O35397 (CASP6_RAT) 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

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	277 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript 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 By similarity.
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-240 By similarity.
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 By similarity. Interacts with BIRC6/bruce By similarity.
Subcellular location	Cytoplasm By similarity.
Post-translational modification	Cleavages by caspase-3, caspase-8 or -10 generate the two active subunits By similarity.
Sequence similarities	Belongs to the peptidase C14A family.

Ontologies

Keywords
Biological process	Apoptosis
Cellular component	Cytoplasm
Molecular function	Hydrolase Protease Thiol protease
PTM	Phosphoprotein Zymogen
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	acute inflammatory response to non-antigenic stimulus Inferred from direct assay PubMed 18175566. Source: RGD apoptotic process Traceable author statement PubMed 12127146. Source: RGD lens development in camera-type eye Inferred from expression pattern PubMed 15161922. Source: RGD positive regulation of neuron apoptotic process Inferred from mutant phenotype PubMed 11433428. Source: RGD positive regulation of retinal cell programmed cell death Inferred from mutant phenotype PubMed 12917395. Source: RGD proteolysis Inferred from electronic annotation. Source: UniProtKB-KW response to cytokine stimulus Inferred from direct assay PubMed 15201138. Source: RGD response to estradiol stimulus Inferred from expression pattern PubMed 12967350. Source: RGD response to gamma radiation Inferred from expression pattern PubMed 10590178. Source: RGD response to glucose stimulus Inferred from mutant phenotype PubMed 12606487. Source: RGD response to heat Inferred from expression pattern PubMed 12810573. Source: RGD response to hydrogen peroxide Inferred from direct assay PubMed 17571084. Source: RGD response to iron ion Inferred from mutant phenotype PubMed 17571084. Source: RGD response to organic nitrogen Inferred from expression pattern PubMed 12538628. Source: RGD response to testosterone stimulus Inferred from expression pattern PubMed 12724284. Source: RGD
Cellular_component	cytosol Inferred from direct assay PubMed 15201138. Source: RGD nucleus Inferred from direct assay PubMed 18175566. Source: RGD
Molecular_function	cysteine-type endopeptidase activity Inferred from electronic annotation. Source: InterPro endopeptidase activity Inferred from direct assay PubMed 12081569. Source: RGD
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Propeptide	1 – 5	5	By similarity		PRO_0000233177
	Chain	6 – 162	157	Caspase-6 subunit p18 By similarity		PRO_0000233178
	Propeptide	163 – 177	15	By similarity		PRO_0000233179
	Chain	178 – 277	100	Caspase-6 subunit p11 By similarity		PRO_0000233180
Sites
	Active site	104	1	By similarity
	Active site	146	1	By similarity
Amino acid modifications
	Modified residue	240	1	Phosphoserine; by NUAK1 By similarity

Sequences

	Sequence		Length	Mass (Da)
	O35397 [UniParc]. Last modified November 1, 1998. Version 2. Checksum: 69D999E729B3BDE2	FASTA	277	31,556
	10 20 30 40 50 60 MTETDGFYRS REVLDPAEQY KMDHKRRGTA LIFNHERFFW HLALPERRGT NADRDNPTRR 70 80 90 100 110 120 FSELGFEVKC FNDLRAEELL LKIHEVSTSS HVDADCFLCV FLSHGEGNHI YAYDAKIEIQ 130 140 150 160 170 180 TLTGLFKGDK CQSLVGKPKI FIIQACRGSQ HDVPLVPLDV VDHQTDKLDD NVTQVDAASV 190 200 210 220 230 240 YTLPAGADFL MCYSVAEGYY SHRETVNGSW YIQDLSEMLA RHGSSLEFTE LLTLVNRKVS 250 260 270 QRRVDFCKDP GAIGKKQVPC FASMLTKKLH FCPKPSK

References

[1]	"Identification of gene family of caspases in rat kidney and altered expression in ischemia-reperfusion injury." Kaushal G.P., Singh A.B., Shah S.V. Am. J. Physiol. 274:F587-F595(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Sprague-Dawley. Tissue: Kidney cortex.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF025670 mRNA. Translation: AAC25433.1.
IPI	IPI00464786.
UniGene	Rn.88160.
3D structure databases
ProteinModelPortal	O35397.
ModBase	Search...
Protein-protein interaction databases
STRING	10116.ENSRNOP00000013049.
Protein family/group databases
MEROPS	C14.005.
PTM databases
PhosphoSite	O35397.
Proteomic databases
PRIDE	O35397.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
UCSC	RGD:70967. rat.
Organism-specific databases
RGD	70967. Casp6.
Phylogenomic databases
eggNOG	NOG278720.
HOGENOM	HOG000231878.
HOVERGEN	HBG050802.
InParanoid	O35397.
OrthoDB	EOG4MKNGQ.
Gene expression databases
ArrayExpress	O35397.
Genevestigator	O35397.
GermOnline	ENSRNOG00000009508. Rattus norvegicus.
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...

Entry information

Entry name

CASP6_RAT

Accession

Primary (citable) accession number: O35397

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 2, 2006
Last sequence update:	November 1, 1998
Last modified:	April 3, 2013
This is version 85 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program