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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)DescriptionActionsGraphical viewLength
Metal bindingi27Zinc; via amino nitrogen and carbonyl oxygen; shared with metalloproteinase partnerBy similarity1
Sitei40Involved in metalloproteinase-bindingBy similarity1
Sitei61Involved in metalloproteinase-bindingBy similarity1
Sitei67Involved in metalloproteinase-bindingBy similarity1

GO - Molecular functioni

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

GO - Biological processi

  • cellular response to organic substance Source: MGI
  • negative regulation of cell proliferation Source: MGI
  • negative regulation of membrane protein ectodomain proteolysis Source: GO_Central
  • negative regulation of metallopeptidase activity Source: MGI
  • regulation of cAMP metabolic process Source: MGI
  • regulation of MAPK cascade Source: MGI
  • regulation of neuron differentiation Source: MGI
  • response to cytokine Source: GO_Central
  • response to hormone Source: GO_Central

Keywordsi

Molecular functionMetalloenzyme inhibitor, Metalloprotease inhibitor, Protease inhibitor
LigandMetal-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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
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
  • extracellular matrix Source: MGI
  • extracellular space Source: BHF-UCL

Keywords - Cellular componenti

Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 26Add BLAST26
ChainiPRO_000003433627 – 220Metalloproteinase inhibitor 2Add BLAST194

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
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.
PeptideAtlasiP25785.
PRIDEiP25785.

PTM databases

PhosphoSitePlusiP25785.

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
  • protease binding Source: MGI

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000017610.

Structurei

3D structure databases

ProteinModelPortaliP25785.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini27 – 152NTRPROSITE-ProRule annotationAdd BLAST126

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni27 – 30Involved in metalloproteinase-bindingBy similarity4
Regioni95 – 96Involved in metalloproteinase-bindingBy similarity2

Sequence similaritiesi

Keywords - Domaini

Signal

Phylogenomic databases

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

Family and domain databases

Gene3Di3.90.370.10. 1 hit.
InterProiView protein in InterPro
IPR001134. Netrin_domain.
IPR001820. TIMP.
IPR008993. TIMP-like_OB-fold.
IPR015613. TIMP2.
IPR027465. TIMP_C.
IPR030490. TIMP_CS.
PANTHERiPTHR11844. PTHR11844. 1 hit.
PTHR11844:SF26. PTHR11844:SF26. 1 hit.
PfamiView protein in Pfam
PF00965. TIMP. 1 hit.
SMARTiView protein in SMART
SM00206. NTR. 1 hit.
SUPFAMiSSF50242. SSF50242. 1 hit.
PROSITEiView protein in PROSITE
PS50189. NTR. 1 hit.
PS00288. TIMP. 1 hit.

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)DescriptionActionsGraphical viewLength
Sequence conflicti12L → H in AAA40446 (PubMed:1639268).Curated1
Sequence conflicti21V → L in AAA40446 (PubMed:1639268).Curated1
Sequence conflicti195K → E in AAA40446 (PubMed:1639268).Curated1

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.

Similar proteinsi

Entry informationi

Entry nameiTIMP2_MOUSE
AccessioniPrimary (citable) accession number: P25785
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 1, 1992
Last sequence update: April 1, 1993
Last modified: August 30, 2017
This is version 139 of the entry and version 2 of the sequence. See 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