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P08253 (MMP2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 181. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
72 kDa type IV collagenase

EC=3.4.24.24
Alternative name(s):
72 kDa gelatinase
Gelatinase A
Matrix metalloproteinase-2
Short name=MMP-2
TBE-1

Cleaved into the following chain:

  1. PEX
Gene names
Name:MMP2
Synonyms:CLG4A
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length660 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Ubiquitinous metalloproteinase that is involved in diverse functions such as remodeling of the vasculature, angiogenesis, tissue repair, tumor invasion, inflammation, and atherosclerotic plaque rupture. As well as degrading extracellular matrix proteins, can also act on several nonmatrix proteins such as big endothelial 1 and beta-type CGRP promoting vasoconstriction. Also cleaves KISS at a Gly-|-Leu bond. Appears to have a role in myocardial cell death pathways. Contributes to myocardial oxidative stress by regulating the activity of GSK3beta. Cleaves GSK3beta in vitro. Involved in the formation of the fibrovascular tissues in association with MMP14. Ref.13 Ref.14 Ref.15 Ref.16 Ref.18 Ref.19 Ref.23 Ref.25

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. Ref.13 Ref.14 Ref.15 Ref.16 Ref.18 Ref.19 Ref.23 Ref.25

Isoform 2:Mediates the proteolysis of CHUK/IKKA and initiates a primary innate immune response by inducing mitochondrial-nuclear stress signaling with activation of the pro-inflammatory NF-kappaB, NFAT and IRF transcriptional pathways. Ref.13 Ref.14 Ref.15 Ref.16 Ref.18 Ref.19 Ref.23 Ref.25

Catalytic activity

Cleavage of gelatin type I and collagen types IV, V, VII, X. Cleaves the collagen-like sequence Pro-Gln-Gly-|-Ile-Ala-Gly-Gln.

Cofactor

Binds 4 calcium ions per subunit.

Binds 2 zinc ions per subunit.

Enzyme regulation

Inhibited by histatin-3 1/24 (histatin-5). Ref.17

Subunit structure

Interacts (via the C-terminal hemopexin-like domains-containing region) with the integrin alpha-V/beta-3; the interaction promotes vascular invasion in angiogenic vessels and melamoma cells. Interacts (via the C-terminal PEX domain) with TIMP2 (via the C-terminal); the interaction inhibits the degradation activity. Interacts with GSK3B. Ref.10 Ref.16 Ref.18 Ref.23

Subcellular location

Isoform 1: Secretedextracellular spaceextracellular matrix. Membrane. Nucleus. Note: Colocalizes with integrin alphaV/beta3 at the membrane surface in angiogenic blood vessels and melanomas. Found in mitochondria, along microfibrils, and in nuclei of cardiomyocytes. Ref.11 Ref.21 Ref.25

Isoform 2: Cytoplasm. Mitochondrion Ref.11 Ref.21 Ref.25.

Tissue specificity

Produced by normal skin fibroblasts. PEX is expressed in a number of tumors including gliomas, breast and prostate. Ref.16

Induction

Aspirin appears to inhibit expression. Ref.17 Ref.24

Domain

The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.

Post-translational modification

Phosphorylation on multiple sites modulates enzymatic activity. Phosphorylated by PKC in vitro. Ref.22

The propeptide is processed by MMP14 (MT-MMP1) and MMP16 (MT-MMP3). Autocatalytic cleavage in the C-terminal produces the anti-angiogenic peptide, PEX. This processing appears to be facilitated by binding integrinv/beta3.

Involvement in disease

Multicentric osteolysis, nodulosis, and arthropathy (MONA) [MIM:259600]: An autosomal recessive syndrome characterized by severe multicentric osteolysis with predominant involvement of the hands and feet. Additional features include coarse face, corneal opacities, patches of thickened, hyperpigmented skin, hypertrichosis and gum hypertrophy.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.35 Ref.36 Ref.37

Sequence similarities

Belongs to the peptidase M10A family.

Contains 3 fibronectin type-II domains.

Contains 4 hemopexin repeats.

Ontologies

Keywords
   Biological processAngiogenesis
Collagen degradation
   Cellular componentCytoplasm
Extracellular matrix
Membrane
Mitochondrion
Nucleus
Secreted
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
   DomainRepeat
Signal
   LigandCalcium
Metal-binding
Zinc
   Molecular functionHydrolase
Metalloprotease
Protease
   PTMAutocatalytic cleavage
Disulfide bond
Glycoprotein
Phosphoprotein
Zymogen
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processangiogenesis

Inferred from electronic annotation. Source: UniProtKB-KW

blood vessel maturation

Inferred from electronic annotation. Source: Ensembl

bone trabecula formation

Inferred from electronic annotation. Source: Ensembl

cellular protein metabolic process

Traceable author statement. Source: Reactome

cellular response to amino acid stimulus

Inferred from electronic annotation. Source: Ensembl

collagen catabolic process

Traceable author statement. Source: Reactome

embryo implantation

Inferred from electronic annotation. Source: Ensembl

extracellular matrix disassembly

Traceable author statement. Source: Reactome

extracellular matrix organization

Traceable author statement. Source: Reactome

face morphogenesis

Inferred from electronic annotation. Source: Ensembl

intramembranous ossification

Inferred from electronic annotation. Source: Ensembl

proteolysis

Traceable author statement Ref.8. Source: ProtInc

response to hypoxia

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentextracellular region

Traceable author statement. Source: Reactome

extracellular space

Inferred from direct assay PubMed 20551380. Source: BHF-UCL

mitochondrion

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

plasma membrane

Inferred from electronic annotation. Source: Ensembl

proteinaceous extracellular matrix

Inferred from electronic annotation. Source: UniProtKB-SubCell

sarcomere

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionmetalloendopeptidase activity

Traceable author statement Ref.8. Source: ProtInc

serine-type endopeptidase activity

Traceable author statement. Source: Reactome

zinc ion binding

Traceable author statement Ref.8. Source: ProtInc

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

SCUBE3Q8IX302EBI-1033518,EBI-4479975

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P08253-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P08253-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-76: Missing.
Note: Induced by oxidative stress.
Isoform 3 (identifier: P08253-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-51: MEALMARGALTGPLRALCLLGCLLSHAAAAPSPIIKFPGDVAPKTDKELAV → M
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2929 Potential
Propeptide30 – 10980Activation peptide
PRO_0000028714
Chain110 – 66055172 kDa type IV collagenase
PRO_0000028715
Chain445 – 660216PEX
PRO_0000391626

Regions

Domain228 – 27649Fibronectin type-II 1
Domain286 – 33449Fibronectin type-II 2
Domain344 – 39249Fibronectin type-II 3
Repeat472 – 51645Hemopexin 1
Repeat517 – 56347Hemopexin 2
Repeat565 – 61349Hemopexin 3
Repeat614 – 66047Hemopexin 4
Region110 – 221112Collagenase-like 1
Region222 – 396175Collagen-binding
Region397 – 46569Collagenase-like 2
Region414 – 660247Required for inhibitor TIMP2 binding
Motif100 – 1078Cysteine switch By similarity

Sites

Active site4041 By similarity
Metal binding1021Zinc 2; in inhibited form By similarity
Metal binding1341Calcium 1 By similarity
Metal binding1681Calcium 2 By similarity
Metal binding1781Zinc 1 By similarity
Metal binding1801Zinc 1 By similarity
Metal binding1851Calcium 3 By similarity
Metal binding1861Calcium 3; via carbonyl oxygen By similarity
Metal binding1931Zinc 1 By similarity
Metal binding2001Calcium 2; via carbonyl oxygen By similarity
Metal binding2021Calcium 2; via carbonyl oxygen By similarity
Metal binding2041Calcium 2 By similarity
Metal binding2061Zinc 1 By similarity
Metal binding2081Calcium 3 By similarity
Metal binding2091Calcium 1 By similarity
Metal binding2111Calcium 3 By similarity
Metal binding4031Zinc 2; catalytic By similarity
Metal binding4071Zinc 2; catalytic By similarity
Metal binding4131Zinc 2; catalytic By similarity
Metal binding4761Calcium 4; via carbonyl oxygen
Metal binding5211Calcium 4; via carbonyl oxygen
Metal binding5691Calcium 4; via carbonyl oxygen
Metal binding6181Calcium 4; via carbonyl oxygen

Amino acid modifications

Glycosylation5731N-linked (GlcNAc...) Potential
Glycosylation6421N-linked (GlcNAc...) Potential
Disulfide bond233 ↔ 259 By similarity
Disulfide bond247 ↔ 274 By similarity
Disulfide bond291 ↔ 317 By similarity
Disulfide bond305 ↔ 332 By similarity
Disulfide bond349 ↔ 375 By similarity
Disulfide bond363 ↔ 390 By similarity
Disulfide bond469 ↔ 660 Ref.29

Natural variations

Alternative sequence1 – 7676Missing in isoform 2.
VSP_044631
Alternative sequence1 – 5151MEALM…KELAV → M in isoform 3.
VSP_045704
Natural variant1011R → H in MONA. Ref.35
VAR_032423
Natural variant2101D → Y. Ref.35
VAR_032424
Natural variant2281A → T in a colorectal cancer sample; somatic mutation. Ref.38
VAR_036136
Natural variant4001Missing in MONA. Ref.37
VAR_054996
Natural variant4041E → K in MONA. Ref.36
VAR_032425
Natural variant4471A → V. Ref.4
Corresponds to variant rs17859943 [ dbSNP | Ensembl ].
VAR_020616
Natural variant4981T → M in a colorectal cancer sample; somatic mutation. Ref.38
VAR_036137
Natural variant6211V → L. Ref.4
Corresponds to variant rs16955280 [ dbSNP | Ensembl ].
VAR_020617
Natural variant6441S → I in a colorectal cancer sample; somatic mutation. Ref.38
VAR_036138

Experimental info

Sequence conflict2351F → S in AK310314. Ref.3
Sequence conflict5461S → G in BAG35588. Ref.3
Sequence conflict6181D → G in BAG35588. Ref.3

Secondary structure

....................................................................................................................................... 660
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified February 1, 1991. Version 2.
Checksum: BC7147DC8B49F289

FASTA66073,882
        10         20         30         40         50         60 
MEALMARGAL TGPLRALCLL GCLLSHAAAA PSPIIKFPGD VAPKTDKELA VQYLNTFYGC 

        70         80         90        100        110        120 
PKESCNLFVL KDTLKKMQKF FGLPQTGDLD QNTIETMRKP RCGNPDVANY NFFPRKPKWD 

       130        140        150        160        170        180 
KNQITYRIIG YTPDLDPETV DDAFARAFQV WSDVTPLRFS RIHDGEADIM INFGRWEHGD 

       190        200        210        220        230        240 
GYPFDGKDGL LAHAFAPGTG VGGDSHFDDD ELWTLGEGQV VRVKYGNADG EYCKFPFLFN 

       250        260        270        280        290        300 
GKEYNSCTDT GRSDGFLWCS TTYNFEKDGK YGFCPHEALF TMGGNAEGQP CKFPFRFQGT 

       310        320        330        340        350        360 
SYDSCTTEGR TDGYRWCGTT EDYDRDKKYG FCPETAMSTV GGNSEGAPCV FPFTFLGNKY 

       370        380        390        400        410        420 
ESCTSAGRSD GKMWCATTAN YDDDRKWGFC PDQGYSLFLV AAHEFGHAMG LEHSQDPGAL 

       430        440        450        460        470        480 
MAPIYTYTKN FRLSQDDIKG IQELYGASPD IDLGTGPTPT LGPVTPEICK QDIVFDGIAQ 

       490        500        510        520        530        540 
IRGEIFFFKD RFIWRTVTPR DKPMGPLLVA TFWPELPEKI DAVYEAPQEE KAVFFAGNEY 

       550        560        570        580        590        600 
WIYSASTLER GYPKPLTSLG LPPDVQRVDA AFNWSKNKKT YIFAGDKFWR YNEVKKKMDP 

       610        620        630        640        650        660 
GFPKLIADAW NAIPDNLDAV VDLQGGGHSY FFKGAYYLKL ENQSLKSVKF GSIKSDWLGC 

« Hide

Isoform 2 [UniParc].

Checksum: EC1C16C91ECBC26C
Show »

FASTA58465,765
Isoform 3 [UniParc].

Checksum: FB214CA4334DC5FC
Show »

FASTA61068,831

References

« Hide 'large scale' references
[1]"Structure of the human type IV collagenase gene."
Huhtala P., Chow L.T., Tryggvason K.
J. Biol. Chem. 265:11077-11082(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]"On the structure and chromosome location of the 72- and 92-kDa human type IV collagenase genes."
Collier I.E., Bruns G.A.P., Goldberg G.I., Gerhard D.S.
Genomics 9:429-434(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3).
Tissue: Teratocarcinoma and Testis.
[4]NIEHS SNPs program
Submitted (AUG-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS VAL-447 AND LEU-621.
[5]"The sequence and analysis of duplication-rich human chromosome 16."
Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J. expand/collapse author list , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A.
Nature 432:988-994(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Brain.
[7]"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."
Huhtala P., Eddy R.L., Fan Y.S., Byers M.G., Shows T.B., Tryggvason K.
Genomics 6:554-559(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-51.
[8]"H-ras oncogene-transformed human bronchial epithelial cells (TBE-1) secrete a single metalloprotease capable of degrading basement membrane collagen."
Collier I.E., Wilhelm S.M., Eisen A.Z., Marmer B.L., Grant G.A., Seltzer J.L., Kronberger A., He C., Bauer E.A., Goldberg G.I.
J. Biol. Chem. 263:6579-6587(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 19-660 (ISOFORM 1), PARTIAL PROTEIN SEQUENCE.
[9]"TIMP-2: identification and characterization of a new member of the metalloproteinase inhibitor family."
Stetler-Stevenson W.G., Krutzsch H.C., Liotta L.A.
Matrix Suppl. 1:299-306(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 30-44.
Tissue: Melanoma.
[10]"Binding of tissue inhibitor of metalloproteinases 2 to two distinct sites on human 72-kDa gelatinase. Identification of a stabilization site."
Howard E.W., Banda M.J.
J. Biol. Chem. 266:17972-17977(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TIMP2.
[11]"Localization of matrix metalloproteinase MMP-2 to the surface of invasive cells by interaction with integrin alpha v beta 3."
Brooks P.C., Stroemblad S., Sanders L.C., von Schalscha T.L., Aimes R.T., Stetler-Stevenson W.G., Quigley J.P., Cheresh D.A.
Cell 85:683-693(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION OF RECEPTOR, SUBCELLULAR LOCATION.
[12]"Membrane-type-2 matrix metalloproteinase can initiate the processing of progelatinase A and is regulated by the tissue inhibitors of metalloproteinases."
Butler G.S., Will H., Atkinson S.J., Murphy G.
Eur. J. Biochem. 244:653-657(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEOLYTIC PROCESSING.
[13]"Disruption of angiogenesis by PEX, a noncatalytic metalloproteinase fragment with integrin binding activity."
Brooks P.C., Silletti S., von Schalscha T.L., Friedlander M., Cheresh D.A.
Cell 92:391-400(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION OF RECEPTOR, FUNCTION.
[14]"Vascular matrix metalloproteinase-2 cleaves big endothelin-1 yielding a novel vasoconstrictor."
Fernandez-Patron C., Radomski M.W., Davidge S.T.
Circ. Res. 85:906-911(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[15]"Vascular matrix metalloproteinase-2-dependent cleavage of calcitonin gene-related peptide promotes vasoconstriction."
Fernandez-Patron C., Stewart K.G., Zhang Y., Koivunen E., Radomski M.W., Davidge S.T.
Circ. Res. 87:670-676(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[16]"Simultaneous inhibition of glioma angiogenesis, cell proliferation, and invasion by a naturally occurring fragment of human metalloproteinase-2."
Bello L., Lucini V., Carrabba G., Giussani C., Machluf M., Pluderi M., Nikas D., Zhang J., Tomei G., Villani R.M., Carroll R.S., Bikfalvi A., Black P.M.
Cancer Res. 61:8730-8736(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION OF PEX, TISSUE SPECIFICITY, INTERACTION WITH TIMP2.
[17]"Salivary histatin 5 is an inhibitor of both host and bacterial enzymes implicated in periodontal disease."
Gusman H., Travis J., Helmerhorst E.J., Potempa J., Troxler R.F., Oppenheim F.G.
Infect. Immun. 69:1402-1408(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION.
[18]"Human cervical tumor cell (SiHa) surface alphavbeta3 integrin receptor has associated matrix metalloproteinase (MMP-2) activity."
Chattopadhyay N., Mitra A., Frei E., Chatterjee A.
J. Cancer Res. Clin. Oncol. 127:653-658(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION OF RECEPTOR, INTERACTION WITH TMP2, FUNCTION.
[19]"Production and activation of matrix metalloproteinase-2 in proliferative diabetic retinopathy."
Noda K., Ishida S., Inoue M., Obata K., Oguchi Y., Okada Y., Ikeda E.
Invest. Ophthalmol. Vis. Sci. 44:2163-2170(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN THE FORMATION OF THE FIBROVASCULAR TISSUES.
[20]"Cleavage of metastasis suppressor gene product KiSS-1 protein/metastin by matrix metalloproteinases."
Takino T., Koshikawa N., Miyamori H., Tanaka M., Sasaki T., Okada Y., Seiki M., Sato H.
Oncogene 22:4617-4626(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEOLYTIC PROCESSING OF KISS1.
[21]"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."
Kwan J.A., Schulze C.J., Wang W., Leon H., Sariahmetoglu M., Sung M., Sawicka J., Sims D.E., Sawicki G., Schulz R.
FASEB J. 18:690-692(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[22]"Regulation of matrix metalloproteinase-2 (MMP-2) activity by phosphorylation."
Sariahmetoglu M., Crawford B.D., Leon H., Sawicka J., Li L., Ballermann B.J., Holmes C., Berthiaume L.G., Holt A., Sawicki G., Schulz R.
FASEB J. 21:2486-2495(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION, IDENTIFICATION BY MASS SPECTROMETRY.
[23]"Glycogen synthase kinase-3beta is activated by matrix metalloproteinase-2 mediated proteolysis in cardiomyoblasts."
Kandasamy A.D., Schulz R.
Cardiovasc. Res. 83:698-706(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH GSK3B, FUNCTION.
[24]"Aspirin inhibits MMP-2 and MMP-9 expressions and activities through upregulation of PPARalpha/gamma and TIMP gene expressions in ox-LDL-stimulated macrophages derived from human monocytes."
Hua Y., Xue J., Sun F., Zhu L., Xie M.
Pharmacology 83:18-25(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION.
[25]"A novel intracellular isoform of matrix metalloproteinase-2 induced by oxidative stress activates innate immunity."
Lovett D.H., Mahimkar R., Raffai R.L., Cape L., Maklashina E., Cecchini G., Karliner J.S.
PLoS ONE 7:E34177-E34177(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ALTERNATIVE SPLICING (ISOFORM 2), FUNCTION, SUBCELLULAR LOCATION.
[26]"Crystal structure of the haemopexin-like C-terminal domain of gelatinase A."
Libson A.M., Gittis A.G., Collier I.E., Marmer B.L., Goldberg G.I., Lattman E.E.
Nat. Struct. Biol. 2:938-942(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 443-660.
[27]"The C-terminal (haemopexin-like) domain structure of human gelatinase A (MMP2): structural implications for its function."
Gohlke U., Gomis-Rueth F.-X., Crabbe T., Murphy G., Docherty A.J., Bode W.
FEBS Lett. 378:126-130(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 458-660.
[28]"Structure of human pro-matrix metalloproteinase-2: activation mechanism revealed."
Morgunova E., Tuuttila A., Bergmann U., Isupov M., Lindqvist Y., Schneider G., Tryggvason K.
Science 284:1667-1670(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 30-660 OF MUTANT ALA-404.
[29]"The second type II module from human matrix metalloproteinase 2: structure, function and dynamics."
Briknarova K., Grishaev A., Banyai L., Tordai H., Patthy L., Llinas M.
Structure 7:1235-1245(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 278-336, DISULFIDE BONDS.
[30]"Gelatin-binding region of human matrix metalloproteinase-2: solution structure, dynamics, and function of the COL-23 two-domain construct."
Briknarova K., Gehrmann M., Banyai L., Tordai H., Patthy L., Llinas M.
J. Biol. Chem. 276:27613-27621(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 337-394 OF WILD TYPE AND IN COMPLEX WITH PPG PEPTIDES.
[31]"Solution structure and backbone dynamics of the catalytic domain of matrix metalloproteinase-2 complexed with a hydroxamic acid inhibitor."
Feng Y., Likos J.J., Zhu L., Woodward H., Munie G., McDonald J.J., Stevens A.M., Howard C.P., De Crescenzo G.A., Welsch D., Shieh H.S., Stallings W.C.
Biochim. Biophys. Acta 1598:10-23(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 110-446 IN COMPLEX WITH A HYDROXAMIC ACID INHIBITOR.
[32]"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."
Gehrmann M., Briknarova K., Banyai L., Patthy L., Llinas M.
Biol. Chem. 383:137-148(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 223-282 OF WILD TYPE AND IN COMPLEX WITH A PPG PEPTIDE.
[33]"Structural insight into the complex formation of latent matrix metalloproteinase 2 with tissue inhibitor of metalloproteinase 2."
Morgunova E., Tuuttila A., Bergmann U., Tryggvason K.
Proc. Natl. Acad. Sci. U.S.A. 99:7414-7419(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) OF 30-660 IN COMPLEX WITH INHIBITOR TIMP2.
[34]"Matrix metalloproteinase target family landscape: a chemometrical approach to ligand selectivity based on protein binding site analysis."
Pirard B., Matter H.
J. Med. Chem. 49:51-69(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 115-449.
[35]"Mutation of the matrix metalloproteinase 2 gene (MMP2) causes a multicentric osteolysis and arthritis syndrome."
Martignetti J.A., Aqeel A.A., Sewairi W.A., Boumah C.E., Kambouris M., Mayouf S.A., Sheth K.V., Eid W.A., Dowling O., Harris J., Glucksman M.J., Bahabri S., Meyer B.F., Desnick R.J.
Nat. Genet. 28:261-265(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MONA HIS-101, VARIANT TYR-210.
[36]"Winchester syndrome caused by a homozygous mutation affecting the active site of matrix metalloproteinase 2."
Zankl A., Bonafe L., Calcaterra V., Di Rocco M., Superti-Furga A.
Clin. Genet. 67:261-266(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MONA LYS-404.
[37]"A novel homozygous MMP2 mutation in a family with Winchester syndrome."
Rouzier C., Vanatka R., Bannwarth S., Philip N., Coussement A., Paquis-Flucklinger V., Lambert J.-C.
Clin. Genet. 69:271-276(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MONA VAL-400 DEL.
[38]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] THR-228; MET-498 AND ILE-644.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M55593 expand/collapse EMBL AC list , M58552, M55582, M55583, M55584, M55585, M55586, M55587, M55588, M55589, M55590, M55591, M55592 Genomic DNA. Translation: AAA52028.1.
AK301536 mRNA. Translation: BAG63035.1.
AK310314 mRNA. No translation available.
AK312711 mRNA. Translation: BAG35588.1.
AY738117 Genomic DNA. Translation: AAU10089.1.
AC007336 Genomic DNA. No translation available.
AC092722 Genomic DNA. No translation available.
BC002576 mRNA. Translation: AAH02576.1.
M33789 Genomic DNA. Translation: AAA52027.1.
J03210 mRNA. Translation: AAA35701.1.
PIRA28153.
RefSeqNP_001121363.1. NM_001127891.1.
NP_004521.1. NM_004530.4.
UniGeneHs.513617.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1CK7X-ray2.80A30-660[»]
1CXWNMR-A278-336[»]
1EAKX-ray2.66A/B/C/D32-452[»]
1GENX-ray2.15A443-660[»]
1GXDX-ray3.10A/B30-660[»]
1HOVNMR-A110-446[»]
1J7MNMR-A337-394[»]
1KS0NMR-A223-282[»]
1QIBX-ray2.80A115-449[»]
1RTGX-ray2.60A451-660[»]
3AYUX-ray2.00A110-450[»]
ProteinModelPortalP08253.
SMRP08253. Positions 30-660.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110457. 18 interactions.
DIPDIP-26N.
IntActP08253. 9 interactions.
STRING9606.ENSP00000219070.

Chemistry

BindingDBP08253.
ChEMBLCHEMBL2095216.
DrugBankDB00786. Marimastat.
DB00605. Sulindac.
GuidetoPHARMACOLOGY1629.

Protein family/group databases

MEROPSM10.003.

PTM databases

PhosphoSiteP08253.

Polymorphism databases

DMDM116856.

Proteomic databases

PaxDbP08253.
PeptideAtlasP08253.
PRIDEP08253.

Protocols and materials databases

DNASU4313.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000219070; ENSP00000219070; ENSG00000087245. [P08253-1]
ENST00000437642; ENSP00000394237; ENSG00000087245. [P08253-3]
ENST00000543485; ENSP00000444143; ENSG00000087245. [P08253-2]
ENST00000570308; ENSP00000461421; ENSG00000087245. [P08253-2]
GeneID4313.
KEGGhsa:4313.
UCSCuc002ehz.4. human. [P08253-1]

Organism-specific databases

CTD4313.
GeneCardsGC16P055424.
HGNCHGNC:7166. MMP2.
HPACAB002788.
HPA001939.
MIM120360. gene.
259600. phenotype.
neXtProtNX_P08253.
Orphanet85196. Nodulosis-arthropathy-osteolysis syndrome.
3460. Torg-Winchester syndrome.
PharmGKBPA30877.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG303159.
HOGENOMHOG000217926.
HOVERGENHBG052484.
InParanoidP08253.
KOK01398.
OMALMAPIYT.
OrthoDBEOG70KGNX.
PhylomeDBP08253.
TreeFamTF315428.

Enzyme and pathway databases

BioCycMetaCyc:HS01565-MONOMER.
BRENDA3.4.24.24. 2681.
ReactomeREACT_118779. Extracellular matrix organization.
REACT_17015. Metabolism of proteins.
REACT_196873. Extracellular matrix organization.

Gene expression databases

ArrayExpressP08253.
BgeeP08253.
CleanExHS_MMP2.
GenevestigatorP08253.

Family and domain databases

Gene3D1.10.101.10. 1 hit.
2.10.10.10. 3 hits.
2.110.10.10. 1 hit.
3.40.390.10. 2 hits.
InterProIPR028708. 72kDa_collagenase.
IPR000562. FN_type2_col-bd.
IPR000585. Hemopexin-like_dom.
IPR018487. Hemopexin-like_repeat.
IPR018486. Hemopexin_CS.
IPR013806. Kringle-like.
IPR024079. MetalloPept_cat_dom.
IPR001818. Pept_M10_metallopeptidase.
IPR021190. Pept_M10A.
IPR021158. Pept_M10A_Zn_BS.
IPR006026. Peptidase_Metallo.
IPR002477. Peptidoglycan-bd-like.
[Graphical view]
PANTHERPTHR10201. PTHR10201. 1 hit.
PTHR10201:SF29. PTHR10201:SF29. 1 hit.
PfamPF00040. fn2. 3 hits.
PF00045. Hemopexin. 4 hits.
PF00413. Peptidase_M10. 1 hit.
PF01471. PG_binding_1. 1 hit.
[Graphical view]
PRINTSPR00138. MATRIXIN.
SMARTSM00059. FN2. 3 hits.
SM00120. HX. 4 hits.
SM00235. ZnMc. 1 hit.
[Graphical view]
SUPFAMSSF47090. SSF47090. 1 hit.
SSF50923. SSF50923. 1 hit.
SSF57440. SSF57440. 3 hits.
PROSITEPS00546. CYSTEINE_SWITCH. 1 hit.
PS00023. FN2_1. 3 hits.
PS51092. FN2_2. 3 hits.
PS00024. HEMOPEXIN. 1 hit.
PS51642. HEMOPEXIN_2. 4 hits.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSMMP2. human.
EvolutionaryTraceP08253.
GeneWikiMMP2.
GenomeRNAi4313.
NextBio16973.
PMAP-CutDBP08253.
PROP08253.
SOURCESearch...

Entry information

Entry nameMMP2_HUMAN
AccessionPrimary (citable) accession number: P08253
Secondary accession number(s): B2R6U1 expand/collapse secondary AC list , B4DWH3, E9PE45, Q9UCJ8
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: February 1, 1991
Last modified: April 16, 2014
This is version 181 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 16

Human chromosome 16: entries, gene names and cross-references to MIM