TIMP1_HUMAN
ID TIMP1_HUMAN Reviewed; 207 AA.
AC P01033; Q14252; Q9UCU1;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 03-AUG-2022, entry version 228.
DE RecName: Full=Metalloproteinase inhibitor 1;
DE AltName: Full=Erythroid-potentiating activity;
DE Short=EPA;
DE AltName: Full=Fibroblast collagenase inhibitor;
DE Short=Collagenase inhibitor;
DE AltName: Full=Tissue inhibitor of metalloproteinases 1;
DE Short=TIMP-1;
DE Flags: Precursor;
GN Name=TIMP1; Synonyms=CLGI, TIMP;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 24-51, FUNCTION,
RP SUBCELLULAR LOCATION, AND GLYCOSYLATION.
RX PubMed=3903517; DOI=10.1038/318066a0;
RA Docherty A.J.P., Lyons A., Smith B.J., Wright E.M., Stephens P.E.,
RA Harris T.J.R., Murphy G., Reynolds J.J.;
RT "Sequence of human tissue inhibitor of metalloproteinases and its identity
RT to erythroid-potentiating activity.";
RL Nature 318:66-69(1985).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 24-49, SUBCELLULAR
RP LOCATION, GLYCOSYLATION, AND FUNCTION.
RX PubMed=3839290; DOI=10.1038/315768a0;
RA Gasson J.C., Golde D.W., Kaufman S.E., Westbrook C.A., Hewick R.M.,
RA Kaufman R.J., Wong G.G., Temple P.A., Leary A.C., Brown E.L., Orr E.C.,
RA Clark S.C.;
RT "Molecular characterization and expression of the gene encoding human
RT erythroid-potentiating activity.";
RL Nature 315:768-771(1985).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 24-207, DISULFIDE BOND,
RP SUBCELLULAR LOCATION, AND GLYCOSYLATION.
RX PubMed=3010309; DOI=10.1073/pnas.83.8.2407;
RA Carmichael D.F., Sommer A., Thompson R.C., Anderson D.C., Smith C.G.,
RA Welgus H.G., Stricklin G.P.;
RT "Primary structure and cDNA cloning of human fibroblast collagenase
RT inhibitor.";
RL Proc. Natl. Acad. Sci. U.S.A. 83:2407-2411(1986).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Kaczorek M., Honore N., Ribes V., Dehoux P., Cornet P., Cartwright T.,
RA Streeck R.E.;
RT "Molecular cloning and synthesis of biologically active human tissue
RT inhibitor of metalloproteinases in yeast.";
RL Biotechnology (N.Y.) 5:595-598(1987).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Ovary;
RX PubMed=2171551; DOI=10.1089/dna.1990.9.479;
RA Rapp G., Freudenstein J., Klaudiny J., Mucha J., Wempe F., Zimmer M.,
RA Scheit K.H.;
RT "Characterization of three abundant mRNAs from human ovarian granulosa
RT cells.";
RL DNA Cell Biol. 9:479-485(1990).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=7507419; DOI=10.3109/02713689309020394;
RA Opbroek A., Kenney M.C., Brown D.;
RT "Characterization of a human corneal metalloproteinase inhibitor (TIMP-
RT 1).";
RL Curr. Eye Res. 12:877-883(1993).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Cervix;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-40.
RX PubMed=9286280;
RA Hardcastle A.J., Thiselton D.L., Nayudu M., Hampson R.M.,
RA Bhattacharya S.S.;
RT "Genomic organization of the human TIMP-1 gene. Investigation of a
RT causative role in the pathogenesis of X-linked retinitis pigmentosa 2.";
RL Invest. Ophthalmol. Vis. Sci. 38:1893-1896(1997).
RN [9]
RP PROTEIN SEQUENCE OF 24-38, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP FUNCTION.
RC TISSUE=Synovial fluid;
RX PubMed=1730286; DOI=10.1016/0014-5793(92)80393-u;
RA Osthues A., Knaueper V., Oberhoff R., Reinke H., Tschesche H.;
RT "Isolation and characterization of tissue inhibitors of metalloproteinases
RT (TIMP-1 and TIMP-2) from human rheumatoid synovial fluid.";
RL FEBS Lett. 296:16-20(1992).
RN [10]
RP PROTEIN SEQUENCE OF 24-52.
RX PubMed=1653055; DOI=10.1016/1043-4666(91)90021-5;
RA van Ranst M., Norga K., Masure S., Proost P., Vandekerckhove F., Auwerx J.,
RA van Damme J., Opdenakker G.;
RT "The cytokine-protease connection: identification of a 96-kD THP-1
RT gelatinase and regulation by interleukin-1 and cytokine inducers.";
RL Cytokine 3:231-239(1991).
RN [11]
RP PROTEIN SEQUENCE OF 24-38.
RX PubMed=15340161; DOI=10.1110/ps.04682504;
RA Zhang Z., Henzel W.J.;
RT "Signal peptide prediction based on analysis of experimentally verified
RT cleavage sites.";
RL Protein Sci. 13:2819-2824(2004).
RN [12]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 42-207.
RA Matsuda T., Kohno K., Kuwano M.;
RL Submitted (JUL-1992) to the EMBL/GenBank/DDBJ databases.
RN [13]
RP DISULFIDE BONDS, AND PARTIAL PROTEIN SEQUENCE.
RX PubMed=2163605; DOI=10.1042/bj2680267;
RA Williamson R.A., Martson F.A.O., Angal S., Koklitis P., Panico M.,
RA Morris H.R., Carne A.F., Smith B.J., Harris T.J.R., Freedman R.B.;
RT "Disulphide bond assignment in human tissue inhibitor of metalloproteinases
RT (TIMP).";
RL Biochem. J. 268:267-274(1990).
RN [14]
RP MUTAGENESIS, AND FUNCTION.
RX PubMed=1420137; DOI=10.1021/bi00157a002;
RA O'Shea M., Willenbrock F., Williamson R.A., Cockett M.I., Freedman R.B.,
RA Reynolds J.J., Docherty A.J.P., Murphy G.;
RT "Site-directed mutations that alter the inhibitory activity of the tissue
RT inhibitor of metalloproteinases-1: importance of the N-terminal region
RT between cysteine 3 and cysteine 13.";
RL Biochemistry 31:10146-10152(1992).
RN [15]
RP FUNCTION AS A GROWTH FACTOR AND PROTEASE INHIBITOR, INTERACTION WITH MMP3,
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF HIS-30 AND GLN-32.
RX PubMed=8541540;
RA Chesler L., Golde D.W., Bersch N., Johnson M.D.;
RT "Metalloproteinase inhibition and erythroid potentiation are independent
RT activities of tissue inhibitor of metalloproteinases-1.";
RL Blood 86:4506-4515(1995).
RN [16]
RP INTERACTION WITH MMP13, AND FUNCTION.
RX PubMed=8576151; DOI=10.1074/jbc.271.3.1544;
RA Knaeuper V., Lopez-Otin C., Smith B., Knight G., Murphy G.;
RT "Biochemical characterization of human collagenase-3.";
RL J. Biol. Chem. 271:1544-1550(1996).
RN [17]
RP INTERACTION WITH MMP13, AND FUNCTION.
RX PubMed=9065415; DOI=10.1074/jbc.272.12.7608;
RA Knaeuper V., Cowell S., Smith B., Lopez-Otin C., O'Shea M., Morris H.,
RA Zardi L., Murphy G.;
RT "The role of the C-terminal domain of human collagenase-3 (MMP-13) in the
RT activation of procollagenase-3, substrate specificity, and tissue inhibitor
RT of metalloproteinase interaction.";
RL J. Biol. Chem. 272:7608-7616(1997).
RN [18]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-53.
RC TISSUE=Plasma;
RX PubMed=16335952; DOI=10.1021/pr0502065;
RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J.,
RA Smith R.D.;
RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT hydrazide chemistry, and mass spectrometry.";
RL J. Proteome Res. 4:2070-2080(2005).
RN [19]
RP FUNCTION, AND INTERACTION WITH CD63.
RX PubMed=16917503; DOI=10.1038/sj.emboj.7601281;
RA Jung K.K., Liu X.W., Chirco R., Fridman R., Kim H.R.;
RT "Identification of CD63 as a tissue inhibitor of metalloproteinase-1
RT interacting cell surface protein.";
RL EMBO J. 25:3934-3942(2006).
RN [20]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-53 AND ASN-101.
RC TISSUE=Saliva;
RX PubMed=16740002; DOI=10.1021/pr050492k;
RA Ramachandran P., Boontheung P., Xie Y., Sondej M., Wong D.T., Loo J.A.;
RT "Identification of N-linked glycoproteins in human saliva by glycoprotein
RT capture and mass spectrometry.";
RL J. Proteome Res. 5:1493-1503(2006).
RN [21]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-53.
RC TISSUE=Platelet;
RX PubMed=16263699; DOI=10.1074/mcp.m500324-mcp200;
RA Lewandrowski U., Moebius J., Walter U., Sickmann A.;
RT "Elucidation of N-glycosylation sites on human platelet proteins: a
RT glycoproteomic approach.";
RL Mol. Cell. Proteomics 5:226-233(2006).
RN [22]
RP GLYCOSYLATION AT ASN-53.
RX PubMed=19139490; DOI=10.1074/mcp.m800504-mcp200;
RA Jia W., Lu Z., Fu Y., Wang H.P., Wang L.H., Chi H., Yuan Z.F., Zheng Z.B.,
RA Song L.N., Han H.H., Liang Y.M., Wang J.L., Cai Y., Zhang Y.K., Deng Y.L.,
RA Ying W.T., He S.M., Qian X.H.;
RT "A strategy for precise and large scale identification of core fucosylated
RT glycoproteins.";
RL Mol. Cell. Proteomics 8:913-923(2009).
RN [23]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [24]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22905912; DOI=10.1021/pr300539b;
RA Rosenow A., Noben J.P., Jocken J., Kallendrusch S., Fischer-Posovszky P.,
RA Mariman E.C., Renes J.;
RT "Resveratrol-induced changes of the human adipocyte secretion profile.";
RL J. Proteome Res. 11:4733-4743(2012).
RN [25]
RP IDENTIFICATION IN A COMPLEX WITH CD63 AND ITGB1.
RX PubMed=23522389; DOI=10.1186/1476-4598-12-22;
RA Toricelli M., Melo F.H., Peres G.B., Silva D.C., Jasiulionis M.G.;
RT "Timp1 interacts with beta-1 integrin and CD63 along melanoma genesis and
RT confers anoikis resistance by activating PI3-K signaling pathway
RT independently of Akt phosphorylation.";
RL Mol. Cancer 12:22-22(2013).
RN [26]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=24635319; DOI=10.1042/bj20131119;
RA Lee S.Y., Kim J.M., Cho S.Y., Kim H.S., Shin H.S., Jeon J.Y., Kausar R.,
RA Jeong S.Y., Lee Y.S., Lee M.A.;
RT "TIMP-1 modulates chemotaxis of human neural stem cells through CD63 and
RT integrin signalling.";
RL Biochem. J. 459:565-576(2014).
RN [27]
RP REVIEW.
RX PubMed=23982756; DOI=10.1007/s00018-013-1457-3;
RA Ries C.;
RT "Cytokine functions of TIMP-1.";
RL Cell. Mol. Life Sci. 71:659-672(2014).
RN [28]
RP PHOSPHORYLATION AT SER-178.
RX PubMed=26091039; DOI=10.1016/j.cell.2015.05.028;
RA Tagliabracci V.S., Wiley S.E., Guo X., Kinch L.N., Durrant E., Wen J.,
RA Xiao J., Cui J., Nguyen K.B., Engel J.L., Coon J.J., Grishin N.,
RA Pinna L.A., Pagliarini D.J., Dixon J.E.;
RT "A single kinase generates the majority of the secreted phosphoproteome.";
RL Cell 161:1619-1632(2015).
RN [29]
RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 24-207 IN COMPLEX WITH MMP3, AND
RP INTERACTION WITH MMP3.
RX PubMed=9288970; DOI=10.1038/37995;
RA Gomis-Rueth F.-X., Maskos K., Betz M., Bergner A., Huber R., Suzuki K.,
RA Yoshida N., Nagase H., Brew K., Bourenkov G.P., Bartunik H., Bode W.;
RT "Mechanism of inhibition of the human matrix metalloproteinase stromelysin-
RT 1 by TIMP-1.";
RL Nature 389:77-81(1997).
RN [30]
RP STRUCTURE BY NMR OF 24-149, AND DISULFIDE BOND.
RX PubMed=10623524; DOI=10.1006/jmbi.1999.3362;
RA Wu B., Arumugam S., Gao G., Lee G.I., Semenchenko V., Huang W., Brew K.,
RA Van Doren S.R.;
RT "NMR structure of tissue inhibitor of metalloproteinases-1 implicates
RT localized induced fit in recognition of matrix metalloproteinases.";
RL J. Mol. Biol. 295:257-268(2000).
RN [31]
RP STRUCTURE BY NMR OF 24-149 IN COMPLEX WITH MMP3, AND INTERACTION WITH MMP3.
RX PubMed=12834347; DOI=10.1021/bi034545s;
RA Arumugam S., Van Doren S.R.;
RT "Global orientation of bound MMP-3 and N-TIMP-1 in solution via residual
RT dipolar couplings.";
RL Biochemistry 42:7950-7958(2003).
RN [32]
RP X-RAY CRYSTALLOGRAPHY (2.54 ANGSTROMS) OF 24-149 IN COMPLEX WITH MMP1,
RP FUNCTION, INTERACTION WITH MMP1 AND MMP3, DISULFIDE BOND, AND MUTAGENESIS
RP OF THR-25.
RX PubMed=17050530; DOI=10.1074/jbc.m607625200;
RA Iyer S., Wei S., Brew K., Acharya K.R.;
RT "Crystal structure of the catalytic domain of matrix metalloproteinase-1 in
RT complex with the inhibitory domain of tissue inhibitor of
RT metalloproteinase-1.";
RL J. Biol. Chem. 282:364-371(2007).
RN [33]
RP X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 24-148 OF MUTANT LEU-121 IN
RP COMPLEX WITH MMP14, FUNCTION, INTERACTION WITH MMP14, DISULFIDE BOND, AND
RP MUTAGENESIS OF THR-121.
RX PubMed=20545310; DOI=10.1021/bi902141x;
RA Grossman M., Tworowski D., Dym O., Lee M.H., Levy Y., Murphy G., Sagi I.;
RT "The intrinsic protein flexibility of endogenous protease inhibitor TIMP-1
RT controls its binding interface and affects its function.";
RL Biochemistry 49:6184-6192(2010).
RN [34]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 24-207 IN COMPLEX WITH MMP10,
RP FUNCTION, INTERACTION WITH MMP10, AND DISULFIDE BOND.
RX PubMed=22427646; DOI=10.1074/jbc.m112.341156;
RA Batra J., Robinson J., Soares A.S., Fields A.P., Radisky D.C.,
RA Radisky E.S.;
RT "Matrix metalloproteinase-10 (MMP10) interaction with tissue inhibitors of
RT metalloproteinases TIMP-1 and TIMP-2: binding studies and crystal
RT structure.";
RL J. Biol. Chem. 287:15935-15946(2012).
CC -!- FUNCTION: Metalloproteinase inhibitor that functions by forming one to
CC one complexes with target metalloproteinases, such as collagenases, and
CC irreversibly inactivates them by binding to their catalytic zinc
CC cofactor. Acts on MMP1, MMP2, MMP3, MMP7, MMP8, MMP9, MMP10, MMP11,
CC MMP12, MMP13 and MMP16. Does not act on MMP14. Also functions as a
CC growth factor that regulates cell differentiation, migration and cell
CC death and activates cellular signaling cascades via CD63 and ITGB1.
CC Plays a role in integrin signaling. Mediates erythropoiesis in vitro;
CC but, unlike IL3, it is species-specific, stimulating the growth and
CC differentiation of only human and murine erythroid progenitors.
CC {ECO:0000269|PubMed:1420137, ECO:0000269|PubMed:16917503,
CC ECO:0000269|PubMed:17050530, ECO:0000269|PubMed:1730286,
CC ECO:0000269|PubMed:20545310, ECO:0000269|PubMed:22427646,
CC ECO:0000269|PubMed:24635319, ECO:0000269|PubMed:3839290,
CC ECO:0000269|PubMed:3903517, ECO:0000269|PubMed:8541540,
CC ECO:0000269|PubMed:8576151, ECO:0000269|PubMed:9065415}.
CC -!- SUBUNIT: Interacts with MMP1, MMP3, MMP10 and MMP13, but has only very
CC low affinity for MMP14. Interacts with CD63; identified in a complex
CC with CD63 and ITGB1. {ECO:0000269|PubMed:12834347,
CC ECO:0000269|PubMed:16917503, ECO:0000269|PubMed:17050530,
CC ECO:0000269|PubMed:20545310, ECO:0000269|PubMed:22427646,
CC ECO:0000269|PubMed:23522389, ECO:0000269|PubMed:8541540,
CC ECO:0000269|PubMed:8576151, ECO:0000269|PubMed:9065415,
CC ECO:0000269|PubMed:9288970}.
CC -!- INTERACTION:
CC P01033; P08962: CD63; NbExp=8; IntAct=EBI-712536, EBI-762053;
CC P01033; P27701: CD82; NbExp=11; IntAct=EBI-712536, EBI-682379;
CC P01033; P20908: COL5A1; NbExp=2; IntAct=EBI-712536, EBI-2464511;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:1730286,
CC ECO:0000269|PubMed:24635319, ECO:0000269|PubMed:3010309,
CC ECO:0000269|PubMed:3839290, ECO:0000269|PubMed:3903517,
CC ECO:0000269|PubMed:8541540}.
CC -!- TISSUE SPECIFICITY: Detected in rheumatoid synovial fluid (at protein
CC level). {ECO:0000269|PubMed:1730286}.
CC -!- PTM: The activity of TIMP1 is dependent on the presence of disulfide
CC bonds. {ECO:0000269|PubMed:10623524, ECO:0000269|PubMed:20545310,
CC ECO:0000269|PubMed:2163605, ECO:0000269|PubMed:22427646,
CC ECO:0000269|PubMed:3010309}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:16263699,
CC ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:16740002,
CC ECO:0000269|PubMed:19139490, ECO:0000269|PubMed:3010309,
CC ECO:0000269|PubMed:3839290, ECO:0000269|PubMed:3903517}.
CC -!- SIMILARITY: Belongs to the protease inhibitor I35 (TIMP) family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; X03124; CAA26902.1; -; mRNA.
DR EMBL; X02598; CAA26443.1; -; mRNA.
DR EMBL; M12670; AAA52436.1; -; mRNA.
DR EMBL; M59906; AAA63234.1; -; mRNA.
DR EMBL; S68252; AAD14009.1; -; mRNA.
DR EMBL; BC000866; AAH00866.1; -; mRNA.
DR EMBL; L47361; AAA75558.1; -; Genomic_DNA.
DR EMBL; D11139; BAA01913.1; -; Genomic_DNA.
DR CCDS; CCDS14281.1; -.
DR PIR; A93372; ZYHUEP.
DR RefSeq; NP_003245.1; NM_003254.2.
DR PDB; 1D2B; NMR; -; A=24-149.
DR PDB; 1OO9; NMR; -; B=24-149.
DR PDB; 1UEA; X-ray; 2.80 A; B/D=24-207.
DR PDB; 2J0T; X-ray; 2.54 A; D/E/F=24-149.
DR PDB; 3MA2; X-ray; 2.05 A; B/C=24-148.
DR PDB; 3V96; X-ray; 1.90 A; A=24-207.
DR PDB; 6MAV; X-ray; 2.37 A; B=24-207.
DR PDB; 6N9D; X-ray; 2.67 A; B=24-207.
DR PDB; 7S7L; X-ray; 2.34 A; B=24-207.
DR PDB; 7S7M; X-ray; 3.00 A; B=24-207.
DR PDBsum; 1D2B; -.
DR PDBsum; 1OO9; -.
DR PDBsum; 1UEA; -.
DR PDBsum; 2J0T; -.
DR PDBsum; 3MA2; -.
DR PDBsum; 3V96; -.
DR PDBsum; 6MAV; -.
DR PDBsum; 6N9D; -.
DR PDBsum; 7S7L; -.
DR PDBsum; 7S7M; -.
DR AlphaFoldDB; P01033; -.
DR BMRB; P01033; -.
DR SMR; P01033; -.
DR BioGRID; 112932; 44.
DR CORUM; P01033; -.
DR DIP; DIP-1107N; -.
DR IntAct; P01033; 12.
DR MINT; P01033; -.
DR STRING; 9606.ENSP00000218388; -.
DR MEROPS; I35.001; -.
DR GlyConnect; 367; 62 N-Linked glycans (2 sites).
DR GlyGen; P01033; 2 sites, 84 N-linked glycans (2 sites).
DR iPTMnet; P01033; -.
DR PhosphoSitePlus; P01033; -.
DR SwissPalm; P01033; -.
DR BioMuta; TIMP1; -.
DR DMDM; 135850; -.
DR CPTAC; CPTAC-680; -.
DR EPD; P01033; -.
DR jPOST; P01033; -.
DR MassIVE; P01033; -.
DR PaxDb; P01033; -.
DR PeptideAtlas; P01033; -.
DR PRIDE; P01033; -.
DR ProteomicsDB; 51310; -.
DR ABCD; P01033; 1 sequenced antibody.
DR Antibodypedia; 11411; 1125 antibodies from 51 providers.
DR CPTC; P01033; 2 antibodies.
DR DNASU; 7076; -.
DR Ensembl; ENST00000218388.9; ENSP00000218388.4; ENSG00000102265.12.
DR GeneID; 7076; -.
DR KEGG; hsa:7076; -.
DR MANE-Select; ENST00000218388.9; ENSP00000218388.4; NM_003254.3; NP_003245.1.
DR CTD; 7076; -.
DR DisGeNET; 7076; -.
DR GeneCards; TIMP1; -.
DR HGNC; HGNC:11820; TIMP1.
DR HPA; ENSG00000102265; Tissue enhanced (urinary).
DR MIM; 305370; gene.
DR neXtProt; NX_P01033; -.
DR OpenTargets; ENSG00000102265; -.
DR PharmGKB; PA36526; -.
DR VEuPathDB; HostDB:ENSG00000102265; -.
DR eggNOG; KOG4745; Eukaryota.
DR GeneTree; ENSGT00940000161081; -.
DR HOGENOM; CLU_084029_0_0_1; -.
DR InParanoid; P01033; -.
DR OMA; TWQSLRP; -.
DR PhylomeDB; P01033; -.
DR TreeFam; TF317409; -.
DR BRENDA; 3.4.24.22; 2681.
DR PathwayCommons; P01033; -.
DR Reactome; R-HSA-114608; Platelet degranulation.
DR Reactome; R-HSA-1592389; Activation of Matrix Metalloproteinases.
DR Reactome; R-HSA-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-HSA-6783783; Interleukin-10 signaling.
DR Reactome; R-HSA-6785807; Interleukin-4 and Interleukin-13 signaling.
DR Reactome; R-HSA-8957275; Post-translational protein phosphorylation.
DR SignaLink; P01033; -.
DR SIGNOR; P01033; -.
DR BioGRID-ORCS; 7076; 16 hits in 716 CRISPR screens.
DR ChiTaRS; TIMP1; human.
DR EvolutionaryTrace; P01033; -.
DR GeneWiki; TIMP1; -.
DR GenomeRNAi; 7076; -.
DR Pharos; P01033; Tbio.
DR PRO; PR:P01033; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; P01033; protein.
DR Bgee; ENSG00000102265; Expressed in right coronary artery and 200 other tissues.
DR ExpressionAtlas; P01033; baseline and differential.
DR Genevisible; P01033; HS.
DR GO; GO:0005604; C:basement membrane; IEA:Ensembl.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0031012; C:extracellular matrix; IBA:GO_Central.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0031093; C:platelet alpha granule lumen; TAS:Reactome.
DR GO; GO:0005125; F:cytokine activity; IDA:UniProtKB.
DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR GO; GO:0008191; F:metalloendopeptidase inhibitor activity; IDA:UniProtKB.
DR GO; GO:0030414; F:peptidase inhibitor activity; IDA:UniProtKB.
DR GO; GO:0002020; F:protease binding; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0051216; P:cartilage development; IEA:Ensembl.
DR GO; GO:0001775; P:cell activation; IEA:Ensembl.
DR GO; GO:0071492; P:cellular response to UV-A; IDA:UniProtKB.
DR GO; GO:0002248; P:connective tissue replacement involved in inflammatory response wound healing; IEA:Ensembl.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:0043086; P:negative regulation of catalytic activity; IDA:UniProtKB.
DR GO; GO:0010951; P:negative regulation of endopeptidase activity; IDA:UniProtKB.
DR GO; GO:0051045; P:negative regulation of membrane protein ectodomain proteolysis; IDA:UniProtKB.
DR GO; GO:1905049; P:negative regulation of metallopeptidase activity; IDA:UniProtKB.
DR GO; GO:1901164; P:negative regulation of trophoblast cell migration; IMP:BHF-UCL.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:UniProtKB.
DR GO; GO:2001044; P:regulation of integrin-mediated signaling pathway; IMP:UniProtKB.
DR GO; GO:0034097; P:response to cytokine; IBA:GO_Central.
DR GO; GO:0009725; P:response to hormone; IBA:GO_Central.
DR GO; GO:0010033; P:response to organic substance; IBA:GO_Central.
DR GO; GO:0043434; P:response to peptide hormone; IEA:Ensembl.
DR Gene3D; 2.40.50.120; -; 1.
DR Gene3D; 3.90.370.10; -; 1.
DR InterPro; IPR001134; Netrin_domain.
DR InterPro; IPR001820; TIMP.
DR InterPro; IPR008993; TIMP-like_OB-fold.
DR InterPro; IPR015611; TIMP1.
DR InterPro; IPR027465; TIMP_C.
DR InterPro; IPR030490; TIMP_CS.
DR PANTHER; PTHR11844; PTHR11844; 1.
DR PANTHER; PTHR11844:SF20; PTHR11844:SF20; 1.
DR Pfam; PF00965; TIMP; 1.
DR SMART; SM00206; NTR; 1.
DR SUPFAM; SSF50242; SSF50242; 1.
DR PROSITE; PS50189; NTR; 1.
DR PROSITE; PS00288; TIMP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Disulfide bond; Glycoprotein;
KW Growth factor; Metal-binding; Metalloenzyme inhibitor;
KW Metalloprotease inhibitor; Phosphoprotein; Protease inhibitor;
KW Reference proteome; Secreted; Signal; Zinc.
FT SIGNAL 1..23
FT /evidence="ECO:0000269|PubMed:15340161,
FT ECO:0000269|PubMed:1653055, ECO:0000269|PubMed:1730286,
FT ECO:0000269|PubMed:3010309, ECO:0000269|PubMed:3839290,
FT ECO:0000269|PubMed:3903517"
FT CHAIN 24..207
FT /note="Metalloproteinase inhibitor 1"
FT /id="PRO_0000034323"
FT DOMAIN 24..147
FT /note="NTR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT REGION 24..27
FT /note="Involved in metalloproteinase-binding"
FT /evidence="ECO:0000269|PubMed:22427646,
FT ECO:0007744|PDB:3V96"
FT REGION 90..91
FT /note="Involved in metalloproteinase-binding"
FT /evidence="ECO:0000269|PubMed:22427646,
FT ECO:0007744|PDB:3V96"
FT REGION 179..180
FT /note="Involved in metalloproteinase-binding"
FT /evidence="ECO:0000269|PubMed:22427646,
FT ECO:0007744|PDB:3V96"
FT BINDING 24
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="ligand shared with metalloproteinase partner"
FT /evidence="ECO:0000269|PubMed:22427646"
FT SITE 57
FT /note="Involved in metalloproteinase-binding"
FT /evidence="ECO:0000269|PubMed:22427646,
FT ECO:0007744|PDB:3V96"
FT SITE 158
FT /note="Involved in metalloproteinase-binding"
FT /evidence="ECO:0000269|PubMed:22427646,
FT ECO:0007744|PDB:3V96"
FT MOD_RES 178
FT /note="Phosphoserine; by FAM20C"
FT /evidence="ECO:0000269|PubMed:26091039"
FT CARBOHYD 53
FT /note="N-linked (GlcNAc...) (complex) asparagine"
FT /evidence="ECO:0000269|PubMed:16263699,
FT ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:16740002,
FT ECO:0000269|PubMed:19139490"
FT /id="CAR_000002"
FT CARBOHYD 101
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16740002"
FT /id="CAR_000003"
FT DISULFID 24..93
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00295,
FT ECO:0000269|PubMed:2163605"
FT DISULFID 26..122
FT /evidence="ECO:0000269|PubMed:10623524,
FT ECO:0000269|PubMed:20545310, ECO:0000269|PubMed:2163605,
FT ECO:0000269|PubMed:22427646, ECO:0000269|PubMed:3010309"
FT DISULFID 36..147
FT /evidence="ECO:0000269|PubMed:10623524,
FT ECO:0000269|PubMed:20545310, ECO:0000269|PubMed:2163605,
FT ECO:0000269|PubMed:22427646, ECO:0000269|PubMed:3010309"
FT DISULFID 150..197
FT /evidence="ECO:0000269|PubMed:10623524,
FT ECO:0000269|PubMed:20545310, ECO:0000269|PubMed:2163605,
FT ECO:0000269|PubMed:22427646, ECO:0000269|PubMed:3010309"
FT DISULFID 155..160
FT /evidence="ECO:0000269|PubMed:10623524,
FT ECO:0000269|PubMed:20545310, ECO:0000269|PubMed:2163605,
FT ECO:0000269|PubMed:22427646, ECO:0000269|PubMed:3010309"
FT DISULFID 168..189
FT /evidence="ECO:0000269|PubMed:10623524,
FT ECO:0000269|PubMed:20545310, ECO:0000269|PubMed:2163605,
FT ECO:0000269|PubMed:22427646, ECO:0000269|PubMed:3010309"
FT MUTAGEN 25
FT /note="T->E,G,K,Q,R: Reduced interaction with
FT metalloproteinase."
FT /evidence="ECO:0000269|PubMed:17050530"
FT MUTAGEN 25
FT /note="T->V: Normal interaction with metalloproteinase."
FT /evidence="ECO:0000269|PubMed:17050530"
FT MUTAGEN 30
FT /note="H->A: Nearly abolishes metalloproteinase
FT inhibition."
FT /evidence="ECO:0000269|PubMed:8541540"
FT MUTAGEN 32
FT /note="Q->A: Nearly abolishes metalloproteinase
FT inhibition."
FT /evidence="ECO:0000269|PubMed:8541540"
FT MUTAGEN 121
FT /note="T->L: Decreases protein flexibility and increases
FT affinity for MMP14."
FT /evidence="ECO:0000269|PubMed:20545310"
FT CONFLICT 23
FT /note="A -> P (in Ref. 2; CAA26443)"
FT /evidence="ECO:0000305"
FT CONFLICT 44
FT /note="A -> P (in Ref. 12; BAA01913)"
FT /evidence="ECO:0000305"
FT STRAND 25..27
FT /evidence="ECO:0007829|PDB:6N9D"
FT HELIX 31..37
FT /evidence="ECO:0007829|PDB:3V96"
FT STRAND 39..46
FT /evidence="ECO:0007829|PDB:3V96"
FT TURN 54..56
FT /evidence="ECO:0007829|PDB:6MAV"
FT STRAND 57..70
FT /evidence="ECO:0007829|PDB:3V96"
FT HELIX 72..74
FT /evidence="ECO:0007829|PDB:1D2B"
FT TURN 77..79
FT /evidence="ECO:0007829|PDB:1UEA"
FT STRAND 83..89
FT /evidence="ECO:0007829|PDB:3V96"
FT HELIX 90..92
FT /evidence="ECO:0007829|PDB:3V96"
FT STRAND 105..113
FT /evidence="ECO:0007829|PDB:3V96"
FT STRAND 116..118
FT /evidence="ECO:0007829|PDB:3V96"
FT STRAND 125..127
FT /evidence="ECO:0007829|PDB:3V96"
FT HELIX 128..130
FT /evidence="ECO:0007829|PDB:3V96"
FT HELIX 133..140
FT /evidence="ECO:0007829|PDB:3V96"
FT HELIX 143..145
FT /evidence="ECO:0007829|PDB:3V96"
FT TURN 146..149
FT /evidence="ECO:0007829|PDB:3V96"
FT STRAND 151..154
FT /evidence="ECO:0007829|PDB:3V96"
FT STRAND 157..159
FT /evidence="ECO:0007829|PDB:3V96"
FT STRAND 167..170
FT /evidence="ECO:0007829|PDB:3V96"
FT HELIX 172..176
FT /evidence="ECO:0007829|PDB:3V96"
FT STRAND 177..181
FT /evidence="ECO:0007829|PDB:3V96"
FT HELIX 182..186
FT /evidence="ECO:0007829|PDB:3V96"
FT STRAND 188..193
FT /evidence="ECO:0007829|PDB:3V96"
FT STRAND 196..200
FT /evidence="ECO:0007829|PDB:3V96"
SQ SEQUENCE 207 AA; 23171 MW; 5AE4F90FFAB2ECDC CRC64;
MAPFEPLASG ILLLLWLIAP SRACTCVPPH PQTAFCNSDL VIRAKFVGTP EVNQTTLYQR
YEIKMTKMYK GFQALGDAAD IRFVYTPAME SVCGYFHRSH NRSEEFLIAG KLQDGLLHIT
TCSFVAPWNS LSLAQRRGFT KTYTVGCEEC TVFPCLSIPC KLQSGTHCLW TDQLLQGSEK
GFQSRHLACL PREPGLCTWQ SLRSQIA
