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UniProtKB/Swiss-Prot entry P29466


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name CASP1_HUMAN
Primary accession number P29466
Secondary accession numbers Q53EY6 Q6DMQ1 Q6GSS3 Q6PI75 Q9UCN3
Integrated into Swiss-Prot on April 1, 1993
Sequence was last modified on April 1, 1993 (Sequence version 1)
Annotations were last modified on    July 22, 2008 (Entry version 101)
Name and origin of the protein
Protein name Caspase-1 [Precursor]
Synonyms CASP-1
EC 3.4.22.36
Interleukin-1 beta convertase
IL-1BC
Interleukin-1 beta-converting enzyme
IL-1 beta-converting enzyme
ICE
p45
Contains Caspase-1 subunit p20
Caspase-1 subunit p10
Gene name
Name: CASP1
Synonyms: IL1BC, IL1BCE
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, AND ACTIVE SITE.
DOI=10.1038/356768a0; PubMed=1574116 [NCBI, ExPASy, EBI, Israel, Japan]
Thornberry N.A., Bull H.G., Calaycay J.R., Chapman K.T., Howard A.D., Kostura M.J., Miller D.K., Molineaux S.M., Weidner J.R., Aunins J., Elliston K.O., Ayala J.M., Casano F.J., Chin J., Ding G.J.-F., Egger L.A., Gaffney E.P., Limjuco G., Palyha O.C., Raju M., Rolando A.M., Salley J.P., Yamin T.-T., Lee T.D., Shively J.E., McCross M., Mumford R.A., Schmidt J.A., Tocci M.J.;
"A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes.";
Nature 356:768-774(1992).
[2]
NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE OF 120-142.
PubMed=1373520 [NCBI, ExPASy, EBI, Israel, Japan]
Cerretti D.P., Kozlosky C.J., Mosley B., Nelson N., van Ness K., Greenstreet T.A., March C.J., Kronheim S.R., Druck T., Cannizzaro L.A., Huebner K., Black R.A.;
"Molecular cloning of the interleukin-1 beta converting enzyme.";
Science 256:97-100(1992).
[3]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ZETA), FUNCTION, MUTAGENESIS OF CYS-285, ALTERNATIVE SPLICING, AND TISSUE SPECIFICITY.
DOI=10.1016/j.ygeno.2004.06.005; PubMed=15498465 [NCBI, ExPASy, EBI, Israel, Japan]
Feng Q., Li P., Leung P.C.K., Auersperg N.;
"Caspase-1 zeta, a new splice variant of caspase-1 gene.";
Genomics 84:587-591(2004).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA).
Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.;
Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM GAMMA), AND NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 4-404 (ISOFORM BETA).
TISSUE=Testis;
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).
[6]
PROTEIN SEQUENCE OF 120-142.
DOI=10.1016/0003-9861(92)90629-B; PubMed=1321594 [NCBI, ExPASy, EBI, Israel, Japan]
Kronheim S.R., Mumma A., Greenstreet T., Glackin P.J., Van Ness K., March C.J., Black R.A.;
"Purification of interleukin-1 beta converting enzyme, the protease that cleaves the interleukin-1 beta precursor.";
Arch. Biochem. Biophys. 296:698-703(1992).
[7]
ALTERNATIVE SPLICING, AND FUNCTION.
DOI=10.1074/jbc.270.9.4312; PubMed=7876192 [NCBI, ExPASy, EBI, Israel, Japan]
Alnemri E.S., Fernandes-Alnemri T., Litwack G.;
"Cloning and expression of four novel isoforms of human interleukin-1 beta converting enzyme with different apoptotic activities.";
J. Biol. Chem. 270:4312-4317(1995).
[8]
COMPONENT OF THE INFLAMMASOME.
DOI=10.1016/S1074-7613(04)00046-9; PubMed=15030775 [NCBI, ExPASy, EBI, Israel, Japan]
Agostini L., Martinon F., Burns K., McDermott M.F., Hawkins P.N., Tschopp J.;
"NALP3 forms an IL-1beta-processing inflammasome with increased activity in Muckle-Wells autoinflammatory disorder.";
Immunity 20:319-325(2004).
[9]
INTERACTION WITH INCA.
DOI=10.1074/jbc.M407891200; PubMed=15383541 [NCBI, ExPASy, EBI, Israel, Japan]
Lamkanfi M., Denecker G., Kalai M., D'hondt K., Meeus A., Declercq W., Saelens X., Vandenabeele P.;
"INCA, a novel human caspase recruitment domain protein that inhibits interleukin-1beta generation.";
J. Biol. Chem. 279:51729-51738(2004).
[10]
X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS), AND SUBUNIT.
DOI=10.1016/0092-8674(94)90303-4; PubMed=8044845 [NCBI, ExPASy, EBI, Israel, Japan]
Walker N.P.C., Talanian R.V., Brady K.D., Dang L.C., Bump N.J., Ferenz C.R., Franklin S., Ghayur T., Hackett M.C., Hammill L.D., Herzog L., Hugunin M., Houy W., Mankovich J.A., McGuiness L., Orlewicz E., Paskind M., Pratt C.A., Reis P., Summani A., Terranova M., Welch J.P., Xiong L., Moeller A., Tracey D.E., Kamen R., Wong W.W.;
"Crystal structure of the cysteine protease interleukin-1 beta-converting enzyme: a (p20/p10)2 homodimer.";
Cell 78:343-352(1994).
[11]
X-RAY CRYSTALLOGRAPHY (2.73 ANGSTROMS).
DOI=10.1016/S1074-5521(97)90258-1; PubMed=9190289 [NCBI, ExPASy, EBI, Israel, Japan]
Rano T.A., Timkey T., Peterson E.P., Rotonda J., Nicholson D.W., Becker J.W., Chapman K.T., Thornberry N.A.;
"A combinatorial approach for determining protease specificities: application to interleukin-1beta converting enzyme (ICE).";
Chem. Biol. 4:149-155(1997).
[12]
X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEX WITH INHIBITORS.
PubMed=9987822 [NCBI, ExPASy, EBI, Israel, Japan]
Okamoto Y., Anan H., Nakai E., Morihira K., Yonetoku Y., Kurihara H., Sakashita H., Terai Y., Takeuchi M., Shibanuma T., Isomura Y.;
"Peptide based interleukin-1 beta converting enzyme (ICE) inhibitors: synthesis, structure activity relationships and crystallographic study of the ICE-inhibitor complex.";
Chem. Pharm. Bull. 47:11-21(1999).
[13]
X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 120-404 OF MUTANT ALA-285.
DOI=10.1016/j.str.2004.05.010; PubMed=15296730 [NCBI, ExPASy, EBI, Israel, Japan]
Romanowski M.J., Scheer J.M., O'Brien T., McDowell R.S.;
"Crystal structures of a ligand-free and malonate-bound human caspase-1: implications for the mechanism of substrate binding.";
Structure 12:1361-1371(2004).
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.
  • CATALYTIC ACTIVITY: Strict requirement for an Asp residue at position P1 and has a preferred cleavage sequence of Tyr-Val-Ala-Asp-|-.
  • ENZYME REGULATION: Specifically inhibited by the cowpox virus Crma protein.
  • SUBUNIT: 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. Interacts with INCA.
  • INTERACTION:
    P09038:FGF2; NbExp=1; IntAct=EBI-516667, EBI-977447;
    P01583:IL1A; NbExp=3; IntAct=EBI-516667, EBI-1749782;
    Q9NPP4:NLRC4; NbExp=1; IntAct=EBI-516667, EBI-1222527;
    Q9C000:NLRP1; NbExp=1; IntAct=EBI-516667, EBI-1220518;
  • SUBCELLULAR LOCATION: Cytoplasm.
  • ALTERNATIVE PRODUCTS: 6 named isoforms [FASTA] produced by alternative splicing. Additional isoforms seem to exist.
    NameAlpha
    Isoform IDP29466-1
    This is the isoform sequence displayed in this entry.
    NameBeta
    Isoform IDP29466-2
    Features which should be applied to build the isoform sequence: VSP_000798.
    NameGamma
    Isoform IDP29466-3
    Features which should be applied to build the isoform sequence: VSP_000799.
    NameDelta
    Isoform IDP29466-4
    Note: Apoptosis inactive.
    Features which should be applied to build the isoform sequence: VSP_000799, VSP_000800.
    NameEpsilon
    Isoform IDP29466-5
    Note: Apoptosis inactive.
    Features which should be applied to build the isoform sequence: VSP_000797.
    NameZeta
    Isoform IDP29466-6
    Note: Can promote apoptosis.
    Features which should be applied to build the isoform sequence: VSP_021670.
  • TISSUE SPECIFICITY: Expressed in larger amounts in spleen and lung. Detected in liver, heart, small intestine, colon, thymus, prostate, skeletal muscle, peripheral blood leukocytes, kidney and testis. No expression in the brain.
  • PTM: The two subunits are derived from the precursor sequence by an autocatalytic mechanism.
  • SIMILARITY: Belongs to the peptidase C14 family [view classification].
  • SIMILARITY: Contains 1 CARD domain.
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
X65019; CAA46153.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M87507; AAA66942.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
U13697; AAC50107.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
U13698; AAC50108.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
U13699; AAC50109.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
U13700; AAC50110.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AY660536; AAT72297.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AK223503; BAD97223.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC041689; AAH41689.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC062327; AAH62327.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
PIR A54263; A42677.
A56084; A56084.
B56084; B56084.
C56084; C56084.
D56084; D56084.
RefSeq NP_001214.1; -.
NP_150634.1; -.
NP_150635.1; -.
NP_150636.1; -.
NP_150637.1; -.
UniGene Hs.2490
3D structure databases
PDB
1BMQ; X-ray; 2.50 A; A=131-297, B=317-404.[ExPASy / RCSB / EBI]
1IBC; X-ray; 2.73 A; A=104-297, B=317-404.[ExPASy / RCSB / EBI]
1ICE; X-ray; 2.60 A; A=131-297, B=317-404.[ExPASy / RCSB / EBI]
1RWK; X-ray; 2.30 A; A=120-297, B=317-404.[ExPASy / RCSB / EBI]
1RWM; X-ray; 2.70 A; A=120-297, B=317-404.[ExPASy / RCSB / EBI]
1RWN; X-ray; 2.00 A; A=120-297, B=317-404.[ExPASy / RCSB / EBI]
1RWO; X-ray; 2.10 A; A=120-297, B=317-404.[ExPASy / RCSB / EBI]
1RWP; X-ray; 2.20 A; A=120-297, B=317-404.[ExPASy / RCSB / EBI]
1RWV; X-ray; 2.10 A; A=120-297, B=317-404.[ExPASy / RCSB / EBI]
1RWW; X-ray; 2.80 A; A=120-297, B=317-404.[ExPASy / RCSB / EBI]
1RWX; X-ray; 1.85 A; A=120-297, B=317-404.[ExPASy / RCSB / EBI]
1SC1; X-ray; 2.60 A; A=120-297, B=317-404.[ExPASy / RCSB / EBI]
1SC3; X-ray; 1.80 A; A=120-297, B=317-404.[ExPASy / RCSB / EBI]
1SC4; X-ray; 2.10 A; A=120-297, B=317-404.[ExPASy / RCSB / EBI]
2FQQ; X-ray; 3.30 A; A=120-297, B=317-404.[ExPASy / RCSB / EBI]
2H48; X-ray; 2.20 A; A=120-297, B=317-404.[ExPASy / RCSB / EBI]
2H4W; X-ray; 2.00 A; A=120-297, B=317-404.[ExPASy / RCSB / EBI]
2H4Y; X-ray; 1.90 A; A=120-297, B=317-404.[ExPASy / RCSB / EBI]
2H51; X-ray; 2.10 A; A=120-297, B=317-404.[ExPASy / RCSB / EBI]
2H54; X-ray; 1.80 A; A=120-297, B=317-404.[ExPASy / RCSB / EBI]
2HBQ; X-ray; 1.80 A; A=120-297, B=317-404.[ExPASy / RCSB / EBI]
2HBR; X-ray; 2.20 A; A=120-297, B=317-404.[ExPASy / RCSB / EBI]
2HBY; X-ray; 2.10 A; A=120-297, B=317-404.[ExPASy / RCSB / EBI]
2HBZ; X-ray; 1.90 A; A=120-297, B=317-404.[ExPASy / RCSB / EBI]
Detailed list of linked structures.
PDBsum 1BMQ; -.
1IBC; -.
1ICE; -.
1RWK; -.
1RWM; -.
1RWN; -.
1RWO; -.
1RWP; -.
1RWV; -.
1RWW; -.
1RWX; -.
1SC1; -.
1SC3; -.
1SC4; -.
2FQQ; -.
2H48; -.
2H4W; -.
2H4Y; -.
2H51; -.
2H54; -.
2HBQ; -.
2HBR; -.
2HBY; -.
2HBZ; -.
ModBase P29466.
Protein-protein interaction databases
DIP DIP:175N; -.
IntAct P29466; -.
Protein family/group databases
MEROPS C14.001; -.
Organism-specific databases
H-InvDB HIX0026261; -.
HIX0035831; -.
HGNC HGNC:1499; CASP1.
GenAtlas CASP1.
HPA CAB002685; -.
HPA003056; -.
MIM 147678; gene. [NCBI / EBI]
PharmGKB PA26083; -.
GeneCards P29466.
Gene expression databases
ArrayExpress P29466; -.
CleanEx HS_CASP1; -.
GermOnline ENSG00000137752; Homo sapiens.
Ontologies
GO
GO:0008656; Molecular function: caspase activator activity (traceable author statement from ProtInc).
GO:0030693; Molecular function: caspase activity (traceable author statement from ProtInc).
GO:0005515; Molecular function: protein binding (inferred from physical interaction from UniProtKB).
GO:0006915; Biological process: apoptosis (traceable author statement from ProtInc).
GO:0043123; Biological process: positive regulation of I-kappaB kinase/NF-kappaB cascade (inferred from expression pattern from UniProtKB).
GO:0006508; Biological process: proteolysis (inferred from direct assay from UniProtKB).
QuickGo view.
Family and domain databases
InterPro IPR001315; CARD.
IPR017350; Caspase_IL-1_beta.
IPR011029; DEATH_like.
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.
Gene3D G3DSA:1.10.533.10; DEATH_like; 1.
PANTHER PTHR10454; Pept_C14_p45; 1.
Pfam PF00619; CARD; 1.
PF00656; Peptidase_C14; 1.
Pfam graphical view of domain structure.
PIRSF PIRSF038001; Caspase_ICE; 1.
PRINTS PR00376; IL1BCENZYME.
SMART SM00114; CARD; 1.
SM00115; CASc; 1.
SMART graphical view of domain structure.
PROSITE PS50209; CARD; 1.
PS01122; CASPASE_CYS; 1.
PS01121; CASPASE_HIS; 1.
PS50207; CASPASE_P10; 1.
PS50208; CASPASE_P20; 1.
PROSITE graphical view of domain structure (profiles).
BLOCKS P29466.
Other
SWISS-3DIMAGE P29466.
Genome annotation databases
Ensembl ENSG00000137752; Homo sapiens. [Contig view]
GeneID 834; -.
KEGG hsa:834; -.
Phylogenomic databases
HOGENOM P29466; -.
HOVERGEN P29466; -.
Other
BindingDB P29466; -.
DrugBank DB01017; Minocycline.
DB00859; Penicillamine.
LinkHub P29466; -.
SOURCE CASP1; Homo sapiens.
ProtoNet P29466.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
3D-structure; Alternative splicing; Apoptosis; Cytoplasm; Direct protein sequencing; Hydrolase; Protease; Thiol protease; Zymogen.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom   To Length Description FTId
PROPEP   1   119  119      PRO_0000004521
CHAIN   120   297  178     Caspase-1 subunit p20. PRO_0000004522
PROPEP   298   316  19      PRO_0000004523
CHAIN   317   404  88     Caspase-1 subunit p10. PRO_0000004524
DOMAIN   1    91  91     CARD. 
ACT_SITE   237   237         
ACT_SITE   285   285         
VAR_SEQ   1    39        Missing (in isoform Zeta). VSP_021670
VAR_SEQ   20   335        Missing (in isoform Epsilon). VSP_000797
VAR_SEQ   20   112        Missing (in isoform Gamma and isoform Delta). VSP_000799
VAR_SEQ   92   112        Missing (in isoform Beta). VSP_000798
VAR_SEQ   288   335        Missing (in isoform Delta). VSP_000800
MUTAGEN   285   285        C->A,S: Loss of activity. 
CONFLICT   319   319        K -> R (in Ref. 4; BAD97223). 
CONFLICT   402   402        P -> L (in Ref. 4; BAD97223). 
TURN   129   132  4      
HELIX   138   147  10      
TURN   158   160  3      
STRAND   164   169  6      
STRAND   174   176  3      
HELIX   182   195  14      
STRAND   199   205  7      
HELIX   208   219  12      
HELIX   222   226  5      
STRAND   230   236  7      
STRAND   242   244  3      
STRAND   250   252  3      
HELIX   258   265  8      
TURN   267   269  3      
HELIX   271   273  3      
STRAND   278   284  7      
STRAND   286   289  4      
STRAND   292   296  5      
STRAND   318   324  7      
STRAND   326   333  8      
TURN   343   345  3      
HELIX   348   360  13      
TURN   361   363  3      
HELIX   366   376  11      
STRAND   388   392  5      
Sequence information
Length: 404 AA [This is the length of the unprocessed precursor] Molecular weight: 45159 Da [This is the MW of the unprocessed precursor] CRC64: ABF33CF33CC71584 [This is a checksum on the sequence]
        10         20         30         40         50         60 
MADKVLKEKR KLFIRSMGEG TINGLLDELL QTRVLNKEEM EKVKRENATV MDKTRALIDS 

        70         80         90        100        110        120 
VIPKGAQACQ ICITYICEED SYLAGTLGLS ADQTSGNYLN MQDSQGVLSS FPAPQAVQDN 

       130        140        150        160        170        180 
PAMPTSSGSE GNVKLCSLEE AQRIWKQKSA EIYPIMDKSS RTRLALIICN EEFDSIPRRT 

       190        200        210        220        230        240 
GAEVDITGMT MLLQNLGYSV DVKKNLTASD MTTELEAFAH RPEHKTSDST FLVFMSHGIR 

       250        260        270        280        290        300 
EGICGKKHSE QVPDILQLNA IFNMLNTKNC PSLKDKPKVI IIQACRGDSP GVVWFKDSVG 

       310        320        330        340        350        360 
VSGNLSLPTT EEFEDDAIKK AHIEKDFIAF CSSTPDNVSW RHPTMGSVFI GRLIEHMQEY 

       370        380        390        400 
ACSCDVEEIF RKVRFSFEQP DGRAQMPTTE RVTLTRCFYL FPGH 

P29466 in FASTA format

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

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