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UniProtKB - P49662 (CASP4_HUMAN)

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 (PubMed:7797510, PubMed:23516580, PubMed:25119034). 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:22246630, PubMed:26174085, PubMed:26173988, PubMed:26508369, PubMed:25964352). Independently of NLRP3 inflammasome and CASP1, promotes pyroptosis, through GSDMD cleavage and activation, and IL1A, IL18 and HMGB1 release in response to non-canonical inflammasome activators (PubMed:24879791, PubMed:25964352). Plays a crucial role in the restriction of Salmonella typhimurium replication in colonic epithelial cells during infection (PubMed:25121752). In later stages of the infection, LPS from cytosolic Salmonella triggers CASP4 activation, which ultimately results in pyroptosis of infected cells and their extrusion into the gut lumen, as well as in IL18 secretion. Pyroptosis limits bacterial replication, while cytokine secretion promotes the recruitment and activation of immune cells and triggers mucosal inflammation. 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:7797592, PubMed:7797510). During non-canonical inflammasome activation, cuts CGAS and may play a role in the regulation of antiviral innate immune activation (PubMed:28314590).15 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 ‘Function’ 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 ‘Function’ 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

    • CARD domain binding Source: UniProtKB
    • cysteine-type endopeptidase activity Source: UniProtKB
    • cysteine-type endopeptidase activity involved in apoptotic signaling pathway Source: GO_Central
    View the complete GO annotation on QuickGO ...

    GO - Biological processi

    View the complete GO annotation on QuickGO ...

    <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

    More...    BRENDAi    		3.4.22.57 2681

    Reactome - a knowledgebase of biological pathways and processes

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

    SABIO-RK: Biochemical Reaction Kinetics Database

    More...    SABIO-RKi    		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-4 (EC:3.4.22.571 Publication)
    Short name:
    CASP-4
    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:
    Caspase-4 subunit 1
    Caspase-4 subunit 2
    <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:CASP4
    Synonyms:ICH2
    <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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
    <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

    Eukaryotic Pathogen Database Resources

    More...    EuPathDBi    		HostDB:ENSG00000196954.12

    Human Gene Nomenclature Database

    More...    HGNCi    		HGNC:1505 CASP4

    Online Mendelian Inheritance in Man (OMIM)

    More...    MIMi    		602664 gene

    neXtProt; the human protein knowledge platform

    More...    neXtProti    		NX_P49662

    <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

    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, 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

    Organism-specific databases

    DisGeNET

    More...    DisGeNETi    		837

    Open Targets

    More...    OpenTargetsi    		ENSG00000196954

    The Pharmacogenetics and Pharmacogenomics Knowledge Base

    More...    PharmGKBi    		PA26088

    Chemistry databases

    ChEMBL database of bioactive drug-like small molecules

    More...    ChEMBLi    		CHEMBL2226

    IUPHAR/BPS Guide to PHARMACOLOGY

    More...    GuidetoPHARMACOLOGYi    		1620

    Polymorphism and mutation 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.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_0000004597?81 – 270Caspase-4 subunit 1Add BLAST190
    PropeptideiPRO_0000004598271 – 289Sequence analysis1 PublicationAdd BLAST19
    ChainiPRO_0000004599290 – 377Caspase-4 subunit 2Add 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 sourcesCurated

    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 sourcesCurated1

    <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.3 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

    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

    More...    PRIDEi    		P49662

    ProteomicsDB human proteome resource

    More...    ProteomicsDBi    		56043
    56044 [P49662-2]

    PTM databases

    iPTMnet integrated resource for PTMs in systems biology context

    More...    iPTMneti    		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 193 organ(s), highest expression level in leukocyte

    CleanEx database of gene expression profiles

    More...    CleanExi    		HS_CASP4

    ExpressionAtlas, Differential and Baseline Expression

    More...    ExpressionAtlasi    		P49662 baseline and differential

    Genevisible search portal to normalized and curated expression data from Genevestigator

    More...    Genevisiblei    		P49662 HS

    Organism-specific databases

    Human Protein Atlas

    More...    HPAi    		CAB037167
    HPA027588

    <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

    Upon direct LPS-binding, forms large homooligomers, resulting in its activation. These oligomers are often referred to as 'non-canonical inflammasomes' (PubMed:25119034). Active as a heterotetramer consisting of two anti-parallel arranged heterodimers, each one formed by a small and a large subunit (By similarity). 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).By similarity4 Publications
    (Microbial infection) Interacts with NleF protein from pathogenic E.coli; this interaction leads to enzyme inhibition.1 Publication

    GO - Molecular functioni

    View the complete GO annotation on QuickGO ...

    Protein-protein interaction databases

    The Biological General Repository for Interaction Datasets (BioGrid)

    More...    BioGridi    		107287, 34 interactors

    Database of interacting proteins

    More...    DIPi    		DIP-44806N

    Protein interaction database and analysis system

    More...    IntActi    		P49662, 5 interactors

    STRING: functional protein association networks

    More...    STRINGi    		9606.ENSP00000388566

    Chemistry databases

    BindingDB database of measured binding affinities

    More...    BindingDBi    		P49662

    <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

    3D structure databases

    Protein Model Portal of the PSI-Nature Structural Biology Knowledgebase

    More...    ProteinModelPortali    		P49662

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

    More...    SMRi    		P49662

    Database of comparative protein structure models

    More...    ModBasei    		Search...

    MobiDB: a database of protein disorder and mobility annotations

    More...    MobiDBi    		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

    <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
    ENOG410ZQIE LUCA

    Ensembl GeneTree

    More...    GeneTreei    		ENSGT00940000161497

    The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

    More...    HOGENOMi    		HOG000234399

    The HOVERGEN Database of Homologous Vertebrate Genes

    More...    HOVERGENi    		HBG076981

    InParanoid: Eukaryotic Ortholog Groups

    More...    InParanoidi    		P49662

    KEGG Orthology (KO)

    More...    KOi    		K04394

    Identification of Orthologs from Complete Genome Data

    More...    OMAi    		RAKAQMP

    Database of Orthologous Groups

    More...    OrthoDBi    		EOG091G07NO

    Database for complete collections of gene phylogenies

    More...    PhylomeDBi    		P49662

    TreeFam database of animal gene trees

    More...    TreeFami    		TF102023

    Family and domain databases

    Conserved Domains Database

    More...    CDDi    		cd00032 CASc, 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

    More...    PANTHERi    		PTHR10454 PTHR10454, 1 hit

    Pfam protein domain database

    More...    Pfami    		View protein in Pfam
    PF00619 CARD, 1 hit

    Protein Motif fingerprint database; a protein domain database

    More...    PRINTSi    		PR00376 IL1BCENZYME

    Simple Modular Architecture Research Tool; a protein domain database

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

    Superfamily database of structural and functional annotation

    More...    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>.<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 '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
    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.

    Note: No experimental confirmation available.Curated
    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.

    Note: No experimental confirmation available.Curated
    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

    Isoform 2 : The sequence AAC99851 differs from that shown. Reason: Frameshift at position 19.Combined sourcesCurated
    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:rs56226603Ensembl.1
    Natural variantiVAR_075654134R → C1 PublicationCorresponds to variant dbSNP:rs181090259Ensembl.1
    Natural variantiVAR_061082284E → D. Corresponds to variant dbSNP:rs55901059Ensembl.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. The information stored in this subsection is used to automatically construct alternative protein sequence(s) for display.<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

    More...    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

    More...    PIRi    		A57511

    NCBI Reference Sequences

    More...    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

    UniGene gene-oriented nucleotide sequence clusters

    More...    UniGenei    		Hs.138378

    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

    More...    GeneIDi    		837

    KEGG: Kyoto Encyclopedia of Genes and Genomes

    More...    KEGGi    		hsa:837

    UCSC genome browser

    More...    UCSCi    		uc001pib.2 human [P49662-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    <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
    UniGeneiHs.138378

    3D structure databases

    ProteinModelPortaliP49662
    SMRiP49662
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi107287, 34 interactors
    DIPiDIP-44806N
    IntActiP49662, 5 interactors
    STRINGi9606.ENSP00000388566

    Chemistry databases

    BindingDBiP49662
    ChEMBLiCHEMBL2226
    GuidetoPHARMACOLOGYi1620

    Protein family/group databases

    MEROPSiC14.007

    PTM databases

    iPTMnetiP49662
    PhosphoSitePlusiP49662

    Polymorphism and mutation databases

    BioMutaiCASP4
    DMDMi1352420

    Proteomic databases

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

    Protocols and materials databases

    The DNASU plasmid repository

    More...    DNASUi    		837
    Structural Biology KnowledgebaseSearch...

    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
    EuPathDBiHostDB:ENSG00000196954.12

    GeneCards: human genes, protein and diseases

    More...    GeneCardsi    		CASP4
    HGNCiHGNC:1505 CASP4
    HPAiCAB037167
    HPA027588
    MIMi602664 gene
    neXtProtiNX_P49662
    OpenTargetsiENSG00000196954
    PharmGKBiPA26088

    GenAtlas: human gene database

    More...    GenAtlasi    		Search...

    Phylogenomic databases

    eggNOGiKOG3573 Eukaryota
    ENOG410ZQIE LUCA
    GeneTreeiENSGT00940000161497
    HOGENOMiHOG000234399
    HOVERGENiHBG076981
    InParanoidiP49662
    KOiK04394
    OMAiRAKAQMP
    OrthoDBiEOG091G07NO
    PhylomeDBiP49662
    TreeFamiTF102023

    Enzyme and pathway databases

    BRENDAi3.4.22.57 2681
    ReactomeiR-HSA-168638 NOD1/2 Signaling Pathway
    SABIO-RKiP49662

    Miscellaneous databases

    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

    Protein Ontology

    More...    PROi    		PR:P49662

    The Stanford Online Universal Resource for Clones and ESTs

    More...    SOURCEi    		Search...

    Gene expression databases

    BgeeiENSG00000196954 Expressed in 193 organ(s), highest expression level in leukocyte
    CleanExiHS_CASP4
    ExpressionAtlasiP49662 baseline and differential
    GenevisibleiP49662 HS

    Family and domain databases

    CDDicd00032 CASc, 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

    ProtoNet; Automatic hierarchical classification of proteins

    More...    ProtoNeti    		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: December 5, 2018
    This is version 185 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

    Complete proteome, Reference proteome

    Documents

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