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
Oryctolagus cuniculus (Rabbit)
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 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

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
OrganismiOryctolagus cuniculus (Rabbit)
Taxonomic identifieri9986 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresLagomorphaLeporidaeOryctolagus
Proteomesi
  • UP000001811 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 – 2929Sequence analysisAdd
BLAST
Propeptidei30 – 10980Activation peptidePRO_0000028718Add
BLAST
Chaini110 – 66255372 kDa type IV collagenasePRO_0000028719Add
BLAST
Chaini445 – 662218PEXBy similarityPRO_0000391628Add
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

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

STRINGi9986.ENSOCUP00000005803.

Structurei

3D structure databases

ProteinModelPortaliP50757.
SMRiP50757. Positions 31-662.
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

eggNOGiKOG1565. Eukaryota.
ENOG410XQ5D. LUCA.
HOGENOMiHOG000217926.
HOVERGENiHBG052484.
InParanoidiP50757.
KOiK01398.

Family and domain databases

Gene3Di2.10.10.10. 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.

P50757-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEALGARGAL AGFLRALCVL GCLLGRATAP PSPVIKFPGD VAPKTDKELA
60 70 80 90 100
VQYLNTFYGC PKDSCNLFVL KDTLKKMQKF FGLPQTGELD QSTIETMRKP
110 120 130 140 150
RCGNPDVANY NFFPRKPKWD KNQITYRIIG YTPDLDPETV DDAFARAFQV
160 170 180 190 200
WSNVTPLRFS RIHDGEADIM INFGRWEHGD GYPFDGKDGL LAHAFAPGTG
210 220 230 240 250
VGGDSHFDDD ELWTLGEGQV VRVKYGNADG EYCKFPFLFN GKEYTSCTDT
260 270 280 290 300
GRSDGFLWCS TTYNFEKDGK YGFCPHEALF TMGGNADGQP CKFPFRFQGT
310 320 330 340 350
SYSSCTTEGR TDGYRWCGTT EDYDRDKKYG FCPETAMSTI GGNSEGAPCV
360 370 380 390 400
FPFTFLGNKY ESCTSAGRSD GKMWCATSTN YDDDRKWGFC PDQGYSLFLV
410 420 430 440 450
AAHEFGHAMG LEHSQDPGAL MAPIYTYTKN FRLSQDDIKG IQELYGASPD
460 470 480 490 500
AGTDAGTGPT PTLGPVTPEI CTQDIVFDGI AQIRGEIFFF KDRFIWRTVT
510 520 530 540 550
PGDKPMGPLL VATFWPELPE KIDAVYEAPQ EEKAVFFAGN EYWVYSASTL
560 570 580 590 600
ERGYPKPLTS LGLPPDVQRV DAAFNWSKNK KTYIFAGDKF WRYNEVKKKM
610 620 630 640 650
DPGFPRLIAD AWNAIPDHLD AVVDLQGSGH SYFFKGTYYL KLENQSLKSV
660
KVGSIKTDWL GC
Length:662
Mass (Da):73,803
Last modified:October 1, 1996 - v1
Checksum:i1CC246B270E440C8
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D63579 mRNA. Translation: BAA09796.1.
PIRiS70365.
RefSeqiNP_001075678.1. NM_001082209.1.
UniGeneiOcu.6274.

Genome annotation databases

GeneIDi100009000.
KEGGiocu:100009000.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D63579 mRNA. Translation: BAA09796.1.
PIRiS70365.
RefSeqiNP_001075678.1. NM_001082209.1.
UniGeneiOcu.6274.

3D structure databases

ProteinModelPortaliP50757.
SMRiP50757. Positions 31-662.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9986.ENSOCUP00000005803.

Protein family/group databases

MEROPSiM10.003.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi100009000.
KEGGiocu:100009000.

Organism-specific databases

CTDi4313.

Phylogenomic databases

eggNOGiKOG1565. Eukaryota.
ENOG410XQ5D. LUCA.
HOGENOMiHOG000217926.
HOVERGENiHBG052484.
InParanoidiP50757.
KOiK01398.

Family and domain databases

Gene3Di2.10.10.10. 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 of rabbit matrix metalloproteinase-2 and its broad expression at several tissues."
    Matsumoto S., Katoh M., Watanabe T., Masuho Y.
    Biochim. Biophys. Acta 1307:137-139(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: Japanese white.
    Tissue: Synovial cell.

Entry informationi

Entry nameiMMP2_RABIT
AccessioniPrimary (citable) accession number: P50757
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: November 11, 2015
This is version 123 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.