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Protein

Calpain-3

Gene

Capn3

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

Functioni

Calcium-regulated non-lysosomal thiol-protease.

Catalytic activityi

Broad endopeptidase activity.

Enzyme regulationi

Activated by micromolar concentrations of calcium and inhibited by calpastatin.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei129 – 1291By similarity
Active sitei334 – 3341By similarity
Active sitei358 – 3581By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Calcium bindingi705 – 716121CuratedAdd
BLAST
Calcium bindingi735 – 746122CuratedAdd
BLAST

GO - Molecular functioni

  • calcium-dependent cysteine-type endopeptidase activity Source: MGI
  • calcium ion binding Source: UniProtKB
  • catalytic activity Source: UniProtKB
  • ligase regulator activity Source: UniProtKB
  • peptidase activity Source: UniProtKB
  • protein complex scaffold Source: UniProtKB
  • sodium ion binding Source: UniProtKB
  • structural constituent of muscle Source: UniProtKB
  • titin binding Source: UniProtKB

GO - Biological processi

  • autolysis Source: UniProtKB
  • cellular response to calcium ion Source: UniProtKB
  • cellular response to salt stress Source: UniProtKB
  • G1 to G0 transition involved in cell differentiation Source: UniProtKB
  • muscle structure development Source: UniProtKB
  • myofibril assembly Source: MGI
  • negative regulation of apoptotic process Source: UniProtKB
  • negative regulation of protein sumoylation Source: UniProtKB
  • negative regulation of skeletal muscle cell differentiation Source: MGI
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
  • positive regulation of proteolysis Source: UniProtKB
  • positive regulation of release of sequestered calcium ion into cytosol Source: UniProtKB
  • positive regulation of satellite cell activation involved in skeletal muscle regeneration Source: UniProtKB
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • protein complex assembly Source: UniProtKB
  • protein localization to membrane Source: UniProtKB
  • proteolysis Source: UniProtKB
  • regulation of catalytic activity Source: UniProtKB
  • regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
  • regulation of myoblast differentiation Source: UniProtKB
  • response to calcium ion Source: UniProtKB
  • response to muscle activity Source: UniProtKB
  • sarcomere organization Source: MGI
  • self proteolysis Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Thiol protease

Keywords - Ligandi

Calcium, Metal-binding

Enzyme and pathway databases

BRENDAi3.4.22.54. 3474.

Protein family/group databases

MEROPSiC02.004.

Names & Taxonomyi

Protein namesi
Recommended name:
Calpain-3 (EC:3.4.22.54)
Alternative name(s):
Calcium-activated neutral proteinase 3
Short name:
CANP 3
Calpain L3
Calpain p94
Muscle-specific calcium-activated neutral protease 3
Gene namesi
Name:Capn3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:107437. Capn3.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: UniProtKB
  • myofibril Source: UniProtKB
  • nucleus Source: UniProtKB
  • plasma membrane Source: UniProtKB
  • protein complex Source: UniProtKB
  • T-tubule Source: UniProtKB
  • Z disc Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 821821Calpain-3PRO_0000207708Add
BLAST

Proteomic databases

MaxQBiQ64691.
PaxDbiQ64691.
PRIDEiQ64691.

PTM databases

iPTMnetiQ64691.
PhosphoSiteiQ64691.

Expressioni

Gene expression databases

BgeeiQ64691.
CleanExiMM_CAPN3.
ExpressionAtlasiQ64691. baseline and differential.
GenevisibleiQ64691. MM.

Interactioni

Subunit structurei

Interacts with TTN/titin. Interacts with CMYA5; this interaction, which results in CMYA5 proteolysis, may protect CAPN3 from autolysis.By similarity

GO - Molecular functioni

  • protein complex scaffold Source: UniProtKB
  • titin binding Source: UniProtKB

Protein-protein interaction databases

BioGridi198472. 2 interactions.
STRINGi10090.ENSMUSP00000028749.

Structurei

3D structure databases

ProteinModelPortaliQ64691.
SMRiQ64691. Positions 59-821.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini74 – 417344Calpain catalyticPROSITE-ProRule annotationAdd
BLAST
Domaini649 – 68335EF-hand 1PROSITE-ProRule annotationAdd
BLAST
Domaini692 – 72534EF-hand 2PROSITE-ProRule annotationAdd
BLAST
Domaini722 – 75736EF-hand 3PROSITE-ProRule annotationAdd
BLAST
Domaini787 – 82135EF-hand 4PROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni418 – 586169Domain IIIAdd
BLAST
Regioni587 – 64963LinkerAdd
BLAST
Regioni650 – 820171Domain IVAdd
BLAST

Sequence similaritiesi

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

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0045. Eukaryota.
ENOG410XP0B. LUCA.
GeneTreeiENSGT00760000118971.
HOGENOMiHOG000232035.
HOVERGENiHBG012645.
InParanoidiQ64691.
KOiK08573.
OrthoDBiEOG7RV9FM.
TreeFamiTF314748.

Family and domain databases

Gene3Di1.10.238.10. 1 hit.
InterProiIPR022684. Calpain_cysteine_protease.
IPR022682. Calpain_domain_III.
IPR022683. Calpain_III.
IPR029531. CAPN3.
IPR011992. EF-hand-dom_pair.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
IPR000169. Pept_cys_AS.
IPR001300. Peptidase_C2_calpain_cat.
[Graphical view]
PANTHERiPTHR10183:SF320. PTHR10183:SF320. 2 hits.
PfamiPF01067. Calpain_III. 1 hit.
PF13202. EF-hand_5. 1 hit.
PF13833. EF-hand_8. 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]
SUPFAMiSSF47473. SSF47473. 1 hit.
SSF49758. SSF49758. 1 hit.
PROSITEiPS50203. CALPAIN_CAT. 1 hit.
PS00018. EF_HAND_1. 2 hits.
PS50222. EF_HAND_2. 4 hits.
PS00139. THIOL_PROTEASE_CYS. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform Long (identifier: Q64691-1) [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

        10         20         30         40         50
MPTVISPTVA PRTGAEPRSP GPVPHPAQGK TTEAGGGHPS GIYSAIISRN
60 70 80 90 100
FPIIGVKEKT FEQLRRKCLE KKVLYLDPEF PPDETSLFYS QKFPIQFVWK
110 120 130 140 150
RPPEICENPR FIIGGANRTD ICQGDLGDCW FLAAIACLTL NERLLFRVIP
160 170 180 190 200
HDQSFTENYA GIFHFQFWRY GDWVDVVIDD CLPTYNNQLV FTKSNHRNEF
210 220 230 240 250
WSALLEKAYA KLHGSYEALK GGNTTEAMED FTGGVTEFFE IKDAPSDMYK
260 270 280 290 300
IMRKAIERGS LMGCSIDDGT NMTYGTSPSG LNMGELIARM VRNMDNSLLR
310 320 330 340 350
DSDLDPRGSD DRPSRTIVPV QYETRMACGL VKGHAYSVTG LEEALFKGEK
360 370 380 390 400
VKLVRLRNPW GQVEWNGSWS DGWKDWSFVD KDEKARLQHQ VTEDGEFWMS
410 420 430 440 450
YDDFVYHFTK LEICNLTADA LESDKLQTWT VSVNEGRWVR GCSAGGCRNF
460 470 480 490 500
PDTFWTNPQY RLKLLEEDDD PEDSEVICSF LVALMQKNRR KDRKLGANLF
510 520 530 540 550
TIGFAIYEVP KEMHGNKQHL QKDFFLYNAS KARSKTYINM REVSQRFRLP
560 570 580 590 600
PSEYVIVPST YEPHQEGEFI LRVFSEKRNL SEEAENTISV DRPVKKKKNK
610 620 630 640 650
PIIFVSDRAN SNKELGVDQE AEEGKDKAGP EKRGETPQPR PGHTDQESEE
660 670 680 690 700
QQQFRNIFRQ IAGDDMEICA DELKNVLNTV VNKHKDLKTQ GFTLESCRSM
710 720 730 740 750
IALMDTDGSG RLNLQEFHHL WKKIKAWQKI FKHYDTDHSG TINSYEMRNA
760 770 780 790 800
VNDAGFHLNS QLYDIITMRY ADKHMNIDFD SFICCFVRLE GMFRAFNAFD
810 820
KDGDGIIKLN VLEWLQLTMY A
Length:821
Mass (Da):94,242
Last modified:July 27, 2011 - v2
Checksum:iC7FC94E31E1084C9
GO
Isoform Short (identifier: Q64691-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     268-315: Missing.
     595-638: Missing.

Show »
Length:729
Mass (Da):84,096
Checksum:i48CF94460279C4EB
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti66 – 661R → K in CAA63301 (PubMed:8661728).Curated
Sequence conflicti66 – 661R → K in AAD28255 (Ref. 2) Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei268 – 31548Missing in isoform Short. 1 PublicationVSP_005230Add
BLAST
Alternative sequencei595 – 63844Missing in isoform Short. 1 PublicationVSP_005231Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X92523 mRNA. Translation: CAA63301.1.
AF127766 mRNA. Translation: AAD28255.2.
AL935121 Genomic DNA. Translation: CAM24140.1.
CCDSiCCDS16620.1. [Q64691-1]
CCDS50679.1. [Q64691-2]
RefSeqiNP_001171270.1. NM_001177799.1. [Q64691-2]
NP_031627.2. NM_007601.3. [Q64691-1]
UniGeneiMm.458021.
Mm.485295.

Genome annotation databases

EnsembliENSMUST00000028749; ENSMUSP00000028749; ENSMUSG00000079110. [Q64691-1]
ENSMUST00000110721; ENSMUSP00000106349; ENSMUSG00000079110. [Q64691-2]
GeneIDi12335.
KEGGimmu:12335.
UCSCiuc008lvz.2. mouse. [Q64691-1]
uc008lwa.2. mouse. [Q64691-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X92523 mRNA. Translation: CAA63301.1.
AF127766 mRNA. Translation: AAD28255.2.
AL935121 Genomic DNA. Translation: CAM24140.1.
CCDSiCCDS16620.1. [Q64691-1]
CCDS50679.1. [Q64691-2]
RefSeqiNP_001171270.1. NM_001177799.1. [Q64691-2]
NP_031627.2. NM_007601.3. [Q64691-1]
UniGeneiMm.458021.
Mm.485295.

3D structure databases

ProteinModelPortaliQ64691.
SMRiQ64691. Positions 59-821.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi198472. 2 interactions.
STRINGi10090.ENSMUSP00000028749.

Protein family/group databases

MEROPSiC02.004.

PTM databases

iPTMnetiQ64691.
PhosphoSiteiQ64691.

Proteomic databases

MaxQBiQ64691.
PaxDbiQ64691.
PRIDEiQ64691.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000028749; ENSMUSP00000028749; ENSMUSG00000079110. [Q64691-1]
ENSMUST00000110721; ENSMUSP00000106349; ENSMUSG00000079110. [Q64691-2]
GeneIDi12335.
KEGGimmu:12335.
UCSCiuc008lvz.2. mouse. [Q64691-1]
uc008lwa.2. mouse. [Q64691-2]

Organism-specific databases

CTDi825.
MGIiMGI:107437. Capn3.

Phylogenomic databases

eggNOGiKOG0045. Eukaryota.
ENOG410XP0B. LUCA.
GeneTreeiENSGT00760000118971.
HOGENOMiHOG000232035.
HOVERGENiHBG012645.
InParanoidiQ64691.
KOiK08573.
OrthoDBiEOG7RV9FM.
TreeFamiTF314748.

Enzyme and pathway databases

BRENDAi3.4.22.54. 3474.

Miscellaneous databases

NextBioi280948.
PROiQ64691.
SOURCEiSearch...

Gene expression databases

BgeeiQ64691.
CleanExiMM_CAPN3.
ExpressionAtlasiQ64691. baseline and differential.
GenevisibleiQ64691. MM.

Family and domain databases

Gene3Di1.10.238.10. 1 hit.
InterProiIPR022684. Calpain_cysteine_protease.
IPR022682. Calpain_domain_III.
IPR022683. Calpain_III.
IPR029531. CAPN3.
IPR011992. EF-hand-dom_pair.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
IPR000169. Pept_cys_AS.
IPR001300. Peptidase_C2_calpain_cat.
[Graphical view]
PANTHERiPTHR10183:SF320. PTHR10183:SF320. 2 hits.
PfamiPF01067. Calpain_III. 1 hit.
PF13202. EF-hand_5. 1 hit.
PF13833. EF-hand_8. 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]
SUPFAMiSSF47473. SSF47473. 1 hit.
SSF49758. SSF49758. 1 hit.
PROSITEiPS50203. CALPAIN_CAT. 1 hit.
PS00018. EF_HAND_1. 2 hits.
PS50222. EF_HAND_2. 4 hits.
PS00139. THIOL_PROTEASE_CYS. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Molecular cloning of mouse canp3, the gene associated with limb-girdle muscular dystrophy 2A in human."
    Richard I., Beckmann J.S.
    Mamm. Genome 7:377-379(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG).
  2. "Alternatively exon-spliced calpain 3 isoform expressed in mouse thymus."
    Dickson J.M.J., Love D., Evans C.W.E.
    Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT).
  3. Dickson J.M.J., Love D., Evans C.W.E.
    Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases
    Cited for: SEQUENCE REVISION TO 638-640.
  4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.

Entry informationi

Entry nameiCAN3_MOUSE
AccessioniPrimary (citable) accession number: Q64691
Secondary accession number(s): A2AVV3, Q9WUC5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: July 27, 2011
Last modified: May 11, 2016
This is version 149 of the entry and version 2 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.