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Protein

Caspase-3

Gene

CASP3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Involved in the activation cascade of caspases responsible for apoptosis execution. At the onset of apoptosis it proteolytically cleaves poly(ADP-ribose) polymerase (PARP) at a '216-Asp-|-Gly-217' bond. Cleaves and activates sterol regulatory element binding proteins (SREBPs) between the basic helix-loop-helix leucine zipper domain and the membrane attachment domain. Cleaves and activates caspase-6, -7 and -9. Involved in the cleavage of huntingtin. Triggers cell adhesion in sympathetic neurons through RET cleavage.2 Publications

Catalytic activityi

Strict requirement for an Asp residue at positions P1 and P4. It has a preferred cleavage sequence of Asp-Xaa-Xaa-Asp-|- with a hydrophobic amino-acid residue at P2 and a hydrophilic amino-acid residue at P3, although Val or Ala are also accepted at this position.

Enzyme regulationi

Inhibited by isatin sulfonamides.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei121By similarity1
Active sitei163By similarity1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Protease, Thiol protease
Biological processApoptosis

Enzyme and pathway databases

BRENDAi3.4.22.56 2681
ReactomeiR-HSA-111459 Activation of caspases through apoptosome-mediated cleavage
R-HSA-111463 SMAC binds to IAPs
R-HSA-111464 SMAC-mediated dissociation of IAP:caspase complexes
R-HSA-111465 Apoptotic cleavage of cellular proteins
R-HSA-1474228 Degradation of the extracellular matrix
R-HSA-2028269 Signaling by Hippo
R-HSA-205025 NADE modulates death signalling
R-HSA-211227 Activation of DNA fragmentation factor
R-HSA-211736 Stimulation of the cell death response by PAK-2p34
R-HSA-264870 Caspase-mediated cleavage of cytoskeletal proteins
R-HSA-351906 Apoptotic cleavage of cell adhesion proteins
R-HSA-418889 Ligand-independent caspase activation via DCC
R-HSA-449836 Other interleukin signaling
SABIO-RKiP42574
SIGNORiP42574

Protein family/group databases

MEROPSiC14.003

Names & Taxonomyi

Protein namesi
Recommended name:
Caspase-3 (EC:3.4.22.56)
Short name:
CASP-3
Alternative name(s):
Apopain
Cysteine protease CPP32
Short name:
CPP-32
Protein Yama
SREBP cleavage activity 1
Short name:
SCA-1
Cleaved into the following 2 chains:
Gene namesi
Name:CASP3
Synonyms:CPP32
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

EuPathDBiHostDB:ENSG00000164305.17
HGNCiHGNC:1504 CASP3
MIMi600636 gene
neXtProtiNX_P42574

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Organism-specific databases

DisGeNETi836
OpenTargetsiENSG00000164305
PharmGKBiPA26087

Chemistry databases

ChEMBLiCHEMBL2334
DrugBankiDB06862 2-HYDROXY-5-(2-MERCAPTO-ETHYLSULFAMOYL)-BENZOIC ACID
DB08251 4-[5-(2-CARBOXY-1-FORMYL-ETHYLCARBAMOYL)-PYRIDIN-3-YL]-BENZOIC ACID
DB03124 5-[4-(1-Carboxymethyl-2-Oxo-Propylcarbamoyl)-Benzylsulfamoyl]-2-Hydroxy-Benzoic Acid
DB08229 [N-(3-DIBENZYLCARBAMOYL-OXIRANECARBONYL)-HYDRAZINO]-ACETIC ACID
DB05408 IDN-6556
DB07696 methyl (3S)-3-[(tert-butoxycarbonyl)amino]-4-oxopentanoate
DB01017 Minocycline
GuidetoPHARMACOLOGYi1619

Polymorphism and mutation databases

BioMutaiCASP3
DMDMi77416852

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
PropeptideiPRO_00000045691 – 99
PropeptideiPRO_000000457010 – 281 PublicationAdd BLAST19
ChainiPRO_000000457129 – 175Caspase-3 subunit p17Add BLAST147
ChainiPRO_0000004572176 – 277Caspase-3 subunit p12Add BLAST102

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei11N6-acetyllysineBy similarity1
Modified residuei26PhosphoserineCombined sources1
Modified residuei163S-nitrosocysteine; in inhibited form1 Publication1

Post-translational modificationi

Cleavage by granzyme B, caspase-6, caspase-8 and caspase-10 generates the two active subunits. Additional processing of the propeptides is likely due to the autocatalytic activity of the activated protease. Active heterodimers between the small subunit of caspase-7 protease and the large subunit of caspase-3 also occur and vice versa.
S-nitrosylated on its catalytic site cysteine in unstimulated human cell lines and denitrosylated upon activation of the Fas apoptotic pathway, associated with an increase in intracellular caspase activity. Fas therefore activates caspase-3 not only by inducing the cleavage of the caspase zymogen to its active subunits, but also by stimulating the denitrosylation of its active site thiol.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein, S-nitrosylation, Zymogen

Proteomic databases

EPDiP42574
MaxQBiP42574
PaxDbiP42574
PeptideAtlasiP42574
PRIDEiP42574
ProteomicsDBi55518

2D gel databases

OGPiP42574

PTM databases

iPTMnetiP42574
PhosphoSitePlusiP42574

Miscellaneous databases

PMAP-CutDBiP42574

Expressioni

Tissue specificityi

Highly expressed in lung, spleen, heart, liver and kidney. Moderate levels in brain and skeletal muscle, and low in testis. Also found in many cell lines, highest expression in cells of the immune system.

Gene expression databases

BgeeiENSG00000164305
CleanExiHS_CASP3
ExpressionAtlasiP42574 baseline and differential
GenevisibleiP42574 HS

Organism-specific databases

HPAiCAB000091
CAB008381
HPA002643

Interactioni

Subunit structurei

Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 17 kDa (p17) and a 12 kDa (p12) subunit. Interacts with BIRC6/bruce.1 Publication

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi107286, 101 interactors
DIPiDIP-268N
ELMiP42574
IntActiP42574, 54 interactors
MINTiP42574
STRINGi9606.ENSP00000311032

Chemistry databases

BindingDBiP42574

Structurei

Secondary structure

1277
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi41 – 51Combined sources11
Helixi57 – 59Combined sources3
Helixi67 – 80Combined sources14
Beta strandi84 – 90Combined sources7
Helixi93 – 105Combined sources13
Helixi108 – 110Combined sources3
Beta strandi111 – 120Combined sources10
Beta strandi126 – 129Combined sources4
Beta strandi132 – 135Combined sources4
Helixi136 – 141Combined sources6
Turni145 – 147Combined sources3
Helixi149 – 151Combined sources3
Beta strandi156 – 162Combined sources7
Beta strandi165 – 167Combined sources3
Beta strandi178 – 181Combined sources4
Turni183 – 185Combined sources3
Turni189 – 192Combined sources4
Beta strandi193 – 199Combined sources7
Beta strandi206 – 208Combined sources3
Turni209 – 211Combined sources3
Helixi214 – 226Combined sources13
Turni227 – 229Combined sources3
Helixi232 – 246Combined sources15
Helixi254 – 256Combined sources3
Beta strandi264 – 267Combined sources4
Beta strandi270 – 272Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1CP3X-ray2.30A/B1-277[»]
1GFWX-ray2.80A29-175[»]
B181-277[»]
1I3OX-ray2.70A/C1-175[»]
B/D176-277[»]
1NMEX-ray1.60A29-174[»]
B186-277[»]
1NMQX-ray2.40A/B29-277[»]
1NMSX-ray1.70A/B29-277[»]
1PAUX-ray2.50A29-175[»]
B176-277[»]
1QX3X-ray1.90A29-277[»]
1RE1X-ray2.50A29-175[»]
B176-277[»]
1RHJX-ray2.20A/C29-175[»]
B/D176-277[»]
1RHKX-ray2.50A29-175[»]
B176-277[»]
1RHMX-ray2.50A/C29-175[»]
B/D176-277[»]
1RHQX-ray3.00A/D29-175[»]
B/E176-277[»]
1RHRX-ray3.00A29-175[»]
B176-277[»]
1RHUX-ray2.51A29-175[»]
B176-277[»]
2C1EX-ray1.77A29-175[»]
B176-277[»]
2C2KX-ray1.87A29-175[»]
B176-277[»]
2C2MX-ray1.94A29-175[»]
B176-277[»]
2C2OX-ray2.45A29-175[»]
B176-277[»]
2CDRX-ray1.70A29-175[»]
B176-277[»]
2CJXX-ray1.70A29-175[»]
B176-277[»]
2CJYX-ray1.67A29-175[»]
B176-277[»]
2CNKX-ray1.75A29-175[»]
B176-277[»]
2CNLX-ray1.67A29-175[»]
B176-277[»]
2CNNX-ray1.70A29-175[»]
B176-277[»]
2CNOX-ray1.95A29-175[»]
B176-277[»]
2DKOX-ray1.06A29-174[»]
B175-277[»]
2H5IX-ray1.69A29-174[»]
B184-277[»]
2H5JX-ray2.00A/C29-174[»]
B/D184-277[»]
2H65X-ray2.30A/C29-174[»]
B/D184-277[»]
2J30X-ray1.40A29-277[»]
2J31X-ray1.50A29-277[»]
2J32X-ray1.30A29-277[»]
2J33X-ray2.00A29-277[»]
2XYGX-ray1.54A29-174[»]
B185-277[»]
2XYHX-ray1.89A29-174[»]
B185-277[»]
2XYPX-ray1.86A29-174[»]
B185-277[»]
2XZDX-ray2.10A/C27-175[»]
B/D176-277[»]
2XZTX-ray2.70A/C29-175[»]
B/D176-277[»]
2Y0BX-ray2.10A/C29-175[»]
B/D176-277[»]
3DEHX-ray2.50A/B/C/D29-277[»]
3DEIX-ray2.80A/B/C/D29-277[»]
3DEJX-ray2.60A/B/C/D29-277[»]
3DEKX-ray2.40A/B/C/D29-277[»]
3EDQX-ray1.61A/C29-175[»]
B/D176-277[»]
3GJQX-ray2.60A/C29-175[»]
B/D176-277[»]
3GJRX-ray2.20A/C29-175[»]
B/D176-277[»]
3GJSX-ray1.90A/C29-175[»]
B/D176-277[»]
3GJTX-ray2.20A/C29-175[»]
B/D176-277[»]
3H0EX-ray2.00A/B29-277[»]
3ITNX-ray1.63A29-277[»]
3KJFX-ray2.00A29-175[»]
B176-277[»]
3PCXX-ray1.50A29-277[»]
3PD0X-ray2.00A29-277[»]
3PD1X-ray1.62A29-277[»]
4DCJX-ray1.70A/D29-175[»]
B/E176-277[»]
4DCOX-ray1.70A/D29-175[»]
B/E176-277[»]
4DCPX-ray1.70A/D29-175[»]
B/E176-277[»]
4EHAX-ray1.70A/C1-277[»]
4EHDX-ray1.58A1-277[»]
4EHFX-ray1.66A1-277[»]
4EHHX-ray1.78A1-277[»]
4EHKX-ray1.67A/C1-277[»]
4EHLX-ray1.80A/C1-277[»]
4EHNX-ray1.69A1-277[»]
4JJEX-ray1.48A29-277[»]
4JQYX-ray2.50A/B34-277[»]
4JQZX-ray2.89A/B34-277[»]
4JR0X-ray1.80A/B34-277[»]
4PRYX-ray1.70A1-277[»]
4PS0X-ray1.63A/B1-277[»]
4QTXX-ray1.97A1-277[»]
4QTYX-ray1.60A29-277[»]
4QU0X-ray1.95A1-277[»]
4QU5X-ray1.91A1-277[»]
4QU8X-ray1.72A1-277[»]
4QU9X-ray1.56A1-277[»]
4QUAX-ray1.89A1-277[»]
4QUBX-ray1.69A1-277[»]
4QUDX-ray2.00A/B1-277[»]
4QUEX-ray1.84A/C1-277[»]
4QUGX-ray1.92A/C1-277[»]
4QUHX-ray1.76A/C1-277[»]
4QUIX-ray1.76A/B1-277[»]
4QUJX-ray1.50A1-277[»]
4QULX-ray1.90A/C1-277[»]
5I9BX-ray1.80A1-277[»]
5I9TX-ray1.95A/C1-277[»]
5IABX-ray1.79A/C1-277[»]
5IAEX-ray1.55A/C1-277[»]
5IAGX-ray1.98A1-277[»]
5IAJX-ray1.58A1-277[»]
5IAKX-ray1.82A1-277[»]
5IANX-ray2.70A1-277[»]
5IARX-ray1.76A1-277[»]
5IASX-ray1.54A1-277[»]
5IBCX-ray1.66A1-277[»]
5IBPX-ray1.38A1-277[»]
5IBRX-ray1.74A/C1-277[»]
5IC4X-ray2.65A/C/E/G1-175[»]
B/D/F/H176-276[»]
ProteinModelPortaliP42574
SMRiP42574
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP42574

Family & Domainsi

Sequence similaritiesi

Belongs to the peptidase C14A family.Curated

Phylogenomic databases

eggNOGiKOG3573 Eukaryota
ENOG410ZQIE LUCA
GeneTreeiENSGT00760000118912
HOGENOMiHOG000231878
HOVERGENiHBG050802
InParanoidiP42574
KOiK02187
OMAiVDDDMAC
OrthoDBiEOG091G05YD
PhylomeDBiP42574
TreeFamiTF102023

Family and domain databases

CDDicd00032 CASc, 1 hit
InterProiView protein in InterPro
IPR029030 Caspase-like_dom_sf
IPR033139 Caspase_cys_AS
IPR016129 Caspase_his_AS
IPR002138 Pept_C14_p10
IPR001309 Pept_C14_p20
IPR015917 Pept_C14A
PRINTSiPR00376 IL1BCENZYME
SMARTiView protein in SMART
SM00115 CASc, 1 hit
SUPFAMiSSF52129 SSF52129, 1 hit
PROSITEiView protein in PROSITE
PS01122 CASPASE_CYS, 1 hit
PS01121 CASPASE_HIS, 1 hit
PS50207 CASPASE_P10, 1 hit
PS50208 CASPASE_P20, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P42574-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MENTENSVDS KSIKNLEPKI IHGSESMDSG ISLDNSYKMD YPEMGLCIII
60 70 80 90 100
NNKNFHKSTG MTSRSGTDVD AANLRETFRN LKYEVRNKND LTREEIVELM
110 120 130 140 150
RDVSKEDHSK RSSFVCVLLS HGEEGIIFGT NGPVDLKKIT NFFRGDRCRS
160 170 180 190 200
LTGKPKLFII QACRGTELDC GIETDSGVDD DMACHKIPVE ADFLYAYSTA
210 220 230 240 250
PGYYSWRNSK DGSWFIQSLC AMLKQYADKL EFMHILTRVN RKVATEFESF
260 270
SFDATFHAKK QIPCIVSMLT KELYFYH
Length:277
Mass (Da):31,608
Last modified:October 11, 2005 - v2
Checksum:i2F35CD3BCF7FF64A
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti31 – 36ISLDNS → MSWDTG in CAC88866 (PubMed:15003516).Curated6

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04861622H → R. Corresponds to variant dbSNP:rs35578277Ensembl.1
Natural variantiVAR_001401190E → D3 PublicationsCorresponds to variant dbSNP:rs1049210Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U13737 mRNA Translation: AAA65015.1
U13738 mRNA Translation: AAB60355.1
U26943 mRNA Translation: AAA74929.1
AJ413269 mRNA Translation: CAC88866.1
AK291337 mRNA Translation: BAF84026.1
AY219866 Genomic DNA Translation: AAO25654.1
CH471056 Genomic DNA Translation: EAX04673.1
CH471056 Genomic DNA Translation: EAX04674.1
CH471056 Genomic DNA Translation: EAX04675.1
BC016926 mRNA Translation: AAH16926.1
CCDSiCCDS3836.1
PIRiA55315
RefSeqiNP_004337.2, NM_004346.3
NP_116786.1, NM_032991.2
XP_011530603.1, XM_011532301.1
UniGeneiHs.141125

Genome annotation databases

EnsembliENST00000308394; ENSP00000311032; ENSG00000164305
ENST00000523916; ENSP00000428929; ENSG00000164305
GeneIDi836
KEGGihsa:836
UCSCiuc003iwh.3 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiCASP3_HUMAN
AccessioniPrimary (citable) accession number: P42574
Secondary accession number(s): A8K5M2
, D3DP53, Q96AN1, Q96KP2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: October 11, 2005
Last modified: June 20, 2018
This is version 213 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Peptidase families
    Classification of peptidase families and list of entries
  7. SIMILARITY comments
    Index of protein domains and families

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