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Entry version 203 (29 Sep 2021)
Sequence version 1 (01 Feb 1996)
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Protein

Caspase-4

Gene

CASP4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Inflammatory caspase that acts as an essential effector of NLRP3 inflammasome-dependent CASP1 activation and IL1B and IL18 secretion in response to non-canonical activators, such as UVB radiation, cholera enterotoxin subunit B and cytosolic LPS (PubMed:23516580, PubMed:24879791, PubMed:25119034, PubMed:22246630, PubMed:26174085, PubMed:26173988, PubMed:26508369, PubMed:25964352).

Thiol protease that cleaves a tetrapeptide after an Asp residue at position P1 (PubMed:7797510, PubMed:23516580).

Independently of NLRP3 inflammasome and CASP1, promotes pyroptosis, through GSDMD cleavage and activation, followed by IL1A, IL18 and HMGB1 release in response to non-canonical inflammasome activators (PubMed:26375003, PubMed:32109412).

Plays a crucial role in the restriction of Salmonella typhimurium replication in colonic epithelial cells during infection: in later stages of the infection, LPS from cytosolic Salmonella triggers CASP4 activation, which catalyzes cleavage of GSDMD, resulting in pyroptosis of infected cells and their extrusion into the gut lumen, as well as in IL18 secretion (PubMed:25121752, PubMed:26375003, PubMed:25964352, PubMed:32109412).

Cleavage of GSDMD is not strictly dependent on the consensus cleavage site but depends on an exosite interface on CASP4 that recognizes and binds the Gasdermin-D, C-terminal (GSDMD-CT) part (PubMed:32109412).

Pyroptosis limits bacterial replication, while cytokine secretion promotes the recruitment and activation of immune cells and triggers mucosal inflammation (PubMed:25121752, PubMed:26375003, PubMed:25964352).

Involved in LPS-induced IL6 secretion; this activity may not require caspase enzymatic activity (PubMed:26508369).

Involved in cell death induced by endoplasmic reticulum stress and by treatment with cytotoxic APP peptides found Alzheimer's patient brains (PubMed:15123740, PubMed:22246630, PubMed:23661706).

Activated by direct binding to LPS without the need of an upstream sensor (PubMed:25119034).

Does not directly process IL1B (PubMed:7743998, PubMed:7797510, PubMed:7797592).

During non-canonical inflammasome activation, cuts CGAS and may play a role in the regulation of antiviral innate immune activation (PubMed:28314590).

17 Publications

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes regulatory mechanisms for enzymes, transporters or microbial transcription factors, and reports the components which regulate (by activation or inhibition) the reaction.<p><a href='/help/activity_regulation' target='_top'>More...</a></p>Activity regulationi

Activated by homooligomerization induced by direct binding to cytosolic LPS, in a TLR4-independent manner (PubMed:25119034).1 Publication

<p>This subsection of the 'Function' section describes biophysical and chemical properties, such as maximal absorption, kinetic parameters, pH dependence, redox potentials and temperature dependence.<p><a href='/help/biophysicochemical_properties' target='_top'>More...</a></p>Kineticsi

Values obtained using the partial C-terminal enzyme sequence of 105-377.1 Publication
  1. KM=681 µM for synthetic peptide acetyl-YVAD-p-nitroanilide1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section is used for enzymes and indicates the residues directly involved in catalysis.<p><a href='/help/act_site' target='_top'>More...</a></p>Active sitei210By similarity1
Active sitei2584 Publications1

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionHydrolase, Protease, Thiol protease
Biological processImmunity, Inflammatory response, Innate immunity, Necrosis

Enzyme and pathway databases

BRENDA Comprehensive Enzyme Information System

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BRENDAi
3.4.22.57, 2681

Pathway Commons web resource for biological pathway data

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PathwayCommonsi
P49662

Reactome - a knowledgebase of biological pathways and processes

More...
Reactomei
R-HSA-168638, NOD1/2 Signaling Pathway
R-HSA-5620971, Pyroptosis

SABIO-RK: Biochemical Reaction Kinetics Database

More...
SABIO-RKi
P49662

SIGNOR Signaling Network Open Resource

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SIGNORi
P49662

Protein family/group databases

MEROPS protease database

More...
MEROPSi
C14.007

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Caspase-41 Publication (EC:3.4.22.572 Publications)
Short name:
CASP-41 Publication
Alternative name(s):
ICE and Ced-3 homolog 21 Publication
Short name:
ICH-21 Publication
ICE(rel)-II1 Publication
Mih11 Publication
Protease TX1 Publication
Cleaved into the following 2 chains:
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: 'Name', 'Synonyms', 'Ordered locus names' and 'ORF names'.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:CASP41 PublicationImported
Synonyms:ICH21 Publication
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the 'taxonomic identifier' or 'taxid'.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">proteome</a> can consist of several components.<br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 11

Organism-specific databases

Human Gene Nomenclature Database

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HGNCi
HGNC:1505, CASP4

Online Mendelian Inheritance in Man (OMIM)

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MIMi
602664, gene

neXtProt; the human protein knowledge platform

More...
neXtProti
NX_P49662

Eukaryotic Pathogen, Vector and Host Database Resources

More...
VEuPathDBi
HostDB:ENSG00000196954

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Keywords - Cellular componenti

Cytoplasm, Endoplasmic reticulum, Inflammasome, Membrane, Mitochondrion, Secreted

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology_and_biotech_section">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi258C → A: Loss of enzymatic activity. Loss of LPS-induced pyroptosis. No effect on the interaction with LPS. Decrease in cell death induced by TMEM214 overexpression. Does not support IL1B and IL18 secretion following UVB irradiation. 4 Publications1
Mutagenesisi258C → S: Loss of autocatalysis. 1 Publication1
Mutagenesisi267W → L or N: Abolished interaction with Gasdermin-D (GSDMD) and ability to mediate its cleavage. 1 Publication1
Mutagenesisi270D → A: Abolished autoprocessing and ability to form a heterotetramer composed of Caspase-4 subunit p10 and Caspase-4 subunit p20, preventing ability to cleave GSDMD and induce pyroptosis. 1 Publication1
Mutagenesisi291V → N: Abolished interaction with Gasdermin-D (GSDMD) and ability to mediate its cleavage. 1 Publication1

Organism-specific databases

DisGeNET

More...
DisGeNETi
837

Open Targets

More...
OpenTargetsi
ENSG00000196954

The Pharmacogenetics and Pharmacogenomics Knowledge Base

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PharmGKBi
PA26088

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

More...
Pharosi
P49662, Tchem

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

More...
ChEMBLi
CHEMBL2226

Drug and drug target database

More...
DrugBanki
DB06255, Incadronic acid

IUPHAR/BPS Guide to PHARMACOLOGY

More...
GuidetoPHARMACOLOGYi
1620

Genetic variation databases

BioMuta curated single-nucleotide variation and disease association database

More...
BioMutai
CASP4

Domain mapping of disease mutations (DMDM)

More...
DMDMi
1352420

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM / Processing</a> section describes a propeptide, which is a part of a protein that is cleaved during maturation or activation. Once cleaved, a propeptide generally has no independent biological function.<p><a href='/help/propep' target='_top'>More...</a></p>PropeptideiPRO_00000045961 – ?80Sequence analysisAdd BLAST80
<p>This subsection of the 'PTM / Processing' section describes the extent of a polypeptide chain in the mature protein following processing or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_0000004597?81 – 270Caspase-4 subunit p101 PublicationAdd BLAST190
PropeptideiPRO_0000004598271 – 289Sequence analysis1 PublicationAdd BLAST19
ChainiPRO_0000004599290 – 377Caspase-4 subunit p201 PublicationAdd BLAST88
Isoform 2 (identifier: P49662-2)
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM / Processing</a> section indicates that the initiator methionine is cleaved from the mature protein.<p><a href='/help/init_met' target='_top'>More...</a></p>Initiator methionineiRemovedCombined sources

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei83PhosphoserineCombined sources1
Isoform 2 (identifier: P49662-2)
Modified residuei2N-acetylalanineCombined sources1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

In response to activation signals, including endoplasmic reticulum stress or treatment with amyloid-beta A4 protein fragments (such as amyloid-beta protein 40), undergoes autoproteolytic cleavage.4 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection describes interesting single amino acid sites on the sequence that are not defined in any other subsection. This subsection can be displayed in different sections ('Function', 'PTM / Processing', 'Pathology and Biotech') according to its content.<p><a href='/help/site' target='_top'>More...</a></p>Sitei289 – 290Cleavage; by autolysis1 Publication2

Keywords - PTMi

Acetylation, Phosphoprotein, Zymogen

Proteomic databases

Encyclopedia of Proteome Dynamics

More...
EPDi
P49662

jPOST - Japan Proteome Standard Repository/Database

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jPOSTi
P49662

MassIVE - Mass Spectrometry Interactive Virtual Environment

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MassIVEi
P49662

MaxQB - The MaxQuant DataBase

More...
MaxQBi
P49662

PaxDb, a database of protein abundance averages across all three domains of life

More...
PaxDbi
P49662

PeptideAtlas

More...
PeptideAtlasi
P49662

PRoteomics IDEntifications database

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PRIDEi
P49662

ProteomicsDB: a multi-organism proteome resource

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ProteomicsDBi
56043 [P49662-1]
56044 [P49662-2]

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

More...
iPTMneti
P49662

MetOSite database of methionine sulfoxide sites

More...
MetOSitei
P49662

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

More...
PhosphoSitePlusi
P49662

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the 'Expression' section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified 'at protein level'.<br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

Widely expressed, including in keratinocytes and colonic and small intestinal epithelial cells (at protein level). Not detected in brain.6 Publications

<p>This subsection of the 'Expression' section reports the experimentally proven effects of inducers and repressors (usually chemical compounds or environmental factors) on the level of protein (or mRNA) expression (up-regulation, down-regulation, constitutive expression).<p><a href='/help/induction' target='_top'>More...</a></p>Inductioni

In peripheral blood mononuclear cells and purified monocytes, up-regulated by bacterial lipopolysaccharides (LPS) and interferon-beta/IFNB1 at the mRNA level (PubMed:16893518, PubMed:24879791). However, this increase is not observed at the protein level, which remains constant in monocytes and other cell types following LPS treatment (PubMed:25121752) (PubMed:26508369). In monocyte-derived macrophages, some up-regulation at the protein level is observed following treatment with LPS and IFNB1 (PubMed:25964352). In SH-EP1 neuroblastoma cell line, up-regulated by NF-kappa-B RELA/p65 at both mRNA and protein levels.3 Publications

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...
Bgeei
ENSG00000196954, Expressed in monocyte and 207 other tissues

ExpressionAtlas, Differential and Baseline Expression

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ExpressionAtlasi
P49662, baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

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Genevisiblei
P49662, HS

Organism-specific databases

Human Protein Atlas

More...
HPAi
ENSG00000196954, Tissue enriched (blood)

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 20 kDa (Caspase-4 subunit p20) and a 10 kDa (Caspase-4 subunit p10) subunit (PubMed:32109412). Upon direct LPS-binding, forms large homooligomers, resulting in its activation (By similarity). These oligomers are often referred to as 'non-canonical inflammasomes' (PubMed:25119034). In its precursor form, interacts with TMEM214; this interaction is required for association with the endoplasmic reticulum membrane (PubMed:23661706).

Interacts with CASP1 (PubMed:22246630).

Interacts with NOD2 (PubMed:18511561).

Interacts with SERPINB1; this interaction regulates CASP4 activity (PubMed:30692621).

By similarity6 Publications

Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 20 kDa (Caspase-4 subunit p20) and a 10 kDa (Caspase-4 subunit p10) subunit.

1 Publication

Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 20 kDa (Caspase-4 subunit p20) and a 10 kDa (Caspase-4 subunit p10) subunit.

1 Publication

(Microbial infection) Interacts with NleF protein from pathogenic E.coli; this interaction leads to enzyme inhibition.

1 Publication

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGRID)

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BioGRIDi
107287, 34 interactors

Database of interacting proteins

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DIPi
DIP-44806N

Protein interaction database and analysis system

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IntActi
P49662, 7 interactors

Molecular INTeraction database

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MINTi
P49662

STRING: functional protein association networks

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STRINGi
9606.ENSP00000388566

Chemistry databases

BindingDB database of measured binding affinities

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BindingDBi
P49662

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

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RNActi
P49662, protein

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

1377
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

SWISS-MODEL Repository - a database of annotated 3D protein structure models

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SMRi
P49662

Database of comparative protein structure models

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ModBasei
Search...

Protein Data Bank in Europe - Knowledge Base

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PDBe-KBi
Search...

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family_and_domains_section">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini1 – 91CARDPROSITE-ProRule annotationAdd BLAST91

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni1 – 59Required for LPS-bindingBy similarityAdd BLAST59
Regioni84 – 104DisorderedSequence analysisAdd BLAST21

<p>This subsection of the 'Family and domains' section provides general information on the biological role of a domain. The term 'domain' is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domaini

The CARD domain mediates LPS recognition and homooligomerization.1 Publication

<p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Belongs to the peptidase C14A family.Curated

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...
eggNOGi
KOG3573, Eukaryota

Ensembl GeneTree

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GeneTreei
ENSGT00940000161497

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...
HOGENOMi
CLU_036904_0_1_1

InParanoid: Eukaryotic Ortholog Groups

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InParanoidi
P49662

Identification of Orthologs from Complete Genome Data

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OMAi
GICGTTH

Database of Orthologous Groups

More...
OrthoDBi
1327703at2759

Database for complete collections of gene phylogenies

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PhylomeDBi
P49662

TreeFam database of animal gene trees

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TreeFami
TF102023

Family and domain databases

Conserved Domains Database

More...
CDDi
cd00032, CASc, 1 hit

Gene3D Structural and Functional Annotation of Protein Families

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Gene3Di
1.10.533.10, 1 hit

Integrated resource of protein families, domains and functional sites

More...
InterProi
View protein in InterPro
IPR001315, CARD
IPR029030, Caspase-like_dom_sf
IPR033139, Caspase_cys_AS
IPR016129, Caspase_his_AS
IPR011029, DEATH-like_dom_sf
IPR002398, Pept_C14
IPR002138, Pept_C14_p10
IPR001309, Pept_C14_p20
IPR015917, Pept_C14A

The PANTHER Classification System

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PANTHERi
PTHR10454, PTHR10454, 1 hit

Pfam protein domain database

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Pfami
View protein in Pfam
PF00619, CARD, 1 hit

Protein Motif fingerprint database; a protein domain database

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PRINTSi
PR00376, IL1BCENZYME

Simple Modular Architecture Research Tool; a protein domain database

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SMARTi
View protein in SMART
SM00114, CARD, 1 hit
SM00115, CASc, 1 hit

Superfamily database of structural and functional annotation

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SUPFAMi
SSF47986, SSF47986, 1 hit
SSF52129, SSF52129, 1 hit

PROSITE; a protein domain and family database

More...
PROSITEi
View 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

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (5+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 5 <p>This subsection of the 'Sequence' section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 5 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: P49662-1) [UniParc]FASTAAdd to basket
Also known as: Alpha

This isoform has been chosen as the <div> <p><b>What is the canonical sequence?</b><p><a href='/help/canonical_and_isoforms' target='_top'>More...</a></p>canonicali 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
MAEGNHRKKP LKVLESLGKD FLTGVLDNLV EQNVLNWKEE EKKKYYDAKT
60 70 80 90 100
EDKVRVMADS MQEKQRMAGQ MLLQTFFNID QISPNKKAHP NMEAGPPESG
110 120 130 140 150
ESTDALKLCP HEEFLRLCKE RAEEIYPIKE RNNRTRLALI ICNTEFDHLP
160 170 180 190 200
PRNGADFDIT GMKELLEGLD YSVDVEENLT ARDMESALRA FATRPEHKSS
210 220 230 240 250
DSTFLVLMSH GILEGICGTV HDEKKPDVLL YDTIFQIFNN RNCLSLKDKP
260 270 280 290 300
KVIIVQACRG ANRGELWVRD SPASLEVASS QSSENLEEDA VYKTHVEKDF
310 320 330 340 350
IAFCSSTPHN VSWRDSTMGS IFITQLITCF QKYSWCCHLE EVFRKVQQSF
360 370
ETPRAKAQMP TIERLSMTRY FYLFPGN
Length:377
Mass (Da):43,262
Last modified:February 1, 1996 - v1
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:iDC7CCEC6E9D483EB
GO
Isoform 2 (identifier: P49662-2) [UniParc]FASTAAdd to basket
Also known as: Gamma, mih1-beta

The sequence of this isoform differs from the canonical sequence as follows:
     1-56: Missing.

Show »
Length:321
Mass (Da):36,705
Checksum:i7336654FD603B65A
GO
Isoform 3 (identifier: P49662-3) [UniParc]FASTAAdd to basket
Also known as: mih1-delta

The sequence of this isoform differs from the canonical sequence as follows:
     88-116: AHPNMEAGPPESGESTDALKLCPHEEFLR → GDKLGHRGRNHNLCSAISCSSSEYGGWTT
     117-377: Missing.

Note: May be due to competing acceptor splice site. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.Curated
Show »
Length:116
Mass (Da):13,264
Checksum:iFD9ED1FF1DF981D3
GO
Isoform 4 (identifier: P49662-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     261-263: ANR → GEC
     264-377: Missing.

Show »
Length:263
Mass (Da):30,000
Checksum:iFED10278B701F0F0
GO
Isoform 5 (identifier: P49662-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     125-157: IYPIKERNNRTRLALIICNTEFDHLPPRNGADF → VLCYLYEIEKKEEISLLSFSAPFLTALNDWGWG
     158-377: Missing.

Show »
Length:157
Mass (Da):18,111
Checksum:i65936259DD31435E
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E9PMT1E9PMT1_HUMAN
Caspase-4
CASP4
147Annotation score:

Annotation score:2 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
H0YD34H0YD34_HUMAN
Caspase-4
CASP4
72Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

<p>This subsection of the 'Sequence' section reports difference(s) between the protein sequence shown in the UniProtKB entry and other available protein sequences derived from the same gene.<p><a href='/help/sequence_caution' target='_top'>More...</a></p>Sequence cautioni

The sequence AAC99851 differs from that shown. Reason: Frameshift.Curated
The sequence AAC99854 differs from that shown. Reason: Erroneous translation. Erroneous CDS prediction.Curated
The sequence EAW67050 differs from that shown. Reason: Erroneous gene model prediction.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_06108147D → N. Corresponds to variant dbSNP:rs56226603EnsemblClinVar.1
Natural variantiVAR_075654134R → C1 PublicationCorresponds to variant dbSNP:rs181090259Ensembl.1
Natural variantiVAR_061082284E → D. Corresponds to variant dbSNP:rs55901059EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_0434951 – 56Missing in isoform 2. 1 PublicationAdd BLAST56
Alternative sequenceiVSP_05817788 – 116AHPNM…EEFLR → GDKLGHRGRNHNLCSAISCS SSEYGGWTT in isoform 3. 1 PublicationAdd BLAST29
Alternative sequenceiVSP_058178117 – 377Missing in isoform 3. 1 PublicationAdd BLAST261
Alternative sequenceiVSP_058179125 – 157IYPIK…NGADF → VLCYLYEIEKKEEISLLSFS APFLTALNDWGWG in isoform 5. 1 PublicationAdd BLAST33
Alternative sequenceiVSP_058180158 – 377Missing in isoform 5. 1 PublicationAdd BLAST220
Alternative sequenceiVSP_058181261 – 263ANR → GEC in isoform 4. 2 Publications3
Alternative sequenceiVSP_058182264 – 377Missing in isoform 4. 2 PublicationsAdd BLAST114

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...
EMBLi

GenBank nucleotide sequence database

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GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...
DDBJi
Links Updated
Z48810 mRNA Translation: CAA88750.1
U28014 mRNA Translation: AAA75171.1
U25804 mRNA Translation: AAA86890.1
U28976 mRNA Translation: AAC99850.1
U28977 mRNA Translation: AAC99851.1 Frameshift.
U28978 mRNA Translation: AAC99852.1
U28979 mRNA Translation: AAC99853.1
U28979 mRNA Translation: AAC99854.1 Sequence problems.
AK057094 mRNA Translation: BAG51861.1
AK296081 mRNA Translation: BAG58837.1
AK304222 mRNA Translation: BAG65094.1
EF636667 Genomic DNA Translation: ABR09278.1
AP001153 Genomic DNA No translation available.
AP002004 Genomic DNA No translation available.
CH471065 Genomic DNA Translation: EAW67050.1 Sequence problems.
CH471065 Genomic DNA Translation: EAW67051.1
CH471065 Genomic DNA Translation: EAW67052.1
BC017839 mRNA Translation: AAH17839.1
AL050391 mRNA Translation: CAB43686.2

The Consensus CDS (CCDS) project

More...
CCDSi
CCDS41704.1 [P49662-2]
CCDS8327.1 [P49662-1]

Protein sequence database of the Protein Information Resource

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PIRi
A57511

NCBI Reference Sequences

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RefSeqi
NP_001216.1, NM_001225.3 [P49662-1]
NP_150649.1, NM_033306.2 [P49662-2]
XP_011541321.1, XM_011543019.1
XP_016873886.1, XM_017018397.1

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...
Ensembli
ENST00000393150; ENSP00000376857; ENSG00000196954 [P49662-2]
ENST00000444739; ENSP00000388566; ENSG00000196954 [P49662-1]

Database of genes from NCBI RefSeq genomes

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GeneIDi
837

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...
KEGGi
hsa:837

UCSC genome browser

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UCSCi
uc001pib.2, human [P49662-1]

Keywords - Coding sequence diversityi

Alternative splicing

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

<p>This subsection of the <a href="http://www.uniprot.org/manual/cross_references_section">Cross-references</a> section provides links to various web resources that are relevant for a specific protein.<p><a href='/help/web_resource' target='_top'>More...</a></p>Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z48810 mRNA Translation: CAA88750.1
U28014 mRNA Translation: AAA75171.1
U25804 mRNA Translation: AAA86890.1
U28976 mRNA Translation: AAC99850.1
U28977 mRNA Translation: AAC99851.1 Frameshift.
U28978 mRNA Translation: AAC99852.1
U28979 mRNA Translation: AAC99853.1
U28979 mRNA Translation: AAC99854.1 Sequence problems.
AK057094 mRNA Translation: BAG51861.1
AK296081 mRNA Translation: BAG58837.1
AK304222 mRNA Translation: BAG65094.1
EF636667 Genomic DNA Translation: ABR09278.1
AP001153 Genomic DNA No translation available.
AP002004 Genomic DNA No translation available.
CH471065 Genomic DNA Translation: EAW67050.1 Sequence problems.
CH471065 Genomic DNA Translation: EAW67051.1
CH471065 Genomic DNA Translation: EAW67052.1
BC017839 mRNA Translation: AAH17839.1
AL050391 mRNA Translation: CAB43686.2
CCDSiCCDS41704.1 [P49662-2]
CCDS8327.1 [P49662-1]
PIRiA57511
RefSeqiNP_001216.1, NM_001225.3 [P49662-1]
NP_150649.1, NM_033306.2 [P49662-2]
XP_011541321.1, XM_011543019.1
XP_016873886.1, XM_017018397.1

3D structure databases

Select the link destinations:

Protein Data Bank Europe

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PDBei

Protein Data Bank RCSB

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RCSB PDBi

Protein Data Bank Japan

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PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
6KMZX-ray3.61A/B/C/D105-377[»]
6NRYX-ray2.18A92-377[»]
SMRiP49662
ModBaseiSearch...
PDBe-KBiSearch...

Protein-protein interaction databases

BioGRIDi107287, 34 interactors
DIPiDIP-44806N
IntActiP49662, 7 interactors
MINTiP49662
STRINGi9606.ENSP00000388566

Chemistry databases

BindingDBiP49662
ChEMBLiCHEMBL2226
DrugBankiDB06255, Incadronic acid
GuidetoPHARMACOLOGYi1620

Protein family/group databases

MEROPSiC14.007

PTM databases

iPTMnetiP49662
MetOSiteiP49662
PhosphoSitePlusiP49662

Genetic variation databases

BioMutaiCASP4
DMDMi1352420

Proteomic databases

EPDiP49662
jPOSTiP49662
MassIVEiP49662
MaxQBiP49662
PaxDbiP49662
PeptideAtlasiP49662
PRIDEiP49662
ProteomicsDBi56043 [P49662-1]
56044 [P49662-2]

Protocols and materials databases

Antibodypedia a portal for validated antibodies

More...
Antibodypediai
18094, 743 antibodies

The DNASU plasmid repository

More...
DNASUi
837

Genome annotation databases

EnsembliENST00000393150; ENSP00000376857; ENSG00000196954 [P49662-2]
ENST00000444739; ENSP00000388566; ENSG00000196954 [P49662-1]
GeneIDi837
KEGGihsa:837
UCSCiuc001pib.2, human [P49662-1]

Organism-specific databases

Comparative Toxicogenomics Database

More...
CTDi
837
DisGeNETi837

GeneCards: human genes, protein and diseases

More...
GeneCardsi
CASP4
HGNCiHGNC:1505, CASP4
HPAiENSG00000196954, Tissue enriched (blood)
MIMi602664, gene
neXtProtiNX_P49662
OpenTargetsiENSG00000196954
PharmGKBiPA26088
VEuPathDBiHostDB:ENSG00000196954

GenAtlas: human gene database

More...
GenAtlasi
Search...

Phylogenomic databases

eggNOGiKOG3573, Eukaryota
GeneTreeiENSGT00940000161497
HOGENOMiCLU_036904_0_1_1
InParanoidiP49662
OMAiGICGTTH
OrthoDBi1327703at2759
PhylomeDBiP49662
TreeFamiTF102023

Enzyme and pathway databases

BRENDAi3.4.22.57, 2681
PathwayCommonsiP49662
ReactomeiR-HSA-168638, NOD1/2 Signaling Pathway
R-HSA-5620971, Pyroptosis
SABIO-RKiP49662
SIGNORiP49662

Miscellaneous databases

BioGRID ORCS database of CRISPR phenotype screens

More...
BioGRID-ORCSi
837, 9 hits in 1014 CRISPR screens

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

More...
ChiTaRSi
CASP4, human

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

More...
GenomeRNAii
837
PharosiP49662, Tchem

Protein Ontology

More...
PROi
PR:P49662
RNActiP49662, protein

The Stanford Online Universal Resource for Clones and ESTs

More...
SOURCEi
Search...

Gene expression databases

BgeeiENSG00000196954, Expressed in monocyte and 207 other tissues
ExpressionAtlasiP49662, baseline and differential
GenevisibleiP49662, HS

Family and domain databases

CDDicd00032, CASc, 1 hit
Gene3Di1.10.533.10, 1 hit
InterProiView protein in InterPro
IPR001315, CARD
IPR029030, Caspase-like_dom_sf
IPR033139, Caspase_cys_AS
IPR016129, Caspase_his_AS
IPR011029, DEATH-like_dom_sf
IPR002398, Pept_C14
IPR002138, Pept_C14_p10
IPR001309, Pept_C14_p20
IPR015917, Pept_C14A
PANTHERiPTHR10454, PTHR10454, 1 hit
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

MobiDB: a database of protein disorder and mobility annotations

More...
MobiDBi
Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the 'Entry information' section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiCASP4_HUMAN
<p>This subsection of the 'Entry information' section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called 'Primary (citable) accession number'.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: P49662
Secondary accession number(s): A2NHL8
, A2NHL9, A2NHM0, B3KPZ9, B4DJH5, B4E2D2, O95601, Q7KYX7, Q9UG96
<p>This subsection of the 'Entry information' section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification ('Last modified'). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: February 1, 1996
Last modified: September 29, 2021
This is version 203 of the entry and version 1 of the sequence. See complete history.
<p>This subsection of the 'Entry information' section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>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.

<p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

3D-structure, Reference proteome

Documents

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