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Protein

Caspase-1

Gene

Casp1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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). Upon inflammasome activation, during DNA virus infection but not RNA virus challenge, controls antiviral immunity through the cleavage of MB21D1/cGAS, rendering it inactive (PubMed:28314590).By similarity1 Publication

Catalytic activityi

Strict requirement for an Asp residue at position P1 and has a preferred cleavage sequence of Tyr-Val-Ala-Asp-|-.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei236By similarity1
Active sitei284By similarity1

GO - Molecular functioni

GO - Biological processi

  • cellular response to interferon-gamma Source: MGI
  • cellular response to lipopolysaccharide Source: MGI
  • cellular response to mechanical stimulus Source: Ensembl
  • cellular response to organic substance Source: MGI
  • interleukin-1 beta production Source: MGI
  • membrane hyperpolarization Source: MGI
  • mitochondrial depolarization Source: MGI
  • positive regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: Ensembl
  • positive regulation of cytokine secretion Source: MGI
  • positive regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
  • positive regulation of interleukin-1 alpha secretion Source: MGI
  • positive regulation of interleukin-1 beta secretion Source: MGI
  • positive regulation of tumor necrosis factor-mediated signaling pathway Source: Ensembl
  • programmed necrotic cell death Source: MGI
  • protein autoprocessing Source: Ensembl
  • protein processing Source: MGI
  • proteolysis Source: MGI
  • pyroptosis Source: MGI
  • regulation of autophagy Source: MGI
  • regulation of inflammatory response Source: MGI
  • response to ATP Source: MGI
  • response to bacterium Source: MGI
  • response to hypoxia Source: MGI
  • response to lipopolysaccharide Source: MGI
  • toxin transport Source: MGI

Keywordsi

Molecular functionHydrolase, Protease, Thiol protease
Biological processApoptosis

Enzyme and pathway databases

BRENDAi3.4.22.36. 3474.
ReactomeiR-MMU-448706. Interleukin-1 processing.
R-MMU-844615. The AIM2 inflammasome.

Protein family/group databases

MEROPSiC14.001.

Names & Taxonomyi

Protein namesi
Recommended name:
Caspase-1 (EC:3.4.22.36)
Short name:
CASP-1
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:
Gene namesi
Name:Casp1
Synonyms:Il1bc
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 9

Organism-specific databases

MGIiMGI:96544. Casp1.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Disruption phenotypei

Mutants are resitant to vaccinia virus (VACV) but not vesicular somatitis virus (VSV) infection. They show lower viral loads in the lungs compared to wild type mice, they produce higher levels of type I IFN, IL6 and RSAD2/Viperin after VCAV INFECTION.1 Publication

Chemistry databases

ChEMBLiCHEMBL4800.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
PropeptideiPRO_00000045251 – ?118Sequence analysisAdd BLAST118
ChainiPRO_0000004526?119 – 296Caspase-1 subunit p20Add BLAST178
PropeptideiPRO_0000004527297 – 314Sequence analysisAdd BLAST18
ChainiPRO_0000004528315 – 402Caspase-1 subunit p10Add BLAST88

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei301PhosphoserineCombined sources1
Modified residuei343Omega-N-methylarginineCombined sources1

Post-translational modificationi

The two subunits are derived from the precursor sequence by a autocatalytic mechanism.

Keywords - PTMi

Methylation, Phosphoprotein, Zymogen

Proteomic databases

EPDiP29452.
MaxQBiP29452.
PaxDbiP29452.
PeptideAtlasiP29452.
PRIDEiP29452.

PTM databases

iPTMnetiP29452.
PhosphoSitePlusiP29452.

Expressioni

Tissue specificityi

High level expression seen in spleen and lung, low level expression seen in brain, heart, liver, kidney, testis and skeletal muscle.

Gene expression databases

BgeeiENSMUSG00000025888.
CleanExiMM_CASP1.
GenevisibleiP29452. MM.

Interactioni

Subunit structurei

Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 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. Both the p20 and p10 subunits interact with MEFV (By similarity). Interacts with CARD17/INCA and CARD18 (By similarity).By similarity

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi198492. 2 interactors.
DIPiDIP-34659N.
IntActiP29452. 5 interactors.
STRINGi10090.ENSMUSP00000027015.

Chemistry databases

BindingDBiP29452.

Structurei

3D structure databases

ProteinModelPortaliP29452.
SMRiP29452.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1 – 91CARDPROSITE-ProRule annotationAdd BLAST91

Sequence similaritiesi

Belongs to the peptidase C14A family.Curated

Phylogenomic databases

eggNOGiKOG3573. Eukaryota.
ENOG410ZQIE. LUCA.
GeneTreeiENSGT00760000118912.
HOGENOMiHOG000234399.
HOVERGENiHBG076981.
InParanoidiP29452.
KOiK01370.
OMAiEYAWSCD.
OrthoDBiEOG091G07NO.
PhylomeDBiP29452.
TreeFamiTF102023.

Family and domain databases

CDDicd00032. CASc. 1 hit.
InterProiView protein in InterPro
IPR001315. CARD.
IPR029030. Caspase-like_dom.
IPR033139. Caspase_cys_AS.
IPR016129. Caspase_his_AS.
IPR011029. DEATH-like_dom.
IPR002138. Pept_C14_p10.
IPR001309. Pept_C14_p20.
IPR015917. Pept_C14A.
PfamiView protein in Pfam
PF00619. CARD. 1 hit.
PRINTSiPR00376. IL1BCENZYME.
SMARTiView protein in SMART
SM00114. CARD. 1 hit.
SM00115. CASc. 1 hit.
SUPFAMiSSF47986. SSF47986. 1 hit.
SSF52129. SSF52129. 1 hit.
PROSITEiView protein in 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.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P29452-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MADKILRAKR KQFINSVSIG TINGLLDELL EKRVLNQEEM DKIKLANITA
60 70 80 90 100
MDKARDLCDH VSKKGPQASQ IFITYICNED CYLAGILELQ SAPSAETFVA
110 120 130 140 150
TEDSKGGHPS SSETKEEQNK EDGTFPGLTG TLKFCPLEKA QKLWKENPSE
160 170 180 190 200
IYPIMNTTTR TRLALIICNT EFQHLSPRVG AQVDLREMKL LLEDLGYTVK
210 220 230 240 250
VKENLTALEM VKEVKEFAAC PEHKTSDSTF LVFMSHGIQE GICGTTYSNE
260 270 280 290 300
VSDILKVDTI FQMMNTLKCP SLKDKPKVII IQACRGEKQG VVLLKDSVRD
310 320 330 340 350
SEEDFLTDAI FEDDGIKKAH IEKDFIAFCS STPDNVSWRH PVRGSLFIES
360 370 380 390 400
LIKHMKEYAW SCDLEDIFRK VRFSFEQPEF RLQMPTADRV TLTKRFYLFP

GH
Length:402
Mass (Da):45,640
Last modified:April 1, 1993 - v1
Checksum:i3BEBCEFA67C69B03
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti3 – 6DKIL → V in AAA56992 (PubMed:8034321).Curated4

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L03799 mRNA. Translation: AAA39306.1.
L28095 mRNA. Translation: AAA20209.1.
U04269 Genomic DNA. Translation: AAA56992.1.
BC008152 mRNA. Translation: AAH08152.1.
CCDSiCCDS22798.1.
PIRiA46495.
RefSeqiNP_033937.2. NM_009807.2.
UniGeneiMm.1051.

Genome annotation databases

EnsembliENSMUST00000027015; ENSMUSP00000027015; ENSMUSG00000025888.
GeneIDi12362.
KEGGimmu:12362.
UCSCiuc009obr.1. mouse.

Similar proteinsi

Entry informationi

Entry nameiCASP1_MOUSE
AccessioniPrimary (citable) accession number: P29452
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: April 1, 1993
Last modified: September 27, 2017
This is version 172 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. SIMILARITY comments
    Index of protein domains and families