Caspase-7

Details

Name
Caspase-7
Synonyms
  • 3.4.22.60
  • Apoptotic protease Mch-3
  • CASP-7
  • CMH-1
  • ICE-LAP3
  • ICE-like apoptotic protease 3
  • MCH3
Gene Name
CASP7
UniProtKB Entry
P55210Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0003618|Caspase-7
MADDQGCIEEQGVEDSANEDSVDAKPDRSSFVPSLFSKKKKNVTMRSIKTTRDRVPTYQY
NMNFEKLGKCIIINNKNFDKVTGMGVRNGTDKDAEALFKCFRSLGFDVIVYNDCSCAKMQ
DLLKKASEEDHTNAACFACILLSHGEENVIYGKDGVTPIKDLTAHFRGDRCKTLLEKPKL
FFIQACRGTELDDGIQADSGPINDTDANPRYKIPVEADFLFAYSTVPGYYSWRSPGRGSW
FVQALCSILEEHGKDLEIMQILTRVNDRVARHFESQSDDPHFHEKKQIPCVVSMLTKELY
FSQ
Number of residues
303
Molecular Weight
34276.48
Theoretical pI
5.93
GO Classification
Functions
aspartic-type endopeptidase activity / cysteine-type endopeptidase activity involved in apoptotic process / peptidase activity / RNA binding
Processes
cellular response to lipopolysaccharide / cellular response to staurosporine / defense response to bacterium / fibroblast apoptotic process / heart development / lymphocyte apoptotic process / neuron apoptotic process / positive regulation of neuron apoptotic process / positive regulation of plasma membrane repair / protein catabolic process / protein maturation / protein processing / response to UV / striated muscle cell differentiation
Components
extracellular space
General 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)
Specific Function
aspartic-type endopeptidase activity
Pfam Domain Function
Signal Regions
Not Available
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm, cytosol
Gene sequence
>lcl|BSEQ0016573|Caspase-7 (CASP7)
ATGGCAGATGATCAGGGCTGTATTGAAGAGCAGGGGGTTGAGGATTCAGCAAATGAAGAT
TCAGTGGATGCTAAGCCAGACCGGTCCTCGTTTGTACCGTCCCTCTTCAGTAAGAAGAAG
AAAAATGTCACCATGCGATCCATCAAGACCACCCGGGACCGAGTGCCTACATATCAGTAC
AACATGAATTTTGAAAAGCTGGGCAAATGCATCATAATAAACAACAAGAACTTTGATAAA
GTGACAGGTATGGGCGTTCGAAACGGAACAGACAAAGATGCCGAGGCGCTCTTCAAGTGC
TTCCGAAGCCTGGGTTTTGACGTGATTGTCTATAATGACTGCTCTTGTGCCAAGATGCAA
GATCTGCTTAAAAAAGCTTCTGAAGAGGACCATACAAATGCCGCCTGCTTCGCCTGCATC
CTCTTAAGCCATGGAGAAGAAAATGTAATTTATGGGAAAGATGGTGTCACACCAATAAAG
GATTTGACAGCCCACTTTAGGGGGGATAGATGCAAAACCCTTTTAGAGAAACCCAAACTC
TTCTTCATTCAGGCTTGCCGAGGGACCGAGCTTGATGATGGCATCCAGGCCGACTCGGGG
CCCATCAATGACACAGATGCTAATCCTCGATACAAGATCCCAGTGGAAGCTGACTTCCTC
TTCGCCTATTCCACGGTTCCAGGCTATTACTCGTGGAGGAGCCCAGGAAGAGGCTCCTGG
TTTGTGCAAGCCCTCTGCTCCATCCTGGAGGAGCACGGAAAAGACCTGGAAATCATGCAG
ATCCTCACCAGGGTGAATGACAGAGTTGCCAGGCACTTTGAGTCTCAGTCTGATGACCCA
CACTTCCATGAGAAGAAGCAGATCCCCTGTGTGGTCTCCATGCTCACCAAGGAACTCTAC
TTCAGTCAATAG
Chromosome Location
10
Locus
10q25.3
External Identifiers
ResourceLink
UniProtKB IDP55210
UniProtKB Entry NameCASP7_HUMAN
GenBank Protein ID1125073
GenBank Gene IDU39613
GeneCard IDCASP7
GenAtlas IDCASP7
HGNC IDHGNC:1508
PDB ID(s)1F1J, 1GQF, 1I4O, 1I51, 1K86, 1K88, 1KMC, 1SHJ, 1SHL, 2QL5, 2QL7, 2QL9, 2QLB, 2QLF, 2QLJ, 3EDR, 3H1P, 3IBC, 3IBF, 3R5K, 4FDL, 4FEA, 4HQ0, 4HQR, 4JB8, 4JJ8, 4JR1, 4JR2, 4LSZ, 4ZVO, 4ZVP, 4ZVQ, 4ZVR, 4ZVS, 4ZVT, 4ZVU, 5IC6, 5K20, 5V6U, 5V6Z, 7WZS, 8DGZ, 8DJ3
KEGG IDhsa:840
IUPHAR/Guide To Pharmacology ID1623
NCBI Gene ID840
General References
  1. Fernandes-Alnemri T, Takahashi A, Armstrong R, Krebs J, Fritz L, Tomaselli KJ, Wang L, Yu Z, Croce CM, Salveson G, et al.: Mch3, a novel human apoptotic cysteine protease highly related to CPP32. Cancer Res. 1995 Dec 15;55(24):6045-52. [Article]
  2. Duan H, Chinnaiyan AM, Hudson PL, Wing JP, He WW, Dixit VM: ICE-LAP3, a novel mammalian homologue of the Caenorhabditis elegans cell death protein Ced-3 is activated during Fas- and tumor necrosis factor-induced apoptosis. J Biol Chem. 1996 Jan 19;271(3):1621-5. [Article]
  3. Lippke JA, Gu Y, Sarnecki C, Caron PR, Su MS: Identification and characterization of CPP32/Mch2 homolog 1, a novel cysteine protease similar to CPP32. J Biol Chem. 1996 Jan 26;271(4):1825-8. [Article]
  4. Juan TS, McNiece IK, Argento JM, Jenkins NA, Gilbert DJ, Copeland NG, Fletcher FA: Identification and mapping of Casp7, a cysteine protease resembling CPP32 beta, interleukin-1 beta converting enzyme, and CED-3. Genomics. 1997 Feb 15;40(1):86-93. [Article]
  5. Goshima N, Kawamura Y, Fukumoto A, Miura A, Honma R, Satoh R, Wakamatsu A, Yamamoto J, Kimura K, Nishikawa T, Andoh T, Iida Y, Ishikawa K, Ito E, Kagawa N, Kaminaga C, Kanehori K, Kawakami B, Kenmochi K, Kimura R, Kobayashi M, Kuroita T, Kuwayama H, Maruyama Y, Matsuo K, Minami K, Mitsubori M, Mori M, Morishita R, Murase A, Nishikawa A, Nishikawa S, Okamoto T, Sakagami N, Sakamoto Y, Sasaki Y, Seki T, Sono S, Sugiyama A, Sumiya T, Takayama T, Takayama Y, Takeda H, Togashi T, Yahata K, Yamada H, Yanagisawa Y, Endo Y, Imamoto F, Kisu Y, Tanaka S, Isogai T, Imai J, Watanabe S, Nomura N: Human protein factory for converting the transcriptome into an in vitro-expressed proteome,. Nat Methods. 2008 Dec;5(12):1011-7. [Article]
  6. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
  7. Deloukas P, Earthrowl ME, Grafham DV, Rubenfield M, French L, Steward CA, Sims SK, Jones MC, Searle S, Scott C, Howe K, Hunt SE, Andrews TD, Gilbert JG, Swarbreck D, Ashurst JL, Taylor A, Battles J, Bird CP, Ainscough R, Almeida JP, Ashwell RI, Ambrose KD, Babbage AK, Bagguley CL, Bailey J, Banerjee R, Bates K, Beasley H, Bray-Allen S, Brown AJ, Brown JY, Burford DC, Burrill W, Burton J, Cahill P, Camire D, Carter NP, Chapman JC, Clark SY, Clarke G, Clee CM, Clegg S, Corby N, Coulson A, Dhami P, Dutta I, Dunn M, Faulkner L, Frankish A, Frankland JA, Garner P, Garnett J, Gribble S, Griffiths C, Grocock R, Gustafson E, Hammond S, Harley JL, Hart E, Heath PD, Ho TP, Hopkins B, Horne J, Howden PJ, Huckle E, Hynds C, Johnson C, Johnson D, Kana A, Kay M, Kimberley AM, Kershaw JK, Kokkinaki M, Laird GK, Lawlor S, Lee HM, Leongamornlert DA, Laird G, Lloyd C, Lloyd DM, Loveland J, Lovell J, McLaren S, McLay KE, McMurray A, Mashreghi-Mohammadi M, Matthews L, Milne S, Nickerson T, Nguyen M, Overton-Larty E, Palmer SA, Pearce AV, Peck AI, Pelan S, Phillimore B, Porter K, Rice CM, Rogosin A, Ross MT, Sarafidou T, Sehra HK, Shownkeen R, Skuce CD, Smith M, Standring L, Sycamore N, Tester J, Thorpe A, Torcasso W, Tracey A, Tromans A, Tsolas J, Wall M, Walsh J, Wang H, Weinstock K, West AP, Willey DL, Whitehead SL, Wilming L, Wray PW, Young L, Chen Y, Lovering RC, Moschonas NK, Siebert R, Fechtel K, Bentley D, Durbin R, Hubbard T, Doucette-Stamm L, Beck S, Smith DR, Rogers J: The DNA sequence and comparative analysis of human chromosome 10. Nature. 2004 May 27;429(6990):375-81. [Article]
  8. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  9. Fernandes-Alnemri T, Armstrong RC, Krebs J, Srinivasula SM, Wang L, Bullrich F, Fritz LC, Trapani JA, Tomaselli KJ, Litwack G, Alnemri ES: In vitro activation of CPP32 and Mch3 by Mch4, a novel human apoptotic cysteine protease containing two FADD-like domains. Proc Natl Acad Sci U S A. 1996 Jul 23;93(15):7464-9. [Article]
  10. Bartke T, Pohl C, Pyrowolakis G, Jentsch S: Dual role of BRUCE as an antiapoptotic IAP and a chimeric E2/E3 ubiquitin ligase. Mol Cell. 2004 Jun 18;14(6):801-11. [Article]
  11. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501. doi: 10.1021/ac9004309. [Article]
  12. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [Article]
  13. Bienvenut WV, Sumpton D, Martinez A, Lilla S, Espagne C, Meinnel T, Giglione C: Comparative large scale characterization of plant versus mammal proteins reveals similar and idiosyncratic N-alpha-acetylation features. Mol Cell Proteomics. 2012 Jun;11(6):M111.015131. doi: 10.1074/mcp.M111.015131. Epub 2012 Jan 5. [Article]
  14. Chai J, Wu Q, Shiozaki E, Srinivasula SM, Alnemri ES, Shi Y: Crystal structure of a procaspase-7 zymogen: mechanisms of activation and substrate binding. Cell. 2001 Nov 2;107(3):399-407. [Article]

Associated Data

Bio-Entities
Bio-EntityType
Caspase-7 (Humans)protein
primary
Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
FicaexperimentalunknowntargetDetails
EmricasaninvestigationalunknowntargetDetails
Incadronic acidexperimentalunknowntargetactivatorDetails