[1]	NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ALPHA AND BETA). TISSUE=T-cell; PubMed=7796396 [NCBI, ExPASy, EBI, Israel, Japan] Fernandes-Alnemri T., Litwack G., Alnemri E.S.; "Mch2, a new member of the apoptotic Ced-3/Ice cysteine protease gene family."; Cancer Res. 55:2737-2742(1995).
[2]	NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT SER-182. NIEHS SNPs program; Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases.
[3]	NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA). TISSUE=Lung; DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan] The MGC Project Team; "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."; Genome Res. 14:2121-2127(2004).
[4]	PROTEOLYTIC PROCESSING. TISSUE=Lymphocyte; DOI=10.1074/jbc.271.43.27099; PubMed=8900201 [NCBI, ExPASy, EBI, Israel, Japan] 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.; "The Ced-3/interleukin 1beta converting enzyme-like homolog Mch6 and the lamin-cleaving enzyme Mch2alpha are substrates for the apoptotic mediator CPP32."; J. Biol. Chem. 271:27099-27106(1996).
[5]	ENZYME REGULATION, PHOSPHORYLATION AT SER-257, AND MUTAGENESIS OF SER-257. DOI=10.1038/sj.onc.1207963; PubMed=15273717 [NCBI, ExPASy, EBI, Israel, Japan] Suzuki A., Kusakai G., Kishimoto A., Shimojo Y., Miyamoto S., Ogura T., Ochiai A., Esumi H.; "Regulation of caspase-6 and FLIP by the AMPK family member ARK5."; Oncogene 23:7067-7075(2004).
[6]	IDENTIFICATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY. Colinge J., Superti-Furga G., Bennett K.L.; Submitted (OCT-2008) to UniProtKB.

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: 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.
ALTERNATIVE PRODUCTS: 2 named isoforms [FASTA] produced by alternative splicing.

Name Alpha

Isoform ID P55212-1

This is the isoform sequence displayed in this entry.

Name Beta

Isoform ID P55212-2

Features which should be applied to build the isoform sequence: VSP_000805.
PTM: Cleavages by caspase-3, caspase-8 or -10 generate the two active subunits.
SIMILARITY: Belongs to the peptidase C14A family [view classification].
WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/casp6/";.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

U20536; AAC50168.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
U20537; AAC50169.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AY254046; AAO63494.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
BC000305; AAH00305.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
BC004460; AAH04460.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

IPI

IPI00023876; -.
IPI00217208; -.

RefSeq

NP_001217.2; -.
NP_116787.1; -.

UniGene

Hs.654616

3D structure databases

PDB

1MI9; Model; -; A=34-175, B=198-290.

[ExPASy / RCSB / EBI]

PDBsum

1MI9; -.

ModBase

P55212.

Protein-protein interaction databases

IntAct

P55212; 1.

Protein family/group databases

MEROPS

C14.005; -.

PTM databases

PhosphoSite

P55212; -.

Enzyme and pathway databases

BRENDA

3.4.22.59; 247.

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.

2D gel databases

OGP

P55212; -.

Organism-specific databases

GC04M110829; -.

HIX0004436; -.

HGNC:1507; CASP6.

CAB003775; -.
HPA011337; -.

MIM

601532; gene. [NCBI / EBI]

PharmGKB

PA26090; -.

Gene expression databases

Bgee

P55212; -.

CleanEx

HS_CASP6; -.

GermOnline

ENSG00000138794; Homo sapiens.

Ontologies

GO:0005737;	Cellular component: cytoplasm (inferred from electronic annotation from UniProtKB-SubCell).
GO:0004197;	Molecular function: cysteine-type endopeptidase activity (inferred from electronic annotation from InterPro).
GO:0005515;	Molecular function: protein binding (inferred from physical interaction from UniProtKB).
GO:0006915;	Biological process: apoptosis (inferred from electronic annotation from UniProtKB-KW).
GO:0006917;	Biological process: induction of apoptosis (traceable author statement from ProtInc).
GO:0006508;	Biological process: proteolysis (inferred from direct assay from UniProtKB).
QuickGo view.

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 of domain structure.

PANTHER

PTHR10454:SF29; Casp6; 1.
PTHR10454; Pept_C14_p45; 1.

Pfam

PF00656; Peptidase_C14; 1.
Pfam graphical view of domain structure.

PRINTS

PR00376; IL1BCENZYME.

SMART

SM00115; CASc; 1.
SMART graphical view of domain structure.

PROSITE

PS01122; CASPASE_CYS; 1.
PS01121; CASPASE_HIS; 1.
PS50207; CASPASE_P10; 1.
PS50208; CASPASE_P20; 1.
PROSITE graphical view of domain structure (profiles).

Proteomic databases

PeptideAtlas

P55212; -.

PRIDE

P55212; -.

Genome annotation databases

Ensembl

ENSG00000138794; Homo sapiens. [Contig view]

GeneID

839; -.

KEGG

hsa:839; -.

Phylogenomic databases

HOGENOM

P55212; -.

HOVERGEN

P55212; -.

OMA

P55212; HERFFWH.

Other

P55212; -.

3494; -.

P55212; -.

CASP6; Homo sapiens.

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

3D-structure; Alternative splicing; Apoptosis; Cytoplasm; Hydrolase; Phosphoprotein; Polymorphism; Protease; Thiol protease; Zymogen.

Features

Feature table viewer

Feature aligner

`Key`	`From To`	`Length`	`Description`	`FTId`
`PROPEP`	`1 23`	`23`		`PRO_0000004608`
`CHAIN`	`24 179`	`156`	`Caspase-6 subunit p18.`	`PRO_0000004609`
`PROPEP`	`180 193`	`14`		`PRO_0000004610`
`CHAIN`	`194 293`	`100`	`Caspase-6 subunit p11.`	`PRO_0000004611`
`ACT_SITE`	`121 121`		`By similarity.`
`ACT_SITE`	`163 163`		`By similarity.`
`MOD_RES`	`257 257`		`Phosphoserine.`
`VAR_SEQ`	`14 102`		`Missing (in isoform Beta).`	`VSP_000805`
`VARIANT`	`35 35`	`1`	`E -> K (in dbSNP:rs11574697 [NCBI]).`	`VAR_029242`
`VARIANT`	`109 109`	`1`	`A -> T (in dbSNP:rs5030674 [NCBI]).`	`VAR_016130`
`VARIANT`	`182 182`	`1`	`T -> S (in dbSNP:rs5030593 [NCBI]).`	`VAR_020126`
`MUTAGEN`	`257 257`		`S->A: Suppression of caspase-6 activation.`
`CONFLICT`	`66 66`		`G -> R (in Ref. 1; AAC50168).`
`STRAND`	`46 51`	`6`
`HELIX`	`57 59`	`3`
`HELIX`	`67 80`	`14`
`STRAND`	`84 90`	`7`
`HELIX`	`93 104`	`12`
`STRAND`	`114 120`	`7`
`STRAND`	`130 132`	`3`
`HELIX`	`137 140`	`4`
`HELIX`	`141 143`	`3`
`TURN`	`145 147`	`3`
`HELIX`	`149 151`	`3`
`STRAND`	`156 162`	`7`
`TURN`	`202 205`	`4`
`STRAND`	`207 212`	`6`
`STRAND`	`219 221`	`3`
`TURN`	`222 224`	`3`
`HELIX`	`227 239`	`13`
`TURN`	`240 242`	`3`
`HELIX`	`245 256`	`12`
`HELIX`	`258 261`	`4`
`STRAND`	`262 265`	`4`
`TURN`	`267 269`	`3`
`STRAND`	`277 280`	`4`

Sequence information

Length: 293 AA [This is the length of the unprocessed precursor]

Molecular weight: 33310 Da [This is the MW of the unprocessed precursor]

CRC64: 0738AE4F9791EBD7 [This is a checksum on the sequence]

        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

P55212 in FASTA format

View entry in raw text format (no links)
Report form for errors/updates in this UniProtKB/Swiss-Prot entry

	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools