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P33436

- MMP2_RAT

UniProt

P33436 - MMP2_RAT

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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.
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.

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 form By similarity
Metal bindingi134 – 1341Calcium 1 By similarity
Metal bindingi168 – 1681Calcium 2 By similarity
Metal bindingi178 – 1781Zinc 1 By similarity
Metal bindingi180 – 1801Zinc 1 By similarity
Metal bindingi185 – 1851Calcium 3 By similarity
Metal bindingi186 – 1861Calcium 3; via carbonyl oxygen By similarity
Metal bindingi193 – 1931Zinc 1 By similarity
Metal bindingi200 – 2001Calcium 2; via carbonyl oxygen By similarity
Metal bindingi202 – 2021Calcium 2; via carbonyl oxygen By similarity
Metal bindingi204 – 2041Calcium 2 By similarity
Metal bindingi206 – 2061Zinc 1 By similarity
Metal bindingi208 – 2081Calcium 3 By similarity
Metal bindingi209 – 2091Calcium 1 By similarity
Metal bindingi211 – 2111Calcium 3 By similarity
Metal bindingi403 – 4031Zinc 2; catalytic By similarity
Active sitei404 – 4041 By similarity
Metal bindingi407 – 4071Zinc 2; catalytic By similarity
Metal bindingi413 – 4131Zinc 2; catalytic By similarity
Metal bindingi478 – 4781Calcium 4; via carbonyl oxygen By similarity
Metal bindingi523 – 5231Calcium 4; via carbonyl oxygen By similarity
Metal bindingi571 – 5711Calcium 4; via carbonyl oxygen By similarity
Metal bindingi620 – 6201Calcium 4; via carbonyl oxygen By 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
Complete GO annotation...

GO - Biological processi

  1. anatomical structure regression 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.

GO - Cellular componenti

  1. cytoplasm Source: RGD
  2. extracellular space Source: RGD
  3. membrane Source: UniProtKB-SubCell
  4. nucleus Source: UniProtKB-SubCell
  5. proteinaceous extracellular matrix Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Extracellular matrix, Membrane, Nucleus, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2929 Reviewed prediction
Add
BLAST
Propeptidei30 – 10980Activation peptide
PRO_0000028720Add
BLAST
Chaini110 – 66255372 kDa type IV collagenase
PRO_0000028721Add
BLAST
Chaini445 – 662218PEX By similarity
PRO_0000391629Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi233 ↔ 259 By similarity
Disulfide bondi247 ↔ 274 By similarity
Disulfide bondi291 ↔ 317 By similarity
Disulfide bondi305 ↔ 332 By similarity
Disulfide bondi349 ↔ 375 By similarity
Disulfide bondi363 ↔ 390 By similarity
Disulfide bondi471 ↔ 662 By similarity
Glycosylationi575 – 5751N-linked (GlcNAc...) Reviewed prediction
Glycosylationi644 – 6441N-linked (GlcNAc...) Reviewed prediction

Post-translational modificationi

Phosphorylation on multiple sites modulates enzymatic activity. Phosphorylated by PKC in vitro 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.

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.

Structurei

3D structure databases

ProteinModelPortaliP33436.
SMRiP33436. Positions 30-662.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini228 – 27649Fibronectin type-II 1
Add
BLAST
Domaini286 – 33449Fibronectin type-II 2
Add
BLAST
Domaini344 – 39249Fibronectin type-II 3
Add
BLAST
Repeati474 – 51845Hemopexin 1
Add
BLAST
Repeati519 – 56547Hemopexin 2
Add
BLAST
Repeati567 – 61549Hemopexin 3
Add
BLAST
Repeati616 – 66247Hemopexin 4
Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni110 – 221112Collagenase-like 1
Add
BLAST
Regioni222 – 396175Collagen-binding
Add
BLAST
Regioni397 – 46771Collagenase-like 2
Add
BLAST
Regioni414 – 662249Required for inhibitor TIMP2 binding By similarity
Add
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi100 – 1078Cysteine switch By 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.
Contains 4 hemopexin repeats.

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

eggNOGiNOG303159.
HOVERGENiHBG052484.
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

MEARLVWGVL VGPLRVLCVL CCLLGHAIAA PSPIIKFPGD VSPKTDKELA    50
VQYLNTFYGC PKESCNLFVL KDTLKKMQKF FGLPQTGDLD QNTIETMRKP 100
RCGNPDVANY NFFPRKPKWD KNQITYRIIG YTPDLDPETV DDAFARALKV 150
WSDVTPLRFS RIHDGEADIM INFGRWEHGD GYPFDGKDGL LAHAFAPGTG 200
VGGDSHFDDD ELWTLGEGQV VRVKYGNADG EYCKFPFLFN GREYSSCTDT 250
GRSDGFLWCS TTYNFEKDGK YGFCPHEALF TMGGNGDGQP CKFPFRFQGT 300
SYNSCTTEGR TDGYRWCGTT EDYDRDKKYG FCPETAMSTV GGNSEGAPCV 350
FPFTFLGNKY ESCTSAGRSD GKVWCATTTN YDDDRKWGFC PDQGYSLFLV 400
AAHEFGHAMG LEHSQDPGAL MAPIYTYTKN FRLSNDDIKG IQELYGPSPD 450
ADTDTGTGPT PTLGPVTPEI CKQDIVFDGI AQIRGEIFFF KDRFIWRTVT 500
PRDKPTGPLL VATFWPELPE KIDAVYEAPQ EEKAVFFAGN EYWVYSASTL 550
ERGYPKPLTS LGLPPDVQQV DAAFNWSKNK KTYIFSGDKF WRYNEVKKKM 600
DPGFPKLIAD SWNAIPDNLD AVVDLQGGGH SYFFKGAYYL KLENQSLKSV 650
KFGSIKSDWL GC 662
Length:662
Mass (Da):74,149
Last modified:May 1, 2007 - v2
Checksum:iC56BD787473FC03E
GO

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti42 – 421S → A in CAA50583. 1 Publication
Sequence conflicti286 – 2861G → A in CAA50583. 1 Publication
Sequence conflicti369 – 3691S → N in CAA50583. 1 Publication
Sequence conflicti435 – 4351N → H in CAA50583. 1 Publication
Sequence conflicti586 – 5861S → A in CAA50583. 1 Publication

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...

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.
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: September 3, 2014
This is version 123 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

Similar proteinsi