Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
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)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi103 – 1031Zinc 2; in inhibited formBy similarity
Metal bindingi135 – 1351Calcium 1By similarity
Metal bindingi169 – 1691Calcium 2By similarity
Metal bindingi179 – 1791Zinc 1By similarity
Metal bindingi181 – 1811Zinc 1By similarity
Metal bindingi186 – 1861Calcium 3By similarity
Metal bindingi187 – 1871Calcium 3; via carbonyl oxygenBy similarity
Metal bindingi194 – 1941Zinc 1By similarity
Metal bindingi201 – 2011Calcium 2; via carbonyl oxygenBy similarity
Metal bindingi203 – 2031Calcium 2; via carbonyl oxygenBy similarity
Metal bindingi205 – 2051Calcium 2By similarity
Metal bindingi207 – 2071Zinc 1By similarity
Metal bindingi209 – 2091Calcium 3By similarity
Metal bindingi210 – 2101Calcium 1By similarity
Metal bindingi212 – 2121Calcium 3By similarity
Metal bindingi404 – 4041Zinc 2; catalyticBy similarity
Active sitei405 – 4051PROSITE-ProRule annotation
Metal bindingi408 – 4081Zinc 2; catalyticBy similarity
Metal bindingi414 – 4141Zinc 2; catalyticBy similarity
Metal bindingi477 – 4771Calcium 4; via carbonyl oxygenBy similarity
Metal bindingi522 – 5221Calcium 4; via carbonyl oxygenBy similarity
Metal bindingi570 – 5701Calcium 4; via carbonyl oxygenBy similarity
Metal bindingi619 – 6191Calcium 4; via carbonyl oxygenBy similarity

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)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 3030By similarityAdd
BLAST
Propeptidei31 – 11080Activation peptideBy similarityPRO_0000244644Add
BLAST
Chaini111 – 66155172 kDa type IV collagenasePRO_0000244645Add
BLAST
Chaini446 – 661216PEXBy similarityPRO_0000391625Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
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
Glycosylationi574 – 5741N-linked (GlcNAc...)Sequence analysis
Glycosylationi643 – 6431N-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). 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.
SMRiQ9GLE5. Positions 31-661.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini229 – 27749Fibronectin type-II 1PROSITE-ProRule annotationAdd
BLAST
Domaini287 – 33549Fibronectin type-II 2PROSITE-ProRule annotationAdd
BLAST
Domaini345 – 39349Fibronectin type-II 3PROSITE-ProRule annotationAdd
BLAST
Repeati469 – 51749Hemopexin 1Add
BLAST
Repeati518 – 56447Hemopexin 2Add
BLAST
Repeati566 – 61449Hemopexin 3Add
BLAST
Repeati615 – 66147Hemopexin 4Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni111 – 222112Collagenase-like 1Add
BLAST
Regioni223 – 397175Collagen-bindingAdd
BLAST
Regioni398 – 46669Collagenase-like 2Add
BLAST
Regioni415 – 661247Required for inhibitor TIMP2 bindingBy similarityAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi101 – 1088Cysteine 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

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

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. 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.
SMRiQ9GLE5. Positions 31-661.
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

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. 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...

Publicationsi

  1. "Molecular cloning and biological characterization of bovine matrix metalloprotease 2 (bMMP-2)."
    Yan L., Zhang B., Tsang P., Fang J., Yu Y., Ingber D.E., Moses M.A.
    Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].

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: June 8, 2016
This is version 88 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.