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P30121

- TIMP2_RAT

UniProt

P30121 - TIMP2_RAT

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Protein
Metalloproteinase inhibitor 2
Gene
Timp2, Timp-2
Organism
Rattus norvegicus (Rat)
Status
Reviewed - 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 partner By similarity

GO - Molecular functioni

  1. enzyme activator activity Source: Ensembl
  2. integrin binding Source: RGD
  3. metal ion binding Source: UniProtKB-KW
  4. metalloendopeptidase inhibitor activity Source: RGD

GO - Biological processi

  1. aging Source: RGD
  2. cellular response to organic substance Source: Ensembl
  3. central nervous system development Source: RGD
  4. negative regulation of Ras protein signal transduction Source: RGD
  5. negative regulation of cell proliferation Source: RGD
  6. negative regulation of endopeptidase activity Source: GOC
  7. negative regulation of mitotic cell cycle Source: RGD
  8. negative regulation of proteolysis Source: RGD
  9. positive regulation of MAPK cascade Source: RGD
  10. positive regulation of adenylate cyclase activity Source: RGD
  11. positive regulation of neuron differentiation Source: RGD
  12. regulation of Rap protein signal transduction Source: RGD
  13. response to cytokine Source: RGD
  14. response to drug Source: RGD
  15. spermatogenesis Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Metalloenzyme inhibitor, Metalloprotease inhibitor, Protease inhibitor

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiREACT_198590. Activation of Matrix Metalloproteinases.

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
ProteomesiUP000002494: Chromosome 10

Organism-specific databases

RGDi61312. Timp2.

Subcellular locationi

GO - Cellular componenti

  1. basement membrane Source: Ensembl
  2. cell surface Source: RGD
  3. extracellular space Source: RGD
  4. growth cone Source: RGD
  5. neuron projection Source: RGD
  6. neuronal cell body Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 26261 Publication
Add
BLAST
Chaini27 – 220194Metalloproteinase inhibitor 2
PRO_0000034337Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi27 ↔ 98 By similarity
Disulfide bondi29 ↔ 127 By similarity
Disulfide bondi39 ↔ 152 By similarity
Disulfide bondi154 ↔ 201 By similarity
Disulfide bondi159 ↔ 164 By similarity
Disulfide bondi172 ↔ 193 By similarity

Post-translational modificationi

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

Keywords - PTMi

Disulfide bond

Proteomic databases

PaxDbiP30121.

Expressioni

Gene expression databases

GenevestigatoriP30121.

Interactioni

Subunit structurei

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

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000004290.

Structurei

3D structure databases

ProteinModelPortaliP30121.
SMRiP30121. Positions 27-208.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini27 – 152126NTR
Add
BLAST

Region

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

Sequence similaritiesi

Contains 1 NTR domain.

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG243625.
GeneTreeiENSGT00390000004555.
HOGENOMiHOG000285981.
HOVERGENiHBG068749.
OMAiSAPEECL.
OrthoDBiEOG79GT74.
PhylomeDBiP30121.

Family and domain databases

Gene3Di3.90.370.10. 1 hit.
InterProiIPR001134. Netrin_domain.
IPR001820. Prot_inh_TIMP.
IPR008993. TIMP-like_OB-fold.
IPR015613. TIMP2.
IPR027465. TIMP_C_dom.
[Graphical view]
PANTHERiPTHR11844. PTHR11844. 1 hit.
PTHR11844:SF7. PTHR11844:SF7. 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

MGAAARSLRL ALGLLLLATL LRPADACSCS PVHPQQAFCN ADVVIRAKAV    50
SEKEVDSGND IYGNPIKRIQ YEIKQIKMFK GPDKDIEFIY TAPSSAVCGV 100
SLDVGGKKEY LIAGKAEGDG KMHITLCDFI VPWDTLSITQ KKSLNHRYQM 150
GCECKITRCP MIPCYISSPD ECLWMDWVTE KSINGHQAKF FACIKRSDGS 200
CAWYRGAAPP KQEFLDIEDP 220
Length:220
Mass (Da):24,356
Last modified:October 1, 1996 - v3
Checksum:i1C97A3F050C3AE7D
GO

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti7 – 71S → T in AAA21553. 1 Publication
Sequence conflicti153 – 1531E → Q in AAA21553. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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:
EMBL
GenBank
DDBJ
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 .
PIRi S45683.
RefSeqi NP_068824.1. NM_021989.2.
UniGenei Rn.10161.

3D structure databases

ProteinModelPortali P30121.
SMRi P30121. Positions 27-208.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

STRINGi 10116.ENSRNOP00000004290.

Protein family/group databases

MEROPSi I35.002.

Proteomic databases

PaxDbi P30121.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSRNOT00000004290 ; ENSRNOP00000004290 ; ENSRNOG00000003148 .
GeneIDi 29543.
KEGGi rno:29543.
UCSCi RGD:61312. rat.

Organism-specific databases

CTDi 7077.
RGDi 61312. Timp2.

Phylogenomic databases

eggNOGi NOG243625.
GeneTreei ENSGT00390000004555.
HOGENOMi HOG000285981.
HOVERGENi HBG068749.
OMAi SAPEECL.
OrthoDBi EOG79GT74.
PhylomeDBi P30121.

Enzyme and pathway databases

Reactomei REACT_198590. Activation of Matrix Metalloproteinases.

Miscellaneous databases

NextBioi 609549.
PROi P30121.

Gene expression databases

Genevestigatori P30121.

Family and domain databases

Gene3Di 3.90.370.10. 1 hit.
InterProi IPR001134. Netrin_domain.
IPR001820. Prot_inh_TIMP.
IPR008993. TIMP-like_OB-fold.
IPR015613. TIMP2.
IPR027465. TIMP_C_dom.
[Graphical view ]
PANTHERi PTHR11844. PTHR11844. 1 hit.
PTHR11844:SF7. PTHR11844:SF7. 1 hit.
Pfami PF00965. TIMP. 1 hit.
[Graphical view ]
SMARTi SM00206. NTR. 1 hit.
[Graphical view ]
SUPFAMi SSF50242. SSF50242. 1 hit.
PROSITEi PS50189. NTR. 1 hit.
PS00288. TIMP. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.

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: September 3, 2014
This is version 113 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

External Data

Dasty 3

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