P55212 (CASP6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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. Caspase-6 subunit p18
2. Caspase-6 subunit p11

Gene names

Name:	CASP6
Synonyms:	MCH2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › 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. Ref.6
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. Interacts with BIRC6/bruce. Ref.5
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 C14A 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 Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular component disassembly involved in execution phase of apoptosis Traceable author statement. Source: Reactome induction of apoptosis Traceable author statement Ref.1. Source: ProtInc proteolysis Inferred from direct assay PubMed 12888622. Source: UniProtKB
Cellular_component	cytosol Inferred from direct assay PubMed 17167422. Source: UniProtKB nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	cysteine-type endopeptidase activity Traceable author statement. Source: Reactome
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
SATB1	Q01826	2	EBI-718729,EBI-743747

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; by NUAK1 Ref.6

Natural variations

Alternative sequence

14 – 102

89

Missing in isoform Beta.

VSP_000805

Natural variant

35

1

E → K.
Corresponds to variant rs11574697 [ dbSNP | Ensembl ].

VAR_029242

Natural variant

109

1

A → T.
Corresponds to variant rs5030674 [ dbSNP | Ensembl ].

VAR_016130

Natural variant

182

1

T → S. Ref.2
Corresponds to variant rs5030593 [ dbSNP | Ensembl ].

VAR_020126

Experimental info

Mutagenesis

257

1

S → A: Suppression of caspase-6 activation. Ref.6

Sequence conflict

66

1

G → R in AAC50168. Ref.1

Secondary structure

1

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293

Helix Strand Turn

Details...

Beta strand

41 – 43

3

Beta strand

46 – 51

6

Helix

57 – 59

3

Helix

67 – 80

14

Beta strand

84 – 90

7

Helix

93 – 105

13

Beta strand

114 – 120

7

Beta strand

126 – 128

3

Beta strand

130 – 135

6

Helix

136 – 141

6

Turn

145 – 147

3

Helix

149 – 151

3

Beta strand

156 – 162

7

Beta strand

165 – 167

3

Beta strand

190 – 194

5

Beta strand

197 – 199

3

Turn

202 – 205

4

Beta strand

206 – 212

7

Beta strand

219 – 221

3

Turn

222 – 224

3

Helix

227 – 239

13

Turn

240 – 242

3

Helix

245 – 258

14

Turn

263 – 265

3

Helix

267 – 269

3

Beta strand

271 – 273

3

Beta strand

277 – 280

4

Beta strand

283 – 285

3

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	FASTA	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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ALPHA AND BETA). Tissue: T-cell.
[2]	NIEHS SNPs program Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT SER-182.
[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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: PROTEOLYTIC PROCESSING. Tissue: Lymphocyte.
[5]	"Dual role of BRUCE as an antiapoptotic IAP and a chimeric E2/E3 ubiquitin ligase." Bartke T., Pohl C., Pyrowolakis G., Jentsch S. Mol. Cell 14:801-811(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH BIRC6/BRUCE.
[6]	"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] [Europe PMC] [Abstract] Cited for: ENZYME REGULATION, PHOSPHORYLATION AT SER-257, MUTAGENESIS OF SER-257.
[7]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

IPI

IPI00023876.
IPI00217208.

RefSeq

NP_001217.2. NM_001226.3.
NP_116787.1. NM_032992.2.

UniGene

Hs.654616.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1MI9	model	-	A	34-175	[»]
			B	198-290	[»]
2WDP	X-ray	1.95	A/B/C/D	1-293	[»]
3K7E	X-ray	3.00	A/B/C/D	24-293	[»]
3NKF	X-ray	2.90	A/B/C/D	24-293	[»]
3NR2	X-ray	2.90	A/B	24-293	[»]
3OD5	X-ray	1.60	A/B	24-293	[»]
3P45	X-ray	2.53	A/C/E/G/I/K/M/O	1-179	[»]
			B/D/F/H/J/L/N/P	193-293	[»]
3P4U	X-ray	1.90	A/C	23-179	[»]
			B/D	193-293	[»]
3QNW	X-ray	2.65	A/C/E/G	24-179	[»]
			B/D/F/H	194-293	[»]
3S70	X-ray	1.62	A/C	24-293	[»]
3S8E	X-ray	2.88	A/B/C/D/E/F/G/H	24-293	[»]
3V6L	X-ray	2.20	A/B	21-293	[»]
3V6M	X-ray	2.69	A/B/C/D/F/G/I/J	24-293	[»]
4EJF	X-ray	2.65	A/B/C/D	24-293	[»]
4FXO	X-ray	2.85	A/B/C/D	1-293	[»]

ProteinModelPortal

P55212.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-44649N.

IntAct

P55212. 4 interactions.

MINT

MINT-1374245.

STRING

9606.ENSP00000265164.

Protein family/group databases

MEROPS

C14.005.

PTM databases

PhosphoSite

P55212.

Polymorphism databases

DMDM

26006981.

2D gel databases

OGP

P55212.

Proteomic databases

PaxDb

P55212.

PeptideAtlas

P55212.

PRIDE

P55212.

Protocols and materials databases

DNASU

839.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000265164; ENSP00000265164; ENSG00000138794.
ENST00000352981; ENSP00000285333; ENSG00000138794.

GeneID

839.

KEGG

hsa:839.

UCSC

uc003hzn.1. human.
uc003hzo.1. human.

Organism-specific databases

CTD

839.

GeneCards

GC04M110609.

HGNC

HGNC:1507. CASP6.

HPA

CAB003775.
HPA011337.
HPA024303.

MIM

601532. gene.

neXtProt

NX_P55212.

PharmGKB

PA26090.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG278720.

HOGENOM

HOG000231878.

HOVERGEN

HBG050802.

InParanoid

P55212.

KO

K04396.

OMA

DFCKDPS.

PhylomeDB

P55212.

Enzyme and pathway databases

BRENDA

3.4.22.59. 2681.

Pathway_Interaction_DB

caspase_pathway. Caspase cascade in apoptosis.
faspathway. FAS signaling pathway (CD95).
hivnefpathway. HIV-1 Nef: Negative effector of Fas and TNF-alpha.
p75ntrpathway. p75(NTR)-mediated signaling.

Reactome

REACT_578. Apoptosis.

Gene expression databases

ArrayExpress

P55212.

Bgee

P55212.

CleanEx

HS_CASP6.

Genevestigator

P55212.

GermOnline

ENSG00000138794. Homo sapiens.

Family and domain databases

InterPro

IPR015469. Caspase_6.
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. PTHR10454. 1 hit.
PTHR10454:SF29. PTHR10454:SF29. 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

BindingDB

P55212.

ChEMBL

CHEMBL3308.

ChiTaRS

CASP6. human.

EvolutionaryTrace

P55212.

GenomeRNAi

839.

NextBio

3494.

PMAP-CutDB

P55212.

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:	May 1, 2013
This is version 145 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.