TIMP3_HUMAN
ID TIMP3_HUMAN Reviewed; 211 AA.
AC P35625; B2RBY9; Q5THV4; Q9UC74; Q9UGS2;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 2.
DT 03-AUG-2022, entry version 208.
DE RecName: Full=Metalloproteinase inhibitor 3;
DE AltName: Full=Protein MIG-5;
DE AltName: Full=Tissue inhibitor of metalloproteinases 3;
DE Short=TIMP-3;
DE Flags: Precursor;
GN Name=TIMP3;
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].
RC TISSUE=Mammary carcinoma;
RX PubMed=8174111;
RA Uria J.A., Ferrando A.A., Velasco G., Freije J.M., Lopez-Otin C.;
RT "Structure and expression in breast tumors of human TIMP-3, a new member of
RT the metalloproteinase inhibitor family.";
RL Cancer Res. 54:2091-2094(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=7772252; DOI=10.1089/dna.1994.13.711;
RA Wilde C.G., Hawkins P.R., Coleman R.T., Levine W.B., Delegeane A.M.,
RA Okamoto P.M., Ito L.Y., Scott R.W., Seilhamer J.J.;
RT "Cloning and characterization of human tissue inhibitor of
RT metalloproteinases-3.";
RL DNA Cell Biol. 13:711-718(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Kidney;
RX PubMed=8163205; DOI=10.1016/0378-1119(94)90588-6;
RA Silbiger S.M., Jacobsen V.L., Cupples R.L., Koski R.A.;
RT "Cloning of cDNAs encoding human TIMP-3, a novel member of the tissue
RT inhibitor of metalloproteinase family.";
RL Gene 141:293-297(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8034652; DOI=10.1016/s0021-9258(17)32259-7;
RA Wick M., Buerger C., Bruesselbach S., Lucibello F., Mueller R.;
RT "A novel member of human tissue inhibitor of metalloproteinases (TIMP) gene
RT family is regulated during G1 progression, mitogenic stimulation,
RT differentiation, and senescence.";
RL J. Biol. Chem. 269:18953-18960(1994).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8808469; DOI=10.1101/gr.5.5.483;
RA Stoehr H., Roomp K., Felbor U., Weber B.H.F.;
RT "Genomic organization of the human tissue inhibitor of metalloproteinases-3
RT (TIMP3).";
RL Genome Res. 5:483-487(1995).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8806658; DOI=10.1006/bbrc.1996.1379;
RA Ruiz A.C., Brett P., Bok D.;
RT "TIMP-3 is expressed in the human retinal pigment epithelium.";
RL Biochem. Biophys. Res. Commun. 226:467-474(1996).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84;
RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A.,
RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J.,
RA Beare D.M., Dunham I.;
RT "A genome annotation-driven approach to cloning the human ORFeome.";
RL Genome Biol. 5:R84.1-R84.11(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10591208; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M.,
RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C.,
RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E.,
RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C.,
RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G.,
RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V.,
RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M.,
RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E.,
RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F.,
RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M.,
RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A.,
RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D.,
RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y.,
RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S.,
RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E.,
RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A.,
RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L.,
RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P.,
RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P.,
RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q.,
RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J.,
RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J.,
RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D.,
RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T.,
RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P.,
RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K.,
RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L.,
RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J.,
RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E.,
RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P.,
RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y.,
RA Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
RN [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [12]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Pancreas;
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 [13]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 14-211.
RC TISSUE=Placenta;
RX PubMed=8188246; DOI=10.1006/geno.1994.1016;
RA Apte S.S., Mattei M.-G., Olsen B.R.;
RT "Cloning of the cDNA encoding human tissue inhibitor of metalloproteinases-
RT 3 (TIMP-3) and mapping of the TIMP3 gene to chromosome 22.";
RL Genomics 19:86-90(1994).
RN [14]
RP PROTEIN SEQUENCE OF 24-41.
RX PubMed=7795886; DOI=10.1016/0945-053x(95)90005-5;
RA Kishnani N.S., Staskus P.W., Yang T.-T., Masiarz F.R., Hawkes S.P.;
RT "Identification and characterization of human tissue inhibitor of
RT metalloproteinase-3 and detection of three additional metalloproteinase
RT inhibitor activities in extracellular matrix.";
RL Matrix Biol. 14:479-488(1995).
RN [15]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 42-211.
RC TISSUE=Placenta;
RX PubMed=8666262; DOI=10.1016/0378-1119(95)00864-0;
RA Hammani K., Henriet P.M., Silbiger S.M., DeClerck Y.A.;
RT "Cloning and partial structure of the gene encoding human tissue inhibitor
RT of metalloproteinases-3.";
RL Gene 170:287-288(1996).
RN [16]
RP INTERACTION WITH EFEMP1.
RX PubMed=15123717; DOI=10.1074/jbc.m403026200;
RA Klenotic P.A., Munier F.L., Marmorstein L.Y., Anand-Apte B.;
RT "Tissue inhibitor of metalloproteinases-3 (TIMP-3) is a binding partner of
RT epithelial growth factor-containing fibulin-like extracellular matrix
RT protein 1 (EFEMP1). Implications for macular degenerations.";
RL J. Biol. Chem. 279:30469-30473(2004).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 24-144 IN COMPLEX WITH TACE, AND
RP DISULFIDE BONDS.
RX PubMed=18638486; DOI=10.1016/j.jmb.2008.06.088;
RA Wisniewska M., Goettig P., Maskos K., Belouski E., Winters D., Hecht R.,
RA Black R., Bode W.;
RT "Structural determinants of the ADAM inhibition by TIMP-3: crystal
RT structure of the TACE-N-TIMP-3 complex.";
RL J. Mol. Biol. 381:1307-1319(2008).
RN [18]
RP VARIANTS SFD CYS-191 AND CYS-204.
RX PubMed=7894485; DOI=10.1038/ng1294-352;
RA Weber B.H.F., Vogt G., Pruett R.C., Stoehr H., Felbor U.;
RT "Mutations in the tissue inhibitor of metalloproteinases-3 (TIMP3) in
RT patients with Sorsby's fundus dystrophy.";
RL Nat. Genet. 8:352-356(1994).
RN [19]
RP VARIANT SFD CYS-179.
RX PubMed=8634721; DOI=10.1093/hmg/4.12.2415;
RA Felbor U., Stoehr H., Amann T., Schoenherr U., Weber B.H.F.;
RT "A novel Ser156Cys mutation in the tissue inhibitor of metalloproteinases-3
RT (TIMP3) in Sorsby's fundus dystrophy with unusual clinical features.";
RL Hum. Mol. Genet. 4:2415-2416(1995).
RN [20]
RP VARIANT SFD CYS-190.
RX PubMed=7550309; DOI=10.1038/ng0995-27;
RA Jacobson S.G., Cideciyan A.V., Regunath G., Rodriguez F.J., Vandenburgh K.,
RA Sheffield V.C., Stone E.M.;
RT "Night blindness in Sorsby's fundus dystrophy reversed by vitamin A.";
RL Nat. Genet. 11:27-32(1995).
RN [21]
RP VARIANT SFD CYS-191.
RX PubMed=8728699; DOI=10.1136/jmg.33.3.233;
RA Felbor U., Stoehr H., Amann T., Schoenherr U., Apfelstedt-Sylla E.,
RA Weber B.H.F.;
RT "A second independent Tyr168Cys mutation in the tissue inhibitor of
RT metalloproteinases-3 (TIMP3) in Sorsby's fundus dystrophy.";
RL J. Med. Genet. 33:233-236(1996).
RN [22]
RP VARIANT SFD CYS-189.
RX PubMed=8981947;
RA Felbor U., Suvanto E.A., Forsius H.R., Eriksson A.W., Weber B.H.;
RT "Autosomal recessive Sorsby fundus dystrophy revisited: molecular evidence
RT for dominant inheritance.";
RL Am. J. Hum. Genet. 60:57-62(1997).
CC -!- FUNCTION: Complexes with metalloproteinases (such as collagenases) and
CC irreversibly inactivates them by binding to their catalytic zinc
CC cofactor. May form part of a tissue-specific acute response to
CC remodeling stimuli. Known to act on MMP-1, MMP-2, MMP-3, MMP-7, MMP-9,
CC MMP-13, MMP-14 and MMP-15.
CC -!- SUBUNIT: Interacts with EFEMP1. {ECO:0000269|PubMed:15123717,
CC ECO:0000269|PubMed:18638486}.
CC -!- INTERACTION:
CC P35625; P50052: AGTR2; NbExp=7; IntAct=EBI-1748085, EBI-1748067;
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix.
CC -!- DISEASE: Sorsby fundus dystrophy (SFD) [MIM:136900]: Rare autosomal
CC dominant macular disorder with an age of onset in the fourth decade. It
CC is characterized by loss of central vision from subretinal
CC neovascularization and atrophy of the ocular tissues. Generally,
CC macular disciform degeneration develops in the patients eye within 6
CC months to 6 years. {ECO:0000269|PubMed:7550309,
CC ECO:0000269|PubMed:7894485, ECO:0000269|PubMed:8634721,
CC ECO:0000269|PubMed:8728699, ECO:0000269|PubMed:8981947}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the protease inhibitor I35 (TIMP) family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Mutations of the TIMP3 gene; Note=Retina
CC International's Scientific Newsletter;
CC URL="https://www.retina-international.org/files/sci-news/timpmut.htm";
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DR EMBL; X76227; CAA53813.1; -; mRNA.
DR EMBL; S78453; AAB34532.1; -; mRNA.
DR EMBL; U14394; AAB60373.1; -; mRNA.
DR EMBL; U02571; AAA17672.1; -; mRNA.
DR EMBL; Z30183; CAA82918.1; -; Genomic_DNA.
DR EMBL; U33114; AAC50393.1; -; Genomic_DNA.
DR EMBL; U33110; AAC50393.1; JOINED; Genomic_DNA.
DR EMBL; U33111; AAC50393.1; JOINED; Genomic_DNA.
DR EMBL; U33112; AAC50393.1; JOINED; Genomic_DNA.
DR EMBL; U33113; AAC50393.1; JOINED; Genomic_DNA.
DR EMBL; U67195; AAB07547.1; -; mRNA.
DR EMBL; CR456593; CAG30479.1; -; mRNA.
DR EMBL; BT006848; AAP35494.1; -; mRNA.
DR EMBL; AK314871; BAG37386.1; -; mRNA.
DR EMBL; AL023282; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z98256; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471095; EAW60038.1; -; Genomic_DNA.
DR EMBL; BC014277; AAH14277.1; -; mRNA.
DR EMBL; L15078; AAA21815.1; -; mRNA.
DR EMBL; U38955; AAB17602.1; -; Genomic_DNA.
DR EMBL; U38952; AAB17602.1; JOINED; Genomic_DNA.
DR EMBL; U38953; AAB17602.1; JOINED; Genomic_DNA.
DR EMBL; U38954; AAB17602.1; JOINED; Genomic_DNA.
DR CCDS; CCDS13911.1; -.
DR PIR; S45317; S45317.
DR RefSeq; NP_000353.1; NM_000362.4.
DR PDB; 3CKI; X-ray; 2.30 A; B=24-144.
DR PDBsum; 3CKI; -.
DR AlphaFoldDB; P35625; -.
DR SMR; P35625; -.
DR BioGRID; 112934; 85.
DR IntAct; P35625; 23.
DR MINT; P35625; -.
DR STRING; 9606.ENSP00000266085; -.
DR DrugBank; DB05383; Pimagedine.
DR MEROPS; I35.003; -.
DR iPTMnet; P35625; -.
DR PhosphoSitePlus; P35625; -.
DR BioMuta; TIMP3; -.
DR DMDM; 730948; -.
DR jPOST; P35625; -.
DR MassIVE; P35625; -.
DR MaxQB; P35625; -.
DR PaxDb; P35625; -.
DR PeptideAtlas; P35625; -.
DR PRIDE; P35625; -.
DR ProteomicsDB; 55117; -.
DR Antibodypedia; 11314; 773 antibodies from 41 providers.
DR DNASU; 7078; -.
DR Ensembl; ENST00000266085.7; ENSP00000266085.5; ENSG00000100234.12.
DR GeneID; 7078; -.
DR KEGG; hsa:7078; -.
DR MANE-Select; ENST00000266085.7; ENSP00000266085.5; NM_000362.5; NP_000353.1.
DR UCSC; uc003anb.4; human.
DR CTD; 7078; -.
DR DisGeNET; 7078; -.
DR GeneCards; TIMP3; -.
DR HGNC; HGNC:11822; TIMP3.
DR HPA; ENSG00000100234; Low tissue specificity.
DR MalaCards; TIMP3; -.
DR MIM; 136900; phenotype.
DR MIM; 188826; gene.
DR neXtProt; NX_P35625; -.
DR OpenTargets; ENSG00000100234; -.
DR Orphanet; 59181; Sorsby pseudoinflammatory fundus dystrophy.
DR PharmGKB; PA36528; -.
DR VEuPathDB; HostDB:ENSG00000100234; -.
DR eggNOG; KOG4745; Eukaryota.
DR GeneTree; ENSGT00940000159601; -.
DR HOGENOM; CLU_084029_0_0_1; -.
DR InParanoid; P35625; -.
DR OMA; QVQYIYT; -.
DR OrthoDB; 1122531at2759; -.
DR PhylomeDB; P35625; -.
DR TreeFam; TF317409; -.
DR PathwayCommons; P35625; -.
DR Reactome; R-HSA-114608; Platelet degranulation.
DR SignaLink; P35625; -.
DR SIGNOR; P35625; -.
DR BioGRID-ORCS; 7078; 11 hits in 1077 CRISPR screens.
DR ChiTaRS; TIMP3; human.
DR EvolutionaryTrace; P35625; -.
DR GeneWiki; TIMP3; -.
DR GenomeRNAi; 7078; -.
DR Pharos; P35625; Tbio.
DR PRO; PR:P35625; -.
DR Proteomes; UP000005640; Chromosome 22.
DR RNAct; P35625; protein.
DR Bgee; ENSG00000100234; Expressed in synovial joint and 215 other tissues.
DR Genevisible; P35625; HS.
DR GO; GO:0005604; C:basement membrane; IEA:Ensembl.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
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; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; HDA:UniProtKB.
DR GO; GO:0031089; C:platelet dense granule lumen; TAS:Reactome.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008191; F:metalloendopeptidase inhibitor activity; IBA:GO_Central.
DR GO; GO:0002020; F:protease binding; IBA:GO_Central.
DR GO; GO:0071310; P:cellular response to organic substance; IEA:Ensembl.
DR GO; GO:0010951; P:negative regulation of endopeptidase activity; IBA:GO_Central.
DR GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; IMP:BHF-UCL.
DR GO; GO:0051045; P:negative regulation of membrane protein ectodomain proteolysis; IMP:BHF-UCL.
DR GO; GO:1904684; P:negative regulation of metalloendopeptidase activity; ISS:BHF-UCL.
DR GO; GO:1903984; P:positive regulation of TRAIL-activated apoptotic signaling pathway; IMP:BHF-UCL.
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:0007601; P:visual perception; IEA:UniProtKB-KW.
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; IPR015612; TIMP3.
DR InterPro; IPR027465; TIMP_C.
DR InterPro; IPR030490; TIMP_CS.
DR PANTHER; PTHR11844; PTHR11844; 1.
DR PANTHER; PTHR11844:SF22; PTHR11844:SF22; 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; Disease variant; Disulfide bond;
KW Extracellular matrix; Metal-binding; Metalloenzyme inhibitor;
KW Metalloprotease inhibitor; Protease inhibitor; Reference proteome;
KW Secreted; Sensory transduction; Signal; Vision; Zinc.
FT SIGNAL 1..23
FT /evidence="ECO:0000269|PubMed:7795886"
FT CHAIN 24..211
FT /note="Metalloproteinase inhibitor 3"
FT /id="PRO_0000034341"
FT DOMAIN 24..143
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:18638486,
FT ECO:0007744|PDB:3CKI"
FT REGION 88..89
FT /note="Involved in metalloproteinase-binding"
FT /evidence="ECO:0000269|PubMed:18638486,
FT ECO:0007744|PDB:3CKI"
FT REGION 105..188
FT /note="Mediates interaction with EFEMP1"
FT /evidence="ECO:0000269|PubMed:15123717"
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:18638486,
FT ECO:0007744|PDB:3CKI"
FT SITE 85
FT /note="Involved in metalloproteinase-binding"
FT /evidence="ECO:0000269|PubMed:18638486,
FT ECO:0007744|PDB:3CKI"
FT DISULFID 24..91
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00295,
FT ECO:0000269|PubMed:18638486, ECO:0007744|PDB:3CKI"
FT DISULFID 26..118
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00295,
FT ECO:0000269|PubMed:18638486, ECO:0007744|PDB:3CKI"
FT DISULFID 36..143
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00295,
FT ECO:0000269|PubMed:18638486, ECO:0007744|PDB:3CKI"
FT DISULFID 145..192
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT DISULFID 150..155
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT DISULFID 163..184
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT VARIANT 179
FT /note="S -> C (in SFD; dbSNP:rs137853300)"
FT /evidence="ECO:0000269|PubMed:8634721"
FT /id="VAR_007508"
FT VARIANT 189
FT /note="G -> C (in SFD; dbSNP:rs137853301)"
FT /evidence="ECO:0000269|PubMed:8981947"
FT /id="VAR_008290"
FT VARIANT 190
FT /note="G -> C (in SFD)"
FT /evidence="ECO:0000269|PubMed:7550309"
FT /id="VAR_010901"
FT VARIANT 191
FT /note="Y -> C (in SFD; dbSNP:rs137853299)"
FT /evidence="ECO:0000269|PubMed:7894485,
FT ECO:0000269|PubMed:8728699"
FT /id="VAR_007509"
FT VARIANT 204
FT /note="S -> C (in SFD; dbSNP:rs137853298)"
FT /evidence="ECO:0000269|PubMed:7894485"
FT /id="VAR_007510"
FT CONFLICT 16..23
FT /note="LGDWGAEA -> WGTGAPR (in Ref. 4; CAA82918)"
FT /evidence="ECO:0000305"
FT CONFLICT 21..22
FT /note="AE -> R (in Ref. 13; AAA21815)"
FT /evidence="ECO:0000305"
FT HELIX 31..37
FT /evidence="ECO:0007829|PDB:3CKI"
FT STRAND 39..42
FT /evidence="ECO:0007829|PDB:3CKI"
FT STRAND 45..52
FT /evidence="ECO:0007829|PDB:3CKI"
FT STRAND 55..57
FT /evidence="ECO:0007829|PDB:3CKI"
FT STRAND 59..65
FT /evidence="ECO:0007829|PDB:3CKI"
FT STRAND 69..71
FT /evidence="ECO:0007829|PDB:3CKI"
FT TURN 73..75
FT /evidence="ECO:0007829|PDB:3CKI"
FT STRAND 76..78
FT /evidence="ECO:0007829|PDB:3CKI"
FT STRAND 81..86
FT /evidence="ECO:0007829|PDB:3CKI"
FT HELIX 88..90
FT /evidence="ECO:0007829|PDB:3CKI"
FT STRAND 102..108
FT /evidence="ECO:0007829|PDB:3CKI"
FT TURN 124..126
FT /evidence="ECO:0007829|PDB:3CKI"
FT HELIX 129..136
FT /evidence="ECO:0007829|PDB:3CKI"
FT TURN 137..140
FT /evidence="ECO:0007829|PDB:3CKI"
SQ SEQUENCE 211 AA; 24145 MW; 15CF831028BABF7A CRC64;
MTPWLGLIVL LGSWSLGDWG AEACTCSPSH PQDAFCNSDI VIRAKVVGKK LVKEGPFGTL
VYTIKQMKMY RGFTKMPHVQ YIHTEASESL CGLKLEVNKY QYLLTGRVYD GKMYTGLCNF
VERWDQLTLS QRKGLNYRYH LGCNCKIKSC YYLPCFVTSK NECLWTDMLS NFGYPGYQSK
HYACIRQKGG YCSWYRGWAP PDKSIINATD P
