Q64691 (CAN3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:

Capn3

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	821 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Calcium-regulated non-lysosomal thiol-protease.
Catalytic activity	Broad endopeptidase activity.
Enzyme regulation	Activated by micromolar concentrations of calcium and inhibited by calpastatin.
Subunit structure	Interacts with TTN/titin By similarity. Interacts with CMYA5; this interaction, which results in CMYA5 proteolysis, may protect CAPN3 from autolysis By similarity.
Subcellular location	Cytoplasm.
Sequence similarities	Belongs to the peptidase C2 family. Contains 1 calpain catalytic domain. Contains 4 EF-hand domains.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing
Domain	Repeat
Ligand	Calcium Metal-binding
Molecular function	Hydrolase Protease Thiol protease
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	G1 to G0 transition involved in cell differentiation Inferred from direct assay PubMed 20139084. Source: UniProtKB autolysis Inferred from direct assay PubMed 20460380. Source: UniProtKB cellular response to calcium ion Inferred from direct assay PubMed 20460380. Source: UniProtKB cellular response to salt stress Inferred from direct assay PubMed 20460380. Source: UniProtKB negative regulation of apoptotic process Inferred from mutant phenotype PubMed 18073330. Source: UniProtKB negative regulation of protein sumoylation Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of transcription, DNA-dependent Inferred from direct assay PubMed 20139084. Source: UniProtKB positive regulation of NF-kappaB transcription factor activity Inferred from mutant phenotype PubMed 18073330. Source: UniProtKB positive regulation of proteolysis Inferred from direct assay PubMed 20139084. Source: UniProtKB positive regulation of release of sequestered calcium ion into cytosol Inferred from mutant phenotype PubMed 18676612. Source: UniProtKB positive regulation of satellite cell activation involved in skeletal muscle regeneration Inferred from direct assay PubMed 20139084. Source: UniProtKB positive regulation of transcription, DNA-dependent Inferred from mutant phenotype PubMed 18073330. Source: UniProtKB protein complex assembly Inferred from mutant phenotype PubMed 18676612. Source: UniProtKB protein localization to membrane Inferred from mutant phenotype PubMed 18676612. Source: UniProtKB regulation of I-kappaB kinase/NF-kappaB cascade Inferred from mutant phenotype PubMed 18073330. Source: UniProtKB regulation of myoblast differentiation Inferred from direct assay PubMed 20139084. Source: UniProtKB response to muscle activity Inferred from sequence or structural similarity. Source: UniProtKB sarcomere organization Inferred from mutant phenotype PubMed 15138196. Source: MGI self proteolysis Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	T-tubule Inferred from sequence or structural similarity. Source: UniProtKB Z disc Inferred from sequence or structural similarity. Source: UniProtKB cytosol Inferred from direct assay PubMed 18676612. Source: UniProtKB nucleus Inferred from sequence or structural similarity. Source: UniProtKB protein complex Inferred from direct assay PubMed 18676612. Source: UniProtKB
Molecular_function	calcium ion binding Inferred from direct assay PubMed 20460380. Source: UniProtKB calcium-dependent cysteine-type endopeptidase activity Inferred from direct assay PubMed 15138196. Source: MGI ligase regulator activity Inferred from sequence or structural similarity. Source: UniProtKB protein complex scaffold Inferred from mutant phenotype PubMed 18676612. Source: UniProtKB sodium ion binding Inferred from direct assay PubMed 20460380. Source: UniProtKB structural constituent of muscle Inferred from mutant phenotype PubMed 18676612. Source: UniProtKB titin binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform Long (identifier: Q64691-1)

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 Short (identifier: Q64691-2)

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

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 821	821	Calpain-3		PRO_0000207708
Regions
	Domain	74 – 417	344	Calpain catalytic
	Domain	649 – 683	35	EF-hand 1
	Domain	692 – 725	34	EF-hand 2
	Domain	722 – 757	36	EF-hand 3
	Domain	787 – 821	35	EF-hand 4
	Calcium binding	705 – 716	12	1 Probable
	Calcium binding	735 – 746	12	2 Probable
	Region	418 – 586	169	Domain III
	Region	587 – 649	63	Linker
	Region	650 – 820	171	Domain IV
Sites
	Active site	129	1	By similarity
	Active site	334	1	By similarity
	Active site	358	1	By similarity
Natural variations
	Alternative sequence	268 – 315	48	Missing in isoform Short.		VSP_005230
	Alternative sequence	595 – 638	44	Missing in isoform Short.		VSP_005231
Experimental info
	Sequence conflict	66	1	R → K in CAA63301. Ref.1
	Sequence conflict	66	1	R → K in AAD28255. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform Long [UniParc]. Last modified July 27, 2011. Version 2. Checksum: C7FC94E31E1084C9	FASTA	821	94,242
	10 20 30 40 50 60 MPTVISPTVA PRTGAEPRSP GPVPHPAQGK TTEAGGGHPS GIYSAIISRN FPIIGVKEKT 70 80 90 100 110 120 FEQLRRKCLE KKVLYLDPEF PPDETSLFYS QKFPIQFVWK RPPEICENPR FIIGGANRTD 130 140 150 160 170 180 ICQGDLGDCW FLAAIACLTL NERLLFRVIP HDQSFTENYA GIFHFQFWRY GDWVDVVIDD 190 200 210 220 230 240 CLPTYNNQLV FTKSNHRNEF WSALLEKAYA KLHGSYEALK GGNTTEAMED FTGGVTEFFE 250 260 270 280 290 300 IKDAPSDMYK IMRKAIERGS LMGCSIDDGT NMTYGTSPSG LNMGELIARM VRNMDNSLLR 310 320 330 340 350 360 DSDLDPRGSD DRPSRTIVPV QYETRMACGL VKGHAYSVTG LEEALFKGEK VKLVRLRNPW 370 380 390 400 410 420 GQVEWNGSWS DGWKDWSFVD KDEKARLQHQ VTEDGEFWMS YDDFVYHFTK LEICNLTADA 430 440 450 460 470 480 LESDKLQTWT VSVNEGRWVR GCSAGGCRNF PDTFWTNPQY RLKLLEEDDD PEDSEVICSF 490 500 510 520 530 540 LVALMQKNRR KDRKLGANLF TIGFAIYEVP KEMHGNKQHL QKDFFLYNAS KARSKTYINM 550 560 570 580 590 600 REVSQRFRLP PSEYVIVPST YEPHQEGEFI LRVFSEKRNL SEEAENTISV DRPVKKKKNK 610 620 630 640 650 660 PIIFVSDRAN SNKELGVDQE AEEGKDKAGP EKRGETPQPR PGHTDQESEE QQQFRNIFRQ 670 680 690 700 710 720 IAGDDMEICA DELKNVLNTV VNKHKDLKTQ GFTLESCRSM IALMDTDGSG RLNLQEFHHL 730 740 750 760 770 780 WKKIKAWQKI FKHYDTDHSG TINSYEMRNA VNDAGFHLNS QLYDIITMRY ADKHMNIDFD 790 800 810 820 SFICCFVRLE GMFRAFNAFD KDGDGIIKLN VLEWLQLTMY A
	Isoform Short [UniParc]. Checksum: 48CF94460279C4EB	FASTA	729	84,096
	10 20 30 40 50 60 MPTVISPTVA PRTGAEPRSP GPVPHPAQGK TTEAGGGHPS GIYSAIISRN FPIIGVKEKT 70 80 90 100 110 120 FEQLRRKCLE KKVLYLDPEF PPDETSLFYS QKFPIQFVWK RPPEICENPR FIIGGANRTD 130 140 150 160 170 180 ICQGDLGDCW FLAAIACLTL NERLLFRVIP HDQSFTENYA GIFHFQFWRY GDWVDVVIDD 190 200 210 220 230 240 CLPTYNNQLV FTKSNHRNEF WSALLEKAYA KLHGSYEALK GGNTTEAMED FTGGVTEFFE 250 260 270 280 290 300 IKDAPSDMYK IMRKAIERGS LMGCSIDTIV PVQYETRMAC GLVKGHAYSV TGLEEALFKG 310 320 330 340 350 360 EKVKLVRLRN PWGQVEWNGS WSDGWKDWSF VDKDEKARLQ HQVTEDGEFW MSYDDFVYHF 370 380 390 400 410 420 TKLEICNLTA DALESDKLQT WTVSVNEGRW VRGCSAGGCR NFPDTFWTNP QYRLKLLEED 430 440 450 460 470 480 DDPEDSEVIC SFLVALMQKN RRKDRKLGAN LFTIGFAIYE VPKEMHGNKQ HLQKDFFLYN 490 500 510 520 530 540 ASKARSKTYI NMREVSQRFR LPPSEYVIVP STYEPHQEGE FILRVFSEKR NLSEEAENTI 550 560 570 580 590 600 SVDRPVPRPG HTDQESEEQQ QFRNIFRQIA GDDMEICADE LKNVLNTVVN KHKDLKTQGF 610 620 630 640 650 660 TLESCRSMIA LMDTDGSGRL NLQEFHHLWK KIKAWQKIFK HYDTDHSGTI NSYEMRNAVN 670 680 690 700 710 720 DAGFHLNSQL YDIITMRYAD KHMNIDFDSF ICCFVRLEGM FRAFNAFDKD GDGIIKLNVL EWLQLTMYA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X92523 mRNA. Translation: CAA63301.1. AF127766 mRNA. Translation: AAD28255.2. AL935121 Genomic DNA. Translation: CAM24140.1.
IPI	IPI00136966. IPI00228659.
RefSeq	NP_001171270.1. NM_001177799.1. NP_031627.2. NM_007601.3.
UniGene	Mm.195877. Mm.458021.
3D structure databases
ProteinModelPortal	Q64691.
SMR	Q64691. Positions 59-821.
ModBase	Search...
Protein family/group databases
MEROPS	C02.004.
PTM databases
PhosphoSite	Q64691.
Proteomic databases
PRIDE	Q64691.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000028749; ENSMUSP00000028749; ENSMUSG00000079110. ENSMUST00000110721; ENSMUSP00000106349; ENSMUSG00000079110.
GeneID	12335.
KEGG	mmu:12335.
UCSC	uc008lvz.2. mouse.
Organism-specific databases
CTD	825.
MGI	MGI:107437. Capn3.
Phylogenomic databases
eggNOG	NOG327523.
GeneTree	ENSGT00700000104110.
HOGENOM	HOG000232035.
HOVERGEN	HBG012645.
InParanoid	A2AVV3.
KO	K08573.
OrthoDB	EOG4MSCXQ.
Enzyme and pathway databases
BRENDA	3.4.22.54. 3474.
Gene expression databases
ArrayExpress	Q64691.
Bgee	Q64691.
CleanEx	MM_CAPN3.
Genevestigator	Q64691.
GermOnline	ENSMUSG00000062646. Mus musculus.
Family and domain databases
Gene3D	1.10.238.10. 1 hit.
InterPro	IPR022684. Calpain_cysteine_protease. IPR022682. Calpain_domain_III. IPR022683. Calpain_III. IPR011992. EF-hand-like_dom. IPR018247. EF_Hand_1_Ca_BS. IPR002048. EF_hand_dom. IPR000169. Pept_cys_AS. IPR001300. Peptidase_C2_calpain_cat. [Graphical view]
Pfam	PF01067. Calpain_III. 1 hit. PF13202. EF_hand_3. 1 hit. PF13405. EF_hand_4. 1 hit. PF00648. Peptidase_C2. 2 hits. [Graphical view]
PRINTS	PR00704. CALPAIN.
SMART	SM00720. calpain_III. 1 hit. SM00230. CysPc. 1 hit. SM00054. EFh. 3 hits. [Graphical view]
SUPFAM	SSF49758. Peptidase_C2. 1 hit.
PROSITE	PS50203. CALPAIN_CAT. 1 hit. PS00018. EF_HAND_1. 2 hits. PS50222. EF_HAND_2. 4 hits. PS00640. THIOL_PROTEASE_ASN. False negative. PS00139. THIOL_PROTEASE_CYS. 1 hit. PS00639. THIOL_PROTEASE_HIS. False negative. [Graphical view]
ProtoNet	Search...
Other
NextBio	280948.
SOURCE	Search...

Entry information

Entry name

CAN3_MOUSE

Accession

Primary (citable) accession number: Q64691
Secondary accession number(s): A2AVV3, Q9WUC5

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	July 27, 2011
Last modified:	May 29, 2013
This is version 127 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program