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UniProtKB - P16368 (TIMP2_BOVIN)
Protein
Metalloproteinase inhibitor 2
Gene
TIMP2
Organism
Bos taurus (Bovine)
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 partnerCombined sources1 Publication | 1 | |
Sitei | 64 | Involved in metalloproteinase-bindingCombined sources1 Publication | 1 | |
Sitei | 96 | Involved in metalloproteinase-bindingCombined sources1 Publication | 1 | |
Sitei | 158 | Involved in metalloproteinase-bindingCombined sources1 Publication | 1 | |
Sitei | 177 | Involved in metalloproteinase-bindingCombined sources1 Publication | 1 |
GO - Molecular functioni
- metal ion binding Source: UniProtKB-KW
- metalloendopeptidase inhibitor activity Source: GO_Central
- protease binding Source: GO_Central
GO - Biological processi
- negative regulation of endopeptidase activity Source: GO_Central
- negative regulation of membrane protein ectodomain proteolysis Source: GO_Central
- 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 |
Protein family/group databases
MEROPSi | I35.002 |
Names & Taxonomyi
Protein namesi | Recommended name: Metalloproteinase inhibitor 2Alternative name(s): Collagenase inhibitor Tissue inhibitor of metalloproteinases 2 Short name: TIMP-2 |
Gene namesi | Name:TIMP2 |
Organismi | Bos taurus (Bovine) |
Taxonomic identifieri | 9913 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Artiodactyla › Ruminantia › Pecora › Bovidae › Bovinae › Bos |
Proteomesi |
|
Subcellular locationi
Extracellular region or secreted
Extracellular region or secreted
- extracellular space Source: GO_Central
Other locations
- extracellular matrix Source: GO_Central
Keywords - Cellular componenti
SecretedPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 26 | 2 PublicationsAdd BLAST | 26 | |
ChainiPRO_0000034331 | 27 – 220 | Metalloproteinase inhibitor 2Add BLAST | 194 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 27 ↔ 98 | Combined sources1 Publication | ||
Disulfide bondi | 29 ↔ 127 | Combined sources1 Publication | ||
Disulfide bondi | 39 ↔ 152 | Combined sources1 Publication | ||
Disulfide bondi | 154 ↔ 201 | Combined sources1 Publication | ||
Disulfide bondi | 159 ↔ 164 | Combined sources1 Publication | ||
Disulfide bondi | 172 ↔ 193 | Combined sources1 Publication |
Post-translational modificationi
The activity of TIMP2 is dependent on the presence of disulfide bonds.
Keywords - PTMi
Disulfide bondProteomic databases
PaxDbi | P16368 |
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
- protease binding Source: GO_Central
Protein-protein interaction databases
IntActi | P16368, 1 interactor |
STRINGi | 9913.ENSBTAP00000014476 |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
AlphaFoldDBi | P16368 |
SMRi | P16368 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P16368 |
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-bindingCombined sources1 Publication | 4 |
Sequence similaritiesi
Keywords - Domaini
SignalPhylogenomic databases
eggNOGi | KOG4745, Eukaryota |
InParanoidi | P16368 |
OrthoDBi | 1122531at2759 |
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 |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
P16368-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MGAAARSLPL AFCLLLLGTL LPRADACSCS PVHPQQAFCN ADIVIRAKAV
60 70 80 90 100
NKKEVDSGND IYGNPIKRIQ YEIKQIKMFK GPDQDIEFIY TAPAAAVCGV
110 120 130 140 150
SLDIGGKKEY LIAGKAEGNG NMHITLCDFI VPWDTLSATQ KKSLNHRYQM
160 170 180 190 200
GCECKITRCP MIPCYISSPD ECLWMDWVTE KNINGHQAKF FACIKRSDGS
210 220
CAWYRGAAPP KQEFLDIEDP
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 15 | L → M in AAI02711 (Ref. 2) Curated | 1 | |
Sequence conflicti | 42 | D → C AA sequence (PubMed:3005321).Curated | 1 | |
Sequence conflicti | 56 | D → E AA sequence (PubMed:3005321).Curated | 1 | |
Sequence conflicti | 68 | R → S AA sequence (PubMed:3005321).Curated | 1 | |
Sequence conflicti | 88 | F → L in AAI02711 (Ref. 2) Curated | 1 | |
Sequence conflicti | 94 – 95 | AA → SS in AAI02711 (Ref. 2) Curated | 2 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M32303 mRNA Translation: AAA30636.1 BC102710 mRNA Translation: AAI02711.1 AF144764 mRNA Translation: AAD30304.1 |
PIRi | A35996 |
RefSeqi | NP_776897.2, NM_174472.4 |
Genome annotation databases
GeneIDi | 282093 |
KEGGi | bta:282093 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M32303 mRNA Translation: AAA30636.1 BC102710 mRNA Translation: AAI02711.1 AF144764 mRNA Translation: AAD30304.1 |
PIRi | A35996 |
RefSeqi | NP_776897.2, NM_174472.4 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1BQQ | X-ray | 2.75 | T | 27-210 | [»] | |
1BUV | X-ray | 2.75 | T | 27-210 | [»] | |
2E2D | X-ray | 2.00 | C | 27-206 | [»] | |
AlphaFoldDBi | P16368 | |||||
SMRi | P16368 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
IntActi | P16368, 1 interactor |
STRINGi | 9913.ENSBTAP00000014476 |
Protein family/group databases
MEROPSi | I35.002 |
Proteomic databases
PaxDbi | P16368 |
Genome annotation databases
GeneIDi | 282093 |
KEGGi | bta:282093 |
Organism-specific databases
CTDi | 7077 |
Phylogenomic databases
eggNOGi | KOG4745, Eukaryota |
InParanoidi | P16368 |
OrthoDBi | 1122531at2759 |
Miscellaneous databases
EvolutionaryTracei | P16368 |
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 |
MobiDBi | Search... |
Entry informationi
Entry namei | TIMP2_BOVIN | |
Accessioni | P16368Primary (citable) accession number: P16368 Secondary accession number(s): Q3SZU3, Q9TVB1 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | August 1, 1990 |
Last sequence update: | May 1, 1991 | |
Last modified: | May 25, 2022 | |
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
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families