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P55212

- CASP6_HUMAN

UniProt

P55212 - CASP6_HUMAN

Protein

Caspase-6

Gene

CASP6

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 160 (01 Oct 2014)
      Sequence version 2 (28 Nov 2002)
      Previous versions | rss
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    Functioni

    Involved in the activation cascade of caspases responsible for apoptosis execution. Cleaves poly(ADP-ribose) polymerase in vitro, as well as lamins. Overexpression promotes programmed cell death.

    Catalytic activityi

    Strict requirement for Asp at position P1 and has a preferred cleavage sequence of Val-Glu-His-Asp-|-.

    Enzyme regulationi

    Activation is suppressed by phosphorylation at Ser-257.1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei121 – 1211By similarity
    Active sitei163 – 1631By similarity

    GO - Molecular functioni

    1. cysteine-type endopeptidase activity Source: RefGenome
    2. cysteine-type peptidase activity Source: ProtInc
    3. identical protein binding Source: IntAct
    4. protein binding Source: UniProtKB

    GO - Biological processi

    1. apoptotic process Source: RefGenome
    2. cellular component disassembly involved in execution phase of apoptosis Source: Reactome
    3. epithelial cell differentiation Source: UniProt
    4. proteolysis Source: UniProtKB

    Keywords - Molecular functioni

    Hydrolase, Protease, Thiol protease

    Keywords - Biological processi

    Apoptosis

    Enzyme and pathway databases

    BRENDAi3.4.22.59. 2681.
    ReactomeiREACT_107. Apoptotic cleavage of cellular proteins.
    REACT_13472. Breakdown of the nuclear lamina.
    REACT_13541. Caspase-mediated cleavage of cytoskeletal proteins.

    Protein family/group databases

    MEROPSiC14.005.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Caspase-6 (EC:3.4.22.59)
    Short name:
    CASP-6
    Alternative name(s):
    Apoptotic protease Mch-2
    Cleaved into the following 2 chains:
    Gene namesi
    Name:CASP6
    Synonyms:MCH2
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 4

    Organism-specific databases

    HGNCiHGNC:1507. CASP6.

    Subcellular locationi

    GO - Cellular componenti

    1. cytosol Source: UniProtKB
    2. nucleoplasm Source: Reactome

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi257 – 2571S → A: Suppression of caspase-6 activation. 1 Publication

    Organism-specific databases

    PharmGKBiPA26090.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Propeptidei1 – 2323PRO_0000004608Add
    BLAST
    Chaini24 – 179156Caspase-6 subunit p18PRO_0000004609Add
    BLAST
    Propeptidei180 – 19314PRO_0000004610Add
    BLAST
    Chaini194 – 293100Caspase-6 subunit p11PRO_0000004611Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei257 – 2571Phosphoserine; by NUAK11 Publication

    Post-translational modificationi

    Cleavages by caspase-3, caspase-8 or -10 generate the two active subunits.

    Keywords - PTMi

    Phosphoprotein, Zymogen

    Proteomic databases

    MaxQBiP55212.
    PaxDbiP55212.
    PeptideAtlasiP55212.
    PRIDEiP55212.

    2D gel databases

    OGPiP55212.

    PTM databases

    PhosphoSiteiP55212.

    Miscellaneous databases

    PMAP-CutDBP55212.

    Expressioni

    Gene expression databases

    ArrayExpressiP55212.
    BgeeiP55212.
    CleanExiHS_CASP6.
    GenevestigatoriP55212.

    Organism-specific databases

    HPAiCAB003775.
    HPA011337.
    HPA024303.

    Interactioni

    Subunit structurei

    Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 18 kDa (p18) and a 11 kDa (p11) subunit. Interacts with BIRC6/bruce.1 Publication

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    itself3EBI-718729,EBI-718729
    SATB1Q018262EBI-718729,EBI-743747

    Protein-protein interaction databases

    BioGridi107289. 17 interactions.
    DIPiDIP-44649N.
    IntActiP55212. 12 interactions.
    MINTiMINT-1374245.
    STRINGi9606.ENSP00000265164.

    Structurei

    Secondary structure

    1
    293
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi41 – 433
    Beta strandi46 – 516
    Helixi57 – 593
    Helixi67 – 8014
    Beta strandi84 – 907
    Helixi93 – 10513
    Beta strandi114 – 1207
    Beta strandi122 – 1243
    Beta strandi126 – 1283
    Beta strandi130 – 1356
    Helixi136 – 1416
    Turni145 – 1473
    Helixi149 – 1513
    Beta strandi156 – 1627
    Beta strandi165 – 1673
    Beta strandi190 – 1945
    Beta strandi197 – 1993
    Turni202 – 2054
    Beta strandi206 – 2127
    Beta strandi219 – 2213
    Turni222 – 2243
    Helixi227 – 23913
    Turni240 – 2423
    Helixi245 – 25814
    Beta strandi263 – 2653
    Helixi267 – 2693
    Beta strandi271 – 2733
    Beta strandi277 – 2804
    Beta strandi283 – 2853

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1MI9model-A34-175[»]
    B198-290[»]
    2WDPX-ray1.95A/B/C/D1-293[»]
    3K7EX-ray3.00A/B/C/D24-293[»]
    3NKFX-ray2.90A/B/C/D24-293[»]
    3NR2X-ray2.90A/B24-293[»]
    3OD5X-ray1.60A/B24-293[»]
    3P45X-ray2.53A/C/E/G/I/K/M/O1-179[»]
    B/D/F/H/J/L/N/P193-293[»]
    3P4UX-ray1.90A/C23-179[»]
    B/D193-293[»]
    3QNWX-ray2.65A/C/E/G24-179[»]
    B/D/F/H194-293[»]
    3S70X-ray1.62A/C24-293[»]
    3S8EX-ray2.88A/B/C/D/E/F/G/H24-293[»]
    3V6LX-ray2.20A/B21-293[»]
    3V6MX-ray2.69A/B/C/D/F/G/I/J24-293[»]
    4EJFX-ray2.65A/B/C/D24-293[»]
    4FXOX-ray2.85A/B/C/D1-293[»]
    4HVAX-ray2.07A/B24-293[»]
    4IYRX-ray2.70A/B1-293[»]
    4N5DX-ray2.06A/B24-293[»]
    4N6GX-ray2.14A/B24-293[»]
    4N7JX-ray1.67A/B24-293[»]
    4N7MX-ray2.12A/B24-293[»]
    4NBKX-ray1.94A/B24-293[»]
    4NBLX-ray1.76A/B24-293[»]
    4NBNX-ray1.75A/B24-293[»]
    ProteinModelPortaliP55212.
    SMRiP55212. Positions 25-292.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP55212.

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the peptidase C14A family.Curated

    Phylogenomic databases

    eggNOGiNOG278720.
    HOGENOMiHOG000231878.
    HOVERGENiHBG050802.
    InParanoidiP55212.
    KOiK04396.
    OMAiDFCKDPS.
    OrthoDBiEOG7TTQ7K.
    PhylomeDBiP55212.
    TreeFamiTF102023.

    Family and domain databases

    Gene3Di3.40.50.1460. 1 hit.
    InterProiIPR029030. Caspase-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]
    PfamiPF00656. Peptidase_C14. 1 hit.
    [Graphical view]
    PRINTSiPR00376. IL1BCENZYME.
    SMARTiSM00115. CASc. 1 hit.
    [Graphical view]
    PROSITEiPS01122. 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 Alpha (identifier: P55212-1) [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

    MSSASGLRRG HPAGGEENMT ETDAFYKREM FDPAEKYKMD HRRRGIALIF    50
    NHERFFWHLT LPERRGTCAD RDNLTRRFSD LGFEVKCFND LKAEELLLKI 100
    HEVSTVSHAD ADCFVCVFLS HGEGNHIYAY DAKIEIQTLT GLFKGDKCHS 150
    LVGKPKIFII QACRGNQHDV PVIPLDVVDN QTEKLDTNIT EVDAASVYTL 200
    PAGADFLMCY SVAEGYYSHR ETVNGSWYIQ DLCEMLGKYG SSLEFTELLT 250
    LVNRKVSQRR VDFCKDPSAI GKKQVPCFAS MLTKKLHFFP KSN 293
    Length:293
    Mass (Da):33,310
    Last modified:November 28, 2002 - v2
    Checksum:i0738AE4F9791EBD7
    GO
    Isoform Beta (identifier: P55212-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         14-102: Missing.

    Show »
    Length:204
    Mass (Da):22,574
    Checksum:i9DCC10C99F81D912
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti66 – 661G → R in AAC50168. (PubMed:7796396)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti35 – 351E → K.
    Corresponds to variant rs11574697 [ dbSNP | Ensembl ].
    VAR_029242
    Natural varianti109 – 1091A → T.
    Corresponds to variant rs5030674 [ dbSNP | Ensembl ].
    VAR_016130
    Natural varianti182 – 1821T → S.1 Publication
    Corresponds to variant rs5030593 [ dbSNP | Ensembl ].
    VAR_020126

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei14 – 10289Missing in isoform Beta. 1 PublicationVSP_000805Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U20536 mRNA. Translation: AAC50168.1.
    U20537 mRNA. Translation: AAC50169.1.
    AY254046 Genomic DNA. Translation: AAO63494.1.
    BC000305 mRNA. Translation: AAH00305.1.
    BC004460 mRNA. Translation: AAH04460.1.
    CCDSiCCDS3684.1. [P55212-1]
    CCDS3685.1. [P55212-2]
    RefSeqiNP_001217.2. NM_001226.3. [P55212-1]
    NP_116787.1. NM_032992.2. [P55212-2]
    UniGeneiHs.654616.

    Genome annotation databases

    EnsembliENST00000265164; ENSP00000265164; ENSG00000138794. [P55212-1]
    ENST00000352981; ENSP00000285333; ENSG00000138794. [P55212-2]
    GeneIDi839.
    KEGGihsa:839.
    UCSCiuc003hzn.1. human. [P55212-1]
    uc003hzo.1. human. [P55212-2]

    Polymorphism databases

    DMDMi26006981.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    NIEHS-SNPs

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U20536 mRNA. Translation: AAC50168.1 .
    U20537 mRNA. Translation: AAC50169.1 .
    AY254046 Genomic DNA. Translation: AAO63494.1 .
    BC000305 mRNA. Translation: AAH00305.1 .
    BC004460 mRNA. Translation: AAH04460.1 .
    CCDSi CCDS3684.1. [P55212-1 ]
    CCDS3685.1. [P55212-2 ]
    RefSeqi NP_001217.2. NM_001226.3. [P55212-1 ]
    NP_116787.1. NM_032992.2. [P55212-2 ]
    UniGenei Hs.654616.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1MI9 model - A 34-175 [» ]
    B 198-290 [» ]
    2WDP X-ray 1.95 A/B/C/D 1-293 [» ]
    3K7E X-ray 3.00 A/B/C/D 24-293 [» ]
    3NKF X-ray 2.90 A/B/C/D 24-293 [» ]
    3NR2 X-ray 2.90 A/B 24-293 [» ]
    3OD5 X-ray 1.60 A/B 24-293 [» ]
    3P45 X-ray 2.53 A/C/E/G/I/K/M/O 1-179 [» ]
    B/D/F/H/J/L/N/P 193-293 [» ]
    3P4U X-ray 1.90 A/C 23-179 [» ]
    B/D 193-293 [» ]
    3QNW X-ray 2.65 A/C/E/G 24-179 [» ]
    B/D/F/H 194-293 [» ]
    3S70 X-ray 1.62 A/C 24-293 [» ]
    3S8E X-ray 2.88 A/B/C/D/E/F/G/H 24-293 [» ]
    3V6L X-ray 2.20 A/B 21-293 [» ]
    3V6M X-ray 2.69 A/B/C/D/F/G/I/J 24-293 [» ]
    4EJF X-ray 2.65 A/B/C/D 24-293 [» ]
    4FXO X-ray 2.85 A/B/C/D 1-293 [» ]
    4HVA X-ray 2.07 A/B 24-293 [» ]
    4IYR X-ray 2.70 A/B 1-293 [» ]
    4N5D X-ray 2.06 A/B 24-293 [» ]
    4N6G X-ray 2.14 A/B 24-293 [» ]
    4N7J X-ray 1.67 A/B 24-293 [» ]
    4N7M X-ray 2.12 A/B 24-293 [» ]
    4NBK X-ray 1.94 A/B 24-293 [» ]
    4NBL X-ray 1.76 A/B 24-293 [» ]
    4NBN X-ray 1.75 A/B 24-293 [» ]
    ProteinModelPortali P55212.
    SMRi P55212. Positions 25-292.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 107289. 17 interactions.
    DIPi DIP-44649N.
    IntActi P55212. 12 interactions.
    MINTi MINT-1374245.
    STRINGi 9606.ENSP00000265164.

    Chemistry

    BindingDBi P55212.
    ChEMBLi CHEMBL3308.
    GuidetoPHARMACOLOGYi 1622.

    Protein family/group databases

    MEROPSi C14.005.

    PTM databases

    PhosphoSitei P55212.

    Polymorphism databases

    DMDMi 26006981.

    2D gel databases

    OGPi P55212.

    Proteomic databases

    MaxQBi P55212.
    PaxDbi P55212.
    PeptideAtlasi P55212.
    PRIDEi P55212.

    Protocols and materials databases

    DNASUi 839.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000265164 ; ENSP00000265164 ; ENSG00000138794 . [P55212-1 ]
    ENST00000352981 ; ENSP00000285333 ; ENSG00000138794 . [P55212-2 ]
    GeneIDi 839.
    KEGGi hsa:839.
    UCSCi uc003hzn.1. human. [P55212-1 ]
    uc003hzo.1. human. [P55212-2 ]

    Organism-specific databases

    CTDi 839.
    GeneCardsi GC04M110609.
    HGNCi HGNC:1507. CASP6.
    HPAi CAB003775.
    HPA011337.
    HPA024303.
    MIMi 601532. gene.
    neXtProti NX_P55212.
    PharmGKBi PA26090.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG278720.
    HOGENOMi HOG000231878.
    HOVERGENi HBG050802.
    InParanoidi P55212.
    KOi K04396.
    OMAi DFCKDPS.
    OrthoDBi EOG7TTQ7K.
    PhylomeDBi P55212.
    TreeFami TF102023.

    Enzyme and pathway databases

    BRENDAi 3.4.22.59. 2681.
    Reactomei REACT_107. Apoptotic cleavage of cellular proteins.
    REACT_13472. Breakdown of the nuclear lamina.
    REACT_13541. Caspase-mediated cleavage of cytoskeletal proteins.

    Miscellaneous databases

    ChiTaRSi CASP6. human.
    EvolutionaryTracei P55212.
    GeneWikii Caspase_6.
    GenomeRNAii 839.
    NextBioi 3494.
    PMAP-CutDB P55212.
    PROi P55212.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P55212.
    Bgeei P55212.
    CleanExi HS_CASP6.
    Genevestigatori P55212.

    Family and domain databases

    Gene3Di 3.40.50.1460. 1 hit.
    InterProi IPR029030. Caspase-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 PF00656. Peptidase_C14. 1 hit.
    [Graphical view ]
    PRINTSi PR00376. IL1BCENZYME.
    SMARTi SM00115. CASc. 1 hit.
    [Graphical view ]
    PROSITEi 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. "Mch2, a new member of the apoptotic Ced-3/Ice cysteine protease gene family."
      Fernandes-Alnemri T., Litwack G., Alnemri E.S.
      Cancer Res. 55:2737-2742(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ALPHA AND BETA).
      Tissue: T-cell.
    2. NIEHS SNPs program
      Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT SER-182.
    3. "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 ALPHA).
      Tissue: Lung.
    4. "The Ced-3/interleukin 1beta converting enzyme-like homolog Mch6 and the lamin-cleaving enzyme Mch2alpha are substrates for the apoptotic mediator CPP32."
      Srinivasula S.M., Fernandes-Alnemri T., Zangrilli J., Robertson N., Armstrong R.C., Wang L., Trapani J.A., Tomaselli K.J., Litwack G., Alnemri E.S.
      J. Biol. Chem. 271:27099-27106(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEOLYTIC PROCESSING.
      Tissue: Lymphocyte.
    5. "Dual role of BRUCE as an antiapoptotic IAP and a chimeric E2/E3 ubiquitin ligase."
      Bartke T., Pohl C., Pyrowolakis G., Jentsch S.
      Mol. Cell 14:801-811(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH BIRC6/BRUCE.
    6. "Regulation of caspase-6 and FLIP by the AMPK family member ARK5."
      Suzuki A., Kusakai G., Kishimoto A., Shimojo Y., Miyamoto S., Ogura T., Ochiai A., Esumi H.
      Oncogene 23:7067-7075(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: ENZYME REGULATION, PHOSPHORYLATION AT SER-257, MUTAGENESIS OF SER-257.
    7. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

    Entry informationi

    Entry nameiCASP6_HUMAN
    AccessioniPrimary (citable) accession number: P55212
    Secondary accession number(s): Q9BQE7
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 1, 1996
    Last sequence update: November 28, 2002
    Last modified: October 1, 2014
    This is version 160 of the entry and version 2 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

    3D-structure, Complete proteome, Reference proteome

    Documents

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

    External Data

    Dasty 3