Calpain: Difference between revisions

← Older edit

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky

@@ Line 1: / Line 1: @@
-<StructureSection load='1kxr' size='400' side='right' caption='Structure of rat cslpsin1 protease domain dimer complex with Ca+2 (PDB entry [[1kxr]])' scene=''>
+<StructureSection load='1zcm' size='350' side='right' caption='Human calpain1 large subunit complex with inhibitor and Ca+2 ions (green) (PDB entry [[1zcm]])' scene='51/517369/Cv/1'>
+__TOC__
+== Function ==
-'''Calpains''' (CAP) are calcium-dependent cysteine proteases.  The CAP family contains 14 members.  CAP is a heterodimer containing a small28kDa regulatory subunit which is identical for all CAPs and a large 80kDa catalytic subunit. The best characterized CAPs are CAP1 (or mu-CAP) and CAP2 (or M-CAP).   CAP7 is atypical CAP that lacks a penta-EF-hand domain.  CAP8 and CAP9 are involved in the mucosal defense against stress-induced gastropathies.  CAP9 has been identified as the tumor suppressor for gastric cancer.  CAP13 is expressed in testis and lungs.  CAPs are regulated by Ca+2 concentration, phosphorylation and calpastatin.
+'''Calpains''' (CAP) are calcium-dependent cysteine proteases.  CAPs are regulated by Ca+2 concentration, phosphorylation and calpastatin.<ref>PMID:12843408</ref> The CAP family contains 14 members.<br />
+*  '''CAP1''' (or mu-CAP) and '''CAP2''' (or M-CAP) T are the best characterized CAPs. <br />
+*  '''CAP2''' limits the extent of neuronal plasticity and learning<ref>PMID:33339205</ref>.
+*  '''CAP3''' is expressed in skeletal muscles and regulates sarcomere remodelling<ref>PMID:16884488</ref>.
+*  '''CAP7''' is atypical CAP that lacks a penta-EF-hand domain.<br />
+*  '''CAP8''' and '''CAP9''' are involved in the mucosal defense against stress-induced gastropathies.<br />
+*  '''CAP9''' has been identified as the tumor suppressor for gastric cancer.<br />
+*  '''CAP13''' is expressed in testis and lungs.
-==3D structures of calpain==
+==Disease==
-===CAP small subunit===
+CAP3 defects lead to a certain muscular dystrophy.  Defective CAPs have a role in neurodegeneration.
-[[1aj5 ]]– rCAP domain VI – rat<br />
+== Structural highlights ==
-[[1dvi]] - rCAP domain VI + Ca<br />
-[[1np8]] – rCAP residues 87-245 - Cd<br />
-[[1alv]], [[1nx2]] - pCAP domain VI + Ca – pig<br />
-[[1alw]], [[1nx3]] - pCAP domain VI + Ca+ inhibitor<br />
-[[1nx0]] - pCAP domain VI + Ca+ Calpastatin peptide + small molecule inhibitor peptide<br />
-[[1nx1]] - pCAP domain VI + Ca+ Calpastatin peptide<br />
-===CAP1===
+CAP is a heterodimer containing a small 28kDa regulatory subunit which is identical for all CAPs and a large 80kDa catalytic subunit.  CAP undergoes conformational change upon binding of Ca+2 ions resulting in closing of its active site cleft and activation as a cysteine protease. <ref>PMID:11893336</ref>
+*<scene name='51/517369/Cv/7'>Inhibitor binding site</scene>. Water molecules are shown as red spheres.
+*<scene name='51/517369/Cv/8'>Covalent bond between Cys 115 of human calpain1 large subunit with inhibitor</scene>.
+*<scene name='51/517369/Cv/4'>1st Ca+2 coordination site</scene>.
+*<scene name='51/517369/Cv/5'>2nd Ca+2 coordination site</scene>.<ref>PMID:16411745</ref>
-[[1kxr]], [[1tlo]], [[1qxp]] - rCAP protease domain + Ca<br />
+==3D structures of calpain==
-[[1tl9]] - rCAP protease domain + Ca+ leupeptin inhibitor<br />
+[[Calpain 3D structures]]
-[[2g8e]], [[2g8j]], [[2nqg]], [[2nqi]], [[2r9c]], [[2r9f]] - rCAP protease domain + Ca+ inhibitor<br />
-[[2ary]] - hCAP protease domain + Ca – human<br />
-[[1zcm]] - hCAP protease domain (mutant) + Ca+ inhibitor<br />
-===CAP2===
+</StructureSection>
-[[1mdw]] – rCAP2 protease core domain I and II (mutant) + Ca<br />
+== References ==
-[[1df0]], [[1u5i]] – rCAP small subunit domain VI + rCAP2 large subunit<br />
+<references/>
-[[3df0]] - hCAP small subunit + hCAP2 large subunit + Calpastatin + Ca<br />
-[[3bow]] - rCAP small subunit + rCAP2 large subunit + Calpastatin + Ca<br />
-[[1kfu]], [[1kfx]] – hCAP small subunit + hCAP2 large subunit
-===CAP7===
-[[2qfe]] - hCAP C2-like domain
-===CAP8===
-[[2nqa]] - hCAP protease domain + Ca+ leupeptin inhibitor<br />
-===CAP9===
-[[1ziv]] – hCAP catalytic domain<br />
-[[2p0r]] - hCAP protease domain + Ca+ leupeptin inhibitor<br />
-===CAP13===
-[[2i7a]] – hCAP domain IV + Ca<br />
-</StructureSection>
 [[Category:Topic Page]]