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Protein

Metalloproteinase inhibitor 1

Gene

Timp1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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)DescriptionActionsGraphical viewLength
Metal bindingi25Zinc; via amino nitrogen and carbonyl oxygen; shared with metalloproteinase partnerBy similarity1
Sitei38Involved in metalloproteinase-bindingBy similarity1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionGrowth factor, Metalloenzyme inhibitor, Metalloprotease inhibitor, Protease inhibitor
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-114608 Platelet degranulation
R-MMU-1592389 Activation of Matrix Metalloproteinases
R-MMU-381426 Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-MMU-8957275 Post-translational protein phosphorylation

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome X

Organism-specific databases

MGIiMGI:98752 Timp1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 24Add BLAST24
ChainiPRO_000003432525 – 205Metalloproteinase inhibitor 1Add BLAST181

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi25 ↔ 94PROSITE-ProRule annotation
Disulfide bondi27 ↔ 123PROSITE-ProRule annotation
Disulfide bondi37 ↔ 148PROSITE-ProRule annotation
Glycosylationi54N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi102N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi151 ↔ 197PROSITE-ProRule annotation
Disulfide bondi156 ↔ 161PROSITE-ProRule annotation
Disulfide bondi169 ↔ 189PROSITE-ProRule annotation
Modified residuei179PhosphoserineBy similarity1

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, Phosphoprotein

Proteomic databases

MaxQBiP12032
PaxDbiP12032
PeptideAtlasiP12032
PRIDEiP12032

PTM databases

PhosphoSitePlusiP12032

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

BgeeiENSMUSG00000001131 Expressed in 207 organ(s), highest expression level in cumulus cell
CleanExiMM_TIMP1
GenevisibleiP12032 MM

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

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000009530

Structurei

3D structure databases

ProteinModelPortaliP12032
SMRiP12032
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini25 – 148NTRPROSITE-ProRule annotationAdd BLAST124

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni25 – 28Involved in metalloproteinase-bindingBy similarity4
Regioni91 – 92Involved in metalloproteinase-bindingBy similarity2

Sequence similaritiesi

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG4745 Eukaryota
ENOG41103NU LUCA
GeneTreeiENSGT00390000004555
HOGENOMiHOG000285981
HOVERGENiHBG068749
InParanoidiP12032
KOiK16451
OMAiWRRTQLY
OrthoDBiEOG091G0NIC
PhylomeDBiP12032
TreeFamiTF317409

Family and domain databases

Gene3Di3.90.370.10, 1 hit
InterProiView protein in InterPro
IPR001134 Netrin_domain
IPR001820 TIMP
IPR008993 TIMP-like_OB-fold
IPR015611 TIMP1
IPR027465 TIMP_C
IPR030490 TIMP_CS
PANTHERiPTHR11844 PTHR11844, 1 hit
PTHR11844:SF20 PTHR11844:SF20, 1 hit
PfamiView protein in Pfam
PF00965 TIMP, 1 hit
SMARTiView protein in SMART
SM00206 NTR, 1 hit
SUPFAMiSSF50242 SSF50242, 1 hit
PROSITEiView protein in PROSITE
PS50189 NTR, 1 hit
PS00288 TIMP, 1 hit

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)DescriptionActionsGraphical viewLength
Sequence conflicti52E → R in AAB42179 (PubMed:3034603).Curated1
Sequence conflicti66M → MM in AAB42179 (PubMed:3034603).Curated1
Sequence conflicti117 – 118NL → KF in AAB42179 (PubMed:3034603).Curated2
Sequence conflicti121S → N in AAB42179 (PubMed:3034603).Curated1
Sequence conflicti139A → V (PubMed:3034603).Curated1
Sequence conflicti143T → KN (PubMed:3034603).Curated1
Sequence conflicti194P → L (PubMed:3034603).Curated1
Sequence conflicti194P → L (PubMed:6179042).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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

3D structure databases

ProteinModelPortaliP12032
SMRiP12032
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000009530

PTM databases

PhosphoSitePlusiP12032

Proteomic databases

MaxQBiP12032
PaxDbiP12032
PeptideAtlasiP12032
PRIDEiP12032

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi7076
MGIiMGI:98752 Timp1

Phylogenomic databases

eggNOGiKOG4745 Eukaryota
ENOG41103NU LUCA
GeneTreeiENSGT00390000004555
HOGENOMiHOG000285981
HOVERGENiHBG068749
InParanoidiP12032
KOiK16451
OMAiWRRTQLY
OrthoDBiEOG091G0NIC
PhylomeDBiP12032
TreeFamiTF317409

Enzyme and pathway databases

ReactomeiR-MMU-114608 Platelet degranulation
R-MMU-1592389 Activation of Matrix Metalloproteinases
R-MMU-381426 Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-MMU-8957275 Post-translational protein phosphorylation

Miscellaneous databases

PROiPR:P12032
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000001131 Expressed in 207 organ(s), highest expression level in cumulus cell
CleanExiMM_TIMP1
GenevisibleiP12032 MM

Family and domain databases

Gene3Di3.90.370.10, 1 hit
InterProiView protein in InterPro
IPR001134 Netrin_domain
IPR001820 TIMP
IPR008993 TIMP-like_OB-fold
IPR015611 TIMP1
IPR027465 TIMP_C
IPR030490 TIMP_CS
PANTHERiPTHR11844 PTHR11844, 1 hit
PTHR11844:SF20 PTHR11844:SF20, 1 hit
PfamiView protein in Pfam
PF00965 TIMP, 1 hit
SMARTiView protein in SMART
SM00206 NTR, 1 hit
SUPFAMiSSF50242 SSF50242, 1 hit
PROSITEiView protein in PROSITE
PS50189 NTR, 1 hit
PS00288 TIMP, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiTIMP1_MOUSE
AccessioniPrimary (citable) accession number: P12032
Secondary accession number(s): P20064, Q61720
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1989
Last sequence update: May 1, 1991
Last modified: November 7, 2018
This is version 168 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
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Main funding by: National Institutes of Health

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