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Protein

Metalloproteinase inhibitor 1

Gene

TIMP1

Organism
Homo sapiens (Human)
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. 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 Publication1
Sitei57Involved in metalloproteinase-bindingCombined sources1 Publication1
Sitei158Involved in metalloproteinase-bindingCombined sources1 Publication1

GO - Molecular functioni

  • cytokine activity Source: UniProtKB
  • growth factor activity Source: UniProtKB-KW
  • metalloendopeptidase inhibitor activity Source: UniProtKB
  • protease binding Source: GO_Central
  • zinc ion binding Source: UniProtKB

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-HSA-114608 Platelet degranulation
R-HSA-1592389 Activation of Matrix Metalloproteinases
R-HSA-381426 Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-6783783 Interleukin-10 signaling
R-HSA-6785807 Interleukin-4 and 13 signaling
R-HSA-8957275 Post-translational protein phosphorylation
SIGNORiP01033

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

EuPathDBiHostDB:ENSG00000102265.11
HGNCiHGNC:11820 TIMP1
MIMi305370 gene
neXtProtiNX_P01033

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

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) asparagine4 Publications1
GlycosylationiCAR_000003101N-linked (GlcNAc...) asparagine1 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

GlyConnecti367
iPTMnetiP01033
PhosphoSitePlusiP01033
SwissPalmiP01033
UniCarbKBiP01033

Miscellaneous databases

PMAP-CutDBiP01033

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

Show more details

GO - Molecular functioni

  • cytokine activity Source: UniProtKB
  • growth factor activity Source: UniProtKB-KW
  • protease binding Source: GO_Central

Protein-protein interaction databases

BioGridi112932, 13 interactors
CORUMiP01033
DIPiDIP-1107N
IntActiP01033, 7 interactors
MINTiP01033
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 – 27Involved in metalloproteinase-bindingCombined sources1 Publication4
Regioni90 – 91Involved in metalloproteinase-bindingCombined sources1 Publication2
Regioni179 – 180Involved in metalloproteinase-bindingCombined sources1 Publication2

Sequence similaritiesi

Keywords - Domaini

Signal

Phylogenomic databases

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

Family and domain databases

Gene3Di3.90.370.10, 2 hits
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.

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

Similar proteinsi

Entry informationi

Entry nameiTIMP1_HUMAN
AccessioniPrimary (citable) accession number: P01033
Secondary accession number(s): Q14252, Q9UCU1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: April 25, 2018
This is version 202 of the entry and version 1 of the sequence. See 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
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Main funding by: National Institutes of Health