Caspases (C14) & Related Cysteine Proteases
 

Group

Caspase No

Other name

KO

gene

locus

3D

binding protein

substrate

for k

kcat(s-1)

cleavage site

Ki (nM) crmA

upstream regulators

expression

memo

CARD caspase

Ced-3 (C.elegans, vulgaris, P. pacificus)

1

1,2

4

RAIDD, Ced-4

DETD

DSVD

9

ICE-LAP6, Mch6 (human), human(short form 1, 2,b.), mouse(S, L), X.l, rat, chicken, sponge

L

1, 2, 3-9

1p36.1-.3

CARD /w Apaf1 CARD, Casp

Apaf-1, c-IAP1, c-IAP2, XIAP, DEFCAP, PACAP

LEHD

LEHD

0.02

PEPD/DQLD

<2.3

AgII, c-Myc, LPS, irrad., calpain2, Expi, camptothecin, cisplatin, RARb, D3, Blimp1, NO

ubiquitous

2

Ich-1/Nedd2  (human, mouse, rat, chick, monkey partial, Xenopus)

L

1

7q35

RAIDD, ARC, ISBP, DEFCAP, PACAP, Cyclin D3

DEHD

DEHD

0.04

DQQD

>10000

STAT1, LPS, cisplatin, doxorubicin, mitomycin C, estrogen, UVC, PG-A2

ubiquitous

DRONC (Dm, Ag)

i

1

67C4-67C5

/w DIAP1

Dapaf1, DIAP1

TAT(D/E)

TQTE

Broad-Complex, E93, DIAP1

1

ICE(human, b, g, d, e, mouse, rat, horse, pig),dog, cat, Mu, XICEa, XICEb(Xenopus)

L

m

11q22.2-.3

1,2

ICEBERG, COP, RICK, Nod1, Asc, CARD8, Ipaf, DEFCAP

WEHD

WEHD

7

WFKD

0.01

NF-kB, AP1, AIRE,  STAT1, p53, c-Myc, IL2, IL4, IL13, IL15, TNFa, IFNa/b, IFNg, LPS, Hp, Hf, St, Sd, IFNg, FSH, CD30, SCF, Subst.P, ER stress, irrad, huntingtin, RA, TGFb1, Galectin-9, Jak1, MK2, calpain, estrogen, RA, doxorubicin, phencyclidine

APCs, NK, T, B

induce NF-kB activation

4

TX,Ich-2./ICErel-II(human, b, g, d), bovine (A, B)

1

11q22.2-.3

(W/L)EHD

WEHD

1

WVRD

1.1

HBx, AIRE, CD3/28, GM-CSF, IFNg, LPS, Ma, Pg, Sp, UVB

APCs, NK, T, B

5

TY,ICErel-III (human)

1

11q22.2-.3

(W/L)EHD

WEHD

2

WVRD

<0.1

Sp

ubiquitous at lower level

(Withdrawn)

13

bovine 13A, (13B), human ( ERICE)

WVSD

11

Ich-3, caspase-11, rodent caspase-4 (mouse, rat)

L

caspase-1

MAED

NF-kB, STAT1, IL1b, LPS, IFNg, Ly49, IKKs, methotrexate

ubiquitous

12

caspase-12 (mouse, rat, human partial)

1, SL

11q22.3

TRAF2

ATAD/ADTD

ubiquitous

Pyrin/PAAD/DAPIN caspase

Caspy, caspa (zebrafish)

1

LG16

Asc

YVAD

Caspy2, caspb  (zebrafish)

LG1

WEHD

amphiCASP-6 (amphioxus)

DED-caspase

8

MACH, FLICE, Mch5(human, a3, b, b1, b3, b4, L, mouse, rat, chicken, X.l.)

L

1

2q33-q34

1, w/p35

vFLIPs, FADD/MORT1, ASC, Ced-4 , Apaf-1, ARC ,CLARP, RIP, NIK, E3 14.7K, IAPs, RNF34, Bap31, polyQ, pUL36

LETD

LETD

0.14

VETD

<0.34

p53, E2F1, Sp1, Ets, c-Myc,  Hoxa5, IRF1, IFNa, IFNb, IFNg, LPS, CSBG, Hp, Ma, RA, irrad., cisplatin, doxorubicin, mitomycin C, butyric acid, calpain2

T, NK, B, APCs

Hp , induce NF-kB activation

10

Mch4, FLICE2(human), isoform c, d (human), X.l.

1

1

2q33-q34

FADD, RIP, NIK, polyQ, RNF34

IEAD

17

BLP, Ma, TNFa, RANKL, TGFb1, heat shock, UVB, irrad., As2O3, phenytoin, NO

NK, T, B, APCs

DCP-2, DREDD[Dm (alpha, deleta, gamma), Ag]

L

1,2

1 1B10

dFADD, Dapaf1

FRID/VSPD

NF-kB processing

Alpha-rich

Casr (sponge)

downstream caspase

3

CPP32/Yama/apopain (human, mouse, chicken, rat, monkey, dog, cat, pig, sheep, rabbit, zebrafish, medaka A, B, fugu A, B), Hydra(A, B)

L

1

4q35,18?

1,2, w/XIAP BIR2

IAPs,  p21WAF1

DEVD

DEVD

10

IETD

1600

STAT1, ATF4, IL1, IL2, IL7, IL15, CD3/28, PMA, RA, RARb, TGFb1, SCF, GH, LPS, Sd, EV71, Expi, irrad., cisplatin, doxorubicin, mitomycin C, calpain2, IFNg, KCl

ubiquitous

Hp, Ub

7

Mch3/ICE-LAP3/CMH-1/LICE2/SCA-2(human, hamster, rat, mouse, Xl, Bf)

1

1

10q25.1-.2

w/XIAP, w/DEVD, pro7

IAPs

DEVD

DEVD

4

IQAD

>10000

TNFa, LPS, Ld, Lm, Mt, Tg, EV71, E2F1, Egr1, ER, IL1, IL5, IL13, calpain2, IFNg

ubiquitous

Ub

6

Mch2(human), mouse(alpha,beta), rat, chicken, X.l., rainbow trout, Sa

1

1

4q25

VEHD

VDHD

TEVD

>10000

p53, IL12, LPS, Sd, Hp, UVB, IFNg, IL10, FSH, insulin, IGF-II, Expi, KCl

endothelial, bone marrow, B, T, NK, APCs

Ub

14

caspase-14 (human), MICE (mouse)

1

19p13.1

casp1,2,4,8,10

(DEVD)

LGGD

1300

digits, epidermis

similar to DrICE(human partial)

14

DCP-1 (D.m.), SF caspase-1(Sf), Ag(ebiP8707, agCP2039), (silk worm)

1

1

2 59E3-59F4

Sf1

TETD

drICE (D.m., Ag[agCP9089, agCP2034, agCP8592] )

1

1

3 99B

TDGD

BG2, Decay (Dm, Ag)[agCP9776, agCP9777, agCP3991])

1,2

3 89C7-89D1

daydream/Damm/CG18188(D.m.)

2 48C6-48D1

DREAM/STRICA([D.m., CG7863], Ag[agCG44442, agCP10440, agCP10446, agCP10439, agCP10592])

2 42A2

DIAPs

csp-1

csp-1A, csp-1B/csh-2, csp 1C[Y48E1B.13]

1

1

2

YVAD

GEID

csp-2

csp-2A, csp-2B/csh-3, [Y48F8, Y73B6]

1

not active?

csp-3

csp-3, [Y47H9C.6]

1

1

not active

paracaspase

MALT1 (human, mouse, rat, zebrafish, C.elegans), slime malt

L

18q21

Bcl10, CARMA1, IKKs, UBC13

PMA

preB, B, T, NK, APCs, tonsil

mediate NF-kB activation

metacaspase

T.brucei[MCA1,2,3,4]A. thaliana [type I (3258570, 3643192, 4455254), II(3152556, 3152557, 3152597, 3152600)], S.c. YCA1/YOR197w, S.p., P.f., H.b.(II)

VEID/IETD?

iPA

bacterial-type Cys protease

C13

Gingipain (R, K), hglobinase (S.j.), aVPE(A.t.), Rsp., S.coelicolor

gR

K/R

C25

legumain (human, mouse, C.e.)

14q32.1

D

ubiquitous

GPI8(human, S.c.)

1

cathepsin

C1

cathepsin (human B, C, F, H, K, L, L2, O, S, V, W, X, Z)

B, K, L, S,

List

B, K, H,

(R/K/F)

NF-kB, NRF2, c-Myc, PU.1,  NF-ATc, AIRE, BRCA1, LPS, b-glucan, IL5, IL13, Ct, Ma, Mt, Tc, IFNg, TNFa, RA,  UVB, irrad, CSV-B3, EBV, IRF1, IKKs, A2aR, Lyn, Ret, insulin, IGF-II, calcineurin, camptothecin

papain(papaya)

1

R/K/F

adenain

C5

AVP(AdV5)

GA

Ulp1

C48

SENP(human 1, 2, 3), Axam (rat), Ulp(yeast 1,2)

12q13.1, 3q27.12 , 17p13

YopJ(Y.p.), AvrA(S.t.), AvrBsT(X,c,)

Tandem gene information: 11q22.3 [Casp4<Casp5<Casp1<COP<ICEBERG], 2q33.1 [Clarp>Casp10>Casp8]

Online references

Nunez, G., Benedict, M.A., Hu, Y., Inohara, N. "Caspases: The proteases of the apoptotic pathway." Oncogene 1998 Dec 24;17(25):3237-45  <<<direct download the PDF file from the publisher's site>>>

Review by Thornberry & Lazebnik (Science 1998)
Review by Cryns & Yuan (Genes Dev. 1998)   containing recent list (incovinient) of substrates
Review by Cohen GM(Biochem J 1997)  containing old list (covinient) of substrates
Human ICE/CED-3 protease nomenclature
Review by Salvesen & Dixit (Cell 1997), Wolf & Green (JBC 1999), Wang et al. (1999), Earnshaw et al. (1999)
Caspase activation: The induced-proximity model by Salvesen GS, Dixit VM (Proc.Natl.Acad.Sci USA 1999)
Review: caspases in development by Los, Wesselborg, Schulze-Osthoff  (Immunity 1999)

Links

List of Caspases in MEROPS peptidase database
"Caspase Gallery" by Gáspár Jékely
"Caspases.com"  :)

Calpain & associated proteins (under construction)
 

Group	CPN	Other name	apoptosis	KO	locus	domain structure	3D	binding protein	regulators	expression	memo
C2(L)	1	mu-Calpain, Calpain 1 (human, mosue, rat, bovine, chicken, Xl, zebrafish, Dm, Ce, At)	mediate/ inhibit	1	11q13	C2/Cal-III/EF1x5		30K	b-Ad., hypoxia, HIV Vpr	ubiquitous (highest in epidermis)
	2	miliM-Calpain, Calpain 2 (human, mouse, rat)	mediate/ inhibit		1q41-q42	C2/Cal-III/EF1x5	L	30K	CD40, RANKL, Ma, PMA, b-Ad., ALK1,, PTH	ubiquitous (highest in epithelium, NK, T, B, APCs)
	3	Calpain 3, p94 (human, mouse, rat, bovine)		1, LGMD2A	15q15.1-q21.1	NS/C2/Cal-III/EF1x5	1	titin	GH,	brain, spinal chord (not muscle-specific)
	5	hTRA-3, Calpain 5 (human, mouse, rat)		1	11q14	C2/Cal-III/Tra-3			Stat4, phenytoin, ErbB4	ubiquitous
	6	Calpain 6 (human, mouse, rat)			Xq23	C2/Cal-III/Tra-3			A2aR, TRRAP, Hoxd10	placenta
	7	Calpain 7, PalBH (human, mouse)			3p24	C2/PBH/Cal-III				ubiquitous
	8	nCL-2, nCL-2', Calpain 8 (human, mouse, rat)			1q32-41					ubiquitous
	9	nCL-4, Calpain 9 (human, mouse)			1q42.11-q42.3	C2/Cal-III/EF1x5			Cdx2, b-catenin	stomach
	10	Calpain 10 (human, mouse, rat)			2q37.3	C2/Cal-IIIx2				ubiquitous
	11	Calpain 11 (human)			6p12	NS/C2/Cal-III/EF1x5				ubiquitous (not testis- specific)
	12	Calpain 12 (mouse)			19q13.2					B, NK, T
	13	Calpain 13 (human)			2p22-p21
	14	Calpain 14 (human)			2
		SOLH (human)			16p13.3	ZF/C2/Cal-III/SOH				NK
30K(S)		30K, CAPNS1, calpain 4 (human, mouse, rat, pig,bovine, chicken)		L	19q13.1	G-rich/EF1x5			GM-CSF	ubiquitous
C2 inhibitor		calpastatin, CAST (human)			5q14-q22	CalpIx3		CLPN1,2, 9		ubiquitous (highest in digits)

Metalloproteinasess (under construction)
 

Group	Other name	apoptosis	KO	locus	domain structure	3D	binding protein	substrates	upstream regulators	memo
MMP	MMP1, collagenase (human, mouse a & b, rat, rabbit, bovine, horse)			11q22.3	PGB /ZnMc(M10/FNx3)/HX x4	1		collagens	PPARg, Bcl3, Fos, HEX, MAZ, TNFa, IL1, IFNa, MIF, VEGF, OSM, PMA,