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P01033 (TIMP1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 165. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:TIMP1
Synonyms:CLGI, TIMP
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length207 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Complexes with metalloproteinases (such as collagenases) and irreversibly inactivates them by binding to their catalytic zinc cofactor. Also mediates erythropoiesis in vitro; but, unlike IL-3, it is species-specific, stimulating the growth and differentiation of only human and murine erythroid progenitors. Known to act on MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-10, MMP-11, MMP-12, MMP-13 and MMP-16. Does not act on MMP-14.

Subcellular location

Secreted.

Post-translational modification

The activity of TIMP1 is dependent on the presence of disulfide bonds.

Sequence similarities

Belongs to the protease inhibitor I35 (TIMP) family. [View classification]

Contains 1 NTR domain.

Ontologies

Keywords
   Biological processErythrocyte maturation
   Cellular componentSecreted
   DomainSignal
   LigandMetal-binding
Zinc
   Molecular functionMetalloenzyme inhibitor
Metalloprotease inhibitor
Protease inhibitor
   PTMDisulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processaging

Inferred from electronic annotation. Source: Ensembl

blood coagulation

Traceable author statement. Source: Reactome

erythrocyte maturation

Inferred from electronic annotation. Source: UniProtKB-KW

extracellular matrix disassembly

Traceable author statement. Source: Reactome

extracellular matrix organization

Traceable author statement. Source: Reactome

negative regulation of apoptotic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of endopeptidase activity

Inferred from direct assay PubMed 12714508. Source: GOC

negative regulation of membrane protein ectodomain proteolysis

Inferred from direct assay PubMed 12714508. Source: UniProtKB

negative regulation of trophoblast cell migration

Inferred from mutant phenotype PubMed 21356369. Source: BHF-UCL

platelet activation

Traceable author statement. Source: Reactome

platelet degranulation

Traceable author statement. Source: Reactome

positive regulation of cell proliferation

Traceable author statement Ref.2. Source: ProtInc

response to cytokine

Inferred from electronic annotation. Source: Ensembl

response to peptide hormone

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentbasement membrane

Inferred from electronic annotation. Source: Ensembl

extracellular region

Non-traceable author statement Ref.10. Source: UniProtKB

platelet alpha granule lumen

Traceable author statement. Source: Reactome

   Molecular_functionmetal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

metalloendopeptidase inhibitor activity

Inferred from direct assay PubMed 12714508. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

CD63P089625EBI-712536,EBI-762053

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2323 Ref.9 Ref.10 Ref.11
Chain24 – 207184Metalloproteinase inhibitor 1
PRO_0000034323

Regions

Domain24 – 147124NTR
Region24 – 285Involved in metalloproteinase-binding
Region90 – 912Involved in metalloproteinase-binding

Sites

Metal binding241Zinc; via amino nitrogen and carbonyl oxygen; shared with metalloproteinase partner

Amino acid modifications

Glycosylation531N-linked (GlcNAc...) (complex) Ref.15 Ref.16 Ref.17 Ref.18
CAR_000002
Glycosylation1011N-linked (GlcNAc...) Ref.16
CAR_000003
Disulfide bond24 ↔ 93 Ref.13
Disulfide bond26 ↔ 122 Ref.13
Disulfide bond36 ↔ 147 Ref.13
Disulfide bond150 ↔ 197 Ref.13
Disulfide bond155 ↔ 160 Ref.13
Disulfide bond168 ↔ 189 Ref.13

Experimental info

Mutagenesis251T → E, G, K, Q or R: Reduced interaction with metalloproteinase. Ref.23
Mutagenesis251T → V: Normal interaction with metalloproteinase. Ref.23
Sequence conflict231A → P in CAA26443. Ref.2
Sequence conflict441A → P in BAA01913. Ref.12

Secondary structure

........................................ 207
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P01033 [UniParc].

Last modified July 21, 1986. Version 1.
Checksum: 5AE4F90FFAB2ECDC

FASTA20723,171
        10         20         30         40         50         60 
MAPFEPLASG ILLLLWLIAP SRACTCVPPH PQTAFCNSDL VIRAKFVGTP EVNQTTLYQR 

        70         80         90        100        110        120 
YEIKMTKMYK GFQALGDAAD IRFVYTPAME SVCGYFHRSH NRSEEFLIAG KLQDGLLHIT 

       130        140        150        160        170        180 
TCSFVAPWNS LSLAQRRGFT KTYTVGCEEC TVFPCLSIPC KLQSGTHCLW TDQLLQGSEK 

       190        200 
GFQSRHLACL PREPGLCTWQ SLRSQIA 

« Hide

References

« Hide 'large scale' references
[1]"Sequence of human tissue inhibitor of metalloproteinases and its identity to erythroid-potentiating activity."
Docherty A.J.P., Lyons A., Smith B.J., Wright E.M., Stephens P.E., Harris T.J.R., Murphy G., Reynolds J.J.
Nature 318:66-69(1985) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Molecular characterization and expression of the gene encoding human erythroid-potentiating activity."
Gasson J.C., Golde D.W., Kaufman S.E., Westbrook C.A., Hewick R.M., Kaufman R.J., Wong G.G., Temple P.A., Leary A.C., Brown E.L., Orr E.C., Clark S.C.
Nature 315:768-771(1985) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"Primary structure and cDNA cloning of human fibroblast collagenase inhibitor."
Carmichael D.F., Sommer A., Thompson R.C., Anderson D.C., Smith C.G., Welgus H.G., Stricklin G.P.
Proc. Natl. Acad. Sci. U.S.A. 83:2407-2411(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]"Molecular cloning and synthesis of biologically active human tissue inhibitor of metalloproteinases in yeast."
Kaczorek M., Honore N., Ribes V., Dehoux P., Cornet P., Cartwright T., Streeck R.E.
Biotechnology (N.Y.) 5:595-598(1987)
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]"Characterization of three abundant mRNAs from human ovarian granulosa cells."
Rapp G., Freudenstein J., Klaudiny J., Mucha J., Wempe F., Zimmer M., Scheit K.H.
DNA Cell Biol. 9:479-485(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Ovary.
[6]"Characterization of a human corneal metalloproteinase inhibitor (TIMP-1)."
Opbroek A., Kenney M.C., Brown D.
Curr. Eye Res. 12:877-883(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[7]"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].
Tissue: Cervix.
[8]"Genomic organization of the human TIMP-1 gene. Investigation of a causative role in the pathogenesis of X-linked retinitis pigmentosa 2."
Hardcastle A.J., Thiselton D.L., Nayudu M., Hampson R.M., Bhattacharya S.S.
Invest. Ophthalmol. Vis. Sci. 38:1893-1896(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-40.
[9]"Isolation and characterization of tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) from human rheumatoid synovial fluid."
Osthues A., Knaueper V., Oberhoff R., Reinke H., Tschesche H.
FEBS Lett. 296:16-20(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 24-38.
Tissue: Synovial fluid.
[10]"The cytokine-protease connection: identification of a 96-kD THP-1 gelatinase and regulation by interleukin-1 and cytokine inducers."
van Ranst M., Norga K., Masure S., Proost P., Vandekerckhove F., Auwerx J., van Damme J., Opdenakker G.
Cytokine 3:231-239(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 24-52.
[11]"Signal peptide prediction based on analysis of experimentally verified cleavage sites."
Zhang Z., Henzel W.J.
Protein Sci. 13:2819-2824(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 24-38.
[12]Matsuda T., Kohno K., Kuwano M.
Submitted (JUL-1992) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 42-207.
[13]"Disulphide bond assignment in human tissue inhibitor of metalloproteinases (TIMP)."
Williamson R.A., Martson F.A.O., Angal S., Koklitis P., Panico M., Morris H.R., Carne A.F., Smith B.J., Harris T.J.R., Freedman R.B.
Biochem. J. 268:267-274(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: DISULFIDE BONDS, PARTIAL PROTEIN SEQUENCE.
[14]"Site-directed mutations that alter the inhibitory activity of the tissue inhibitor of metalloproteinases-1: importance of the N-terminal region between cysteine 3 and cysteine 13."
O'Shea M., Willenbrock F., Williamson R.A., Cockett M.I., Freedman R.B., Reynolds J.J., Docherty A.J.P., Murphy G.
Biochemistry 31:10146-10152(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS.
[15]"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry."
Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D.
J. Proteome Res. 4:2070-2080(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-53.
Tissue: Plasma.
[16]"Identification of N-linked glycoproteins in human saliva by glycoprotein capture and mass spectrometry."
Ramachandran P., Boontheung P., Xie Y., Sondej M., Wong D.T., Loo J.A.
J. Proteome Res. 5:1493-1503(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-53 AND ASN-101.
Tissue: Saliva.
[17]"Elucidation of N-glycosylation sites on human platelet proteins: a glycoproteomic approach."
Lewandrowski U., Moebius J., Walter U., Sickmann A.
Mol. Cell. Proteomics 5:226-233(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-53.
Tissue: Platelet.
[18]"A strategy for precise and large scale identification of core fucosylated glycoproteins."
Jia W., Lu Z., Fu Y., Wang H.P., Wang L.H., Chi H., Yuan Z.F., Zheng Z.B., Song L.N., Han H.H., Liang Y.M., Wang J.L., Cai Y., Zhang Y.K., Deng Y.L., Ying W.T., He S.M., Qian X.H.
Mol. Cell. Proteomics 8:913-923(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION AT ASN-53.
[19]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[20]"Mechanism of inhibition of the human matrix metalloproteinase stromelysin-1 by TIMP-1."
Gomis-Rueth F.-X., Maskos K., Betz M., Bergner A., Huber R., Suzuki K., Yoshida N., Nagase H., Brew K., Bourenkov G.P., Bartunik H., Bode W.
Nature 389:77-81(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 24-207 IN COMPLEX WITH MMP-3.
[21]"NMR structure of tissue inhibitor of metalloproteinases-1 implicates localized induced fit in recognition of matrix metalloproteinases."
Wu B., Arumugam S., Gao G., Lee G.I., Semenchenko V., Huang W., Brew K., Van Doren S.R.
J. Mol. Biol. 295:257-268(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 24-149.
[22]"Global orientation of bound MMP-3 and N-TIMP-1 in solution via residual dipolar couplings."
Arumugam S., Van Doren S.R.
Biochemistry 42:7950-7958(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 24-149 IN COMPLEX WITH MMP-3.
[23]"Crystal structure of the catalytic domain of matrix metalloproteinase-1 in complex with the inhibitory domain of tissue inhibitor of metalloproteinase-1."
Iyer S., Wei S., Brew K., Acharya K.R.
J. Biol. Chem. 282:364-371(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.54 ANGSTROMS) OF 24-149 IN COMPLEX WITH MMP-1, COFACTOR, MUTAGENESIS OF THR-25.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRZYHUEP. A93372.
RefSeqNP_003245.1. NM_003254.2.
UniGeneHs.522632.

3D structure databases

PDBe
RCSB PDB
PDBj
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[»]
ProteinModelPortalP01033.
SMRP01033. Positions 24-204.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112932. 9 interactions.
DIPDIP-1107N.
IntActP01033. 5 interactions.
MINTMINT-2981826.
STRING9606.ENSP00000218388.

Protein family/group databases

MEROPSI35.001.

PTM databases

PhosphoSiteP01033.
UniCarbKBP01033.

Polymorphism databases

DMDM135850.

Proteomic databases

PaxDbP01033.
PRIDEP01033.

Protocols and materials databases

DNASU7076.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000218388; ENSP00000218388; ENSG00000102265.
GeneID7076.
KEGGhsa:7076.
UCSCuc004dif.3. human.

Organism-specific databases

CTD7076.
GeneCardsGC0XP047441.
HGNCHGNC:11820. TIMP1.
HPACAB022360.
MIM305370. gene.
neXtProtNX_P01033.
PharmGKBPA36526.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG259409.
HOGENOMHOG000285981.
HOVERGENHBG068749.
InParanoidP01033.
KOK16451.
OMASSIPCKL.
OrthoDBEOG79GT74.
PhylomeDBP01033.
TreeFamTF317409.

Enzyme and pathway databases

ReactomeREACT_118779. Extracellular matrix organization.
REACT_604. Hemostasis.

Gene expression databases

ArrayExpressP01033.
BgeeP01033.
CleanExHS_TIMP1.
GenevestigatorP01033.

Family and domain databases

Gene3D3.90.370.10. 1 hit.
InterProIPR001134. Netrin_domain.
IPR001820. Prot_inh_TIMP.
IPR008993. TIMP-like_OB-fold.
IPR015611. TIMP1.
IPR027465. TIMP_C_dom.
[Graphical view]
PANTHERPTHR11844. PTHR11844. 1 hit.
PTHR11844:SF5. PTHR11844:SF5. 1 hit.
PfamPF00965. TIMP. 1 hit.
[Graphical view]
SMARTSM00206. NTR. 1 hit.
[Graphical view]
SUPFAMSSF50242. SSF50242. 1 hit.
PROSITEPS50189. NTR. 1 hit.
PS00288. TIMP. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP01033.
GeneWikiTIMP1.
GenomeRNAi7076.
NextBio27675.
PMAP-CutDBP01033.
PROP01033.
SOURCESearch...

Entry information

Entry nameTIMP1_HUMAN
AccessionPrimary (citable) accession number: P01033
Secondary accession number(s): Q14252, Q9UCU1
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: April 16, 2014
This is version 165 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome X

Human chromosome X: entries, gene names and cross-references to MIM