Reviewed, UniProtKB/Swiss-Prot P55210 (CASP7_HUMAN)

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

Name:	CASP7
Synonyms:	MCH3

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	Cytoplasm.
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 proteolysis Inferred from direct assay. Source: UniProtKB
Cellular component	cytosol Inferred from Experiment. Source: Reactome endoplasmic reticulum membrane Traceable author statement. Source: UniProtKB mitochondrial membrane Traceable author statement. Source: UniProtKB
Molecular function	cysteine-type endopeptidase activity Inferred from electronic annotation. Source: InterPro protein binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
BIRC2	Q13490	2	EBI-523958,EBI-514538

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

1

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303

Helix Strand Turn

Details...

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

	Sequence		Length	Mass (Da)
	Isoform Alpha [UniParc]. Last modified October 1, 1996. Version 1. Checksum: CD373EE54A232CA4	FASTA	303	34,277
	10 20 30 40 50 60 MADDQGCIEE QGVEDSANED SVDAKPDRSS FVPSLFSKKK KNVTMRSIKT TRDRVPTYQY 70 80 90 100 110 120 NMNFEKLGKC IIINNKNFDK VTGMGVRNGT DKDAEALFKC FRSLGFDVIV YNDCSCAKMQ 130 140 150 160 170 180 DLLKKASEED HTNAACFACI LLSHGEENVI YGKDGVTPIK DLTAHFRGDR CKTLLEKPKL 190 200 210 220 230 240 FFIQACRGTE LDDGIQADSG PINDTDANPR YKIPVEADFL FAYSTVPGYY SWRSPGRGSW 250 260 270 280 290 300 FVQALCSILE EHGKDLEIMQ ILTRVNDRVA RHFESQSDDP HFHEKKQIPC VVSMLTKELY FSQ
	Isoform Beta [UniParc]. Checksum: 514964EF3F6229E1		253	28,030
	10 20 30 40 50 60 MADDQGCIEE QGVEDSANED SVDAKPDRSS FVPSLFSKKK KNVTMRSIKT TRDRVPTYQY 70 80 90 100 110 120 NMNFEKLGKC IIINNKNFDK VTGMGVRNGT DKDAEALFKC FRSLGFDVIV YNDCSCAKMQ 130 140 150 160 170 180 DLLKKASEED HTNAACFACI LLSHGEENME SCSVTQAGVQ RRDLGRLQPP PPRLAEGPSL 190 200 210 220 230 240 MMASRPTRGP SMTQMLILDT RSQWKLTSSS PIPRFQAITR GGAQEEAPGL CKPSAPSWRS 250 TEKTWKSCRS SPG
	Isoform Alpha' (Beta) [UniParc]. Checksum: 34EEFF8AF5C318A2		336	37,815
	10 20 30 40 50 60 MDCVGWPPGR KWHLEKNTSC GGSSGICASY VTQMADDQGC IEEQGVEDSA NEDSVDAKPD 70 80 90 100 110 120 RSSFVPSLFS KKKKNVTMRS IKTTRDRVPT YQYNMNFEKL GKCIIINNKN FDKVTGMGVR 130 140 150 160 170 180 NGTDKDAEAL FKCFRSLGFD VIVYNDCSCA KMQDLLKKAS EEDHTNAACF ACILLSHGEE 190 200 210 220 230 240 NVIYGKDGVT PIKDLTAHFR GDRCKTLLEK PKLFFIQACR GTELDDGIQA DSGPINDTDA 250 260 270 280 290 300 NPRYKIPVEA DFLFAYSTVP GYYSWRSPGR GSWFVQALCS ILEEHGKDLE IMQILTRVND 310 320 330 RVARHFESQS DDPHFHEKKQ IPCVVSMLTK ELYFSQ

References

	« Hide 'large scale' referencesShow '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. , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., 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 A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., 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. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., 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

EMBLGenBankDDBJ

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

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1F1J	X-ray	2.35	A/B	2-303	[»]
1GQF	X-ray	2.90	A/B	47-303	[»]
1I4O	X-ray	2.40	A/B	24-303	[»]
1I51	X-ray	2.45	A/C	51-198	[»]
			B/D	199-303	[»]
1K86	X-ray	2.60	A/B	51-303	[»]
1K88	X-ray	2.70	A/B	51-303	[»]
1KMC	X-ray	2.90	A/B	1-303	[»]
1MIA	model	-	A	57-193	[»]
			B	211-303	[»]
1SHJ	X-ray	2.80	A/B	50-303	[»]
1SHL	X-ray	3.00	A/B	57-303	[»]
2QL5	X-ray	2.34	A/C	24-196	[»]
			B/D	207-303	[»]
2QL7	X-ray	2.40	A/C	24-196	[»]
			B/D	207-303	[»]
2QL9	X-ray	2.14	A/C	24-196	[»]
			B/D	207-303	[»]
2QLB	X-ray	2.25	A/C	24-196	[»]
			B/D	207-303	[»]
2QLF	X-