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P12032

- TIMP1_MOUSE

UniProt

P12032 - TIMP1_MOUSE

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Protein

Metalloproteinase inhibitor 1

Gene

Timp1

Organism
Mus musculus (Mouse)
Status
Reviewed - 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 By similarity. 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.By similarity1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi25 – 251Zinc; via amino nitrogen and carbonyl oxygen; shared with metalloproteinase partnerBy similarity

GO - Molecular functioni

  1. cytokine activity Source: UniProtKB
  2. metal ion binding Source: UniProtKB-KW
  3. metalloendopeptidase inhibitor activity Source: UniProtKB

GO - Biological processi

  1. aging Source: Ensembl
  2. cell activation Source: Ensembl
  3. negative regulation of apoptotic process Source: Ensembl
  4. negative regulation of endopeptidase activity Source: UniProtKB
  5. negative regulation of membrane protein ectodomain proteolysis Source: Ensembl
  6. negative regulation of metalloenzyme activity Source: UniProtKB
  7. negative regulation of trophoblast cell migration Source: Ensembl
  8. positive regulation of cell proliferation Source: UniProtKB
  9. regulation of integrin-mediated signaling pathway Source: UniProtKB
  10. response to cytokine Source: Ensembl
  11. response to peptide hormone Source: Ensembl
  12. wound healing Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Growth factor, Metalloenzyme inhibitor, Metalloprotease inhibitor, Protease inhibitor

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiREACT_199000. Activation of Matrix Metalloproteinases.

Names & Taxonomyi

Protein namesi
Recommended name:
Metalloproteinase inhibitor 1
Alternative name(s):
Collagenase inhibitor 16C8 fibroblast
Erythroid-potentiating activity
Short name:
EPA
TPA-S1
TPA-induced protein
Tissue inhibitor of metalloproteinases 1
Short name:
TIMP-1
Gene namesi
Name:Timp1
Synonyms:Timp, Timp-1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome X

Organism-specific databases

MGIiMGI:98752. Timp1.

Subcellular locationi

Secreted 1 Publication

GO - Cellular componenti

  1. basement membrane Source: MGI
  2. extracellular space Source: UniProtKB
  3. extracellular vesicular exosome Source: Ensembl
  4. proteinaceous extracellular matrix Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2424Add
BLAST
Chaini25 – 205181Metalloproteinase inhibitor 1PRO_0000034325Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi25 ↔ 94PROSITE-ProRule annotation
Disulfide bondi27 ↔ 123PROSITE-ProRule annotation
Disulfide bondi37 ↔ 148PROSITE-ProRule annotation
Glycosylationi54 – 541N-linked (GlcNAc...)Sequence Analysis
Glycosylationi102 – 1021N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi151 ↔ 197PROSITE-ProRule annotation
Disulfide bondi156 ↔ 161PROSITE-ProRule annotation
Disulfide bondi169 ↔ 189PROSITE-ProRule annotation

Post-translational modificationi

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

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiP12032.
PaxDbiP12032.
PRIDEiP12032.

PTM databases

PhosphoSiteiP12032.

Expressioni

Tissue specificityi

Found in fetal and adult tissues. Highest levels are found in bone. Also found in lung, ovary and uterus.

Developmental stagei

Present in unfertilized eggs and at the zygote and cleavage stages. Levels increase at the blastocyst stage and with endoderm differentiation.1 Publication

Inductioni

Regulated by tumor promoters and mitogens through protein kinase C. Also induced by viruses.

Gene expression databases

BgeeiP12032.
CleanExiMM_TIMP1.
GenevestigatoriP12032.

Interactioni

Subunit structurei

Interacts with MMP1, MMP3, MMP10 and MMP13, but has only very low affinity for MMP14 By similarity. Interacts with CD63; identified in a complex with CD63 and ITGB1.By similarity1 Publication

Protein-protein interaction databases

MINTiMINT-4996416.
STRINGi10090.ENSMUSP00000110999.

Structurei

3D structure databases

ProteinModelPortaliP12032.
SMRiP12032. Positions 25-202.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini25 – 148124NTRPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni25 – 295Involved in metalloproteinase-bindingBy similarity
Regioni91 – 922Involved in metalloproteinase-bindingBy similarity

Sequence similaritiesi

Contains 1 NTR domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG259409.
GeneTreeiENSGT00390000004555.
HOGENOMiHOG000285981.
HOVERGENiHBG068749.
InParanoidiP12032.
KOiK16451.
OMAiDKGFQSR.
OrthoDBiEOG79GT74.
PhylomeDBiP12032.
TreeFamiTF317409.

Family and domain databases

Gene3Di3.90.370.10. 1 hit.
InterProiIPR001134. Netrin_domain.
IPR001820. Prot_inh_TIMP.
IPR008993. TIMP-like_OB-fold.
IPR015611. TIMP1.
IPR027465. TIMP_C_dom.
[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.

P12032-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MMAPFASLAS GILLLLSLIA SSKACSCAPP HPQTAFCNSD LVIRAKFMGS
60 70 80 90 100
PEINETTLYQ RYKIKMTKML KGFKAVGNAA DIRYAYTPVM ESLCGYAHKS
110 120 130 140 150
QNRSEEFLIT GRLRNGNLHI SACSFLVPWR TLSPAQQRAF SKTYSAGCGV
160 170 180 190 200
CTVFPCLSIP CKLESDTHCL WTDQVLVGSE DYQSRHFACL PRNPGLCTWR

SLGAR
Length:205
Mass (Da):22,628
Last modified:May 1, 1991 - v2
Checksum:iFACA952D49A50FD7
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti52 – 521E → R in AAB42179. (PubMed:3034603)Curated
Sequence conflicti66 – 661M → MM in AAB42179. (PubMed:3034603)Curated
Sequence conflicti117 – 1182NL → KF in AAB42179. (PubMed:3034603)Curated
Sequence conflicti121 – 1211S → N in AAB42179. (PubMed:3034603)Curated
Sequence conflicti139 – 1391A → V(PubMed:3034603)Curated
Sequence conflicti143 – 1431T → KN(PubMed:3034603)Curated
Sequence conflicti194 – 1941P → L(PubMed:3034603)Curated
Sequence conflicti194 – 1941P → L(PubMed:6179042)Curated

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M28312
, M28308, M28309, M28310, M28311 Genomic DNA. Translation: AAB42179.1.
X04684 mRNA. Translation: CAA28387.1.
M17243 mRNA. Translation: AAA40471.1.
BC008107 mRNA. Translation: AAH08107.1.
BC034260 mRNA. Translation: AAH34260.1.
BC051260 mRNA. Translation: AAH51260.1.
V00755 mRNA. Translation: CAA24132.1.
CCDSiCCDS30046.1.
PIRiA26917. A26106.
RefSeqiNP_001037849.1. NM_001044384.1.
NP_035723.2. NM_011593.2.
UniGeneiMm.8245.

Genome annotation databases

EnsembliENSMUST00000009530; ENSMUSP00000009530; ENSMUSG00000001131.
ENSMUST00000115342; ENSMUSP00000110999; ENSMUSG00000001131.
GeneIDi21857.
KEGGimmu:21857.
UCSCiuc009sty.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M28312
, M28308 , M28309 , M28310 , M28311 Genomic DNA. Translation: AAB42179.1 .
X04684 mRNA. Translation: CAA28387.1 .
M17243 mRNA. Translation: AAA40471.1 .
BC008107 mRNA. Translation: AAH08107.1 .
BC034260 mRNA. Translation: AAH34260.1 .
BC051260 mRNA. Translation: AAH51260.1 .
V00755 mRNA. Translation: CAA24132.1 .
CCDSi CCDS30046.1.
PIRi A26917. A26106.
RefSeqi NP_001037849.1. NM_001044384.1.
NP_035723.2. NM_011593.2.
UniGenei Mm.8245.

3D structure databases

ProteinModelPortali P12032.
SMRi P12032. Positions 25-202.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

MINTi MINT-4996416.
STRINGi 10090.ENSMUSP00000110999.

PTM databases

PhosphoSitei P12032.

Proteomic databases

MaxQBi P12032.
PaxDbi P12032.
PRIDEi P12032.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000009530 ; ENSMUSP00000009530 ; ENSMUSG00000001131 .
ENSMUST00000115342 ; ENSMUSP00000110999 ; ENSMUSG00000001131 .
GeneIDi 21857.
KEGGi mmu:21857.
UCSCi uc009sty.1. mouse.

Organism-specific databases

CTDi 7076.
MGIi MGI:98752. Timp1.

Phylogenomic databases

eggNOGi NOG259409.
GeneTreei ENSGT00390000004555.
HOGENOMi HOG000285981.
HOVERGENi HBG068749.
InParanoidi P12032.
KOi K16451.
OMAi DKGFQSR.
OrthoDBi EOG79GT74.
PhylomeDBi P12032.
TreeFami TF317409.

Enzyme and pathway databases

Reactomei REACT_199000. Activation of Matrix Metalloproteinases.

Miscellaneous databases

NextBioi 301350.
PROi P12032.
SOURCEi Search...

Gene expression databases

Bgeei P12032.
CleanExi MM_TIMP1.
Genevestigatori P12032.

Family and domain databases

Gene3Di 3.90.370.10. 1 hit.
InterProi IPR001134. Netrin_domain.
IPR001820. Prot_inh_TIMP.
IPR008993. TIMP-like_OB-fold.
IPR015611. TIMP1.
IPR027465. TIMP_C_dom.
[Graphical view ]
PANTHERi PTHR11844. PTHR11844. 1 hit.
PTHR11844:SF20. PTHR11844:SF20. 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. "Characterization and expression of a murine gene homologous to human EPA/TIMP: a virus-induced gene in the mouse."
    Gewert D.R., Coulombe B., Castelino M., Skup D., Williams B.R.G.
    EMBO J. 6:651-657(1987) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  2. "A growth-responsive gene (16C8) in normal mouse fibroblasts homologous to a human collagenase inhibitor with erythroid-potentiating activity: evidence for inducible and constitutive transcripts."
    Edwards D.R., Waterhouse P., Holman M.L., Denhardt D.T.
    Nucleic Acids Res. 14:8863-8878(1986) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Fibroblast.
  3. "Molecular cloning of gene sequences regulated by tumor promoters and mitogens through protein kinase C."
    Johnson M.D., Housey G.M., Kirschmeier P.T., Weinstein I.B.
    Mol. Cell. Biol. 7:2821-2829(1987) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: C3H.
  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].
    Strain: FVB/N.
    Tissue: Mammary gland and Osteoblast.
  5. "Genes for extracellular-matrix-degrading metalloproteinases and their inhibitor, TIMP, are expressed during early mammalian development."
    Brenner C.A., Adler R.R., Rappolee D.A., Pedersen R.A., Werb Z.
    Genes Dev. 3:848-859(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: PARTIAL NUCLEOTIDE SEQUENCE, DEVELOPMENTAL STAGE.
    Tissue: Embryo.
  6. "Molecular cloning of partial cDNA copies of two distinct mouse IFN-beta mRNAs."
    Skup D., Windass J.D., Sor F.S., George H., Williams B.R., Fukuhara H., de Maeyer-Guignard J., de Maeyer E.
    Nucleic Acids Res. 10:3069-3084(1982) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE OF 168-205.
  7. "Timp1 interacts with beta-1 integrin and CD63 along melanoma genesis and confers anoikis resistance by activating PI3-K signaling pathway independently of Akt phosphorylation."
    Toricelli M., Melo F.H., Peres G.B., Silva D.C., Jasiulionis M.G.
    Mol. Cancer 12:22-22(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH CD63, IDENTIFICATION IN A COMPLEX WITH CD63 AND ITGB1.

Entry informationi

Entry nameiTIMP1_MOUSE
AccessioniPrimary (citable) accession number: P12032
Secondary accession number(s): P20064, Q61720
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1989
Last sequence update: May 1, 1991
Last modified: October 29, 2014
This is version 138 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, 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

External Data

Dasty 3