Meprins, membrane-bound and secreted astacin metalloproteinases.
The astacins are a subfamily of the metzincin superfamily of metalloproteinases. The first to be characterized was the crayfish enzyme astacin. To date more than 200 members of this family have been identified in species ranging from bacteria to humans. Astacins are involved in developmental morphogenesis, matrix assembly, tissue differentiation and digestion. Family members include the procollagen C-proteinase (BMP1, bone morphogenetic protein 1), tolloid and mammalian tolloid-like, HMP (Hydra vulgaris metalloproteinase), sea urchin BP10 (blastula protein) and SPAN (Strongylocentrotus purpuratus astacin), the 'hatching' subfamily comprising alveolin, ovastacin, LCE, HCE ('low' and 'high' choriolytic enzymes), nephrosin (from carp head kidney), UVS.2 from frog, and the meprins. In the human and mouse genomes, there are six astacin family genes (two meprins, three BMP1/tolloid-like, one ovastacin), but in Caenorhabditis elegans there are 40. Meprins are the only astacin proteinases that function on the membrane and extracellularly by virtue of the fact that they can be membrane-bound or secreted. They are unique in their domain structure and covalent subunit dimerization, oligomerization propensities, and expression patterns. They are normally highly regulated at the transcriptional and post-translational levels, localize to specific membranes or extracellular spaces, and can hydrolyse biologically active peptides, cytokines, extracellular matrix (ECM) proteins and cell-surface proteins. The in vivo substrates of meprins are unknown, but the abundant expression of these proteinases in the epithelial cells of the intestine, kidney and skin provide clues to their functions.
Sterchi
Erwin E
EE
Institute of Biochemistry and Molecular Biology, University of Berne, Buehlstrasse 28, CH-3012 Berne, Switzerland. erwin.sterchi@mci.unibe.ch
Stöcker
Walter
W
Bond
Judith S
JS
D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000201:enzymology; D008666:Metalloendopeptidases / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010802:Phylogeny; D011487:Protein Conformation; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity; D014018:Tissue Distribution
D021122:Protein Subunits; D008666:Metalloendopeptidases; C053833:meprin A; C071288:astacin
J Biol Chem. 2002 Oct 25;277(43):40650-8
12189145
Biochem J. 1996 Aug 1;317 ( Pt 3):731-8
8760356
Science. 1988 Dec 16;242(4885):1528-34
3201241
J Biol Chem. 2003 Jan 24;278(4):2522-32
12399461
Science. 2007 Jul 6;317(5834):86-94
17615350
Biol Chem. 2007 May;388(5):523-31
17516848
J Biol Chem. 1998 Dec 25;273(52):35260-7
9857066
Biochim Biophys Acta. 2001 Mar 19;1518(1-2):106-14
11267665
Eur J Biochem. 1999 Apr;261(2):421-9
10215852
Arch Biochem Biophys. 1997 Jan 15;337(2):300-7
9016826
Science. 1996 Jan 19;271(5247):360-2
8553073
Eur J Biochem. 1996 May 1;237(3):752-8
8647122
Trends Biochem Sci. 1993 Feb;18(2):40-1
8387703
J Biol Chem. 2001 Jun 29;276(26):24242-52
11279055
Cancer Res. 1999 Mar 1;59(5):1127-33
10070973
J Biol Chem. 1995 Jun 16;270(24):14247-50
7782276
Am J Pathol. 2007 Jul;171(1):139-52
17591961
Proc Natl Acad Sci U S A. 1984 Sep;81(17):5542-5
6382265
Arch Biochem Biophys. 1988 Aug 15;265(1):119-27
3261962
Proc Natl Acad Sci U S A. 1996 May 14;93(10):5127-30
8643539
Eur J Biochem. 1999 Jan;259(1-2):496-504
9914532
Science. 1983 Mar 18;219(4590):1351-3
6338590
FEBS Lett. 1993 Dec 13;335(3):376-9
8262186
Eur J Biochem. 1991 Sep 1;200(2):563-71
1889419
Development. 1992 Mar;114(3):769-86
1618141
Biochem Biophys Res Commun. 1995 Mar 17;208(2):498-505
7695599
Eur J Biochem. 1998 May 1;253(3):796-803
9654081
Development. 1992 Jan;114(1):147-63
1339338
J Biol Chem. 2001 Sep 7;276(36):34182-8
11447218
FEBS Lett. 2002 Oct 23;530(1-3):1-3
12387856
Dev Biol. 2000 Mar 1;219(1):115-28
10677259
Biol Chem. 2007 Mar;388(3):337-41
17338642
Arch Biochem Biophys. 1998 Jan 1;349(1):192-200
9439598
J Cell Sci. 2002 Oct 15;115(Pt 20):3861-3
12244123
Mol Cell Biol. 1998 May;18(5):2901-11
9566909
J Mol Histol. 2005 Feb;36(1-2):15-24
15703995
J Chromatogr B Biomed Sci Appl. 1999 Apr 16;726(1-2):25-35
10348167
Microbes Infect. 2007 Apr;9(4):498-506
17347015
J Biol Chem. 1994 May 27;269(21):15388-93
8195177
Biochem J. 2000 Feb 15;346 Pt 1:83-91
10657243
Eur J Biochem. 2001 Sep;268(18):4892-8
11559358
Development. 2000 Jan;127(1):129-41
10654607
J Biol Chem. 2005 Apr 8;280(14):13895-901
15695509
J Biol Chem. 1995 Mar 10;270(10):5449-56
7890660
Adv Exp Med Biol. 2007;597:1-24
17633013
Cell. 1991 Nov 1;67(3):469-81
1840509
J Immunol. 2004 Apr 1;172(7):4510-9
15034068
J Mol Biol. 2002 Nov 22;324(2):237-46
12441103
FEBS Lett. 1999 Dec 3;462(3):368-72
10622727
EMBO J. 1990 Jul;9(7):2241-6
2162765
Kidney Int. 1998 Jun;53(6):1673-80
9607199
J Biol Chem. 1996 Sep 27;271(39):24236-41
8798668
Nat Struct Biol. 2001 Jul;8(7):573-4
11427880
Am J Physiol Renal Physiol. 2008 Mar;294(3):F480-90
18172000
J Biol Chem. 1993 May 15;268(14):10380-5
7683677
FEBS Lett. 1993 Dec 13;335(3):367-75
8262185
J Biol Chem. 2000 Mar 24;275(12):8349-54
10722665
Biochem J. 1981 Dec 1;199(3):591-8
7041888
Biochem J. 1987 Jul 15;245(2):515-24
3117045
Annu Rev Physiol. 1985;47:231-45
3888075
J Biol Chem. 2000 Aug 18;275(33):25577-84
10837482
Dev Genes Evol. 1998 Jul;208(5):259-66
9683741
Parasitol Res. 2003 May;90(1):27-37
12743801
Nat Struct Biol. 1996 Aug;3(8):671-5
8756323
Genomics. 1995 Sep 1;29(1):9-15
8530106
EMBO J. 2006 Feb 22;25(4):701-12
16456543
Development. 1994 Apr;120(4):861-70
7600963
FEBS J. 2008 Sep;275(18):4490-509
18671728
J Biol Chem. 1997 Oct 31;272(44):28126-32
9346968
Hum Genet. 2005 Oct;118(1):12-22
16133184
J Immunol. 1985 Oct;135(4):2400-8
2411795
J Biol Chem. 2002 Sep 13;277(37):34413-23
12093806
Biochemistry. 1990 Nov 13;29(45):10418-25
2261483
J Biol Chem. 1993 Oct 5;268(28):21035-43
8407940
Biochem J. 2004 Mar 1;378(Pt 2):383-9
14594449
J Invest Dermatol. 2007 May;127(5):1115-25
17195012
J Biol Chem. 2004 Nov 26;279(48):49835-41
15381708
Arch Biochem Biophys. 1996 Jul 1;331(1):87-94
8660687
J Cell Biol. 1994 Sep;126(5):1319-27
8063866
Mol Phylogenet Evol. 2005 Oct;37(1):62-72
15927490
J Cell Biol. 2004 Nov 22;167(4):673-86
15557119
Matrix Biol. 2007 Sep;26(7):508-23
17560775
Biochim Biophys Acta. 1994 Jan 18;1217(1):1-8
8286408
FEBS Lett. 1992 Dec 21;314(3):224-8
1468552
J Biol Chem. 2001 Apr 20;276(16):13248-55
11278902
J Biol Chem. 2004 Aug 13;279(33):34856-64
15187079
Biochemistry. 1991 Aug 27;30(34):8488-93
1883833
Eur J Biochem. 1997 Aug 1;247(3):933-41
9288917
J Biol Chem. 1988 Sep 15;263(26):13419-26
3047123
J Biol Chem. 2008 Nov 7;283(45):30433-7
18650443
Protein Sci. 1995 Jul;4(7):1247-61
7670368
Evol Dev. 2006 Mar-Apr;8(2):223-31
16509900
Trends Biochem Sci. 1996 Jul;21(7):244-5
8755243
Arch Biochem Biophys. 2000 Jul 15;379(2):183-7
10898933
Arch Biochem Biophys. 2002 Jan 15;397(2):191-8
11795871
Biol Chem. 2003 May;384(5):825-31
12817480
Eur J Biochem. 1997 Aug 1;247(3):920-32
9288916
J Biol Chem. 2001 Jun 22;276(25):23207-11
11301339
Am J Physiol. 1987 Oct;253(4 Pt 1):C535-40
3310653
Mol Carcinog. 1999 Jul;25(3):169-78
10411143
Science. 1995 Mar 10;267(5203):1494-8
7533327
J Biol Chem. 2005 Mar 18;280(11):9823-32
15647258
J Biol Chem. 1997 May 23;272(21):13772-8
9153232
Biol Chem. 2002 Jul-Aug;383(7-8):1175-83
12437103
J Struct Biol. 2001 May-Jun;134(2-3):95-102
11551172
Mol Biotechnol. 2003 Jun;24(2):157-202
12746556
Biochem J. 1987 Jan 1;241(1):229-35
3105525
J Biol Chem. 2003 Oct 31;278(44):42829-39
12941954
Nature. 1992 Jul 9;358(6382):164-7
1319561
J Biol Chem. 1991 Sep 15;266(26):17350-7
1894622
Cell. 1996 Aug 23;86(4):607-17
8752215
Adv Exp Med Biol. 2002;515:55-69
12613543
Clin Sci (Lond). 1982 May;62(5):557-60
7042181
Gene. 2000 May 2;248(1-2):77-87
10806353
Eur J Biochem. 2003 Dec;270(24):4909-20
14653817
Clin Exp Metastasis. 2005;22(4):331-9
16170669
Kidney Int. 2006 Jan;69(2):358-68
16408127
J Biol Chem. 2004 Jun 18;279(25):26627-34
15087446
Biol Chem. 2007 Nov;388(11):1163-72
17976009
Birth Defects Res C Embryo Today. 2006 Mar;78(1):47-68
16622848
J Biol Chem. 2003 Oct 24;278(43):42545-50
12888571
Exp Nephrol. 1999 Mar-Apr;7(2):160-6
10213869
J Biol Chem. 1992 May 5;267(13):9185-93
1374387
Biochemistry. 2000 Mar 28;39(12):3231-9
10727214
Biochemistry. 2006 May 30;45(21):6741-8
16716085
Am J Physiol Renal Physiol. 2005 Oct;289(4):F911-21
15942051
Cytokine. 2005 Sep 7;31(5):394-403
16095909
PLoS One. 2008 May 14;3(5):e2153
18478055
J Biol Chem. 2004 Jul 9;279(28):29670-80
15033991
J Immunol. 2005 Sep 1;175(5):3177-85
16116208
Kidney Int. 2003 Aug;64(2):480-92
12846743
Am J Physiol. 1996 Apr;270(4 Pt 2):F669-76
8967345
Kidney Int. 2002 Mar;61(3):959-66
11849450
J Biol Chem. 1991 Nov 15;266(32):21381-5
1939172
Protein Sci. 1995 May;4(5):823-40
7663339
Biol Chem. 2007 May;388(5):513-21
17516847
Methods Enzymol. 1995;248:305-25
7674929
Gene. 1997 Apr 11;189(1):65-71
9161413
J Biochem. 2002 Nov;132(5):751-8
12417025
Eur J Biochem. 1993 May 15;214(1):215-31
8508794
PLoS One. 2008 May 28;3(5):e2278
18509531
Curr Top Dev Biol. 2003;54:145-66
12696749
Mol Cell Biol. 2003 Feb;23(4):1221-30
12556482
Biochem J. 2003 Feb 1;369(Pt 3):659-65
12387727
Biochem J. 1989 Dec 1;264(2):335-46
2690825
Int J Biochem. 1985;17(5):565-74
3896890
J Biol Chem. 1998 Oct 30;273(44):29043-51
9786910
Arch Biochem Biophys. 1988 Aug 15;265(1):105-18
3261961
J Biol Chem. 2006 Dec 8;281(49):37404-15
17040911
Biochem Biophys Res Commun. 1967 Apr 20;27(2):157-62
6035483
J Pediatr Gastroenterol Nutr. 1983;2(3):539-47
6352892
Parasitology. 2005 Jan;130(Pt 1):89-98
15700760
APMIS. 1999 Jan;107(1):19-27
10190276
FEBS Lett. 2000 Jan 7;465(1):2-7
10620696
Life Sci. 1994;54(5):381-6
8289600
Neuron. 1998 Dec;21(6):1283-90
9883722
Biochem J. 1998 Apr 15;331 ( Pt 2):375-9
9531473