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Protein

72 kDa type IV collagenase

Gene

MMP2

Organism
Bos taurus (Bovine)
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

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 bindingi103Zinc 2; in inhibited formBy similarity1
Metal bindingi135Calcium 1By similarity1
Metal bindingi169Calcium 2By similarity1
Metal bindingi179Zinc 1By similarity1
Metal bindingi181Zinc 1By similarity1
Metal bindingi186Calcium 3By similarity1
Metal bindingi187Calcium 3; via carbonyl oxygenBy similarity1
Metal bindingi194Zinc 1By similarity1
Metal bindingi201Calcium 2; via carbonyl oxygenBy similarity1
Metal bindingi203Calcium 2; via carbonyl oxygenBy similarity1
Metal bindingi205Calcium 2By similarity1
Metal bindingi207Zinc 1By similarity1
Metal bindingi209Calcium 3By similarity1
Metal bindingi210Calcium 1By similarity1
Metal bindingi212Calcium 3By similarity1
Metal bindingi404Zinc 2; catalyticBy similarity1
Active sitei405PROSITE-ProRule annotation1
Metal bindingi408Zinc 2; catalyticBy similarity1
Metal bindingi414Zinc 2; catalyticBy similarity1
Metal bindingi477Calcium 4; via carbonyl oxygenBy similarity1
Metal bindingi522Calcium 4; via carbonyl oxygenBy similarity1
Metal bindingi570Calcium 4; via carbonyl oxygenBy similarity1
Metal bindingi619Calcium 4; via carbonyl oxygenBy similarity1

GO - Molecular functioni

GO - Biological processi

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
Matrix metalloproteinase-2
Short name:
MMP-2
Cleaved into the following chain:
Gene namesi
Name:MMP2
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Unplaced

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

Complete GO annotation...

Keywords - Cellular componenti

Extracellular matrix, Membrane, Nucleus, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 30By similarityAdd BLAST30
PropeptideiPRO_000024464431 – 110Activation peptideBy similarityAdd BLAST80
ChainiPRO_0000244645111 – 66172 kDa type IV collagenaseAdd BLAST551
ChainiPRO_0000391625446 – 661PEXBy similarityAdd BLAST216

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi234 ↔ 260PROSITE-ProRule annotation
Disulfide bondi248 ↔ 275PROSITE-ProRule annotation
Disulfide bondi292 ↔ 318PROSITE-ProRule annotation
Disulfide bondi306 ↔ 333PROSITE-ProRule annotation
Disulfide bondi350 ↔ 376PROSITE-ProRule annotation
Disulfide bondi364 ↔ 391PROSITE-ProRule annotation
Disulfide bondi470 ↔ 661PROSITE-ProRule annotation
Glycosylationi574N-linked (GlcNAc...)Sequence analysis1
Glycosylationi643N-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). 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

Disulfide bond, Glycoprotein, Phosphoprotein, Zymogen

Proteomic databases

PaxDbiQ9GLE5.
PRIDEiQ9GLE5.

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

STRINGi9913.ENSBTAP00000025657.

Structurei

3D structure databases

ProteinModelPortaliQ9GLE5.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini229 – 277Fibronectin type-II 1PROSITE-ProRule annotationAdd BLAST49
Domaini287 – 335Fibronectin type-II 2PROSITE-ProRule annotationAdd BLAST49
Domaini345 – 393Fibronectin type-II 3PROSITE-ProRule annotationAdd BLAST49
Repeati469 – 517Hemopexin 1Add BLAST49
Repeati518 – 564Hemopexin 2Add BLAST47
Repeati566 – 614Hemopexin 3Add BLAST49
Repeati615 – 661Hemopexin 4Add BLAST47

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni111 – 222Collagenase-like 1Add BLAST112
Regioni223 – 397Collagen-bindingAdd BLAST175
Regioni398 – 466Collagenase-like 2Add BLAST69
Regioni415 – 661Required for inhibitor TIMP2 bindingBy similarityAdd BLAST247

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi101 – 108Cysteine 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.
HOGENOMiHOG000217926.
HOVERGENiHBG052484.
InParanoidiQ9GLE5.
KOiK01398.

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.

Q9GLE5-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTEARVSRGA LAALLRALCA LGCLLGRAAA APSPIIKFPG DVAPKTDKEL
60 70 80 90 100
AVQYLNTFYG CPKESCNLFV LKDTLKKMQK FFGLPQTGEL DQSTIETMRK
110 120 130 140 150
PRCGNPDVAN YNFFPRKPKW DKNQITYRII GYTPDLDPQT VDDAFARAFQ
160 170 180 190 200
VWSDVTPLRF SRIHDGEADI MINFGRWEHG DGYPFDGKDG LLAHAFAPGP
210 220 230 240 250
GVGGDSHFDD DELRTLGEGQ VVRVKYGNAD GEYCKFPFRF NGKEYTSCTD
260 270 280 290 300
TGRSDGFLWC STTYNFDKDG KYGFCPHEAL FTMGGNADGQ PCKFPFRFQG
310 320 330 340 350
TSYDSCTTEG RTDGYRWCGT TEDYDRDKEY GFCPETAMST VGGNSEGAPC
360 370 380 390 400
VLPFTFLGNK HESCTSAGRS DGKLWCATTS NYDDDRKWGF CPDQGYSLFL
410 420 430 440 450
VAAHEFGHAM GLEHSQDPGA LMAPIYTYTK NFRLSHDDIQ GIQELYGASP
460 470 480 490 500
DIDTGTGPTP TLGPVTPELC KQDIVFDGIS QIRGEIFFFK DRFIWRTVTP
510 520 530 540 550
RDKPTGPLLV ATFWPELPEK IDAVYEDPQE EKAVFFAGNE YWVYSASTLE
560 570 580 590 600
RGYPKPLTSL GLPPGVQKVD AAFNWSKNKK TYIFAGDKFW RYNEVKKKMD
610 620 630 640 650
PGFPKLIADA WNAIPDNLDA VVDLQGGGHS YFFKGAYYLK LENQSLKSVK
660
FGSIKSDWLG C
Length:661
Mass (Da):73,777
Last modified:March 1, 2001 - v1
Checksum:i90545F7645E5F84D
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF290428 mRNA. Translation: AAG28169.1.
RefSeqiNP_777170.1. NM_174745.2.
UniGeneiBt.5313.

Genome annotation databases

GeneIDi282872.
KEGGibta:282872.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF290428 mRNA. Translation: AAG28169.1.
RefSeqiNP_777170.1. NM_174745.2.
UniGeneiBt.5313.

3D structure databases

ProteinModelPortaliQ9GLE5.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000025657.

Protein family/group databases

MEROPSiM10.003.

Proteomic databases

PaxDbiQ9GLE5.
PRIDEiQ9GLE5.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi282872.
KEGGibta:282872.

Organism-specific databases

CTDi4313.

Phylogenomic databases

eggNOGiKOG1565. Eukaryota.
ENOG410XQ5D. LUCA.
HOGENOMiHOG000217926.
HOVERGENiHBG052484.
InParanoidiQ9GLE5.
KOiK01398.

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_BOVIN
AccessioniPrimary (citable) accession number: Q9GLE5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 27, 2006
Last sequence update: March 1, 2001
Last modified: November 30, 2016
This is version 91 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. 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.