Reviewed,
UniProtKB/Swiss-Prot P55210 (CASP7_HUMAN)
Last modified
November 25, 2008.
Version 96.
History...
Clusters with 100%,
90%,
50% identity |
Documents (6) |
Third-party data |
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Names and origin
| Protein names | Recommended name: Caspase-7 Short name=CASP-7 EC=3.4.22.60 Alternative name(s): ICE-like apoptotic protease 3 Short name=ICE-LAP3 Apoptotic protease Mch-3 CMH-1 Cleaved into the following 2 chains: 1- Recommended name: Caspase-7 subunit p20 2- Recommended name: Caspase-7 subunit p11 | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 303 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is further processed into a mature form. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | Involved in the activation cascade of caspases responsible for apoptosis execution. Cleaves and activates sterol regulatory element binding proteins (SREBPs). Proteolytically cleaves poly(ADP-ribose) polymerase (PARP) at a '216-Asp-|-Gly-217' bond. Overexpression promotes programmed cell death. |
| Catalytic activity | Strict requirement for an Asp residue at position P1 and has a preferred cleavage sequence of Asp-Glu-Val-Asp-|-. |
| Enzyme regulation | Inhibited by isatin sulfonamides. |
| Subunit structure | Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 20 kDa (p20) and a 11 kDa (p11) subunit. |
| Subcellular location | |
| Tissue specificity | Highly expressed in lung, skeletal muscle, liver, kidney, spleen and heart, and moderately in testis. No expression in the brain. |
| Post-translational modification | Cleavages by granzyme B or caspase-10 generate the two active subunits. Propeptide domains can also be cleaved efficiently by caspase-3. Active heterodimers between the small subunit of caspase-7 and the large subunit of caspase-3, and vice versa, also occur. |
| Sequence similarities | Belongs to the peptidase C14 family. |
Ontologies
Keywords | |
|---|---|
| Biological process | Apoptosis |
| Cellular component | Cytoplasm |
| Coding sequence diversity | Alternative splicing |
| Molecular function | Hydrolase Protease Thiol protease |
| PTM | Zymogen |
| Technical term | 3D-structure |
Gene Ontology (GO) | |
| Uncategorized | caspase activity Inferred from Experiment. Source: Reactome |
| Biological process | apoptotic program Ref.2 Traceable author statement. Source: ProtInc proteolysisInferred from direct assay. Source: UniProtKB |
| Cellular component | cytosol Inferred from Experiment. Source: Reactome endoplasmic reticulum membraneTraceable author statement. Source: UniProtKB mitochondrial membraneTraceable author statement. Source: UniProtKB |
| Molecular function | cysteine-type endopeptidase activity Inferred from electronic annotation. Source: InterPro protein bindingInferred from physical interaction. Source: UniProtKB |
| Complete GO annotation... | |
Alternative products
| This entry describes 3 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform Alpha (identifier: P55210-1) This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. | ||||||
| Isoform Beta (identifier: P55210-2) The sequence of this isoform differs from the canonical sequence as follows: 149-303: VIYGKDGVTP...MLTKELYFSQ → MESCSVTQAG...TWKSCRSSPG | ||||||
| Notes: Not proteolytically active. | ||||||
| Isoform Alpha' (identifier: P55210-3) Also known as: Beta; The sequence of this isoform differs from the canonical sequence as follows: 1-1: M → MDCVGWPPGRKWHLEKNTSCGGSSGICASYVTQM | ||||||
| Notes: What we call isoform Alpha' is known in Ref.4 as Beta. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | |||||||||||||||||||||||||||||||||||||||||||||||
Molecule processing | ||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Propeptide | 1 – 23 | 23 | PRO_0000004616 | |||||||||||||||||||||||||||||||||||||||||||||||||
| Chain | 24 – 198 | 175 | Caspase-7 subunit p20 | PRO_0000004617 | ||||||||||||||||||||||||||||||||||||||||||||||||
| Propeptide | 199 – 206 | 8 | PRO_0000004618 | |||||||||||||||||||||||||||||||||||||||||||||||||
| Chain | 207 – 303 | 97 | Caspase-7 subunit p11 | PRO_0000004619 | ||||||||||||||||||||||||||||||||||||||||||||||||
Sites | ||||||||||||||||||||||||||||||||||||||||||||||||||||
| Active site | 144 | 1 | By similarity | |||||||||||||||||||||||||||||||||||||||||||||||||
| Active site | 186 | 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||
Natural variations | ||||||||||||||||||||||||||||||||||||||||||||||||||||
| Alternative sequence | 1 | 1 | M → MDCVGWPPGRKWHLEKNTSC GGSSGICASYVTQM in isoform Alpha'. | VSP_000806 | ||||||||||||||||||||||||||||||||||||||||||||||||
| Alternative sequence | 149 – 303 | 155 | VIYGK…LYFSQ → MESCSVTQAGVQRRDLGRLQ PPPPRLAEGPSLMMASRPTR GPSMTQMLILDTRSQWKLTS SSPIPRFQAITRGGAQEEAP GLCKPSAPSWRSTEKTWKSC RSSPG in isoform Beta. | VSP_000807 | ||||||||||||||||||||||||||||||||||||||||||||||||
Experimental info | ||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mutagenesis | 186 | 1 | C → A: No apoptotic activity | |||||||||||||||||||||||||||||||||||||||||||||||||
| Sequence conflict | 4 | 1 | D → E in AAH15799. Ref.7 | |||||||||||||||||||||||||||||||||||||||||||||||||
| Sequence conflict | 194 | 1 | G → A in AAC50346. Ref.2 | |||||||||||||||||||||||||||||||||||||||||||||||||
Secondary structure | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Helix Strand Turn | ||||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 64 – 74 | 11 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Turn | 80 – 82 | 3 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Helix | 90 – 104 | 15 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 106 – 113 | 8 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Helix | 116 – 128 | 13 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Helix | 131 – 133 | 3 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 134 – 143 | 10 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 149 – 151 | 3 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 153 – 158 | 6 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Helix | 159 – 164 | 6 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Turn | 168 – 170 | 3 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Helix | 172 – 174 | 3 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 179 – 185 | 7 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 188 – 190 | 3 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Turn | 215 – 218 | 4 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 219 – 225 | 7 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 232 – 234 | 3 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Turn | 235 – 237 | 3 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Helix | 240 – 252 | 13 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Turn | 253 – 255 | 3 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Helix | 258 – 272 | 15 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Helix | 280 – 282 | 3 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 290 – 293 | 4 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 296 – 298 | 3 | ||||||||||||||||||||||||||||||||||||||||||||||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Mch3, a novel human apoptotic cysteine protease highly related to CPP32." Fernandes-Alnemri T., Takahashi A., Armstrong R.C., Krebs J., Fritz L.C., Tomaselli K.J., Wang L., Yu Z., Croce C.M., Salveson G., Earnshaw W.C., Litwack G., Alnemri E.S. Cancer Res. 55:6045-6052(1995) [PubMed: 8521391] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ALPHA AND BETA). Tissue: T-cell. |
| [2] | "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." Duan H., Chinnaiyan A.M., Hudson P.L., Wing J.P., He W.-W., Dixit V.M. J. Biol. Chem. 271:1621-1625(1996) [PubMed: 8576161] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA). |
| [3] | "Identification and characterization of CPP32/Mch2 homolog 1, a novel cysteine protease similar to CPP32." Lippke J.A., Gu Y., Sarnecki C., Caron P.R., Su M.S.-S. J. Biol. Chem. 271:1825-1828(1996) [PubMed: 8567622] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA). Tissue: Spleen. |
| [4] | "Identification and mapping of Casp7, a cysteine protease resembling CPP32 beta, interleukin-1 beta converting enzyme, and CED-3." Juan T.S.-C., McNiece I.K., Argento J.M., Jenkins N.A., Gilbert D.J., Copeland N.G., Fletcher F.A. Genomics 40:86-93(1997) [PubMed: 9070923] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ALPHA AND ALPHA'). Tissue: Fetal lung and Fetal spleen. |
| [5] | "The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. Rogers J.Nature 429:375-381(2004) [PubMed: 15164054] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [6] | Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. Venter J.C.Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [7] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA). Tissue: Skin. |
| [8] | "In vitro activation of CPP32 and Mch3 by Mch4, a novel human apoptotic cysteine protease containing two FADD-like domains." Fernandes-Alnemri T., Armstrong R.C., Krebs J.F., Srinivasula S.M., Wang L., Bullrich F., Fritz L.C., Trapani J.A., Tomaselli K.J., Litwack G., Alnemri E.S. Proc. Natl. Acad. Sci. U.S.A. 93:7464-7469(1996) [PubMed: 8755496] [Abstract] Cited for: PROTEOLYTIC PROCESSING. |
| [9] | "Crystal structure of a procaspase-7 zymogen: mechanisms of activation and substrate binding." Chai J., Wu Q., Shiozaki E., Srinivasula S.M., Alnemri E.S., Shi Y. Cell 107:399-407(2001) [PubMed: 11701129] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 51-303, SUBUNIT. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| U37448 mRNA. Translation: AAC50303.1. U37449 mRNA. Translation: AAC50304.1. U39613 mRNA. Translation: AAC50346.1. U40281 mRNA. Translation: AAC50352.1. U67319 mRNA. Translation: AAC51152.1. U67320 mRNA. Translation: AAC51153.1. U67206 mRNA. Translation: AAF21460.1. AL592546, AL627395 Genomic DNA. Translation: CAI12638.1. AL627395, AL592546 Genomic DNA. Translation: CAI16004.1. CH471066 Genomic DNA. Translation: EAW49495.1. BC015799 mRNA. Translation: AAH15799.1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| RefSeq | NP_001218.1. NP_203124.1. NP_203125.1. NP_203126.1. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| UniGene | Hs.9216 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
3D structure databases | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Clusters with