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Reviewed, UniProtKB/Swiss-Prot P29466 (CASP1_HUMAN)

Last modified November 25, 2008. Version 103. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended 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=IL-1 beta-converting enzyme
      Short name=ICE
    p45
Cleaved into the following 2 chains:
    1- Recommended name:
            Caspase-1 subunit p20
    2- Recommended name:
            Caspase-1 subunit p10
Gene names
Name: CASP1
Synonyms: IL1BC, IL1BCE
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length404 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein 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.

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 structure

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.

Subcellular location

Cytoplasm.

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.

Post-translational modification

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

Sequence similarities

Belongs to the peptidase C14 family.

Contains 1 CARD domain.

Ontologies

Keywords

   Biological processApoptosis
   Cellular componentCytoplasm
   Coding sequence diversityAlternative splicing
   Molecular functionHydrolase
Protease
Thiol protease
   PTMZymogen
   Technical term3D-structure
Direct protein sequencing

Gene Ontology (GO)

   Biological processpositive regulation of I-kappaB kinase/NF-kappaB cascade

Inferred from expression pattern. Source: UniProtKB

proteolysis Ref.7

Inferred from direct assay. Source: UniProtKB

   Cellular componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-KW

nucleus

Inferred from direct assay. Source: HPA

   Molecular functioncaspase activator activity

Traceable author statement. Source: ProtInc

cysteine-type endopeptidase activity

Traceable author statement. Source: ProtInc

protein binding Ref.8

Inferred from physical interaction. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 6 isoforms produced by alternative splicing. [Align] [Select]

Notes: Additional isoforms seem to exist.
Isoform Alpha (identifier: P29466-1)

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 Beta (identifier: P29466-2)

The sequence of this isoform differs from the canonical sequence as follows:
     92-112: Missing.
Isoform Gamma (identifier: P29466-3)

The sequence of this isoform differs from the canonical sequence as follows:
     20-112: Missing.
Isoform Delta (identifier: P29466-4)

The sequence of this isoform differs from the canonical sequence as follows:
     20-112: Missing.
     288-335: Missing.
Notes: Apoptosis inactive.
Isoform Epsilon (identifier: P29466-5)

The sequence of this isoform differs from the canonical sequence as follows:
     20-335: Missing.
Notes: Apoptosis inactive.
Isoform Zeta (identifier: P29466-6)

The sequence of this isoform differs from the canonical sequence as follows:
     1-39: Missing.
Notes: Can promote apoptosis.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Propeptide1 – 119119
PRO_0000004521
Chain120 – 297178Caspase-1 subunit p20
PRO_0000004522
Propeptide298 – 31619
PRO_0000004523
Chain317 – 40488Caspase-1 subunit p10
PRO_0000004524

Regions

Domain1 – 9191CARD

Sites

Active site2371
Active site2851

Natural variations

Alternative sequence1 – 3939Missing in isoform Zeta.
VSP_021670
Alternative sequence20 – 335316Missing in isoform Epsilon.
VSP_000797
Alternative sequence20 – 11293Missing in isoform Gamma and isoform Delta.
VSP_000799
Alternative sequence92 – 11221Missing in isoform Beta.
VSP_000798
Alternative sequence288 – 33548Missing in isoform Delta.
VSP_000800

Experimental info

Mutagenesis2851C → A or S: Loss of activity
Sequence conflict3191K → R in BAD97223. Ref.4
Sequence conflict4021P → L in BAD97223. Ref.4

Secondary structure

.................................................. 404
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform Alpha [UniParc].

Last modified April 1, 1993. Version 1.
Checksum: ABF33CF33CC71584

FASTA40445,159
        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 

« Hide

Isoform Beta [UniParc].

Checksum: C8D92A9B235B2E6F
Show »

38342,888
Isoform Gamma [UniParc].

Checksum: 902A4384E49282C8
Show »

31135,019
Isoform Delta [UniParc].

Checksum: 5ED98AC7864EB0BA
Show »

26329,821
Isoform Epsilon [UniParc].

Checksum: F3D811149FCDF159
Show »

8810,417
Isoform Zeta [UniParc].

Checksum: 13EDDE92AEB115E0
Show »

36540,659

References

« Hide 'large scale' references
[1]"A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes."
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. expand/collapse author list , 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.
Nature 356:768-774(1992) [PubMed: 1574116] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, ACTIVE SITE.
[2]"Molecular cloning of the interleukin-1 beta converting enzyme."
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.
Science 256:97-100(1992) [PubMed: 1373520] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE OF 120-142.
[3]"Caspase-1 zeta, a new splice variant of caspase-1 gene."
Feng Q., Li P., Leung P.C.K., Auersperg N.
Genomics 84:587-591(2004) [PubMed: 15498465] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ZETA), FUNCTION, MUTAGENESIS OF CYS-285, ALTERNATIVE SPLICING, TISSUE SPECIFICITY.
[4]Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.
Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA).
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM GAMMA), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 4-404 (ISOFORM BETA).
Tissue: Testis.
[6]"Purification of interleukin-1 beta converting enzyme, the protease that cleaves the interleukin-1 beta precursor."
Kronheim S.R., Mumma A., Greenstreet T., Glackin P.J., Van Ness K., March C.J., Black R.A.
Arch. Biochem. Biophys. 296:698-703(1992) [PubMed: 1321594] [Abstract]
Cited for: PROTEIN SEQUENCE OF 120-142.
[7]"Cloning and expression of four novel isoforms of human interleukin-1 beta converting enzyme with different apoptotic activities."
Alnemri E.S., Fernandes-Alnemri T., Litwack G.
J. Biol. Chem. 270:4312-4317(1995) [PubMed: 7876192] [Abstract]
Cited for: ALTERNATIVE SPLICING, FUNCTION.
[8]"NALP3 forms an IL-1beta-processing inflammasome with increased activity in Muckle-Wells autoinflammatory disorder."
Agostini L., Martinon F., Burns K., McDermott M.F., Hawkins P.N., Tschopp J.
Immunity 20:319-325(2004) [PubMed: 15030775] [Abstract]
Cited for: COMPONENT OF THE INFLAMMASOME.
[9]"INCA, a novel human caspase recruitment domain protein that inhibits interleukin-1beta generation."
Lamkanfi M., Denecker G., Kalai M., D'hondt K., Meeus A., Declercq W., Saelens X., Vandenabeele P.
J. Biol. Chem. 279:51729-51738(2004) [PubMed: 15383541] [Abstract]
Cited for: INTERACTION WITH INCA.
[10]"Crystal structure of the cysteine protease interleukin-1 beta-converting enzyme: a (p20/p10)2 homodimer."
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. expand/collapse author list , Reis P., Summani A., Terranova M., Welch J.P., Xiong L., Moeller A., Tracey D.E., Kamen R., Wong W.W.
Cell 78:343-352(1994) [PubMed: 8044845] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS), SUBUNIT.
[11]"A combinatorial approach for determining protease specificities: application to interleukin-1beta converting enzyme (ICE)."
Rano T.A., Timkey T., Peterson E.P., Rotonda J., Nicholson D.W., Becker J.W., Chapman K.T., Thornberry N.A.
Chem. Biol. 4:149-155(1997) [PubMed: 9190289] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.73 ANGSTROMS).
[12]"Peptide based interleukin-1 beta converting enzyme (ICE) inhibitors: synthesis, structure activity relationships and crystallographic study of the ICE-inhibitor complex."
Okamoto Y., Anan H., Nakai E., Morihira K., Yonetoku Y., Kurihara H., Sakashita H., Terai Y., Takeuchi M., Shibanuma T., Isomura Y.
Chem. Pharm. Bull. 47:11-21(1999) [PubMed: 9987822] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEX WITH INHIBITORS.
[13]"Crystal structures of a ligand-free and malonate-bound human caspase-1: implications for the mechanism of substrate binding."
Romanowski M.J., Scheer J.M., O'Brien T., McDowell R.S.
Structure 12:1361-1371(2004) [PubMed: 15296730] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 120-404 OF MUTANT ALA-285.
+Additional computationally mapped references.

Cross-references

Sequence databases