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Protein

Metalloproteinase inhibitor 2

Gene

Timp2

Organism
Rattus norvegicus (Rat)
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

GO - Molecular functioni

  • integrin binding Source: RGD
  • metal ion binding Source: UniProtKB-KW
  • metalloendopeptidase inhibitor activity Source: RGD
  • protease binding Source: GO_Central

GO - Biological processi

  • aging Source: RGD
  • central nervous system development Source: RGD
  • negative regulation of cell proliferation Source: RGD
  • negative regulation of membrane protein ectodomain proteolysis Source: GO_Central
  • negative regulation of mitotic cell cycle Source: RGD
  • negative regulation of proteolysis Source: RGD
  • negative regulation of Ras protein signal transduction Source: RGD
  • positive regulation of adenylate cyclase activity Source: RGD
  • positive regulation of MAPK cascade Source: RGD
  • positive regulation of neuron differentiation Source: RGD
  • regulation of Rap protein signal transduction Source: RGD
  • response to cytokine Source: RGD
  • response to drug Source: RGD
  • response to hormone Source: GO_Central
  • spermatogenesis Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Metalloenzyme inhibitor, Metalloprotease inhibitor, Protease inhibitor

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-RNO-1592389. Activation of Matrix Metalloproteinases.
R-RNO-6798695. Neutrophil degranulation.

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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 10

Organism-specific databases

RGDi61312. Timp2.

Subcellular locationi

GO - Cellular componenti

  • cell surface Source: RGD
  • extracellular exosome Source: Ensembl
  • extracellular space Source: RGD
  • growth cone Source: RGD
  • neuronal cell body Source: RGD
  • neuron projection Source: RGD
  • proteinaceous extracellular matrix Source: GO_Central
Complete GO annotation...

Keywords - Cellular componenti

Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 261 PublicationAdd BLAST26
ChainiPRO_000003433727 – 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

PaxDbiP30121.
PRIDEiP30121.

PTM databases

PhosphoSitePlusiP30121.

Expressioni

Gene expression databases

BgeeiENSRNOG00000003148.
GenevisibleiP30121. RN.

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: RGD
  • protease binding Source: GO_Central

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000004290.

Structurei

3D structure databases

ProteinModelPortaliP30121.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

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

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni27 – 31Involved in metalloproteinase-bindingBy similarity5
Regioni95 – 96Involved in metalloproteinase-bindingBy similarity2

Sequence similaritiesi

Contains 1 NTR domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG4745. Eukaryota.
ENOG41103NU. LUCA.
GeneTreeiENSGT00390000004555.
HOGENOMiHOG000285981.
HOVERGENiHBG068749.
InParanoidiP30121.
OMAiKMFKGPE.
OrthoDBiEOG091G0NIC.
PhylomeDBiP30121.

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.

P30121-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGAAARSLRL ALGLLLLATL LRPADACSCS 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):24,356
Last modified:October 1, 1996 - v3
Checksum:i1C97A3F050C3AE7D
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti7S → T in AAA21553 (PubMed:8203893).Curated1
Sequence conflicti153E → Q in AAA21553 (PubMed:8203893).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U14526 mRNA. Translation: AAA21553.1.
L31884 mRNA. Translation: AAA84581.1.
S72594 mRNA. Translation: AAC60687.1.
S82718 mRNA. Translation: AAB49507.1.
AJ409332 mRNA. Translation: CAC35060.1.
BC084714 mRNA. Translation: AAH84714.1.
PIRiS45683.
RefSeqiNP_068824.1. NM_021989.2.
UniGeneiRn.10161.

Genome annotation databases

EnsembliENSRNOT00000004290; ENSRNOP00000004290; ENSRNOG00000003148.
GeneIDi29543.
KEGGirno:29543.
UCSCiRGD:61312. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U14526 mRNA. Translation: AAA21553.1.
L31884 mRNA. Translation: AAA84581.1.
S72594 mRNA. Translation: AAC60687.1.
S82718 mRNA. Translation: AAB49507.1.
AJ409332 mRNA. Translation: CAC35060.1.
BC084714 mRNA. Translation: AAH84714.1.
PIRiS45683.
RefSeqiNP_068824.1. NM_021989.2.
UniGeneiRn.10161.

3D structure databases

ProteinModelPortaliP30121.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000004290.

Protein family/group databases

MEROPSiI35.002.

PTM databases

PhosphoSitePlusiP30121.

Proteomic databases

PaxDbiP30121.
PRIDEiP30121.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000004290; ENSRNOP00000004290; ENSRNOG00000003148.
GeneIDi29543.
KEGGirno:29543.
UCSCiRGD:61312. rat.

Organism-specific databases

CTDi7077.
RGDi61312. Timp2.

Phylogenomic databases

eggNOGiKOG4745. Eukaryota.
ENOG41103NU. LUCA.
GeneTreeiENSGT00390000004555.
HOGENOMiHOG000285981.
HOVERGENiHBG068749.
InParanoidiP30121.
OMAiKMFKGPE.
OrthoDBiEOG091G0NIC.
PhylomeDBiP30121.

Enzyme and pathway databases

ReactomeiR-RNO-1592389. Activation of Matrix Metalloproteinases.
R-RNO-6798695. Neutrophil degranulation.

Miscellaneous databases

PROiP30121.

Gene expression databases

BgeeiENSRNOG00000003148.
GenevisibleiP30121. RN.

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...

Entry informationi

Entry nameiTIMP2_RAT
AccessioniPrimary (citable) accession number: P30121
Secondary accession number(s): Q546J4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: October 1, 1996
Last modified: November 30, 2016
This is version 131 of the entry and version 3 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. 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.