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Protein

Metalloproteinase inhibitor 1

Gene

TIMP1

Organism
Homo sapiens (Human)
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. Mediates erythropoiesis in vitro; but, unlike IL3, it is species-specific, stimulating the growth and differentiation of only human and murine erythroid progenitors.12 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi24Zinc; via amino nitrogen and carbonyl oxygen; shared with metalloproteinase partner1

GO - Molecular functioni

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

GO - Biological processi

  • aging Source: Ensembl
  • cartilage development Source: Ensembl
  • cell activation Source: Ensembl
  • extracellular matrix disassembly Source: Reactome
  • negative regulation of apoptotic process Source: Ensembl
  • negative regulation of catalytic activity Source: UniProtKB
  • negative regulation of endopeptidase activity Source: UniProtKB
  • negative regulation of membrane protein ectodomain proteolysis Source: UniProtKB
  • negative regulation of trophoblast cell migration Source: BHF-UCL
  • platelet degranulation Source: Reactome
  • positive regulation of cell proliferation Source: UniProtKB
  • regulation of integrin-mediated signaling pathway Source: UniProtKB
  • response to cytokine Source: GO_Central
  • response to hormone Source: GO_Central
  • response to peptide hormone Source: Ensembl
  • 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

BioCyciZFISH:ENSG00000102265-MONOMER.
ReactomeiR-HSA-114608. Platelet degranulation.
R-HSA-1592389. Activation of Matrix Metalloproteinases.

Protein family/group databases

MEROPSiI35.001.

Names & Taxonomyi

Protein namesi
Recommended name:
Metalloproteinase inhibitor 1
Alternative name(s):
Erythroid-potentiating activity
Short name:
EPA
Fibroblast collagenase inhibitor
Short name:
Collagenase inhibitor
Tissue inhibitor of metalloproteinases 1
Short name:
TIMP-1
Gene namesi
Name:TIMP1
Synonyms:CLGI, TIMP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome X

Organism-specific databases

HGNCiHGNC:11820. TIMP1.

Subcellular locationi

GO - Cellular componenti

  • basement membrane Source: Ensembl
  • extracellular exosome Source: UniProtKB
  • extracellular region Source: UniProtKB
  • extracellular space Source: UniProtKB
  • platelet alpha granule lumen Source: Reactome
  • proteinaceous extracellular matrix Source: GO_Central
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi25T → E, G, K, Q or R: Reduced interaction with metalloproteinase. 1 Publication1
Mutagenesisi25T → V: Normal interaction with metalloproteinase. 1 Publication1
Mutagenesisi30H → A: Nearly abolishes metalloproteinase inhibition. 1 Publication1
Mutagenesisi32Q → A: Nearly abolishes metalloproteinase inhibition. 1 Publication1
Mutagenesisi121T → L: Decreases protein flexibility and increases affinity for MMP14. 1 Publication1

Organism-specific databases

DisGeNETi7076.
OpenTargetsiENSG00000102265.
PharmGKBiPA36526.

Polymorphism and mutation databases

BioMutaiTIMP1.
DMDMi135850.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 236 PublicationsAdd BLAST23
ChainiPRO_000003432324 – 207Metalloproteinase inhibitor 1Add BLAST184

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi24 ↔ 93PROSITE-ProRule annotation1 Publication
Disulfide bondi26 ↔ 1225 Publications
Disulfide bondi36 ↔ 1475 Publications
GlycosylationiCAR_00000253N-linked (GlcNAc...) (complex)4 Publications1
GlycosylationiCAR_000003101N-linked (GlcNAc...)1 Publication1
Disulfide bondi150 ↔ 1975 Publications
Disulfide bondi155 ↔ 1605 Publications
Disulfide bondi168 ↔ 1895 Publications
Modified residuei178Phosphoserine; by FAM20C1 Publication1

Post-translational modificationi

The activity of TIMP1 is dependent on the presence of disulfide bonds.5 Publications
N-glycosylated.7 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

EPDiP01033.
PaxDbiP01033.
PeptideAtlasiP01033.
PRIDEiP01033.

PTM databases

iPTMnetiP01033.
PhosphoSitePlusiP01033.
SwissPalmiP01033.
UniCarbKBiP01033.

Miscellaneous databases

PMAP-CutDBP01033.

Expressioni

Tissue specificityi

Detected in rheumatoid synovial fluid (at protein level).1 Publication

Gene expression databases

BgeeiENSG00000102265.
CleanExiHS_TIMP1.
ExpressionAtlasiP01033. baseline and differential.
GenevisibleiP01033. HS.

Organism-specific databases

HPAiCAB022360.
HPA053417.

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 ITGB1.10 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CD63P089625EBI-712536,EBI-762053
MMP9P147802EBI-712536,EBI-1382326

GO - Molecular functioni

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

Protein-protein interaction databases

BioGridi112932. 12 interactors.
DIPiDIP-1107N.
IntActiP01033. 6 interactors.
MINTiMINT-2981826.
STRINGi9606.ENSP00000218388.

Structurei

Secondary structure

1207
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi31 – 37Combined sources7
Beta strandi39 – 46Combined sources8
Beta strandi57 – 70Combined sources14
Helixi72 – 74Combined sources3
Turni77 – 79Combined sources3
Beta strandi83 – 89Combined sources7
Helixi90 – 92Combined sources3
Beta strandi105 – 113Combined sources9
Beta strandi116 – 118Combined sources3
Beta strandi125 – 127Combined sources3
Helixi128 – 130Combined sources3
Helixi133 – 140Combined sources8
Helixi143 – 145Combined sources3
Turni146 – 149Combined sources4
Beta strandi151 – 154Combined sources4
Beta strandi157 – 159Combined sources3
Beta strandi167 – 170Combined sources4
Helixi172 – 176Combined sources5
Beta strandi177 – 181Combined sources5
Helixi182 – 186Combined sources5
Beta strandi188 – 193Combined sources6
Beta strandi196 – 200Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1D2BNMR-A24-149[»]
1LQNmodel-A1-207[»]
1OO9NMR-B24-149[»]
1UEAX-ray2.80B/D24-207[»]
2J0TX-ray2.54D/E/F24-149[»]
3MA2X-ray2.05B/C24-148[»]
3V96X-ray1.90A24-207[»]
ProteinModelPortaliP01033.
SMRiP01033.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP01033.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini24 – 147NTRPROSITE-ProRule annotationAdd BLAST124

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni24 – 28Involved in metalloproteinase-binding5
Regioni90 – 91Involved in metalloproteinase-binding2

Sequence similaritiesi

Contains 1 NTR domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG4745. Eukaryota.
ENOG41103NU. LUCA.
GeneTreeiENSGT00390000004555.
HOGENOMiHOG000285981.
HOVERGENiHBG068749.
InParanoidiP01033.
KOiK16451.
OMAiTYSAGCG.
OrthoDBiEOG091G0NIC.
PhylomeDBiP01033.
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.

P01033-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAPFEPLASG ILLLLWLIAP SRACTCVPPH PQTAFCNSDL VIRAKFVGTP
60 70 80 90 100
EVNQTTLYQR YEIKMTKMYK GFQALGDAAD IRFVYTPAME SVCGYFHRSH
110 120 130 140 150
NRSEEFLIAG KLQDGLLHIT TCSFVAPWNS LSLAQRRGFT KTYTVGCEEC
160 170 180 190 200
TVFPCLSIPC KLQSGTHCLW TDQLLQGSEK GFQSRHLACL PREPGLCTWQ

SLRSQIA
Length:207
Mass (Da):23,171
Last modified:July 21, 1986 - v1
Checksum:i5AE4F90FFAB2ECDC
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti23A → P in CAA26443 (PubMed:3839290).Curated1
Sequence conflicti44A → P in BAA01913 (Ref. 12) Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X03124 mRNA. Translation: CAA26902.1.
X02598 mRNA. Translation: CAA26443.1.
M12670 mRNA. Translation: AAA52436.1.
M59906 mRNA. Translation: AAA63234.1.
S68252 mRNA. Translation: AAD14009.1.
BC000866 mRNA. Translation: AAH00866.1.
L47361 Genomic DNA. Translation: AAA75558.1.
D11139 Genomic DNA. Translation: BAA01913.1.
CCDSiCCDS14281.1.
PIRiA93372. ZYHUEP.
RefSeqiNP_003245.1. NM_003254.2.
UniGeneiHs.522632.

Genome annotation databases

EnsembliENST00000218388; ENSP00000218388; ENSG00000102265.
GeneIDi7076.
KEGGihsa:7076.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X03124 mRNA. Translation: CAA26902.1.
X02598 mRNA. Translation: CAA26443.1.
M12670 mRNA. Translation: AAA52436.1.
M59906 mRNA. Translation: AAA63234.1.
S68252 mRNA. Translation: AAD14009.1.
BC000866 mRNA. Translation: AAH00866.1.
L47361 Genomic DNA. Translation: AAA75558.1.
D11139 Genomic DNA. Translation: BAA01913.1.
CCDSiCCDS14281.1.
PIRiA93372. ZYHUEP.
RefSeqiNP_003245.1. NM_003254.2.
UniGeneiHs.522632.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1D2BNMR-A24-149[»]
1LQNmodel-A1-207[»]
1OO9NMR-B24-149[»]
1UEAX-ray2.80B/D24-207[»]
2J0TX-ray2.54D/E/F24-149[»]
3MA2X-ray2.05B/C24-148[»]
3V96X-ray1.90A24-207[»]
ProteinModelPortaliP01033.
SMRiP01033.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112932. 12 interactors.
DIPiDIP-1107N.
IntActiP01033. 6 interactors.
MINTiMINT-2981826.
STRINGi9606.ENSP00000218388.

Protein family/group databases

MEROPSiI35.001.

PTM databases

iPTMnetiP01033.
PhosphoSitePlusiP01033.
SwissPalmiP01033.
UniCarbKBiP01033.

Polymorphism and mutation databases

BioMutaiTIMP1.
DMDMi135850.

Proteomic databases

EPDiP01033.
PaxDbiP01033.
PeptideAtlasiP01033.
PRIDEiP01033.

Protocols and materials databases

DNASUi7076.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000218388; ENSP00000218388; ENSG00000102265.
GeneIDi7076.
KEGGihsa:7076.

Organism-specific databases

CTDi7076.
DisGeNETi7076.
GeneCardsiTIMP1.
HGNCiHGNC:11820. TIMP1.
HPAiCAB022360.
HPA053417.
MIMi305370. gene.
neXtProtiNX_P01033.
OpenTargetsiENSG00000102265.
PharmGKBiPA36526.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4745. Eukaryota.
ENOG41103NU. LUCA.
GeneTreeiENSGT00390000004555.
HOGENOMiHOG000285981.
HOVERGENiHBG068749.
InParanoidiP01033.
KOiK16451.
OMAiTYSAGCG.
OrthoDBiEOG091G0NIC.
PhylomeDBiP01033.
TreeFamiTF317409.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000102265-MONOMER.
ReactomeiR-HSA-114608. Platelet degranulation.
R-HSA-1592389. Activation of Matrix Metalloproteinases.

Miscellaneous databases

EvolutionaryTraceiP01033.
GeneWikiiTIMP1.
GenomeRNAii7076.
PMAP-CutDBP01033.
PROiP01033.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000102265.
CleanExiHS_TIMP1.
ExpressionAtlasiP01033. baseline and differential.
GenevisibleiP01033. HS.

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_HUMAN
AccessioniPrimary (citable) accession number: P01033
Secondary accession number(s): Q14252, Q9UCU1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: November 2, 2016
This is version 189 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome X
    Human chromosome X: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. 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.