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Protein

Metalloproteinase inhibitor 1

Gene

Timp1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Metalloproteinase inhibitor that functions by forming one to one complexes with target metalloproteinases, such as collagenases, and irreversibly inactivates them by binding to their catalytic zinc cofactor. Acts on MMP1, MMP2, MMP3, MMP7, MMP8, MMP9, MMP10, MMP11, MMP12, MMP13 and MMP16. Does not act on MMP14. Also functions as a growth factor that regulates cell differentiation, migration and cell death and activates cellular signaling cascades via CD63 and ITGB1. Plays a role in integrin signaling. Also stimulates steroidogenesis by Leydig and ovarian granuloma cells; procathepsin L is required for maximal activity.2 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi24 – 241Zinc; via amino nitrogen and carbonyl oxygen; shared with metalloproteinase partnerBy similarity

GO - Molecular functioni

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

GO - Biological processi

  • aging Source: RGD
  • cartilage development Source: RGD
  • cell activation Source: RGD
  • negative regulation of apoptotic process Source: RGD
  • negative regulation of endopeptidase activity Source: UniProtKB
  • negative regulation of membrane protein ectodomain proteolysis Source: Ensembl
  • negative regulation of metalloenzyme activity Source: UniProtKB
  • negative regulation of trophoblast cell migration Source: Ensembl
  • positive regulation of cell proliferation Source: UniProtKB
  • regulation of integrin-mediated signaling pathway Source: UniProtKB
  • response to cytokine Source: RGD
  • response to organic substance Source: RGD
  • response to peptide hormone Source: RGD
  • steroid biosynthetic process Source: UniProtKB-KW
  • wound healing Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Growth factor, Metalloenzyme inhibitor, Metalloprotease inhibitor, Protease inhibitor

Keywords - Biological processi

Steroidogenesis

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-RNO-114608. Platelet degranulation.
R-RNO-1592389. Activation of Matrix Metalloproteinases.

Names & Taxonomyi

Protein namesi
Recommended name:
Metalloproteinase inhibitor 1
Alternative name(s):
Tissue inhibitor of metalloproteinases 1
Short name:
TIMP-1
Gene namesi
Name:Timp1
Synonyms:Timp-1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome X

Organism-specific databases

RGDi621675. Timp1.

Subcellular locationi

GO - Cellular componenti

  • basement membrane Source: Ensembl
  • extracellular exosome Source: Ensembl
  • extracellular matrix Source: RGD
  • extracellular space Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 23232 PublicationsAdd
BLAST
Chaini24 – 217194Metalloproteinase inhibitor 1PRO_0000034329Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi24 ↔ 93PROSITE-ProRule annotation
Disulfide bondi26 ↔ 122PROSITE-ProRule annotation
Disulfide bondi36 ↔ 147PROSITE-ProRule annotation
Glycosylationi77 – 771N-linked (GlcNAc...)Sequence analysis
Glycosylationi101 – 1011N-linked (GlcNAc...)Sequence analysis
Disulfide bondi150 ↔ 197PROSITE-ProRule annotation
Disulfide bondi155 ↔ 160PROSITE-ProRule annotation
Disulfide bondi168 ↔ 189PROSITE-ProRule annotation
Modified residuei178 – 1781PhosphoserineBy similarity

Post-translational modificationi

The activity of TIMP1 is dependent on the presence of disulfide bonds.By similarity
N-glycosylated.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiP30120.
PRIDEiP30120.

Expressioni

Inductioni

By follicle-stimulating hormone (FSH).1 Publication

Gene expression databases

GenevisibleiP30120. RN.

Interactioni

Subunit structurei

Interacts with MMP1, MMP3, MMP10 and MMP13, but has only very low affinity for MMP14. Interacts with CD63; identified in a complex with CD63 and ITGB1 (By similarity).By similarity

GO - Molecular functioni

  • cytokine activity Source: UniProtKB
  • protease binding Source: RGD

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000013745.

Structurei

3D structure databases

ProteinModelPortaliP30120.
SMRiP30120. Positions 24-202.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini24 – 147124NTRPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni24 – 285Involved in metalloproteinase-bindingBy similarity
Regioni90 – 912Involved in metalloproteinase-bindingBy similarity

Sequence similaritiesi

Contains 1 NTR domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG4745. Eukaryota.
ENOG41103NU. LUCA.
GeneTreeiENSGT00390000004555.
HOGENOMiHOG000285981.
HOVERGENiHBG068749.
InParanoidiP30120.
KOiK16451.
OMAiTYSAGCG.
OrthoDBiEOG79GT74.
PhylomeDBiP30120.
TreeFamiTF317409.

Family and domain databases

Gene3Di3.90.370.10. 1 hit.
InterProiIPR001134. Netrin_domain.
IPR001820. TIMP.
IPR008993. TIMP-like_OB-fold.
IPR015611. TIMP1.
IPR027465. TIMP_C.
IPR030490. TIMP_CS.
[Graphical view]
PANTHERiPTHR11844. PTHR11844. 1 hit.
PTHR11844:SF20. PTHR11844:SF20. 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.

P30120-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAPFASLASG ILLLLSLIAS SKACSCAPTH PQTAFCNSDL VIRAKFMGSP
60 70 80 90 100
EIIETTLYQR YEIKMTKMLK GFDAVGNATG FRFAYTPAME SLCGYVHKSQ
110 120 130 140 150
NRSEEFLIAG RLRNGNLHIT ACSFLVPWHN LSPAQQKAFV KTYSAGCGVC
160 170 180 190 200
TVFPCSAIPC KLESDSHCLW TDQILMGSEK GYQSDHFACL PRNPDLCTWQ
210
YLGVSMTRSL PLAKAEA
Length:217
Mass (Da):23,794
Last modified:November 1, 1995 - v2
Checksum:iC5AC240A61C1A1DF
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti80 – 812GF → DI in AAB08483 (PubMed:8707259).Curated
Sequence conflicti88 – 881A → V in AAA51653 (PubMed:7777858).Curated
Sequence conflicti103 – 1031S → R in AAB08483 (PubMed:8707259).Curated
Sequence conflicti129 – 1302HN → AS in AAB08483 (PubMed:8707259).Curated
Sequence conflicti136 – 1405QKAFV → RKGLT in AAB08483 (PubMed:8707259).Curated
Sequence conflicti149 – 1491V → L in AAA51653 (PubMed:7777858).Curated
Sequence conflicti157 – 1571A → V in AAB08483 (PubMed:8707259).Curated
Sequence conflicti166 – 1661S → T in AAB08483 (PubMed:8707259).Curated
Sequence conflicti185 – 1873DHF → RHL in AAB08483 (PubMed:8707259).Curated
Sequence conflicti195 – 1951D → G in AAB08483 (PubMed:8707259).Curated
Sequence conflicti201 – 2011Y → S in AAB08483 (PubMed:8707259).Curated
Sequence conflicti204 – 2052VS → SR in AAB08483 (PubMed:8707259).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U06179 mRNA. Translation: AAA85780.1.
L31883 mRNA. Translation: AAA85373.1.
AY550026 mRNA. Translation: AAS55641.1.
BC099821 mRNA. Translation: AAH99821.1.
L29512 mRNA. Translation: AAB08483.1.
U16022 mRNA. Translation: AAA51653.1. Sequence problems.
PIRiJC2557.
RefSeqiNP_446271.1. NM_053819.1.
XP_006256670.1. XM_006256608.2.
XP_008771256.1. XM_008773034.1.
UniGeneiRn.25754.

Genome annotation databases

EnsembliENSRNOT00000013745; ENSRNOP00000013745; ENSRNOG00000010208.
GeneIDi116510.
KEGGirno:116510.
UCSCiRGD:621675. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U06179 mRNA. Translation: AAA85780.1.
L31883 mRNA. Translation: AAA85373.1.
AY550026 mRNA. Translation: AAS55641.1.
BC099821 mRNA. Translation: AAH99821.1.
L29512 mRNA. Translation: AAB08483.1.
U16022 mRNA. Translation: AAA51653.1. Sequence problems.
PIRiJC2557.
RefSeqiNP_446271.1. NM_053819.1.
XP_006256670.1. XM_006256608.2.
XP_008771256.1. XM_008773034.1.
UniGeneiRn.25754.

3D structure databases

ProteinModelPortaliP30120.
SMRiP30120. Positions 24-202.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000013745.

Proteomic databases

PaxDbiP30120.
PRIDEiP30120.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000013745; ENSRNOP00000013745; ENSRNOG00000010208.
GeneIDi116510.
KEGGirno:116510.
UCSCiRGD:621675. rat.

Organism-specific databases

CTDi7076.
RGDi621675. Timp1.

Phylogenomic databases

eggNOGiKOG4745. Eukaryota.
ENOG41103NU. LUCA.
GeneTreeiENSGT00390000004555.
HOGENOMiHOG000285981.
HOVERGENiHBG068749.
InParanoidiP30120.
KOiK16451.
OMAiTYSAGCG.
OrthoDBiEOG79GT74.
PhylomeDBiP30120.
TreeFamiTF317409.

Enzyme and pathway databases

ReactomeiR-RNO-114608. Platelet degranulation.
R-RNO-1592389. Activation of Matrix Metalloproteinases.

Miscellaneous databases

NextBioi619133.
PROiP30120.

Gene expression databases

GenevisibleiP30120. RN.

Family and domain databases

Gene3Di3.90.370.10. 1 hit.
InterProiIPR001134. Netrin_domain.
IPR001820. TIMP.
IPR008993. TIMP-like_OB-fold.
IPR015611. TIMP1.
IPR027465. TIMP_C.
IPR030490. TIMP_CS.
[Graphical view]
PANTHERiPTHR11844. PTHR11844. 1 hit.
PTHR11844:SF20. PTHR11844:SF20. 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 of the cDNA encoding rat tissue inhibitor of metalloproteinase 1 (TIMP-1), amino acid comparison with other TIMPs, and gene expression in rat tissues."
    Okada A., Garnier J.-M., Vicaire S., Basset P.
    Gene 147:301-302(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: Wistar.
    Tissue: Dorsal skin.
  2. "Analysis of the cDNA encoding rat tissue inhibitor of metalloproteinases-1."
    Gibbons K.L., O'Grady R.L., Piper A.A.
    Submitted (JAN-1996) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Mammary gland.
  3. "Rat TIMP-1 mRNA sequence."
    Dai W.-J., Jiang H.-C., Fu S.-B.
    Submitted (FEB-2004) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  4. "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: Prostate.
  5. "Tissue inhibitor of metalloproteinase-1 messenger RNA expression is enhanced relative to interstitial collagenase messenger RNA in experimental liver injury and fibrosis."
    Iredale J.P., Benyon R.C., Arthur M.J.P., Ferris W.F., Alcolado R., Winwood P.J., Clark N., Murphy G.
    Hepatology 24:176-184(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 30-205.
    Tissue: Liver.
  6. "Identification of a stimulator of steroid hormone synthesis isolated from testis."
    Boujrad N., Ogwuegbu S.O., Garnier M., Lee C.-H., Martin B.M., Papadopoulos V.
    Science 268:1609-1612(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 39-156, PROTEIN SEQUENCE OF 24-38, INDUCTION, FUNCTION, SUBCELLULAR LOCATION.
    Strain: Sprague-Dawley.
    Tissue: Sertoli cell.
  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 24-45, FUNCTION, SUBCELLULAR LOCATION, GLYCOSYLATION.

Entry informationi

Entry nameiTIMP1_RAT
AccessioniPrimary (citable) accession number: P30120
Secondary accession number(s): P70533, Q53YM7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: November 1, 1995
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. 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.