GSDMD_HUMAN
ID GSDMD_HUMAN Reviewed; 484 AA.
AC P57764; A8K702; D3DWJ9; Q96Q98;
DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT 21-FEB-2001, sequence version 1.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Gasdermin-D {ECO:0000303|PubMed:26375259};
DE AltName: Full=Gasdermin domain-containing protein 1 {ECO:0000303|PubMed:15289881};
DE Contains:
DE RecName: Full=Gasdermin-D, N-terminal {ECO:0000305};
DE Short=GSDMD-NT {ECO:0000250|UniProtKB:Q9D8T2};
DE Short=hGSDMD-NTD {ECO:0000303|PubMed:31097341};
DE Contains:
DE RecName: Full=Gasdermin-D, C-terminal {ECO:0000305};
DE Short=GSDMD-CT {ECO:0000250|UniProtKB:Q9D8T2};
DE Short=hGSDMD-CTD {ECO:0000303|PubMed:31097341};
GN Name=GSDMD {ECO:0000303|PubMed:26375003, ECO:0000312|HGNC:HGNC:25697};
GN Synonyms=DFNA5L {ECO:0000303|PubMed:15289881},
GN GSDMDC1 {ECO:0000303|PubMed:15289881}; ORFNames=FKSG10 {ECO:0000303|Ref.1};
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].
RA Wang Y.-G.;
RT "Identification of FKSG10, a novel gene related to breast cancer.";
RL Submitted (SEP-2000) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Mammary gland;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16421571; DOI=10.1038/nature04406;
RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M.,
RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L.,
RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S.,
RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A.,
RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III,
RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K.,
RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B.,
RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K.,
RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L.,
RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G.,
RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W.,
RA Platzer M., Shimizu N., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 8.";
RL Nature 439:331-335(2006).
RN [4]
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lymph, and Salivary gland;
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 [6]
RP PROTEIN SEQUENCE OF 88-94, ACTIVITY REGULATION, AND PROTEOLYTIC CLEAVAGE.
RX PubMed=28392147; DOI=10.1016/j.chembiol.2017.03.009;
RA Taabazuing C.Y., Okondo M.C., Bachovchin D.A.;
RT "Pyroptosis and apoptosis pathways engage in bidirectional crosstalk in
RT monocytes and macrophages.";
RL Cell Chem. Biol. 24:507-514(2017).
RN [7]
RP PROTEIN SEQUENCE OF 276-281, FUNCTION, CLEAVAGE BY CASP1 AND CASP4,
RP MUTAGENESIS OF ASP-275, AND AUTOINHIBITION.
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 GENE STRUCTURE.
RX PubMed=15289881;
RA Katoh M., Katoh M.;
RT "Identification and characterization of human DFNA5L, mouse Dfna5l, and rat
RT Dfna5l genes in silico.";
RL Int. J. Oncol. 25:765-770(2004).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-37 AND TYR-158, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [11]
RP TISSUE SPECIFICITY.
RX PubMed=19051310; DOI=10.1002/gcc.20636;
RA Saeki N., Usui T., Aoyagi K., Kim D.H., Sato M., Mabuchi T., Yanagihara K.,
RA Ogawa K., Sakamoto H., Yoshida T., Sasaki H.;
RT "Distinctive expression and function of four GSDM family genes (GSDMA-D) in
RT normal and malignant upper gastrointestinal epithelium.";
RL Genes Chromosomes Cancer 48:261-271(2009).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
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 [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-185, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [16]
RP FUNCTION, AND CLEAVAGE BY 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 [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [18]
RP FUNCTION (GASDERMIN-D, N-TERMINAL), CLEAVAGE BY CASP1, AND MUTAGENESIS OF
RP ILE-104.
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 [19]
RP FUNCTION (GASDERMIN-D, N-TERMINAL), LIPID-BINDING, SUBCELLULAR LOCATION,
RP AND MUTAGENESIS OF GLU-15; LEU-192; LEU-290; TYR-373 AND ALA-377.
RX PubMed=27281216; DOI=10.1038/nature18590;
RA Ding J., Wang K., Liu W., She Y., Sun Q., Shi J., Sun H., Wang D.C.,
RA Shao F.;
RT "Pore-forming activity and structural autoinhibition of the gasdermin
RT family.";
RL Nature 535:111-116(2016).
RN [20]
RP CLEAVAGE BY CASP3.
RX PubMed=28045099; DOI=10.1038/ncomms14128;
RA Rogers C., Fernandes-Alnemri T., Mayes L., Alnemri D., Cingolani G.,
RA Alnemri E.S.;
RT "Cleavage of DFNA5 by caspase-3 during apoptosis mediates progression to
RT secondary necrotic/pyroptotic cell death.";
RL Nat. Commun. 8:14128-14128(2017).
RN [21]
RP FUNCTION, CLEAVAGE BY CASP5, AND SUBCELLULAR LOCATION.
RX PubMed=29898893; DOI=10.15252/embj.201798321;
RA Mulvihill E., Sborgi L., Mari S.A., Pfreundschuh M., Hiller S.,
RA Mueller D.J.;
RT "Mechanism of membrane pore formation by human gasdermin-D.";
RL EMBO J. 37:0-0(2018).
RN [22]
RP MUTAGENESIS OF 7-ARG--ARG-11.
RX PubMed=29695864; DOI=10.1038/s41586-018-0058-6;
RA Ruan J., Xia S., Liu X., Lieberman J., Wu H.;
RT "Cryo-EM structure of the gasdermin A3 membrane pore.";
RL Nature 557:62-67(2018).
RN [23]
RP FUNCTION, AND SUCCINATION AT CYS-56; CYS-191; CYS-268; CYS-309 AND CYS-467.
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 [24] {ECO:0007744|PDB:5WQT}
RP X-RAY CRYSTALLOGRAPHY (2.64 ANGSTROMS) OF 276-484, DOMAIN, ACTIVITY
RP REGULATION, AND MUTAGENESIS OF GLU-15; LEU-192; 277-VAL--THR-296 AND
RP PHE-283.
RX PubMed=28928145; DOI=10.1073/pnas.1708194114;
RA Kuang S., Zheng J., Yang H., Li S., Duan S., Shen Y., Ji C., Gan J.,
RA Xu X.W., Li J.;
RT "Structure insight of GSDMD reveals the basis of GSDMD autoinhibition in
RT cell pyroptosis.";
RL Proc. Natl. Acad. Sci. U.S.A. 114:10642-10647(2017).
RN [25] {ECO:0007744|PDB:6AO4}
RP X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) OF 277-484, DOMAIN, AND ACTIVITY
RP REGULATION.
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 [26] {ECO:0007744|PDB:6N9O}
RP X-RAY CRYSTALLOGRAPHY (3.50 ANGSTROMS).
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 [27] {ECO:0007744|PDB:6KN0}
RP X-RAY CRYSTALLOGRAPHY (2.79 ANGSTROMS) OF 283-480 IN COMPLEX WITH CASP1,
RP ACTIVITY REGULATION, SUBCELLULAR LOCATION, PROTEOLYTIC CLEAVAGE, AND
RP MUTAGENESIS OF 272-PHE--THR-274; ASP-275; 304-LEU--LEU-308 AND
RP 364-VAL--LEU-367.
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 [28] {ECO:0007744|PDB:6VFE}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.90 ANGSTROMS) OF 1-241, SUBCELLULAR
RP LOCATION, SUBUNIT, AND MUTAGENESIS OF 42-ARG--ARG-53; 48-TRP--TRP-50;
RP 63-ASP--ASP-73; 87-ASP--GLU-95; ARG-174 AND LYS-204.
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).
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:27281216). 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:27281216). {ECO:0000269|PubMed:26375003,
CC ECO:0000269|PubMed:26375259, ECO:0000269|PubMed:27281216}.
CC -!- FUNCTION: [Gasdermin-D, N-terminal]: Promotes pyroptosis in response to
CC microbial infection and danger signals (PubMed:26375003,
CC PubMed:26375259, PubMed:27418190, PubMed:28392147, PubMed:32820063).
CC Produced by the cleavage of gasdermin-D by inflammatory caspases CASP1,
CC CASP4 or CASP5 in response to canonical, as well as non-canonical (such
CC as cytosolic LPS) inflammasome activators (PubMed:26375003,
CC PubMed:26375259, PubMed:27418190). After cleavage, moves to the plasma
CC membrane where it strongly binds to inner leaflet lipids, including
CC monophosphorylated phosphatidylinositols, such as phosphatidylinositol
CC 4-phosphate, bisphosphorylated phosphatidylinositols, such as
CC phosphatidylinositol (4,5)-bisphosphate, as well as
CC phosphatidylinositol (3,4,5)-bisphosphate, and more weakly to
CC phosphatidic acid and phosphatidylserine (PubMed:27281216,
CC PubMed:29898893). Homooligomerizes within the membrane and forms pores
CC of 10-15 nanometers (nm) of inner diameter, allowing the release of
CC mature interleukin-1 (IL1B and IL18) and triggering pyroptosis
CC (PubMed:27418190, PubMed:27281216, PubMed:29898893, PubMed:33883744).
CC Exhibits bactericidal activity (PubMed:27281216). Gasdermin-D, N-
CC terminal released from pyroptotic cells into the extracellular milieu
CC rapidly binds to and kills both Gram-negative and Gram-positive
CC bacteria, without harming neighboring mammalian cells, as it does not
CC disrupt the plasma membrane from the outside due to lipid-binding
CC specificity (PubMed:27281216). Under cell culture conditions, also
CC active against intracellular bacteria, such as Listeria monocytogenes
CC (By similarity). Also active in response to MAP3K7/TAK1 inactivation by
CC Yersinia toxin YopJ, which triggers cleavage by CASP8 and subsequent
CC activation (By similarity). Strongly binds to bacterial and
CC mitochondrial lipids, including cardiolipin (PubMed:27281216). Does not
CC bind to unphosphorylated phosphatidylinositol, phosphatidylethanolamine
CC nor phosphatidylcholine (PubMed:27281216).
CC {ECO:0000250|UniProtKB:Q9D8T2, ECO:0000269|PubMed:26375003,
CC ECO:0000269|PubMed:26375259, ECO:0000269|PubMed:27281216,
CC ECO:0000269|PubMed:27418190, ECO:0000269|PubMed:28392147,
CC ECO:0000269|PubMed:29898893, ECO:0000269|PubMed:32820063,
CC 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:28928145, PubMed:29576317,
CC PubMed:32109412). The intrinsic pyroptosis-inducing activity is carried
CC by the released N-terminal moiety (Gasdermin-D, N-terminal) following
CC cleavage by caspases CASP1, CASP4, CASP5 or CASP8 (PubMed:26375003,
CC PubMed:26375259, PubMed:27418190, PubMed:29898893, PubMed:32109412).
CC Cleavage at Asp-87 by CASP3 or CAPS7 inactivates the ability to mediate
CC pyroptosis (PubMed:28392147). {ECO:0000269|PubMed:26375003,
CC ECO:0000269|PubMed:26375259, ECO:0000269|PubMed:27418190,
CC ECO:0000269|PubMed:28392147, ECO:0000269|PubMed:28928145,
CC ECO:0000269|PubMed:29576317, ECO:0000269|PubMed:29898893,
CC ECO:0000269|PubMed:32109412}.
CC -!- SUBUNIT: [Gasdermin-D, N-terminal]: Homooligomer; homooligomeric ring-
CC shaped pore complex containing 27-28 subunits when inserted in the
CC membrane (PubMed:33883744). 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 (By similarity).
CC Although this recruitment is also observed in the absence of PYCARD, it
CC is more efficient in its presence (By similarity).
CC {ECO:0000250|UniProtKB:Q5Y4Y6, ECO:0000250|UniProtKB:Q9D8T2,
CC ECO:0000269|PubMed:33883744}.
CC -!- INTERACTION:
CC P57764; Q86U10: ASPG; NbExp=3; IntAct=EBI-2798865, EBI-19946665;
CC P57764; P29466: CASP1; NbExp=4; IntAct=EBI-2798865, EBI-516667;
CC P57764; Q8NC69: KCTD6; NbExp=7; IntAct=EBI-2798865, EBI-2511344;
CC P57764; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-2798865, EBI-16439278;
CC P57764; P25786: PSMA1; NbExp=3; IntAct=EBI-2798865, EBI-359352;
CC P57764; Q86T24: ZBTB33; NbExp=3; IntAct=EBI-2798865, EBI-2515625;
CC P57764; Q9BUY5: ZNF426; NbExp=3; IntAct=EBI-2798865, EBI-743265;
CC P57764; Q96NG5: ZNF558; NbExp=3; IntAct=EBI-2798865, EBI-373363;
CC P57764; P0DTC9: N; Xeno; NbExp=13; IntAct=EBI-2798865, EBI-25475856;
CC -!- SUBCELLULAR LOCATION: [Gasdermin-D]: Cytoplasm, cytosol
CC {ECO:0000269|PubMed:27281216}. Inflammasome
CC {ECO:0000250|UniProtKB:Q9D8T2}. Note=In response to a canonical
CC inflammasome stimulus, such as nigericin, recruited to NLRP3
CC inflammasone with similar kinetics to that of uncleaved CASP1
CC precursor. {ECO:0000250|UniProtKB:Q9D8T2}.
CC -!- SUBCELLULAR LOCATION: [Gasdermin-D, N-terminal]: Cell membrane
CC {ECO:0000269|PubMed:27281216, ECO:0000269|PubMed:32109412,
CC ECO:0000269|PubMed:33883744}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:33883744, ECO:0000305|PubMed:29898893}. Secreted
CC {ECO:0000250|UniProtKB:Q9D8T2}. Note=Released in the extracellular
CC milieu following pyroptosis. {ECO:0000250|UniProtKB:Q9D8T2}.
CC -!- SUBCELLULAR LOCATION: [Gasdermin-D, C-terminal]: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q9D8T2}.
CC -!- TISSUE SPECIFICITY: Expressed in the suprabasal cells of esophagus, as
CC well as in the isthmus/neck, pit, and gland of the stomach, suggesting
CC preferential expression in differentiating cells.
CC {ECO:0000269|PubMed:19051310}.
CC -!- DOMAIN: Intramolecular interactions between N- and C-terminal domains
CC mediate autoinhibition in the absence of cleavage by inflammatory
CC caspases CASP1, CASP4 or CASP5 (PubMed:26375003, PubMed:29898893,
CC PubMed:28928145, PubMed:29576317). The linker helix loop inserts into
CC the N-terminal domain (PubMed:28928145). The intrinsic pyroptosis-
CC inducing activity is carried by Gasdermin-D, N-terminal, that is
CC released upon cleavage by inflammatory caspases (PubMed:26375003).
CC {ECO:0000269|PubMed:26375003, ECO:0000269|PubMed:28928145,
CC ECO:0000269|PubMed:29576317, ECO:0000269|PubMed:29898893}.
CC -!- DOMAIN: [Gasdermin-D, N-terminal]: Forms a ring-shaped pore complex
CC containing 27-28 subunits that inserts into the membrane
CC (PubMed:33883744). The pore conduit is predominantly negatively
CC charged, facilitating the release of mature interleukin-1 (IL1B and
CC IL18) (PubMed:33883744). In contrast interleukin-1 precursors are not
CC released, due to the presence of an acidic region that is
CC proteolytically removed by CASP1 during maturation (PubMed:33883744).
CC {ECO:0000269|PubMed:33883744}.
CC -!- PTM: Cleavage at Asp-275 by CASP1 (mature and uncleaved precursor
CC forms), CASP4, CASP5 or CASP8 relieves autoinhibition and is sufficient
CC to initiate pyroptosis (PubMed:26375003, PubMed:29898893,
CC PubMed:32109412). Cleavage by CASP1 and CASP4 is not strictly dependent
CC on the consensus cleavage site on GSDMD but depends on an exosite
CC interface on CASP1 that recognizes and binds the Gasdermin-D, C-
CC terminal (GSDMD-CT) part (PubMed:32109412). Cleavage by CASP8 takes
CC place following inactivation of MAP3K7/TAK1 by Yersinia toxin YopJ (By
CC similarity). Cleavage at Asp-87 by CASP3 or CAPS7 inactivates the
CC ability to mediate pyroptosis (PubMed:28392147, PubMed:28045099).
CC {ECO:0000250|UniProtKB:Q9D8T2, ECO:0000269|PubMed:26375003,
CC ECO:0000269|PubMed:28045099, ECO:0000269|PubMed:28392147,
CC ECO:0000269|PubMed:29898893, ECO:0000269|PubMed:32109412}.
CC -!- PTM: [Gasdermin-D]: Succination of Cys-191 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 -!- SIMILARITY: Belongs to the gasdermin family. {ECO:0000305}.
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DR EMBL; AY008304; AAG22861.1; -; mRNA.
DR EMBL; AK022212; BAB13986.1; -; mRNA.
DR EMBL; AK291817; BAF84506.1; -; mRNA.
DR EMBL; AC067930; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471162; EAW82243.1; -; Genomic_DNA.
DR EMBL; CH471162; EAW82245.1; -; Genomic_DNA.
DR EMBL; BC008904; AAH08904.1; -; mRNA.
DR EMBL; BC069000; AAH69000.1; -; mRNA.
DR CCDS; CCDS34956.1; -.
DR RefSeq; NP_001159709.1; NM_001166237.1.
DR RefSeq; NP_079012.3; NM_024736.6.
DR PDB; 5NH1; X-ray; 2.04 A; A=278-484.
DR PDB; 5WQT; X-ray; 2.64 A; A/B=276-484.
DR PDB; 6AO4; X-ray; 2.90 A; A=277-484.
DR PDB; 6KN0; X-ray; 2.79 A; E/F=283-480.
DR PDB; 6N9O; X-ray; 3.50 A; A/B/C/D=1-484.
DR PDB; 6VFE; EM; 3.90 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V/W/X/Y/Z/a/b/c/d=1-241.
DR PDBsum; 5NH1; -.
DR PDBsum; 5WQT; -.
DR PDBsum; 6AO4; -.
DR PDBsum; 6KN0; -.
DR PDBsum; 6N9O; -.
DR PDBsum; 6VFE; -.
DR AlphaFoldDB; P57764; -.
DR SMR; P57764; -.
DR BioGRID; 122891; 17.
DR DIP; DIP-61775N; -.
DR IntAct; P57764; 16.
DR STRING; 9606.ENSP00000433209; -.
DR ChEMBL; CHEMBL4523247; -.
DR TCDB; 1.C.123.1.1; the pore-forming gasdermin (gasdermin) family.
DR iPTMnet; P57764; -.
DR PhosphoSitePlus; P57764; -.
DR BioMuta; GSDMD; -.
DR DMDM; 13124058; -.
DR EPD; P57764; -.
DR jPOST; P57764; -.
DR MassIVE; P57764; -.
DR MaxQB; P57764; -.
DR PaxDb; P57764; -.
DR PeptideAtlas; P57764; -.
DR PRIDE; P57764; -.
DR ProteomicsDB; 57029; -.
DR ABCD; P57764; 1 sequenced antibody.
DR Antibodypedia; 27909; 171 antibodies from 30 providers.
DR DNASU; 79792; -.
DR Ensembl; ENST00000262580.9; ENSP00000262580.4; ENSG00000104518.11.
DR Ensembl; ENST00000526406.5; ENSP00000433209.1; ENSG00000104518.11.
DR Ensembl; ENST00000615119.2; ENSP00000482096.1; ENSG00000278718.3.
DR Ensembl; ENST00000631751.1; ENSP00000488012.1; ENSG00000278718.3.
DR GeneID; 79792; -.
DR KEGG; hsa:79792; -.
DR MANE-Select; ENST00000262580.9; ENSP00000262580.4; NM_024736.7; NP_079012.3.
DR UCSC; uc003yyg.4; human.
DR CTD; 79792; -.
DR DisGeNET; 79792; -.
DR GeneCards; GSDMD; -.
DR HGNC; HGNC:25697; GSDMD.
DR HPA; ENSG00000104518; Low tissue specificity.
DR MIM; 617042; gene.
DR neXtProt; NX_P57764; -.
DR OpenTargets; ENSG00000104518; -.
DR PharmGKB; PA162390357; -.
DR VEuPathDB; HostDB:ENSG00000104518; -.
DR eggNOG; ENOG502S0IQ; Eukaryota.
DR GeneTree; ENSGT00950000183140; -.
DR HOGENOM; CLU_040752_1_0_1; -.
DR InParanoid; P57764; -.
DR OMA; STPWQEQ; -.
DR OrthoDB; 747086at2759; -.
DR PhylomeDB; P57764; -.
DR TreeFam; TF331886; -.
DR PathwayCommons; P57764; -.
DR Reactome; R-HSA-111457; Release of apoptotic factors from the mitochondria.
DR Reactome; R-HSA-448706; Interleukin-1 processing.
DR Reactome; R-HSA-5620971; Pyroptosis.
DR Reactome; R-HSA-5686938; Regulation of TLR by endogenous ligand.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR Reactome; R-HSA-9660826; Purinergic signaling in leishmaniasis infection.
DR SignaLink; P57764; -.
DR SIGNOR; P57764; -.
DR BioGRID-ORCS; 79792; 26 hits in 1077 CRISPR screens.
DR ChiTaRS; GSDMD; human.
DR GenomeRNAi; 79792; -.
DR Pharos; P57764; Tchem.
DR PRO; PR:P57764; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; P57764; protein.
DR Bgee; ENSG00000104518; Expressed in spleen and 95 other tissues.
DR ExpressionAtlas; P57764; baseline and differential.
DR Genevisible; P57764; HS.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR GO; GO:1904813; C:ficolin-1-rich granule lumen; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0072559; C:NLRP3 inflammasome complex; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0035580; C:specific granule lumen; TAS:Reactome.
DR GO; GO:1904724; C:tertiary granule lumen; TAS:Reactome.
DR GO; GO:1901612; F:cardiolipin binding; ISS:UniProtKB.
DR GO; GO:0070300; F:phosphatidic acid binding; ISS:UniProtKB.
DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; ISS:UniProtKB.
DR GO; GO:0070273; F:phosphatidylinositol-4-phosphate binding; ISS:UniProtKB.
DR GO; GO:0001786; F:phosphatidylserine binding; ISS:UniProtKB.
DR GO; GO:0022829; F:wide pore channel activity; IDA:UniProtKB.
DR GO; GO:0031668; P:cellular response to extracellular stimulus; IEA:Ensembl.
DR GO; GO:0042742; P:defense response to bacterium; IBA:GO_Central.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; ISS:UniProtKB.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; ISS: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; ISS:UniProtKB.
DR GO; GO:0035915; P:pore formation in membrane of another organism; ISS:UniProtKB.
DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; ISS:UniProtKB.
DR GO; GO:0032732; P:positive regulation of interleukin-1 production; IDA:UniProtKB.
DR GO; GO:0032741; P:positive regulation of interleukin-18 production; IDA:UniProtKB.
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..484
FT /note="Gasdermin-D"
FT /id="PRO_0000148175"
FT CHAIN 1..275
FT /note="Gasdermin-D, N-terminal"
FT /evidence="ECO:0000305|PubMed:26375003"
FT /id="PRO_0000437526"
FT CHAIN 276..484
FT /note="Gasdermin-D, C-terminal"
FT /evidence="ECO:0000305|PubMed:26375003"
FT /id="PRO_0000437527"
FT TRANSMEM 91..97
FT /note="Beta stranded"
FT /evidence="ECO:0000269|PubMed:33883744,
FT ECO:0007744|PDB:6VFE"
FT TRANSMEM 103..108
FT /note="Beta stranded"
FT /evidence="ECO:0000269|PubMed:33883744,
FT ECO:0007744|PDB:6VFE"
FT TRANSMEM 180..186
FT /note="Beta stranded"
FT /evidence="ECO:0000269|PubMed:33883744,
FT ECO:0007744|PDB:6VFE"
FT TRANSMEM 191..197
FT /note="Beta stranded"
FT /evidence="ECO:0000269|PubMed:33883744,
FT ECO:0007744|PDB:6VFE"
FT REGION 277..296
FT /note="Linker helix loop"
FT /evidence="ECO:0000269|PubMed:28928145"
FT SITE 87..88
FT /note="Cleavage; by CASP3 or CASP7"
FT /evidence="ECO:0000269|PubMed:28045099,
FT ECO:0000269|PubMed:28392147"
FT SITE 275..276
FT /note="Cleavage; by caspases CASP1, CASP4, CASP5 and CASP8"
FT /evidence="ECO:0000269|PubMed:26375003,
FT ECO:0000269|PubMed:32109412, ECO:0000305|PubMed:29898893"
FT MOD_RES 37
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:15592455"
FT MOD_RES 56
FT /note="S-(2-succinyl)cysteine"
FT /evidence="ECO:0000269|PubMed:32820063"
FT MOD_RES 158
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:15592455"
FT MOD_RES 185
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 191
FT /note="S-(2-succinyl)cysteine"
FT /evidence="ECO:0000269|PubMed:32820063"
FT MOD_RES 268
FT /note="S-(2-succinyl)cysteine"
FT /evidence="ECO:0000269|PubMed:32820063"
FT MOD_RES 309
FT /note="S-(2-succinyl)cysteine"
FT /evidence="ECO:0000269|PubMed:32820063"
FT MOD_RES 467
FT /note="S-(2-succinyl)cysteine"
FT /evidence="ECO:0000269|PubMed:32820063"
FT MUTAGEN 7..11
FT /note="RVVRR->AVVAA: Impaired pore-formation."
FT /evidence="ECO:0000269|PubMed:29695864"
FT MUTAGEN 15
FT /note="E->K: No spontaneous pyroptosis-inducing activity;
FT when associated with D-192."
FT /evidence="ECO:0000269|PubMed:27281216,
FT ECO:0000269|PubMed:28928145"
FT MUTAGEN 42..53
FT /note="RKPSSSWFWKPR->EEPSSSWFWEPE: Abolished ability to
FT form a pore."
FT /evidence="ECO:0000269|PubMed:33883744"
FT MUTAGEN 48..50
FT /note="WFW->GFG: Abolished ability to form a pore."
FT /evidence="ECO:0000269|PubMed:33883744"
FT MUTAGEN 63..73
FT /note="DILEPDAAEPD->AILAPDAAAPA: In AP1; promotes ability
FT to release of interleukin-1 (IL1B and IL18) precursors."
FT /evidence="ECO:0000269|PubMed:33883744"
FT MUTAGEN 87..95
FT /note="DGQIQGSVE->AGQIQGSVA: In AP2; promotes ability to
FT release of interleukin-1 (IL1B and IL18) precursors."
FT /evidence="ECO:0000269|PubMed:33883744"
FT MUTAGEN 104
FT /note="I->N: Decreased effectiveness in pore formation and
FT pyroptosis induction. No effect on cleavage by CASP1."
FT /evidence="ECO:0000269|PubMed:27418190"
FT MUTAGEN 174
FT /note="R->E: Reduced ability to form a pore."
FT /evidence="ECO:0000269|PubMed:33883744"
FT MUTAGEN 192
FT /note="L->D: Decreased induction of pyroptosis and defects
FT in liposome-binding. No spontaneous pyroptosis-inducing
FT activity; when associated with K-15."
FT /evidence="ECO:0000269|PubMed:27281216,
FT ECO:0000269|PubMed:28928145"
FT MUTAGEN 204
FT /note="K->E: Reduced ability to form a pore."
FT /evidence="ECO:0000269|PubMed:33883744"
FT MUTAGEN 272..274
FT /note="FLT->AAA: Does not affect interaction with CASP4."
FT /evidence="ECO:0000269|PubMed:32109412"
FT MUTAGEN 275
FT /note="D->A: Loss of cleavage by CASP1 and CASP4 and of
FT LPS-induced pyroptosis. Does not affect interaction with
FT CASP1 and CASP4."
FT /evidence="ECO:0000269|PubMed:26375003,
FT ECO:0000269|PubMed:32109412"
FT MUTAGEN 277..296
FT /note="VPAEGAFTEDFQGLRAEVET->SGGGS: Constitutively active
FT mutant; promotes activation of pyroptosis."
FT /evidence="ECO:0000269|PubMed:28928145"
FT MUTAGEN 283
FT /note="F->A,R: Constitutively active mutant; promotes
FT activation of pyroptosis."
FT /evidence="ECO:0000269|PubMed:28928145"
FT MUTAGEN 283
FT /note="F->Y: No effect."
FT /evidence="ECO:0000269|PubMed:28928145"
FT MUTAGEN 290
FT /note="L->D: Spontaneous pyroptosis-inducing activity."
FT /evidence="ECO:0000269|PubMed:27281216"
FT MUTAGEN 304..308
FT /note="LDREL->ADREA: Impairs interaction with CASP1 and
FT CASP4 and subsequent cleavage."
FT /evidence="ECO:0000269|PubMed:32109412"
FT MUTAGEN 364..367
FT /note="VPEL->APEA: Impairs interaction with CASP1 and CASP4
FT and subsequent cleavage."
FT /evidence="ECO:0000269|PubMed:32109412"
FT MUTAGEN 373
FT /note="Y->D: Spontaneous pyroptosis-inducing activity."
FT /evidence="ECO:0000269|PubMed:27281216"
FT MUTAGEN 377
FT /note="A->D: Spontaneous pyroptosis-inducing activity."
FT /evidence="ECO:0000269|PubMed:27281216"
FT CONFLICT 360..483
FT /note="SGMLVPELAIPVVYLLGALTMLSETQHKLLAEALESQTLLGPLELVGSLLEQ
FT SAPWQERSTMSLPPGLLGNSWGEGAPAWVLLDECGLELGEDTPHVCWEPQAQGRMCALY
FT ASLALLSGLSQEP -> PECWCRNSLSLLSTCWG (in Ref. 1; AAG22861)"
FT /evidence="ECO:0000305"
FT CONFLICT 386
FT /note="H -> R (in Ref. 2; BAF84506)"
FT /evidence="ECO:0000305"
FT HELIX 4..16
FT /evidence="ECO:0007829|PDB:6N9O"
FT TURN 29..31
FT /evidence="ECO:0007829|PDB:6N9O"
FT STRAND 39..42
FT /evidence="ECO:0007829|PDB:6N9O"
FT TURN 62..64
FT /evidence="ECO:0007829|PDB:6N9O"
FT STRAND 65..67
FT /evidence="ECO:0007829|PDB:6N9O"
FT STRAND 121..123
FT /evidence="ECO:0007829|PDB:6N9O"
FT HELIX 127..136
FT /evidence="ECO:0007829|PDB:6N9O"
FT HELIX 147..153
FT /evidence="ECO:0007829|PDB:6N9O"
FT STRAND 156..165
FT /evidence="ECO:0007829|PDB:6N9O"
FT STRAND 215..221
FT /evidence="ECO:0007829|PDB:6N9O"
FT STRAND 229..232
FT /evidence="ECO:0007829|PDB:6N9O"
FT HELIX 287..298
FT /evidence="ECO:0007829|PDB:5NH1"
FT HELIX 299..301
FT /evidence="ECO:0007829|PDB:5NH1"
FT HELIX 306..320
FT /evidence="ECO:0007829|PDB:5NH1"
FT HELIX 323..333
FT /evidence="ECO:0007829|PDB:5NH1"
FT HELIX 347..355
FT /evidence="ECO:0007829|PDB:5NH1"
FT STRAND 359..361
FT /evidence="ECO:0007829|PDB:6AO4"
FT HELIX 365..378
FT /evidence="ECO:0007829|PDB:5NH1"
FT HELIX 383..394
FT /evidence="ECO:0007829|PDB:5NH1"
FT HELIX 399..411
FT /evidence="ECO:0007829|PDB:5NH1"
FT STRAND 412..417
FT /evidence="ECO:0007829|PDB:6AO4"
FT STRAND 419..421
FT /evidence="ECO:0007829|PDB:5NH1"
FT HELIX 425..428
FT /evidence="ECO:0007829|PDB:5NH1"
FT STRAND 429..431
FT /evidence="ECO:0007829|PDB:6KN0"
FT HELIX 437..443
FT /evidence="ECO:0007829|PDB:5NH1"
FT TURN 444..446
FT /evidence="ECO:0007829|PDB:5NH1"
FT STRAND 451..458
FT /evidence="ECO:0007829|PDB:5NH1"
FT HELIX 460..462
FT /evidence="ECO:0007829|PDB:5NH1"
FT HELIX 463..479
FT /evidence="ECO:0007829|PDB:5NH1"
SQ SEQUENCE 484 AA; 52801 MW; F7CE8073E0C0194D CRC64;
MGSAFERVVR RVVQELDHGG EFIPVTSLQS STGFQPYCLV VRKPSSSWFW KPRYKCVNLS
IKDILEPDAA EPDVQRGRSF HFYDAMDGQI QGSVELAAPG QAKIAGGAAV SDSSSTSMNV
YSLSVDPNTW QTLLHERHLR QPEHKVLQQL RSRGDNVYVV TEVLQTQKEV EVTRTHKREG
SGRFSLPGAT CLQGEGQGHL SQKKTVTIPS GSTLAFRVAQ LVIDSDLDVL LFPDKKQRTF
QPPATGHKRS TSEGAWPQLP SGLSMMRCLH NFLTDGVPAE GAFTEDFQGL RAEVETISKE
LELLDRELCQ LLLEGLEGVL RDQLALRALE EALEQGQSLG PVEPLDGPAG AVLECLVLSS
GMLVPELAIP VVYLLGALTM LSETQHKLLA EALESQTLLG PLELVGSLLE QSAPWQERST
MSLPPGLLGN SWGEGAPAWV LLDECGLELG EDTPHVCWEP QAQGRMCALY ASLALLSGLS
QEPH
