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Calpain

Primary information about calpain:
Basic chemical and physical information	Basic biological information	Basic genomic information	Metal ion binding constants	Interspecies sequence alignment	Information on function
Summary of structural studies	Information on the conformational change	List of available structures	Information about mutations	References about calpain	Other web resources about calpain

Basic Information

Basic Chemical and Physical Information:
Additional names and abbreviations:	calpain: calcium-activated neutral protease (CANP); calcium-dependent protease calpain large subunit: calpain I large subunit; mu-calpain large subunit calpain large subunit: calpain II large subunit; m-calpain large subunit calpain large subunit: calpain III large subunit; n-calpain large subunit
Isoforms:	large subunit isoform I large subunit isoform II large subunit isoform III large subunit lower animal isoform small subunit
Yeast Protein Database Entries:	No links to the YPD are stored in the database

Number of amino acids:	large subunit isoform I: 714 (all species) large subunit isoform II: 700 (all species) large subunit isoform III: 810 (Gallus gallus) - 821 (Rattus norvegicus, Mus musculus, Homo sapiens) large subunit lower animal isoform: 758 (Schistosoma mansoni) - 828 (Drosophila melanogaster) small subunit: 263 (Bos taurus) - 268 (Homo sapiens) View a list of all sources stored in the database
Molecular weight:	large subunit isoform I: 81.889 kD (all species) large subunit isoform II: 79.228 kD (Gallus gallus) - 80.006 kD (Homo sapiens) large subunit isoform III: 93.56 kD (Gallus gallus) - 94.253 kD (Homo sapiens) large subunit lower animal isoform: 86.863 kD (Schistosoma mansoni) - 93.985 kD (Drosophila melanogaster) small subunit: 27.931 kD (Bos taurus) - 28.316 kD (Homo sapiens) View a list of all sources stored in the database
pI:	not yet available in the data library
Number of functional calcium binding sites:	not yet available in the data library
Macroscopic calcium binding constants:	not yet available in the data library
Other metal binding constants:	not yet available in the data library
Protein stability:	not yet available in the data library
Post-translational modifications:	large subunit isoform I, all sources: auto-proteolysis (made by: self effect: seems to be required for full protease activiy, and also reduces the calcium requirement) (InfoCard) large subunit isoform II, all sources: auto-proteolysis (made by: self effect: seems to be required for full protease activiy, and also reduces the calcium requirement) (InfoCard) small subunit, all sources: auto-proteolysis (made by: self effect: seems to be required for full protease activiy, and also reduces the calcium requirement) (InfoCard)

Basic Biological Information:
Source organisms:	large subunit isoform I: Homo sapiens large subunit isoform II: Gallus gallus, Homo sapiens, Mus musculus, Rattus norvegicus large subunit isoform III: Gallus gallus, Homo sapiens, Mus musculus, Rattus norvegicus large subunit lower animal isoform: Schistosoma mansoni, Drosophila melanogaster small subunit: Bos taurus, Homo sapiens, Sus scrofa, Oryctolagus cuniculus View an annotated list of all sources stored in the database
Tissues:	large subunit isoform I, mammals: skeletal msucle (InfoCard) large subunit isoform I, mammals: kidney (InfoCard) large subunit isoform I, mammals: erythrocytes (InfoCard) large subunit isoform II, mammals: skeletal muscle (InfoCard) large subunit isoform II, mammals: kidney (InfoCard)
Subcellular localization:	not yet available in the data library
Regulation:	not yet available in the data library

Genomic Information:
GenBank entries:	View a list of GenBank entries stored in the database
Gene length:	not yet available in the data library
Gene structure:	not yet available in the data library
Promoter:	not yet available in the data library
Gene copies:	not yet available in the data library
Alleles:	no alleles are currently stored in the data library
Chromosomal localization:	large subunit isoform III, Homo sapiens, expressed (GenBank code X85030): chromosome 15 (InfoCard)

Interspecies Sequence Alignment



                        |-helixI-|--loop1----|helixII|
                         En**nn**nX*Y*ZG#Ix**zn**nn*n                          

Calpain-I (mu-calpain) large subunit
HUMAN   (541):   ....EEIDENFKALFRQLAGEDMEISVKELRTILNRIISKHKDLRTKGFSLE
RABBIT (frag):         IDENFKALFRQLAGEDLEISVRELQTILNRITSKHKDLRTKGFSME

Calpain-II (m-calpain) large subunit
HUMAN   (531):      ....DDGVRRLFAQLAGEDAEISAFELQTILRRVLAKRQDIKSDGFSIE
MOUSE   (531):      ....DDGFRRLFVQLAGEDAEISAFELQTILRRVLAKRQDIKSDGFSIE
RAT     (531):      ....GDGFRRLFAQLAGEDAEISAFELQTILRRVLAKREDIKSDGFSIE
RABBIT (frag):    ....DIDDGFRRLFAQLAGEDAEISAFELQNILRRVLAKRQDIKTDGLSIE
PORCINE    (frag):  ....EDDIDDGFRRLFAQLAGEDAEISAFELQTILRRVLAKRQDIKSDGFSIE
CHICK   (531):      ....EPSFKKLFGQLAGSDAEISAFELRSILNKILAKRQDIKSDGFSIE

Calpain-III (calpain p94) large subunit
HUMAN   (651):      ....QQQFRNIFKQIAGDDMEICADELKKVLNTVVNKHKDLKTHGFTLE
MOUSE   (651):      ....QQQFRNIFRQIAGDDMEICADELKNVLNTVVNKHKDLKTQGFTLE
RAT     (651):      ....QQQFRNIFRQIAGDDMEICADELKNVLNTVVNKHKDLKTQGFTLE
CHICK   (641):       ....TQFRNIFRQIAGDDMEICREELRNVLNNVVKKHKDLKTEGFELE

Small subunit
HUMAN    (91):...EANESEEVRQFRRLFAQLAGDDMEVSATELMNILNKVVTRHPDLKTDGFGID
RAT    (frag):   ....SEEERQFRKLFVQLAGDDMEVSATELMNILNKVVTRHPDLKTDGFGID
RABBIT   (91): ....NESEEVRQFRRLFAQLAGDDMEVSATELMNILNKVVTRHPDLKTDGFGLD
BOVINE   (91):    ....EEVRQFRRLFAQLAGDDMEVSATELMNILNKVVTRHPDLKTDGFGID
PORCINE      (91): ....NESEEVRQFRRLFAQLAGDDMEVSATELMNILNKVVTRHPDLKTDGFGID


              |helixIII|--loop2----|helixIV| |helixV-|-loop3-----|helixVI|
               En**nn**nX*Y*ZG#Ix**zn**nn*n  En**nn**nX*Y*ZG#Ix**zn**nn*n

Calpain-I (mu-calpain) large subunit
HUMAN        : SCRSMVNLMDRDGNGKLGLVEFNILWNRIRNYLSIFRKFDLDKSGSMSAYEMRMAIESAGFKLN
RABBIT       : SCRSMVNLMDRDGNGKLGLVEFNILWNRIRNYLAIFRKFDLDKSGSMSAYEMRMAIESAGFKLN

Calpain-II (m-calpain) large subunit
HUMAN        : TCKIMVDMLDSDGSGKLGLKEFYILWTKIQKYQKIYREIDVDRSGTMNSYEMRKALEEAGFKMP
MOUSE        : TCKIMVDMLDEDGSGKLGLKEFYILWTKIQKYQKIYREIDVDRSGTMNSYEMRKALEEAGFKLP
RAT          : TCKIMVDMLDEDGSGKLGLKEFYILWTKIQKYQKIYREIDVDRSGTMNSYEMRKALEEAGFKLP
RABBIT       : TCKIMVDMLDSDGTGKLGLKEFYVLWTKIQKYQKIYREIDVDRSGTMNSYEMRKALEEAGFKLP
PORCINE          : TCRIMVDMLDSDGSAKLGLKEFYILWTKIQKYQKIYREIDVDRSGTMNSYEMRKALEEAGFKLP
CHICK        : TCKIMVDLLDNDGSGKLGLKEFHTLWTKIQKYQKIYREIDVDRSGTMNSYEMRRALEAAGFKLS

Calpain-III (calpain p94) large subunit
HUMAN        : SCRSMIALMDTDGSGKLNLQEFHHLWNKIKAWQKIFKHYDTDQSGTINSYEMRNAVNDAGFHLN
MOUSE        : SCRSMIALMDTDGSGRLNLQEFHHLWKKIKAWQKIFKHYDTDHSGTINSYEMRNAVNDAGFHLN
RAT          : SCRSMIALMDTDGSGRLNLQEFHHLWKKIKAWQKIFKHYDTDHSGTINSYEMRNAVNDAGFHLN
CHICK        : SSRSMIALMDTDGSGKINFDEFRHLWDKIKSWQKIFKHYDADHSGTINSYEMRNAVKDAGFRLN

Small subunit
HUMAN        : TCRSMVAVMDSDTTGKLGFEEFKYLWNNIKRWQAIYKQFDTDRSGTICSSELPGAFEAAGFHLN
RAT          : TCRSMVAVMDSDTTGKLGFEEFKYLWNNIKKWQGIYKRFDTDRSGTIGSNELPGAFEAAGFHLN
RABBIT       : TCRSMVAVMDSDTTGKLGFEEFKYLWNNIKKWQAIYKQFDVDRSGTICSRELPGAFEAAGFHLN
BOVINE       : TCRSMVAVMDSDTTGKLGFEEFKYLWNNIKKWQAVYKQFDVDRSGTIGSSELPGAFEAAGFRLN
PORCINE          : TCRSMVAVMDSDTTGKLGFEEFKYLWNNIKKWQAIYKQFDVDRSGTIGSSELPGAFEAAGFHLN

               |helixVII|--loop4-----|hlxVIII| |hlxIX--|--loop5----|helixX| 
                En**nn**nX*Y*ZG#Ix**zn**nn*n  En**nn**nX*Y*ZG#Ix**zn**nn*n
 
Calpain-I (mu-calpain) large subunit
HUMAN        : KKLYELIITRYSEPDLAVDFDNFVCCLVRLETMFRFFKTLDTDLDGVVTFDLFKWLQLTMFA(714)
RABBIT       : KKLYELIITRYSEPDLAVDFDNFVCCLVRLETMFRFFKTLDTDLDGVVTFDLFKWLQLTMFA

Calpain-II (m-calpain) large subunit
HUMAN        : CQLHQVIVARFADDQLIIDFDNFVRCLVRLETLFKIFKQLDPENTGTIELDLISWLCFSVL(700)
MOUSE        : CQLHQVIVARFADDELIIDFDNFVRCLVRLETLFKIFKQLDPENTGTIQLNLASWLSFSVL(700)
RAT          : CQLHQVIVARFADDELIIDFDNFVRCLVRLEILFKIFKQLDPENTGTIQLDLISWLSFSVL(700)
RABBIT       : CQLHEVIVARFADDQLIIDFDNFVRCLVRLETLFKIFKQLDPDNTGMIQLDLISWLCFSVL
PORCINE          : CQLHQVIVARFADDQLIIDFDNFVRCLVRLETLFRISKQLDSENTGTIELDLISWLCFSVL
CHICK        : CQLHQIIVARFADEDLIIDFDNCVRCLIRLETLYKMFRKLDTEKTGTIELNLINWLFFTVI(700)

Calpain-III (calpain p94) large subunit
HUMAN        : NQLYDIITMRYADKHMNIDFDSFICCFVRLEGMFRAFHAFDKDGDGIIKLNVLEWLQLTMYA(821)
MOUSE        : SQLYDIITMRYADKHMNIDFDSFICCFVRLEGMFRAFNAFDKDGDGIIKLNVLEWLQLTMYA(821)
RAT          : SQLYDIITMRYADKHMNIDFDSFICCFVRLEGMFRAFHAFDKDGDGIIKLNVLEWLQLTMYA(821)
CHICK        : NQLYDIITMRYADKNMNIDFDSFICCFVRLDAMFRAFHAFDKDGDGIIKLNVLEWLQLTMYA(810)

Small subunit
HUMAN        : EHLYNMIIRRYSDESGNMDFDNFISCLVRLDAMFRAFKSLDKDGTGQIQVNIQEWLQLTMYS(268)
RAT          : QHIYSMIIRRYSDETGNMDFDNFISCLVRLDAMFRAFRSLDKNGTGQIQVNIQEWLQLTMYS
RABBIT       : EHLYNMIIRRYSDEAGNMDFDNFISCLVRLDAMFRAFKSLDKDGTGQIQVNIQEWLQLTMYS(266)
BOVINE       : EHLYNMIIRRYSDEGGNMDFDNFISCLVRLDAMFRAFKSLDKDGTGQIQVNIQEWLQLTMYS(263)
PORCINE      : EHLYSMIIRRYSDEGGNMDFDNFISCLVRLDAMFRAFKSLDKDGTGQIQVNIQEWLQLTMYS(266)

Sequence alignment for the entire calpain subfamily

Functional Information:

General information:

no general functional information is currently stored in the database

Biological roles:

remodeling and disassembling the cytoskeleton (This function may be particularly important in areas where the cytoskeleton attaches to the plasma membrane or other subcellular structures)
biochemical evidence in Sus scrofa: Calpain cleaves microtubule associated protein (InfoCard)

Disease states:

not yet available in the data library

Target molecules:

small subunit: PD150606
structural evidence for interaction in Sus scrofa: This drug is seen bound to the calpain domain VI homodimers in the crystal structure (InfoCard)

Structural Information:

Calcium-coordination:
small subunit, Rattus norvegicus:	EF1 ; X = A111 O; Y = H₂O; Z = D114 OD1; -X = H₂O; -Y = E116 O; -Z1 = E121 OE1; -Z2 = E121 OE2 EF2 ; X = D154 OD1; Y = D156 OD1; Z = T158 OG1; -X = H₂O; -Y = K160 O; -Z1 = E195 OE1; -Z2 = E195 OE2 EF3 ; X = D184 OD1; Y = D186 OD1; Z = S188 OG; -X = H₂O; -Y = T190 OG1; -Z1 = E165 OE1; -Z2 = E165 OE2 (InfoCard)
small subunit, Sus scrofa:	EF1 ; X = A107 O; Y = H₂O; Z = D110 OD1; -X = H₂O; -Y = E112 O; -Z1 = E117 OE1; -Z2 = E117 OE2 EF2 ; X = D150 OD1; Y = D152 OD1; Z = T154 OG1; -X = H₂O; -Y = K156 O; -Z1 = E161 OE1; -Z2 = E161 OE2 EF3 ; X = D180 OD1; Y = D182 OD1; Z = S184 OG; -X = H₂O; -Y = T186 O; -Z1 = E191 OE1; -Z2 = E191 OE2 (InfoCard)

Nature of the conformational changes:
Conformational change between apo and three calcium ions bound states of small subunit:	The structuiral information available is for homodimers of domain VI from the small subunit of calpain. These homodimers are thought to mimic the biologically relevant heterodimers of domain VI with domain IV from the large subunit. The calcium-induced conformational changes in the homodimers of domain VI are relatively small. The largest changes are in EF-1, and in the positioning of the linker between EF1 and EF2, which moves closer to EF3/EF4 upon calcium binding. (InfoCard)

Secondary structure: (as reported in the PDB file and its accompanying reference)
small subunit, Rattus norvegicus, three calcium ions bound state:	Helices: helix 1: 99 - 114, helix 2: 119 - 132, helix 3: 143 - 153, helix 4: 163 - 183, helix 5: 193 - 202, helix 6: 209 - 219, helix 7: 228 - 248, helix 8: 260 - 268 (pdb code 1DVI: InfoCard)
small subunit, Sus scrofa, three calcium ions bound state:	Helices: helix 1: 95 - 110, helix 2: 115 - 128, helix 3: 139 - 149, helix 4: 159 - 179, helix 5: 189 - 199, helix 6: 205 - 215, helix 7: 224 - 244, helix 8: 256 - 264 (pdb code 1ALV: InfoCard)

Additional structural information:
View a table of interhelical angles from various structures

Available structures: (follow the links from the PDB code to the retrieve the PDB files)
Apo Structures:	1AJ5: small subunit, Rattus norvegicus, homodimers of domain VI, thought to be representative of the domain IV-domain VI heterodimers, pH 6.8 Crystal structure, 2.3 angstrom resolution, R-value = 22, R-free = 30 (InfoCard)
Calcium Loaded Structures:	1DVI: small subunit, Rattus norvegicus, homodimers of domain VI, thought to be representative of the domain IV-domain VI heterodimers, pH 6.5 Crystal structure, 2.3 angstrom resolution, R-value = 24, R-free = 32 3 Ca ions bound (InfoCard) 1ALV: small subunit, Sus scrofa, homodimers of domain VI, thought to be representative of the domain IV-domain VI heterodimers, pH 7.4 Crystal structure, 1.9 angstrom resolution, R-value = 19.8, R-free = 23.9 3 Ca ions bound (InfoCard)
Drug Bound Structures:	1ALW: small subunit, Sus scrofa, homodimers of domain VI, thought to be representative of the domain IV-domain VI heterodimers, pH 7.4 Crystal structure, 21.4 angstrom resolution, R-value = 27.3 3 Ca ions bound , bound to 1 equivalentsof the following portion of PD150606: complete molecule (InfoCard)

Information about mutants:

no mutants are currently stored in the database