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Protein

Metalloproteinase inhibitor 2

Gene

Timp2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Complexes with metalloproteinases (such as collagenases) and irreversibly inactivates them by binding to their catalytic zinc cofactor.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi27 – 271Zinc; via amino nitrogen and carbonyl oxygen; shared with metalloproteinase partnerBy similarity

GO - Molecular functioni

  • enzyme activator activity Source: MGI
  • integrin binding Source: MGI
  • metal ion binding Source: UniProtKB-KW
  • metalloendopeptidase inhibitor activity Source: MGI

GO - Biological processi

  • cellular response to organic substance Source: MGI
  • negative regulation of cell proliferation Source: MGI
  • positive regulation of catalytic activity Source: GOC
  • regulation of cAMP metabolic process Source: MGI
  • regulation of MAPK cascade Source: MGI
  • regulation of neuron differentiation Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Metalloenzyme inhibitor, Metalloprotease inhibitor, Protease inhibitor

Keywords - Ligandi

Metal-binding, Zinc

Protein family/group databases

MEROPSiI35.002.

Names & Taxonomyi

Protein namesi
Recommended name:
Metalloproteinase inhibitor 2
Alternative name(s):
Tissue inhibitor of metalloproteinases 2
Short name:
TIMP-2
Gene namesi
Name:Timp2
Synonyms:Timp-2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:98753. Timp2.

Subcellular locationi

GO - Cellular componenti

  • basement membrane Source: MGI
  • cell surface Source: MGI
  • extracellular exosome Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2626Add
BLAST
Chaini27 – 220194Metalloproteinase inhibitor 2PRO_0000034336Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi27 ↔ 98PROSITE-ProRule annotation
Disulfide bondi29 ↔ 127PROSITE-ProRule annotation
Disulfide bondi39 ↔ 152PROSITE-ProRule annotation
Disulfide bondi154 ↔ 201PROSITE-ProRule annotation
Disulfide bondi159 ↔ 164PROSITE-ProRule annotation
Disulfide bondi172 ↔ 193PROSITE-ProRule annotation

Post-translational modificationi

The activity of TIMP2 is dependent on the presence of disulfide bonds.

Keywords - PTMi

Disulfide bond

Proteomic databases

MaxQBiP25785.
PaxDbiP25785.
PRIDEiP25785.

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

Gene expression databases

CleanExiMM_TIMP2.

Interactioni

Subunit structurei

Interacts (via the C-terminal) with MMP2 (via the C-terminal PEX domain); the interaction inhibits the MMP2 activity.By similarity

GO - Molecular functioni

  • integrin binding Source: MGI

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000017610.

Structurei

3D structure databases

ProteinModelPortaliP25785.
SMRiP25785. Positions 27-208.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini27 – 152126NTRPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni27 – 315Involved in metalloproteinase-bindingBy similarity
Regioni95 – 962Involved in metalloproteinase-bindingBy similarity

Sequence similaritiesi

Contains 1 NTR domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG4745. Eukaryota.
ENOG41103NU. LUCA.
HOGENOMiHOG000285981.
HOVERGENiHBG068749.
InParanoidiP25785.
PhylomeDBiP25785.

Family and domain databases

Gene3Di3.90.370.10. 1 hit.
InterProiIPR001134. Netrin_domain.
IPR001820. TIMP.
IPR008993. TIMP-like_OB-fold.
IPR015613. TIMP2.
IPR027465. TIMP_C.
IPR030490. TIMP_CS.
[Graphical view]
PANTHERiPTHR11844. PTHR11844. 1 hit.
PTHR11844:SF24. PTHR11844:SF24. 1 hit.
PfamiPF00965. TIMP. 1 hit.
[Graphical view]
SMARTiSM00206. NTR. 1 hit.
[Graphical view]
SUPFAMiSSF50242. SSF50242. 1 hit.
PROSITEiPS50189. NTR. 1 hit.
PS00288. TIMP. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P25785-1 [UniParc]FASTAAdd to basket

« Hide

        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
Length:220
Mass (Da):24,328
Last modified:April 1, 1993 - v2
Checksum:i1D0A16CEDA023F0D
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti12 – 121L → H in AAA40446 (PubMed:1639268).Curated
Sequence conflicti21 – 211V → L in AAA40446 (PubMed:1639268).Curated
Sequence conflicti195 – 1951K → E in AAA40446 (PubMed:1639268).Curated

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.
PIRiJH0683.
UniGeneiMm.206505.

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.
PIRiJH0683.
UniGeneiMm.206505.

3D structure databases

ProteinModelPortaliP25785.
SMRiP25785. Positions 27-208.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000017610.

Protein family/group databases

MEROPSiI35.002.

Proteomic databases

MaxQBiP25785.
PaxDbiP25785.
PRIDEiP25785.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Organism-specific databases

MGIiMGI:98753. Timp2.

Phylogenomic databases

eggNOGiKOG4745. Eukaryota.
ENOG41103NU. LUCA.
HOGENOMiHOG000285981.
HOVERGENiHBG068749.
InParanoidiP25785.
PhylomeDBiP25785.

Miscellaneous databases

PROiP25785.
SOURCEiSearch...

Gene expression databases

CleanExiMM_TIMP2.

Family and domain databases

Gene3Di3.90.370.10. 1 hit.
InterProiIPR001134. Netrin_domain.
IPR001820. TIMP.
IPR008993. TIMP-like_OB-fold.
IPR015613. TIMP2.
IPR027465. TIMP_C.
IPR030490. TIMP_CS.
[Graphical view]
PANTHERiPTHR11844. PTHR11844. 1 hit.
PTHR11844:SF24. PTHR11844:SF24. 1 hit.
PfamiPF00965. TIMP. 1 hit.
[Graphical view]
SMARTiSM00206. NTR. 1 hit.
[Graphical view]
SUPFAMiSSF50242. SSF50242. 1 hit.
PROSITEiPS50189. NTR. 1 hit.
PS00288. TIMP. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning and sequencing of the cDNA encoding a mouse tissue inhibitor of metalloproteinase-2."
    Shimizu S., Malik K., Sejima H., Kishi J.I., Hayakawa T., Koiwai O.
    Gene 114:291-292(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: BALB/cJ.
  2. "Differential regulation of TIMP-1 and TIMP-2 mRNA expression in normal and Ha-ras-transformed murine fibroblasts."
    Leco K.J., Hayden L.J., Sharma R.R., Rocheleau H., Greenberg A.H., Edwards D.R.
    Gene 117:209-217(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  3. "Purification and characterization of a new tissue inhibitor of metalloproteinases (TIMP-2) from mouse colon 26 tumor cells."
    Kishi J.I., Ogawa K., Yamamoto S., Hayakawa T.
    Matrix 11:10-16(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: PRELIMINARY PROTEIN SEQUENCE OF 27-62.
  4. "Potential regulatory relationship between the nested gene DDC8 and its host gene tissue inhibitor of metalloproteinase-2."
    Jaworski D.M., Beem-Miller M., Lluri G., Barrantes-Reynolds R.
    Physiol. Genomics 28:168-178(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY, INDUCTION BY INJURY.
  5. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Brain, Lung, Spleen and Testis.

Entry informationi

Entry nameiTIMP2_MOUSE
AccessioniPrimary (citable) accession number: P25785
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 1, 1992
Last sequence update: April 1, 1993
Last modified: May 11, 2016
This is version 131 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, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  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.