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P33436 (MMP2_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 119. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·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

Cleaved into the following chain:

  1. PEX
Gene names
Name:Mmp2
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length662 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at transcript 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 By similarity.

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 integrin alpha-v/beta3 on the surface of blood vessels By similarity.

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 By similarity.

Binds 2 zinc ions per subunit By similarity.

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 By similarity.

Subcellular location

Secretedextracellular spaceextracellular matrix By similarity. Membrane By similarity. Nucleus By similarity. 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 By similarity.

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 By similarity.

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

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 componentExtracellular matrix
Membrane
Nucleus
Secreted
   DomainRepeat
Signal
   LigandCalcium
Metal-binding
Zinc
   Molecular functionHydrolase
Metalloprotease
Protease
   PTMAutocatalytic cleavage
Disulfide bond
Glycoprotein
Phosphoprotein
Zymogen
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processanatomical structure regression

Inferred from expression pattern PubMed 19906188. Source: RGD

angiogenesis

Inferred from expression pattern PubMed 12234794. Source: RGD

cell growth

Inferred from expression pattern PubMed 16563274. Source: RGD

cell migration

Inferred from mutant phenotype PubMed 20371087. Source: RGD

cellular response to estradiol stimulus

Inferred from mutant phenotype PubMed 19861308. Source: RGD

cellular response to fluid shear stress

Inferred from expression pattern PubMed 21637818. Source: RGD

cellular response to interleukin-1

Inferred from expression pattern PubMed 16046515PubMed 20371087. Source: RGD

collagen catabolic process

Inferred from direct assay PubMed 22410640. Source: RGD

female pregnancy

Inferred from expression pattern PubMed 15044600. Source: RGD

luteinization

Inferred from expression pattern PubMed 10537164. Source: RGD

negative regulation of cell adhesion

Inferred from direct assay PubMed 14645107. Source: RGD

negative regulation of vasoconstriction

Inferred from direct assay PubMed 19482300. Source: RGD

ovarian follicle development

Inferred from direct assay PubMed 15617683. Source: RGD

ovulation from ovarian follicle

Inferred from expression pattern PubMed 14668206. Source: RGD

parturition

Inferred from expression pattern PubMed 19923067. Source: RGD

peripheral nervous system axon regeneration

Inferred from direct assay PubMed 15026117. Source: RGD

positive regulation of apoptotic process

Inferred from direct assay PubMed 16857167. Source: RGD

positive regulation of cell migration

Inferred from mutant phenotype PubMed 21637818. Source: RGD

prostate gland epithelium morphogenesis

Inferred from mutant phenotype PubMed 20108352. Source: RGD

proteolysis

Inferred from direct assay PubMed 16899336. Source: RGD

response to activity

Inferred from expression pattern PubMed 19685505. Source: RGD

response to drug

Inferred from direct assay PubMed 16846501. Source: RGD

response to electrical stimulus

Inferred from expression pattern PubMed 19660200. Source: RGD

response to hydrogen peroxide

Inferred from direct assay PubMed 16934674. Source: RGD

response to hyperoxia

Inferred from expression pattern PubMed 19099751. Source: RGD

response to hypoxia

Inferred from direct assay PubMed 16980344. Source: RGD

response to mechanical stimulus

Inferred from direct assay PubMed 15350851. Source: RGD

response to nicotine

Inferred from expression pattern PubMed 19879865. Source: RGD

response to radiation

Inferred from expression pattern PubMed 19922364. Source: RGD

response to retinoic acid

Inferred from expression pattern PubMed 19099751. Source: RGD

tissue remodeling

Inferred from direct assay PubMed 16740171. Source: RGD

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 16740171PubMed 20213142. Source: RGD

membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

proteinaceous extracellular matrix

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionmetalloendopeptidase activity

Inferred from electronic annotation. Source: InterPro

metallopeptidase activity

Traceable author statement PubMed 11826121. Source: RGD

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2929 Potential
Propeptide30 – 10980Activation peptide
PRO_0000028720
Chain110 – 66255372 kDa type IV collagenase
PRO_0000028721
Chain445 – 662218PEX By similarity
PRO_0000391629

Regions

Domain228 – 27649Fibronectin type-II 1
Domain286 – 33449Fibronectin type-II 2
Domain344 – 39249Fibronectin type-II 3
Repeat474 – 51845Hemopexin 1
Repeat519 – 56547Hemopexin 2
Repeat567 – 61549Hemopexin 3
Repeat616 – 66247Hemopexin 4
Region110 – 221112Collagenase-like 1
Region222 – 396175Collagen-binding
Region397 – 46771Collagenase-like 2
Region414 – 662249Required for inhibitor TIMP2 binding By similarity
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 binding4781Calcium 4; via carbonyl oxygen By similarity
Metal binding5231Calcium 4; via carbonyl oxygen By similarity
Metal binding5711Calcium 4; via carbonyl oxygen By similarity
Metal binding6201Calcium 4; via carbonyl oxygen By similarity

Amino acid modifications

Glycosylation5751N-linked (GlcNAc...) Potential
Glycosylation6441N-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 bond471 ↔ 662 By similarity

Experimental info

Sequence conflict421S → A in CAA50583. Ref.1
Sequence conflict2861G → A in CAA50583. Ref.1
Sequence conflict3691S → N in CAA50583. Ref.1
Sequence conflict4351N → H in CAA50583. Ref.1
Sequence conflict5861S → A in CAA50583. Ref.1

Sequences

Sequence LengthMass (Da)Tools
P33436 [UniParc].

Last modified May 1, 2007. Version 2.
Checksum: C56BD787473FC03E

FASTA66274,149
        10         20         30         40         50         60 
MEARLVWGVL VGPLRVLCVL CCLLGHAIAA PSPIIKFPGD VSPKTDKELA VQYLNTFYGC 

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

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

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

       250        260        270        280        290        300 
GREYSSCTDT GRSDGFLWCS TTYNFEKDGK YGFCPHEALF TMGGNGDGQP CKFPFRFQGT 

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

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

       430        440        450        460        470        480 
MAPIYTYTKN FRLSNDDIKG IQELYGPSPD ADTDTGTGPT PTLGPVTPEI CKQDIVFDGI 

       490        500        510        520        530        540 
AQIRGEIFFF KDRFIWRTVT PRDKPTGPLL VATFWPELPE KIDAVYEAPQ EEKAVFFAGN 

       550        560        570        580        590        600 
EYWVYSASTL ERGYPKPLTS LGLPPDVQQV DAAFNWSKNK KTYIFSGDKF WRYNEVKKKM 

       610        620        630        640        650        660 
DPGFPKLIAD SWNAIPDNLD AVVDLQGGGH SYFFKGAYYL KLENQSLKSV KFGSIKSDWL 


GC 

« Hide

References

« Hide 'large scale' references
[1]"Homology cloning of rat 72 kDa type IV collagenase: cytokine and second-messenger inducibility in glomerular mesangial cells."
Marti H.P., McNeil L., Davies M., Martin J., Lovett D.H.
Biochem. J. 291:441-446(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"The cloning of the cDNA encoding rat gelatinase A from a rat skin wound cDNA library."
Okada A., Basset P.
Submitted (JUL-1996) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: Wistar.
Tissue: Skin.
[3]"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].
Tissue: Lung.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X71466 mRNA. Translation: CAA50583.1.
U65656 mRNA. Translation: AAB41692.1.
BC074013 mRNA. Translation: AAH74013.1.
PIRS34780.
RefSeqNP_112316.2. NM_031054.2.
UniGeneRn.6422.

3D structure databases

ProteinModelPortalP33436.
SMRP33436. Positions 30-662.
ModBaseSearch...
MobiDBSearch...

Chemistry

BindingDBP33436.
ChEMBLCHEMBL1075175.

Protein family/group databases

MEROPSM10.003.

Proteomic databases

PaxDbP33436.
PRIDEP33436.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID81686.
KEGGrno:81686.

Organism-specific databases

CTD4313.
RGD621316. Mmp2.

Phylogenomic databases

eggNOGNOG303159.
HOVERGENHBG052484.
KOK01398.

Gene expression databases

GenevestigatorP33436.

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

NextBio615320.
PROP33436.

Entry information

Entry nameMMP2_RAT
AccessionPrimary (citable) accession number: P33436
Secondary accession number(s): P97581, Q6GMM9
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: May 1, 2007
Last modified: March 19, 2014
This is version 119 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries