Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.

P33436

- MMP2_RAT

UniProt

P33436 - MMP2_RAT

(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

Protein

72 kDa type IV collagenase

Gene

Mmp2

Organism
Rattus norvegicus (Rat)
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).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

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 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

  1. fibronectin binding Source: RGD
  2. metalloendopeptidase activity Source: InterPro
  3. metallopeptidase activity Source: RGD
  4. peptidase activity Source: RGD
  5. zinc ion binding Source: InterPro

GO - Biological processi

  1. aging Source: RGD
  2. angiogenesis Source: RGD
  3. cell migration Source: RGD
  4. cellular response to cytokine stimulus Source: RGD
  5. cellular response to estradiol stimulus Source: RGD
  6. cellular response to fluid shear stress Source: RGD
  7. cellular response to interleukin-1 Source: RGD
  8. collagen catabolic process Source: RGD
  9. female pregnancy Source: RGD
  10. luteinization Source: RGD
  11. negative regulation of cell adhesion Source: RGD
  12. negative regulation of vasoconstriction Source: RGD
  13. ovarian follicle development Source: RGD
  14. ovulation from ovarian follicle Source: RGD
  15. parturition Source: RGD
  16. peripheral nervous system axon regeneration Source: RGD
  17. positive regulation of apoptotic process Source: RGD
  18. positive regulation of cell migration Source: RGD
  19. prostate gland epithelium morphogenesis Source: RGD
  20. proteolysis Source: RGD
  21. response to activity Source: RGD
  22. response to cytokine Source: RGD
  23. response to drug Source: RGD
  24. response to electrical stimulus Source: RGD
  25. response to estrogen Source: RGD
  26. response to hydrogen peroxide Source: RGD
  27. response to hyperoxia Source: RGD
  28. response to hypoxia Source: RGD
  29. response to mechanical stimulus Source: RGD
  30. response to nicotine Source: RGD
  31. response to oxidative stress Source: RGD
  32. response to radiation Source: RGD
  33. response to retinoic acid Source: RGD
  34. 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
ProteomesiUP000002494: 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

  1. cytoplasm Source: RGD
  2. extracellular space Source: RGD
  3. membrane Source: UniProtKB-KW
  4. nucleus Source: UniProtKB-KW
  5. proteinaceous extracellular matrix Source: UniProtKB-KW
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_0000028720Add
BLAST
Chaini110 – 66255372 kDa type IV collagenasePRO_0000028721Add
BLAST
Chaini445 – 662218PEXBy similarityPRO_0000391629Add
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 integrin integrinv/beta3 (By similarity).By similarity

Keywords - PTMi

Autocatalytic cleavage, Disulfide bond, Glycoprotein, Phosphoprotein, Zymogen

Proteomic databases

PaxDbiP33436.
PRIDEiP33436.

Expressioni

Gene expression databases

GenevestigatoriP33436.

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

Structurei

3D structure databases

ProteinModelPortaliP33436.
SMRiP33436. Positions 30-662.
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

eggNOGiNOG303159.
HOVERGENiHBG052484.
InParanoidiP33436.
KOiK01398.
PhylomeDBiP33436.

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]

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti42 – 421S → A in CAA50583. (PubMed:7916617)Curated
Sequence conflicti286 – 2861G → A in CAA50583. (PubMed:7916617)Curated
Sequence conflicti369 – 3691S → N in CAA50583. (PubMed:7916617)Curated
Sequence conflicti435 – 4351N → H in CAA50583. (PubMed:7916617)Curated
Sequence conflicti586 – 5861S → A in CAA50583. (PubMed:7916617)Curated

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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:
EMBL
GenBank
DDBJ
Links Updated
X71466 mRNA. Translation: CAA50583.1 .
U65656 mRNA. Translation: AAB41692.1 .
BC074013 mRNA. Translation: AAH74013.1 .
PIRi S34780.
RefSeqi NP_112316.2. NM_031054.2.
UniGenei Rn.6422.

3D structure databases

ProteinModelPortali P33436.
SMRi P33436. Positions 30-662.
ModBasei Search...
MobiDBi Search...

Chemistry

BindingDBi P33436.
ChEMBLi CHEMBL1075175.

Protein family/group databases

MEROPSi M10.003.

Proteomic databases

PaxDbi P33436.
PRIDEi P33436.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 81686.
KEGGi rno:81686.

Organism-specific databases

CTDi 4313.
RGDi 621316. Mmp2.

Phylogenomic databases

eggNOGi NOG303159.
HOVERGENi HBG052484.
InParanoidi P33436.
KOi K01398.
PhylomeDBi P33436.

Miscellaneous databases

NextBioi 615320.
PROi P33436.

Gene expression databases

Genevestigatori P33436.

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. "Homology cloning of rat 72 kDa type IV collagenase: cytokine and second-messenger inducibility in glomerular mesangial cells."
    Marti H.P., McNeil L., Davies M., Martin J., Lovett D.H.
    Biochem. J. 291:441-446(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "The cloning of the cDNA encoding rat gelatinase A from a rat skin wound cDNA library."
    Okada A., Basset P.
    Submitted (JUL-1996) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: Wistar.
    Tissue: Skin.
  3. "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].
    Tissue: Lung.

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: October 29, 2014
This is version 125 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

External Data

Dasty 3