P55215 (CASP2_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Caspase-2
Short name=CASP-2
EC=3.4.22.55

Alternative name(s):
Protease ICH-1

Cleaved into the following 3 chains:

1. Caspase-2 subunit p18
2. Caspase-2 subunit p13
3. Caspase-2 subunit p12

Gene names

Name:	Casp2
Synonyms:	Ich1

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	452 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. Might function by either activating some proteins required for cell death or inactivating proteins necessary for cell survival By similarity.
Catalytic activity	Strict requirement for an Asp residue at P1, with 316-asp being essential for proteolytic activity and has a preferred cleavage sequence of Val-Asp-Val-Ala-Asp-|-.
Subunit structure	Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a p18 subunit and a p12 subunit. Interacts with LRDD By similarity.
Post-translational modification	The mature protease can process its own propeptide, but not that of other caspases By similarity.
Sequence similarities	Belongs to the peptidase C14A family. Contains 1 CARD domain.
Sequence caution	The sequence AAB82567.1 differs from that shown. Reason: Frameshift at positions 137 and 189.

Ontologies

Keywords
Biological process	Apoptosis
Coding sequence diversity	Alternative splicing
Molecular function	Hydrolase Protease Thiol protease
PTM	Phosphoprotein Zymogen
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest Inferred from electronic annotation. Source: Compara aging Inferred from expression pattern PubMed 12175478. Source: RGD apoptotic process Inferred from mutant phenotype PubMed 18614702. Source: RGD brain development Inferred from expression pattern PubMed 11741299. Source: RGD cellular response to mechanical stimulus Inferred from electronic annotation. Source: Compara induction of apoptosis Inferred from electronic annotation. Source: Compara luteolysis Inferred from expression pattern PubMed 16940287. Source: RGD neural retina development Inferred from expression pattern PubMed 9809666. Source: RGD positive regulation of neuron apoptotic process Inferred from mutant phenotype Ref.2. Source: RGD protein processing Inferred from electronic annotation. Source: Compara proteolysis Traceable author statement Ref.1. Source: RGD
Cellular_component	membrane Inferred from direct assay PubMed 16123172. Source: RGD mitochondrion Inferred from direct assay PubMed 11716979. Source: RGD nucleus Inferred from electronic annotation. Source: Compara
Molecular_function	cysteine-type endopeptidase activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: P55215-1)

Also known as: caspase-2L;

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 2 (identifier: P55215-2)

Also known as: caspase-2S;

The sequence of this isoform differs from the canonical sequence as follows:
     323-343: DETDRGVDQQDGKNHAQSPGC → GAIGSLGPLLLFTAATASLAL
     344-452: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Propeptide	1 – 169	169			PRO_0000043403
	Chain	170 – 325	156	Caspase-2 subunit p18 By similarity		PRO_0000044573
	Propeptide	326 – 333	8			PRO_0000044574
	Chain	334 – 452	119	Caspase-2 subunit p13 By similarity		PRO_0000004551
	Chain	348 – 452	105	Caspase-2 subunit p12 By similarity		PRO_0000004552
Regions
	Domain	32 – 121	90	CARD
Sites
	Active site	277	1	By similarity
	Active site	320	1	By similarity
Amino acid modifications
	Modified residue	340	1	Phosphoserine By similarity
Natural variations
	Alternative sequence	323 – 343	21	DETDR…QSPGC → GAIGSLGPLLLFTAATASLA L in isoform 2.		VSP_016555
	Alternative sequence	344 – 452	109	Missing in isoform 2.		VSP_016556
Experimental info
	Sequence conflict	145	1	C → Y in AAB82567. Ref.3
	Sequence conflict	166	1	D → H in AAB82567. Ref.3
	Sequence conflict	177	1	K → E in AAB82567. Ref.3
	Sequence conflict	197	1	Q → R in AAB82567. Ref.3
	Sequence conflict	340	1	S → P in AAC52260. Ref.4
	Sequence conflict	348 – 349	2	AG → TV in AAC52260. Ref.4
	Sequence conflict	367	1	G → V in AAC52260. Ref.4
	Sequence conflict	373	1	G → D in AAC52260. Ref.4
	Sequence conflict	376 – 377	2	AM → PI in AAC52260. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (caspase-2L) [UniParc]. Last modified December 6, 2005. Version 3. Checksum: 03F9D096BB741CE3	FASTA	452	50,728
	10 20 30 40 50 60 MAASSGRSQS SLHRKGLMAA DRRSRILAVC GMHPDHQETL KKNRVVLAKQ LLLSELLEHL 70 80 90 100 110 120 LEKDIITLEM RELIQAKGGS FSQNVELLNL LPKRGPQAFD AFCEALRETR QGHLEDLLLT 130 140 150 160 170 180 TLSDIQHILP PLSCDYDSSL PFSVCESCPP HKQSRLSTDT MEHSLDNGDG PPCLQVKPCT 190 200 210 220 230 240 PEFYQAHYQL AYRLQSQPRG LALVMSNVHF TGEKDLEFRS GGDVDHTTLV TLFKLLGYNV 250 260 270 280 290 300 HVLYDQTAQE MQEKLQNFAQ LPAHRVTDSC IVALLSHGVE GGIYGVDGKL LQLQEVFRLF 310 320 330 340 350 360 DNANCPSLQN KPKMFFIQAC RGDETDRGVD QQDGKNHAQS PGCEESDAGK EELMKMRLPT 370 380 390 400 410 420 RSDMICGYAC LKGNAAMRNT KRGSWYIEAL TQVFSERACD MHVADMLVKV NALIKEREGY 430 440 450 APGTEFHRCK EMSEYCSTLC QQLYLFPGYP PT
	Isoform 2 (caspase-2S) [UniParc]. Checksum: 0292D6130C63F641	FASTA	343	38,004
	10 20 30 40 50 60 MAASSGRSQS SLHRKGLMAA DRRSRILAVC GMHPDHQETL KKNRVVLAKQ LLLSELLEHL 70 80 90 100 110 120 LEKDIITLEM RELIQAKGGS FSQNVELLNL LPKRGPQAFD AFCEALRETR QGHLEDLLLT 130 140 150 160 170 180 TLSDIQHILP PLSCDYDSSL PFSVCESCPP HKQSRLSTDT MEHSLDNGDG PPCLQVKPCT 190 200 210 220 230 240 PEFYQAHYQL AYRLQSQPRG LALVMSNVHF TGEKDLEFRS GGDVDHTTLV TLFKLLGYNV 250 260 270 280 290 300 HVLYDQTAQE MQEKLQNFAQ LPAHRVTDSC IVALLSHGVE GGIYGVDGKL LQLQEVFRLF 310 320 330 340 DNANCPSLQN KPKMFFIQAC RGGAIGSLGP LLLFTAATAS LAL

References

[1]	"Cloning and expression of the cDNA encoding rat caspase-2." Sato N., Milligan C.E., Uchiyama Y., Oppenheim R.W. Gene 202:127-132(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Two caspase-2 transcripts are expressed in rat hippocampus after global cerebral ischemia." Jin K., Nagayama T., Mao X., Kawaguchi K., Hickey R.W., Greenberg D.A., Simon R.P., Graham S.H. J. Neurochem. 81:25-35(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2). Strain: Sprague-Dawley. Tissue: Brain.
[3]	"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] OF 67-324. Strain: Sprague-Dawley. Tissue: Kidney cortex.
[4]	"Interleukin-1 beta-converting enzyme-related proteases (IRPs) and mammalian cell death: dissociation of IRP-induced oligonucleosomal endonuclease activity from morphological apoptosis in granulosa cells of the ovarian follicle." Flaws J.A., Kugu K., Trbovich A.M., Desanti A., Tilly K.I., Hirshfield A.N., Tilly J.L. Endocrinology 136:5042-5053(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 198-379. Tissue: Ovary.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U77933 mRNA. Translation: AAB96379.1. AF136231 mRNA. Translation: AAD33684.1. AF136232 mRNA. Translation: AAD33685.1. AF025671 mRNA. Translation: AAB82567.1. Frameshift. U34684 mRNA. Translation: AAC52260.1.
IPI	IPI00196055. IPI00325993.
PIR	I67436. JC6507.
RefSeq	NP_071967.2. NM_022522.2.
UniGene	Rn.1438.
3D structure databases
ProteinModelPortal	P55215.
SMR	P55215. Positions 173-333, 355-452.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-48602N.
STRING	10116.ENSRNOP00000022672.
Protein family/group databases
MEROPS	C14.006.
PTM databases
PhosphoSite	P55215.
Proteomic databases
PaxDb	P55215.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000022672; ENSRNOP00000022672; ENSRNOG00000016707.
GeneID	64314.
KEGG	rno:64314.
UCSC	RGD:69274. rat.
Organism-specific databases
CTD	835.
RGD	69274. Casp2.
Phylogenomic databases
eggNOG	NOG305976.
GeneTree	ENSGT00700000104134.
HOGENOM	HOG000290714.
HOVERGEN	HBG103962.
InParanoid	P55215.
KO	K02186.
OMA	PCLQVKP.
OrthoDB	EOG4WDDBP.
Enzyme and pathway databases
BRENDA	3.4.22.55. 5301.
Gene expression databases
ArrayExpress	P55215.
Genevestigator	P55215.
GermOnline	ENSRNOG00000016707. Rattus norvegicus.
Family and domain databases
Gene3D	1.10.533.10. 1 hit.
InterPro	IPR001315. CARD. IPR017350. Caspase_IL-1_beta. IPR011029. DEATH-like_dom. 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.
Pfam	PF00619. CARD. 1 hit. PF00656. Peptidase_C14. 1 hit. [Graphical view]
PIRSF	PIRSF038001. Caspase_ICE. 1 hit.
PRINTS	PR00376. IL1BCENZYME.
SMART	SM00114. CARD. 1 hit. SM00115. CASc. 1 hit. [Graphical view]
SUPFAM	SSF47986. DEATH_like. 1 hit.
PROSITE	PS50209. CARD. 1 hit. 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
NextBio	612988.

Entry information

Entry name

CASP2_RAT

Accession

Primary (citable) accession number: P55215
Secondary accession number(s): O35398, O55194, Q9WUI6

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	December 6, 2005
Last modified:	April 3, 2013
This is version 115 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program