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Identification
HMDB Protein ID HMDBP02804
Secondary Accession Numbers
  • 8310
Name 72 kDa type IV collagenase
Synonyms
  1. 72 kDa gelatinase
  2. Gelatinase A
  3. MMP-2
  4. Matrix metalloproteinase-2
  5. PEX
  6. TBE-1
Gene Name MMP2
Protein Type Unknown
Biological Properties
General Function Involved in metalloendopeptidase activity
Specific Function PEX, the C-terminal non-catalytic fragment of MMP2, posseses anti-angiogenic and anti-tumor properties and inhibits cell migration and cell adhesion to FGF2 and vitronectin. Ligand for integrinv/beta3 on the surface of blood vessels
Pathways Not Available
Reactions Not Available
GO Classification
Component
extracellular region part
extracellular matrix
Function
endopeptidase activity
ion binding
cation binding
metal ion binding
binding
catalytic activity
hydrolase activity
transition metal ion binding
zinc ion binding
metalloendopeptidase activity
peptidase activity
peptidase activity, acting on l-amino acid peptides
metallopeptidase activity
Process
metabolic process
macromolecule metabolic process
protein metabolic process
proteolysis
Cellular Location
  1. Nucleus
  2. Secreted
  3. Membrane
  4. extracellular space
  5. extracellular matrix
Gene Properties
Chromosome Location Chromosome:1
Locus 16q13-q21
SNPs MMP2
Gene Sequence
>1983 bp
ATGGAGGCGCTAATGGCCCGGGGCGCGCTCACGGGTCCCCTGAGGGCGCTCTGTCTCCTG
GGCTGCCTGCTGAGCCACGCCGCCGCCGCGCCGTCGCCCATCATCAAGTTCCCCGGCGAT
GTCGCCCCCAAAACGGACAAAGAGTTGGCAGTGCAATACCTGAACACCTTCTATGGCTGC
CCCAAGGAGAGCTGCAACCTGTTTGTGCTGAAGGACACACTAAAGAAGATGCAGAAGTTC
TTTGGACTGCCCCAGACAGGTGATCTTGACCAGAATACCATCGAGACCATGCGGAAGCCA
CGCTGCGGCAACCCAGATGTGGCCAACTACAACTTCTTCCCTCGCAAGCCCAAGTGGGAC
AAGAACCAGATCACATACAGGATCATTGGCTACACACCTGATCTGGACCCAGAGACAGTG
GATGATGCCTTTGCTCGTGCCTTCCAAGTCTGGAGCGATGTGACCCCACTGCGGTTTTCT
CGAATCCATGATGGAGAGGCAGACATCATGATCAACTTTGGCCGCTGGGAGCATGGCGAT
GGATACCCCTTTGACGGTAAGGACGGACTCCTGGCTCATGCCTTCGCCCCAGGCACTGGT
GTTGGGGGAGACTCCCATTTTGATGACGATGAGCTATGGACCTTGGGAGAAGGCCAAGTG
GTCCGTGTGAAGTATGGGAACGCCGATGGGGAGTACTGCAAGTTCCCCTTCTTGTTCAAT
GGCAAGGAGTACAACAGCTGCACTGATACCGGCCGCAGCGATGGCTTCCTCTGGTGCTCC
ACCACCTACAACTTTGAGAAGGATGGCAAGTACGGCTTCTGTCCCCATGAAGCCCTGTTC
ACCATGGGCGGCAACGCTGAAGGACAGCCCTGCAAGTTTCCATTCCGCTTCCAGGGCACA
TCCTATGACAGCTGCACCACTGAGGGCCGCACGGATGGCTACCGCTGGTGCGGCACCACT
GAGGACTACGACCGCGACAAGAAGTATGGCTTCTGCCCTGAGACCGCCATGTCCACTGTT
GGTGGGAACTCAGAAGGTGCCCCCTGTGTCTTCCCCTTCACTTTCCTGGGCAACAAATAT
GAGAGCTGCACCAGCGCCGGCCGCAGTGACGGAAAGATGTGGTGTGCGACCACAGCCAAC
TACGATGACGACCGCAAGTGGGGCTTCTGCCCTGACCAAGGGTACAGCCTGTTCCTCGTG
GCAGCCCACGAGTTTGGCCACGCCATGGGGCTGGAGCACTCCCAAGACCCTGGGGCCCTG
ATGGCACCCATTTACACCTACACCAAGAACTTCCGTCTGTCCCAGGATGACATCAAGGGC
ATTCAGGAGCTCTATGGGGCCTCTCCTGACATTGACCTTGGCACCGGCCCCACCCCCACG
CTGGGCCCTGTCACTCCTGAGATCTGCAAACAGGACATTGTATTTGATGGCATCGCTCAG
ATCCGTGGTGAGATCTTCTTCTTCAAGGACCGGTTCATTTGGCGGACTGTGACGCCACGT
GACAAGCCCATGGGGCCCCTGCTGGTGGCCACATTCTGGCCTGAGCTCCCGGAAAAGATT
GATGCGGTATACGAGGCCCCACAGGAGGAGAAGGCTGTGTTCTTTGCAGGGAATGAATAC
TGGATCTACTCAGCCGGCACCCTGGAGCGAGGGTACCCCAAGCCACTGACCAGCCTGGGA
CTGCCCCCTGATGTCCAGCGAGTGGATGCCGCCTTTAACTGGAGCAAAAACAAGAAGACA
TACATCTTTGCTGGAGACAAATTCTGGAGATACAATGAGGTGAAGAAGAAAATGGATCCT
GGCTTCCCCAAGCTCATCGCAGATGCCTGGAATGCCATCCCCGATAACCTGGGTGCCGTC
GTGGACCTGCAGGGCGGCGGTCACAGCTACTTCTTCAAGGGTGCCTATTACCTGAAGCTG
GAGAACCAAAGTCTGAAGAGCGTGAAGTTTGGAAGCATCAAATCCGACTGGCTAGGCTGC
TGA
Protein Properties
Number of Residues 660
Molecular Weight 73881.7
Theoretical pI 5.09
Pfam Domain Function
Signals
  • 1-29
Transmembrane Regions
  • None
Protein Sequence
>72 kDa type IV collagenase
MEALMARGALTGPLRALCLLGCLLSHAAAAPSPIIKFPGDVAPKTDKELAVQYLNTFYGC
PKESCNLFVLKDTLKKMQKFFGLPQTGDLDQNTIETMRKPRCGNPDVANYNFFPRKPKWD
KNQITYRIIGYTPDLDPETVDDAFARAFQVWSDVTPLRFSRIHDGEADIMINFGRWEHGD
GYPFDGKDGLLAHAFAPGTGVGGDSHFDDDELWTLGEGQVVRVKYGNADGEYCKFPFLFN
GKEYNSCTDTGRSDGFLWCSTTYNFEKDGKYGFCPHEALFTMGGNAEGQPCKFPFRFQGT
SYDSCTTEGRTDGYRWCGTTEDYDRDKKYGFCPETAMSTVGGNSEGAPCVFPFTFLGNKY
ESCTSAGRSDGKMWCATTANYDDDRKWGFCPDQGYSLFLVAAHEFGHAMGLEHSQDPGAL
MAPIYTYTKNFRLSQDDIKGIQELYGASPDIDLGTGPTPTLGPVTPEICKQDIVFDGIAQ
IRGEIFFFKDRFIWRTVTPRDKPMGPLLVATFWPELPEKIDAVYEAPQEEKAVFFAGNEY
WIYSASTLERGYPKPLTSLGLPPDVQRVDAAFNWSKNKKTYIFAGDKFWRYNEVKKKMDP
GFPKLIADAWNAIPDNLDAVVDLQGGGHSYFFKGAYYLKLENQSLKSVKFGSIKSDWLGC
GenBank ID Protein 189053422
UniProtKB/Swiss-Prot ID P08253
UniProtKB/Swiss-Prot Entry Name MMP2_HUMAN
PDB IDs
GenBank Gene ID AK312711
GeneCard ID MMP2
GenAtlas ID MMP2
HGNC ID HGNC:7166
References
General References
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  3. Sjoblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, Mandelker D, Leary RJ, Ptak J, Silliman N, Szabo S, Buckhaults P, Farrell C, Meeh P, Markowitz SD, Willis J, Dawson D, Willson JK, Gazdar AF, Hartigan J, Wu L, Liu C, Parmigiani G, Park BH, Bachman KE, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE: The consensus coding sequences of human breast and colorectal cancers. Science. 2006 Oct 13;314(5797):268-74. Epub 2006 Sep 7. [PubMed:16959974 ]
  4. Kandasamy AD, Schulz R: Glycogen synthase kinase-3beta is activated by matrix metalloproteinase-2 mediated proteolysis in cardiomyoblasts. Cardiovasc Res. 2009 Sep 1;83(4):698-706. doi: 10.1093/cvr/cvp175. Epub 2009 Jun 3. [PubMed:19493954 ]
  5. Gusman H, Travis J, Helmerhorst EJ, Potempa J, Troxler RF, Oppenheim FG: Salivary histatin 5 is an inhibitor of both host and bacterial enzymes implicated in periodontal disease. Infect Immun. 2001 Mar;69(3):1402-8. [PubMed:11179305 ]
  6. Takino T, Koshikawa N, Miyamori H, Tanaka M, Sasaki T, Okada Y, Seiki M, Sato H: Cleavage of metastasis suppressor gene product KiSS-1 protein/metastin by matrix metalloproteinases. Oncogene. 2003 Jul 24;22(30):4617-26. [PubMed:12879005 ]
  7. Stetler-Stevenson WG, Krutzsch HC, Liotta LA: TIMP-2: identification and characterization of a new member of the metalloproteinase inhibitor family. Matrix Suppl. 1992;1:299-306. [PubMed:1480041 ]
  8. Huhtala P, Chow LT, Tryggvason K: Structure of the human type IV collagenase gene. J Biol Chem. 1990 Jul 5;265(19):11077-82. [PubMed:2162831 ]
  9. Collier IE, Bruns GA, Goldberg GI, Gerhard DS: On the structure and chromosome location of the 72- and 92-kDa human type IV collagenase genes. Genomics. 1991 Mar;9(3):429-34. [PubMed:1851724 ]
  10. Huhtala P, Eddy RL, Fan YS, Byers MG, Shows TB, Tryggvason K: Completion of the primary structure of the human type IV collagenase preproenzyme and assignment of the gene (CLG4) to the q21 region of chromosome 16. Genomics. 1990 Mar;6(3):554-9. [PubMed:2158484 ]
  11. Collier IE, Wilhelm SM, Eisen AZ, Marmer BL, Grant GA, Seltzer JL, Kronberger A, He CS, Bauer EA, Goldberg GI: H-ras oncogene-transformed human bronchial epithelial cells (TBE-1) secrete a single metalloprotease capable of degrading basement membrane collagen. J Biol Chem. 1988 May 15;263(14):6579-87. [PubMed:2834383 ]
  12. Howard EW, Banda MJ: Binding of tissue inhibitor of metalloproteinases 2 to two distinct sites on human 72-kDa gelatinase. Identification of a stabilization site. J Biol Chem. 1991 Sep 25;266(27):17972-7. [PubMed:1655733 ]
  13. Brooks PC, Stromblad S, Sanders LC, von Schalscha TL, Aimes RT, Stetler-Stevenson WG, Quigley JP, Cheresh DA: Localization of matrix metalloproteinase MMP-2 to the surface of invasive cells by interaction with integrin alpha v beta 3. Cell. 1996 May 31;85(5):683-93. [PubMed:8646777 ]
  14. Butler GS, Will H, Atkinson SJ, Murphy G: Membrane-type-2 matrix metalloproteinase can initiate the processing of progelatinase A and is regulated by the tissue inhibitors of metalloproteinases. Eur J Biochem. 1997 Mar 1;244(2):653-7. [PubMed:9119036 ]
  15. Brooks PC, Silletti S, von Schalscha TL, Friedlander M, Cheresh DA: Disruption of angiogenesis by PEX, a noncatalytic metalloproteinase fragment with integrin binding activity. Cell. 1998 Feb 6;92(3):391-400. [PubMed:9476898 ]
  16. Fernandez-Patron C, Radomski MW, Davidge ST: Vascular matrix metalloproteinase-2 cleaves big endothelin-1 yielding a novel vasoconstrictor. Circ Res. 1999 Nov 12;85(10):906-11. [PubMed:10559137 ]
  17. Fernandez-Patron C, Stewart KG, Zhang Y, Koivunen E, Radomski MW, Davidge ST: Vascular matrix metalloproteinase-2-dependent cleavage of calcitonin gene-related peptide promotes vasoconstriction. Circ Res. 2000 Oct 13;87(8):670-6. [PubMed:11029402 ]
  18. Bello L, Lucini V, Carrabba G, Giussani C, Machluf M, Pluderi M, Nikas D, Zhang J, Tomei G, Villani RM, Carroll RS, Bikfalvi A, Black PM: Simultaneous inhibition of glioma angiogenesis, cell proliferation, and invasion by a naturally occurring fragment of human metalloproteinase-2. Cancer Res. 2001 Dec 15;61(24):8730-6. [PubMed:11751392 ]
  19. Chattopadhyay N, Mitra A, Frei E, Chatterjee A: Human cervical tumor cell (SiHa) surface alphavbeta3 integrin receptor has associated matrix metalloproteinase (MMP-2) activity. J Cancer Res Clin Oncol. 2001 Nov;127(11):653-8. [PubMed:11710594 ]
  20. Kwan JA, Schulze CJ, Wang W, Leon H, Sariahmetoglu M, Sung M, Sawicka J, Sims DE, Sawicki G, Schulz R: Matrix metalloproteinase-2 (MMP-2) is present in the nucleus of cardiac myocytes and is capable of cleaving poly (ADP-ribose) polymerase (PARP) in vitro. FASEB J. 2004 Apr;18(6):690-2. Epub 2004 Feb 6. [PubMed:14766804 ]
  21. Sariahmetoglu M, Crawford BD, Leon H, Sawicka J, Li L, Ballermann BJ, Holmes C, Berthiaume LG, Holt A, Sawicki G, Schulz R: Regulation of matrix metalloproteinase-2 (MMP-2) activity by phosphorylation. FASEB J. 2007 Aug;21(10):2486-95. Epub 2007 Apr 13. [PubMed:17435175 ]
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  23. Libson AM, Gittis AG, Collier IE, Marmer BL, Goldberg GI, Lattman EE: Crystal structure of the haemopexin-like C-terminal domain of gelatinase A. Nat Struct Biol. 1995 Nov;2(11):938-42. [PubMed:7583664 ]
  24. Gohlke U, Gomis-Ruth FX, Crabbe T, Murphy G, Docherty AJ, Bode W: The C-terminal (haemopexin-like) domain structure of human gelatinase A (MMP2): structural implications for its function. FEBS Lett. 1996 Jan 8;378(2):126-30. [PubMed:8549817 ]
  25. Morgunova E, Tuuttila A, Bergmann U, Isupov M, Lindqvist Y, Schneider G, Tryggvason K: Structure of human pro-matrix metalloproteinase-2: activation mechanism revealed. Science. 1999 Jun 4;284(5420):1667-70. [PubMed:10356396 ]
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  27. Briknarova K, Gehrmann M, Banyai L, Tordai H, Patthy L, Llinas M: Gelatin-binding region of human matrix metalloproteinase-2: solution structure, dynamics, and function of the COL-23 two-domain construct. J Biol Chem. 2001 Jul 20;276(29):27613-21. Epub 2001 Apr 24. [PubMed:11320090 ]
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  29. Gehrmann M, Briknarova K, Banyai L, Patthy L, Llinas M: The col-1 module of human matrix metalloproteinase-2 (MMP-2): structural/functional relatedness between gelatin-binding fibronectin type II modules and lysine-binding kringle domains. Biol Chem. 2002 Jan;383(1):137-48. [PubMed:11928808 ]
  30. Morgunova E, Tuuttila A, Bergmann U, Tryggvason K: Structural insight into the complex formation of latent matrix metalloproteinase 2 with tissue inhibitor of metalloproteinase 2. Proc Natl Acad Sci U S A. 2002 May 28;99(11):7414-9. [PubMed:12032297 ]
  31. Pirard B, Matter H: Matrix metalloproteinase target family landscape: a chemometrical approach to ligand selectivity based on protein binding site analysis. J Med Chem. 2006 Jan 12;49(1):51-69. [PubMed:16392792 ]
  32. Martignetti JA, Aqeel AA, Sewairi WA, Boumah CE, Kambouris M, Mayouf SA, Sheth KV, Eid WA, Dowling O, Harris J, Glucksman MJ, Bahabri S, Meyer BF, Desnick RJ: Mutation of the matrix metalloproteinase 2 gene (MMP2) causes a multicentric osteolysis and arthritis syndrome. Nat Genet. 2001 Jul;28(3):261-5. [PubMed:11431697 ]
  33. Zankl A, Bonafe L, Calcaterra V, Di Rocco M, Superti-Furga A: Winchester syndrome caused by a homozygous mutation affecting the active site of matrix metalloproteinase 2. Clin Genet. 2005 Mar;67(3):261-6. [PubMed:15691365 ]
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