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Q91VA3

- CAN8_MOUSE

UniProt

Q91VA3 - CAN8_MOUSE

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Protein

Calpain-8

Gene

Capn8

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

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

Ca2+CuratedNote: 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. digestion Source: InterPro
  2. proteolysis Source: RefGenome
Complete GO annotation...

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-KW
Complete GO annotation...

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.
GeneTreeiENSGT00760000118971.
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

        10         20         30         40         50
MAALAAGISK QRAAAQGLGS NQNAVKYLGQ DFETLRKQCL NSGVLFKDPE
60 70 80 90 100
FPACPSALGY RDLGPGSAET QGIIWKRPTE LCSNPQFIVG GATRTDIRQG
110 120 130 140 150
GLGDCWLLAA IASLTLNEKL LYRVVPRDQS FQKNYAGIFH FQFWQYGEWV
160 170 180 190 200
EVVIDDRLPT KNGQLLFLHS EEGNEFWSAL LEKAYAKLNG SYEALAGGST
210 220 230 240 250
IEGFEDFTGG ISEFYDLRKP PGNLYYTIQK ALRKGSLLGC SIDVSNAAEA
260 270 280 290 300
EATTRQKLVK GHAYSVTGVE EVDFRGLPEK LIRLRNPWGE VEWTGAWSDS
310 320 330 340 350
APEWNYIDPQ KKGELDKRAE DGEFWMSFSD FLKQFSRLEI CNLSPDSLSS
360 370 380 390 400
EEIHKWNLVL FNGRWTRGST AGGCQNYPAT YWTNPQFKIH LDEVDEDQEE
410 420 430 440 450
GTSEPCCTVL LGLMQKNRRR QRRIGQGMLS IGYAVYQIPK ELENHTDEHL
460 470 480 490 500
GRDFFQGRQP STCSSTYMNL REVSSRVQLP PGQYLVVPST FEPFKDGDFC
510 520 530 540 550
LRVFSEKKAQ ALEIGDAVPG DPHEPHPRDM DGEDEHFWSL SEEFADKDSE
560 570 580 590 600
ISAHQLKRVL NGLLSKRTDM KFDGFNINTC REMISLLDGD GTGSLRPVEF
610 620 630 640 650
KTLWLKICKY LEIYQEMDHS RAGTIDAHEM RTALKKAGFT LNNQVQQTIA
660 670 680 690 700
TRYACSKLGV DFDGFVACMI RLEILFKLFR LLDKDQNGIV QLSLAEWLCR

ALV
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:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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 ENSGT00760000118971.
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

« Hide 'large scale' publications
  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: November 26, 2014
This is version 104 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