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Protein

72 kDa type IV collagenase

Gene

Mmp2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

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).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/beta-3 on the surface of blood vessels (By similarity).By similarity
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.1 Publication

Catalytic activityi

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

Cofactori

Protein has several cofactor binding sites:
  • Ca2+By similarityNote: Binds 4 Ca2+ ions per subunit.By similarity
  • Zn2+By similarityNote: Binds 2 Zn2+ ions per subunit.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi102 – 1021Zinc 2; in inhibited formBy similarity
Metal bindingi134 – 1341Calcium 1By similarity
Metal bindingi168 – 1681Calcium 2By similarity
Metal bindingi178 – 1781Zinc 1By similarity
Metal bindingi180 – 1801Zinc 1By similarity
Metal bindingi185 – 1851Calcium 3By similarity
Metal bindingi186 – 1861Calcium 3; via carbonyl oxygenBy similarity
Metal bindingi193 – 1931Zinc 1By similarity
Metal bindingi200 – 2001Calcium 2; via carbonyl oxygenBy similarity
Metal bindingi202 – 2021Calcium 2; via carbonyl oxygenBy similarity
Metal bindingi204 – 2041Calcium 2By similarity
Metal bindingi206 – 2061Zinc 1By similarity
Metal bindingi208 – 2081Calcium 3By similarity
Metal bindingi209 – 2091Calcium 1By similarity
Metal bindingi211 – 2111Calcium 3By similarity
Metal bindingi403 – 4031Zinc 2; catalyticBy similarity
Active sitei404 – 4041PROSITE-ProRule annotation
Metal bindingi407 – 4071Zinc 2; catalyticBy similarity
Metal bindingi413 – 4131Zinc 2; catalyticBy similarity
Metal bindingi478 – 4781Calcium 4; via carbonyl oxygenBy similarity
Metal bindingi523 – 5231Calcium 4; via carbonyl oxygenBy similarity
Metal bindingi571 – 5711Calcium 4; via carbonyl oxygenBy similarity
Metal bindingi620 – 6201Calcium 4; via carbonyl oxygenBy similarity

GO - Molecular functioni

GO - Biological processi

  • angiogenesis Source: UniProtKB-KW
  • blood vessel maturation Source: MGI
  • bone trabecula formation Source: MGI
  • cellular response to amino acid stimulus Source: MGI
  • collagen catabolic process Source: MGI
  • embryo implantation Source: MGI
  • endodermal cell differentiation Source: Ensembl
  • face morphogenesis Source: MGI
  • intramembranous ossification Source: MGI
  • positive regulation of innate immune response Source: MGI
  • proteolysis Source: MGI
  • response to hypoxia Source: MGI
  • skeletal system morphogenesis Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Metalloprotease, Protease

Keywords - Biological processi

Angiogenesis, Collagen degradation

Keywords - Ligandi

Calcium, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiREACT_275864. Degradation of the extracellular matrix.
REACT_313067. Collagen degradation.
REACT_314615. EPH-ephrin mediated repulsion of cells.
REACT_331346. Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
REACT_332323. Activation of Matrix Metalloproteinases.

Protein family/group databases

MEROPSiM10.003.

Names & Taxonomyi

Protein namesi
Recommended 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:
Gene namesi
Name:Mmp2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 8

Organism-specific databases

MGIiMGI:97009. Mmp2.

Subcellular locationi

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).By similarity

GO - Cellular componenti

  • cytoplasm Source: MGI
  • extracellular space Source: MGI
  • mitochondrion Source: MGI
  • nucleus Source: UniProtKB-SubCell
  • plasma membrane Source: MGI
  • proteinaceous extracellular matrix Source: UniProtKB-SubCell
  • sarcomere Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Extracellular matrix, Membrane, Mitochondrion, Nucleus, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2929Sequence AnalysisAdd
BLAST
Propeptidei30 – 10980Activation peptidePRO_0000028716Add
BLAST
Chaini110 – 66255372 kDa type IV collagenasePRO_0000028717Add
BLAST
Chaini445 – 662218PEXBy similarityPRO_0000391627Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi233 ↔ 259PROSITE-ProRule annotation
Disulfide bondi247 ↔ 274PROSITE-ProRule annotation
Disulfide bondi291 ↔ 317PROSITE-ProRule annotation
Disulfide bondi305 ↔ 332PROSITE-ProRule annotation
Disulfide bondi349 ↔ 375PROSITE-ProRule annotation
Disulfide bondi363 ↔ 390PROSITE-ProRule annotation
Disulfide bondi471 ↔ 662PROSITE-ProRule annotation
Glycosylationi575 – 5751N-linked (GlcNAc...)Sequence Analysis
Glycosylationi644 – 6441N-linked (GlcNAc...)Sequence Analysis

Post-translational modificationi

Phosphorylation on multiple sites modulates enzymatic activity. Phosphorylated by PKC in vitro (By similarity).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).By similarity

Keywords - PTMi

Autocatalytic cleavage, Disulfide bond, Glycoprotein, Phosphoprotein, Zymogen

Proteomic databases

MaxQBiP33434.
PaxDbiP33434.
PRIDEiP33434.

PTM databases

PhosphoSiteiP33434.

Expressioni

Developmental stagei

Present in unfertilized eggs and at the zygote and cleavage stages. Levels increase at the blastocyst stage and with endoderm differentiation.1 Publication

Gene expression databases

BgeeiP33434.
CleanExiMM_MMP2.
ExpressionAtlasiP33434. baseline and differential.
GenevisibleiP33434. MM.

Interactioni

Subunit structurei

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).By similarity

Protein-protein interaction databases

IntActiP33434. 1 interaction.
STRINGi10090.ENSMUSP00000034187.

Structurei

3D structure databases

ProteinModelPortaliP33434.
SMRiP33434. Positions 30-662.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini228 – 27649Fibronectin type-II 1PROSITE-ProRule annotationAdd
BLAST
Domaini286 – 33449Fibronectin type-II 2PROSITE-ProRule annotationAdd
BLAST
Domaini344 – 39249Fibronectin type-II 3PROSITE-ProRule annotationAdd
BLAST
Repeati474 – 51845Hemopexin 1Add
BLAST
Repeati519 – 56547Hemopexin 2Add
BLAST
Repeati567 – 61549Hemopexin 3Add
BLAST
Repeati616 – 66247Hemopexin 4Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni110 – 221112Collagenase-like 1Add
BLAST
Regioni222 – 396175Collagen-bindingAdd
BLAST
Regioni397 – 46771Collagenase-like 2Add
BLAST
Regioni414 – 662249Required for inhibitor TIMP2 bindingBy similarityAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi100 – 1078Cysteine switchBy similarity

Domaini

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.

Sequence similaritiesi

Belongs to the peptidase M10A family.Curated
Contains 3 fibronectin type-II domains.PROSITE-ProRule annotation
Contains 4 hemopexin repeats.Curated

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

eggNOGiNOG303159.
GeneTreeiENSGT00760000119132.
HOGENOMiHOG000217926.
HOVERGENiHBG052484.
InParanoidiP33434.
KOiK01398.
OMAiKHESCTS.
OrthoDBiEOG70KGNX.
PhylomeDBiP33434.
TreeFamiTF315428.

Family and domain databases

Gene3Di1.10.101.10. 1 hit.
2.10.10.10. 3 hits.
2.110.10.10. 1 hit.
3.40.390.10. 2 hits.
InterProiIPR028708. 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]
PANTHERiPTHR10201:SF29. PTHR10201:SF29. 1 hit.
PfamiPF00040. fn2. 3 hits.
PF00045. Hemopexin. 4 hits.
PF00413. Peptidase_M10. 1 hit.
PF01471. PG_binding_1. 1 hit.
[Graphical view]
PRINTSiPR00138. MATRIXIN.
SMARTiSM00059. FN2. 3 hits.
SM00120. HX. 4 hits.
SM00235. ZnMc. 1 hit.
[Graphical view]
SUPFAMiSSF47090. SSF47090. 1 hit.
SSF50923. SSF50923. 1 hit.
SSF57440. SSF57440. 3 hits.
PROSITEiPS00546. 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]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P33434-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MEARVAWGAL AGPLRVLCVL CCLLGRAIAA PSPIIKFPGD VAPKTDKELA
60 70 80 90 100
VQYLNTFYGC PKESCNLFVL KDTLKKMQKF FGLPQTGDLD QNTIETMRKP
110 120 130 140 150
RCGNPDVANY NFFPRKPKWD KNQITYRIIG YTPDLDPETV DDAFARALKV
160 170 180 190 200
WSDVTPLRFS RIHDGEADIM INFGRWEHGD GYPFDGKDGL LAHAFAPGTG
210 220 230 240 250
VGGDSHFDDD ELWTLGEGQV VRVKYGNADG EYCKFPFLFN GREYSSCTDT
260 270 280 290 300
GRSDGFLWCS TTYNFEKDGK YGFCPHEALF TMGGNADGQP CKFPFRFQGT
310 320 330 340 350
SYNSCTTEGR TDGYRWCGTT EDYDRDKKYG FCPETAMSTV GGNSEGAPCV
360 370 380 390 400
FPFTFLGNKY ESCTSAGRND GKVWCATTTN YDDDRKWGFC PDQGYSLFLV
410 420 430 440 450
AAHEFGHAMG LEHSQDPGAL MAPIYTYTKN FRLSHDDIKG IQELYGPSPD
460 470 480 490 500
ADTDTGTGPT PTLGPVTPEI CKQDIVFDGI AQIRGEIFFF KDRFIWRTVT
510 520 530 540 550
PRDKPTGPLL VATFWPELPE KIDAVYEAPQ EEKAVFFAGN EYWVYSASTL
560 570 580 590 600
ERGYPKPLTS LGLPPDVQQV DAAFNWSKNK KTYIFAGDKF WRYNEVKKKM
610 620 630 640 650
DPGFPKLIAD SWNAIPDNLD AVVDLQGGGH SYFFKGAYYL KLENQSLKSV
660
KFGSIKSDWL GC
Length:662
Mass (Da):74,102
Last modified:February 1, 1994 - v1
Checksum:iC630A7DBDB272F02
GO
Isoform 2 (identifier: P33434-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-76: Missing.

Note: Induced by oxidative stress.
Show »
Length:586
Mass (Da):65,883
Checksum:iB8EE47CF5723C3D6
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 7676Missing in isoform 2. CuratedVSP_044632Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M84324 mRNA. Translation: AAA39338.1.
BC070430 mRNA. Translation: AAH70430.1.
CCDSiCCDS22523.1. [P33434-1]
PIRiA42496.
RefSeqiNP_032636.1. NM_008610.2. [P33434-1]
UniGeneiMm.29564.

Genome annotation databases

EnsembliENSMUST00000034187; ENSMUSP00000034187; ENSMUSG00000031740. [P33434-1]
GeneIDi17390.
KEGGimmu:17390.
UCSCiuc009mue.1. mouse. [P33434-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M84324 mRNA. Translation: AAA39338.1.
BC070430 mRNA. Translation: AAH70430.1.
CCDSiCCDS22523.1. [P33434-1]
PIRiA42496.
RefSeqiNP_032636.1. NM_008610.2. [P33434-1]
UniGeneiMm.29564.

3D structure databases

ProteinModelPortaliP33434.
SMRiP33434. Positions 30-662.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP33434. 1 interaction.
STRINGi10090.ENSMUSP00000034187.

Chemistry

BindingDBiP33434.
ChEMBLiCHEMBL3095.

Protein family/group databases

MEROPSiM10.003.

PTM databases

PhosphoSiteiP33434.

Proteomic databases

MaxQBiP33434.
PaxDbiP33434.
PRIDEiP33434.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000034187; ENSMUSP00000034187; ENSMUSG00000031740. [P33434-1]
GeneIDi17390.
KEGGimmu:17390.
UCSCiuc009mue.1. mouse. [P33434-1]

Organism-specific databases

CTDi4313.
MGIiMGI:97009. Mmp2.

Phylogenomic databases

eggNOGiNOG303159.
GeneTreeiENSGT00760000119132.
HOGENOMiHOG000217926.
HOVERGENiHBG052484.
InParanoidiP33434.
KOiK01398.
OMAiKHESCTS.
OrthoDBiEOG70KGNX.
PhylomeDBiP33434.
TreeFamiTF315428.

Enzyme and pathway databases

ReactomeiREACT_275864. Degradation of the extracellular matrix.
REACT_313067. Collagen degradation.
REACT_314615. EPH-ephrin mediated repulsion of cells.
REACT_331346. Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
REACT_332323. Activation of Matrix Metalloproteinases.

Miscellaneous databases

ChiTaRSiMmp2. mouse.
NextBioi292012.
PROiP33434.
SOURCEiSearch...

Gene expression databases

BgeeiP33434.
CleanExiMM_MMP2.
ExpressionAtlasiP33434. baseline and differential.
GenevisibleiP33434. MM.

Family and domain databases

Gene3Di1.10.101.10. 1 hit.
2.10.10.10. 3 hits.
2.110.10.10. 1 hit.
3.40.390.10. 2 hits.
InterProiIPR028708. 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]
PANTHERiPTHR10201:SF29. PTHR10201:SF29. 1 hit.
PfamiPF00040. fn2. 3 hits.
PF00045. Hemopexin. 4 hits.
PF00413. Peptidase_M10. 1 hit.
PF01471. PG_binding_1. 1 hit.
[Graphical view]
PRINTSiPR00138. MATRIXIN.
SMARTiSM00059. FN2. 3 hits.
SM00120. HX. 4 hits.
SM00235. ZnMc. 1 hit.
[Graphical view]
SUPFAMiSSF47090. SSF47090. 1 hit.
SSF50923. SSF50923. 1 hit.
SSF57440. SSF57440. 3 hits.
PROSITEiPS00546. 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]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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.

Entry informationi

Entry nameiMMP2_MOUSE
AccessioniPrimary (citable) accession number: P33434
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: February 1, 1994
Last modified: July 22, 2015
This is version 150 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.