CASP1_HUMAN
ID CASP1_HUMAN Reviewed; 404 AA.
AC P29466; B5MDZ1; Q53EY6; Q6DMQ1; Q6GSS3; Q6PI75; Q9UCN3;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1993, sequence version 1.
DT 03-AUG-2022, entry version 232.
DE RecName: Full=Caspase-1;
DE Short=CASP-1;
DE EC=3.4.22.36 {ECO:0000269|PubMed:1574116};
DE AltName: Full=Interleukin-1 beta convertase {ECO:0000303|PubMed:1574116};
DE Short=IL-1BC {ECO:0000303|PubMed:1574116};
DE AltName: Full=Interleukin-1 beta-converting enzyme {ECO:0000303|PubMed:11051551, ECO:0000303|PubMed:1574116};
DE Short=ICE {ECO:0000303|PubMed:11051551, ECO:0000303|PubMed:1574116};
DE Short=IL-1 beta-converting enzyme {ECO:0000303|PubMed:11051551, ECO:0000303|PubMed:1574116};
DE AltName: Full=p45;
DE Contains:
DE RecName: Full=Caspase-1 subunit p20 {ECO:0000303|PubMed:8044845};
DE Contains:
DE RecName: Full=Caspase-1 subunit p10 {ECO:0000303|PubMed:8044845};
DE Flags: Precursor;
GN Name=CASP1; Synonyms=IL1BC, IL1BCE;
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 ALPHA), PARTIAL PROTEIN SEQUENCE,
RP ACTIVE SITE, FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=1574116; DOI=10.1038/356768a0;
RA Thornberry N.A., Bull H.G., Calaycay J.R., Chapman K.T., Howard A.D.,
RA Kostura M.J., Miller D.K., Molineaux S.M., Weidner J.R., Aunins J.,
RA Elliston K.O., Ayala J.M., Casano F.J., Chin J., Ding G.J.-F., Egger L.A.,
RA Gaffney E.P., Limjuco G., Palyha O.C., Raju M., Rolando A.M., Salley J.P.,
RA Yamin T.-T., Lee T.D., Shively J.E., McCross M., Mumford R.A.,
RA Schmidt J.A., Tocci M.J.;
RT "A novel heterodimeric cysteine protease is required for interleukin-1 beta
RT processing in monocytes.";
RL Nature 356:768-774(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA), AND PROTEIN SEQUENCE OF
RP 120-142.
RX PubMed=1373520; DOI=10.1126/science.1373520;
RA Cerretti D.P., Kozlosky C.J., Mosley B., Nelson N., van Ness K.,
RA Greenstreet T.A., March C.J., Kronheim S.R., Druck T., Cannizzaro L.A.,
RA Huebner K., Black R.A.;
RT "Molecular cloning of the interleukin-1 beta converting enzyme.";
RL Science 256:97-100(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS BETA; DELTA; EPSILON AND GAMMA),
RP ALTERNATIVE SPLICING, AND FUNCTION.
RX PubMed=7876192; DOI=10.1074/jbc.270.9.4312;
RA Alnemri E.S., Fernandes-Alnemri T., Litwack G.;
RT "Cloning and expression of four novel isoforms of human interleukin-1 beta
RT converting enzyme with different apoptotic activities.";
RL J. Biol. Chem. 270:4312-4317(1995).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA).
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM GAMMA), AND NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 4-404 (ISOFORM BETA).
RC TISSUE=Testis;
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 [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 32-404 (ISOFORM ALPHA), FUNCTION, MUTAGENESIS
RP OF CYS-285, ALTERNATIVE SPLICING, AND TISSUE SPECIFICITY.
RX PubMed=15498465; DOI=10.1016/j.ygeno.2004.06.005;
RA Feng Q., Li P., Leung P.C.K., Auersperg N.;
RT "Caspase-1 zeta, a new splice variant of caspase-1 gene.";
RL Genomics 84:587-591(2004).
RN [8]
RP PROTEIN SEQUENCE OF 120-142.
RX PubMed=1321594; DOI=10.1016/0003-9861(92)90629-b;
RA Kronheim S.R., Mumma A., Greenstreet T., Glackin P.J., Van Ness K.,
RA March C.J., Black R.A.;
RT "Purification of interleukin-1 beta converting enzyme, the protease that
RT cleaves the interleukin-1 beta precursor.";
RL Arch. Biochem. Biophys. 296:698-703(1992).
RN [9]
RP ACTIVITY REGULATION.
RX PubMed=1339309; DOI=10.1016/0092-8674(92)90223-y;
RA Ray C.A., Black R.A., Kronheim S.R., Greenstreet T.A., Sleath P.R.,
RA Salvesen G.S., Pickup D.J.;
RT "Viral inhibition of inflammation: cowpox virus encodes an inhibitor of the
RT interleukin-1 beta converting enzyme.";
RL Cell 69:597-604(1992).
RN [10]
RP INTERACTION WITH CARD18.
RX PubMed=11051551; DOI=10.1016/s0092-8674(00)00108-2;
RA Humke E.W., Shriver S.K., Starovasnik M.A., Fairbrother W.J., Dixit V.M.;
RT "ICEBERG: a novel inhibitor of interleukin-1beta generation.";
RL Cell 103:99-111(2000).
RN [11]
RP COMPONENT OF THE INFLAMMASOME.
RX PubMed=15030775; DOI=10.1016/s1074-7613(04)00046-9;
RA Agostini L., Martinon F., Burns K., McDermott M.F., Hawkins P.N.,
RA Tschopp J.;
RT "NALP3 forms an IL-1beta-processing inflammasome with increased activity in
RT Muckle-Wells autoinflammatory disorder.";
RL Immunity 20:319-325(2004).
RN [12]
RP INTERACTION WITH CARD17.
RX PubMed=15383541; DOI=10.1074/jbc.m407891200;
RA Lamkanfi M., Denecker G., Kalai M., D'hondt K., Meeus A., Declercq W.,
RA Saelens X., Vandenabeele P.;
RT "INCA, a novel human caspase recruitment domain protein that inhibits
RT interleukin-1beta generation.";
RL J. Biol. Chem. 279:51729-51738(2004).
RN [13]
RP FUNCTION.
RX PubMed=15326478; DOI=10.1038/sj.onc.1208036;
RA Gaggero A., De Ambrosis A., Mezzanzanica D., Piazza T., Rubartelli A.,
RA Figini M., Canevari S., Ferrini S.;
RT "A novel isoform of pro-interleukin-18 expressed in ovarian tumors is
RT resistant to caspase-1 and -4 processing.";
RL Oncogene 23:7552-7560(2004).
RN [14]
RP INTERACTION WITH MEFV.
RX PubMed=16785446; DOI=10.1073/pnas.0602081103;
RA Chae J.J., Wood G., Masters S.L., Richard K., Park G., Smith B.J.,
RA Kastner D.L.;
RT "The B30.2 domain of pyrin, the familial Mediterranean fever protein,
RT interacts directly with caspase-1 to modulate IL-1beta production.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:9982-9987(2006).
RN [15]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF CYS-285.
RX PubMed=20197547; DOI=10.1182/blood-2009-10-243444;
RA Weigert A., Cremer S., Schmidt M.V., von Knethen A., Angioni C.,
RA Geisslinger G., Bruene B.;
RT "Cleavage of sphingosine kinase 2 by caspase-1 provokes its release from
RT apoptotic cells.";
RL Blood 115:3531-3540(2010).
RN [16]
RP INDUCTION BY M.TUBERCULOSIS.
RC TISSUE=Macrophage;
RX PubMed=20148899; DOI=10.1111/j.1462-5822.2010.01450.x;
RA Mishra B.B., Moura-Alves P., Sonawane A., Hacohen N., Griffiths G.,
RA Moita L.F., Anes E.;
RT "Mycobacterium tuberculosis protein ESAT-6 is a potent activator of the
RT NLRP3/ASC inflammasome.";
RL Cell. Microbiol. 12:1046-1063(2010).
RN [17]
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 [18]
RP FUNCTION, AND CATALYTIC ACTIVITY.
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 [19]
RP FUNCTION.
RX PubMed=28314590; DOI=10.1016/j.immuni.2017.02.011;
RA Wang Y., Ning X., Gao P., Wu S., Sha M., Lv M., Zhou X., Gao J., Fang R.,
RA Meng G., Su X., Jiang Z.;
RT "Inflammasome activation triggers caspase-1-mediated cleavage of cGAS to
RT regulate responses to DNA virus infection.";
RL Immunity 46:393-404(2017).
RN [20]
RP UBIQUITINATION AT LYS-134.
RX PubMed=30065070; DOI=10.15252/embj.201899347;
RA Zheng Y., Liu Q., Wu Y., Ma L., Zhang Z., Liu T., Jin S., She Y., Li Y.P.,
RA Cui J.;
RT "Zika virus elicits inflammation to evade antiviral response by cleaving
RT cGAS via NS1-caspase-1 axis.";
RL EMBO J. 37:0-0(2018).
RN [21]
RP INTERACTION WITH SERPINB1.
RX PubMed=30692621; DOI=10.1038/s41590-018-0303-z;
RA Choi Y.J., Kim S., Choi Y., Nielsen T.B., Yan J., Lu A., Ruan J., Lee H.R.,
RA Wu H., Spellberg B., Jung J.U.;
RT "SERPINB1-mediated checkpoint of inflammatory caspase activation.";
RL Nat. Immunol. 20:276-287(2019).
RN [22]
RP FUNCTION, INTERACTION WITH CARD8, PROTEOLYTIC CLEAVAGE, AND MUTAGENESIS OF
RP CYS-285; ASP-297 AND 315-ASP-ASP-316.
RX PubMed=32051255; DOI=10.26508/lsa.202000664;
RA Ball D.P., Taabazuing C.Y., Griswold A.R., Orth E.L., Rao S.D.,
RA Kotliar I.B., Vostal L.E., Johnson D.C., Bachovchin D.A.;
RT "Caspase-1 interdomain linker cleavage is required for pyroptosis.";
RL Life. Sci Alliance 3:0-0(2020).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS), AND SUBUNIT.
RX PubMed=8044845; DOI=10.1016/0092-8674(94)90303-4;
RA Walker N.P.C., Talanian R.V., Brady K.D., Dang L.C., Bump N.J.,
RA Ferenz C.R., Franklin S., Ghayur T., Hackett M.C., Hammill L.D., Herzog L.,
RA Hugunin M., Houy W., Mankovich J.A., McGuiness L., Orlewicz E., Paskind M.,
RA Pratt C.A., Reis P., Summani A., Terranova M., Welch J.P., Xiong L.,
RA Moeller A., Tracey D.E., Kamen R., Wong W.W.;
RT "Crystal structure of the cysteine protease interleukin-1 beta-converting
RT enzyme: a (p20/p10)2 homodimer.";
RL Cell 78:343-352(1994).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (2.73 ANGSTROMS).
RX PubMed=9190289; DOI=10.1016/s1074-5521(97)90258-1;
RA Rano T.A., Timkey T., Peterson E.P., Rotonda J., Nicholson D.W.,
RA Becker J.W., Chapman K.T., Thornberry N.A.;
RT "A combinatorial approach for determining protease specificities:
RT application to interleukin-1beta converting enzyme (ICE).";
RL Chem. Biol. 4:149-155(1997).
RN [25]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEX WITH INHIBITORS.
RX PubMed=9987822; DOI=10.1248/cpb.47.11;
RA Okamoto Y., Anan H., Nakai E., Morihira K., Yonetoku Y., Kurihara H.,
RA Sakashita H., Terai Y., Takeuchi M., Shibanuma T., Isomura Y.;
RT "Peptide based interleukin-1 beta converting enzyme (ICE) inhibitors:
RT synthesis, structure activity relationships and crystallographic study of
RT the ICE-inhibitor complex.";
RL Chem. Pharm. Bull. 47:11-21(1999).
RN [26]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 120-404 OF MUTANT ALA-285.
RX PubMed=15296730; DOI=10.1016/j.str.2004.05.010;
RA Romanowski M.J., Scheer J.M., O'Brien T., McDowell R.S.;
RT "Crystal structures of a ligand-free and malonate-bound human caspase-1:
RT implications for the mechanism of substrate binding.";
RL Structure 12:1361-1371(2004).
RN [27] {ECO:0007744|PDB:6KN0}
RP X-RAY CRYSTALLOGRAPHY (2.79 ANGSTROMS) OF 131-297 AND 317-404 IN COMPLEX
RP WITH GSDMD, FUNCTION, SUBUNIT, PROTEOLYTIC CLEAVAGE, AND MUTAGENESIS OF
RP CYS-285; TRP-294 AND ILE-318.
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:6VIE}
RP X-RAY CRYSTALLOGRAPHY (3.40 ANGSTROMS) OF 120-303 AND 317-404 IN COMPLEX
RP WITH GSDMD, FUNCTION, SUBUNIT, AND MUTAGENESIS OF CYS-285; TRP-294; ILE-318
RP AND LYS-320.
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).
RN [29] {ECO:0007744|PDB:7KEU}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.90 ANGSTROMS) OF 2-86 IN COMPLEX WITH
RP PYCARD, AND INTERACTION WITH PYCARD.
RX PubMed=33420033; DOI=10.1038/s41467-020-20320-y;
RA Robert Hollingsworth L., David L., Li Y., Griswold A.R., Ruan J.,
RA Sharif H., Fontana P., Orth-He E.L., Fu T.M., Bachovchin D.A., Wu H.;
RT "Mechanism of filament formation in UPA-promoted CARD8 and NLRP1
RT inflammasomes.";
RL Nat. Commun. 12:189-189(2021).
CC -!- FUNCTION: Thiol protease involved in a variety of inflammatory
CC processes by proteolytically cleaving other proteins, such as the
CC precursors of the inflammatory cytokines interleukin-1 beta (IL1B) and
CC interleukin 18 (IL18) as well as the pyroptosis inducer Gasdermin-D
CC (GSDMD), into active mature peptides (PubMed:15326478, PubMed:1574116,
CC PubMed:7876192, PubMed:15498465, PubMed:26375003, PubMed:32051255).
CC Plays a key role in cell immunity as an inflammatory response
CC initiator: once activated through formation of an inflammasome complex,
CC it initiates a pro-inflammatory response through the cleavage of the
CC two inflammatory cytokines IL1B and IL18, releasing the mature
CC cytokines which are involved in a variety of inflammatory processes
CC (PubMed:1574116, PubMed:7876192, PubMed:15498465, PubMed:15326478,
CC PubMed:32051255). Cleaves a tetrapeptide after an Asp residue at
CC position P1 (PubMed:1574116, PubMed:7876192, PubMed:15498465). Also
CC initiates pyroptosis, a programmed lytic cell death pathway, through
CC cleavage of GSDMD (PubMed:26375003). In contrast to cleavage of
CC interleukins IL1B and IL1B, recognition and cleavage of GSDMD is not
CC strictly dependent on the consensus cleavage site but depends on an
CC exosite interface on CASP1 that recognizes and binds the Gasdermin-D,
CC C-terminal (GSDMD-CT) part (PubMed:32051255, PubMed:32109412,
CC PubMed:32553275). Upon inflammasome activation, during DNA virus
CC infection but not RNA virus challenge, controls antiviral immunity
CC through the cleavage of CGAS, rendering it inactive (PubMed:28314590).
CC In apoptotic cells, cleaves SPHK2 which is released from cells and
CC remains enzymatically active extracellularly (PubMed:20197547).
CC {ECO:0000269|PubMed:15326478, ECO:0000269|PubMed:15498465,
CC ECO:0000269|PubMed:1574116, ECO:0000269|PubMed:20197547,
CC ECO:0000269|PubMed:26375003, ECO:0000269|PubMed:28314590,
CC ECO:0000269|PubMed:32051255, ECO:0000269|PubMed:32109412,
CC ECO:0000269|PubMed:32553275, ECO:0000269|PubMed:7876192}.
CC -!- FUNCTION: [Isoform Delta]: Apoptosis inactive.
CC {ECO:0000269|PubMed:7876192}.
CC -!- FUNCTION: [Isoform Epsilon]: Apoptosis inactive.
CC {ECO:0000269|PubMed:7876192}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Strict requirement for an Asp residue at position P1 and has a
CC preferred cleavage sequence of Tyr-Val-Ala-Asp-|-.; EC=3.4.22.36;
CC Evidence={ECO:0000269|PubMed:1574116};
CC -!- ACTIVITY REGULATION: (Microbial infection) Specifically inhibited by
CC the cowpox virus Crma protein. {ECO:0000269|PubMed:1339309}.
CC -!- SUBUNIT: Heterotetramer that consists of two anti-parallel arranged
CC heterodimers, each one formed by a 20 kDa (Caspase-1 subunit p20) and a
CC 10 kDa (Caspase-1 subunit p10) subunit (PubMed:8044845, PubMed:9987822,
CC PubMed:32109412, PubMed:32553275). May be a component of the
CC inflammasome, a protein complex which also includes PYCARD, CARD8 and
CC NLRP2 and whose function would be the activation of pro-inflammatory
CC caspases (PubMed:15030775, PubMed:33420033). Component of the AIM2
CC PANoptosome complex, a multiprotein complex that drives inflammatory
CC cell death (PANoptosis) (By similarity). Interacts with CARD8;
CC interacts with the released C-terminus of CARD8 which forms an
CC inflammasome and directly activates CASP1 to promote pyroptosis
CC (PubMed:32051255). Both the p10 and p20 subunits interact with MEFV
CC (PubMed:16785446). Interacts with CARD17/INCA and CARD18
CC (PubMed:15383541, PubMed:11051551). Interacts with SERPINB1; this
CC interaction regulates CASP1 activity (PubMed:30692621).
CC {ECO:0000250|UniProtKB:P29452, ECO:0000269|PubMed:11051551,
CC ECO:0000269|PubMed:15030775, ECO:0000269|PubMed:15383541,
CC ECO:0000269|PubMed:16785446, ECO:0000269|PubMed:30692621,
CC ECO:0000269|PubMed:32051255, ECO:0000269|PubMed:32109412,
CC ECO:0000269|PubMed:32553275, ECO:0000269|PubMed:8044845,
CC ECO:0000269|PubMed:9987822}.
CC -!- SUBUNIT: [Caspase-1 subunit p20]: Heterotetramer that consists of two
CC anti-parallel arranged heterodimers, each one formed by a 20 kDa
CC (Caspase-1 subunit p20) and a 10 kDa (Caspase-1 subunit p10) subunit
CC (PubMed:8044845, PubMed:32109412, PubMed:32553275). Can form a
CC heterodimer with isoform epsilon which then has an inhibitory effect
CC (PubMed:7876192). {ECO:0000269|PubMed:32109412,
CC ECO:0000269|PubMed:32553275, ECO:0000269|PubMed:7876192,
CC ECO:0000269|PubMed:8044845}.
CC -!- SUBUNIT: [Caspase-1 subunit p10]: Heterotetramer that consists of two
CC anti-parallel arranged heterodimers, each one formed by a 20 kDa
CC (Caspase-1 subunit p20) and a 10 kDa (Caspase-1 subunit p10) subunit.
CC {ECO:0000269|PubMed:32109412, ECO:0000269|PubMed:32553275,
CC ECO:0000269|PubMed:8044845}.
CC -!- SUBUNIT: [Isoform Epsilon]: Can form a heterodimer with Caspase-1
CC subunit p20 which then has an inhibitory effect.
CC {ECO:0000269|PubMed:7876192}.
CC -!- INTERACTION:
CC P29466; Q5XLA6: CARD17; NbExp=3; IntAct=EBI-516667, EBI-16203934;
CC P29466; P57730: CARD18; NbExp=3; IntAct=EBI-516667, EBI-16203975;
CC P29466; P29466: CASP1; NbExp=2; IntAct=EBI-516667, EBI-516667;
CC P29466; P09038: FGF2; NbExp=2; IntAct=EBI-516667, EBI-977447;
CC P29466; P57764: GSDMD; NbExp=4; IntAct=EBI-516667, EBI-2798865;
CC P29466; P01583: IL1A; NbExp=3; IntAct=EBI-516667, EBI-1749782;
CC P29466; O15553: MEFV; NbExp=2; IntAct=EBI-516667, EBI-7644532;
CC P29466; O15553-2: MEFV; NbExp=3; IntAct=EBI-516667, EBI-15588296;
CC P29466; Q9NPP4: NLRC4; NbExp=4; IntAct=EBI-516667, EBI-1222527;
CC P29466; Q9C000: NLRP1; NbExp=3; IntAct=EBI-516667, EBI-1220518;
CC P29466; Q9HC29: NOD2; NbExp=4; IntAct=EBI-516667, EBI-7445625;
CC P29466; Q9ULZ3: PYCARD; NbExp=9; IntAct=EBI-516667, EBI-751215;
CC P29466; P58753-2: TIRAP; NbExp=5; IntAct=EBI-516667, EBI-528654;
CC P29466; Q08AM6: VAC14; NbExp=4; IntAct=EBI-516667, EBI-2107455;
CC P29466-3; P05067: APP; NbExp=3; IntAct=EBI-12248206, EBI-77613;
CC P29466-3; P54252: ATXN3; NbExp=9; IntAct=EBI-12248206, EBI-946046;
CC P29466-3; Q13867: BLMH; NbExp=3; IntAct=EBI-12248206, EBI-718504;
CC P29466-3; P14136: GFAP; NbExp=3; IntAct=EBI-12248206, EBI-744302;
CC P29466-3; P42858: HTT; NbExp=3; IntAct=EBI-12248206, EBI-466029;
CC P29466-3; Q13387-4: MAPK8IP2; NbExp=3; IntAct=EBI-12248206, EBI-12345753;
CC P29466-3; P27986-2: PIK3R1; NbExp=3; IntAct=EBI-12248206, EBI-9090282;
CC P29466-3; O14494: PLPP1; NbExp=3; IntAct=EBI-12248206, EBI-2865290;
CC P29466-3; O60260-5: PRKN; NbExp=6; IntAct=EBI-12248206, EBI-21251460;
CC P29466-3; P49810: PSEN2; NbExp=3; IntAct=EBI-12248206, EBI-2010251;
CC P29466-3; P84022: SMAD3; NbExp=3; IntAct=EBI-12248206, EBI-347161;
CC P29466-3; Q9BX74: TM2D1; NbExp=3; IntAct=EBI-12248206, EBI-25832057;
CC P29466-3; O60784-2: TOM1; NbExp=3; IntAct=EBI-12248206, EBI-12117154;
CC P29466-3; Q08AM6: VAC14; NbExp=3; IntAct=EBI-12248206, EBI-2107455;
CC P29466-3; Q9UBQ0-2: VPS29; NbExp=3; IntAct=EBI-12248206, EBI-11141397;
CC P29466-3; O76024: WFS1; NbExp=3; IntAct=EBI-12248206, EBI-720609;
CC PRO_0000004522; P01583: IL1A; NbExp=4; IntAct=EBI-1749839, EBI-1749782;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:20197547}. Cell
CC membrane {ECO:0000269|PubMed:20197547}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Comment=Additional isoforms seem to exist.;
CC Name=Alpha;
CC IsoId=P29466-1; Sequence=Displayed;
CC Name=Beta;
CC IsoId=P29466-2; Sequence=VSP_000798;
CC Name=Gamma;
CC IsoId=P29466-3; Sequence=VSP_000799;
CC Name=Delta;
CC IsoId=P29466-4; Sequence=VSP_000799, VSP_000800;
CC Name=Epsilon;
CC IsoId=P29466-5; Sequence=VSP_000797;
CC -!- TISSUE SPECIFICITY: Expressed in larger amounts in spleen and lung.
CC Detected in liver, heart, small intestine, colon, thymus, prostate,
CC skeletal muscle, peripheral blood leukocytes, kidney and testis. No
CC expression in the brain. {ECO:0000269|PubMed:15498465}.
CC -!- INDUCTION: Transcription and translation induced by M.tuberculosis and
CC a number of different M.tuberculosis components; EsxA is the most
CC potent activator tested (at protein level) (PubMed:20148899).
CC {ECO:0000269|PubMed:20148899}.
CC -!- PTM: The two subunits are derived from the precursor sequence by an
CC autocatalytic mechanism. {ECO:0000269|PubMed:32109412,
CC ECO:0000269|PubMed:8044845}.
CC -!- PTM: Ubiquitinated via 'Lys-11'-linked polyubiquitination.
CC Deubiquitinated by USP8. {ECO:0000269|PubMed:30065070}.
CC -!- PTM: Cleavage in the interdomain linker region is required to induce
CC pyroptosis. {ECO:0000269|PubMed:32051255}.
CC -!- SIMILARITY: Belongs to the peptidase C14A family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAT72297.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAT72297.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/CASP1ID145ch11q22.html";
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DR EMBL; X65019; CAA46153.1; -; mRNA.
DR EMBL; M87507; AAA66942.1; -; mRNA.
DR EMBL; U13697; AAC50107.1; -; mRNA.
DR EMBL; U13698; AAC50108.1; -; mRNA.
DR EMBL; U13699; AAC50109.1; -; mRNA.
DR EMBL; U13700; AAC50110.1; -; mRNA.
DR EMBL; AK223503; BAD97223.1; -; mRNA.
DR EMBL; AP001153; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC041689; AAH41689.1; -; mRNA.
DR EMBL; BC062327; AAH62327.1; -; mRNA.
DR EMBL; AY660536; AAT72297.1; ALT_SEQ; mRNA.
DR CCDS; CCDS53704.1; -. [P29466-3]
DR CCDS; CCDS8329.1; -. [P29466-2]
DR CCDS; CCDS8330.1; -. [P29466-1]
DR CCDS; CCDS8331.1; -. [P29466-4]
DR CCDS; CCDS8332.1; -. [P29466-5]
DR PIR; A54263; A42677.
DR PIR; A56084; A56084.
DR PIR; B56084; B56084.
DR PIR; C56084; C56084.
DR PIR; D56084; D56084.
DR RefSeq; NP_001214.1; NM_001223.4. [P29466-2]
DR RefSeq; NP_001244047.1; NM_001257118.2. [P29466-1]
DR RefSeq; NP_001244048.1; NM_001257119.2. [P29466-2]
DR RefSeq; NP_150634.1; NM_033292.3. [P29466-1]
DR RefSeq; NP_150635.1; NM_033293.3. [P29466-3]
DR RefSeq; NP_150636.1; NM_033294.3. [P29466-4]
DR RefSeq; NP_150637.1; NM_033295.3. [P29466-5]
DR PDB; 1BMQ; X-ray; 2.50 A; A=131-297, B=317-404.
DR PDB; 1IBC; X-ray; 2.73 A; A=104-297, B=317-404.
DR PDB; 1ICE; X-ray; 2.60 A; A=131-297, B=317-404.
DR PDB; 1RWK; X-ray; 2.30 A; A=120-297, B=317-404.
DR PDB; 1RWM; X-ray; 2.70 A; A=120-297, B=317-404.
DR PDB; 1RWN; X-ray; 2.00 A; A=120-297, B=317-404.
DR PDB; 1RWO; X-ray; 2.10 A; A=120-297, B=317-404.
DR PDB; 1RWP; X-ray; 2.20 A; A=120-297, B=317-404.
DR PDB; 1RWV; X-ray; 2.10 A; A=120-297, B=317-404.
DR PDB; 1RWW; X-ray; 2.80 A; A=120-297, B=317-404.
DR PDB; 1RWX; X-ray; 1.85 A; A=120-297, B=317-404.
DR PDB; 1SC1; X-ray; 2.60 A; A=120-297, B=317-404.
DR PDB; 1SC3; X-ray; 1.80 A; A=120-297, B=317-404.
DR PDB; 1SC4; X-ray; 2.10 A; A=120-297, B=317-404.
DR PDB; 2FQQ; X-ray; 3.30 A; A=120-297, B=317-404.
DR PDB; 2H48; X-ray; 2.20 A; A=120-297, B=317-404.
DR PDB; 2H4W; X-ray; 2.00 A; A=120-297, B=317-404.
DR PDB; 2H4Y; X-ray; 1.90 A; A=120-297, B=317-404.
DR PDB; 2H51; X-ray; 2.10 A; A=120-297, B=317-404.
DR PDB; 2H54; X-ray; 1.80 A; A=120-297, B=317-404.
DR PDB; 2HBQ; X-ray; 1.80 A; A=120-297, B=317-404.
DR PDB; 2HBR; X-ray; 2.20 A; A=120-297, B=317-404.
DR PDB; 2HBY; X-ray; 2.10 A; A=120-297, B=317-404.
DR PDB; 2HBZ; X-ray; 1.90 A; A=120-297, B=317-404.
DR PDB; 3D6F; X-ray; 1.90 A; A=120-297, B=317-404.
DR PDB; 3D6H; X-ray; 2.00 A; A=120-297, B=317-404.
DR PDB; 3D6M; X-ray; 1.80 A; A=120-297, B=317-404.
DR PDB; 3E4C; X-ray; 2.05 A; A/B=104-404.
DR PDB; 3NS7; X-ray; 2.60 A; A=136-297, B=317-404.
DR PDB; 5FNA; EM; 4.80 A; A/B/C/D/E/F/G/H=2-86.
DR PDB; 5MMV; X-ray; 2.15 A; A=120-297, B=317-404.
DR PDB; 5MTK; X-ray; 2.53 A; A=120-297, B=317-404.
DR PDB; 6BZ9; X-ray; 1.80 A; A=120-297, B=317-404.
DR PDB; 6F6R; X-ray; 1.80 A; A=118-297, B=317-404.
DR PDB; 6KN0; X-ray; 2.79 A; A/C=131-297, B/D=317-404.
DR PDB; 6PZP; X-ray; 1.94 A; A=120-297, B=317-404.
DR PDB; 6VIE; X-ray; 3.40 A; A=120-303, B=317-404.
DR PDB; 7KEU; EM; 3.90 A; E/F/G/H=2-86.
DR PDBsum; 1BMQ; -.
DR PDBsum; 1IBC; -.
DR PDBsum; 1ICE; -.
DR PDBsum; 1RWK; -.
DR PDBsum; 1RWM; -.
DR PDBsum; 1RWN; -.
DR PDBsum; 1RWO; -.
DR PDBsum; 1RWP; -.
DR PDBsum; 1RWV; -.
DR PDBsum; 1RWW; -.
DR PDBsum; 1RWX; -.
DR PDBsum; 1SC1; -.
DR PDBsum; 1SC3; -.
DR PDBsum; 1SC4; -.
DR PDBsum; 2FQQ; -.
DR PDBsum; 2H48; -.
DR PDBsum; 2H4W; -.
DR PDBsum; 2H4Y; -.
DR PDBsum; 2H51; -.
DR PDBsum; 2H54; -.
DR PDBsum; 2HBQ; -.
DR PDBsum; 2HBR; -.
DR PDBsum; 2HBY; -.
DR PDBsum; 2HBZ; -.
DR PDBsum; 3D6F; -.
DR PDBsum; 3D6H; -.
DR PDBsum; 3D6M; -.
DR PDBsum; 3E4C; -.
DR PDBsum; 3NS7; -.
DR PDBsum; 5FNA; -.
DR PDBsum; 5MMV; -.
DR PDBsum; 5MTK; -.
DR PDBsum; 6BZ9; -.
DR PDBsum; 6F6R; -.
DR PDBsum; 6KN0; -.
DR PDBsum; 6PZP; -.
DR PDBsum; 6VIE; -.
DR PDBsum; 7KEU; -.
DR AlphaFoldDB; P29466; -.
DR SMR; P29466; -.
DR BioGRID; 107284; 65.
DR ComplexPortal; CPX-4082; NLRP1 inflammasome.
DR ComplexPortal; CPX-4141; NLRP3 inflammasome.
DR ComplexPortal; CPX-4142; AIM2 inflammasome.
DR ComplexPortal; CPX-4143; Pyrin inflammasome.
DR ComplexPortal; CPX-4144; NLRC4 inflammasome.
DR ComplexPortal; CPX-952; Caspase-1 complex.
DR CORUM; P29466; -.
DR DIP; DIP-175N; -.
DR IntAct; P29466; 43.
DR MINT; P29466; -.
DR STRING; 9606.ENSP00000433138; -.
DR BindingDB; P29466; -.
DR ChEMBL; CHEMBL4801; -.
DR DrugBank; DB07733; 1-METHYL-3-TRIFLUOROMETHYL-1H-THIENO[2,3-C]PYRAZOLE-5-CARBOXYLIC ACID (2-MERCAPTO-ETHYL)-AMIDE.
DR DrugBank; DB07916; 3-{6-[(8-HYDROXY-QUINOLINE-2-CARBONYL)-AMINO]-2-THIOPHEN-2-YL-HEXANOYLAMINO}-4-OXO-BUTYRI ACID.
DR DrugBank; DB00945; Acetylsalicylic acid.
DR DrugBank; DB05408; Emricasan.
DR DrugBank; DB05301; LAX-101.
DR DrugBank; DB01017; Minocycline.
DR DrugBank; DB04875; Pralnacasan.
DR DrugBank; DB05507; VX-765.
DR DrugBank; DB07744; Z-Val-Ala-Asp fluoromethyl ketone.
DR DrugCentral; P29466; -.
DR GuidetoPHARMACOLOGY; 1617; -.
DR MEROPS; C14.001; -.
DR iPTMnet; P29466; -.
DR PhosphoSitePlus; P29466; -.
DR BioMuta; CASP1; -.
DR DMDM; 266321; -.
DR EPD; P29466; -.
DR jPOST; P29466; -.
DR MassIVE; P29466; -.
DR MaxQB; P29466; -.
DR PaxDb; P29466; -.
DR PeptideAtlas; P29466; -.
DR PRIDE; P29466; -.
DR ProteomicsDB; 54571; -. [P29466-1]
DR ProteomicsDB; 54572; -. [P29466-2]
DR ProteomicsDB; 54573; -. [P29466-3]
DR ProteomicsDB; 54574; -. [P29466-4]
DR ProteomicsDB; 54575; -. [P29466-5]
DR Antibodypedia; 1075; 1138 antibodies from 47 providers.
DR DNASU; 834; -.
DR Ensembl; ENST00000353247.9; ENSP00000344132.5; ENSG00000137752.24. [P29466-5]
DR Ensembl; ENST00000436863.7; ENSP00000410076.3; ENSG00000137752.24. [P29466-1]
DR Ensembl; ENST00000446369.5; ENSP00000403260.1; ENSG00000137752.24. [P29466-4]
DR Ensembl; ENST00000525825.5; ENSP00000434779.1; ENSG00000137752.24. [P29466-2]
DR Ensembl; ENST00000526568.5; ENSP00000434250.1; ENSG00000137752.24. [P29466-3]
DR Ensembl; ENST00000531166.5; ENSP00000434303.1; ENSG00000137752.24. [P29466-5]
DR Ensembl; ENST00000533400.6; ENSP00000433138.1; ENSG00000137752.24. [P29466-1]
DR Ensembl; ENST00000534497.5; ENSP00000436875.1; ENSG00000137752.24. [P29466-4]
DR GeneID; 834; -.
DR KEGG; hsa:834; -.
DR MANE-Select; ENST00000533400.6; ENSP00000433138.1; NM_001257118.3; NP_001244047.1.
DR UCSC; uc001pig.5; human. [P29466-1]
DR CTD; 834; -.
DR DisGeNET; 834; -.
DR GeneCards; CASP1; -.
DR HGNC; HGNC:1499; CASP1.
DR HPA; ENSG00000137752; Tissue enhanced (intestine, lymphoid tissue).
DR MIM; 147678; gene.
DR neXtProt; NX_P29466; -.
DR OpenTargets; ENSG00000137752; -.
DR PharmGKB; PA26083; -.
DR VEuPathDB; HostDB:ENSG00000137752; -.
DR eggNOG; KOG3573; Eukaryota.
DR GeneTree; ENSGT00940000159114; -.
DR HOGENOM; CLU_036904_0_0_1; -.
DR InParanoid; P29466; -.
DR OMA; NTENCKA; -.
DR OrthoDB; 1327703at2759; -.
DR PhylomeDB; P29466; -.
DR TreeFam; TF102023; -.
DR BRENDA; 3.4.22.36; 2681.
DR PathwayCommons; P29466; -.
DR Reactome; R-HSA-168638; NOD1/2 Signaling Pathway.
DR Reactome; R-HSA-448706; Interleukin-1 processing.
DR Reactome; R-HSA-5620971; Pyroptosis.
DR Reactome; R-HSA-6803207; TP53 Regulates Transcription of Caspase Activators and Caspases.
DR Reactome; R-HSA-844456; The NLRP3 inflammasome.
DR Reactome; R-HSA-844615; The AIM2 inflammasome.
DR Reactome; R-HSA-844623; The IPAF inflammasome.
DR Reactome; R-HSA-9008059; Interleukin-37 signaling.
DR Reactome; R-HSA-9660826; Purinergic signaling in leishmaniasis infection.
DR SABIO-RK; P29466; -.
DR SignaLink; P29466; -.
DR SIGNOR; P29466; -.
DR BioGRID-ORCS; 834; 7 hits in 1069 CRISPR screens.
DR ChiTaRS; CASP1; human.
DR EvolutionaryTrace; P29466; -.
DR GeneWiki; Caspase_1; -.
DR GenomeRNAi; 834; -.
DR Pharos; P29466; Tchem.
DR PRO; PR:P29466; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; P29466; protein.
DR Bgee; ENSG00000137752; Expressed in monocyte and 179 other tissues.
DR ExpressionAtlas; P29466; baseline and differential.
DR Genevisible; P29466; HS.
DR GO; GO:0097169; C:AIM2 inflammasome complex; IDA:UniProtKB.
DR GO; GO:0008303; C:caspase complex; IPI:ComplexPortal.
DR GO; GO:0005737; C:cytoplasm; IDA:ComplexPortal.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:ComplexPortal.
DR GO; GO:0061702; C:inflammasome complex; IPI:ComplexPortal.
DR GO; GO:0072557; C:IPAF inflammasome complex; ISS:UniProtKB.
DR GO; GO:0005874; C:microtubule; IC:ComplexPortal.
DR GO; GO:0072558; C:NLRP1 inflammasome complex; IDA:UniProtKB.
DR GO; GO:0072559; C:NLRP3 inflammasome complex; IDA:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IC:ComplexPortal.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0097179; C:protease inhibitor complex; IMP:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0050700; F:CARD domain binding; IPI:UniProtKB.
DR GO; GO:0008656; F:cysteine-type endopeptidase activator activity involved in apoptotic process; TAS:ProtInc.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IDA:UniProtKB.
DR GO; GO:0097199; F:cysteine-type endopeptidase activity involved in apoptotic signaling pathway; IBA:GO_Central.
DR GO; GO:0004175; F:endopeptidase activity; IDA:ParkinsonsUK-UCL.
DR GO; GO:0042802; F:identical protein binding; IMP:UniProtKB.
DR GO; GO:0019900; F:kinase binding; IPI:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; TAS:ProtInc.
DR GO; GO:0071346; P:cellular response to interferon-gamma; IMP:UniProtKB.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IMP:UniProtKB.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEP:UniProtKB.
DR GO; GO:0071310; P:cellular response to organic substance; IDA:MGI.
DR GO; GO:0140447; P:cytokine precursor processing; IGI:ARUK-UCL.
DR GO; GO:0051607; P:defense response to virus; IC:ComplexPortal.
DR GO; GO:0046456; P:icosanoid biosynthetic process; IC:ComplexPortal.
DR GO; GO:0007231; P:osmosensory signaling pathway; IC:ComplexPortal.
DR GO; GO:0002221; P:pattern recognition receptor signaling pathway; IC:ComplexPortal.
DR GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; IMP:UniProtKB.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IMP:UniProtKB.
DR GO; GO:0050729; P:positive regulation of inflammatory response; IDA:ComplexPortal.
DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; IDA:UniProtKB.
DR GO; GO:1903265; P:positive regulation of tumor necrosis factor-mediated signaling pathway; IMP:UniProtKB.
DR GO; GO:0016540; P:protein autoprocessing; IDA:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IDA:UniProtKB.
DR GO; GO:0070269; P:pyroptosis; IDA:UniProtKB.
DR GO; GO:0042981; P:regulation of apoptotic process; IEA:InterPro.
DR GO; GO:0050727; P:regulation of inflammatory response; IDA:UniProtKB.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR GO; GO:0140448; P:signaling receptor ligand precursor processing; IGI:ARUK-UCL.
DR CDD; cd00032; CASc; 1.
DR Gene3D; 1.10.533.10; -; 1.
DR InterPro; IPR001315; CARD.
DR InterPro; IPR029030; Caspase-like_dom_sf.
DR InterPro; IPR033139; Caspase_cys_AS.
DR InterPro; IPR016129; Caspase_his_AS.
DR InterPro; IPR011029; DEATH-like_dom_sf.
DR InterPro; IPR002398; Pept_C14.
DR InterPro; IPR002138; Pept_C14_p10.
DR InterPro; IPR001309; Pept_C14_p20.
DR InterPro; IPR015917; Pept_C14A.
DR PANTHER; PTHR10454; PTHR10454; 1.
DR Pfam; PF00619; CARD; 1.
DR PRINTS; PR00376; IL1BCENZYME.
DR SMART; SM00114; CARD; 1.
DR SMART; SM00115; CASc; 1.
DR SUPFAM; SSF47986; SSF47986; 1.
DR SUPFAM; SSF52129; SSF52129; 1.
DR PROSITE; PS50209; CARD; 1.
DR PROSITE; PS01122; CASPASE_CYS; 1.
DR PROSITE; PS01121; CASPASE_HIS; 1.
DR PROSITE; PS50207; CASPASE_P10; 1.
DR PROSITE; PS50208; CASPASE_P20; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Apoptosis; Cell membrane; Cytoplasm;
KW Direct protein sequencing; Hydrolase; Isopeptide bond; Membrane;
KW Phosphoprotein; Protease; Reference proteome; Thiol protease;
KW Ubl conjugation; Zymogen.
FT PROPEP 1..119
FT /id="PRO_0000004521"
FT CHAIN 120..297
FT /note="Caspase-1 subunit p20"
FT /evidence="ECO:0000305|PubMed:32109412,
FT ECO:0000305|PubMed:32553275, ECO:0000305|PubMed:8044845"
FT /id="PRO_0000004522"
FT PROPEP 298..316
FT /note="Interdomain linker"
FT /evidence="ECO:0000303|PubMed:32051255"
FT /id="PRO_0000004523"
FT CHAIN 317..404
FT /note="Caspase-1 subunit p10"
FT /evidence="ECO:0000305|PubMed:32109412,
FT ECO:0000305|PubMed:32553275, ECO:0000305|PubMed:8044845"
FT /id="PRO_0000004524"
FT DOMAIN 1..91
FT /note="CARD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00046"
FT ACT_SITE 237
FT /evidence="ECO:0000269|PubMed:1574116"
FT ACT_SITE 285
FT /evidence="ECO:0000269|PubMed:1574116,
FT ECO:0000305|PubMed:32051255"
FT MOD_RES 302
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P29452"
FT CROSSLNK 134
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:30065070"
FT VAR_SEQ 20..335
FT /note="Missing (in isoform Epsilon)"
FT /evidence="ECO:0000303|PubMed:7876192"
FT /id="VSP_000797"
FT VAR_SEQ 20..112
FT /note="Missing (in isoform Gamma and isoform Delta)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:7876192"
FT /id="VSP_000799"
FT VAR_SEQ 92..112
FT /note="Missing (in isoform Beta)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:7876192"
FT /id="VSP_000798"
FT VAR_SEQ 288..335
FT /note="Missing (in isoform Delta)"
FT /evidence="ECO:0000303|PubMed:7876192"
FT /id="VSP_000800"
FT VARIANT 15
FT /note="R -> H (in dbSNP:rs1042743)"
FT /id="VAR_048615"
FT MUTAGEN 285
FT /note="C->A,S: Loss of protease activity. Loss of SPHK2
FT cleavage and release in apoptotic cells."
FT /evidence="ECO:0000269|PubMed:15498465,
FT ECO:0000269|PubMed:20197547, ECO:0000269|PubMed:32051255,
FT ECO:0000269|PubMed:32109412, ECO:0000269|PubMed:32553275"
FT MUTAGEN 294
FT /note="W->A: Mediates autoprocessing but is unable to
FT interact with Gasdermin-D (GSDMD) and mediate its
FT cleavage."
FT /evidence="ECO:0000269|PubMed:32109412,
FT ECO:0000269|PubMed:32553275"
FT MUTAGEN 297
FT /note="D->N: In IDL(uncl); abolished cleavage in the
FT interdomain region; when associated with 315-N-N-316."
FT /evidence="ECO:0000269|PubMed:32051255"
FT MUTAGEN 315..316
FT /note="DD->NN: In IDL(uncl); abolished cleavage in the
FT interdomain region; when associated with N-297."
FT /evidence="ECO:0000269|PubMed:32051255"
FT MUTAGEN 318
FT /note="I->N: Mediates autoprocessing but is unable to
FT interact with Gasdermin-D (GSDMD) and mediate its
FT cleavage."
FT /evidence="ECO:0000269|PubMed:32109412,
FT ECO:0000269|PubMed:32553275"
FT MUTAGEN 320
FT /note="K->A: Abolishes cleavage of Gasdermin-D (GSDMD)."
FT /evidence="ECO:0000269|PubMed:32553275"
FT CONFLICT 319
FT /note="K -> R (in Ref. 4; BAD97223)"
FT /evidence="ECO:0000305"
FT CONFLICT 402
FT /note="P -> L (in Ref. 4; BAD97223)"
FT /evidence="ECO:0000305"
FT TURN 129..132
FT /evidence="ECO:0007829|PDB:6BZ9"
FT HELIX 138..147
FT /evidence="ECO:0007829|PDB:6BZ9"
FT HELIX 149..151
FT /evidence="ECO:0007829|PDB:6BZ9"
FT TURN 158..160
FT /evidence="ECO:0007829|PDB:6BZ9"
FT STRAND 164..169
FT /evidence="ECO:0007829|PDB:6BZ9"
FT STRAND 174..176
FT /evidence="ECO:0007829|PDB:6BZ9"
FT HELIX 182..195
FT /evidence="ECO:0007829|PDB:6BZ9"
FT STRAND 199..205
FT /evidence="ECO:0007829|PDB:6BZ9"
FT HELIX 208..219
FT /evidence="ECO:0007829|PDB:6BZ9"
FT HELIX 222..226
FT /evidence="ECO:0007829|PDB:6BZ9"
FT STRAND 230..236
FT /evidence="ECO:0007829|PDB:6BZ9"
FT STRAND 242..244
FT /evidence="ECO:0007829|PDB:1SC3"
FT STRAND 250..252
FT /evidence="ECO:0007829|PDB:6BZ9"
FT STRAND 255..257
FT /evidence="ECO:0007829|PDB:1SC4"
FT HELIX 258..265
FT /evidence="ECO:0007829|PDB:6BZ9"
FT TURN 267..269
FT /evidence="ECO:0007829|PDB:6BZ9"
FT HELIX 271..273
FT /evidence="ECO:0007829|PDB:6BZ9"
FT STRAND 278..284
FT /evidence="ECO:0007829|PDB:6BZ9"
FT STRAND 286..289
FT /evidence="ECO:0007829|PDB:6BZ9"
FT STRAND 291..298
FT /evidence="ECO:0007829|PDB:3E4C"
FT HELIX 316..319
FT /evidence="ECO:0007829|PDB:3E4C"
FT STRAND 326..333
FT /evidence="ECO:0007829|PDB:6BZ9"
FT STRAND 340..342
FT /evidence="ECO:0007829|PDB:6BZ9"
FT TURN 343..345
FT /evidence="ECO:0007829|PDB:6BZ9"
FT HELIX 348..360
FT /evidence="ECO:0007829|PDB:6BZ9"
FT TURN 361..363
FT /evidence="ECO:0007829|PDB:6BZ9"
FT HELIX 366..376
FT /evidence="ECO:0007829|PDB:6BZ9"
FT STRAND 381..383
FT /evidence="ECO:0007829|PDB:6F6R"
FT STRAND 388..391
FT /evidence="ECO:0007829|PDB:6BZ9"
FT STRAND 395..397
FT /evidence="ECO:0007829|PDB:1RWM"
SQ SEQUENCE 404 AA; 45159 MW; ABF33CF33CC71584 CRC64;
MADKVLKEKR KLFIRSMGEG TINGLLDELL QTRVLNKEEM EKVKRENATV MDKTRALIDS
VIPKGAQACQ ICITYICEED SYLAGTLGLS ADQTSGNYLN MQDSQGVLSS FPAPQAVQDN
PAMPTSSGSE GNVKLCSLEE AQRIWKQKSA EIYPIMDKSS RTRLALIICN EEFDSIPRRT
GAEVDITGMT MLLQNLGYSV DVKKNLTASD MTTELEAFAH RPEHKTSDST FLVFMSHGIR
EGICGKKHSE QVPDILQLNA IFNMLNTKNC PSLKDKPKVI IIQACRGDSP GVVWFKDSVG
VSGNLSLPTT EEFEDDAIKK AHIEKDFIAF CSSTPDNVSW RHPTMGSVFI GRLIEHMQEY
ACSCDVEEIF RKVRFSFEQP DGRAQMPTTE RVTLTRCFYL FPGH
