UniProtKB - P25785 (TIMP2_MOUSE)
Protein
Metalloproteinase inhibitor 2
Gene
Timp2
Organism
Mus musculus (Mouse)
Status
Functioni
Complexes with metalloproteinases (such as collagenases) and irreversibly inactivates them by binding to their catalytic zinc cofactor.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 27 | Zinc; via amino nitrogen and carbonyl oxygen; shared with metalloproteinase partnerBy similarity | 1 | |
Sitei | 40 | Involved in metalloproteinase-bindingBy similarity | 1 | |
Sitei | 61 | Involved in metalloproteinase-bindingBy similarity | 1 | |
Sitei | 67 | Involved in metalloproteinase-bindingBy similarity | 1 |
GO - Molecular functioni
- enzyme activator activity Source: MGI
- integrin binding Source: MGI
- metalloendopeptidase inhibitor activity Source: MGI
- peptidase inhibitor activity Source: MGI
- protease binding Source: MGI
- zinc ion binding Source: UniProtKB
GO - Biological processi
- cellular response to organic substance Source: MGI
- negative regulation of cell population proliferation Source: MGI
- negative regulation of endopeptidase activity Source: GO_Central
- negative regulation of membrane protein ectodomain proteolysis Source: GO_Central
- negative regulation of metallopeptidase activity Source: MGI
- negative regulation of mitotic cell cycle Source: MGI
- negative regulation of proteolysis Source: MGI
- negative regulation of Ras protein signal transduction Source: MGI
- positive regulation of adenylate cyclase activity Source: MGI
- positive regulation of MAPK cascade Source: MGI
- positive regulation of neuron differentiation Source: MGI
- regulation of MAPK cascade Source: MGI
- regulation of neuron differentiation Source: MGI
- regulation of Rap protein signal transduction Source: MGI
- response to cytokine Source: GO_Central
- response to hormone Source: GO_Central
- response to organic substance Source: GO_Central
Keywordsi
Molecular function | Metalloenzyme inhibitor, Metalloprotease inhibitor, Protease inhibitor |
Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
Reactomei | R-MMU-1592389, Activation of Matrix Metalloproteinases R-MMU-6798695, Neutrophil degranulation |
Protein family/group databases
MEROPSi | I35.002 |
Names & Taxonomyi
Protein namesi | Recommended name: Metalloproteinase inhibitor 2Alternative name(s): Tissue inhibitor of metalloproteinases 2 Short name: TIMP-2 |
Gene namesi | Name:Timp2 Synonyms:Timp-2 |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:98753, Timp2 |
Subcellular locationi
Extracellular region or secreted
Extracellular region or secreted
- basement membrane Source: MGI
- extracellular matrix Source: GO_Central
- extracellular space Source: BHF-UCL
Other locations
- cell surface Source: MGI
- growth cone Source: MGI
- neuron projection Source: MGI
- neuronal cell body Source: MGI
Keywords - Cellular componenti
SecretedPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 26 | Add BLAST | 26 | |
ChainiPRO_0000034336 | 27 – 220 | Metalloproteinase inhibitor 2Add BLAST | 194 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 27 ↔ 98 | PROSITE-ProRule annotation | ||
Disulfide bondi | 29 ↔ 127 | PROSITE-ProRule annotation | ||
Disulfide bondi | 39 ↔ 152 | PROSITE-ProRule annotation | ||
Disulfide bondi | 154 ↔ 201 | PROSITE-ProRule annotation | ||
Disulfide bondi | 159 ↔ 164 | PROSITE-ProRule annotation | ||
Disulfide bondi | 172 ↔ 193 | PROSITE-ProRule annotation |
Post-translational modificationi
The activity of TIMP2 is dependent on the presence of disulfide bonds.
Keywords - PTMi
Disulfide bondProteomic databases
CPTACi | non-CPTAC-3356 |
MaxQBi | P25785 |
PaxDbi | P25785 |
PeptideAtlasi | P25785 |
PRIDEi | P25785 |
PTM databases
PhosphoSitePlusi | P25785 |
Expressioni
Tissue specificityi
Detected in testis, retina, hippocampus and cerebral cortex.1 Publication
Inductioni
After intracranial injury, expression peaks at 4 days post-injury and slightly declines at 7 days post-injury.1 Publication
Interactioni
Subunit structurei
Interacts (via the C-terminal) with MMP2 (via the C-terminal PEX domain); the interaction inhibits the MMP2 activity.
By similarityGO - Molecular functioni
- integrin binding Source: MGI
- protease binding Source: MGI
Protein-protein interaction databases
STRINGi | 10090.ENSMUSP00000017610 |
Miscellaneous databases
RNActi | P25785, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 27 – 152 | NTRPROSITE-ProRule annotationAdd BLAST | 126 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 27 – 30 | Involved in metalloproteinase-bindingBy similarity | 4 | |
Regioni | 95 – 96 | Involved in metalloproteinase-bindingBy similarity | 2 |
Sequence similaritiesi
Keywords - Domaini
SignalPhylogenomic databases
eggNOGi | KOG4745, Eukaryota |
InParanoidi | P25785 |
PhylomeDBi | P25785 |
Family and domain databases
Gene3Di | 2.40.50.120, 1 hit 3.90.370.10, 1 hit |
InterProi | View protein in InterPro IPR001134, Netrin_domain IPR001820, TIMP IPR008993, TIMP-like_OB-fold IPR015613, TIMP2 IPR027465, TIMP_C IPR030490, TIMP_CS |
PANTHERi | PTHR11844, PTHR11844, 1 hit PTHR11844:SF24, PTHR11844:SF24, 1 hit |
Pfami | View protein in Pfam PF00965, TIMP, 1 hit |
SMARTi | View protein in SMART SM00206, NTR, 1 hit |
SUPFAMi | SSF50242, SSF50242, 1 hit |
PROSITEi | View protein in PROSITE PS50189, NTR, 1 hit PS00288, TIMP, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All
P25785-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MGAAARSLRL ALGLLLLASL VRPADACSCS PVHPQQAFCN ADVVIRAKAV
60 70 80 90 100
SEKEVDSGND IYGNPIKRIQ YEIKQIKMFK GPDKDIEFIY TAPSSAVCGV
110 120 130 140 150
SLDVGGKKEY LIAGKAEGDG KMHITLCDFI VPWDTLSITQ KKSLNHRYQM
160 170 180 190 200
GCECKITRCP MIPCYISSPD ECLWMDWVTE KSINGHQAKF FACIKRSDGS
210 220
CAWYRGAAPP KQEFLDIEDP
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketQ6PI17 | Q6PI17_MOUSE | Metalloproteinase inhibitor 2 | Timp2 | 220 | Annotation score: | ||
B1AQJ3 | B1AQJ3_MOUSE | Metalloproteinase inhibitor 2 | Timp2 | 143 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 12 | L → H in AAA40446 (PubMed:1639268).Curated | 1 | |
Sequence conflicti | 21 | V → L in AAA40446 (PubMed:1639268).Curated | 1 | |
Sequence conflicti | 195 | K → E in AAA40446 (PubMed:1639268).Curated | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | X62622 mRNA Translation: CAA44491.1 M82858 mRNA Translation: AAA40445.1 M93954 mRNA Translation: AAA40446.1 |
PIRi | JH0683 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | X62622 mRNA Translation: CAA44491.1 M82858 mRNA Translation: AAA40445.1 M93954 mRNA Translation: AAA40446.1 |
PIRi | JH0683 |
3D structure databases
BMRBi | P25785 |
SMRi | P25785 |
ModBasei | Search... |
Protein-protein interaction databases
STRINGi | 10090.ENSMUSP00000017610 |
Protein family/group databases
MEROPSi | I35.002 |
PTM databases
PhosphoSitePlusi | P25785 |
Proteomic databases
CPTACi | non-CPTAC-3356 |
MaxQBi | P25785 |
PaxDbi | P25785 |
PeptideAtlasi | P25785 |
PRIDEi | P25785 |
Organism-specific databases
MGIi | MGI:98753, Timp2 |
Phylogenomic databases
eggNOGi | KOG4745, Eukaryota |
InParanoidi | P25785 |
PhylomeDBi | P25785 |
Enzyme and pathway databases
Reactomei | R-MMU-1592389, Activation of Matrix Metalloproteinases R-MMU-6798695, Neutrophil degranulation |
Miscellaneous databases
ChiTaRSi | Timp2, mouse |
PROi | PR:P25785 |
RNActi | P25785, protein |
SOURCEi | Search... |
Family and domain databases
Gene3Di | 2.40.50.120, 1 hit 3.90.370.10, 1 hit |
InterProi | View protein in InterPro IPR001134, Netrin_domain IPR001820, TIMP IPR008993, TIMP-like_OB-fold IPR015613, TIMP2 IPR027465, TIMP_C IPR030490, TIMP_CS |
PANTHERi | PTHR11844, PTHR11844, 1 hit PTHR11844:SF24, PTHR11844:SF24, 1 hit |
Pfami | View protein in Pfam PF00965, TIMP, 1 hit |
SMARTi | View protein in SMART SM00206, NTR, 1 hit |
SUPFAMi | SSF50242, SSF50242, 1 hit |
PROSITEi | View protein in PROSITE PS50189, NTR, 1 hit PS00288, TIMP, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | TIMP2_MOUSE | |
Accessioni | P25785Primary (citable) accession number: P25785 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | May 1, 1992 |
Last sequence update: | April 1, 1993 | |
Last modified: | October 7, 2020 | |
This is version 158 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Direct protein sequencing, Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families