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P30121 (TIMP2_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 111. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Metalloproteinase inhibitor 2
Alternative name(s):
Tissue inhibitor of metalloproteinases 2
Short name=TIMP-2
Gene names
Name:Timp2
Synonyms:Timp-2
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length220 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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

Subunit structure

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

Subcellular location

Secreted.

Post-translational modification

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

Sequence similarities

Belongs to the protease inhibitor I35 (TIMP) family. [View classification]

Contains 1 NTR domain.

Ontologies

Keywords
   Cellular componentSecreted
   DomainSignal
   LigandMetal-binding
Zinc
   Molecular functionMetalloenzyme inhibitor
Metalloprotease inhibitor
Protease inhibitor
   PTMDisulfide bond
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processaging

Inferred from expression pattern PubMed 18278151. Source: RGD

cellular response to organic substance

Inferred from electronic annotation. Source: Ensembl

central nervous system development

Inferred from expression pattern PubMed 11044612. Source: RGD

negative regulation of Ras protein signal transduction

Inferred from direct assay PubMed 15901773. Source: RGD

negative regulation of cell proliferation

Inferred from direct assay PubMed 15901773. Source: RGD

negative regulation of endopeptidase activity

Inferred from mutant phenotype PubMed 15901773. Source: GOC

negative regulation of mitotic cell cycle

Inferred from direct assay PubMed 15901773. Source: RGD

negative regulation of proteolysis

Inferred from mutant phenotype PubMed 17532789. Source: RGD

positive regulation of MAPK cascade

Inferred from direct assay PubMed 15901773. Source: RGD

positive regulation of adenylate cyclase activity

Inferred from mutant phenotype PubMed 15901773. Source: RGD

positive regulation of neuron differentiation

Inferred from direct assay PubMed 15901773. Source: RGD

regulation of Rap protein signal transduction

Inferred from direct assay PubMed 15901773. Source: RGD

response to cytokine

Inferred from expression pattern PubMed 17822627. Source: RGD

response to drug

Inferred from expression pattern PubMed 17491697. Source: RGD

spermatogenesis

Non-traceable author statement Ref.4. Source: RGD

   Cellular_componentbasement membrane

Inferred from electronic annotation. Source: Ensembl

cell surface

Inferred from direct assay PubMed 15901773. Source: RGD

extracellular space

Inferred from direct assay PubMed 15901773. Source: RGD

growth cone

Inferred from direct assay PubMed 15901773. Source: RGD

neuron projection

Inferred from direct assay PubMed 15901773. Source: RGD

neuronal cell body

Inferred from direct assay PubMed 15901773. Source: RGD

   Molecular_functionenzyme activator activity

Inferred from electronic annotation. Source: Ensembl

integrin binding

Inferred from physical interaction PubMed 15901773. Source: RGD

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

metalloendopeptidase inhibitor activity

Inferred from mutant phenotype PubMed 15901773. Source: RGD

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2626 Ref.7
Chain27 – 220194Metalloproteinase inhibitor 2
PRO_0000034337

Regions

Domain27 – 152126NTR
Region27 – 315Involved in metalloproteinase-binding By similarity
Region95 – 962Involved in metalloproteinase-binding By similarity

Sites

Metal binding271Zinc; via amino nitrogen and carbonyl oxygen; shared with metalloproteinase partner By similarity

Amino acid modifications

Disulfide bond27 ↔ 98 By similarity
Disulfide bond29 ↔ 127 By similarity
Disulfide bond39 ↔ 152 By similarity
Disulfide bond154 ↔ 201 By similarity
Disulfide bond159 ↔ 164 By similarity
Disulfide bond172 ↔ 193 By similarity

Experimental info

Sequence conflict71S → T in AAA21553. Ref.1
Sequence conflict1531E → Q in AAA21553. Ref.1

Sequences

Sequence LengthMass (Da)Tools
P30121 [UniParc].

Last modified October 1, 1996. Version 3.
Checksum: 1C97A3F050C3AE7D

FASTA22024,356
        10         20         30         40         50         60 
MGAAARSLRL ALGLLLLATL LRPADACSCS PVHPQQAFCN ADVVIRAKAV SEKEVDSGND 

        70         80         90        100        110        120 
IYGNPIKRIQ YEIKQIKMFK GPDKDIEFIY TAPSSAVCGV SLDVGGKKEY LIAGKAEGDG 

       130        140        150        160        170        180 
KMHITLCDFI VPWDTLSITQ KKSLNHRYQM GCECKITRCP MIPCYISSPD ECLWMDWVTE 

       190        200        210        220 
KSINGHQAKF FACIKRSDGS CAWYRGAAPP KQEFLDIEDP 

« Hide

References

« Hide 'large scale' references
[1]"Cloning and regulation of rat tissue inhibitor of metalloproteinases-2 in osteoblastic cells."
Cook T.F., Burke J.S., Bergman K.D., Quinn C.O., Jeffrey J.J., Partridge N.C.
Arch. Biochem. Biophys. 311:313-320(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: Sprague-Dawley.
Tissue: Bone.
[2]Gibbons K.L., O'Grady R.L., Piper A.A.
Submitted (JUN-1995) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Mammary gland.
[3]"Cloning of the rat tissue inhibitor of metalloproteinases type 2 (TIMP-2) gene: analysis of its expression in normal and transformed thyroid cells."
Santoro M., Battaglia C., Zhang L., Carlomagno F., Martelli M.L., Salvatore D., Fusco A.
Exp. Cell Res. 213:398-403(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]"Purification, cDNA cloning, and developmental changes in the steady-state mRNA level of rat testicular tissue inhibitor of metalloproteases-2 (TIMP-2)."
Grima J., Calcagno K., Cheng C.Y.
J. Androl. 17:263-275(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Testis.
[5]"Cardiac remodeling after long term norepinephrine treatment in rats."
Briest W., Hoelzl A., Rassler B., Deten A., Leicht M., Baba H.A., Zimmer H.G.
Cardiovasc. Res. 52:265-273(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: Sprague-Dawley.
Tissue: Heart.
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Ovary.
[7]"Purification and sequence analysis of two rat tissue inhibitors of metalloproteinases."
Roswit W.T., McCourt D.W., Partridge N.C., Jeffrey J.J.
Arch. Biochem. Biophys. 292:402-410(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 27-48.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRS45683.
RefSeqNP_068824.1. NM_021989.2.
UniGeneRn.10161.

3D structure databases

ProteinModelPortalP30121.
SMRP30121. Positions 27-208.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING10116.ENSRNOP00000004290.

Protein family/group databases

MEROPSI35.002.

Proteomic databases

PaxDbP30121.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000004290; ENSRNOP00000004290; ENSRNOG00000003148.
GeneID29543.
KEGGrno:29543.
UCSCRGD:61312. rat.

Organism-specific databases

CTD7077.
RGD61312. Timp2.

Phylogenomic databases

eggNOGNOG243625.
GeneTreeENSGT00390000004555.
HOGENOMHOG000285981.
HOVERGENHBG068749.
OMAKMFKGPE.
OrthoDBEOG79GT74.
PhylomeDBP30121.

Gene expression databases

GenevestigatorP30121.

Family and domain databases

Gene3D3.90.370.10. 1 hit.
InterProIPR001134. Netrin_domain.
IPR001820. Prot_inh_TIMP.
IPR008993. TIMP-like_OB-fold.
IPR015613. TIMP2.
IPR027465. TIMP_C_dom.
[Graphical view]
PANTHERPTHR11844. PTHR11844. 1 hit.
PTHR11844:SF7. PTHR11844:SF7. 1 hit.
PfamPF00965. TIMP. 1 hit.
[Graphical view]
SMARTSM00206. NTR. 1 hit.
[Graphical view]
SUPFAMSSF50242. SSF50242. 1 hit.
PROSITEPS50189. NTR. 1 hit.
PS00288. TIMP. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio609549.
PROP30121.

Entry information

Entry nameTIMP2_RAT
AccessionPrimary (citable) accession number: P30121
Secondary accession number(s): Q546J4
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: October 1, 1996
Last modified: April 16, 2014
This is version 111 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families