34;
RP   CYS-98 AND ILE-178, AND CHARACTERIZATION OF VARIANTS IMD68 GLU-52 DEL;
RP   PRO-93 AND CYS-196.
RX   PubMed=24316379; DOI=10.1016/j.molimm.2013.11.008;
RA   Yamamoto T., Tsutsumi N., Tochio H., Ohnishi H., Kubota K., Kato Z.,
RA   Shirakawa M., Kondo N.;
RT   "Functional assessment of the mutational effects of human IRAK4 and MyD88
RT   genes.";
RL   Mol. Immunol. 58:66-76(2014).
RN   [22]
RP   INTERACTION WITH E.FAECALIS PROTEIN TCPF (MICROBIAL INFECTION).
RX   PubMed=25369374; DOI=10.1371/journal.pone.0112010;
RA   Zou J., Baghdayan A.S., Payne S.J., Shankar N.;
RT   "A TIR domain protein from E. faecalis attenuates MyD88-mediated signaling
RT   and NF-kappaB activation.";
RL   PLoS ONE 9:E112010-E112010(2014).
RN   [23]
RP   INTERACTION WITH OTUD4, AND UBIQUITINATION.
RX   PubMed=29395066; DOI=10.1016/j.molcel.2018.01.009;
RA   Zhao Y., Mudge M.C., Soll J.M., Rodrigues R.B., Byrum A.K.,
RA   Schwarzkopf E.A., Bradstreet T.R., Gygi S.P., Edelson B.T.,
RA   Mosammaparast N.;
RT   "OTUD4 Is a Phospho-Activated K63 Deubiquitinase that Regulates MyD88-
RT   Dependent Signaling.";
RL   Mol. Cell 69:505-516(2018).
RN   [24]
RP   FUNCTION.
RX   PubMed=33718825; DOI=10.1016/j.isci.2021.102295;
RA   Campbell G.R., To R.K., Hanna J., Spector S.A.;
RT   "SARS-CoV-2, SARS-CoV-1, and HIV-1 derived ssRNA sequences activate the
RT   NLRP3 inflammasome in human macrophages through a non-classical pathway.";
RL   IScience 1:102295-102295(2021).
RN   [25]
RP   STRUCTURE BY NMR OF 148-296, FUNCTION, INTERACTION WITH TIRAP AND IRAK4,
RP   MUTAGENESIS OF ARG-196; ASP-197; ARG-217; LYS-282 AND ARG-288, AND
RP   CHARACTERIZATION OF VARIANT IMD68 CYS-196.
RX   PubMed=19506249; DOI=10.1073/pnas.0812956106;
RA   Ohnishi H., Tochio H., Kato Z., Orii K.E., Li A., Kimura T., Hiroaki H.,
RA   Kondo N., Shirakawa M.;
RT   "Structural basis for the multiple interactions of the MyD88 TIR domain in
RT   TLR4 signaling.";
RL   Proc. Natl. Acad. Sci. U.S.A. 106:10260-10265(2009).
RN   [26]
RP   STRUCTURE BY NMR OF 146-296.
RG   Northeast structural genomics consortium (NESG);
RT   "Solution NMR structure of human myeloid differentiation primary response
RT   (MYD88).";
RL   Submitted (FEB-2009) to the PDB data bank.
RN   [27] {ECO:0007744|PDB:4DOM, ECO:0007744|PDB:4EO7}
RP   X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS) OF 157-296, MUTAGENESIS OF ILE-179;
RP   CYS-203 AND CYS-280, AND INTERACTION WITH E.COLI PROTEIN TCPC (MICROBIAL
RP   INFECTION).
RX   PubMed=23569230; DOI=10.1073/pnas.1215770110;
RA   Snyder G.A., Cirl C., Jiang J., Chen K., Waldhuber A., Smith P.,
RA   Roemmler F., Snyder N., Fresquez T., Duerr S., Tjandra N., Miethke T.,
RA   Xiao T.S.;
RT   "Molecular mechanisms for the subversion of MyD88 signaling by TcpC from
RT   virulent uropathogenic Escherichia coli.";
RL   Proc. Natl. Acad. Sci. U.S.A. 110:6985-6990(2013).
RN   [28]
RP   VARIANTS IMD68 PRO-93 AND CYS-196, AND CHARACTERIZATION OF VARIANTS IMD68
RP   PRO-93 AND CYS-196.
RX   PubMed=18669862; DOI=10.1126/science.1158298;
RA   von Bernuth H., Picard C., Jin Z., Pankla R., Xiao H., Ku C.-L.,
RA   Chrabieh M., Mustapha I.B., Ghandil P., Camcioglu Y., Vasconcelos J.,
RA   Sirvent N., Guedes M., Vitor A.B., Herrero-Mata M.J., Arostegui J.I.,
RA   Rodrigo C., Alsina L., Ruiz-Ortiz E., Juan M., Fortuny C., Yaguee J.,
RA   Anton J., Pascal M., Chang H.-H., Janniere L., Rose Y., Garty B.-Z.,
RA   Chapel H., Issekutz A., Marodi L., Rodriguez-Gallego C., Banchereau J.,
RA   Abel L., Li X., Chaussabel D., Puel A., Casanova J.-L.;
RT   "Pyogenic bacterial infections in humans with MyD88 deficiency.";
RL   Science 321:691-696(2008).
RN   [29]
RP   INVOLVEMENT IN IMD68, AND VARIANTS IMD68 GLU-52 DEL; PRO-93 AND CYS-196.
RX   PubMed=21057262; DOI=10.1097/md.0b013e3181fd8ec3;
RA   Picard C., von Bernuth H., Ghandil P., Chrabieh M., Levy O.,
RA   Arkwright P.D., McDonald D., Geha R.S., Takada H., Krause J.C.,
RA   Creech C.B., Ku C.L., Ehl S., Marodi L., Al-Muhsen S., Al-Hajjar S.,
RA   Al-Ghonaium A., Day-Good N.K., Holland S.M., Gallin J.I., Chapel H.,
RA   Speert D.P., Rodriguez-Gallego C., Colino E., Garty B.Z., Roifman C.,
RA   Hara T., Yoshikawa H., Nonoyama S., Domachowske J., Issekutz A.C., Tang M.,
RA   Smart J., Zitnik S.E., Hoarau C., Kumararatne D.S., Thrasher A.J.,
RA   Davies E.G., Bethune C., Sirvent N., de Ricaud D., Camcioglu Y.,
RA   Vasconcelos J., Guedes M., Vitor A.B., Rodrigo C., Almazan F., Mendez M.,
RA   Arostegui J.I., Alsina L., Fortuny C., Reichenbach J., Verbsky J.W.,
RA   Bossuyt X., Doffinger R., Abel L., Puel A., Casanova J.L.;
RT   "Clinical features and outcome of patients with IRAK-4 and MyD88
RT   deficiency.";
RL   Medicine (Baltimore) 89:403-425(2010).
RN   [30]
RP   VARIANTS MET-39; GLY-136; ILE-136; PHE-204; ARG-205; CYS-206; THR-207;
RP   ARG-209; THR-219; ASN-230 AND PRO-281, CHARACTERIZATION OF VARIANTS
RP   ARG-209; THR-219; ASN-230 AND PRO-281, INTERACTION WITH IRAK4, VARIANT WM1
RP   PRO-252, AND CHARACTERIZATION OF VARIANT WM1 PRO-252.
RX   PubMed=21179087; DOI=10.1038/nature09671;
RA   Ngo V.N., Young R.M., Schmitz R., Jhavar S., Xiao W., Lim K.H.,
RA   Kohlhammer H., Xu W., Yang Y., Zhao H., Shaffer A.L., Romesser P.,
RA   Wright G., Powell J., Rosenwald A., Muller-Hermelink H.K., Ott G.,
RA   Gascoyne R.D., Connors J.M., Rimsza L.M., Campo E., Jaffe E.S., Delabie J.,
RA   Smeland E.B., Fisher R.I., Braziel R.M., Tubbs R.R., Cook J.R.,
RA   Weisenburger D.D., Chan W.C., Staudt L.M.;
RT   "Oncogenically active MYD88 mutations in human lymphoma.";
RL   Nature 470:115-119(2011).
RN   [31]
RP   VARIANT WM1 PRO-252.
RX   PubMed=22931316; DOI=10.1056/nejmoa1200710;
RA   Treon S.P., Xu L., Yang G., Zhou Y., Liu X., Cao Y., Sheehy P.,
RA   Manning R.J., Patterson C.J., Tripsas C., Arcaini L., Pinkus G.S.,
RA   Rodig S.J., Sohani A.R., Harris N.L., Laramie J.M., Skifter D.A.,
RA   Lincoln S.E., Hunter Z.R.;
RT   "MYD88 L265P somatic mutation in Waldenstrom's macroglobulinemia.";
RL   N. Engl. J. Med. 367:826-833(2012).
RN   [32]
RP   VARIANT WM1 PRO-252.
RX   PubMed=24366360; DOI=10.1182/blood-2013-09-525808;
RA   Hunter Z.R., Xu L., Yang G., Zhou Y., Liu X., Cao Y., Manning R.J.,
RA   Tripsas C., Patterson C.J., Sheehy P., Treon S.P.;
RT   "The genomic landscape of Waldenstrom macroglobulinemia is characterized by
RT   highly recurring MYD88 and WHIM-like CXCR4 mutations, and small somatic
RT   deletions associated with B-cell lymphomagenesis.";
RL   Blood 123:1637-1646(2014).
CC   -!- FUNCTION: Adapter protein involved in the Toll-like receptor and IL-1
CC       receptor signaling pathway in the innate immune response
CC       (PubMed:15361868, PubMed:18292575, PubMed:33718825). Acts via IRAK1,
CC       IRAK2, IRF7 and TRAF6, leading to NF-kappa-B activation, cytokine
CC       secretion and the inflammatory response (PubMed:15361868,
CC       PubMed:24316379, PubMed:19506249). Increases IL-8 transcription
CC       (PubMed:9013863). Involved in IL-18-mediated signaling pathway.
CC       Activates IRF1 resulting in its rapid migration into the nucleus to
CC       mediate an efficient induction of IFN-beta, NOS2/INOS, and IL12A genes.
CC       Upon TLR8 activation by GU-rich single-stranded RNA (GU-rich RNA)
CC       derived from viruses such as SARS-CoV-2, SARS-CoV and HIV-1, induces
CC       IL1B release through NLRP3 inflammasome activation (PubMed:33718825).
CC       MyD88-mediated signaling in intestinal epithelial cells is crucial for
CC       maintenance of gut homeostasis and controls the expression of the
CC       antimicrobial lectin REG3G in the small intestine (By similarity).
CC       {ECO:0000250|UniProtKB:P22366, ECO:0000269|PubMed:15361868,
CC       ECO:0000269|PubMed:18292575, ECO:0000269|PubMed:19506249,
CC       ECO:0000269|PubMed:20855887, ECO:0000269|PubMed:24316379,
CC       ECO:0000269|PubMed:33718825, ECO:0000269|PubMed:9013863}.
CC   -!- SUBUNIT: Homodimer. Also forms heterodimers with TIRAP. Binds to TLR2,
CC       TLR4, TLR5, IRAK1, IRAK2 and IRAK4 via their respective TIR domains.
CC       Interacts with IL18R1. Interacts with BMX, IL1RL1, IKBKE and IRF7.
CC       Interacts with LRRFIP1 and LRRFIP2; this interaction positively
CC       regulates Toll-like receptor (TLR) signaling in response to agonist.
CC       Interacts with FLII. LRRFIP1 and LRRFIP2 compete with FLII for MYD88-
CC       binding. Interacts with IRF1. Upon IL1B treatment, forms a complex with
CC       PELI1, IRAK1, IRAK4 and TRAF6; this complex recruits MAP3K7/TAK1, TAB1
CC       and TAB2 to mediate NF-kappa-B activation. Direct binding of SMAD6 to
CC       PELI1 prevents the complex formation and hence negatively regulates
CC       IL1R-TLR signaling and eventually NF-kappa-B-mediated gene expression.
CC       May interact with PIK3AP1. Interacts (via TIR domain) with DHX9 (via
CC       H2A and OB-fold regions); this interaction is direct (PubMed:20696886).
CC       Interacts with OTUD4 deubiquitinase; the interaction is direct
CC       (PubMed:29395066). {ECO:0000269|PubMed:15361868,
CC       ECO:0000269|PubMed:15492225, ECO:0000269|PubMed:16286016,
CC       ECO:0000269|PubMed:16951688, ECO:0000269|PubMed:18292575,
CC       ECO:0000269|PubMed:19265123, ECO:0000269|PubMed:19506249,
CC       ECO:0000269|PubMed:19948740, ECO:0000269|PubMed:20696886,
CC       ECO:0000269|PubMed:20855887, ECO:0000269|PubMed:20966070,
CC       ECO:0000269|PubMed:21179087, ECO:0000269|PubMed:23453969,
CC       ECO:0000269|PubMed:24316379, ECO:0000269|PubMed:29395066}.
CC   -!- SUBUNIT: (Microbial infection) In case of infection, interacts with
CC       uropathogenic E.coli protein TcpC; suppressing Toll-like receptor
CC       (TLR)-mediated cytokine production. {ECO:0000269|PubMed:23569230}.
CC   -!- SUBUNIT: (Microbial infection) In case of infection, interacts with
CC       uropathogenic E.faecalis protein TcpF; suppressing Toll-like receptor
CC       (TLR)-mediated cytokine production. {ECO:0000269|PubMed:25369374}.
CC   -!- INTERACTION:
CC       Q99836; Q8NF50: DOCK8; NbExp=3; IntAct=EBI-447677, EBI-2548605;
CC       Q99836; Q13158: FADD; NbExp=3; IntAct=EBI-447677, EBI-494804;
CC       Q99836; Q9UBN7: HDAC6; NbExp=6; IntAct=EBI-447677, EBI-301697;
CC       Q99836; P51617: IRAK1; NbExp=2; IntAct=EBI-447677, EBI-358664;
CC       Q99836; Q69FE3: IRAK4; NbExp=5; IntAct=EBI-447677, EBI-10249217;
CC       Q99836; Q9NWZ3: IRAK4; NbExp=15; IntAct=EBI-447677, EBI-448378;
CC       Q99836; Q99836: MYD88; NbExp=40; IntAct=EBI-447677, EBI-447677;
CC       Q99836; Q96HA8: NTAQ1; NbExp=3; IntAct=EBI-447677, EBI-741158;
CC       Q99836; P78317: RNF4; NbExp=3; IntAct=EBI-447677, EBI-2340927;
CC       Q99836; Q6SZW1: SARM1; NbExp=5; IntAct=EBI-447677, EBI-11693532;
CC       Q99836; Q8IUQ4: SIAH1; NbExp=3; IntAct=EBI-447677, EBI-747107;
CC       Q99836; P84022: SMAD3; NbExp=3; IntAct=EBI-447677, EBI-347161;
CC       Q99836; O43791: SPOP; NbExp=7; IntAct=EBI-447677, EBI-743549;
CC       Q99836; Q6IQ16: SPOPL; NbExp=3; IntAct=EBI-447677, EBI-2822161;
CC       Q99836; Q9UGK3: STAP2; NbExp=3; IntAct=EBI-447677, EBI-1553984;
CC       Q99836; P58753: TIRAP; NbExp=8; IntAct=EBI-447677, EBI-528644;
CC       Q99836; O60603: TLR2; NbExp=4; IntAct=EBI-447677, EBI-973722;
CC       Q99836; O00206: TLR4; NbExp=4; IntAct=EBI-447677, EBI-528701;
CC       Q99836; O14836: TNFRSF13B; NbExp=12; IntAct=EBI-447677, EBI-519160;
CC       Q99836; P10599: TXN; NbExp=4; IntAct=EBI-447677, EBI-594644;
CC       Q99836; Q93009: USP7; NbExp=3; IntAct=EBI-447677, EBI-302474;
CC       Q99836; P13682: ZNF35; NbExp=3; IntAct=EBI-447677, EBI-11041653;
CC       Q99836; Q8YF33: BMEI1694; Xeno; NbExp=4; IntAct=EBI-447677, EBI-11616155;
CC       Q99836; PRO_0000278740 [Q03463]; Xeno; NbExp=3; IntAct=EBI-447677, EBI-8803426;
CC       Q99836-1; Q99418: CYTH2; NbExp=3; IntAct=EBI-15855480, EBI-448974;
CC       Q99836-1; Q9NWZ3: IRAK4; NbExp=9; IntAct=EBI-15855480, EBI-448378;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15361868,
CC       ECO:0000269|PubMed:15492225}. Nucleus {ECO:0000269|PubMed:21057262}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=6;
CC       Name=1;
CC         IsoId=Q99836-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q99836-2; Sequence=VSP_038887;
CC       Name=3;
CC         IsoId=Q99836-3; Sequence=VSP_043500;
CC       Name=4;
CC         IsoId=Q99836-4; Sequence=VSP_043498, VSP_043499, VSP_043500;
CC       Name=5;
CC         IsoId=Q99836-5; Sequence=VSP_053764;
CC       Name=6;
CC         IsoId=Q99836-6; Sequence=VSP_053765;
CC   -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:8957090}.
CC   -!- DOMAIN: The intermediate domain (ID) is required for the
CC       phosphorylation and activation of IRAK. {ECO:0000250|UniProtKB:P22366}.
CC   -!- PTM: Ubiquitinated; undergoes 'Lys-63'-linked polyubiquitination. OTUD4
CC       specifically hydrolyzes 'Lys-63'-linked polyubiquitinated MYD88.
CC       {ECO:0000269|PubMed:29395066}.
CC   -!- DISEASE: Immunodeficiency 68 (IMD68) [MIM:612260]: An autosomal
CC       recessive primary immunodeficiency characterized by life-threatening,
CC       often recurrent, pyogenic bacterial infections, including invasive
CC       pneumococcal disease, beginning in infancy or early childhood.
CC       {ECO:0000269|PubMed:18669862, ECO:0000269|PubMed:19506249,
CC       ECO:0000269|PubMed:21057262, ECO:0000269|PubMed:24316379}. Note=The
CC       disease is caused by variants affecting the gene represented in this
CC       entry.
CC   -!- DISEASE: Macroglobulinemia, Waldenstrom, 1 (WM1) [MIM:153600]: A
CC       malignant B-cell neoplasm characterized by lymphoplasmacytic
CC       infiltration of the bone marrow and hypersecretion of monoclonal
CC       immunoglobulin M (IgM) protein. Clinical features are variable and
CC       include anemia, thrombocytopenia, hepatosplenomegaly, and
CC       lymphadenopathy. Many patients have asymptomatic or indolent disease.
CC       {ECO:0000269|PubMed:21179087, ECO:0000269|PubMed:22931316,
CC       ECO:0000269|PubMed:24366360}. Note=The disease is caused by variants
CC       affecting the gene represented in this entry.
CC   -!- DISEASE: Note=Defects in MYD88 are frequently found in many
CC       hematological malignancies, such as activated B-cell type diffuse large
CC       B-cell lymphoma (ABC-DLBCL), cutaneous diffuse large B cell lymphoma
CC       (CBCL) and primary central nervous system lymphoma (PCNSL).
CC       {ECO:0000269|PubMed:21179087, ECO:0000269|PubMed:22931316}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAG60822.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC       Sequence=BAG60834.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC       Sequence=EAW64521.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR   EMBL; U70451; AAB49967.1; -; mRNA.
DR   EMBL; U84408; AAC50954.1; -; mRNA.
DR   EMBL; AB446470; BAG55247.1; -; mRNA.
DR   EMBL; BT007376; AAP36040.1; -; mRNA.
DR   EMBL; AK296570; BAG59190.1; -; mRNA.
DR   EMBL; AK296716; BAG59306.1; -; mRNA.
DR   EMBL; AK298650; BAG60822.1; ALT_INIT; mRNA.
DR   EMBL; AK298666; BAG60834.1; ALT_INIT; mRNA.
DR   EMBL; AP006309; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471055; EAW64521.1; ALT_SEQ; Genomic_DNA.
DR   EMBL; BC013589; AAH13589.1; -; mRNA.
DR   EMBL; BI524129; -; NOT_ANNOTATED_CDS; mRNA.
DR   CCDS; CCDS2674.2; -. [Q99836-1]
DR   CCDS; CCDS54565.1; -. [Q99836-6]
DR   CCDS; CCDS54566.1; -. [Q99836-3]
DR   CCDS; CCDS54567.1; -. [Q99836-2]
DR   CCDS; CCDS54568.1; -. [Q99836-4]
DR   RefSeq; NP_001166037.1; NM_001172566.1. [Q99836-4]
DR   RefSeq; NP_001166039.1; NM_001172568.1. [Q99836-2]
DR   RefSeq; NP_001166040.1; NM_001172569.1. [Q99836-3]
DR   RefSeq; NP_002459.2; NM_002468.4. [Q99836-1]
DR   PDB; 2JS7; NMR; -; A=146-296.
DR   PDB; 2Z5V; NMR; -; A=148-296.
DR   PDB; 3MOP; X-ray; 3.40 A; A/B/C/D/E/F=20-117.
DR   PDB; 4DOM; X-ray; 1.80 A; A=157-296.
DR   PDB; 4EO7; X-ray; 1.45 A; A=157-296.
DR   PDB; 6I3N; EM; 3.10 A; A/B/C/D/E/F/G/H/I/J/K/L/M=1-151.
DR   PDB; 7BEQ; EM; 3.00 A; A=154-296.
DR   PDB; 7BER; X-ray; 2.30 A; A=154-296.
DR   PDB; 7L6W; X-ray; 2.30 A; A=159-296.
DR   PDBsum; 2JS7; -.
DR   PDBsum; 2Z5V; -.
DR   PDBsum; 3MOP; -.
DR   PDBsum; 4DOM; -.
DR   PDBsum; 4EO7; -.
DR   PDBsum; 6I3N; -.
DR   PDBsum; 7BEQ; -.
DR   PDBsum; 7BER; -.
DR   PDBsum; 7L6W; -.
DR   AlphaFoldDB; Q99836; -.
DR   SMR; Q99836; -.
DR   BioGRID; 110700; 78.
DR   DIP; DIP-31349N; -.
DR   IntAct; Q99836; 46.
DR   MINT; Q99836; -.
DR   STRING; 9606.ENSP00000401399; -.
DR   BindingDB; Q99836; -.
DR   ChEMBL; CHEMBL5919; -.
DR   iPTMnet; Q99836; -.
DR   PhosphoSitePlus; Q99836; -.
DR   SwissPalm; Q99836; -.
DR   BioMuta; MYD88; -.
DR   DMDM; 18202671; -.
DR   EPD; Q99836; -.
DR   jPOST; Q99836; -.
DR   MassIVE; Q99836; -.
DR   MaxQB; Q99836; -.
DR   PaxDb; Q99836; -.
DR   PeptideAtlas; Q99836; -.
DR   PRIDE; Q99836; -.
DR   ProteomicsDB; 78500; -. [Q99836-1]
DR   ProteomicsDB; 78501; -. [Q99836-2]
DR   ProteomicsDB; 78502; -. [Q99836-3]
DR   ProteomicsDB; 78503; -. [Q99836-4]
DR   TopDownProteomics; Q99836-4; -. [Q99836-4]
DR   Antibodypedia; 3965; 977 antibodies from 51 providers.
DR   DNASU; 4615; -.
DR   Ensembl; ENST00000396334.8; ENSP00000379625.4; ENSG00000172936.16. [Q99836-1]
DR   Ensembl; ENST00000417037.8; ENSP00000401399.4; ENSG00000172936.16. [Q99836-2]
DR   Ensembl; ENST00000421516.3; ENSP00000391753.3; ENSG00000172936.16. [Q99836-6]
DR   Ensembl; ENST00000650112.2; ENSP00000497991.2; ENSG00000172936.16. [Q99836-4]
DR   Ensembl; ENST00000650905.2; ENSP00000498360.2; ENSG00000172936.16. [Q99836-1]
DR   Ensembl; ENST00000651800.2; ENSP00000499012.2; ENSG00000172936.16. [Q99836-3]
DR   GeneID; 4615; -.
DR   KEGG; hsa:4615; -.
DR   MANE-Select; ENST00000650905.2; ENSP00000498360.2; NM_002468.5; NP_002459.3.
DR   UCSC; uc011ayj.3; human. [Q99836-1]
DR   CTD; 4615; -.
DR   DisGeNET; 4615; -.
DR   GeneCards; MYD88; -.
DR   HGNC; HGNC:7562; MYD88.
DR   HPA; ENSG00000172936; Low tissue specificity.
DR   MalaCards; MYD88; -.
DR   MIM; 153600; phenotype.
DR   MIM; 602170; gene.
DR   MIM; 612260; phenotype.
DR   neXtProt; NX_Q99836; -.
DR   OpenTargets; ENSG00000172936; -.
DR   Orphanet; 183713; Bacterial susceptibility due to TLR signaling pathway deficiency.
DR   Orphanet; 33226; Waldenstroem macroglobulinemia.
DR   PharmGKB; PA31361; -.
DR   VEuPathDB; HostDB:ENSG00000172936; -.
DR   eggNOG; ENOG502QWKI; Eukaryota.
DR   GeneTree; ENSGT00510000048324; -.
DR   HOGENOM; CLU_116540_0_0_1; -.
DR   InParanoid; Q99836; -.
DR   OMA; CTQSWFW; -.
DR   PhylomeDB; Q99836; -.
DR   TreeFam; TF326264; -.
DR   PathwayCommons; Q99836; -.
DR   Reactome; R-HSA-1236974; ER-Phagosome pathway.
DR   Reactome; R-HSA-1257604; PIP3 activates AKT signaling.
DR   Reactome; R-HSA-166058; MyD88:MAL(TIRAP) cascade initiated on plasma membrane.
DR   Reactome; R-HSA-1810476; RIP-mediated NFkB activation via ZBP1.
DR   Reactome; R-HSA-209543; p75NTR recruits signalling complexes.
DR   Reactome; R-HSA-3134963; DEx/H-box helicases activate type I IFN and inflammatory cytokines production.
DR   Reactome; R-HSA-5602498; MyD88 deficiency (TLR2/4).
DR   Reactome; R-HSA-5602680; MyD88 deficiency (TLR5).
DR   Reactome; R-HSA-5603037; IRAK4 deficiency (TLR5).
DR   Reactome; R-HSA-5603041; IRAK4 deficiency (TLR2/4).
DR   Reactome; R-HSA-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR   Reactome; R-HSA-9020702; Interleukin-1 signaling.
DR   Reactome; R-HSA-975110; TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling.
DR   Reactome; R-HSA-975138; TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation.
DR   Reactome; R-HSA-975155; MyD88 dependent cascade initiated on endosome.
DR   Reactome; R-HSA-975871; MyD88 cascade initiated on plasma membrane.
DR   SignaLink; Q99836; -.
DR   SIGNOR; Q99836; -.
DR   BioGRID-ORCS; 4615; 26 hits in 1083 CRISPR screens.
DR   ChiTaRS; MYD88; human.
DR   EvolutionaryTrace; Q99836; -.
DR   GeneWiki; MYD88; -.
DR   GenomeRNAi; 4615; -.
DR   Pharos; Q99836; Tbio.
DR   PRO; PR:Q99836; -.
DR   Proteomes; UP000005640; Chromosome 3.
DR   RNAct; Q99836; protein.
DR   Bgee; ENSG00000172936; Expressed in leukocyte and 198 other tissues.
DR   ExpressionAtlas; Q99836; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; IDA:AgBase.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0010008; C:endosome membrane; TAS:Reactome.
DR   GO; GO:0005634; C:nucleus; IDA:AgBase.
DR   GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR   GO; GO:0014069; C:postsynaptic density; IEA:Ensembl.
DR   GO; GO:0032991; C:protein-containing complex; IEA:Ensembl.
DR   GO; GO:0005123; F:death receptor binding; TAS:ProtInc.
DR   GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR   GO; GO:0005149; F:interleukin-1 receptor binding; IEA:Ensembl.
DR   GO; GO:0043621; F:protein self-association; IDA:AgBase.
DR   GO; GO:0070976; F:TIR domain binding; IPI:BHF-UCL.
DR   GO; GO:0005121; F:Toll binding; IEA:Ensembl.
DR   GO; GO:0035325; F:Toll-like receptor binding; IBA:GO_Central.
DR   GO; GO:0070935; P:3'-UTR-mediated mRNA stabilization; IDA:BHF-UCL.
DR   GO; GO:0006915; P:apoptotic process; IMP:AgBase.
DR   GO; GO:0007166; P:cell surface receptor signaling pathway; TAS:ProtInc.
DR   GO; GO:0071222; P:cellular response to lipopolysaccharide; ISS:ARUK-UCL.
DR   GO; GO:0071260; P:cellular response to mechanical stimulus; IEP:UniProtKB.
DR   GO; GO:0140052; P:cellular response to oxidised low-density lipoprotein particle stimulus; ISS:ARUK-UCL.
DR   GO; GO:0042742; P:defense response to bacterium; IMP:BHF-UCL.
DR   GO; GO:0050830; P:defense response to Gram-positive bacterium; ISS:UniProtKB.
DR   GO; GO:0042832; P:defense response to protozoan; ISS:ARUK-UCL.
DR   GO; GO:0051607; P:defense response to virus; IDA:UniProtKB.
DR   GO; GO:0090557; P:establishment of endothelial intestinal barrier; IEA:Ensembl.
DR   GO; GO:0007249; P:I-kappaB kinase/NF-kappaB signaling; IEA:Ensembl.
DR   GO; GO:0016064; P:immunoglobulin mediated immune response; IEA:Ensembl.
DR   GO; GO:0009682; P:induced systemic resistance; IEA:Ensembl.
DR   GO; GO:0045087; P:innate immune response; IBA:GO_Central.
DR   GO; GO:0070498; P:interleukin-1-mediated signaling pathway; IEA:Ensembl.
DR   GO; GO:0007254; P:JNK cascade; IEA:Ensembl.
DR   GO; GO:0002269; P:leukocyte activation involved in inflammatory response; IEA:Ensembl.
DR   GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; IEA:Ensembl.
DR   GO; GO:0002755; P:MyD88-dependent toll-like receptor signaling pathway; IEA:Ensembl.
DR   GO; GO:0002283; P:neutrophil activation involved in immune response; IEA:Ensembl.
DR   GO; GO:0070944; P:neutrophil-mediated killing of bacterium; IEA:Ensembl.
DR   GO; GO:0006909; P:phagocytosis; IMP:UniProtKB.
DR   GO; GO:0032722; P:positive regulation of chemokine production; IEA:Ensembl.
DR   GO; GO:1900017; P:positive regulation of cytokine production involved in inflammatory response; IMP:BHF-UCL.
DR   GO; GO:0010628; P:positive regulation of gene expression; ISS:ARUK-UCL.
DR   GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IEP:UniProtKB.
DR   GO; GO:0032731; P:positive regulation of interleukin-1 beta production; IDA:UniProtKB.
DR   GO; GO:0032740; P:positive regulation of interleukin-17 production; ISS:BHF-UCL.
DR   GO; GO:0032747; P:positive regulation of interleukin-23 production; ISS:BHF-UCL.
DR   GO; GO:0032755; P:positive regulation of interleukin-6 production; ISS:BHF-UCL.
DR   GO; GO:0032757; P:positive regulation of interleukin-8 production; IMP:BHF-UCL.
DR   GO; GO:0046330; P:positive regulation of JNK cascade; IEA:Ensembl.
DR   GO; GO:0050671; P:positive regulation of lymphocyte proliferation; IEA:Ensembl.
DR   GO; GO:0060907; P:positive regulation of macrophage cytokine production; IEA:Ensembl.
DR   GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IMP:AgBase.
DR   GO; GO:1900227; P:positive regulation of NLRP3 inflammasome complex assembly; IMP:UniProtKB.
DR   GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; IEA:Ensembl.
DR   GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IEA:Ensembl.
DR   GO; GO:0032481; P:positive regulation of type I interferon production; IMP:BHF-UCL.
DR   GO; GO:2000338; P:regulation of chemokine (C-X-C motif) ligand 1 production; IEA:Ensembl.
DR   GO; GO:2000341; P:regulation of chemokine (C-X-C motif) ligand 2 production; IEA:Ensembl.
DR   GO; GO:0050727; P:regulation of inflammatory response; ISS:BHF-UCL.
DR   GO; GO:1902622; P:regulation of neutrophil migration; IEA:Ensembl.
DR   GO; GO:0014075; P:response to amine; IEA:Ensembl.
DR   GO; GO:0043200; P:response to amino acid; IEA:Ensembl.
DR   GO; GO:0045471; P:response to ethanol; IEA:Ensembl.
DR   GO; GO:0070555; P:response to interleukin-1; IMP:BHF-UCL.
DR   GO; GO:0002238; P:response to molecule of fungal origin; IEA:Ensembl.
DR   GO; GO:0014070; P:response to organic cyclic compound; IEA:Ensembl.
DR   GO; GO:0032494; P:response to peptidoglycan; IEA:Ensembl.
DR   GO; GO:0007165; P:signal transduction; NAS:ProtInc.
DR   GO; GO:0008063; P:Toll signaling pathway; IBA:GO_Central.
DR   GO; GO:0034158; P:toll-like receptor 8 signaling pathway; IDA:UniProtKB.
DR   GO; GO:0060337; P:type I interferon signaling pathway; IMP:BHF-UCL.
DR   CDD; cd08312; Death_MyD88; 1.
DR   Gene3D; 1.10.533.10; -; 1.
DR   Gene3D; 3.40.50.10140; -; 1.
DR   InterPro; IPR011029; DEATH-like_dom_sf.
DR   InterPro; IPR000488; Death_domain.
DR   InterPro; IPR034249; MyD88_Death.
DR   InterPro; IPR017281; Myelin_different_resp_MyD88.
DR   InterPro; IPR000157; TIR_dom.
DR   InterPro; IPR035897; Toll_tir_struct_dom_sf.
DR   PANTHER; PTHR15079; PTHR15079; 1.
DR   Pfam; PF00531; Death; 1.
DR   Pfam; PF01582; TIR; 1.
DR   PIRSF; PIRSF037756; MyD88; 1.
DR   SMART; SM00005; DEATH; 1.
DR   SMART; SM00255; TIR; 1.
DR   SUPFAM; SSF47986; SSF47986; 1.
DR   SUPFAM; SSF52200; SSF52200; 1.
DR   PROSITE; PS50017; DEATH_DOMAIN; 1.
DR   PROSITE; PS50104; TIR; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Antiviral defense; Cytoplasm;
KW   Disease variant; Immunity; Inflammatory response; Innate immunity; Nucleus;
KW   Phosphoprotein; Reference proteome; Ubl conjugation.
FT   CHAIN           1..296
FT                   /note="Myeloid differentiation primary response protein
FT                   MyD88"
FT                   /id="PRO_0000096666"
FT   DOMAIN          54..109
FT                   /note="Death"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00064"
FT   DOMAIN          159..293
FT                   /note="TIR"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00204"
FT   REGION          110..155
FT                   /note="Intermediate domain"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         244
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   VAR_SEQ         1..22
FT                   /note="MAAGGPGAGSAAPVSSTSSLPL -> M (in isoform 5)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_053764"
FT   VAR_SEQ         110..154
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_038887"
FT   VAR_SEQ         110
FT                   /note="E -> G (in isoform 4)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_043498"
FT   VAR_SEQ         111..155
FT                   /note="Missing (in isoform 4)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_043499"
FT   VAR_SEQ         156..296
FT                   /note="HMPERFDAFICYCPSDIQFVQEMIRQLEQTNYRLKLCVSDRDVLPGTCVWSI
FT                   ASELIEKRCRRMVVVVSDDYLQSKECDFQTKFALSLSPGAHQKRLIPIKYKAMKKEFPS
FT                   ILRFITVCDYTNPCTKSWFWTRLAKALSLP -> AAGWWWLSLMITCRARNVTSRPNLH
FT                   SASLQVPIRSD (in isoform 3 and isoform 4)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_043500"
FT   VAR_SEQ         215
FT                   /note="R -> RLARRPRGG (in isoform 6)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_053765"
FT   VARIANT         34
FT                   /note="S -> Y (rare variant; unknown pathological
FT                   significance; loss of NF-kappa-B complex activation; loss
FT                   of interaction with IRAK4; reduces homooligomerization;
FT                   dbSNP:rs1319438)"
FT                   /evidence="ECO:0000269|PubMed:20966070,
FT                   ECO:0000269|PubMed:24316379"
FT                   /id="VAR_072893"
FT   VARIANT         39
FT                   /note="V -> M (found in hematological malignancies; somatic
FT                   mutation; unknown pathological significance;
FT                   dbSNP:rs770387646)"
FT                   /evidence="ECO:0000269|PubMed:21179087"
FT                   /id="VAR_073252"
FT   VARIANT         52
FT                   /note="Missing (in IMD68; loss of NF-kappa-B complex
FT                   activation)"
FT                   /evidence="ECO:0000269|PubMed:21057262,
FT                   ECO:0000269|PubMed:24316379"
FT                   /id="VAR_072894"
FT   VARIANT         93
FT                   /note="L -> P (in IMD68; results in a loss of function;
FT                   loss of NF-kappa-B complex activation; dbSNP:rs137853065)"
FT                   /evidence="ECO:0000269|PubMed:18669862,
FT                   ECO:0000269|PubMed:21057262, ECO:0000269|PubMed:24316379"
FT                   /id="VAR_047953"
FT   VARIANT         98
FT                   /note="R -> C (found in hematological malignancies; somatic
FT                   mutation; unknown pathological significance; loss of NF-
FT                   kappa-B complex activation; loss of interaction with IRAK4;
FT                   reduces homooligomerization; dbSNP:rs199396)"
FT                   /evidence="ECO:0000269|PubMed:20966070,
FT                   ECO:0000269|PubMed:24316379, ECO:0000269|PubMed:8957090"
FT                   /id="VAR_072895"
FT   VARIANT         136
FT                   /note="S -> G (found in hematological malignancies; somatic
FT                   mutation; unknown pathological significance)"
FT                   /evidence="ECO:0000269|PubMed:21179087"
FT                   /id="VAR_073253"
FT   VARIANT         136
FT                   /note="S -> I (found in hematological malignancies; somatic
FT                   mutation; unknown pathological significance)"
FT                   /evidence="ECO:0000269|PubMed:21179087"
FT                   /id="VAR_073254"
FT   VARIANT         178
FT                   /note="M -> I (found in hematological malignancies; somatic
FT                   mutation; unknown pathological significance; no effect on
FT                   NF-kappaB complex activation; dbSNP:rs41285117)"
FT                   /evidence="ECO:0000269|PubMed:20966070,
FT                   ECO:0000269|PubMed:24316379"
FT                   /id="VAR_072896"
FT   VARIANT         196
FT                   /note="R -> C (in IMD68; results in a loss of function;
FT                   decreases NF-kappa-B complex activation;
FT                   dbSNP:rs137853064)"
FT                   /evidence="ECO:0000269|PubMed:18669862,
FT                   ECO:0000269|PubMed:19506249, ECO:0000269|PubMed:21057262,
FT                   ECO:0000269|PubMed:24316379"
FT                   /id="VAR_047954"
FT   VARIANT         204
FT                   /note="V -> F (found in hematological malignancies; somatic
FT                   mutation; unknown pathological significance;
FT                   dbSNP:rs776995408)"
FT                   /evidence="ECO:0000269|PubMed:21179087"
FT                   /id="VAR_073255"
FT   VARIANT         205
FT                   /note="W -> R (found in hematological malignancies; somatic
FT                   mutation; unknown pathological significance)"
FT                   /evidence="ECO:0000269|PubMed:21179087"
FT                   /id="VAR_073256"
FT   VARIANT         206
FT                   /note="S -> C (found in hematological malignancies; somatic
FT                   mutation; unknown pathological significance)"
FT                   /evidence="ECO:0000269|PubMed:21179087"
FT                   /id="VAR_073257"
FT   VARIANT         207
FT                   /note="I -> T (found in hematological malignancies; somatic
FT                   mutation; unknown pathological significance)"
FT                   /evidence="ECO:0000269|PubMed:21179087"
FT                   /id="VAR_073258"
FT   VARIANT         209
FT                   /note="S -> R (found in hematological malignancies; somatic
FT                   mutation; unknown pathological significance; constitutively
FT                   activates NF-kappaB complex activation)"
FT                   /evidence="ECO:0000269|PubMed:21179087"
FT                   /id="VAR_073259"
FT   VARIANT         219
FT                   /note="M -> T (found in hematological malignancies; somatic
FT                   mutation; unknown pathological significance; constitutively
FT                   activates NF-kappaB complex activation)"
FT                   /evidence="ECO:0000269|PubMed:21179087"
FT                   /id="VAR_073260"
FT   VARIANT         230
FT                   /note="S -> N (found in hematological malignancies; somatic
FT                   mutation; unknown pathological significance; constitutively
FT                   activates NF-kappaB complex activation;
FT                   dbSNP:rs1353791431)"
FT                   /evidence="ECO:0000269|PubMed:21179087"
FT                   /id="VAR_073261"
FT   VARIANT         252
FT                   /note="L -> P (in WM1; found in hematological malignancies;
FT                   somatic mutation; unknown pathological significance;
FT                   constitutively activates NF-kappaB complex activation;
FT                   gain-of-function mutation; does not affect interaction with
FT                   IRAK4; dbSNP:rs387907272)"
FT                   /evidence="ECO:0000269|PubMed:21179087,
FT                   ECO:0000269|PubMed:22931316, ECO:0000269|PubMed:24366360"
FT                   /id="VAR_073262"
FT   VARIANT         281
FT                   /note="T -> P (found in hematological malignancies; somatic
FT                   mutation; unknown pathological significance; no effect on
FT                   NF-kappaB complex activation)"
FT                   /evidence="ECO:0000269|PubMed:21179087"
FT                   /id="VAR_073263"
FT   MUTAGEN         179
FT                   /note="I->N: In Pococurante (Poc); abolished MYD88-
FT                   dependent sensing of most Toll-like receptor (TLR)
FT                   ligands."
FT                   /evidence="ECO:0000269|PubMed:23569230"
FT   MUTAGEN         196
FT                   /note="R->A: Reduced interaction with TIRAP, and strongly
FT                   reduced activity. Strongly reduced interaction with TIRAP;
FT                   when associated with A-288."
FT                   /evidence="ECO:0000269|PubMed:19506249"
FT   MUTAGEN         197
FT                   /note="D->A: Slightly reduced activity."
FT                   /evidence="ECO:0000269|PubMed:19506249"
FT   MUTAGEN         203
FT                   /note="C->S: Abolished interaction with E.coli TcpC without
FT                   affecting ability to promote Toll-like receptor (TLR)-
FT                   mediated cytokine production; when associated with S-280."
FT                   /evidence="ECO:0000269|PubMed:23569230"
FT   MUTAGEN         217
FT                   /note="R->A: Strongly reduced activity."
FT                   /evidence="ECO:0000269|PubMed:19506249"
FT   MUTAGEN         280
FT                   /note="C->S: Abolished interaction with E.coli TcpC without
FT                   affecting ability to promote Toll-like receptor (TLR)-
FT                   mediated cytokine production; when associated with S-203."
FT                   /evidence="ECO:0000269|PubMed:23569230"
FT   MUTAGEN         282
FT                   /note="K->A: Slightly reduced activity."
FT                   /evidence="ECO:0000269|PubMed:19506249"
FT   MUTAGEN         288
FT                   /note="R->A: Slightly reduced activity, and reduced
FT                   interaction with TIRAP. Strongly reduced interaction with
FT                   TIRAP; when associated with A-196."
FT                   /evidence="ECO:0000269|PubMed:19506249"
FT   CONFLICT        190
FT                   /note="K -> T (in Ref. 8; BI524129)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        223..224
FT                   /note="VS -> WL (in Ref. 8; BI524129)"
FT                   /evidence="ECO:0000305"
FT   HELIX           22..24
FT                   /evidence="ECO:0007829|PDB:6I3N"
FT   HELIX           27..37
FT                   /evidence="ECO:0007829|PDB:6I3N"
FT   STRAND          42..44
FT                   /evidence="ECO:0007829|PDB:6I3N"
FT   HELIX           47..53
FT                   /evidence="ECO:0007829|PDB:6I3N"
FT   HELIX           58..64
FT                   /evidence="ECO:0007829|PDB:6I3N"
FT   STRAND          66..69
FT                   /evidence="ECO:0007829|PDB:3MOP"
FT   HELIX           70..77
FT                   /evidence="ECO:0007829|PDB:6I3N"
FT   STRAND          79..81
FT                   /evidence="ECO:0007829|PDB:6I3N"
FT   HELIX           86..95
FT                   /evidence="ECO:0007829|PDB:6I3N"
FT   HELIX           100..104
FT                   /evidence="ECO:0007829|PDB:6I3N"
FT   HELIX           106..120
FT                   /evidence="ECO:0007829|PDB:6I3N"
FT   STRAND          159..166
FT                   /evidence="ECO:0007829|PDB:4EO7"
FT   HELIX           169..171
FT                   /evidence="ECO:0007829|PDB:4EO7"
FT   HELIX           172..183
FT                   /evidence="ECO:0007829|PDB:4EO7"
FT   STRAND          185..187
FT                   /evidence="ECO:0007829|PDB:4EO7"
FT   STRAND          191..194
FT                   /evidence="ECO:0007829|PDB:4EO7"
FT   HELIX           196..198
FT                   /evidence="ECO:0007829|PDB:4EO7"
FT   HELIX           209..211
FT                   /evidence="ECO:0007829|PDB:4EO7"
FT   HELIX           212..215
FT                   /evidence="ECO:0007829|PDB:4EO7"
FT   STRAND          216..223
FT                   /evidence="ECO:0007829|PDB:4EO7"
FT   HELIX           227..229
FT                   /evidence="ECO:0007829|PDB:4EO7"
FT   HELIX           231..242
FT                   /evidence="ECO:0007829|PDB:4EO7"
FT   HELIX           247..251
FT                   /evidence="ECO:0007829|PDB:4EO7"
FT   STRAND          252..256
FT                   /evidence="ECO:0007829|PDB:4EO7"
FT   HELIX           266..268
FT                   /evidence="ECO:0007829|PDB:4EO7"
FT   STRAND          269..271
FT                   /evidence="ECO:0007829|PDB:4DOM"
FT   STRAND          274..277
FT                   /evidence="ECO:0007829|PDB:7BER"
FT   HELIX           279..281
FT                   /evidence="ECO:0007829|PDB:4EO7"
FT   HELIX           282..284
FT                   /evidence="ECO:0007829|PDB:7BER"
FT   HELIX           285..294
FT                   /evidence="ECO:0007829|PDB:4EO7"
SQ   SEQUENCE   296 AA;  33233 MW;  CEAE3F6B99524333 CRC64;
     MAAGGPGAGS AAPVSSTSSL PLAALNMRVR RRLSLFLNVR TQVAADWTAL AEEMDFEYLE
     IRQLETQADP TGRLLDAWQG RPGASVGRLL ELLTKLGRDD VLLELGPSIE EDCQKYILKQ
     QQEEAEKPLQ VAAVDSSVPR TAELAGITTL DDPLGHMPER FDAFICYCPS DIQFVQEMIR
     QLEQTNYRLK LCVSDRDVLP GTCVWSIASE LIEKRCRRMV VVVSDDYLQS KECDFQTKFA
     LSLSPGAHQK RLIPIKYKAM KKEFPSILRF ITVCDYTNPC TKSWFWTRLA KALSLP
 
 
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