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Protein

72 kDa type IV collagenase

Gene

Mmp2

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein 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/beta3 on the surface of blood vessels (By similarity).By similarity

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)DescriptionActionsGraphical viewLength
Metal bindingi102Zinc 2; in inhibited formBy similarity1
Metal bindingi134Calcium 1By similarity1
Metal bindingi168Calcium 2By similarity1
Metal bindingi178Zinc 1By similarity1
Metal bindingi180Zinc 1By similarity1
Metal bindingi185Calcium 3By similarity1
Metal bindingi186Calcium 3; via carbonyl oxygenBy similarity1
Metal bindingi193Zinc 1By similarity1
Metal bindingi200Calcium 2; via carbonyl oxygenBy similarity1
Metal bindingi202Calcium 2; via carbonyl oxygenBy similarity1
Metal bindingi204Calcium 2By similarity1
Metal bindingi206Zinc 1By similarity1
Metal bindingi208Calcium 3By similarity1
Metal bindingi209Calcium 1By similarity1
Metal bindingi211Calcium 3By similarity1
Metal bindingi403Zinc 2; catalyticBy similarity1
Active sitei404PROSITE-ProRule annotation1
Metal bindingi407Zinc 2; catalyticBy similarity1
Metal bindingi413Zinc 2; catalyticBy similarity1
Metal bindingi478Calcium 4; via carbonyl oxygenBy similarity1
Metal bindingi523Calcium 4; via carbonyl oxygenBy similarity1
Metal bindingi571Calcium 4; via carbonyl oxygenBy similarity1
Metal bindingi620Calcium 4; via carbonyl oxygenBy similarity1

GO - Molecular functioni

  • fibronectin binding Source: RGD
  • metalloendopeptidase activity Source: InterPro
  • metallopeptidase activity Source: RGD
  • peptidase activity Source: RGD
  • zinc ion binding Source: InterPro

GO - Biological processi

  • aging Source: RGD
  • angiogenesis Source: RGD
  • cell migration Source: RGD
  • cellular response to cytokine stimulus Source: RGD
  • cellular response to estradiol stimulus Source: RGD
  • cellular response to fluid shear stress Source: RGD
  • cellular response to interleukin-1 Source: RGD
  • collagen catabolic process Source: RGD
  • female pregnancy Source: RGD
  • heart development Source: RGD
  • luteinization Source: RGD
  • negative regulation of cell adhesion Source: RGD
  • negative regulation of vasoconstriction Source: RGD
  • ovarian follicle development Source: RGD
  • ovulation from ovarian follicle Source: RGD
  • parturition Source: RGD
  • peripheral nervous system axon regeneration Source: RGD
  • positive regulation of apoptotic process Source: RGD
  • positive regulation of cell migration Source: RGD
  • prostate gland epithelium morphogenesis Source: RGD
  • proteolysis Source: RGD
  • response to activity Source: RGD
  • response to cytokine Source: RGD
  • response to drug Source: RGD
  • response to electrical stimulus Source: RGD
  • response to estrogen Source: RGD
  • response to hydrogen peroxide Source: RGD
  • response to hyperoxia Source: RGD
  • response to hypoxia Source: RGD
  • response to mechanical stimulus Source: RGD
  • response to nicotine Source: RGD
  • response to oxidative stress Source: RGD
  • response to radiation Source: RGD
  • response to retinoic acid Source: RGD
  • tissue remodeling Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Metalloprotease, Protease

Keywords - Biological processi

Angiogenesis, Collagen degradation

Keywords - Ligandi

Calcium, Metal-binding, Zinc

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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi621316. Mmp2.

Subcellular locationi

  • 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: RGD
  • extracellular space Source: RGD
  • membrane Source: UniProtKB-SubCell
  • nucleus Source: UniProtKB-SubCell
  • proteinaceous extracellular matrix Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Extracellular matrix, Membrane, Nucleus, Secreted

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL1075175.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 291 PublicationAdd BLAST29
PropeptideiPRO_000002872030 – 109Activation peptideAdd BLAST80
ChainiPRO_0000028721110 – 66272 kDa type IV collagenaseAdd BLAST553
ChainiPRO_0000391629445 – 662PEXBy similarityAdd BLAST218

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
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
Glycosylationi575N-linked (GlcNAc...)Sequence analysis1
Glycosylationi644N-linked (GlcNAc...)Sequence analysis1

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 integrin integrinv/beta3 (By similarity).By similarity

Keywords - PTMi

Autocatalytic cleavage, Disulfide bond, Glycoprotein, Phosphoprotein, Zymogen

Proteomic databases

PaxDbiP33436.
PRIDEiP33436.

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

GO - Molecular functioni

  • fibronectin binding Source: RGD

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000022679.

Chemistry databases

BindingDBiP33436.

Structurei

3D structure databases

ProteinModelPortaliP33436.
SMRiP33436.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini228 – 276Fibronectin type-II 1PROSITE-ProRule annotationAdd BLAST49
Domaini286 – 334Fibronectin type-II 2PROSITE-ProRule annotationAdd BLAST49
Domaini344 – 392Fibronectin type-II 3PROSITE-ProRule annotationAdd BLAST49
Repeati474 – 518Hemopexin 1Add BLAST45
Repeati519 – 565Hemopexin 2Add BLAST47
Repeati567 – 615Hemopexin 3Add BLAST49
Repeati616 – 662Hemopexin 4Add BLAST47

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni110 – 221Collagenase-like 1Add BLAST112
Regioni222 – 396Collagen-bindingAdd BLAST175
Regioni397 – 467Collagenase-like 2Add BLAST71
Regioni414 – 662Required for inhibitor TIMP2 bindingBy similarityAdd BLAST249

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi100 – 107Cysteine switchBy similarity8

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

eggNOGiKOG1565. Eukaryota.
ENOG410XQ5D. LUCA.
HOVERGENiHBG052484.
InParanoidiP33436.
KOiK01398.
PhylomeDBiP33436.

Family and domain databases

CDDicd00062. FN2. 3 hits.
cd00094. HX. 1 hit.
cd04278. ZnMc_MMP. 1 hit.
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.
IPR033739. M10A_MMP.
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. 2 hits.
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]

Sequencei

Sequence statusi: Complete.

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

P33436-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEARLVWGVL VGPLRVLCVL CCLLGHAIAA PSPIIKFPGD VSPKTDKELA
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 TMGGNGDGQP CKFPFRFQGT
310 320 330 340 350
SYNSCTTEGR TDGYRWCGTT EDYDRDKKYG FCPETAMSTV GGNSEGAPCV
360 370 380 390 400
FPFTFLGNKY ESCTSAGRSD GKVWCATTTN YDDDRKWGFC PDQGYSLFLV
410 420 430 440 450
AAHEFGHAMG LEHSQDPGAL MAPIYTYTKN FRLSNDDIKG 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 KTYIFSGDKF WRYNEVKKKM
610 620 630 640 650
DPGFPKLIAD SWNAIPDNLD AVVDLQGGGH SYFFKGAYYL KLENQSLKSV
660
KFGSIKSDWL GC
Length:662
Mass (Da):74,149
Last modified:May 1, 2007 - v2
Checksum:iC56BD787473FC03E
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti42S → A in CAA50583 (PubMed:7916617).Curated1
Sequence conflicti286G → A in CAA50583 (PubMed:7916617).Curated1
Sequence conflicti369S → N in CAA50583 (PubMed:7916617).Curated1
Sequence conflicti435N → H in CAA50583 (PubMed:7916617).Curated1
Sequence conflicti586S → A in CAA50583 (PubMed:7916617).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X71466 mRNA. Translation: CAA50583.1.
U65656 mRNA. Translation: AAB41692.1.
BC074013 mRNA. Translation: AAH74013.1.
PIRiS34780.
RefSeqiNP_112316.2. NM_031054.2.
UniGeneiRn.6422.

Genome annotation databases

GeneIDi81686.
KEGGirno:81686.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X71466 mRNA. Translation: CAA50583.1.
U65656 mRNA. Translation: AAB41692.1.
BC074013 mRNA. Translation: AAH74013.1.
PIRiS34780.
RefSeqiNP_112316.2. NM_031054.2.
UniGeneiRn.6422.

3D structure databases

ProteinModelPortaliP33436.
SMRiP33436.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000022679.

Chemistry databases

BindingDBiP33436.
ChEMBLiCHEMBL1075175.

Protein family/group databases

MEROPSiM10.003.

Proteomic databases

PaxDbiP33436.
PRIDEiP33436.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi81686.
KEGGirno:81686.

Organism-specific databases

CTDi4313.
RGDi621316. Mmp2.

Phylogenomic databases

eggNOGiKOG1565. Eukaryota.
ENOG410XQ5D. LUCA.
HOVERGENiHBG052484.
InParanoidiP33436.
KOiK01398.
PhylomeDBiP33436.

Miscellaneous databases

PROiP33436.

Family and domain databases

CDDicd00062. FN2. 3 hits.
cd00094. HX. 1 hit.
cd04278. ZnMc_MMP. 1 hit.
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.
IPR033739. M10A_MMP.
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. 2 hits.
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...

Entry informationi

Entry nameiMMP2_RAT
AccessioniPrimary (citable) accession number: P33436
Secondary accession number(s): P97581, Q6GMM9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: May 1, 2007
Last modified: November 30, 2016
This is version 137 of the entry and version 2 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. Peptidase families
    Classification of peptidase families and list of entries
  2. SIMILARITY comments
    Index of protein domains and families

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 one 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.