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P01033 (TIMP1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified January 25, 2012. Version 144. 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·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)
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.

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...) Ref.15 Ref.16 Ref.17
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.22
Mutagenesis251T → V: Normal interaction with metalloproteinase. Ref.22
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: 3903517] [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: 3839290] [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: 3010309] [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: 2171551] [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: 7507419] [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: 15489334] [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: 9286280] [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: 1730286] [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: 1653055] [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: 15340161] [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: 2163605] [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: 1420137] [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: 16335952] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-53, MASS SPECTROMETRY.
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: 16740002] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-53 AND ASN-101, MASS SPECTROMETRY.
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: 16263699] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-53, MASS SPECTROMETRY.
Tissue: Platelet.
[18]"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: 21269460] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[19]"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: 9288970] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 24-207 IN COMPLEX WITH MMP-3.
[20]"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: 10623524] [Abstract]
Cited for: STRUCTURE BY NMR OF 24-149.
[21]"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: 12834347] [Abstract]
Cited for: STRUCTURE BY NMR OF 24-149 IN COMPLEX WITH MMP-3.
[22]"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: 17050530] [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.
IPIIPI00032292.
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[»]
ProteinModelPortalP01033.
SMRP01033. Positions 24-204.
ModBaseSearch...

Protein-protein interaction databases

DIPDIP-1107N.
IntActP01033. 4 interactions.
MINTMINT-2981826.
STRINGP01033.

Protein family/group databases

MEROPSI35.001.

PTM databases

GlycoSuiteDBP01033.

Polymorphism databases

DMDM135850.

Proteomic databases

PRIDEP01033.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000218388; ENSP00000218388; ENSG00000102265.
GeneID7076.
KEGGhsa:7076.
UCSCuc004dif.1. human.

Organism-specific databases

CTD7076.
GeneCardsGC0XP047441.
H-InvDBHIX0016764.
HGNCHGNC:11820. TIMP1.
HPACAB022360.
MIM305370. gene.
neXtProtNX_P01033.
PharmGKBPA36526.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG14834.
HOVERGENHBG068749.
InParanoidP01033.
OMASSIPCKL.
OrthoDBEOG44J2K2.
PhylomeDBP01033.

Enzyme and pathway databases

Pathway_Interaction_DBil6_7pathway. IL6-mediated signaling events.
ReactomeREACT_604. Hemostasis.

Gene expression databases

ArrayExpressP01033.
BgeeP01033.
CleanExHS_TIMP1.
GenevestigatorP01033.
GermOnlineENSG00000102265. Homo sapiens.

Family and domain databases

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

Other

NextBio27675.
PMAP-CutDBP01033.
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: January 25, 2012
This is version 144 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.

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

MIM cross-references

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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families