P43527 (CASP1_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Caspase-1
Short name=CASP-1
EC=3.4.22.36

Alternative name(s):
Interleukin-1 beta convertase
Short name=IL-1BC
Interleukin-1 beta-converting enzyme
Short name=ICE
Short name=IL-1 beta-converting enzyme
p45

Cleaved into the following 2 chains:

1. Caspase-1 subunit p20
2. Caspase-1 subunit p10

Gene names

Name:	Casp1
Synonyms:	Il1bc, Il1bce

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	402 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	Thiol protease that cleaves IL-1 beta between an Asp and an Ala, releasing the mature cytokine which is involved in a variety of inflammatory processes. Important for defense against pathogens. Cleaves and activates sterol regulatory element binding proteins (SREBPs). Can also promote apoptosis By similarity.
Catalytic activity	Strict requirement for an Asp residue at position P1 and has a preferred cleavage sequence of Tyr-Val-Ala-Asp-|-.
Subunit structure	Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed bya 20 kDa (p20) and a 10 kDa (p10) subunit. The p20 subunit can also form a heterodimer with the epsilon isoform which then has an inhibitory effect. May be a component of the inflammasome, a protein complex which also includes PYCARD, CARD8 and NALP2 and whose function would be the activation of proinflammatory caspases. Interacts with CARD17/INCA and CARD18 By similarity.
Subcellular location	Cytoplasm.
Post-translational modification	The two subunits are derived from the precursor sequence by a autocatalytic mechanism.
Sequence similarities	Belongs to the peptidase C14A family. Contains 1 CARD domain.

Ontologies

Keywords
Biological process	Apoptosis
Cellular component	Cytoplasm
Molecular function	Hydrolase Protease Thiol protease
PTM	Zymogen
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic process Inferred from expression pattern PubMed 11404793. Source: RGD lung development Inferred from expression pattern PubMed 12396474. Source: RGD memory Inferred from mutant phenotype PubMed 16197515. Source: RGD microglial cell activation Inferred from mutant phenotype PubMed 15149850. Source: RGD midgut development Inferred from expression pattern PubMed 12396474. Source: RGD myoblast fusion Inferred from mutant phenotype PubMed 12832042. Source: RGD positive regulation of apoptotic process Inferred from mutant phenotype PubMed 15663890. Source: RGD positive regulation of circadian sleep/wake cycle, non-REM sleep Inferred from mutant phenotype PubMed 16455762. Source: RGD positive regulation of interleukin-1 beta secretion Inferred from mutant phenotype PubMed 16942597. Source: RGD proteolysis Inferred from electronic annotation. Source: UniProtKB-KW response to drug Inferred from direct assay PubMed 16165281. Source: RGD response to hypoxia Inferred from direct assay PubMed 12829320. Source: RGD response to lipopolysaccharide Inferred from mutant phenotype PubMed 17384935. Source: RGD response to organic cyclic compound Inferred from direct assay PubMed 17561093. Source: RGD response to toxin Inferred from expression pattern PubMed 20638366. Source: RGD
Cellular_component	AIM2 inflammasome complex Inferred from sequence or structural similarity. Source: UniProtKB IPAF inflammasome complex Inferred from sequence or structural similarity. Source: UniProtKB NLRP1 inflammasome complex Inferred from sequence or structural similarity. Source: UniProtKB NLRP3 inflammasome complex Inferred from sequence or structural similarity. Source: UniProtKB cytoplasm Inferred from direct assay PubMed 18367607PubMed 19401709. Source: RGD neuron projection Inferred from direct assay PubMed 19401709. Source: RGD nucleus Inferred from direct assay PubMed 18367607. Source: RGD
Molecular_function	cysteine-type endopeptidase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Propeptide	1 – ?118	118	Potential		PRO_0000004533
	Chain	?119 – 296	178	Caspase-1 subunit p20		PRO_0000004534
	Propeptide	297 – 314	18	Potential		PRO_0000004535
	Chain	315 – 402	88	Caspase-1 subunit p10		PRO_0000004536
Regions
	Domain	1 – 91	91	CARD
Sites
	Active site	236	1	By similarity
	Active site	284	1	By similarity
Experimental info
	Sequence conflict	252	1	A → G in AAC52259. Ref.2
	Sequence conflict	252	1	A → G in AAB35431. Ref.2
	Sequence conflict	256	1	K → E in AAC52259. Ref.2
	Sequence conflict	256	1	K → E in AAB35431. Ref.2
	Sequence conflict	260	1	I → L in AAC52259. Ref.2
	Sequence conflict	260	1	I → L in AAB35431. Ref.2
	Sequence conflict	262	1	Q → H in AAC52259. Ref.2
	Sequence conflict	262	1	Q → H in AAB35431. Ref.2
	Sequence conflict	343	1	R → Q in AAC52259. Ref.2
	Sequence conflict	343	1	R → Q in AAB35431. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P43527 [UniParc]. Last modified November 1, 1995. Version 1. Checksum: D2E8FA2BEA76FD40	FASTA	402	45,576
	10 20 30 40 50 60 MADKVLRAKR KQFINSVSVG TINGLLDELL EKRVLNQEEM DTIKLANITV MEKARDLCDH 70 80 90 100 110 120 VTKKGPRASQ MFITYICNED CYLAEILELQ SGPSAETVFV TEDSKGGHPF SSETKEKLNK 130 140 150 160 170 180 EGGAFPGPSG SLKFCPLEIA QKLWKENHSE IYPIMKTPTR TRLALIICNT DFQHLSRRVG 190 200 210 220 230 240 ADVDLREMKL LLQDLGYTVK VKENLTALEM TKELKEFAAC PEHKTSDSTF LVFMSHGLQE 250 260 270 280 290 300 GICGITYSNE VADILKVDTI FQMMNTLKCP SLKDKPKVII IQACRGEKQG VVLLKDSVGN 310 320 330 340 350 360 SEEGFLTDAI FEDDGIKKAH IEKDFIAFCS STPDNVSWRH PVRGSLFIES LIKHMKEYAW 370 380 390 400 SCDLEDIFRK VRFSFEQPDS RLQMPTTERV TLTKRFYLFP GH

References

[1]	"Cloning, tissue expression and regulation of rat interleukin 1 beta converting enzyme." Keane K.M., Giegel D.A., Lipinski W.J., Callahan M.J., Shivers B.D. Cytokine 7:105-110(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Spleen.
[2]	"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 228-362. Tissue: Ovary.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U14647 mRNA. Translation: AAA85812.1. U34621 mRNA. Translation: AAC52259.1. S79676 mRNA. Translation: AAB35431.1.
IPI	IPI00201423.
UniGene	Rn.37508.
3D structure databases
ProteinModelPortal	P43527.
SMR	P43527. Positions 2-90, 127-296, 315-402.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-29840N.
STRING	10116.ENSRNOP00000009993.
Protein family/group databases
MEROPS	C14.001.
Proteomic databases
PaxDb	P43527.
PRIDE	P43527.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
UCSC	RGD:2274. rat.
Organism-specific databases
RGD	2274. Casp1.
Phylogenomic databases
eggNOG	NOG326166.
HOGENOM	HOG000234399.
HOVERGEN	HBG076981.
InParanoid	P43527.
OrthoDB	EOG49W2FS.
Enzyme and pathway databases
BRENDA	3.4.22.36. 5301.
Gene expression databases
ArrayExpress	P43527.
Genevestigator	P43527.
GermOnline	ENSRNOG00000007372. 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...

Entry information

Entry name

CASP1_RAT

Accession

Primary (citable) accession number: P43527

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	November 1, 1995
Last modified:	April 3, 2013
This is version 104 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program