ID   TIMP3_MOUSE             Reviewed;         211 AA.
AC   P39876; Q91WL9;
DT   01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1995, sequence version 1.
DT   27-MAR-2024, entry version 186.
DE   RecName: Full=Metalloproteinase inhibitor 3;
DE   AltName: Full=Tissue inhibitor of metalloproteinases 3;
DE            Short=TIMP-3;
DE   Flags: Precursor;
GN   Name=Timp3; Synonyms=Sun, Timp-3;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=8132674; DOI=10.1016/s0021-9258(17)37115-6;
RA   Leco K.J., Khokha R., Pavloff N., Hawkes S.P., Edwards D.R.;
RT   "Tissue inhibitor of metalloproteinases-3 (TIMP-3) is an extracellular
RT   matrix-associated protein with a distinctive pattern of expression in mouse
RT   cells and tissues.";
RL   J. Biol. Chem. 269:9352-9360(1994).
RN   [2]
RP   NUCLEOTIDE SEQUENCE.
RC   STRAIN=BALB/cJ; TISSUE=Lung, and Skin;
RX   PubMed=8118794;
RA   Sun Y., Hegamyer G., Colburn N.H.;
RT   "Molecular cloning of five messenger RNAs differentially expressed in
RT   preneoplastic or neoplastic JB6 mouse epidermal cells: one is homologous to
RT   human tissue inhibitor of metalloproteinases-3.";
RL   Cancer Res. 54:1139-1144(1994).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Lung;
RX   PubMed=7949367; DOI=10.1002/aja.1002000302;
RA   Apte S.S., Hayashi K., Seldin M.F., Mattei M.-G., Hayashi M., Olsen B.R.;
RT   "Gene encoding a novel murine tissue inhibitor of metalloproteinases
RT   (TIMP), TIMP-3, is expressed in developing mouse epithelia, cartilage, and
RT   muscle, and is located on mouse chromosome 10.";
RL   Dev. Dyn. 200:177-197(1994).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=7642607; DOI=10.1074/jbc.270.33.19312;
RA   Sun Y., Hegamyer G., Kim H., Sithanandam K., Li H., Watts R., Colburn N.H.;
RT   "Molecular cloning of mouse tissue inhibitor of metalloproteinases-3 and
RT   its promoter. Specific lack of expression in neoplastic JB6 cells may
RT   reflect altered gene methylation.";
RL   J. Biol. Chem. 270:19312-19319(1995).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=129/Sv;
RX   PubMed=7782289; DOI=10.1074/jbc.270.24.14313;
RA   Apte S.S., Olsen B.R., Murphy G.;
RT   "The gene structure of tissue inhibitor of metalloproteinases (TIMP)-3 and
RT   its inhibitory activities define the distinct TIMP gene family.";
RL   J. Biol. Chem. 270:14313-14318(1995).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Spinal ganglion;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=FVB/N; TISSUE=Kidney;
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   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Lung;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
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.
CC   -!- SUBUNIT: Interacts with EFEMP1. {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC       matrix.
CC   -!- TISSUE SPECIFICITY: Highest levels are found in kidney, lung and brain
CC       followed by ovary and uterus. Low levels are found in bone.
CC   -!- INDUCTION: Highly induced by phorbol ester (PMA), EGF and transforming
CC       growth factor-beta 1. Also induced by dexamethasone.
CC   -!- SIMILARITY: Belongs to the protease inhibitor I35 (TIMP) family.
CC       {ECO:0000305}.
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DR   EMBL; L27424; AAA40447.1; -; mRNA.
DR   EMBL; Z30970; CAA83218.1; -; mRNA.
DR   EMBL; L19622; AAC37669.1; -; mRNA.
DR   EMBL; U26437; AAA85860.1; -; Genomic_DNA.
DR   EMBL; U26433; AAA85860.1; JOINED; Genomic_DNA.
DR   EMBL; U26434; AAA85860.1; JOINED; Genomic_DNA.
DR   EMBL; U26435; AAA85860.1; JOINED; Genomic_DNA.
DR   EMBL; U26436; AAA85860.1; JOINED; Genomic_DNA.
DR   EMBL; AK083905; BAC39055.1; -; mRNA.
DR   EMBL; BC014713; AAH14713.1; -; mRNA.
DR   CCDS; CCDS24097.1; -.
DR   PIR; A53532; A53532.
DR   RefSeq; NP_035725.1; NM_011595.2.
DR   AlphaFoldDB; P39876; -.
DR   SMR; P39876; -.
DR   BioGRID; 204204; 1.
DR   STRING; 10090.ENSMUSP00000020234; -.
DR   MEROPS; I35.003; -.
DR   PhosphoSitePlus; P39876; -.
DR   PaxDb; 10090-ENSMUSP00000020234; -.
DR   PeptideAtlas; P39876; -.
DR   ProteomicsDB; 258886; -.
DR   Pumba; P39876; -.
DR   Antibodypedia; 11314; 818 antibodies from 41 providers.
DR   DNASU; 21859; -.
DR   Ensembl; ENSMUST00000020234.14; ENSMUSP00000020234.8; ENSMUSG00000020044.14.
DR   GeneID; 21859; -.
DR   KEGG; mmu:21859; -.
DR   UCSC; uc007gnr.1; mouse.
DR   AGR; MGI:98754; -.
DR   CTD; 7078; -.
DR   MGI; MGI:98754; Timp3.
DR   VEuPathDB; HostDB:ENSMUSG00000020044; -.
DR   eggNOG; KOG4745; Eukaryota.
DR   GeneTree; ENSGT00940000159601; -.
DR   HOGENOM; CLU_084029_0_0_1; -.
DR   InParanoid; P39876; -.
DR   OMA; RGFDKMP; -.
DR   OrthoDB; 5403389at2759; -.
DR   PhylomeDB; P39876; -.
DR   TreeFam; TF317409; -.
DR   Reactome; R-MMU-114608; Platelet degranulation.
DR   BioGRID-ORCS; 21859; 3 hits in 75 CRISPR screens.
DR   ChiTaRS; Timp3; mouse.
DR   PRO; PR:P39876; -.
DR   Proteomes; UP000000589; Chromosome 10.
DR   RNAct; P39876; Protein.
DR   Bgee; ENSMUSG00000020044; Expressed in pigmented layer of retina and 263 other cell types or tissues.
DR   ExpressionAtlas; P39876; baseline and differential.
DR   GO; GO:0005604; C:basement membrane; IDA:MGI.
DR   GO; GO:0031012; C:extracellular matrix; IBA:GO_Central.
DR   GO; GO:0005615; C:extracellular space; HDA:BHF-UCL.
DR   GO; GO:0008191; F:metalloendopeptidase inhibitor activity; IBA:GO_Central.
DR   GO; GO:0002020; F:protease binding; IBA:GO_Central.
DR   GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR   GO; GO:0071310; P:cellular response to organic substance; IDA:MGI.
DR   GO; GO:1901706; P:mesenchymal cell differentiation involved in bone development; ISO:MGI.
DR   GO; GO:0051045; P:negative regulation of membrane protein ectodomain proteolysis; ISO:MGI.
DR   GO; GO:1904684; P:negative regulation of metalloendopeptidase activity; IMP:BHF-UCL.
DR   GO; GO:0045861; P:negative regulation of proteolysis; ISO:MGI.
DR   GO; GO:1904706; P:negative regulation of vascular associated smooth muscle cell proliferation; ISO:MGI.
DR   GO; GO:0034097; P:response to cytokine; IBA:GO_Central.
DR   GO; GO:0009725; P:response to hormone; IBA:GO_Central.
DR   CDD; cd03585; NTR_TIMP; 1.
DR   Gene3D; 2.40.50.120; -; 1.
DR   Gene3D; 3.90.370.10; Tissue inhibitor of metalloproteinase-1. Chain B, domain 1; 1.
DR   InterPro; IPR001134; Netrin_domain.
DR   InterPro; IPR001820; TIMP.
DR   InterPro; IPR008993; TIMP-like_OB-fold.
DR   InterPro; IPR027465; TIMP_C.
DR   InterPro; IPR030490; TIMP_CS.
DR   PANTHER; PTHR11844; METALLOPROTEASE INHIBITOR; 1.
DR   PANTHER; PTHR11844:SF22; METALLOPROTEINASE INHIBITOR 3; 1.
DR   Pfam; PF00965; TIMP; 1.
DR   SMART; SM00206; NTR; 1.
DR   SUPFAM; SSF50242; TIMP-like; 1.
DR   PROSITE; PS50189; NTR; 1.
DR   PROSITE; PS00288; TIMP; 1.
DR   Genevisible; P39876; MM.
PE   1: Evidence at protein level;
KW   Disulfide bond; Extracellular matrix; Metal-binding;
KW   Metalloenzyme inhibitor; Metalloprotease inhibitor; Protease inhibitor;
KW   Reference proteome; Secreted; Signal; Zinc.
FT   SIGNAL          1..23
FT                   /evidence="ECO:0000255"
FT   CHAIN           24..211
FT                   /note="Metalloproteinase inhibitor 3"
FT                   /id="PRO_0000034344"
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:0000250|UniProtKB:P16035"
FT   REGION          88..89
FT                   /note="Involved in metalloproteinase-binding"
FT                   /evidence="ECO:0000250|UniProtKB:P16035"
FT   REGION          105..188
FT                   /note="Mediates interaction with EFEMP1"
FT                   /evidence="ECO:0000250"
FT   BINDING         24
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="ligand shared with metalloproteinase partner"
FT                   /evidence="ECO:0000250|UniProtKB:P16035"
FT   SITE            37
FT                   /note="Involved in metalloproteinase-binding"
FT                   /evidence="ECO:0000250|UniProtKB:P16035"
FT   DISULFID        24..91
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT   DISULFID        26..118
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT   DISULFID        36..143
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
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   CONFLICT        31
FT                   /note="P -> S (in Ref. 7; AAH14713)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        53
FT                   /note="K -> T (in Ref. 7; AAH14713)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        148
FT                   /note="K -> N (in Ref. 7; AAH14713)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   211 AA;  24182 MW;  184EDF5B8D69B07B CRC64;
     MTPWLGLVVL LSCWSLGHWG AEACTCSPSH PQDAFCNSDI VIRAKVVGKK LVKEGPFGTL
     VYTIKQMKMY RGFSKMPHVQ YIHTEASESL CGLKLEVNKY QYLLTGRVYE GKMYTGLCNF
     VERWDHLTLS QRKGLNYRYH LGCNCKIKSC YYLPCFVTSK NECLWTDMLS NFGYPGYQSK
     HYACIRQKGG YCSWYRGWAP PDKSISNATD P
//