title: Domain structure and function of matrix metalloprotease 23 (MMP23): role in potassium channel trafficking.
abstract: MMP23 is a member of the matrix metalloprotease family of zinc- and calcium-dependent endopeptidases, which are involved in a wide variety of cellular functions. Its catalytic domain displays a high degree of structural homology with those of other metalloproteases, but its atypical domain architecture suggests that it may possess unique functional properties. The N-terminal MMP23 pro-domain contains a type-II transmembrane domain that anchors the protein to the plasma membrane and lacks the cysteine-switch motif that is required to maintain other MMPs in a latent state during passage to the cell surface. Instead of the C-terminal hemopexin domain common to other MMPs, MMP23 contains a small toxin-like domain (TxD) and an immunoglobulin-like cell adhesion molecule (IgCAM) domain. The MMP23 pro-domain can trap Kv1.3 but not closely-related Kv1.2 channels in the endoplasmic reticulum, preventing their passage to the cell surface, while the TxD can bind to the channel pore and block the passage of potassium ions. The MMP23 C-terminal IgCAM domain displays some similarity to Ig-like C2-type domains found in IgCAMs of the immunoglobulin superfamily, which are known to mediate protein-protein and protein-lipid interactions. MMP23 and Kv1.3 are co-expressed in a variety of tissues and together are implicated in diseases including cancer and inflammatory disorders. Further studies are required to elucidate the mechanism of action of this unique member of the MMP family.
authors.affiliation: Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, 3052, Australia, charles.galea@monash.edu.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Galea
authors.forename: Hai M
authors.initials: HM
authors.lastname: Nguyen
authors.forename: K
authors.initials: K
authors.lastname: George Chandy
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Smith
authors.forename: Raymond S
authors.initials: RS
authors.lastname: Norton
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D020134:Catalytic Domain; D006801:Humans; D020782:Matrix Metalloproteinases / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000737:chemistry* / Q000378:metabolism; D021381:Protein Transport; D016415:Sequence Alignment
chemical_list: D015221:Potassium Channels; D020782:Matrix Metalloproteinases; D011188:Potassium
references.citation: Genomics. 1998 Aug 15;52(1):101-6
references.pmid: 9740677
references.citation: Cell Mol Life Sci. 2011 Dec;68(23):3853-68
references.pmid: 21744247
references.citation: Nat Struct Biol. 1996 Apr;3(4):317-20
references.pmid: 8599755
references.citation: Int J Dev Biol. 2012;56(6-8):605-11
references.pmid: 22689366
references.citation: Nature. 1997 Feb 20;385(6618):729-33
references.pmid: 9034190
references.citation: Cancer Cell. 2007 Apr;11(4):375-88
references.pmid: 17418413
references.citation: Curr Mol Med. 2011 Nov;11(8):609-22
references.pmid: 21707518
references.citation: Genomics. 1995 Feb 10;25(3):630-7
references.pmid: 7759096
references.citation: Annu Rev Cell Dev Biol. 2001;17:463-516
references.pmid: 11687497
references.citation: Biochimie. 2005 Mar-Apr;87(3-4):249-63
references.pmid: 15781312
references.citation: BMC Evol Biol. 2007 Apr 17;7:63
references.pmid: 17439641
references.citation: Cell Death Differ. 2003 Jan;10(1):45-65
references.pmid: 12655295
references.citation: Bone. 2003 Jul;33(1):46-63
references.pmid: 12919699
references.citation: Toxicon. 2009 Dec 15;54(8):1075-88
references.pmid: 19285996
references.citation: Biochim Biophys Acta. 2010 Jan;1803(1):3-19
references.pmid: 19631700
references.citation: Blood. 2013 Jan 17;121(3):431-9
references.pmid: 23086754
references.citation: Biochemistry. 2002 Mar 5;41(9):2886-94
references.pmid: 11863426
references.citation: Nat Rev Cancer. 2004 Feb;4(2):118-32
references.pmid: 14964308
references.citation: Thyroid. 2000 Dec;10(12):1061-9
references.pmid: 11201850
references.citation: Proc Natl Acad Sci U S A. 2007 Aug 7;104(32):13022-7
references.pmid: 17666528
references.citation: FEBS J. 2011 Jan;278(1):28-45
references.pmid: 21087458
references.citation: Cardiovasc Res. 2006 Feb 15;69(3):562-73
references.pmid: 16405877
references.citation: Biophys J. 2011 Sep 21;101(6):1364-75
references.pmid: 21943417
references.citation: Development. 2000 Jan;127(1):129-41
references.pmid: 10654607
references.citation: J Biol Chem. 1998 Dec 4;273(49):32697-707
references.pmid: 9830012
references.citation: J Biol Chem. 2010 Sep 24;285(39):29951-64
references.pmid: 20663879
references.citation: Eur J Hum Genet. 2005 Feb;13(2):139-49
references.pmid: 15483646
references.citation: J Neurochem. 2010 Jan;112(1):134-49
references.pmid: 19840223
references.citation: Circ Cardiovasc Genet. 2013 Feb;6(1):106-17
references.pmid: 23255316
references.citation: Mol Aspects Med. 2012 Apr;33(2):119-208
references.pmid: 22100792
references.citation: J Biol Chem. 2001 Oct 19;276(42):39419-27
references.pmid: 11487588
references.citation: Biochem J. 2005 Sep 15;390(Pt 3):641-53
references.pmid: 16134966
references.citation: Curr Top Med Chem. 2012;12(10):1095-112
references.pmid: 22519442
references.citation: Genome Biol. 2011 Nov 11;12(11):233
references.pmid: 22078297
references.citation: Amino Acids. 2011 Jul;41(2):271-90
references.pmid: 20640864
references.citation: Mol Cell Biol. 2008 Apr;28(7):2391-413
references.pmid: 18172013
references.citation: Matrix Biol. 2007 Oct;26(8):587-96
references.pmid: 17669641
references.citation: Nat Clin Pract Rheumatol. 2008 Feb;4(2):82-9
references.pmid: 18235537
references.citation: Oncol Lett. 2012 Aug;4(2):227-230
references.pmid: 22844358
references.citation: FASEB J. 2004 Apr;18(6):690-2
references.pmid: 14766804
references.citation: Neuropharmacology. 2004 Nov;47(6):787-821
references.pmid: 15527815
references.citation: Immunol Rev. 2010 May;235(1):35-54
references.pmid: 20536554
references.citation: Ann N Y Acad Sci. 2008 Nov;1144:42-52
references.pmid: 19076362
references.citation: J Biol Chem. 1999 Dec 10;274(50):35653-61
references.pmid: 10585444
references.citation: FEBS Lett. 1993 Sep 27;331(1-2):134-40
references.pmid: 8405391
references.citation: Arthritis Rheum. 2006 Mar;54(3):832-42
references.pmid: 16508964
references.citation: Structure. 1995 Jun 15;3(6):527-30
references.pmid: 8590012
references.citation: Biokhimiia. 1995 Aug;60(8):1221-30
references.pmid: 7578577
references.citation: Int J Biochem Cell Biol. 2008;40(6-7):1334-47
references.pmid: 18083622
references.citation: Proc Natl Acad Sci U S A. 1990 Jan;87(1):364-8
references.pmid: 2153297
references.citation: Crit Rev Oncol Hematol. 2004 Mar;49(3):187-98
references.pmid: 15036259
references.citation: Crit Rev Biochem Mol Biol. 2007 May-Jun;42(3):113-85
references.pmid: 17562450
references.citation: Semin Cancer Biol. 2010 Jun;20(3):161-8
references.pmid: 20470890
references.citation: Ann N Y Acad Sci. 2003 May;995:109-16
references.pmid: 12814943
references.citation: Nat Methods. 2012 May 20;9(8):834-9
references.pmid: 22609626
references.citation: J Biol Chem. 2010 Apr 30;285(18):13958-65
references.pmid: 20202938
references.citation: Toxicon. 2012 Mar 15;59(4):529-46
references.pmid: 21867724
references.citation: Dev Biol. 2007 Dec 1;312(1):353-66
references.pmid: 17959165
references.citation: J Biol Chem. 2001 Dec 28;276(52):49427-34
references.pmid: 11679591
references.citation: Front Physiol. 2012 Jun 28;3:231
references.pmid: 22754540
references.citation: Mol Biotechnol. 2002 Sep;22(1):51-86
references.pmid: 12353914
references.citation: Curr Med Chem. 2012;19(5):661-74
references.pmid: 22204339
references.citation: Am J Pathol. 2005 May;166(5):1555-63
references.pmid: 15855654
references.citation: Dev Cell. 2010 Jan 19;18(1):77-89
references.pmid: 20152179
references.citation: Exp Lung Res. 2009 Feb;35(1):59-75
references.pmid: 19191105
references.citation: Cancer Cell. 2007 Dec;12(6):559-71
references.pmid: 18068632
references.citation: Neurosci Lett. 2010 Dec 10;486(2):53-9
references.pmid: 20600605
references.citation: Biochemistry. 2009 Nov 24;48(46):10830-45
references.pmid: 19817485
references.citation: Dev Genes Evol. 1998 Jul;208(5):259-66
references.pmid: 9683741
references.citation: J Cell Physiol. 2008 Aug;216(2):480-5
references.pmid: 18286480
references.citation: Science. 2012 Jun 1;336(6085):1168-71
references.pmid: 22654059
references.citation: J Biol Chem. 2010 Dec 17;285(51):40201-11
references.pmid: 20937825
references.citation: J Neurooncol. 2008 Jul;88(3):281-91
references.pmid: 18398573
references.citation: J Neurosci. 2008 May 28;28(22):5731-9
references.pmid: 18509034
references.citation: Anticancer Agents Med Chem. 2012 Sep;12(7):707-17
references.pmid: 22292747
references.citation: J Gen Physiol. 2000 Sep;116(3):379-90
references.pmid: 10962015
references.citation: Nat Rev Mol Cell Biol. 2007 Mar;8(3):221-33
references.pmid: 17318226
references.citation: J Biol Chem. 2013 Mar 1;288(9):6451-64
references.pmid: 23300077
references.citation: J Proteome Res. 2004 Jan-Feb;3(1):21-31
references.pmid: 14998159
references.citation: J Assist Reprod Genet. 2002 Oct;19(10):483-6
references.pmid: 12416653
references.citation: Angew Chem Int Ed Engl. 2012 Apr 2;51(14):3340-4
references.pmid: 22290936
references.citation: Int J Biochem Cell Biol. 2012 May;44(5):698-702
references.pmid: 22326621
references.citation: FEBS Lett. 2008 Feb 6;582(3):399-404
references.pmid: 18164686
references.citation: Clin Exp Nephrol. 2012 Feb;16(1):44-8
references.pmid: 22038264
references.citation: Prog Histochem Cytochem. 2012 Mar;47(1):27-58
references.pmid: 22226510
references.citation: Arthritis Res Ther. 2006;8(4):R124
references.pmid: 16859525
references.citation: FEBS J. 2011 Jan;278(1):2-15
references.pmid: 21087456
references.citation: J Gen Physiol. 2012 Oct;140(4):375-89
references.pmid: 22966015
references.citation: Trends Immunol. 2012 Aug;33(8):406-12
references.pmid: 22608996
references.citation: Proteomics Clin Appl. 2013 Aug;7(7-8):516-27
references.pmid: 23532927
references.citation: J Biol Chem. 1999 Feb 19;274(8):4570-6
references.pmid: 9988691
references.citation: Future Med Chem. 2010 May;2(5):745-55
references.pmid: 21426201
references.citation: Curr Cancer Drug Targets. 2009 Dec;9(8):904-14
references.pmid: 20025600
references.citation: Matrix Suppl. 1992;1:237-44
references.pmid: 1480033
references.citation: J Cell Mol Med. 2011 Jun;15(6):1254-65
references.pmid: 21418514
references.citation: Curr Opin Cell Biol. 2004 Oct;16(5):558-64
references.pmid: 15363807
references.citation: EMBO J. 2004 Aug 4;23(15):3020-30
references.pmid: 15257288
references.citation: Nature. 2010 Nov 18;468(7322):447-51
references.pmid: 21037563
references.citation: FEBS J. 2010 Aug;277(15):3158-75
references.pmid: 20608975
references.citation: Genes Dev. 2000 Sep 1;14(17):2123-33
references.pmid: 10970876
references.citation: Biochim Biophys Acta. 2010 Jan;1803(1):20-8
references.pmid: 19374923
references.citation: Nature. 1995 Nov 2;378(6552):85-8
references.pmid: 7477295
references.citation: Proc Natl Acad Sci U S A. 1990 Jul;87(14):5578-82
references.pmid: 2164689
references.citation: Cancer Res. 2006 Mar 15;66(6):3034-43
references.pmid: 16540652
references.citation: FEBS Lett. 2012 Aug 14;586(17):2609-14
references.pmid: 22710157
references.citation: Biochem Soc Trans. 2011 Dec;39(6):1628-32
references.pmid: 22103498
references.citation: Semin Cell Dev Biol. 2008 Feb;19(1):2-13
references.pmid: 17689277
references.citation: FEBS Lett. 2012 Nov 16;586(22):3996-4001
references.pmid: 23063513
references.citation: Proc Natl Acad Sci U S A. 2001 Nov 20;98(24):14055-9
references.pmid: 11698661
references.citation: FEBS J. 2011 Jan;278(1):16-27
references.pmid: 21087457
references.citation: Cancer Invest. 2012 Mar;30(3):203-8
references.pmid: 22360360
references.citation: J Biol Chem. 1989 Jul 15;264(20):11539-42
references.pmid: 2473064
references.citation: Hepatology. 2010 Dec;52(6):2158-66
references.pmid: 21064033
references.citation: Cancer Cell. 2007 Apr;11(4):349-60
references.pmid: 17418411
references.citation: Curr Top Med Chem. 2012;12(10):1132-48
references.pmid: 22519444
references.citation: Biochemistry. 2002 Oct 8;41(40):11963-71
references.pmid: 12356296
references.citation: Clin Calcium. 2009 Nov;19(11):1593-601
references.pmid: 19880991
references.citation: J Biol Chem. 1997 Feb 14;272(7):4302-9
references.pmid: 9020148
references.citation: Epilepsia. 2012 Dec;53 Suppl 9:21-31
references.pmid: 23216576
references.citation: Biomed Biochim Acta. 1991;50(4-6):749-54
references.pmid: 1666284
references.citation: J Cell Sci. 2009 Oct 15;122(Pt 20):3738-48
references.pmid: 19773357
references.citation: Eur J Biochem. 2003 Dec;270(24):4909-20
references.pmid: 14653817
references.citation: Methods Mol Biol. 2010;622:435-50
references.pmid: 20135297
references.citation: FASEB J. 2007 Mar;21(3):906-14
references.pmid: 17185748
references.citation: Br J Cancer. 2005 Jun 20;92(12):2171-80
references.pmid: 15928670
references.citation: Am J Pathol. 2006 Oct;169(4):1390-401
references.pmid: 17003494
references.citation: Biochimie. 2005 Mar-Apr;87(3-4):329-42
references.pmid: 15781320
references.citation: Biochim Biophys Acta. 2010 Jan;1803(1):39-54
references.pmid: 19800373
references.citation: J Biol Chem. 1995 May 12;270(19):11555-66
references.pmid: 7744795
references.citation: J Biol Chem. 2010 Mar 19;285(12):9124-36
references.pmid: 19965868
references.citation: Matrix Biol. 1997 Mar;15(8-9):511-8
references.pmid: 9138283
references.citation: FEBS Lett. 1999 Aug 27;457(2):262-70
references.pmid: 10471791
references.citation: Circulation. 2002 Sep 17;106(12):1543-9
references.pmid: 12234962
references.citation: J Biol Chem. 1990 Oct 15;265(29):17401-4
references.pmid: 1698775
references.citation: J Mol Biol. 2008 Oct 24;382(5):1113-20
references.pmid: 18706912
references.citation: Curr Opin Struct Biol. 2011 Apr;21(2):283-91
references.pmid: 21296569
references.citation: Curr Top Dev Biol. 2003;54:1-74
references.pmid: 12696745
references.citation: Eur J Biochem. 1997 Feb 15;244(1):192-202
references.pmid: 9063464
references.citation: Endocr Rev. 2007 Jun;28(4):365-86
references.pmid: 17431229
references.citation: Protein Sci. 1995 May;4(5):823-40
references.pmid: 7663339
references.citation: Eur J Cell Biol. 2012 Nov-Dec;91(11-12):889-95
references.pmid: 22939226
references.citation: Mol Carcinog. 2007 Mar;46(3):225-30
references.pmid: 17219425
references.citation: J Biol Chem. 1999 Jul 30;274(31):21885-92
references.pmid: 10419508
references.citation: Biochim Biophys Acta. 2010 Jan;1803(1):55-71
references.pmid: 20080133
references.citation: Respir Res. 2001;2(1):10-9
references.pmid: 11686860
references.citation: Int J Biochem Cell Biol. 2004 May;36(5):942-56
references.pmid: 15006646
references.citation: Curr Med Chem. 2010;17(31):3751-68
references.pmid: 20846107
references.citation: Eur J Biochem. 1998 Jan 15;251(1-2):133-41
references.pmid: 9492277
references.citation: Curr Drug Targets. 2009 Dec;10(12):1245-54
references.pmid: 19909233
references.citation: Curr Opin Cell Biol. 2009 Oct;21(5):645-53
references.pmid: 19616423
references.citation: Biochem Soc Trans. 2008 Apr;36(Pt 2):251-6
references.pmid: 18363568
references.citation: J Biol Chem. 2000 Apr 21;275(16):11597-602
references.pmid: 10766775
references.citation: Nucleic Acids Res. 1994 Nov 11;22(22):4673-80
references.pmid: 7984417
references.citation: Proc Natl Acad Sci U S A. 2006 Nov 14;103(46):17414-9
references.pmid: 17088564
references.citation: J Biol Chem. 2000 Oct 27;275(43):33988-97
references.pmid: 10945999
references.citation: Cell Cycle. 2006 Mar;5(6):573-7
references.pmid: 16582610
references.citation: J Biol Chem. 2008 Oct 31;283(44):30421-32
references.pmid: 18640987
references.citation: Int J Biol Sci. 2011;7(8):1101-13
references.pmid: 21927579
references.citation: Curr Pharm Des. 2009;15(12):1349-57
references.pmid: 19355973
references.citation: J Biol Chem. 2013 Feb 22;288(8):5790-802
references.pmid: 23288842
references.citation: Eur J Biochem. 1990 Apr 30;189(2):295-300
references.pmid: 2159879
references.citation: J Biol Chem. 2004 Dec 10;279(50):52132-40
references.pmid: 15466865
references.citation: Biol Chem. 2012 Oct;393(10):1027-41
references.pmid: 23092796
references.citation: Proc Natl Acad Sci U S A. 2012 Nov 6;109(45):18577-82
references.pmid: 23090990
references.citation: Pflugers Arch. 2012 Oct;464(4):353-65
references.pmid: 22864553
references.citation: J Biol Chem. 2003 Apr 25;278(17):15056-64
references.pmid: 12586837
references.citation: EMBO Mol Med. 2012 Jul;4(7):577-93
references.pmid: 22496117
references.citation: Am J Physiol Gastrointest Liver Physiol. 2006 Apr;290(4):G583-9
references.pmid: 16537970
references.citation: Biochem J. 1989 Oct 1;263(1):201-6
references.pmid: 2557822
references.citation: Proc Natl Acad Sci U S A. 2007 Sep 18;104(38):14923-8
references.pmid: 17848514
references.citation: Mol Cancer. 2011 Jan 10;10:6
references.pmid: 21219645
references.citation: Mol Endocrinol. 2001 May;15(5):747-64
references.pmid: 11328856