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Q91VA3 (CAN8_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 88. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
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to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Calpain-8
EC=3.4.22.53
Alternative name(s):
New calpain 2
Short name=nCL-2
Stomach-specific M-type calpain
Gene names
Name:Capn8
Synonyms:Ncl2
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length703 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.3

Catalytic activity

Broad endopeptidase specificity.

Cofactor

Binds 2 calcium ions Potential.

Enzyme regulation

The concentration of calcium for half-maximal activity is 0.3mM. Inhibited by calpastatin and calpeptin. Ref.4

Subunit structure

Monomer and homooligomer. Interacts with COPS1/GPS1, COPB1, EYA2, NME2, NME4 and TOMM70A. Ref.3 Ref.4

Subcellular location

Cytoplasm By similarity. Golgi apparatus Ref.3.

Tissue specificity

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. Ref.1 Ref.3

Domain

The domain III mediates oligomerization. Ref.4

Post-translational modification

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.

Sequence similarities

Belongs to the peptidase C2 family.

Contains 1 calpain catalytic domain.

Contains 4 EF-hand domains.

Biophysicochemical properties

pH dependence:

Optimum pH is 6. Ref.4

Temperature dependence:

Optimum temperature is 20 degrees Celsius.

Ontologies

Keywords
   Cellular componentCytoplasm
Golgi apparatus
   Coding sequence diversityAlternative splicing
   DomainRepeat
   LigandCalcium
Metal-binding
   Molecular functionHydrolase
Protease
Thiol protease
   PTMAutocatalytic cleavage
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processproteolysis

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentGolgi apparatus

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functioncalcium ion binding

Inferred from electronic annotation. Source: InterPro

calcium-dependent cysteine-type endopeptidase activity

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q91VA3-1)

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.
Isoform 2 (identifier: Q91VA3-2)

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 703703Calpain-8
PRO_0000349281

Regions

Domain45 – 344300Calpain catalytic
Domain531 – 56636EF-hand 1
Domain575 – 61036EF-hand 2
Domain605 – 64036EF-hand 3
Domain670 – 70334EF-hand 4
Calcium binding588 – 599121 Potential
Calcium binding618 – 629122 Potential
Region355 – 512158Domain III
Region513 – 53119Linker By similarity
Region532 – 703172Domain IV By similarity

Sites

Active site1051 By similarity
Active site2621 By similarity
Active site2861 By similarity

Natural variations

Alternative sequence379 – 3813ATY → GSF in isoform 2.
VSP_035306
Alternative sequence382 – 703322Missing in isoform 2.
VSP_035307

Experimental info

Mutagenesis1051C → S: Loss of activity. Ref.4
Sequence conflict3541H → Q in BAB70479. Ref.1
Sequence conflict5191P → A in AAI25505. Ref.2
Sequence conflict5191P → A in AAI25509. Ref.2
Sequence conflict7001R → C in AAI25505. Ref.2
Sequence conflict7001R → C in AAI25509. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (nCL-2) [UniParc].

Last modified December 1, 2001. Version 1.
Checksum: 50F2F9CCF2192FB6

FASTA70379,335
        10         20         30         40         50         60 
MAALAAGISK QRAAAQGLGS NQNAVKYLGQ DFETLRKQCL NSGVLFKDPE FPACPSALGY 

        70         80         90        100        110        120 
RDLGPGSAET QGIIWKRPTE LCSNPQFIVG GATRTDIRQG GLGDCWLLAA IASLTLNEKL 

       130        140        150        160        170        180 
LYRVVPRDQS FQKNYAGIFH FQFWQYGEWV EVVIDDRLPT KNGQLLFLHS EEGNEFWSAL 

       190        200        210        220        230        240 
LEKAYAKLNG SYEALAGGST IEGFEDFTGG ISEFYDLRKP PGNLYYTIQK ALRKGSLLGC 

       250        260        270        280        290        300 
SIDVSNAAEA EATTRQKLVK GHAYSVTGVE EVDFRGLPEK LIRLRNPWGE VEWTGAWSDS 

       310        320        330        340        350        360 
APEWNYIDPQ KKGELDKRAE DGEFWMSFSD FLKQFSRLEI CNLSPDSLSS EEIHKWNLVL 

       370        380        390        400        410        420 
FNGRWTRGST AGGCQNYPAT YWTNPQFKIH LDEVDEDQEE GTSEPCCTVL LGLMQKNRRR 

       430        440        450        460        470        480 
QRRIGQGMLS IGYAVYQIPK ELENHTDEHL GRDFFQGRQP STCSSTYMNL REVSSRVQLP 

       490        500        510        520        530        540 
PGQYLVVPST FEPFKDGDFC LRVFSEKKAQ ALEIGDAVPG DPHEPHPRDM DGEDEHFWSL 

       550        560        570        580        590        600 
SEEFADKDSE ISAHQLKRVL NGLLSKRTDM KFDGFNINTC REMISLLDGD GTGSLRPVEF 

       610        620        630        640        650        660 
KTLWLKICKY LEIYQEMDHS RAGTIDAHEM RTALKKAGFT LNNQVQQTIA TRYACSKLGV 

       670        680        690        700 
DFDGFVACMI RLEILFKLFR LLDKDQNGIV QLSLAEWLCR ALV

« Hide

Isoform 2 (Calpain 8b) (nCL-2') [UniParc].

Checksum: ECCF74CE9840256F
Show »

FASTA38142,434

References

« Hide 'large scale' references
[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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		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.
IPIIPI00126630.
IPI00903421.
RefSeqNP_001139278.1. NM_001145806.1.
NP_570960.2. NM_130890.2.
UniGeneMm.189201.

3D structure databases

HSSPHSSP built from PDB template 1DF0 based on UniProtKB Q07009.
ProteinModelPortalQ91VA3.
SMRQ91VA3. Positions 23-698.
ModBaseSearch...

Protein family/group databases

MEROPSC02.007.

PTM databases

PhosphoSiteQ91VA3.

Proteomic databases

PRIDEQ91VA3.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000048941; ENSMUSP00000047164; ENSMUSG00000038599.
ENSMUST00000168514; ENSMUSP00000129549; ENSMUSG00000038599.
GeneID170725.
KEGGmmu:170725.
UCSCuc007dyh.2. mouse.
uc007dyi.2. mouse.

Organism-specific databases

CTD388743.
MGIMGI:2181366. Capn8.

Phylogenomic databases

eggNOGNOG327523.
GeneTreeENSGT00700000104379.
HOGENOMHOG000232035.
HOVERGENHBG012645.
InParanoidQ91VA3.
KOK08577.
OrthoDBEOG4HX50K.

Gene expression databases

BgeeQ91VA3.
CleanExMM_CAPN8.
GenevestigatorQ91VA3.

Family and domain databases

Gene3D1.10.238.10. 1 hit.
InterProIPR022684. Calpain_cysteine_protease.
IPR022682. Calpain_domain_III.
IPR022683. Calpain_III.
IPR011992. EF-hand-like_dom.
IPR002048. EF_hand_dom.
IPR000169. Pept_cys_AS.
IPR001300. Peptidase_C2_calpain_cat.
[Graphical view]
PfamPF01067. Calpain_III. 1 hit.
PF00648. Peptidase_C2. 1 hit.
[Graphical view]
PRINTSPR00704. CALPAIN.
SMARTSM00720. calpain_III. 1 hit.
SM00230. CysPc. 1 hit.
SM00054. EFh. 3 hits.
[Graphical view]
SUPFAMSSF49758. Peptidase_C2. 1 hit.
PROSITEPS50203. CALPAIN_CAT. 1 hit.
PS00018. EF_HAND_1. False negative.
PS50222. EF_HAND_2. False negative.
PS00640. THIOL_PROTEASE_ASN. False negative.
PS00139. THIOL_PROTEASE_CYS. 1 hit.
PS00639. THIOL_PROTEASE_HIS. False negative.
[Graphical view]
ProtoNetSearch...

Other

NextBio370250.
SOURCESearch...

Entry information

Entry nameCAN8_MOUSE
AccessionPrimary (citable) accession number: Q91VA3
Secondary accession number(s): Q059W1, Q91UZ9, Q920R7
Entry history
Integrated into UniProtKB/Swiss-Prot: September 2, 2008
Last sequence update: December 1, 2001
Last modified: May 1, 2013
This is version 88 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

Peptidase families

Classification of peptidase families and list of entries

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents