Reviewed, UniProtKB/Swiss-Prot P55212 (CASP6_HUMAN)

Names and origin

Protein names

Recommended name:
    Caspase-6
      Short name=CASP-6
    EC=3.4.22.59
Alternative name(s):
    Apoptotic protease Mch-2
Cleaved into the following 2 chains:
    1- Recommended name:
            Caspase-6 subunit p18
    2- Recommended name:
            Caspase-6 subunit p11

Gene names

Name:	CASP6
Synonyms:	MCH2

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	293 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 poly(ADP-ribose) polymerase in vitro, as well as lamins. Overexpression promotes programmed cell death.
Catalytic activity	Strict requirement for Asp at position P1 and has a preferred cleavage sequence of Val-Glu-His-Asp-|-.
Enzyme regulation	Activation is suppressed by phosphorylation at Ser-257.
Subunit structure	Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 18 kDa (p18) and a 11 kDa (p11) subunit.
Subcellular location	Cytoplasm.
Post-translational modification	Cleavages by caspase-3, caspase-8 or -10 generate the two active subunits.
Sequence similarities	Belongs to the peptidase C14 family.

Ontologies

Keywords
Biological process	Apoptosis
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
Molecular function	Hydrolase Protease Thiol protease
PTM	Phosphoprotein Zymogen
Technical term	3D-structure
Gene Ontology (GO)
Biological process	induction of apoptosis Ref.1 Traceable author statement. Source: ProtInc proteolysis Ref.1 Inferred from direct assay. Source: UniProtKB
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	cysteine-type endopeptidase activity Inferred from electronic annotation. Source: InterPro protein binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform Alpha (identifier: P55212-1)

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: P55212-2)

The sequence of this isoform differs from the canonical sequence as follows:
     14-102: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Propeptide

1 – 23

23

PRO_0000004608

Chain

24 – 179

156

Caspase-6 subunit p18

PRO_0000004609

Propeptide

180 – 193

14

PRO_0000004610

Chain

194 – 293

100

Caspase-6 subunit p11

PRO_0000004611

Sites

Active site

121

1

By similarity

Active site

163

1

By similarity

Amino acid modifications

Modified residue

257

1

Phosphoserine

Natural variations

Alternative sequence

14 – 102

89

Missing in isoform Beta.

VSP_000805

Natural variant

35

1

E → K: dbSNP rs11574697.

VAR_029242

Natural variant

109

1

A → T: dbSNP rs5030674.

VAR_016130

Natural variant

182

1

T → S: dbSNP rs5030593.

VAR_020126

Experimental info

Mutagenesis

257

1

S → A: Suppression of caspase-6 activation

Sequence conflict

66

1

G → R in AAC50168. Ref.1

Secondary structure

1

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293

Helix Strand Turn

Details...

Beta strand

46 – 51

6

Helix

57 – 59

3

Helix

67 – 80

14

Beta strand

84 – 90

7

Helix

93 – 104

12

Beta strand

114 – 120

7

Beta strand

130 – 132

3

Helix

137 – 140

4

Helix

141 – 143

3

Turn

145 – 147

3

Helix

149 – 151

3

Beta strand

156 – 162

7

Turn

202 – 205

4

Beta strand

207 – 212

6

Beta strand

219 – 221

3

Turn

222 – 224

3

Helix

227 – 239

13

Turn

240 – 242

3

Helix

245 – 256

12

Helix

258 – 261

4

Beta strand

262 – 265

4

Turn

267 – 269

3

Beta strand

277 – 280

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform Alpha [UniParc]. Last modified November 28, 2002. Version 2. Checksum: 0738AE4F9791EBD7	FASTA	293	33,310
	10 20 30 40 50 60 MSSASGLRRG HPAGGEENMT ETDAFYKREM FDPAEKYKMD HRRRGIALIF NHERFFWHLT 70 80 90 100 110 120 LPERRGTCAD RDNLTRRFSD LGFEVKCFND LKAEELLLKI HEVSTVSHAD ADCFVCVFLS 130 140 150 160 170 180 HGEGNHIYAY DAKIEIQTLT GLFKGDKCHS LVGKPKIFII QACRGNQHDV PVIPLDVVDN 190 200 210 220 230 240 QTEKLDTNIT EVDAASVYTL PAGADFLMCY SVAEGYYSHR ETVNGSWYIQ DLCEMLGKYG 250 260 270 280 290 SSLEFTELLT LVNRKVSQRR VDFCKDPSAI GKKQVPCFAS MLTKKLHFFP KSN
	Isoform Beta [UniParc]. Checksum: 9DCC10C99F81D912		204	22,574
	10 20 30 40 50 60 MSSASGLRRG HPAVSTVSHA DADCFVCVFL SHGEGNHIYA YDAKIEIQTL TGLFKGDKCH 70 80 90 100 110 120 SLVGKPKIFI IQACRGNQHD VPVIPLDVVD NQTEKLDTNI TEVDAASVYT LPAGADFLMC 130 140 150 160 170 180 YSVAEGYYSH RETVNGSWYI QDLCEMLGKY GSSLEFTELL TLVNRKVSQR RVDFCKDPSA 190 200 IGKKQVPCFA SMLTKKLHFF PKSN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Mch2, a new member of the apoptotic Ced-3/Ice cysteine protease gene family." Fernandes-Alnemri T., Litwack G., Alnemri E.S. Cancer Res. 55:2737-2742(1995) [PubMed: 7796396] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ALPHA AND BETA). Tissue: T-cell.
[2]	"NIEHS-SNPs, environmental genome project, NIEHS ES15478, Department of Genome Sciences, Seattle, WA (URL: http://egp.gs.washington.edu)." Rieder M.J., Livingston R.J., Daniels M.R., Chung M.-W., Miyamoto K.E., Nguyen C.P., Nguyen D.A., Poel C.L., Robertson P.D., Schackwitz W.S., Sherwood J.K., Witrak L.A., Nickerson D.A. Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"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: Lung.
[4]	"The Ced-3/interleukin 1beta converting enzyme-like homolog Mch6 and the lamin-cleaving enzyme Mch2alpha are substrates for the apoptotic mediator CPP32." Srinivasula S.M., Fernandes-Alnemri T., Zangrilli J., Robertson N., Armstrong R.C., Wang L., Trapani J.A., Tomaselli K.J., Litwack G., Alnemri E.S. J. Biol. Chem. 271:27099-27106(1996) [PubMed: 8900201] [Abstract] Cited for: PROTEOLYTIC PROCESSING. Tissue: Lymphocyte.
[5]	"Regulation of caspase-6 and FLIP by the AMPK family member ARK5." Suzuki A., Kusakai G., Kishimoto A., Shimojo Y., Miyamoto S., Ogura T., Ochiai A., Esumi H. Oncogene 23:7067-7075(2004) [PubMed: 15273717] [Abstract] Cited for: ENZYME REGULATION, PHOSPHORYLATION AT SER-257, MUTAGENESIS OF SER-257.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

U20536 mRNA. Translation: AAC50168.1.
U20537 mRNA. Translation: AAC50169.1.
AY254046 Genomic DNA. Translation: AAO63494.1.
BC000305 mRNA. Translation: AAH00305.1.
BC004460 mRNA. Translation: AAH04460.1.

RefSeq

NP_001217.2.
NP_116787.1.

UniGene

Hs.654616

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1MI9	model	-	A	34-175	[»]
			B	198-290	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P55212.

Protein family/group databases

MEROPS

C14.005.

PTM databases

PhosphoSite

P55212.

Polymorphism databases

NIEHS-SNPs

Search...

2-D gel databases

OGP

P55212.

Proteomic databases

PeptideAtlas

P55212.

Genome annotation databases

Ensembl

ENSG00000138794. Homo sapiens. [Contig view]

GeneID

839.

KEGG

hsa:839.

Organism-specific databases

H-InvDB

HIX0004436.

HGNC

HGNC:1507. CASP6.

HPA

CAB003775.
HPA011337.

MIM

601532. gene.

PharmGKB

PA26090.

GenAtlas

Search...

GeneCards

Search...

Phylogenomic databases

HOGENOM

P55212.

HOVERGEN

P55212.

Gene expression databases

CleanEx

HS_CASP6.

GermOnline

ENSG00000138794. Homo sapiens.

Family and domain databases

InterPro

IPR015469. Casp6.
IPR011600. Pept_C14_cat.
IPR001309. Pept_C14_ICE_p20.
IPR016129. Pept_C14_ICE_p20_AS.
IPR002138. Pept_C14_p10.
IPR002398. Pept_C14_p45.
IPR015917. Pept_C14_p45_core.
[Graphical view]

PANTHER

PTHR10454:SF29. Casp6. 1 hit.
PTHR10454. Pept_C14_p45. 1 hit.

Pfam

PF00656. Peptidase_C14. 1 hit.
[Graphical view]

PRINTS

PR00376. IL1BCENZYME.

SMART

SM00115. CASc. 1 hit.
[Graphical view]

PROSITE

PS01122. CASPASE_CYS. 1 hit.
PS01121. CASPASE_HIS. 1 hit.
PS50207. CASPASE_P10. 1 hit.
PS50208. CASPASE_P20. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

BindingDB

P55212.

NextBio

3494.

SOURCE

Search...

Entry information

Entry name

CASP6_HUMAN

Accession

Primary (citable) accession number: P55212
Secondary accession number(s): Q9BQE7

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	November 28, 2002
Last modified:	November 25, 2008
This is version 97 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)