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Protein

Caspase-1

Gene

CASP1

Organism
Homo sapiens (Human)
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. 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).4 Publications

Catalytic activityi

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

Enzyme regulationi

Specifically inhibited by the cowpox virus Crma protein.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei2371 Publication1
Active sitei2851 Publication1

GO - Molecular functioni

  • CARD domain binding Source: UniProtKB
  • cysteine-type endopeptidase activator activity involved in apoptotic process Source: ProtInc
  • cysteine-type endopeptidase activity Source: UniProtKB
  • cysteine-type endopeptidase activity involved in apoptotic process Source: GO_Central
  • endopeptidase activity Source: ParkinsonsUK-UCL
  • identical protein binding Source: UniProtKB
  • kinase binding Source: UniProtKB

GO - Biological processi

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

Keywordsi

Molecular functionHydrolase, Protease, Thiol protease
Biological processApoptosis

Enzyme and pathway databases

BRENDAi3.4.22.36. 2681.
ReactomeiR-HSA-168638. NOD1/2 Signaling Pathway.
R-HSA-448706. Interleukin-1 processing.
R-HSA-6803207. TP53 Regulates Transcription of Caspase Activators and Caspases.
R-HSA-844456. The NLRP3 inflammasome.
R-HSA-844615. The AIM2 inflammasome.
R-HSA-844623. The IPAF inflammasome.
SABIO-RKiP29466.
SignaLinkiP29466.
SIGNORiP29466.

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, IL1BCE
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

EuPathDBiHostDB:ENSG00000137752.22.
HGNCiHGNC:1499. 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

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi285C → A or S: Loss of activity. 1 Publication1

Organism-specific databases

DisGeNETi834.
OpenTargetsiENSG00000137752.
PharmGKBiPA26083.

Chemistry databases

ChEMBLiCHEMBL4801.
DrugBankiDB07744. 3-[2-(2-BENZYLOXYCARBONYLAMINO-3-METHYL-BUTYRYLAMINO)-PROPIONYLAMINO]-4-OXO-PENTANOIC ACID.
DB07916. 3-{6-[(8-HYDROXY-QUINOLINE-2-CARBONYL)-AMINO]-2-THIOPHEN-2-YL-HEXANOYLAMINO}-4-OXO-BUTYRI ACID.
DB05408. IDN-6556.
DB05301. LAX-101.
DB01017. Minocycline.
DB04875. Pralnacasan.
DB05507. VX-765.
GuidetoPHARMACOLOGYi1617.

Polymorphism and mutation databases

BioMutaiCASP1.
DMDMi266321.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
PropeptideiPRO_00000045211 – 119Add BLAST119
ChainiPRO_0000004522120 – 297Caspase-1 subunit p20Add BLAST178
PropeptideiPRO_0000004523298 – 316Add BLAST19
ChainiPRO_0000004524317 – 404Caspase-1 subunit p10Add BLAST88

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei302PhosphoserineBy similarity1

Post-translational modificationi

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

Keywords - PTMi

Phosphoprotein, Zymogen

Proteomic databases

EPDiP29466.
MaxQBiP29466.
PaxDbiP29466.
PeptideAtlasiP29466.
PRIDEiP29466.

PTM databases

iPTMnetiP29466.
PhosphoSitePlusiP29466.

Miscellaneous databases

PMAP-CutDBiP29466.

Expressioni

Tissue specificityi

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.1 Publication

Inductioni

Transcription and translation induced by M.tuberculosis and a number of different M.tuberculosis components; EsxA is the most potent activator tested (at protein level) (PubMed:20148899).1 Publication

Gene expression databases

BgeeiENSG00000137752.
CleanExiHS_CASP1.
ExpressionAtlasiP29466. baseline and differential.
GenevisibleiP29466. HS.

Organism-specific databases

HPAiCAB002685.
HPA003056.

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 p10 and p20 subunits interact with MEFV. Interacts with CARD17/INCA and CARD18.5 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • CARD domain binding Source: UniProtKB
  • identical protein binding Source: UniProtKB
  • kinase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi107284. 38 interactors.
CORUMiP29466.
DIPiDIP-175N.
IntActiP29466. 13 interactors.
MINTiMINT-201196.
STRINGi9606.ENSP00000410076.

Chemistry databases

BindingDBiP29466.

Structurei

Secondary structure

1404
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni129 – 132Combined sources4
Helixi138 – 147Combined sources10
Beta strandi148 – 150Combined sources3
Turni158 – 160Combined sources3
Beta strandi164 – 169Combined sources6
Beta strandi174 – 176Combined sources3
Helixi182 – 195Combined sources14
Beta strandi199 – 205Combined sources7
Helixi208 – 219Combined sources12
Helixi222 – 226Combined sources5
Beta strandi230 – 236Combined sources7
Beta strandi242 – 244Combined sources3
Beta strandi250 – 252Combined sources3
Beta strandi255 – 257Combined sources3
Helixi258 – 265Combined sources8
Turni267 – 269Combined sources3
Helixi271 – 273Combined sources3
Beta strandi278 – 283Combined sources6
Beta strandi287 – 289Combined sources3
Beta strandi291 – 298Combined sources8
Helixi316 – 319Combined sources4
Beta strandi326 – 333Combined sources8
Beta strandi340 – 342Combined sources3
Turni343 – 345Combined sources3
Helixi348 – 360Combined sources13
Turni361 – 363Combined sources3
Helixi366 – 376Combined sources11
Beta strandi381 – 383Combined sources3
Beta strandi388 – 391Combined sources4
Beta strandi395 – 397Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1BMQX-ray2.50A131-297[»]
B317-404[»]
1IBCX-ray2.73A104-297[»]
B317-404[»]
1ICEX-ray2.60A131-297[»]
B317-404[»]
1RWKX-ray2.30A120-297[»]
B317-404[»]
1RWMX-ray2.70A120-297[»]
B317-404[»]
1RWNX-ray2.00A120-297[»]
B317-404[»]
1RWOX-ray2.10A120-297[»]
B317-404[»]
1RWPX-ray2.20A120-297[»]
B317-404[»]
1RWVX-ray2.10A120-297[»]
B317-404[»]
1RWWX-ray2.80A120-297[»]
B317-404[»]
1RWXX-ray1.85A120-297[»]
B317-404[»]
1SC1X-ray2.60A120-297[»]
B317-404[»]
1SC3X-ray1.80A120-297[»]
B317-404[»]
1SC4X-ray2.10A120-297[»]
B317-404[»]
2FQQX-ray3.30A120-297[»]
B317-404[»]
2H48X-ray2.20A120-297[»]
B317-404[»]
2H4WX-ray2.00A120-297[»]
B317-404[»]
2H4YX-ray1.90A120-297[»]
B317-404[»]
2H51X-ray2.10A120-297[»]
B317-404[»]
2H54X-ray1.80A120-297[»]
B317-404[»]
2HBQX-ray1.80A120-297[»]
B317-404[»]
2HBRX-ray2.20A120-297[»]
B317-404[»]
2HBYX-ray2.10A120-297[»]
B317-404[»]
2HBZX-ray1.90A120-297[»]
B317-404[»]
3D6FX-ray1.90A120-297[»]
B317-404[»]
3D6HX-ray2.00A120-297[»]
B317-404[»]
3D6MX-ray1.80A120-297[»]
B317-404[»]
3E4CX-ray2.05A/B104-404[»]
3NS7X-ray2.60A136-297[»]
B317-404[»]
5FNAelectron microscopy4.80A/B/C/D/E/F/G/H2-86[»]
ProteinModelPortaliP29466.
SMRiP29466.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP29466.

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.
HOVERGENiHBG076981.
InParanoidiP29466.
KOiK01370.
OMAiEYAWSCD.
OrthoDBiEOG091G07NO.
PhylomeDBiP29466.
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.

Sequences (5)i

Sequence statusi: Complete.

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

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Additional isoforms seem to exist.
Isoform Alpha (identifier: P29466-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MADKVLKEKR KLFIRSMGEG TINGLLDELL QTRVLNKEEM EKVKRENATV
60 70 80 90 100
MDKTRALIDS VIPKGAQACQ ICITYICEED SYLAGTLGLS ADQTSGNYLN
110 120 130 140 150
MQDSQGVLSS FPAPQAVQDN PAMPTSSGSE GNVKLCSLEE AQRIWKQKSA
160 170 180 190 200
EIYPIMDKSS RTRLALIICN EEFDSIPRRT GAEVDITGMT MLLQNLGYSV
210 220 230 240 250
DVKKNLTASD MTTELEAFAH RPEHKTSDST FLVFMSHGIR EGICGKKHSE
260 270 280 290 300
QVPDILQLNA IFNMLNTKNC PSLKDKPKVI IIQACRGDSP GVVWFKDSVG
310 320 330 340 350
VSGNLSLPTT EEFEDDAIKK AHIEKDFIAF CSSTPDNVSW RHPTMGSVFI
360 370 380 390 400
GRLIEHMQEY ACSCDVEEIF RKVRFSFEQP DGRAQMPTTE RVTLTRCFYL

FPGH
Length:404
Mass (Da):45,159
Last modified:April 1, 1993 - v1
Checksum:iABF33CF33CC71584
GO
Isoform Beta (identifier: P29466-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     92-112: Missing.

Show »
Length:383
Mass (Da):42,888
Checksum:iC8D92A9B235B2E6F
GO
Isoform Gamma (identifier: P29466-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     20-112: Missing.

Show »
Length:311
Mass (Da):35,019
Checksum:i902A4384E49282C8
GO
Isoform Delta (identifier: P29466-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     20-112: Missing.
     288-335: Missing.

Note: Apoptosis inactive.
Show »
Length:263
Mass (Da):29,821
Checksum:i5ED98AC7864EB0BA
GO
Isoform Epsilon (identifier: P29466-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     20-335: Missing.

Note: Apoptosis inactive.
Show »
Length:88
Mass (Da):10,417
Checksum:iF3D811149FCDF159
GO

Sequence cautioni

The sequence AAT72297 differs from that shown. Probable cloning artifact.Curated
The sequence AAT72297 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti319K → R in BAD97223 (Ref. 4) Curated1
Sequence conflicti402P → L in BAD97223 (Ref. 4) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04861515R → H. Corresponds to variant dbSNP:rs1042743Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_00079720 – 335Missing in isoform Epsilon. 1 PublicationAdd BLAST316
Alternative sequenceiVSP_00079920 – 112Missing in isoform Gamma and isoform Delta. 2 PublicationsAdd BLAST93
Alternative sequenceiVSP_00079892 – 112Missing in isoform Beta. 2 PublicationsAdd BLAST21
Alternative sequenceiVSP_000800288 – 335Missing in isoform Delta. 1 PublicationAdd BLAST48

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X65019 mRNA. Translation: CAA46153.1.
M87507 mRNA. Translation: AAA66942.1.
U13697 mRNA. Translation: AAC50107.1.
U13698 mRNA. Translation: AAC50108.1.
U13699 mRNA. Translation: AAC50109.1.
U13700 mRNA. Translation: AAC50110.1.
AK223503 mRNA. Translation: BAD97223.1.
AP001153 Genomic DNA. No translation available.
BC041689 mRNA. Translation: AAH41689.1.
BC062327 mRNA. Translation: AAH62327.1.
AY660536 mRNA. Translation: AAT72297.1. Sequence problems.
CCDSiCCDS53704.1. [P29466-3]
CCDS8329.1. [P29466-2]
CCDS8330.1. [P29466-1]
CCDS8331.1. [P29466-4]
CCDS8332.1. [P29466-5]
PIRiA54263. A42677.
A56084.
B56084.
C56084.
D56084.
RefSeqiNP_001214.1. NM_001223.4. [P29466-2]
NP_001244047.1. NM_001257118.2. [P29466-1]
NP_001244048.1. NM_001257119.2. [P29466-2]
NP_150634.1. NM_033292.3. [P29466-1]
NP_150635.1. NM_033293.3. [P29466-3]
NP_150636.1. NM_033294.3. [P29466-4]
NP_150637.1. NM_033295.3. [P29466-5]
UniGeneiHs.2490.

Genome annotation databases

EnsembliENST00000353247; ENSP00000344132; ENSG00000137752. [P29466-5]
ENST00000436863; ENSP00000410076; ENSG00000137752. [P29466-1]
ENST00000446369; ENSP00000403260; ENSG00000137752. [P29466-4]
ENST00000525825; ENSP00000434779; ENSG00000137752. [P29466-2]
ENST00000526568; ENSP00000434250; ENSG00000137752. [P29466-3]
ENST00000531166; ENSP00000434303; ENSG00000137752. [P29466-5]
ENST00000533400; ENSP00000433138; ENSG00000137752. [P29466-1]
ENST00000534497; ENSP00000436875; ENSG00000137752. [P29466-4]
GeneIDi834.
KEGGihsa:834.
UCSCiuc001pig.5. human. [P29466-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiCASP1_HUMAN
AccessioniPrimary (citable) accession number: P29466
Secondary accession number(s): B5MDZ1
, Q53EY6, Q6DMQ1, Q6GSS3, Q6PI75, Q9UCN3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: April 1, 1993
Last modified: September 27, 2017
This is version 197 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Peptidase families
    Classification of peptidase families and list of entries
  7. SIMILARITY comments
    Index of protein domains and families