Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

P49662

- CASP4_HUMAN

UniProt

P49662 - CASP4_HUMAN

Protein

Caspase-4

Gene

CASP4

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 142 (01 Oct 2014)
      Sequence version 1 (01 Feb 1996)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

    Functioni

    Involved in the activation cascade of caspases responsible for apoptosis execution. Involved in ER-stress induced apoptosis. Cleaves caspase-1.2 Publications

    Catalytic activityi

    Strict requirement for Asp at the P1 position. It has a preferred cleavage sequence of Tyr-Val-Ala-Asp-|- but also cleaves at Asp-Glu-Val-Asp-|-.1 Publication

    Enzyme regulationi

    Inhibited by the effector protein NleF that is produced by pathogenic E.coli; this inhibits apoptosis.1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei210 – 2101By similarity
    Active sitei258 – 2581

    GO - Molecular functioni

    1. cysteine-type endopeptidase activity Source: RefGenome

    GO - Biological processi

    1. apoptotic process Source: ProtInc
    2. execution phase of apoptosis Source: RefGenome
    3. proteolysis Source: ProtInc
    4. regulation of apoptotic process Source: InterPro
    5. regulation of inflammatory response Source: RefGenome

    Keywords - Molecular functioni

    Hydrolase, Protease, Thiol protease

    Keywords - Biological processi

    Apoptosis

    Enzyme and pathway databases

    BRENDAi3.4.22.57. 2681.
    ReactomeiREACT_75776. NOD1/2 Signaling Pathway.
    SABIO-RKP49662.

    Protein family/group databases

    MEROPSiC14.007.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Caspase-4 (EC:3.4.22.57)
    Short name:
    CASP-4
    Alternative name(s):
    ICE(rel)-II
    Protease ICH-2
    Protease TX
    Cleaved into the following 2 chains:
    Gene namesi
    Name:CASP4
    Synonyms:ICH2
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 11

    Organism-specific databases

    HGNCiHGNC:1505. CASP4.

    Subcellular locationi

    GO - Cellular componenti

    1. AIM2 inflammasome complex Source: RefGenome
    2. cytoplasm Source: RefGenome
    3. endoplasmic reticulum membrane Source: UniProtKB-SubCell
    4. IPAF inflammasome complex Source: RefGenome
    5. mitochondrion Source: UniProtKB-SubCell
    6. NLRP3 inflammasome complex Source: RefGenome

    Keywords - Cellular componenti

    Endoplasmic reticulum, Membrane, Mitochondrion

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi258 – 2581C → S: Loss of activity. 1 Publication

    Organism-specific databases

    PharmGKBiPA26088.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Propeptidei1 – ?8080Sequence AnalysisPRO_0000004596Add
    BLAST
    Chaini?81 – 270190Caspase-4 subunit 1PRO_0000004597Add
    BLAST
    Propeptidei271 – 28919Sequence AnalysisPRO_0000004598Add
    BLAST
    Chaini290 – 37788Caspase-4 subunit 2PRO_0000004599Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei83 – 831Phosphoserine2 Publications

    Post-translational modificationi

    The two subunits are derived from the precursor sequence by an autocatalytic mechanism or by cleavage by Caspase-8.

    Keywords - PTMi

    Phosphoprotein, Zymogen

    Proteomic databases

    MaxQBiP49662.
    PaxDbiP49662.
    PRIDEiP49662.

    PTM databases

    PhosphoSiteiP49662.

    Expressioni

    Tissue specificityi

    Widely expressed, with highest levels in spleen and lung. Moderate expression in heart and liver, low expression in skeletal muscle, kidney and testis. Not found in the brain.

    Gene expression databases

    ArrayExpressiP49662.
    BgeeiP49662.
    CleanExiHS_CASP4.
    GenevestigatoriP49662.

    Organism-specific databases

    HPAiHPA027588.

    Interactioni

    Subunit structurei

    Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a small and a large subunit By similarity. Interacts with NleF from pathogenic E.coli. Interacts with TMEM214, the interaction is required for ER membrane localization.By similarity2 Publications

    Protein-protein interaction databases

    BioGridi107287. 32 interactions.
    DIPiDIP-44806N.
    IntActiP49662. 3 interactions.
    MINTiMINT-1533864.
    STRINGi9606.ENSP00000388566.

    Structurei

    3D structure databases

    ProteinModelPortaliP49662.
    SMRiP49662. Positions 99-377.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini1 – 9191CARDPROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Belongs to the peptidase C14A family.Curated
    Contains 1 CARD domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiNOG326166.
    HOGENOMiHOG000234399.
    HOVERGENiHBG076981.
    InParanoidiP49662.
    KOiK04394.
    OMAiRAKAQMP.
    OrthoDBiEOG7FXZZ6.
    PhylomeDBiP49662.
    TreeFamiTF102023.

    Family and domain databases

    Gene3Di1.10.533.10. 1 hit.
    3.40.50.1460. 1 hit.
    InterProiIPR001315. CARD.
    IPR029030. Caspase-like_dom.
    IPR017350. Caspase_ICE-type.
    IPR011029. DEATH-like_dom.
    IPR011600. Pept_C14_caspase.
    IPR001309. Pept_C14_ICE_p20.
    IPR016129. Pept_C14_ICE_p20_AS.
    IPR002138. Pept_C14_p10.
    IPR015917. Pept_C14A_p45_core.
    [Graphical view]
    PfamiPF00619. CARD. 1 hit.
    PF00656. Peptidase_C14. 1 hit.
    [Graphical view]
    PIRSFiPIRSF038001. Caspase_ICE. 1 hit.
    PRINTSiPR00376. IL1BCENZYME.
    SMARTiSM00114. CARD. 1 hit.
    SM00115. CASc. 1 hit.
    [Graphical view]
    SUPFAMiSSF47986. SSF47986. 1 hit.
    PROSITEiPS50209. CARD. 1 hit.
    PS01122. CASPASE_CYS. 1 hit.
    PS01121. CASPASE_HIS. 1 hit.
    PS50207. CASPASE_P10. 1 hit.
    PS50208. CASPASE_P20. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

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

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: P49662-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MAEGNHRKKP LKVLESLGKD FLTGVLDNLV EQNVLNWKEE EKKKYYDAKT    50
    EDKVRVMADS MQEKQRMAGQ MLLQTFFNID QISPNKKAHP NMEAGPPESG 100
    ESTDALKLCP HEEFLRLCKE RAEEIYPIKE RNNRTRLALI ICNTEFDHLP 150
    PRNGADFDIT GMKELLEGLD YSVDVEENLT ARDMESALRA FATRPEHKSS 200
    DSTFLVLMSH GILEGICGTV HDEKKPDVLL YDTIFQIFNN RNCLSLKDKP 250
    KVIIVQACRG ANRGELWVRD SPASLEVASS QSSENLEEDA VYKTHVEKDF 300
    IAFCSSTPHN VSWRDSTMGS IFITQLITCF QKYSWCCHLE EVFRKVQQSF 350
    ETPRAKAQMP TIERLSMTRY FYLFPGN 377
    Length:377
    Mass (Da):43,262
    Last modified:February 1, 1996 - v1
    Checksum:iDC7CCEC6E9D483EB
    GO
    Isoform 2 (identifier: P49662-2) [UniParc]FASTAAdd to Basket

    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

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti47 – 471D → N.
    Corresponds to variant rs56226603 [ dbSNP | Ensembl ].
    VAR_061081
    Natural varianti284 – 2841E → D.
    Corresponds to variant rs55901059 [ dbSNP | Ensembl ].
    VAR_061082

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 5656Missing in isoform 2. 1 PublicationVSP_043495Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    Z48810 mRNA. Translation: CAA88750.1.
    U28014 mRNA. Translation: AAA75171.1.
    U25804 mRNA. Translation: AAA86890.1.
    U28976 mRNA. Translation: AAC99850.1.
    U28978 mRNA. Translation: AAC99852.1.
    EF636667 Genomic DNA. Translation: ABR09278.1.
    AP001153 Genomic DNA. No translation available.
    AP002004 Genomic DNA. No translation available.
    CH471065 Genomic DNA. Translation: EAW67051.1.
    CH471065 Genomic DNA. Translation: EAW67052.1.
    BC017839 mRNA. Translation: AAH17839.1.
    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]
    UniGeneiHs.138378.

    Genome annotation databases

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

    Polymorphism databases

    DMDMi1352420.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    NIEHS-SNPs

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    Z48810 mRNA. Translation: CAA88750.1 .
    U28014 mRNA. Translation: AAA75171.1 .
    U25804 mRNA. Translation: AAA86890.1 .
    U28976 mRNA. Translation: AAC99850.1 .
    U28978 mRNA. Translation: AAC99852.1 .
    EF636667 Genomic DNA. Translation: ABR09278.1 .
    AP001153 Genomic DNA. No translation available.
    AP002004 Genomic DNA. No translation available.
    CH471065 Genomic DNA. Translation: EAW67051.1 .
    CH471065 Genomic DNA. Translation: EAW67052.1 .
    BC017839 mRNA. Translation: AAH17839.1 .
    CCDSi CCDS41704.1. [P49662-2 ]
    CCDS8327.1. [P49662-1 ]
    PIRi A57511.
    RefSeqi NP_001216.1. NM_001225.3. [P49662-1 ]
    NP_150649.1. NM_033306.2. [P49662-2 ]
    UniGenei Hs.138378.

    3D structure databases

    ProteinModelPortali P49662.
    SMRi P49662. Positions 99-377.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 107287. 32 interactions.
    DIPi DIP-44806N.
    IntActi P49662. 3 interactions.
    MINTi MINT-1533864.
    STRINGi 9606.ENSP00000388566.

    Chemistry

    BindingDBi P49662.
    ChEMBLi CHEMBL2226.

    Protein family/group databases

    MEROPSi C14.007.

    PTM databases

    PhosphoSitei P49662.

    Polymorphism databases

    DMDMi 1352420.

    Proteomic databases

    MaxQBi P49662.
    PaxDbi P49662.
    PRIDEi P49662.

    Protocols and materials databases

    DNASUi 837.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000393150 ; ENSP00000376857 ; ENSG00000196954 . [P49662-2 ]
    ENST00000444739 ; ENSP00000388566 ; ENSG00000196954 . [P49662-1 ]
    GeneIDi 837.
    KEGGi hsa:837.
    UCSCi uc001pib.1. human. [P49662-1 ]

    Organism-specific databases

    CTDi 837.
    GeneCardsi GC11M104806.
    HGNCi HGNC:1505. CASP4.
    HPAi HPA027588.
    MIMi 602664. gene.
    neXtProti NX_P49662.
    PharmGKBi PA26088.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG326166.
    HOGENOMi HOG000234399.
    HOVERGENi HBG076981.
    InParanoidi P49662.
    KOi K04394.
    OMAi RAKAQMP.
    OrthoDBi EOG7FXZZ6.
    PhylomeDBi P49662.
    TreeFami TF102023.

    Enzyme and pathway databases

    BRENDAi 3.4.22.57. 2681.
    Reactomei REACT_75776. NOD1/2 Signaling Pathway.
    SABIO-RK P49662.

    Miscellaneous databases

    GenomeRNAii 837.
    NextBioi 3484.
    PROi P49662.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P49662.
    Bgeei P49662.
    CleanExi HS_CASP4.
    Genevestigatori P49662.

    Family and domain databases

    Gene3Di 1.10.533.10. 1 hit.
    3.40.50.1460. 1 hit.
    InterProi IPR001315. CARD.
    IPR029030. Caspase-like_dom.
    IPR017350. Caspase_ICE-type.
    IPR011029. DEATH-like_dom.
    IPR011600. Pept_C14_caspase.
    IPR001309. Pept_C14_ICE_p20.
    IPR016129. Pept_C14_ICE_p20_AS.
    IPR002138. Pept_C14_p10.
    IPR015917. Pept_C14A_p45_core.
    [Graphical view ]
    Pfami PF00619. CARD. 1 hit.
    PF00656. Peptidase_C14. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF038001. Caspase_ICE. 1 hit.
    PRINTSi PR00376. IL1BCENZYME.
    SMARTi SM00114. CARD. 1 hit.
    SM00115. CASc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF47986. SSF47986. 1 hit.
    PROSITEi PS50209. CARD. 1 hit.
    PS01122. CASPASE_CYS. 1 hit.
    PS01121. CASPASE_HIS. 1 hit.
    PS50207. CASPASE_P10. 1 hit.
    PS50208. CASPASE_P20. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "A novel human protease similar to the interleukin-1 beta converting enzyme induces apoptosis in transfected cells."
      Faucheu C., Diu A., Chan A.W.E., Blanchet A.-M., Miossec C., Herve F., Collard-Dutilleul V., Gu Y., Aldape R.A., Lippke J.A., Rocher C., Su M.S.-S., Livingston D.J., Hercend T., Lalanne J.-L.
      EMBO J. 14:1914-1922(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), MUTAGENESIS OF CYS-258, 3D-STRUCTURE MODELING.
      Tissue: Placenta.
    2. "Molecular cloning and pro-apoptotic activity of ICErelII and ICErelIII, members of the ICE/CED-3 family of cysteine proteases."
      Munday N.A., Vaillancourt J.P., Ali A., Casano F.J., Miller D.K., Molineaux S.M., Yamin T.-T., Yu V.L., Nicholson D.W.
      J. Biol. Chem. 270:15870-15876(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    3. "Identification and characterization of ICH-2, a novel member of the interleukin-1 beta-converting enzyme family of cysteine proteases."
      Kamens J., Paskind M., Hugunin M., Talanian R.V., Allen H., Banach D., Bump N.J., Hackett M.C., Johnston C.G., Li P., Mankovich J.A., Terranova M., Ghayur T.
      J. Biol. Chem. 270:15250-15256(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CHARACTERIZATION.
      Tissue: Thymus.
    4. "Cloning of human ICE homolog Mih1."
      Fernandes-Alnemri T., Litwack G., Alnemri E.S.
      Submitted (JUN-1995) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
    5. NIEHS SNPs program
      Submitted (MAY-2007) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    6. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    7. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    8. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
      Tissue: Testis.
    9. "Involvement of caspase-4 in endoplasmic reticulum stress-induced apoptosis and Abeta-induced cell death."
      Hitomi J., Katayama T., Eguchi Y., Kudo T., Taniguchi M., Koyama Y., Manabe T., Yamagishi S., Bando Y., Imaizumi K., Tsujimoto Y., Tohyama M.
      J. Cell Biol. 165:347-356(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION.
    10. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-83, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    11. "Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
      Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
      Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-83, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    12. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    13. "Transmembrane protein 214 (TMEM214) mediates endoplasmic reticulum stress-induced caspase 4 enzyme activation and apoptosis."
      Li C., Wei J., Li Y., He X., Zhou Q., Yan J., Zhang J., Liu Y., Liu Y., Shu H.B.
      J. Biol. Chem. 288:17908-17917(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, INTERACTION WITH TMEM214.
    14. "The E.coli effector protein NleF is a caspase inhibitor."
      Blasche S., Moertl M., Steuber H., Siszler G., Nisa S., Schwarz F., Lavrik I., Gronewold T.M.A., Maskos K., Donnenberg M.S., Ullmann D., Uetz P., Koegl M.
      PLoS ONE 0:0-0(2013)
      Cited for: INTERACTION WITH E.COLI NLEF, CATALYTIC ACTIVITY, FUNCTION, ENZYME REGULATION.

    Entry informationi

    Entry nameiCASP4_HUMAN
    AccessioniPrimary (citable) accession number: P49662
    Secondary accession number(s): A2NHL8, A2NHM0
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 1, 1996
    Last sequence update: February 1, 1996
    Last modified: October 1, 2014
    This is version 142 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

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

    External Data

    Dasty 3