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P33434 (MMP2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 136. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·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
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

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. Ref.4

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/beta-3 on the surface of blood vessels By similarity. Ref.4

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.4

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

Isoform 1: 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. Ref.4

Isoform 2: Cytoplasm. Mitochondrion Ref.4.

Developmental stage

Present in unfertilized eggs and at the zygote and cleavage stages. Levels increase at the blastocyst stage and with endoderm differentiation. Ref.3

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 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 componentCytoplasm
Extracellular matrix
Membrane
Mitochondrion
Nucleus
Secreted
   Coding sequence diversityAlternative splicing
   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_processangiogenesis

Inferred from electronic annotation. Source: UniProtKB-KW

blood vessel maturation

Inferred from genetic interaction PubMed 11747814. Source: MGI

bone trabecula formation

Inferred from genetic interaction PubMed 17440987. Source: MGI

cellular response to amino acid stimulus

Inferred from direct assay PubMed 20548288. Source: MGI

collagen catabolic process

Inferred from electronic annotation. Source: UniProtKB-KW

embryo implantation

Inferred from direct assay PubMed 18556655. Source: MGI

face morphogenesis

Inferred from genetic interaction PubMed 17440987. Source: MGI

intramembranous ossification

Inferred from genetic interaction PubMed 17440987. Source: MGI

positive regulation of innate immune response

Inferred from direct assay Ref.4. Source: MGI

proteolysis

Inferred from electronic annotation. Source: UniProtKB-KW

response to hypoxia

Inferred from direct assay PubMed 17382917. Source: MGI

skeletal system morphogenesis

Inferred from genetic interaction PubMed 17440987. Source: MGI

   Cellular_componentcytoplasm

Inferred from direct assay Ref.4. Source: MGI

extracellular space

Inferred from direct assay Ref.4. Source: MGI

membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

mitochondrion

Inferred from direct assay Ref.4. Source: MGI

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

plasma membrane

Inferred from direct assay PubMed 17349656. Source: MGI

proteinaceous extracellular matrix

Inferred from electronic annotation. Source: UniProtKB-SubCell

sarcomere

Inferred from direct assay PubMed 17349656. Source: MGI

   Molecular_functionmetalloendopeptidase activity

Inferred from direct assay PubMed 12419962PubMed 15212943. Source: MGI

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P33434-1)

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: P33434-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-76: Missing.
Note: Induced by oxidative stress.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2929 Potential
Propeptide30 – 10980Activation peptide
PRO_0000028716
Chain110 – 66255372 kDa type IV collagenase
PRO_0000028717
Chain445 – 662218PEX By similarity
PRO_0000391627

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

Natural variations

Alternative sequence1 – 7676Missing in isoform 2.
VSP_044632

Sequences

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

Last modified February 1, 1994. Version 1.
Checksum: C630A7DBDB272F02

FASTA66274,102
        10         20         30         40         50         60 
MEARVAWGAL AGPLRVLCVL CCLLGRAIAA PSPIIKFPGD VAPKTDKELA 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 TMGGNADGQP CKFPFRFQGT 

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

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

       430        440        450        460        470        480 
MAPIYTYTKN FRLSHDDIKG 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 KTYIFAGDKF WRYNEVKKKM 

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


GC 

« Hide

Isoform 2 [UniParc].

Checksum: B8EE47CF5723C3D6
Show »

FASTA58665,883

References

« Hide 'large scale' references
[1]"Molecular cloning of murine 72-kDa type IV collagenase and its expression during mouse development."
Reponen P., Sahlberg C., Huhtala P., Hurskainen T., Thesleff I., Tryggvason K.
J. Biol. Chem. 267:7856-7862(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"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).
Strain: C57BL/6.
Tissue: Brain.
[3]"Genes for extracellular-matrix-degrading metalloproteinases and their inhibitor, TIMP, are expressed during early mammalian development."
Brenner C.A., Adler R.R., Rappolee D.A., Pedersen R.A., Werb Z.
Genes Dev. 3:848-859(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: DEVELOPMENTAL STAGE.
Tissue: Embryo.
[4]"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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M84324 mRNA. Translation: AAA39338.1.
BC070430 mRNA. Translation: AAH70430.1.
PIRA42496.
RefSeqNP_032636.1. NM_008610.2.
UniGeneMm.29564.

3D structure databases

ProteinModelPortalP33434.
SMRP33434. Positions 30-662.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActP33434. 1 interaction.

Chemistry

BindingDBP33434.
ChEMBLCHEMBL3095.

Protein family/group databases

MEROPSM10.003.

PTM databases

PhosphoSiteP33434.

Proteomic databases

PaxDbP33434.
PRIDEP33434.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000034187; ENSMUSP00000034187; ENSMUSG00000031740. [P33434-1]
GeneID17390.
KEGGmmu:17390.
UCSCuc009mue.1. mouse. [P33434-1]

Organism-specific databases

CTD4313.
MGIMGI:97009. Mmp2.

Phylogenomic databases

eggNOGNOG303159.
HOGENOMHOG000217926.
HOVERGENHBG052484.
InParanoidP33434.
KOK01398.
OMALMAPIYT.
OrthoDBEOG70KGNX.
PhylomeDBP33434.
TreeFamTF315428.

Gene expression databases

ArrayExpressP33434.
BgeeP33434.
CleanExMM_MMP2.
GenevestigatorP33434.

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. mouse.
NextBio292012.
PROP33434.
SOURCESearch...

Entry information

Entry nameMMP2_MOUSE
AccessionPrimary (citable) accession number: P33434
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: February 1, 1994
Last modified: April 16, 2014
This is version 136 of the entry and version 1 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

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot