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P33434

- MMP2_MOUSE

UniProt

P33434 - MMP2_MOUSE

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Protein
72 kDa type IV collagenase
Gene
Mmp2
Organism
Mus musculus (Mouse)
Status
Reviewed - 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.1 Publication
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.1 Publication
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

Binds 4 calcium ions per subunit By similarity.
Binds 2 zinc ions per subunit By similarity.

Sites

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

GO - Molecular functioni

  1. metalloendopeptidase activity Source: MGI
  2. zinc ion binding Source: InterPro

GO - Biological processi

  1. angiogenesis Source: UniProtKB-KW
  2. blood vessel maturation Source: MGI
  3. bone trabecula formation Source: MGI
  4. cellular response to amino acid stimulus Source: MGI
  5. collagen catabolic process Source: MGI
  6. embryo implantation Source: MGI
  7. face morphogenesis Source: MGI
  8. intramembranous ossification Source: MGI
  9. positive regulation of innate immune response Source: MGI
  10. response to hypoxia Source: MGI
  11. 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_199000. Activation of Matrix Metalloproteinases.
REACT_199052. Degradation of the extracellular matrix.
REACT_199055. Collagen degradation.

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: 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.1 Publication
Isoform 2 : Cytoplasm. Mitochondrion 1 Publication

GO - Cellular componenti

  1. cytoplasm Source: MGI
  2. extracellular space Source: MGI
  3. mitochondrion Source: MGI
  4. nucleus Source: UniProtKB-SubCell
  5. plasma membrane Source: MGI
  6. proteinaceous extracellular matrix Source: UniProtKB-SubCell
  7. 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 – 2929 Reviewed prediction
Add
BLAST
Propeptidei30 – 10980Activation peptide
PRO_0000028716Add
BLAST
Chaini110 – 66255372 kDa type IV collagenase
PRO_0000028717Add
BLAST
Chaini445 – 662218PEX By similarity
PRO_0000391627Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi233 ↔ 259 By similarity
Disulfide bondi247 ↔ 274 By similarity
Disulfide bondi291 ↔ 317 By similarity
Disulfide bondi305 ↔ 332 By similarity
Disulfide bondi349 ↔ 375 By similarity
Disulfide bondi363 ↔ 390 By similarity
Disulfide bondi471 ↔ 662 By similarity
Glycosylationi575 – 5751N-linked (GlcNAc...) Reviewed prediction
Glycosylationi644 – 6441N-linked (GlcNAc...) Reviewed prediction

Post-translational modificationi

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.

Keywords - PTMi

Autocatalytic cleavage, Disulfide bond, Glycoprotein, Phosphoprotein, Zymogen

Proteomic databases

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

ArrayExpressiP33434.
BgeeiP33434.
CleanExiMM_MMP2.
GenevestigatoriP33434.

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.

Protein-protein interaction databases

IntActiP33434. 1 interaction.

Structurei

3D structure databases

ProteinModelPortaliP33434.
SMRiP33434. Positions 30-662.

Family & Domainsi

Domains and Repeats

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

Region

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

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi100 – 1078Cysteine switch By 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.
Contains 4 hemopexin repeats.

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

eggNOGiNOG303159.
HOGENOMiHOG000217926.
HOVERGENiHBG052484.
InParanoidiP33434.
KOiK01398.
OMAiPCKFPFR.
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. Align

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

MEARVAWGAL AGPLRVLCVL CCLLGRAIAA PSPIIKFPGD VAPKTDKELA    50
VQYLNTFYGC PKESCNLFVL KDTLKKMQKF FGLPQTGDLD QNTIETMRKP 100
RCGNPDVANY NFFPRKPKWD KNQITYRIIG YTPDLDPETV DDAFARALKV 150
WSDVTPLRFS RIHDGEADIM INFGRWEHGD GYPFDGKDGL LAHAFAPGTG 200
VGGDSHFDDD ELWTLGEGQV VRVKYGNADG EYCKFPFLFN GREYSSCTDT 250
GRSDGFLWCS TTYNFEKDGK YGFCPHEALF TMGGNADGQP CKFPFRFQGT 300
SYNSCTTEGR TDGYRWCGTT EDYDRDKKYG FCPETAMSTV GGNSEGAPCV 350
FPFTFLGNKY ESCTSAGRND GKVWCATTTN YDDDRKWGFC PDQGYSLFLV 400
AAHEFGHAMG LEHSQDPGAL MAPIYTYTKN FRLSHDDIKG IQELYGPSPD 450
ADTDTGTGPT PTLGPVTPEI CKQDIVFDGI AQIRGEIFFF KDRFIWRTVT 500
PRDKPTGPLL VATFWPELPE KIDAVYEAPQ EEKAVFFAGN EYWVYSASTL 550
ERGYPKPLTS LGLPPDVQQV DAAFNWSKNK KTYIFAGDKF WRYNEVKKKM 600
DPGFPKLIAD SWNAIPDNLD AVVDLQGGGH SYFFKGAYYL KLENQSLKSV 650
KFGSIKSDWL GC 662
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.
VSP_044632Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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:
EMBL
GenBank
DDBJ
Links Updated
M84324 mRNA. Translation: AAA39338.1 .
BC070430 mRNA. Translation: AAH70430.1 .
CCDSi CCDS22523.1. [P33434-1 ]
PIRi A42496.
RefSeqi NP_032636.1. NM_008610.2. [P33434-1 ]
UniGenei Mm.29564.

3D structure databases

ProteinModelPortali P33434.
SMRi P33434. Positions 30-662.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

IntActi P33434. 1 interaction.

Chemistry

BindingDBi P33434.
ChEMBLi CHEMBL3095.

Protein family/group databases

MEROPSi M10.003.

PTM databases

PhosphoSitei P33434.

Proteomic databases

PaxDbi P33434.
PRIDEi P33434.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000034187 ; ENSMUSP00000034187 ; ENSMUSG00000031740 . [P33434-1 ]
GeneIDi 17390.
KEGGi mmu:17390.
UCSCi uc009mue.1. mouse. [P33434-1 ]

Organism-specific databases

CTDi 4313.
MGIi MGI:97009. Mmp2.

Phylogenomic databases

eggNOGi NOG303159.
HOGENOMi HOG000217926.
HOVERGENi HBG052484.
InParanoidi P33434.
KOi K01398.
OMAi PCKFPFR.
OrthoDBi EOG70KGNX.
PhylomeDBi P33434.
TreeFami TF315428.

Enzyme and pathway databases

Reactomei REACT_199000. Activation of Matrix Metalloproteinases.
REACT_199052. Degradation of the extracellular matrix.
REACT_199055. Collagen degradation.

Miscellaneous databases

ChiTaRSi MMP2. mouse.
NextBioi 292012.
PROi P33434.
SOURCEi Search...

Gene expression databases

ArrayExpressi P33434.
Bgeei P33434.
CleanExi MM_MMP2.
Genevestigatori P33434.

Family and domain databases

Gene3Di 1.10.101.10. 1 hit.
2.10.10.10. 3 hits.
2.110.10.10. 1 hit.
3.40.390.10. 2 hits.
InterProi IPR028708. 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 ]
PANTHERi PTHR10201:SF29. PTHR10201:SF29. 1 hit.
Pfami PF00040. fn2. 3 hits.
PF00045. Hemopexin. 4 hits.
PF00413. Peptidase_M10. 1 hit.
PF01471. PG_binding_1. 1 hit.
[Graphical view ]
PRINTSi PR00138. MATRIXIN.
SMARTi SM00059. FN2. 3 hits.
SM00120. HX. 4 hits.
SM00235. ZnMc. 1 hit.
[Graphical view ]
SUPFAMi SSF47090. SSF47090. 1 hit.
SSF50923. SSF50923. 1 hit.
SSF57440. SSF57440. 3 hits.
PROSITEi PS00546. 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 ]
ProtoNeti Search...

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: September 3, 2014
This is version 140 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

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