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Protein

Metalloproteinase inhibitor 1

Gene

Timp1

Organism
Mus musculus (Mouse)
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 (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

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Growth factor, Metalloenzyme inhibitor, Metalloprotease inhibitor, Protease inhibitor

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-114608. Platelet degranulation.
R-MMU-1592389. 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
Proteomesi
  • UP000000589 Componenti: Chromosome X

Organism-specific databases

MGIiMGI:98752. Timp1.

Subcellular locationi

  • Secreted 1 Publication

GO - Cellular componenti

  • basement membrane Source: MGI
  • extracellular exosome Source: MGI
  • extracellular space Source: UniProtKB
  • proteinaceous extracellular matrix Source: MGI
Complete GO annotation...

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...)Sequence analysis1
Glycosylationi102N-linked (GlcNAc...)Sequence 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.
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

MINTiMINT-4996416.
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 – 29Involved in metalloproteinase-bindingBy similarity5
Regioni91 – 92Involved in metalloproteinase-bindingBy similarity2

Sequence similaritiesi

Contains 1 NTR domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG4745. Eukaryota.
ENOG41103NU. LUCA.
GeneTreeiENSGT00390000004555.
HOGENOMiHOG000285981.
HOVERGENiHBG068749.
InParanoidiP12032.
KOiK16451.
OMAiTYSAGCG.
OrthoDBiEOG091G0NIC.
PhylomeDBiP12032.
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.

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.

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

MINTiMINT-4996416.
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.
OMAiTYSAGCG.
OrthoDBiEOG091G0NIC.
PhylomeDBiP12032.
TreeFamiTF317409.

Enzyme and pathway databases

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

Miscellaneous databases

PROiP12032.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000001131.
CleanExiMM_TIMP1.
GenevisibleiP12032. MM.

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...

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: November 2, 2016
This is version 153 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

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.