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Q91VA3

- CAN8_MOUSE

UniProt

Q91VA3 - CAN8_MOUSE

Protein

Calpain-8

Gene

Capn8

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 102 (01 Oct 2014)
      Sequence version 1 (01 Dec 2001)
      Previous versions | rss
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    Functioni

    Calcium-regulated non-lysosomal thiol-protease By similarity. Involved in membrane trafficking in the gastric surface mucus cells (pit cells) and may involve the membrane trafficking of mucus cells via interactions with coat protein. Proteolytically cleaves the beta-subunit of coatomer complex.By similarity1 Publication

    Catalytic activityi

    Broad endopeptidase specificity.

    Cofactori

    Binds 2 calcium ions.Curated

    Enzyme regulationi

    The concentration of calcium for half-maximal activity is 0.3mM. Inhibited by calpastatin and calpeptin.1 Publication

    pH dependencei

    Optimum pH is 6.1 Publication

    Temperature dependencei

    Optimum temperature is 20 degrees Celsius.1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei105 – 1051By similarity
    Active sitei262 – 2621By similarity
    Active sitei286 – 2861By similarity

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Calcium bindingi588 – 599121Sequence AnalysisAdd
    BLAST
    Calcium bindingi618 – 629122Sequence AnalysisAdd
    BLAST

    GO - Molecular functioni

    1. calcium-dependent cysteine-type endopeptidase activity Source: RefGenome
    2. calcium ion binding Source: InterPro

    GO - Biological processi

    1. proteolysis Source: RefGenome

    Keywords - Molecular functioni

    Hydrolase, Protease, Thiol protease

    Keywords - Ligandi

    Calcium, Metal-binding

    Protein family/group databases

    MEROPSiC02.007.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Calpain-8 (EC:3.4.22.53)
    Alternative name(s):
    New calpain 2
    Short name:
    nCL-2
    Stomach-specific M-type calpain
    Gene namesi
    Name:Capn8
    Synonyms:Ncl2
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 1

    Organism-specific databases

    MGIiMGI:2181366. Capn8.

    Subcellular locationi

    Cytoplasm By similarity. Golgi apparatus 1 Publication

    GO - Cellular componenti

    1. cytoplasm Source: RefGenome
    2. Golgi apparatus Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cytoplasm, Golgi apparatus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi105 – 1051C → S: Loss of activity. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 703703Calpain-8PRO_0000349281Add
    BLAST

    Post-translational modificationi

    Undergoes autolytic cleavage between Ala-5 and Ala-6 which gives rise to fragments extending from Ala-6 to the C-terminus, Ala-6 to the EF-hand 2 domain and from Ala-6 to the beginning of domain III.

    Keywords - PTMi

    Autocatalytic cleavage

    Proteomic databases

    MaxQBiQ91VA3.
    PRIDEiQ91VA3.

    PTM databases

    PhosphoSiteiQ91VA3.

    Expressioni

    Tissue specificityi

    Predominantly expressed in the stomach. Localizes strictly to the surface mucus cells in the gastric epithelium and the mucus-secreting goblet cells in the duodenum.2 Publications

    Gene expression databases

    BgeeiQ91VA3.
    CleanExiMM_CAPN8.
    GenevestigatoriQ91VA3.

    Interactioni

    Subunit structurei

    Monomer and homooligomer. Interacts with COPS1/GPS1, COPB1, EYA2, NME2, NME4 and TOMM70A.2 Publications

    Structurei

    3D structure databases

    ProteinModelPortaliQ91VA3.
    SMRiQ91VA3. Positions 23-698.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini45 – 344300Calpain catalyticPROSITE-ProRule annotationAdd
    BLAST
    Domaini531 – 56636EF-hand 1Add
    BLAST
    Domaini575 – 61036EF-hand 2Add
    BLAST
    Domaini605 – 64036EF-hand 3Add
    BLAST
    Domaini670 – 70334EF-hand 4Add
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni355 – 512158Domain IIIAdd
    BLAST
    Regioni513 – 53119LinkerBy similarityAdd
    BLAST
    Regioni532 – 703172Domain IVBy similarityAdd
    BLAST

    Domaini

    The domain III mediates oligomerization.1 Publication

    Sequence similaritiesi

    Belongs to the peptidase C2 family.Curated
    Contains 1 calpain catalytic domain.PROSITE-ProRule annotation
    Contains 4 EF-hand domains.Curated

    Keywords - Domaini

    Repeat

    Phylogenomic databases

    eggNOGiNOG327523.
    GeneTreeiENSGT00750000117457.
    HOGENOMiHOG000232035.
    HOVERGENiHBG012645.
    InParanoidiQ91VA3.
    KOiK08577.
    OrthoDBiEOG7RV9FM.
    PhylomeDBiQ91VA3.
    TreeFamiTF314748.

    Family and domain databases

    Gene3Di1.10.238.10. 1 hit.
    InterProiIPR022684. Calpain_cysteine_protease.
    IPR022682. Calpain_domain_III.
    IPR022683. Calpain_III.
    IPR029543. CAPN8.
    IPR011992. EF-hand-dom_pair.
    IPR002048. EF_hand_dom.
    IPR000169. Pept_cys_AS.
    IPR001300. Peptidase_C2_calpain_cat.
    [Graphical view]
    PANTHERiPTHR10183:SF52. PTHR10183:SF52. 1 hit.
    PfamiPF01067. Calpain_III. 1 hit.
    PF00648. Peptidase_C2. 1 hit.
    [Graphical view]
    PRINTSiPR00704. CALPAIN.
    SMARTiSM00720. calpain_III. 1 hit.
    SM00230. CysPc. 1 hit.
    SM00054. EFh. 3 hits.
    [Graphical view]
    SUPFAMiSSF49758. SSF49758. 1 hit.
    PROSITEiPS50203. CALPAIN_CAT. 1 hit.
    PS00139. THIOL_PROTEASE_CYS. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q91VA3-1) [UniParc]FASTAAdd to Basket

    Also known as: nCL-2

    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

    MAALAAGISK QRAAAQGLGS NQNAVKYLGQ DFETLRKQCL NSGVLFKDPE    50
    FPACPSALGY RDLGPGSAET QGIIWKRPTE LCSNPQFIVG GATRTDIRQG 100
    GLGDCWLLAA IASLTLNEKL LYRVVPRDQS FQKNYAGIFH FQFWQYGEWV 150
    EVVIDDRLPT KNGQLLFLHS EEGNEFWSAL LEKAYAKLNG SYEALAGGST 200
    IEGFEDFTGG ISEFYDLRKP PGNLYYTIQK ALRKGSLLGC SIDVSNAAEA 250
    EATTRQKLVK GHAYSVTGVE EVDFRGLPEK LIRLRNPWGE VEWTGAWSDS 300
    APEWNYIDPQ KKGELDKRAE DGEFWMSFSD FLKQFSRLEI CNLSPDSLSS 350
    EEIHKWNLVL FNGRWTRGST AGGCQNYPAT YWTNPQFKIH LDEVDEDQEE 400
    GTSEPCCTVL LGLMQKNRRR QRRIGQGMLS IGYAVYQIPK ELENHTDEHL 450
    GRDFFQGRQP STCSSTYMNL REVSSRVQLP PGQYLVVPST FEPFKDGDFC 500
    LRVFSEKKAQ ALEIGDAVPG DPHEPHPRDM DGEDEHFWSL SEEFADKDSE 550
    ISAHQLKRVL NGLLSKRTDM KFDGFNINTC REMISLLDGD GTGSLRPVEF 600
    KTLWLKICKY LEIYQEMDHS RAGTIDAHEM RTALKKAGFT LNNQVQQTIA 650
    TRYACSKLGV DFDGFVACMI RLEILFKLFR LLDKDQNGIV QLSLAEWLCR 700
    ALV 703
    Length:703
    Mass (Da):79,335
    Last modified:December 1, 2001 - v1
    Checksum:i50F2F9CCF2192FB6
    GO
    Isoform 2 (identifier: Q91VA3-2) [UniParc]FASTAAdd to Basket

    Also known as: Calpain 8b, nCL-2'

    The sequence of this isoform differs from the canonical sequence as follows:
         379-381: ATY → GSF
         382-703: Missing.

    Show »
    Length:381
    Mass (Da):42,434
    Checksum:iECCF74CE9840256F
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti354 – 3541H → Q in BAB70479. (PubMed:11523006)Curated
    Sequence conflicti519 – 5191P → A in AAI25505. (PubMed:15489334)Curated
    Sequence conflicti519 – 5191P → A in AAI25509. (PubMed:15489334)Curated
    Sequence conflicti700 – 7001R → C in AAI25505. (PubMed:15489334)Curated
    Sequence conflicti700 – 7001R → C in AAI25509. (PubMed:15489334)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei379 – 3813ATY → GSF in isoform 2. 1 PublicationVSP_035306
    Alternative sequencei382 – 703322Missing in isoform 2. 1 PublicationVSP_035307Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB050201 Genomic DNA. Translation: BAB70479.1.
    AB050202 mRNA. Translation: BAB70480.1.
    AB050203 mRNA. Translation: BAB70481.1.
    AB061518 mRNA. Translation: BAB55000.1.
    AB061519 mRNA. Translation: BAB55001.1.
    BC125504 mRNA. Translation: AAI25505.1.
    BC125508 mRNA. Translation: AAI25509.1.
    CCDSiCCDS35814.1. [Q91VA3-1]
    CCDS48477.1. [Q91VA3-2]
    RefSeqiNP_001139278.1. NM_001145806.1. [Q91VA3-2]
    NP_570960.2. NM_130890.2.
    UniGeneiMm.189201.

    Genome annotation databases

    EnsembliENSMUST00000048941; ENSMUSP00000047164; ENSMUSG00000038599.
    ENSMUST00000168514; ENSMUSP00000129549; ENSMUSG00000038599. [Q91VA3-2]
    GeneIDi170725.
    KEGGimmu:170725.
    UCSCiuc007dyh.2. mouse. [Q91VA3-2]
    uc007dyi.2. mouse. [Q91VA3-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB050201 Genomic DNA. Translation: BAB70479.1 .
    AB050202 mRNA. Translation: BAB70480.1 .
    AB050203 mRNA. Translation: BAB70481.1 .
    AB061518 mRNA. Translation: BAB55000.1 .
    AB061519 mRNA. Translation: BAB55001.1 .
    BC125504 mRNA. Translation: AAI25505.1 .
    BC125508 mRNA. Translation: AAI25509.1 .
    CCDSi CCDS35814.1. [Q91VA3-1 ]
    CCDS48477.1. [Q91VA3-2 ]
    RefSeqi NP_001139278.1. NM_001145806.1. [Q91VA3-2 ]
    NP_570960.2. NM_130890.2.
    UniGenei Mm.189201.

    3D structure databases

    ProteinModelPortali Q91VA3.
    SMRi Q91VA3. Positions 23-698.
    ModBasei Search...
    MobiDBi Search...

    Protein family/group databases

    MEROPSi C02.007.

    PTM databases

    PhosphoSitei Q91VA3.

    Proteomic databases

    MaxQBi Q91VA3.
    PRIDEi Q91VA3.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000048941 ; ENSMUSP00000047164 ; ENSMUSG00000038599 .
    ENSMUST00000168514 ; ENSMUSP00000129549 ; ENSMUSG00000038599 . [Q91VA3-2 ]
    GeneIDi 170725.
    KEGGi mmu:170725.
    UCSCi uc007dyh.2. mouse. [Q91VA3-2 ]
    uc007dyi.2. mouse. [Q91VA3-1 ]

    Organism-specific databases

    CTDi 388743.
    MGIi MGI:2181366. Capn8.

    Phylogenomic databases

    eggNOGi NOG327523.
    GeneTreei ENSGT00750000117457.
    HOGENOMi HOG000232035.
    HOVERGENi HBG012645.
    InParanoidi Q91VA3.
    KOi K08577.
    OrthoDBi EOG7RV9FM.
    PhylomeDBi Q91VA3.
    TreeFami TF314748.

    Miscellaneous databases

    NextBioi 370250.
    PROi Q91VA3.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q91VA3.
    CleanExi MM_CAPN8.
    Genevestigatori Q91VA3.

    Family and domain databases

    Gene3Di 1.10.238.10. 1 hit.
    InterProi IPR022684. Calpain_cysteine_protease.
    IPR022682. Calpain_domain_III.
    IPR022683. Calpain_III.
    IPR029543. CAPN8.
    IPR011992. EF-hand-dom_pair.
    IPR002048. EF_hand_dom.
    IPR000169. Pept_cys_AS.
    IPR001300. Peptidase_C2_calpain_cat.
    [Graphical view ]
    PANTHERi PTHR10183:SF52. PTHR10183:SF52. 1 hit.
    Pfami PF01067. Calpain_III. 1 hit.
    PF00648. Peptidase_C2. 1 hit.
    [Graphical view ]
    PRINTSi PR00704. CALPAIN.
    SMARTi SM00720. calpain_III. 1 hit.
    SM00230. CysPc. 1 hit.
    SM00054. EFh. 3 hits.
    [Graphical view ]
    SUPFAMi SSF49758. SSF49758. 1 hit.
    PROSITEi PS50203. CALPAIN_CAT. 1 hit.
    PS00139. THIOL_PROTEASE_CYS. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Both the conserved and the unique gene structure of stomach-specific calpains reveal processes of calpain gene evolution."
      Hata S., Nishi K., Kawamoto T., Lee H.-J., Kawahara H., Maeda T., Shintani Y., Sorimachi H., Suzuki K.
      J. Mol. Evol. 53:191-203(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY.
    2. "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: Brain.
    3. "Stomach-specific calpain, nCL-2, localizes in mucus cells and proteolyzes the beta-subunit of coatomer complex, beta-COP."
      Hata S., Koyama S., Kawahara H., Doi N., Maeda T., Toyama-Sorimachi N., Abe K., Suzuki K., Sorimachi H.
      J. Biol. Chem. 281:11214-11224(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH COPS1; COPB1; EYA2; NME2; NME4 AND TOMM70A, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
    4. "Stomach-specific calpain, nCL-2/calpain 8, is active without calpain regulatory subunit and oligomerizes through C2-like domains."
      Hata S., Doi N., Kitamura F., Sorimachi H.
      J. Biol. Chem. 282:27847-27856(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBUNIT, ENZYME REGULATION, DOMAIN, BIOPHYSICOCHEMICAL PROPERTIES, PTM, MUTAGENESIS OF CYS-105.

    Entry informationi

    Entry nameiCAN8_MOUSE
    AccessioniPrimary (citable) accession number: Q91VA3
    Secondary accession number(s): Q059W1, Q91UZ9, Q920R7
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: September 2, 2008
    Last sequence update: December 1, 2001
    Last modified: October 1, 2014
    This is version 102 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. Peptidase families
      Classification of peptidase families and list of entries
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3