Entry
Name
caspase-3;
CPP32;
apopain;
yama protein
Class
Hydrolases;
Acting on peptide bonds (peptidases);
Cysteine endopeptidases
BRITE hierarchy
Reaction(IUBMB)
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
Comment
Caspase-3 is an effector/executioner caspase, as are caspase-6 (EC
3.4.22.59 ) and caspase-7 (EC
3.4.22.60 ) [5]. These caspases are responsible for the proteolysis of the majority of cellular polypeptides [e.g. poly(ADP-ribose) polymerase (PARP)], which leads to the apoptotic phenotype [3,5]. Procaspase-3 can be activated by caspase-1 (EC
3.4.22.36 ), caspase-8 (EC
3.4.22.61 ), caspase-9 (EC
3.4.22.62 ) and caspase-10 (EC
3.4.22.63 ) as well as by the serine protease granzyme B [1]. Caspase-3 can activate procaspase-2 (EC
3.4.22.55 ) [2]. Activation occurs by inter-domain cleavage followed by removal of the N-terminal prodomain [6]. Although Asp-Glu-(Val/Ile)-Asp is thought to be the preferred cleavage sequence, the enzyme can accommodate different residues at P2 and P3 of the substrate [4]. Like caspase-2, a hydrophobic residue at P5 of caspase-3 leads to more efficient hydrolysis, e.g. (Val/Leu)-Asp-Val-Ala-Asp! is a better substrate than Asp-Val-Ala-Asp! . This is not the case for caspase-7 [4]. Belongs in peptidase family C14.
History
EC 3.4.22.56 created 2007
Orthology
Genes
MNI : 105466747(CASP3) 105492342
CATY : 105593734 105597738(CASP3)
TGE : 112622580 112625066(CASP3)
MLEU : 105552669 105553959(CASP3)
RRO : 104666783 104673791(CASP3)
TFN : 117075139 117083313 117086196(CASP3)
PTEH : 111548479(CASP3) 111551382
CIMI : 108288114(CASP3) 108310786
MMUR : 105880624 105882502(CASP3)
MFOT : 126495899 126504830
NGI : 103744668 103750475(Casp3)
HGL : 101696390 101712867(Casp3) 101723884
CCAN : 109678444 109678454
NCAR : 124972492 124983898
MMMA : 107142678(Casp3) 107158031
TUP : 102472926(CASP3) 102487119
BMUS : 118887867(CASP3) 118889206
SETR : 126006887 126007206 126007207
MDO : 654273(CASP3) 654275
GAS : 123232391 123251682(CASP3) 123251883 123252074 123255551
SHR : 100922500(CASP3) 100922757
TVP : 118853359(CASP3) 118853360
PMUA : 114585959 114604250(CASP3)
XLA : 100036910(casp3.2.L) 397720(casp3.2.S)
XTR : 100151728(casp3.2) 100486222(casp3.1)
RTEM : 120921481(CASP3) 120921507
BBUF : 120990143 120990145
BGAR : 122934399 122940788
DRE : 140621(casp3a) 566604(casp3b)
SRX : 107710482(casp3) 107716035 107716036 107746030 107754122
SANH : 107656460 107678640 107688004(casp3) 107702336
SGH : 107556843 107558201(casp3) 107562747 107589121
CCAR : 109068105 109068106 109071297 109089113 109093929 109096565
CAUA : 113044167 113074954 113074955 113105596 113113788 113113799
CGIB : 127949347 127966708 127970959 128027693
PTET : 122347890(casp3a) 122358134(casp3b)
LROH : 127164613(casp3a) 127176487(casp3b) 127176488
OMC : 131537993(casp3a) 131552912(casp3b)
PPRM : 120462979 120465362(casp3b) 120488777(casp3a)
RKG : 130078661(casp3b) 130089485(casp3a)
MAMB : 125266884(casp3b) 125272552(casp3a)
CIDE : 127494251 127517789
CERY : 137025574(casp3b) 137032207(casp3a)
MASI : 127413339 127418172 127444133 127444697
TROS : 130552814(casp3a) 130563511(casp3b)
TDW : 130438496(casp3b) 130438623(casp3a)
MANU : 129422652 129422653 129444794(casp3a)
IPU : 100528811(casp3b) 108260860(casp3a)
IFU : 128604109(casp3a) 128611217(casp3b)
PHYP : 113529132 113547376
SMEO : 124381088(casp3a) 124386509(casp3b)
TFD : 113635419(casp3a) 113635854(casp3b)
TVC : 132841980(casp3a) 132855819(casp3b)
TRN : 134319663(casp3b) 134326362(casp3a)
AMEX : 103025383(casp3b) 103039001(casp3a)
CMAO : 118806926 118806927 118817001
EEE : 113581517(casp3) 113586537
CHAR : 105892611(casp3a) 105894697
LCO : 104928227 104936945(caspase-3)
NCC : 104959742 104967108(casp3)
TBEN : 117475166 117482205(casp3a)
CGOB : 115010976(casp3) 115014922
PGEO : 117440899 117448400(casp3a)
GACU : 117550380 117556108(casp3a)
EMAC : 134859666 134864823(casp3a)
ELY : 117254954(casp3a) 117261186(casp3b)
EFO : 125886058(casp3a) 125894522(casp3b)
PLEP : 121942065(casp3a) 121948074(casp3b) 121963193
SLUC : 116034351(casp3a) 116036562 116036563 116036564
ECRA : 117951380 117960699(casp3a)
PFLV : 114563090 114563091 114570899
GAT : 120818221 120818253 120824960(casp3a)
PPUG : 119211291(casp3b) 119217562(casp3a)
CLUM : 117730679(casp3a) 117737645
PSWI : 130190550(casp3a) 130210015
CANA : 137788494 137793270(casp3a)
CVE : 137875193 137885023(casp3a)
MSAM : 119888653 119898808(casp3a)
SCHU : 122873701(casp3a) 122879777
CUD : 121506610 121508374(casp3a)
ALAT : 119007045 119010646(casp3a)
ASTR : 137599674(casp3a) 137602368 137603089
MZE : 101463771 101464077 101478576
ONL : 100534438(casp3a) 100695417 100695678
OAU : 116333961 116334002(casp3a) 120432681
OLA : 100049215(casp3) 100049265
OML : 112137236(casp3a) 112153020
XCO : 114139499 114144355(casp3)
PRET : 103461041 103471007
PFOR : 103136385(casp3) 103151710 103151718
PLAI : 106934607 106964569(casp3)
PMEI : 106906082 106931037
GAF : 122830167(casp3a) 122837161
PPRL : 129362835 129376856(casp3a)
CVG : 107090480 107094160(casp3)
CTUL : 119774386(casp3a) 119794097
GMU : 124860636 124868646(casp3a)
NFU : 107390752(casp3) 107397381
KMR : 108234461(casp3a) 108240012
ALIM : 106525841 106532390 106532391
NWH : 119408300(casp3b) 119422562(casp3a)
AOCE : 111577084 111580236 111580983
MCEP : 125004376(casp3a) 125007842
CSEM : 103383467 103391460(casp3)
SSEN : 122770713(casp3a) 122778867(casp3b)
HHIP : 117768955 117768956 117770486(casp3a)
HSP : 118112335 118112812 118125353(casp3a)
PPLT : 128437083(casp3a) 128446070 128446071
SMAU : 118312563(casp3a) 118319217
LCF : 108893087 108901489(casp3b)
SLAL : 111663309 111667597
XGL : 120785392 120800586(casp3a)
SSCV : 125969100(casp3a) 125977455
SBIA : 133505663(casp3a) 133509169(casp3b)
PEE : 133403901(casp3a) 133407620(casp3b)
PTAO : 133476745(casp3a) 133484344(casp3b)
BPEC : 110157710 110157737 110157738 110157739 110160793 110167549
MALB : 109957512(casp3) 109972113
BSPL : 114858837(casp3a) 114864529(casp3b)
SJO : 128362971(casp3b) 128369792(casp3a)
SASA : 100194892(casp3) 106602722(CASP3) 106612018
STRU : 115164279 115192071 115205518
OTW : 112231666(casp3a) 112248666 112255992(casp3b) 112261439
OMY : 100653443(casp3b) 110497496 110525880 110534285(casp3a)
OGO : 124001817 124010499(casp3b) 124012367(casp3a) 124034151
ONE : 115111788 115129259 115137223(casp3) 115145810
OKI : 109882220 109894209 109901037 109905000
OKE : 118362899 118363298(casp3b) 118393409 118395316(casp3a)
SALP : 111967296 111974694 112068696
SNH : 120035095 120040359 120052764(casp3a) 120062476(casp3b)
CCLU : 121561955(casp3a) 121585038 121586839(casp3b)
ELS : 105006735(casp3) 105029385(casp3)
SFM : 108924572(casp3) 114912449
AANG : 118228056(casp3a) 118231090
PSPA : 121297547 121320508
ARUT : 117409020 117420645 117420663
SCLV : 120329950 120330440 120343279
SPU : 100888153 100891400 105440861 115924745 577169 590727 752445
LPIC : 129262862 129276743 129280887
SCAC : 106083170 106085300
PJA : 122244525 122252835 122266857
PCHN : 125025456 125027331 125038862 125045343
CSCU : 111622357 111630059
LGI : LOTGIDRAFT_134425 LOTGIDRAFT_154127
PVUL : 126810934 126825563
BGT : 106054357 106055843 106060604 106060606
GAE : 121371420 121373089 121373751 121379721 121380116 121380117
HRF : 124110711 124138235 124145235 124149347 124151146
HRJ : 124271978 124273441 124275872 124277155 124280186 124282813 124284013
HASI : 137255718 137283582 137284629 137284820 137287107
CANU : 128157037 128177778
CVN : 111103742 111124840 111124890 111124931 111135767
PMAX : 117318643 117319579 117324924 117329263 117329267 117337756 117344515
MMER : 123540593 123564484
RPHI : 132712765 132712767 132719291 132720393 132744926 132752043 132752568
DPOL : 127842540 127866357 127875975
MAEA : 128231422 128231423 128242425 128243624 128243627
OSN : 115211714 115211715 115212057 115212312 115213954 115221299 115222278 115226488 115226968 115227436 115227469 118761171
ATEN : 116289657 116305833
ADF : 107330835 107333405 107341447 107353606 107353617 107354064 107358411
AMIL : 114957900 114960829
PDAM : 113666028 113679245
SPIS : 111325011 111325026 111331296 111331297 111337613 111345079
DGT : 114519758 114524348 114529411 114532953
XEN : 124433995 124434117 124452401 124458257
HMG : 100202915 100208555 105844712
HSY : 130625346 130635864 130657493
AQU : 105315042 105315216 105315492 105315880 105316185 109583632 109586426 109588926
» show all
Taxonomy
Reference
Authors
Krebs JF, Srinivasan A, Wong AM, Tomaselli KJ, Fritz LC, Wu JC.
Title
Heavy membrane-associated caspase 3: identification, isolation, and characterization.
Journal
Reference
Authors
Li H, Bergeron L, Cryns V, Pasternack MS, Zhu H, Shi L, Greenberg A, Yuan J.
Title
Activation of caspase-2 in apoptosis.
Journal
Reference
3
Authors
Nicholson D, Thornberry NA.
Title
Caspase-3 and caspase-7.
Journal
In: Barrett AJ, Rawlings ND, Woessner JF (eds). Handbook of Proteolytic Enzymes. 2nd ed. London: Elsevier; 2004. p. 1298-1302.
Reference
Authors
Fang B, Boross PI, Tozser J, Weber IT.
Title
Structural and kinetic analysis of caspase-3 reveals role for s5 binding site in substrate recognition.
Journal
Reference
Authors
Chang HY, Yang X.
Title
Proteases for cell suicide: functions and regulation of caspases.
Journal
Reference
Authors
Martin SJ, Amarante-Mendes GP, Shi L, Chuang TH, Casiano CA, O'Brien GA, Fitzgerald P, Tan EM, Bokoch GM, Greenberg AH, Green DR.
Title
The cytotoxic cell protease granzyme B initiates apoptosis in a cell-free system by proteolytic processing and activation of the ICE/CED-3 family protease, CPP32, via a novel two-step mechanism.
Journal
Other DBs
ExPASy - ENZYME nomenclature database: 3.4.22.56