CASP7
entrez
840
canonical
uniprot
P55210
canonical
ensembl
ENSG00000165806
resolver
ensp
ENSP00000298701
resolver
ensp
ENSP00000358324
resolver
ensp
ENSP00000358327
resolver
ensp
ENSP00000358337
resolver
ensp
ENSP00000398107
resolver
ensp
ENSP00000478999
resolver
ensp
ENSP00000480584
resolver
enst
ENST00000369321
resolver
genesymbol
CASP7
resolver
genesymbol_syn
MCH3
resolver
hgnc
HGNC:1508
resolver
uniprot
A0A0A0MRL7
resolver
uniprot
B4DQU7
resolver
uniprot
B4DWA2
resolver
uniprot
B5BU45
resolver
uniprot
D3DRB8
resolver
uniprot
Q13364
resolver
uniprot
Q53YD5
resolver
uniprot
Q5SVL0
resolver
uniprot
Q5SVL3
resolver
uniprot
Q96BA0
resolver
uniprot_entry
A0A0A0MRL7_HUMAN
resolver
uniprot_entry
B4DWA2_HUMAN
resolver
uniprot_entry
CASP7_HUMAN
resolver
uniprot_sec
B4DQU7
resolver
uniprot_sec
B5BU45
resolver
uniprot_sec
D3DRB8
resolver
uniprot_sec
Q13364
resolver
uniprot_sec
Q53YD5
resolver
uniprot_sec
Q5SVL0
resolver
uniprot_sec
Q5SVL3
resolver
uniprot_sec
Q96BA0
resolver
activity_regulation
ACTIVITY REGULATION: During activation, the N-terminal disordered prodomain is removed by cleavage (PubMed:12824163, PubMed:16916640). Concomitantly, double cleavage gives rise to a large Caspase-7 subunit p20 and a small Caspase-7 subunit p11 (PubMed:16916640). The two large and two small subunits then assemble to form the active CASP7 complex (PubMed:16916640). Can be cleaved and activated by different caspases, depending on the context (PubMed:16916640). Cleaved and activated by initiator caspases (CASP8, CASP9 and/or CASP10), leading to execution phase of apoptosis (PubMed:16352606, PubMed:16916640). Inhibited by XIAP, which directly binds to the active site pocket and obstructs substrate entry (PubMed:11257230, PubMed:11257231, PubMed:16352606, PubMed:16916640). Cleavage and maturation by GZMB regulates granzyme-mediated programmed cell death (By similarity). Cleavage and maturation by CASP1 regulates pyroptosis (By similarity). Phosphorylation at Ser-30 and Ser-239 by PAK2 inhibits its activity (PubMed:21555521, PubMed:27889207). Inhibited by isatin sulfonamides (PubMed:10821855). Inhibited by 2-(2,4-Dichlorophenoxy)- N-(2-mercapto-ethyl)-acetamide (DICA) and 5-Fluoro-1H-indole-2- carboxylic acid (2-mercapto-ethyl)-amide (FICA) allosteric inhibitors, which disrupt an interaction between Arg-187 and Tyr-223 (PubMed:15314233, PubMed:19581639). Specifically inhibited by DARPin D7.18 and D7.43, which specifically bind to the precursor CASP7 and prevent its processing and activation (PubMed:24779913). Inhibited by BIRC6; following inhibition of BIRC6-caspase binding by DIABLO/SMAC, BIRC6 is subjected to caspase cleavage, leading to an increase in active caspases (PubMed:36758104, PubMed:36758106). {ECO:0000250|UniProtKB:P97864, ECO:0000269|PubMed:10821855, ECO:0000269|PubMed:11257230, ECO:0000269|PubMed:11257231, ECO:0000269|PubMed:12824163, ECO:0000269|PubMed:15314233, ECO:0000269|PubMed:16352606, ECO:0000269|PubMed:16916640, ECO:0000269|PubMed:19581639, ECO:0000269|PubMed:21555521, ECO:0000269|PubMed:24779913, ECO:0000269|PubMed:27889207, ECO:0000269|PubMed:36758104, ECO:0000269|PubMed:36758106}.
uniprot
proteins
amino_acid_sequence
MADDQGCIEEQGVEDSANEDSVDAKPDRSSFVPSLFSKKKKNVTMRSIKTTRDRVPTYQYNMNFEKLGKCIIINNKNFDKVTGMGVRNGTDKDAEALFKCFRSLGFDVIVYNDCSCAKMQDLLKKASEEDHTNAACFACILLSHGEENVIYGKDGVTPIKDLTAHFRGDRCKTLLEKPKLFFIQACRGTELDDGIQADSGPINDTDANPRYKIPVEADFLFAYSTVPGYYSWRSPGRGSWFVQALCSILEEHGKDLEIMQILTRVNDRVARHFESQSDDPHFHEKKQIPCVVSMLTKELYFSQ
uniprot
proteins
ec_number
3.4.22.60
uniprot
proteins
function
FUNCTION: Thiol protease involved in different programmed cell death processes, such as apoptosis, pyroptosis or granzyme-mediated programmed cell death, by proteolytically cleaving target proteins (PubMed:11257230, PubMed:11257231, PubMed:11701129, PubMed:15314233, PubMed:16916640, PubMed:17646170, PubMed:18723680, PubMed:19581639, PubMed:8521391, PubMed:8567622, PubMed:8576161, PubMed:9070923). Has a marked preference for Asp-Glu-Val-Asp (DEVD) consensus sequences, with some plasticity for alternate non-canonical sequences (PubMed:12824163, PubMed:15314233, PubMed:17697120, PubMed:19581639, PubMed:20566630, PubMed:23650375, PubMed:23897474, PubMed:27032039). Its involvement in the different programmed cell death processes is probably determined by upstream proteases that activate CASP7 (By similarity). Acts as an effector caspase involved in the execution phase of apoptosis: following cleavage and activation by initiator caspases (CASP8, CASP9 and/or CASP10), mediates execution of apoptosis by catalyzing cleavage of proteins, such as CLSPN, PARP1, PTGES3 and YY1 (PubMed:10497198, PubMed:16123041, PubMed:16374543, PubMed:16916640, PubMed:18723680, PubMed:20566630, PubMed:21555521, PubMed:22184066, PubMed:22451931, PubMed:27889207, PubMed:28863261, PubMed:31586028, PubMed:34156061, PubMed:35338844, PubMed:35446120). Compared to CASP3, acts as a minor executioner caspase and cleaves a limited set of target proteins (PubMed:18723680). Acts as a key regulator of the inflammatory response in response to bacterial infection by catalyzing cleavage and activation of the sphingomyelin phosphodiesterase SMPD1 in the extracellular milieu, thereby promoting membrane repair (PubMed:21157428). Regulates pyroptosis in intestinal epithelial cells: cleaved and activated by CASP1 in response to S.typhimurium infection, promoting its secretion to the extracellular milieu, where it catalyzes activation of SMPD1, generating ceramides that repair membranes and counteract the action of gasdermin-D (GSDMD) pores (By similarity). Regulates granzyme-mediated programmed cell death in hepatocytes: cleaved and activated by granzyme B (GZMB) in response to bacterial infection, promoting its secretion to the extracellular milieu, where it catalyzes activation of SMPD1, generating ceramides that repair membranes and counteract the action of perforin (PRF1) pores (By similarity). Following cleavage by CASP1 in response to inflammasome activation, catalyzes processing and inactivation of PARP1, alleviating the transcription repressor activity of PARP1 (PubMed:22464733). Acts as an inhibitor of type I interferon production during virus-induced apoptosis by mediating cleavage of antiviral proteins CGAS, IRF3 and MAVS, thereby preventing cytokine overproduction (By similarity). Cleaves and activates sterol regulatory element binding proteins (SREBPs) (PubMed:8643593). Cleaves phospholipid scramblase proteins XKR4, XKR8 and XKR9 (By similarity). In case of infection, catalyzes cleavage of Kaposi sarcoma-associated herpesvirus protein ORF57, thereby preventing expression of viral lytic genes (PubMed:20159985). Cleaves BIRC6 following inhibition of BIRC6-caspase binding by DIABLO/SMAC (PubMed:36758104, PubMed:36758106). {ECO:0000250|UniProtKB:P97864, ECO:0000269|PubMed:10497198, ECO:0000269|PubMed:11257230, ECO:0000269|PubMed:11257231, ECO:0000269|PubMed:11701129, ECO:0000269|PubMed:12824163, ECO:0000269|PubMed:15314233, ECO:0000269|PubMed:16123041, ECO:0000269|PubMed:16374543, ECO:0000269|PubMed:16916640, ECO:0000269|PubMed:17646170, ECO:0000269|PubMed:17697120, ECO:0000269|PubMed:18723680, ECO:0000269|PubMed:19581639, ECO:0000269|PubMed:20159985, ECO:0000269|PubMed:20566630, ECO:0000269|PubMed:21157428, ECO:0000269|PubMed:21555521, ECO:0000269|PubMed:22184066, ECO:0000269|PubMed:22451931, ECO:0000269|PubMed:22464733, ECO:0000269|PubMed:23650375, ECO:0000269|PubMed:23897474, ECO:0000269|PubMed:27032039, ECO:0000269|PubMed:27889207, ECO:0000269|PubMed:28863261, ECO:0000269|PubMed:31586028, ECO:0000269|PubMed:34156061, ECO:0000269|PubMed:35338844, ECO:0000269|PubMed:35446120, ECO:0000269|PubMed:36758104, ECO:0000269|PubMed:36758106, ECO:0000269|PubMed:8521391, ECO:0000269|PubMed:8567622, ECO:0000269|PubMed:8576161, ECO:0000269|PubMed:8643593, ECO:0000269|PubMed:9070923}.; FUNCTION: [Isoform Beta]: Lacks enzymatic activity. {ECO:0000269|PubMed:8521391}.
uniprot
proteins
mass_dalton
34277
uniprot
proteins
mutagenesis
MUTAGEN 23; /note="D->A: Abolished cleavage at the N-terminus, leading to impaired activation and thiol protease activity. In P7-D2A mutant; abolished cleavage and activation, leading to decreased but mesureable activity; when associated with A-198."; /evidence="ECO:0000269|PubMed:12824163, ECO:0000269|PubMed:22451931, ECO:0000269|PubMed:23650375, ECO:0000269|PubMed:34156061"; MUTAGEN 30; /note="S->A: Abolished phosphorylation by PAK2; when associated with A-173 and A-239."; /evidence="ECO:0000269|PubMed:21555521"; MUTAGEN 30; /note="S->E: Mimics phosphorylation; does not affect thiol protease activity."; /evidence="ECO:0000269|PubMed:27889207"; MUTAGEN 38..41; /note="KKKK->AAAA: Decreased ability to cleave PARP1 and PTGES3."; /evidence="ECO:0000269|PubMed:22451931, ECO:0000269|PubMed:28863261"; MUTAGEN 38..41; /note="KKKK->AKKA: Decreased ability to cleave PARP1."; /evidence="ECO:0000269|PubMed:31586028"; MUTAGEN 39..40; /note="KK->AA: Does not affect ability to cleave PARP1."; /evidence="ECO:0000269|PubMed:22451931, ECO:0000269|PubMed:31586028"; MUTAGEN 39..40; /note="KK->EE: Decreased ability to cleave PARP1. Decreased RNA-binding."; /evidence="ECO:0000269|PubMed:22451931, ECO:0000269|PubMed:31586028, ECO:0000269|PubMed:34156061"; MUTAGEN 39; /note="K->E: Decreased ability to cleave PARP1."; /evidence="ECO:0000269|PubMed:22451931"; MUTAGEN 173; /note="T->A: Abolished phosphorylation by PAK2; when associated with A-30 and A-239."; /evidence="ECO:0000269|PubMed:21555521"; MUTAGEN 186; /note="C->A: Abolished thiol protease activity."; /evidence="ECO:0000269|PubMed:11701129, ECO:0000269|PubMed:11752425, ECO:0000269|PubMed:12824163, ECO:0000269|PubMed:16916640, ECO:0000269|PubMed:27889207, ECO:0000269|PubMed:8576161"; MUTAGEN 187; /note="R->K: Does not significantly affect thiol protease catalytic efficiency."; /evidence="ECO:0000269|PubMed:19581639"; MUTAGEN 187; /note="R->M,A,G: Reduced thiol protease catalytic efficiency."; /evidence="ECO:0000269|PubMed:19581639"; MUTAGEN 187; /note="R->W,N: Strongly reduced thiol protease catalytic efficiency."; /evidence="ECO:0000269|PubMed:19581639"; MUTAGEN 192; /note="D->A: Strongly reduced thiol protease activity."; /evidence="ECO:0000269|PubMed:16916640"; MUTAGEN 195..206; /note="IQADSGPINDTD->LVPRGS: In mutant II; prevents cleavage of loop L2 region; retains significant thiol protease activity."; /evidence="ECO:0000269|PubMed:23897474"; MUTAGEN 195..200; /note="IQADSG->LVPRGS: In mutant III; prevents cleavage of loop L2 region; abolished thiol protease activity."; /evidence="ECO:0000269|PubMed:23897474"; MUTAGEN 198..204; /note="DSGPIND->ASGPINDLVPRGS: In mutant IV; prevents cleavage of loop L2 region; retains significant thiol protease activity."; /evidence="ECO:0000269|PubMed:23897474"; MUTAGEN 198; /note="D->A: Strongly reduced cleavage and activation by initiator caspases. Abolished cleavage and activation by initiator caspases; when associated with A-206. In P7-D2A mutant; abolished cleavage and activation, leading to decreased but mesureable activity; when associated with A-23."; /evidence="ECO:0000269|PubMed:12824163, ECO:0000269|PubMed:16916640, ECO:0000269|PubMed:23650375"; MUTAGEN 206; /note="D->A: Reduced cleavage and activation by initiator caspases. Abolished cleavage and activation by initiator caspases; when associated with A-198."; /evidence="ECO:0000269|PubMed:12824163, ECO:0000269|PubMed:16916640"; MUTAGEN 223; /note="Y->A,F,W,D,E: Does not significantly affect thiol protease catalytic efficiency."; /evidence="ECO:0000269|PubMed:19581639"; MUTAGEN 229; /note="Y->W: Strongly reduced thiol protease catalytic efficiency."; /evidence="ECO:0000269|PubMed:19581639"; MUTAGEN 230..234; /note="YSWRS->VSYRV: In esCasp-7 V3 mutant; promotes specificity toward alternate peptides with VEID, YVAD, WEHD, LETD or LEHD sequence; when associated with C-276. In esCasp-7 V4 mutant; promotes specificity toward alternate peptides with VEID, YVAD, WEHD, LETD or LEHD sequence; when associated with D-276."; /evidence="ECO:0000269|PubMed:27032039"; MUTAGEN 232..234; /note="WRS->HRE: In dsCasp-7 mutant; unable to cleave DEVD and VEID peptides; when associated with F-276."; /evidence="ECO:0000269|PubMed:27032039"; MUTAGEN 233; /note="R->A: Abolished ADP-riboxanation by C.violaceum CopC."; /evidence="ECO:0000269|PubMed:35446120"; MUTAGEN 239; /note="S->A: Abolished phosphorylation by PAK2; when associated with A-30 and A-173."; /evidence="ECO:0000269|PubMed:21555521"; MUTAGEN 239; /note="S->E: Mimics phosphorylation; leading to inactivate thiol protease activity."; /evidence="ECO:0000269|PubMed:27889207"; MUTAGEN 276; /note="Q->C: In esCasp-7 V3 mutant; promotes specificity toward alternate peptides with VEID, YVAD, WEHD, LETD or LEHD sequence; when associated with 230-V--V-234."; /evidence="ECO:0000269|PubMed:27032039"; MUTAGEN 276; /note="Q->D: In esCasp-7 V4 mutant; promotes specificity toward alternate peptides with VEID, YVAD, WEHD, LETD or LEHD sequence; when associated with 230-V--V-234."; /evidence="ECO:0000269|PubMed:27032039"; MUTAGEN 276; /note="Q->F: In dsCasp-7 mutant; unable to cleave DEVD sand VEID peptides; when associated with 232-H--E-234."; /evidence="ECO:0000269|PubMed:27032039"; MUTAGEN 290; /note="C->S: Decreased phosphorylation by PAK2."; /evidence="ECO:0000269|PubMed:27889207"; MUTAGEN 290; /note="C->T,N: Does not significantly affect thiol protease catalytic activity."; /evidence="ECO:0000269|PubMed:19581639
uniprot
proteins
post_translational_modification
PTM: Cleavage by different proteases, such as granzyme B (GZMB), caspase-1 (CASP1), caspase-8 (CASP8), caspase-9 (CASP9) or caspase-10 (CASP10) generate the two active subunits (PubMed:12824163, PubMed:16352606, PubMed:16916640, PubMed:35338844, PubMed:35446120, PubMed:9852092). Its involvement in different programmed cell death processes is probably specified by the protease that activates CASP7 (PubMed:16916640, PubMed:9852092). Cleaved and activated by initiator caspases (CASP8, CASP9 and/or CASP10), leading to execution phase of apoptosis (PubMed:16352606, PubMed:16916640, PubMed:21555521, PubMed:27889207). Cleavage and maturation by GZMB regulates granzyme-mediated programmed cell death (By similarity). Cleaved and activated by CASP1 in response to bacterial infection (By similarity). Propeptide domains can also be cleaved efficiently by CASP3 (PubMed:8755496). Active heterodimers between the small subunit of caspase-7 and the large subunit of CASP3, and vice versa, also occur (PubMed:8755496). Also cleaved at the N-terminus at alternative sites by CAPN1, leading to its activation (PubMed:19617626). {ECO:0000250|UniProtKB:P97864, ECO:0000269|PubMed:12824163, ECO:0000269|PubMed:16352606, ECO:0000269|PubMed:16916640, ECO:0000269|PubMed:19617626, ECO:0000269|PubMed:21555521, ECO:0000269|PubMed:27889207, ECO:0000269|PubMed:35338844, ECO:0000269|PubMed:35446120, ECO:0000269|PubMed:8755496, ECO:0000269|PubMed:9852092}.; PTM: Phosphorylation at Ser-30 and Ser-239 by PAK2 inhibits its activity (PubMed:21555521, PubMed:27889207). Phosphorylation at Ser-30 prevents cleavage and activation by initiator caspase CASP9, while phosphorylation at Ser-239 prevents thiol protease activity by preventing substrate-binding (PubMed:21555521, PubMed:27889207). {ECO:0000269|PubMed:21555521, ECO:0000269|PubMed:27889207}.; PTM: (Microbial infection) ADP-riboxanation by C.violaceum CopC blocks CASP7 processing, preventing CASP7 activation and ability to recognize and cleave substrates. {ECO:0000269|PubMed:35338844, ECO:0000269|PubMed:35446120}.; PTM: Ubiquitinated by BIRC6; this activity is inhibited by DIABLO/SMAC. {ECO:0000269|PubMed:36758104, ECO:0000269|PubMed:36758106}.
uniprot
proteins
protein_family
Peptidase C14A family
uniprot
proteins
pubmed
10497198
uniprot
proteins
pubmed
10821855
uniprot
proteins
pubmed
11257230
uniprot
proteins
pubmed
11257231
uniprot
proteins
pubmed
11701129
uniprot
proteins
pubmed
11752425
uniprot
proteins
pubmed
12824163
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15164054
uniprot
proteins
pubmed
15200957
uniprot
proteins
pubmed
15314233
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16123041
uniprot
proteins
pubmed
16352606
uniprot
proteins
pubmed
16374543
uniprot
proteins
pubmed
16916640
uniprot
proteins
pubmed
17646170
uniprot
proteins
pubmed
17697120
uniprot
proteins
pubmed
18723680
uniprot
proteins
pubmed
19054851
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19581639
uniprot
proteins
pubmed
19617626
uniprot
proteins
pubmed
20159985
uniprot
proteins
pubmed
20566630
uniprot
proteins
pubmed
21157428
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21555521
uniprot
proteins
pubmed
22184066
uniprot
proteins
pubmed
22223895
uniprot
proteins
pubmed
22451931
uniprot
proteins
pubmed
22464733
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23650375
uniprot
proteins
pubmed
23897474
uniprot
proteins
pubmed
24779913
uniprot
proteins
pubmed
26045166
uniprot
proteins
pubmed
27032039
uniprot
proteins
pubmed
27889207
uniprot
proteins
pubmed
28863261
uniprot
proteins
pubmed
30455355
uniprot
proteins
pubmed
31586028
uniprot
proteins
pubmed
34156061
uniprot
proteins
pubmed
35338844
uniprot
proteins
pubmed
35446120
uniprot
proteins
pubmed
36758104
uniprot
proteins
pubmed
36758106
uniprot
proteins
pubmed
8521391
uniprot
proteins
pubmed
8567622
uniprot
proteins
pubmed
8576161
uniprot
proteins
pubmed
8643593
uniprot
proteins
pubmed
8755496
uniprot
proteins
pubmed
9070923
uniprot
proteins
pubmed
9852092
uniprot
proteins
sequence_length
303
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:12824163, ECO:0000305|PubMed:21555521, ECO:0000305|PubMed:8576161}. Nucleus {ECO:0000269|PubMed:19617626, ECO:0000269|PubMed:21555521}. Secreted, extracellular space {ECO:0000250|UniProtKB:P97864}. Note=Following cleavage and activation by CASP1 or granzyme B (GZMB), secreted into the extracellular milieu by passing through the gasdermin-D (GSDMD) pores or perforin (PRF1) pore, respectively. {ECO:0000250|UniProtKB:P97864}.
uniprot
proteins