GSDME_HORSE
ID GSDME_HORSE Reviewed; 497 AA.
AC Q7YS54;
DT 10-MAY-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2003, sequence version 1.
DT 25-MAY-2022, entry version 62.
DE RecName: Full=Gasdermin-E {ECO:0000250|UniProtKB:O60443};
DE AltName: Full=Non-syndromic hearing impairment protein 5 homolog {ECO:0000305};
DE Contains:
DE RecName: Full=Gasdermin-E, N-terminal {ECO:0000250|UniProtKB:O60443};
DE Short=GSDME-NT {ECO:0000250|UniProtKB:O60443};
DE Contains:
DE RecName: Full=Gasdermin-E, C-terminal {ECO:0000250|UniProtKB:O60443};
DE Short=GSDME-CT {ECO:0000250|UniProtKB:O60443};
GN Name=GSDME {ECO:0000250|UniProtKB:O60443};
GN Synonyms=DFNA5 {ECO:0000250|UniProtKB:O60443};
OS Equus caballus (Horse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Perissodactyla; Equidae; Equus.
OX NCBI_TaxID=9796;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=12853124; DOI=10.1016/s0925-4439(03)00083-8;
RA Gregan J., Van Laer L., Lieto L.D., Van Camp G., Kearsey S.E.;
RT "A yeast model for the study of human DFNA5, a gene mutated in nonsyndromic
RT hearing impairment.";
RL Biochim. Biophys. Acta 1638:179-186(2003).
CC -!- FUNCTION: [Gasdermin-E]: Precursor of a pore-forming protein that
CC converts non-inflammatory apoptosis to pyroptosis. This form
CC constitutes the precursor of the pore-forming protein: upon cleavage,
CC the released N-terminal moiety (Gasdermin-E, N-terminal) binds to
CC membranes and forms pores, triggering pyroptosis.
CC {ECO:0000250|UniProtKB:O60443}.
CC -!- FUNCTION: [Gasdermin-E, N-terminal]: Pore-forming protein produced by
CC cleavage by CASP3 or granzyme B (GZMB), which converts non-inflammatory
CC apoptosis to pyroptosis or promotes granzyme-mediated pyroptosis,
CC respectively. After cleavage, moves to the plasma membrane,
CC homooligomerizes within the membrane and forms pores of 10-15
CC nanometers (nm) of inner diameter, triggering pyroptosis. Binds to
CC inner leaflet lipids, bisphosphorylated phosphatidylinositols, such as
CC phosphatidylinositol (4,5)-bisphosphate. Cleavage by CASP3 switches
CC CASP3-mediated apoptosis induced by TNF or danger signals, such as
CC chemotherapy drugs, to pyroptosis. Mediates secondary necrosis
CC downstream of the mitochondrial apoptotic pathway and CASP3 activation
CC as well as in response to viral agents. Exhibits bactericidal activity.
CC Cleavage by GZMB promotes tumor suppressor activity by triggering
CC robust anti-tumor immunity. Suppresses tumors by mediating granzyme-
CC mediated pyroptosis in target cells of natural killer (NK) cells:
CC cleavage by granzyme B (GZMB), delivered to target cells from NK-cells,
CC triggers pyroptosis of tumor cells and tumor suppression. May play a
CC role in the p53/TP53-regulated cellular response to DNA damage.
CC {ECO:0000250|UniProtKB:O60443}.
CC -!- ACTIVITY REGULATION: [Gasdermin-E]: 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. The intrinsic pyroptosis-inducing activity is carried by the
CC released N-terminal moiety (Gasdermin-E, N-terminal) following cleavage
CC by CASP3 or granzyme B (GZMB). {ECO:0000250|UniProtKB:O60443}.
CC -!- SUBUNIT: [Gasdermin-E, N-terminal]: Homooligomer; homooligomeric ring-
CC shaped pore complex containing 27-28 subunits when inserted in the
CC membrane. {ECO:0000250|UniProtKB:Q5Y4Y6}.
CC -!- SUBCELLULAR LOCATION: [Gasdermin-E, N-terminal]: Cell membrane
CC {ECO:0000250|UniProtKB:O60443}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q5Y4Y6}.
CC -!- SUBCELLULAR LOCATION: [Gasdermin-E]: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:O60443}.
CC -!- DOMAIN: Intramolecular interactions between N- and C-terminal domains
CC may be important for autoinhibition in the absence of activation
CC signal. The intrinsic pyroptosis-inducing activity is carried by the N-
CC terminal domain, that is released upon cleavage by CASP3 or granzyme B
CC (GZMB). {ECO:0000250|UniProtKB:O60443}.
CC -!- PTM: Cleavage at Asp-270 by CASP3 (mature and uncleaved precursor
CC forms) or granzyme B (GZMB) relieves autoinhibition and is sufficient
CC to initiate pyroptosis. {ECO:0000250|UniProtKB:O60443}.
CC -!- PTM: [Gasdermin-E]: Succination by the Krebs cycle intermediate
CC fumarate, which leads to S-(2-succinyl)cysteine residues, inhibits
CC processing by caspases, and ability to initiate pyroptosis. Succination
CC modification is catalyzed by a non-enzymatic reaction caused by an
CC accumulation of fumarate. {ECO:0000250|UniProtKB:O60443}.
CC -!- SIMILARITY: Belongs to the gasdermin family. {ECO:0000305}.
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DR EMBL; AY194290; AAP35046.1; -; mRNA.
DR RefSeq; NP_001075358.1; NM_001081889.1.
DR AlphaFoldDB; Q7YS54; -.
DR STRING; 9796.ENSECAP00000018779; -.
DR PaxDb; Q7YS54; -.
DR GeneID; 100033992; -.
DR KEGG; ecb:100033992; -.
DR CTD; 1687; -.
DR InParanoid; Q7YS54; -.
DR OrthoDB; 1397132at2759; -.
DR Proteomes; UP000002281; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:1901612; F:cardiolipin binding; ISS:UniProtKB.
DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; ISS:UniProtKB.
DR GO; GO:0022829; F:wide pore channel activity; ISS:UniProtKB.
DR GO; GO:0008219; P:cell death; ISS:UniProtKB.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; ISS:UniProtKB.
DR GO; GO:0098586; P:cellular response to virus; ISS:UniProtKB.
DR GO; GO:0140507; P:granzyme-mediated programmed cell death signaling pathway; ISS:UniProtKB.
DR GO; GO:0070265; P:necrotic cell death; ISS:UniProtKB.
DR GO; GO:0002839; P:positive regulation of immune response to tumor cell; ISS:UniProtKB.
DR GO; GO:2001244; P:positive regulation of intrinsic apoptotic signaling pathway; ISS:UniProtKB.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISS:UniProtKB.
DR GO; GO:0070269; P:pyroptosis; ISS:UniProtKB.
DR InterPro; IPR040460; Gasdermin_pore.
DR InterPro; IPR041263; Gasdermin_PUB.
DR InterPro; IPR042377; GSDME.
DR PANTHER; PTHR15207; PTHR15207; 1.
DR Pfam; PF04598; Gasdermin; 1.
DR Pfam; PF17708; Gasdermin_C; 1.
PE 2: Evidence at transcript level;
KW Cell membrane; Cytoplasm; Membrane; Necrosis; Reference proteome;
KW Transmembrane; Transmembrane beta strand.
FT CHAIN 1..497
FT /note="Gasdermin-E"
FT /id="PRO_0000148177"
FT CHAIN 1..270
FT /note="Gasdermin-E, N-terminal"
FT /evidence="ECO:0000250|UniProtKB:O60443"
FT /id="PRO_0000442747"
FT CHAIN 271..497
FT /note="Gasdermin-E, C-terminal"
FT /evidence="ECO:0000250|UniProtKB:O60443"
FT /id="PRO_0000442748"
FT REGION 1..56
FT /note="Membrane targeting domain"
FT /evidence="ECO:0000250|UniProtKB:O60443"
FT SITE 270..271
FT /note="Cleavage; by CASP3 or granzyme B"
FT /evidence="ECO:0000250|UniProtKB:O60443"
FT MOD_RES 45
FT /note="S-(2-succinyl)cysteine"
FT /evidence="ECO:0000250|UniProtKB:O60443"
FT MOD_RES 156
FT /note="S-(2-succinyl)cysteine"
FT /evidence="ECO:0000250|UniProtKB:O60443"
FT MOD_RES 168
FT /note="S-(2-succinyl)cysteine"
FT /evidence="ECO:0000250|UniProtKB:O60443"
FT MOD_RES 180
FT /note="S-(2-succinyl)cysteine"
FT /evidence="ECO:0000250|UniProtKB:O60443"
FT MOD_RES 235
FT /note="S-(2-succinyl)cysteine"
FT /evidence="ECO:0000250|UniProtKB:O60443"
FT MOD_RES 371
FT /note="S-(2-succinyl)cysteine"
FT /evidence="ECO:0000250|UniProtKB:O60443"
FT MOD_RES 409
FT /note="S-(2-succinyl)cysteine"
FT /evidence="ECO:0000250|UniProtKB:O60443"
FT MOD_RES 418
FT /note="S-(2-succinyl)cysteine"
FT /evidence="ECO:0000250|UniProtKB:O60443"
FT MOD_RES 491
FT /note="S-(2-succinyl)cysteine"
FT /evidence="ECO:0000250|UniProtKB:O60443"
SQ SEQUENCE 497 AA; 54883 MW; 229FAA7C7770D369 CRC64;
MFAKATRSFL REVDAEGDLI AVSNLNDSDK SQLLSLVTKK KRFWCWQRPK YQFLSVTLGD
VLTEAQCLSP VVVESDFVKY EGKFENHVSG TIETALGKVK LNFGDKGLRE SQSSFGTLRK
QEVDLQQLIR DSVERTINLK NPVLQQMLES KNEVLCILTQ KIVTTQKCVI SEHIQTEEKC
GGMVGIKTKT VQVSVTKDEN IIKDASVALE IPAPTTIAYS VIELYVKLDG QFEFCLLRGK
HGGFEHQRRS DIVFPDAGAL QDFPFWDVPD AGQGLPTPDG PLSVLKQGTR LLEKNFFPFV
ELPEQHRTAL NTVLQAVLSD EELLAVLEQV CDDLVHSLSP PLAMLGELKP PHRQDLTAFL
RLVGYRVQGG CPCLEDGVGS QKLFSTAYFL VSALAEMPDN AAALLGTCCK LQIIPALCHL
LHAMSHDGVC DLEDPALAPL KDTERFGVAQ RLFASADINL ERVQSSVKAV TPLKDPSVLP
LILYISLKGL CALGREH
