GSDMD_MOUSE
ID GSDMD_MOUSE Reviewed; 487 AA.
AC Q9D8T2; Q3TBD9;
DT 19-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 131.
DE RecName: Full=Gasdermin-D {ECO:0000303|PubMed:26611636};
DE AltName: Full=Gasdermin domain-containing protein 1;
DE Contains:
DE RecName: Full=Gasdermin-D, N-terminal {ECO:0000305};
DE Short=GSDMD-NT {ECO:0000303|PubMed:27383986};
DE Short=mGSDMD-NTD {ECO:0000303|PubMed:31097341};
DE Short=p30 {ECO:0000303|PubMed:27339137};
DE Contains:
DE RecName: Full=Gasdermin-D, C-terminal {ECO:0000305};
DE Short=GSDMD-CT {ECO:0000303|PubMed:27383986};
DE Short=mGSDMD-CTD {ECO:0000303|PubMed:31097341};
DE Short=p20 {ECO:0000303|PubMed:27339137};
GN Name=Gsdmd {ECO:0000303|PubMed:26611636, ECO:0000312|MGI:MGI:1916396};
GN Synonyms=Gsdmdc1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD; TISSUE=Lung, and Pancreas;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Liver;
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 [3]
RP PROTEIN SEQUENCE OF 11-44; 84-125; 139-152 AND 204-218, FUNCTION,
RP ASSOCIATION WITH NLRP3 INFLAMMASOME, SUBCELLULAR LOCATION, MASS
RP SPECTROMETRY, MUTAGENESIS OF ASP-276, AND CLEAVAGE BY CASP1.
RX PubMed=26611636; DOI=10.1038/cr.2015.139;
RA He W.T., Wan H., Hu L., Chen P., Wang X., Huang Z., Yang Z.H., Zhong C.Q.,
RA Han J.;
RT "Gasdermin D is an executor of pyroptosis and required for interleukin-
RT 1beta secretion.";
RL Cell Res. 25:1285-1298(2015).
RN [4]
RP PROTEIN SEQUENCE OF 277-288, FUNCTION, DISRUPTION PHENOTYPE, MUTAGENESIS OF
RP ILE-105 AND ASP-276, AND CLEAVAGE BY CASP1 AND CASP4.
RX PubMed=26375259; DOI=10.1038/nature15541;
RA Kayagaki N., Stowe I.B., Lee B.L., O'Rourke K., Anderson K., Warming S.,
RA Cuellar T., Haley B., Roose-Girma M., Phung Q.T., Liu P.S., Lill J.R.,
RA Li H., Wu J., Kummerfeld S., Zhang J., Lee W.P., Snipas S.J.,
RA Salvesen G.S., Morris L.X., Fitzgerald L., Zhang Y., Bertram E.M.,
RA Goodnow C.C., Dixit V.M.;
RT "Caspase-11 cleaves gasdermin D for non-canonical inflammasome
RT signalling.";
RL Nature 526:666-671(2015).
RN [5]
RP DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=18693275; DOI=10.1002/dvg.20412;
RA Fujii T., Tamura M., Tanaka S., Kato Y., Yamamoto H., Mizushina Y.,
RA Shiroishi T.;
RT "Gasdermin D (Gsdmd) is dispensable for mouse intestinal epithelium
RT development.";
RL Genesis 46:418-423(2008).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver, Lung, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
RP FUNCTION, DISRUPTION PHENOTYPE, AND ACTIVITY REGULATION.
RX PubMed=26375003; DOI=10.1038/nature15514;
RA Shi J., Zhao Y., Wang K., Shi X., Wang Y., Huang H., Zhuang Y., Cai T.,
RA Wang F., Shao F.;
RT "Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell
RT death.";
RL Nature 526:660-665(2015).
RN [8]
RP FUNCTION (GASDERMIN-D, N-TERMINAL), SUBCELLULAR LOCATION, AND ACTIVATION
RP WITH NLRC4 INFLAMMASOME.
RX PubMed=27418190; DOI=10.15252/embj.201694696;
RA Sborgi L., Ruehl S., Mulvihill E., Pipercevic J., Heilig R., Stahlberg H.,
RA Farady C.J., Mueller D.J., Broz P., Hiller S.;
RT "GSDMD membrane pore formation constitutes the mechanism of pyroptotic cell
RT death.";
RL EMBO J. 35:1766-1778(2016).
RN [9]
RP FUNCTION.
RX PubMed=27385778; DOI=10.4049/jimmunol.1600699;
RA Russo H.M., Rathkey J., Boyd-Tressler A., Katsnelson M.A., Abbott D.W.,
RA Dubyak G.R.;
RT "Active caspase-1 induces plasma membrane pores that precede pyroptotic
RT lysis and are blocked by lanthanides.";
RL J. Immunol. 197:1353-1367(2016).
RN [10]
RP FUNCTION (GASDERMIN-D, N-TERMINAL), CLEAVAGE BY CASP4, LIPID-BINDING,
RP HOMOOLIGOMERIZATION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF CYS-39;
RP CYS-57; CYS-77; CYS-122; ARG-138; LYS-146; ARG-152; ARG-154; CYS-192;
RP LYS-237; ARG-239; ARG-248; LYS-249 AND CYS-265.
RX PubMed=27383986; DOI=10.1038/nature18629;
RA Liu X., Zhang Z., Ruan J., Pan Y., Magupalli V.G., Wu H., Lieberman J.;
RT "Inflammasome-activated gasdermin D causes pyroptosis by forming membrane
RT pores.";
RL Nature 535:153-158(2016).
RN [11]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=27339137; DOI=10.1073/pnas.1607769113;
RA Aglietti R.A., Estevez A., Gupta A., Ramirez M.G., Liu P.S., Kayagaki N.,
RA Ciferri C., Dixit V.M., Dueber E.C.;
RT "GsdmD p30 elicited by caspase-11 during pyroptosis forms pores in
RT membranes.";
RL Proc. Natl. Acad. Sci. U.S.A. 113:7858-7863(2016).
RN [12]
RP FUNCTION (GASDERMIN-D, AND N-TERMINAL).
RX PubMed=29274245; DOI=10.1002/eji.201747404;
RA Heilig R., Dick M.S., Sborgi L., Meunier E., Hiller S., Broz P.;
RT "The Gasdermin-D pore acts as a conduit for IL-1beta secretion in mice.";
RL Eur. J. Immunol. 48:584-592(2018).
RN [13]
RP FUNCTION (GASDERMIN-D, AND N-TERMINAL).
RX PubMed=29195811; DOI=10.1016/j.immuni.2017.11.013;
RA Evavold C.L., Ruan J., Tan Y., Xia S., Wu H., Kagan J.C.;
RT "The pore-forming protein gasdermin D regulates interleukin-1 secretion
RT from living macrophages.";
RL Immunity 48:35-44(2018).
RN [14]
RP FUNCTION, PROTEOLYTIC CLEAVAGE, AND ACTIVITY REGULATION.
RX PubMed=30381458; DOI=10.1073/pnas.1809548115;
RA Sarhan J., Liu B.C., Muendlein H.I., Li P., Nilson R., Tang A.Y.,
RA Rongvaux A., Bunnell S.C., Shao F., Green D.R., Poltorak A.;
RT "Caspase-8 induces cleavage of gasdermin D to elicit pyroptosis during
RT Yersinia infection.";
RL Proc. Natl. Acad. Sci. U.S.A. 115:E10888-E10897(2018).
RN [15]
RP FUNCTION, PROTEOLYTIC CLEAVAGE, ACTIVITY REGULATION, AND MUTAGENESIS OF
RP ASP-276.
RX PubMed=30361383; DOI=10.1126/science.aau2818;
RA Orning P., Weng D., Starheim K., Ratner D., Best Z., Lee B., Brooks A.,
RA Xia S., Wu H., Kelliher M.A., Berger S.B., Gough P.J., Bertin J.,
RA Proulx M.M., Goguen J.D., Kayagaki N., Fitzgerald K.A., Lien E.;
RT "Pathogen blockade of TAK1 triggers caspase-8-dependent cleavage of
RT gasdermin D and cell death.";
RL Science 362:1064-1069(2018).
RN [16]
RP ACTIVITY REGULATION, AND PROTEOLYTIC CLEAVAGE.
RX PubMed=32554464; DOI=10.1074/jbc.ra120.014259;
RA Bibo-Verdugo B., Snipas S.J., Kolt S., Poreba M., Salvesen G.S.;
RT "Extended subsite profiling of the pyroptosis effector protein gasdermin D
RT reveals a region recognized by inflammatory caspase-11.";
RL J. Biol. Chem. 295:11292-11302(2020).
RN [17]
RP FUNCTION, SUCCINATION AT CYS-39; CYS-57; CYS-77; CYS-122; CYS-192; CYS-265;
RP CYS-299; CYS-434 AND CYS-487, AND MUTAGENESIS OF CYS-192.
RX PubMed=32820063; DOI=10.1126/science.abb9818;
RA Humphries F., Shmuel-Galia L., Ketelut-Carneiro N., Li S., Wang B.,
RA Nemmara V.V., Wilson R., Jiang Z., Khalighinejad F., Muneeruddin K.,
RA Shaffer S.A., Dutta R., Ionete C., Pesiridis S., Yang S., Thompson P.R.,
RA Fitzgerald K.A.;
RT "Succination inactivates gasdermin D and blocks pyroptosis.";
RL Science 369:1633-1637(2020).
RN [18]
RP FUNCTION (GASDERMIN-D, N-TERMINAL), AND MUTAGENESIS OF 50-PHE-TRP-51.
RX PubMed=33883744; DOI=10.1038/s41586-021-03478-3;
RA Xia S., Zhang Z., Magupalli V.G., Pablo J.L., Dong Y., Vora S.M., Wang L.,
RA Fu T.M., Jacobson M.P., Greka A., Lieberman J., Ruan J., Wu H.;
RT "Gasdermin D pore structure reveals preferential release of mature
RT interleukin-1.";
RL Nature 593:607-611(2021).
RN [19] {ECO:0007744|PDB:6AO3}
RP X-RAY CRYSTALLOGRAPHY (1.76 ANGSTROMS) OF 277-487, ACTIVITY REGULATION,
RP DOMAIN, AND MUTAGENESIS OF ILE-105 AND TYR-376.
RX PubMed=29576317; DOI=10.1016/j.str.2018.03.002;
RA Liu Z., Wang C., Rathkey J.K., Yang J., Dubyak G.R., Abbott D.W.,
RA Xiao T.S.;
RT "Structures of the Gasdermin D C-terminal domains reveal mechanisms of
RT autoinhibition.";
RL Structure 26:778-784(2018).
RN [20] {ECO:0007744|PDB:6N9N}
RP X-RAY CRYSTALLOGRAPHY (3.30 ANGSTROMS), ACTIVITY REGULATION, DOMAIN, AND
RP MUTAGENESIS OF 7-LYS--LYS-14; LEU-29; 43-ARG--ARG-54; 50-PHE-TRP-51;
RP LEU-60; PHE-81; ILE-91; VAL-95; LEU-193; 230-ILE--VAL-233; LEU-292;
RP GLU-295; ALA-380; SER-470 AND ALA-474.
RX PubMed=31097341; DOI=10.1016/j.immuni.2019.04.017;
RA Liu Z., Wang C., Yang J., Zhou B., Yang R., Ramachandran R., Abbott D.W.,
RA Xiao T.S.;
RT "Crystal structures of the full-length murine and human Gasdermin D reveal
RT mechanisms of autoinhibition, lipid binding, and oligomerization.";
RL Immunity 51:43-49(2019).
RN [21] {ECO:0007744|PDB:6KMV}
RP X-RAY CRYSTALLOGRAPHY (3.35 ANGSTROMS) OF 287-484 AND 289-484 IN COMPLEX
RP WITH GSDMD.
RX PubMed=32109412; DOI=10.1016/j.cell.2020.02.002;
RA Wang K., Sun Q., Zhong X., Zeng M., Zeng H., Shi X., Li Z., Wang Y.,
RA Zhao Q., Shao F., Ding J.;
RT "Structural mechanism for GSDMD targeting by autoprocessed caspases in
RT pyroptosis.";
RL Cell 180:941-955(2020).
RN [22] {ECO:0007744|PDB:6VIE}
RP X-RAY CRYSTALLOGRAPHY (3.40 ANGSTROMS) IN COMPLEX WITH CASP1, PROTEOLYTIC
RP CLEAVAGE, ACTIVITY REGULATION, AND MUTAGENESIS OF LEU-273; ASP-276;
RP 306-LEU--LEU-310; 361-LEU--LEU-370 AND GLU-369.
RX PubMed=32553275; DOI=10.1016/j.immuni.2020.06.007;
RA Liu Z., Wang C., Yang J., Chen Y., Zhou B., Abbott D.W., Xiao T.S.;
RT "Caspase-1 engages full-length Gasdermin D through two distinct interfaces
RT that mediate caspase recruitment and substrate cleavage.";
RL Immunity 53:106-114(2020).
CC -!- FUNCTION: [Gasdermin-D]: Precursor of a pore-forming protein that plays
CC a key role in host defense against pathogen infection and danger
CC signals (PubMed:26375003, PubMed:26375259, PubMed:26611636,
CC PubMed:27383986, PubMed:27385778, PubMed:27418190). This form
CC constitutes the precursor of the pore-forming protein: upon cleavage,
CC the released N-terminal moiety (Gasdermin-D, N-terminal) binds to
CC membranes and forms pores, triggering pyroptosis (PubMed:26375003,
CC PubMed:26375259, PubMed:26611636, PubMed:27383986, PubMed:27385778,
CC PubMed:27418190). {ECO:0000269|PubMed:26375003,
CC ECO:0000269|PubMed:26375259, ECO:0000269|PubMed:26611636,
CC ECO:0000269|PubMed:27383986, ECO:0000269|PubMed:27385778,
CC ECO:0000269|PubMed:27418190}.
CC -!- FUNCTION: [Gasdermin-D, N-terminal]: Promotes pyroptosis in response to
CC microbial infection and danger signals (PubMed:26375003,
CC PubMed:26375259, PubMed:26611636, PubMed:27383986, PubMed:27385778,
CC PubMed:27418190, PubMed:32820063). Produced by the cleavage of
CC gasdermin-D by inflammatory caspases CASP1 or CASP4/CASP11 in response
CC to canonical, as well as non-canonical (such as cytosolic LPS)
CC inflammasome activators (PubMed:26375003, PubMed:26375259,
CC PubMed:26611636, PubMed:27383986, PubMed:27385778, PubMed:27418190).
CC After cleavage, moves to the plasma membrane where it strongly binds to
CC inner leaflet lipids, including monophosphorylated
CC phosphatidylinositols, such as phosphatidylinositol 4-phosphate,
CC bisphosphorylated phosphatidylinositols, such as phosphatidylinositol
CC (4,5)-bisphosphate, as well as phosphatidylinositol (3,4,5)-
CC bisphosphate, and more weakly to phosphatidic acid and
CC phosphatidylserine (PubMed:27383986, PubMed:27339137). Homooligomerizes
CC within the membrane and forms pores of 10-15 nanometers (nm) of inner
CC diameter, allowing the release of mature interleukin-1 (IL1B and IL18)
CC and triggering pyroptosis (PubMed:27383986, PubMed:29274245,
CC PubMed:29195811, PubMed:33883744). Exhibits bactericidal activity
CC (PubMed:27383986). Gasdermin-D, N-terminal released from pyroptotic
CC cells into the extracellular milieu rapidly binds to and kills both
CC Gram-negative and Gram-positive bacteria, without harming neighboring
CC mammalian cells, as it does not disrupt the plasma membrane from the
CC outside due to lipid-binding specificity (PubMed:27383986). Under cell
CC culture conditions, also active against intracellular bacteria, such as
CC Listeria monocytogenes (PubMed:27383986). Also active in response to
CC MAP3K7/TAK1 inactivation by Yersinia toxin YopJ, which triggers
CC cleavage by CASP8 and subsequent activation (PubMed:30361383,
CC PubMed:30381458). Strongly binds to bacterial and mitochondrial lipids,
CC including cardiolipin. Does not bind to unphosphorylated
CC phosphatidylinositol, phosphatidylethanolamine nor phosphatidylcholine
CC (PubMed:27383986). {ECO:0000269|PubMed:26375003,
CC ECO:0000269|PubMed:26375259, ECO:0000269|PubMed:26611636,
CC ECO:0000269|PubMed:27339137, ECO:0000269|PubMed:27383986,
CC ECO:0000269|PubMed:27385778, ECO:0000269|PubMed:27418190,
CC ECO:0000269|PubMed:29195811, ECO:0000269|PubMed:29274245,
CC ECO:0000269|PubMed:30361383, ECO:0000269|PubMed:30381458,
CC ECO:0000269|PubMed:32820063, ECO:0000269|PubMed:33883744}.
CC -!- ACTIVITY REGULATION: [Gasdermin-D]: The full-length protein before
CC cleavage is inactive: intramolecular interactions between N- and C-
CC terminal domains mediate autoinhibition in the absence of activation
CC signal (PubMed:26375003, PubMed:26375259, PubMed:26611636,
CC PubMed:29576317, PubMed:31097341). The intrinsic pyroptosis-inducing
CC activity is carried by the released N-terminal moiety (Gasdermin-D, N-
CC terminal) following cleavage by inflammatory caspases CASP1,
CC CASP4/CASP11 or CASP8 (PubMed:26375003, PubMed:26375259,
CC PubMed:26611636, PubMed:30361383, PubMed:30381458, PubMed:32554464,
CC PubMed:32553275). Cleavage at Asp-88 by CASP3 or CAPS7 inactivates the
CC ability to mediate pyroptosis (By similarity).
CC {ECO:0000250|UniProtKB:P57764, ECO:0000269|PubMed:26375003,
CC ECO:0000269|PubMed:26375259, ECO:0000269|PubMed:26611636,
CC ECO:0000269|PubMed:29576317, ECO:0000269|PubMed:30361383,
CC ECO:0000269|PubMed:30381458, ECO:0000269|PubMed:31097341,
CC ECO:0000269|PubMed:32553275, ECO:0000269|PubMed:32554464}.
CC -!- SUBUNIT: [Gasdermin-D, N-terminal]: Homooligomer; homooligomeric ring-
CC shaped pore complex containing 27-28 subunits when inserted in the
CC membrane (By similarity). In response to a canonical inflammasome
CC stimulus, such as nigericin, recruited to NLRP3 inflammasone with
CC similar kinetics to that of uncleaved CASP1 precursor
CC (PubMed:26611636). Although this recruitment is also observed in the
CC absence of PYCARD, it is more efficient in its presence
CC (PubMed:26611636). {ECO:0000250|UniProtKB:Q5Y4Y6,
CC ECO:0000269|PubMed:26611636}.
CC -!- SUBCELLULAR LOCATION: [Gasdermin-D]: Cytoplasm, cytosol
CC {ECO:0000269|PubMed:27383986, ECO:0000269|PubMed:27418190}.
CC Inflammasome {ECO:0000269|PubMed:26611636}. Note=In response to a
CC canonical inflammasome stimulus, such as nigericin, recruited to NLRP3
CC inflammasone with similar kinetics to that of uncleaved CASP1
CC precursor. {ECO:0000269|PubMed:26611636}.
CC -!- SUBCELLULAR LOCATION: [Gasdermin-D, N-terminal]: Cell membrane
CC {ECO:0000269|PubMed:27339137, ECO:0000269|PubMed:27383986,
CC ECO:0000269|PubMed:27418190}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P57764}. Secreted {ECO:0000269|PubMed:27383986}.
CC Note=Released in the extracellular milieu following pyroptosis.
CC {ECO:0000269|PubMed:27383986}.
CC -!- SUBCELLULAR LOCATION: [Gasdermin-D, C-terminal]: Cytoplasm, cytosol
CC {ECO:0000305|PubMed:27339137}.
CC -!- DEVELOPMENTAL STAGE: Expression starts at 8.5 dpc and increases from
CC 13.5 dpc on. Still detected after birth. {ECO:0000269|PubMed:18693275}.
CC -!- DOMAIN: Intramolecular interactions between N- and C-terminal domains
CC mediate autoinhibition in the absence of cleavage by inflammatory
CC caspases CASP1 or CASP4/CASP11 (PubMed:26375003, PubMed:26375259,
CC PubMed:26611636, PubMed:29576317, PubMed:31097341). The linker helix
CC loop inserts into the N-terminal domain (By similarity). The intrinsic
CC pyroptosis-inducing activity is carried by Gasdermin-D, N-terminal,
CC that is released upon cleavage by inflammatory caspases
CC (PubMed:26375003, PubMed:26375259, PubMed:26611636).
CC {ECO:0000250|UniProtKB:P57764, ECO:0000269|PubMed:26375003,
CC ECO:0000269|PubMed:26375259, ECO:0000269|PubMed:26611636,
CC ECO:0000269|PubMed:29576317, ECO:0000269|PubMed:31097341}.
CC -!- DOMAIN: [Gasdermin-D, N-terminal]: Forms a ring-shaped pore complex
CC containing 27-28 subunits that inserts into the membrane. The pore
CC conduit is predominantly negatively charged, facilitating the release
CC of mature interleukin-1 (IL1B and IL18). In contrast interleukin-1
CC precursors are not released, due to the presence of an acidic region
CC that is proteolytically removed by CASP1 during maturation.
CC {ECO:0000250|UniProtKB:P57764}.
CC -!- PTM: Cleavage at Asp-276 by CASP1 (mature and uncleaved precursor
CC forms), CASP4/CASP11 or CASP8 relieves autoinhibition and is sufficient
CC to initiate pyroptosis (PubMed:26375259, PubMed:26611636,
CC PubMed:32554464, PubMed:32553275). Cleavage by CASP1 and CASP4/CASP11
CC is not strictly dependent on the consensus cleavage site on GSDMD but
CC depends on an exosite interface on CASP1 that recognizes and binds the
CC Gasdermin-D, C-terminal (GSDMD-CT) part (PubMed:32554464,
CC PubMed:32553275). Cleavage by CASP8 takes place following inactivation
CC of MAP3K7/TAK1 by Yersinia toxin YopJ (PubMed:30361383,
CC PubMed:30381458). Cleavage at Asp-88 by CASP3 or CAPS7 inactivates the
CC ability to mediate pyroptosis (By similarity).
CC {ECO:0000250|UniProtKB:P57764, ECO:0000269|PubMed:26375259,
CC ECO:0000269|PubMed:26611636, ECO:0000269|PubMed:30361383,
CC ECO:0000269|PubMed:30381458, ECO:0000269|PubMed:32553275,
CC ECO:0000269|PubMed:32554464}.
CC -!- PTM: [Gasdermin-D]: Succination of Cys-192 by the Krebs cycle
CC intermediate fumarate, which leads to S-(2-succinyl)cysteine residues,
CC inhibits processing by caspases, and ability to initiate pyroptosis
CC (PubMed:32820063). Succination modification is catalyzed by a non-
CC enzymatic reaction caused by an accumulation of fumarate
CC (PubMed:32820063). {ECO:0000269|PubMed:32820063}.
CC -!- DISRUPTION PHENOTYPE: Knockout mice are born at the expected Mendelian
CC rate and do not exhibit any overt phenotype in normal housing
CC conditions. The gastrointestinal tract develops normally. They are
CC however resistant to LPS-induced lethal septic shock. Primary bone
CC marrow-derived macrophages fail to undergo pyroptosis in response to
CC canonical (acting via CASP1), as well as to non-canonical (acting via
CC CASP4) inflammasome activators. CASP1-mediated IL1B release is also
CC impaired, but not CASP1 autoprocessing, nor IL1B maturation.
CC {ECO:0000269|PubMed:18693275, ECO:0000269|PubMed:26375003,
CC ECO:0000269|PubMed:26375259}.
CC -!- SIMILARITY: Belongs to the gasdermin family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AK007710; BAB25204.1; -; mRNA.
DR EMBL; AK165858; BAE38418.1; -; mRNA.
DR EMBL; AK171294; BAE42374.1; -; mRNA.
DR EMBL; BC029813; AAH29813.1; -; mRNA.
DR CCDS; CCDS27551.1; -.
DR RefSeq; NP_081236.1; NM_026960.4.
DR PDB; 6AO3; X-ray; 1.76 A; A/B/C/D=277-487.
DR PDB; 6KMV; X-ray; 3.35 A; C/G/O=287-484, D/K/S/T/W/b/f=288-484, H=294-484, L/P/e=271-484, X=286-484, a=289-484.
DR PDB; 6N9N; X-ray; 3.30 A; A/B=1-487.
DR PDB; 6VIE; X-ray; 3.40 A; C/D=1-487.
DR PDBsum; 6AO3; -.
DR PDBsum; 6KMV; -.
DR PDBsum; 6N9N; -.
DR PDBsum; 6VIE; -.
DR AlphaFoldDB; Q9D8T2; -.
DR SMR; Q9D8T2; -.
DR DIP; DIP-61777N; -.
DR IntAct; Q9D8T2; 2.
DR STRING; 10090.ENSMUSP00000023238; -.
DR ChEMBL; CHEMBL4523446; -.
DR iPTMnet; Q9D8T2; -.
DR PhosphoSitePlus; Q9D8T2; -.
DR SwissPalm; Q9D8T2; -.
DR EPD; Q9D8T2; -.
DR MaxQB; Q9D8T2; -.
DR PaxDb; Q9D8T2; -.
DR PeptideAtlas; Q9D8T2; -.
DR PRIDE; Q9D8T2; -.
DR ProteomicsDB; 269843; -.
DR ABCD; Q9D8T2; 1 sequenced antibody.
DR Antibodypedia; 27909; 171 antibodies from 30 providers.
DR DNASU; 69146; -.
DR Ensembl; ENSMUST00000023238; ENSMUSP00000023238; ENSMUSG00000022575.
DR GeneID; 69146; -.
DR KEGG; mmu:69146; -.
DR UCSC; uc007whh.1; mouse.
DR CTD; 79792; -.
DR MGI; MGI:1916396; Gsdmd.
DR VEuPathDB; HostDB:ENSMUSG00000022575; -.
DR eggNOG; ENOG502S0IQ; Eukaryota.
DR GeneTree; ENSGT00950000183140; -.
DR HOGENOM; CLU_040752_1_0_1; -.
DR InParanoid; Q9D8T2; -.
DR OMA; STPWQEQ; -.
DR OrthoDB; 747086at2759; -.
DR PhylomeDB; Q9D8T2; -.
DR TreeFam; TF331886; -.
DR Reactome; R-MMU-111457; Release of apoptotic factors from the mitochondria.
DR Reactome; R-MMU-448706; Interleukin-1 processing.
DR Reactome; R-MMU-5620971; Pyroptosis.
DR Reactome; R-MMU-5686938; Regulation of TLR by endogenous ligand.
DR Reactome; R-MMU-6798695; Neutrophil degranulation.
DR BioGRID-ORCS; 69146; 2 hits in 72 CRISPR screens.
DR PRO; PR:Q9D8T2; -.
DR Proteomes; UP000000589; Chromosome 15.
DR RNAct; Q9D8T2; protein.
DR Bgee; ENSMUSG00000022575; Expressed in small intestine Peyer's patch and 141 other tissues.
DR ExpressionAtlas; Q9D8T2; baseline and differential.
DR Genevisible; Q9D8T2; MM.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; ISO:MGI.
DR GO; GO:0072559; C:NLRP3 inflammasome complex; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:1901612; F:cardiolipin binding; IDA:UniProtKB.
DR GO; GO:0070300; F:phosphatidic acid binding; IDA:UniProtKB.
DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; IDA:UniProtKB.
DR GO; GO:0070273; F:phosphatidylinositol-4-phosphate binding; IDA:UniProtKB.
DR GO; GO:0001786; F:phosphatidylserine binding; IDA:UniProtKB.
DR GO; GO:0022829; F:wide pore channel activity; IDA:UniProtKB.
DR GO; GO:0031668; P:cellular response to extracellular stimulus; IDA:MGI.
DR GO; GO:0042742; P:defense response to bacterium; IBA:GO_Central.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; IDA:UniProtKB.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IDA:UniProtKB.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0046931; P:pore complex assembly; IDA:UniProtKB.
DR GO; GO:0035915; P:pore formation in membrane of another organism; IDA:UniProtKB.
DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; IDA:UniProtKB.
DR GO; GO:0032732; P:positive regulation of interleukin-1 production; ISO:MGI.
DR GO; GO:0032741; P:positive regulation of interleukin-18 production; ISO:MGI.
DR GO; GO:0051260; P:protein homooligomerization; IDA:UniProtKB.
DR GO; GO:0070269; P:pyroptosis; IDA:UniProtKB.
DR InterPro; IPR007677; Gasdermin.
DR InterPro; IPR040460; Gasdermin_pore.
DR InterPro; IPR041263; Gasdermin_PUB.
DR PANTHER; PTHR16399; PTHR16399; 1.
DR Pfam; PF04598; Gasdermin; 1.
DR Pfam; PF17708; Gasdermin_C; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Cytoplasm; Direct protein sequencing;
KW Immunity; Inflammasome; Inflammatory response; Innate immunity;
KW Lipid-binding; Membrane; Necrosis; Phosphoprotein; Reference proteome;
KW Secreted; Transmembrane; Transmembrane beta strand.
FT CHAIN 1..487
FT /note="Gasdermin-D"
FT /id="PRO_0000148176"
FT CHAIN 1..276
FT /note="Gasdermin-D, N-terminal"
FT /evidence="ECO:0000305|PubMed:27383986,
FT ECO:0000305|PubMed:32553275"
FT /id="PRO_0000437528"
FT CHAIN 277..487
FT /note="Gasdermin-D, C-terminal"
FT /evidence="ECO:0000305|PubMed:27383986,
FT ECO:0000305|PubMed:32553275"
FT /id="PRO_0000437529"
FT TRANSMEM 92..98
FT /note="Beta stranded"
FT /evidence="ECO:0000250|UniProtKB:P57764"
FT TRANSMEM 104..109
FT /note="Beta stranded"
FT /evidence="ECO:0000250|UniProtKB:P57764"
FT TRANSMEM 181..187
FT /note="Beta stranded"
FT /evidence="ECO:0000250|UniProtKB:P57764"
FT TRANSMEM 192..198
FT /note="Beta stranded"
FT /evidence="ECO:0000250|UniProtKB:P57764"
FT REGION 278..298
FT /note="Linker helix loop"
FT /evidence="ECO:0000250|UniProtKB:P57764"
FT SITE 88..89
FT /note="Cleavage; by CASP3"
FT /evidence="ECO:0000250|UniProtKB:P57764"
FT SITE 276..277
FT /note="Cleavage; by caspases CASP1, CASP4/CASP11 and CASP8"
FT /evidence="ECO:0000269|PubMed:26375259,
FT ECO:0000269|PubMed:30361383, ECO:0000269|PubMed:32553275"
FT MOD_RES 38
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P57764"
FT MOD_RES 39
FT /note="S-(2-succinyl)cysteine"
FT /evidence="ECO:0000269|PubMed:32820063"
FT MOD_RES 57
FT /note="S-(2-succinyl)cysteine"
FT /evidence="ECO:0000269|PubMed:32820063"
FT MOD_RES 77
FT /note="S-(2-succinyl)cysteine"
FT /evidence="ECO:0000269|PubMed:32820063"
FT MOD_RES 122
FT /note="S-(2-succinyl)cysteine"
FT /evidence="ECO:0000269|PubMed:32820063"
FT MOD_RES 192
FT /note="S-(2-succinyl)cysteine"
FT /evidence="ECO:0000269|PubMed:32820063"
FT MOD_RES 265
FT /note="S-(2-succinyl)cysteine"
FT /evidence="ECO:0000269|PubMed:32820063"
FT MOD_RES 299
FT /note="S-(2-succinyl)cysteine"
FT /evidence="ECO:0000269|PubMed:32820063"
FT MOD_RES 434
FT /note="S-(2-succinyl)cysteine"
FT /evidence="ECO:0000269|PubMed:32820063"
FT MOD_RES 487
FT /note="S-(2-succinyl)cysteine"
FT /evidence="ECO:0000269|PubMed:32820063"
FT MUTAGEN 7..14
FT /note="KVVKNVIK->AVVANVIA: Reduced ability to induct
FT pyroptosis."
FT /evidence="ECO:0000269|PubMed:31097341"
FT MUTAGEN 29
FT /note="L->A: Reduced homoolimerization, leading to reduced
FT ability to induce pyroptosis."
FT /evidence="ECO:0000269|PubMed:31097341"
FT MUTAGEN 39
FT /note="C->A: Loss of oligomerization of Gasdermin-D, N-
FT terminal."
FT /evidence="ECO:0000269|PubMed:27383986"
FT MUTAGEN 43..54
FT /note="RKFSSSRFWKPR->AAFSSSRFWAPA: Reduced ability to
FT induce pyroptosis."
FT /evidence="ECO:0000269|PubMed:31097341"
FT MUTAGEN 50..51
FT /note="FW->GG: Abolished ability to form a pore, leading to
FT educed ability to induce pyroptosis."
FT /evidence="ECO:0000269|PubMed:31097341,
FT ECO:0000269|PubMed:33883744"
FT MUTAGEN 57
FT /note="C->A: No effect on oligomerization."
FT /evidence="ECO:0000269|PubMed:27383986"
FT MUTAGEN 60
FT /note="L->G: Reduced homoolimerization, leading to reduced
FT ability to induce pyroptosis."
FT /evidence="ECO:0000269|PubMed:31097341"
FT MUTAGEN 77
FT /note="C->A: No effect on oligomerization."
FT /evidence="ECO:0000269|PubMed:27383986"
FT MUTAGEN 81
FT /note="F->D: Reduced homoolimerization, leading to reduced
FT ability to induce pyroptosis."
FT /evidence="ECO:0000269|PubMed:31097341"
FT MUTAGEN 91
FT /note="I->D: Reduced homoolimerization, leading to reduced
FT ability to induce pyroptosis."
FT /evidence="ECO:0000269|PubMed:31097341"
FT MUTAGEN 95
FT /note="V->D: Reduced homoolimerization, leading to reduced
FT ability to induce pyroptosis."
FT /evidence="ECO:0000269|PubMed:31097341"
FT MUTAGEN 105
FT /note="I->N: Reduced ability to induce pyroptosis. No
FT effect on protein expression. No effect on cleavage by
FT CASP4."
FT /evidence="ECO:0000269|PubMed:26375259,
FT ECO:0000269|PubMed:29576317"
FT MUTAGEN 122
FT /note="C->A: No effect on oligomerization."
FT /evidence="ECO:0000269|PubMed:27383986"
FT MUTAGEN 138
FT /note="R->A,S: Complete loss of homooligomerization, lipid-
FT binding, relocalization of Gasdermin-D, N-terminal to the
FT plasma membrane and pyroptosis, as well as loss of
FT bactericidal activity; when associated with A-146; A-152
FT and A-154. Partial loss of homooligomerization and
FT pyroptosis; when associated with A-146."
FT /evidence="ECO:0000269|PubMed:27383986"
FT MUTAGEN 146
FT /note="K->A: Complete loss of homooligomerization, lipid-
FT binding, relocalization of Gasdermin-D, N-terminal to the
FT plasma membrane and pyroptosis, as well as loss of
FT bactericidal activity; when associated with A-138 or with
FT S-138; A-152 and A-154. Partial loss of homooligomerization
FT and pyroptosis; when associated with A-138, with A-152 or
FT with A-152 and A-154."
FT /evidence="ECO:0000269|PubMed:27383986"
FT MUTAGEN 152
FT /note="R->A: Complete loss of homooligomerization, lipid-
FT binding, relocalization of Gasdermin-D, N-terminal to the
FT plasma membrane and pyroptosis, as well as loss of
FT bactericidal activity; when associated with A-138 or with
FT S-138; A-146 and A-154. Partial loss of homooligomerization
FT and pyroptosis; when associated with A-146 or with A-154,
FT or with A-146 and A-154."
FT /evidence="ECO:0000269|PubMed:27383986"
FT MUTAGEN 154
FT /note="R->A: Complete loss of homooligomerization, lipid-
FT binding, relocalization of Gasdermin-D, N-terminal to the
FT plasma membrane and pyroptosis, as well as loss of
FT bactericidal activity; when associated with A-138 or with
FT S-138; A-146 and A-152. Partial loss of homooligomerization
FT and pyroptosis; when associated with A-152 or with A-146
FT and A-152."
FT /evidence="ECO:0000269|PubMed:27383986"
FT MUTAGEN 192
FT /note="C->A: Loss of oligomerization of Gasdermin-D, N-
FT terminal."
FT /evidence="ECO:0000269|PubMed:27383986,
FT ECO:0000269|PubMed:32820063"
FT MUTAGEN 193
FT /note="L->D: Reduced homoolimerization, leading to reduced
FT ability to induce pyroptosis."
FT /evidence="ECO:0000269|PubMed:31097341"
FT MUTAGEN 230..233
FT /note="ILLV->ALLA: Reduced homoolimerization, leading to
FT reduced ability to induce pyroptosis."
FT /evidence="ECO:0000269|PubMed:31097341"
FT MUTAGEN 237
FT /note="K->A: No effect on pyroptosis; when associated with
FT A-239 or with A-239; A-248 and A-249."
FT /evidence="ECO:0000269|PubMed:27383986"
FT MUTAGEN 239
FT /note="R->A: No effect on pyroptosis; when associated with
FT A-237 or with A-237; A-248 and A-249."
FT /evidence="ECO:0000269|PubMed:27383986"
FT MUTAGEN 248
FT /note="R->A: No effect on pyroptosis; when associated with
FT A-237; A-239 and A-249."
FT /evidence="ECO:0000269|PubMed:27383986"
FT MUTAGEN 249
FT /note="K->A: No effect on pyroptosis; when associated with
FT A-237; A-239 and A-248."
FT /evidence="ECO:0000269|PubMed:27383986"
FT MUTAGEN 265
FT /note="C->A: No effect on oligomerization."
FT /evidence="ECO:0000269|PubMed:27383986"
FT MUTAGEN 273
FT /note="L->A: Impaired interaction and cleavage by CASP1."
FT /evidence="ECO:0000269|PubMed:32553275"
FT MUTAGEN 276
FT /note="D->A,N: Loss of CASP1-induced cleavage, pyroptosis
FT and IL1B release. Does not impair interaction with CASP1.
FT Abolished ability to induce pyroptosis following
FT inactivation of MAP3K7/TAK1 by Yersinia toxin YopJ."
FT /evidence="ECO:0000269|PubMed:26375259,
FT ECO:0000269|PubMed:26611636, ECO:0000269|PubMed:30361383,
FT ECO:0000269|PubMed:32553275"
FT MUTAGEN 292
FT /note="L->D: Disrupts intramolecular interactions and
FT autoinhibition, leading to spontaneous pyroptosis-inducing
FT activity."
FT /evidence="ECO:0000269|PubMed:31097341"
FT MUTAGEN 295
FT /note="E->R: Disrupts intramolecular interactions and
FT autoinhibition, leading to spontaneous pyroptosis-inducing
FT activity."
FT /evidence="ECO:0000269|PubMed:31097341"
FT MUTAGEN 306..310
FT /note="LEMEL->AEMEA: In 5A mutant; abolished interaction
FT with CASP1; when associated with 361-L--L370."
FT /evidence="ECO:0000269|PubMed:32553275"
FT MUTAGEN 361..370
FT /note="LDSGELVPEL->ADSGELAPEA: In 5A mutant; abolished
FT interaction with CASP1; when associated with 306-L--L310."
FT /evidence="ECO:0000269|PubMed:32553275"
FT MUTAGEN 369
FT /note="E->K: Impaired interaction and cleavage by CASP1."
FT /evidence="ECO:0000269|PubMed:32553275"
FT MUTAGEN 376
FT /note="Y->D: Spontaneous pyroptosis-inducing activity."
FT /evidence="ECO:0000269|PubMed:29576317"
FT MUTAGEN 380
FT /note="A->D: Disrupts intramolecular interactions and
FT autoinhibition, leading to spontaneous pyroptosis-inducing
FT activity."
FT /evidence="ECO:0000269|PubMed:31097341"
FT MUTAGEN 470
FT /note="S->R: Disrupts intramolecular interactions and
FT autoinhibition, leading to spontaneous pyroptosis-inducing
FT activity."
FT /evidence="ECO:0000269|PubMed:31097341"
FT MUTAGEN 474
FT /note="A->D: Disrupts intramolecular interactions and
FT autoinhibition, leading to spontaneous pyroptosis-inducing
FT activity."
FT /evidence="ECO:0000269|PubMed:31097341"
FT HELIX 6..15
FT /evidence="ECO:0007829|PDB:6N9N"
FT STRAND 19..21
FT /evidence="ECO:0007829|PDB:6N9N"
FT HELIX 32..35
FT /evidence="ECO:0007829|PDB:6N9N"
FT STRAND 40..43
FT /evidence="ECO:0007829|PDB:6N9N"
FT TURN 63..65
FT /evidence="ECO:0007829|PDB:6N9N"
FT STRAND 66..68
FT /evidence="ECO:0007829|PDB:6N9N"
FT STRAND 87..89
FT /evidence="ECO:0007829|PDB:6N9N"
FT STRAND 119..125
FT /evidence="ECO:0007829|PDB:6N9N"
FT HELIX 128..137
FT /evidence="ECO:0007829|PDB:6N9N"
FT HELIX 148..152
FT /evidence="ECO:0007829|PDB:6N9N"
FT TURN 153..155
FT /evidence="ECO:0007829|PDB:6N9N"
FT STRAND 157..167
FT /evidence="ECO:0007829|PDB:6N9N"
FT STRAND 171..173
FT /evidence="ECO:0007829|PDB:6N9N"
FT STRAND 207..209
FT /evidence="ECO:0007829|PDB:6N9N"
FT STRAND 214..223
FT /evidence="ECO:0007829|PDB:6N9N"
FT STRAND 225..227
FT /evidence="ECO:0007829|PDB:6N9N"
FT STRAND 229..233
FT /evidence="ECO:0007829|PDB:6N9N"
FT STRAND 274..277
FT /evidence="ECO:0007829|PDB:6VIE"
FT STRAND 280..285
FT /evidence="ECO:0007829|PDB:6KMV"
FT HELIX 289..304
FT /evidence="ECO:0007829|PDB:6AO3"
FT HELIX 308..321
FT /evidence="ECO:0007829|PDB:6AO3"
FT HELIX 325..341
FT /evidence="ECO:0007829|PDB:6AO3"
FT HELIX 350..356
FT /evidence="ECO:0007829|PDB:6AO3"
FT HELIX 357..359
FT /evidence="ECO:0007829|PDB:6AO3"
FT STRAND 364..366
FT /evidence="ECO:0007829|PDB:6AO3"
FT HELIX 368..383
FT /evidence="ECO:0007829|PDB:6AO3"
FT HELIX 386..396
FT /evidence="ECO:0007829|PDB:6AO3"
FT HELIX 400..414
FT /evidence="ECO:0007829|PDB:6AO3"
FT STRAND 418..420
FT /evidence="ECO:0007829|PDB:6VIE"
FT STRAND 422..424
FT /evidence="ECO:0007829|PDB:6AO3"
FT HELIX 428..431
FT /evidence="ECO:0007829|PDB:6AO3"
FT STRAND 436..439
FT /evidence="ECO:0007829|PDB:6VIE"
FT HELIX 440..446
FT /evidence="ECO:0007829|PDB:6AO3"
FT TURN 447..449
FT /evidence="ECO:0007829|PDB:6AO3"
FT STRAND 454..457
FT /evidence="ECO:0007829|PDB:6AO3"
FT STRAND 459..461
FT /evidence="ECO:0007829|PDB:6AO3"
FT HELIX 463..465
FT /evidence="ECO:0007829|PDB:6AO3"
FT HELIX 466..482
FT /evidence="ECO:0007829|PDB:6AO3"
SQ SEQUENCE 487 AA; 53238 MW; 6702C95B0F92BC49 CRC64;
MPSAFEKVVK NVIKEVSGSR GDLIPVDSLR NSTSFRPYCL LNRKFSSSRF WKPRYSCVNL
SIKDILEPSA PEPEPECFGS FKVSDVVDGN IQGRVMLSGM GEGKISGGAA VSDSSSASMN
VCILRVTQKT WETMQHERHL QQPENKILQQ LRSRGDDLFV VTEVLQTKEE VQITEVHSQE
GSGQFTLPGA LCLKGEGKGH QSRKKMVTIP AGSILAFRVA QLLIGSKWDI LLVSDEKQRT
FEPSSGDRKA VGQRHHGLNV LAALCSIGKQ LSLLSDGIDE EELIEAADFQ GLYAEVKACS
SELESLEMEL RQQILVNIGK ILQDQPSMEA LEASLGQGLC SGGQVEPLDG PAGCILECLV
LDSGELVPEL AAPIFYLLGA LAVLSETQQQ LLAKALETTV LSKQLELVKH VLEQSTPWQE
QSSVSLPTVL LGDCWDEKNP TWVLLEECGL RLQVESPQVH WEPTSLIPTS ALYASLFLLS
SLGQKPC
