Calpain: Difference between revisions

Revision as of 16:32, 18 November 2015

Function

Calpains (CAP) are calcium-dependent cysteine proteases. CAPs are regulated by Ca+2 concentration, phosphorylation and calpastatin. The CAP family contains 14 members.

CAP1 (or mu-CAP) and CAP2 (or M-CAP) T are the best characterized CAPs.
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.^[1]

Disease

CAP3 defects lead to a certain muscular dystrophy. Defective CAPs have a role in neurodegeneration.

Structural highlights

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. ^[2]

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.^[3]

Human calpain1 large subunit complex with inhibitor and Ca+2 ions (green) (PDB entry 1zcm)

Drag the structure with the mouse to rotate

3D structures of calpain3D structures of calpain

Updated on 18-November-2015

ReferencesReferences

↑ Goll DE, Thompson VF, Li H, Wei W, Cong J. The calpain system. Physiol Rev. 2003 Jul;83(3):731-801. PMID:12843408 doi:http://dx.doi.org/10.1152/physrev.00029.2002
↑ Moldoveanu T, Hosfield CM, Lim D, Elce JS, Jia Z, Davies PL. A Ca(2+) switch aligns the active site of calpain. Cell. 2002 Mar 8;108(5):649-60. PMID:11893336
↑ Li Q, Hanzlik RP, Weaver RF, Schonbrunn E. Molecular mode of action of a covalently inhibiting peptidomimetic on the human calpain protease core. Biochemistry. 2006 Jan 24;45(3):701-8. PMID:16411745 doi:http://dx.doi.org/10.1021/bi052077b

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

Michal Harel, Alexander Berchansky

[1] Goll DE, Thompson VF, Li H, Wei W, Cong J. The calpain system. Physiol Rev. 2003 Jul;83(3):731-801. PMID:12843408 doi:http://dx.doi.org/10.1152/physrev.00029.2002

[2] Moldoveanu T, Hosfield CM, Lim D, Elce JS, Jia Z, Davies PL. A Ca(2+) switch aligns the active site of calpain. Cell. 2002 Mar 8;108(5):649-60. PMID:11893336

[3] Li Q, Hanzlik RP, Weaver RF, Schonbrunn E. Molecular mode of action of a covalently inhibiting peptidomimetic on the human calpain protease core. Biochemistry. 2006 Jan 24;45(3):701-8. PMID:16411745 doi:http://dx.doi.org/10.1021/bi052077b

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@@ Line 8: / Line 8: @@
 *  '''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.
+*  '''CAP13''' is expressed in testis and lungs.<ref>PMID:12843408</ref>
 ==Disease==