TIMP3_MOUSE
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 03-AUG-2022, entry version 177.
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; P39876; -.
DR PeptideAtlas; P39876; -.
DR PRIDE; P39876; -.
DR ProteomicsDB; 258886; -.
DR Antibodypedia; 11314; 773 antibodies from 41 providers.
DR DNASU; 21859; -.
DR Ensembl; ENSMUST00000020234; ENSMUSP00000020234; ENSMUSG00000020044.
DR GeneID; 21859; -.
DR KEGG; mmu:21859; -.
DR UCSC; uc007gnr.1; mouse.
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; QVQYIYT; -.
DR OrthoDB; 799740at2759; -.
DR PhylomeDB; P39876; -.
DR TreeFam; TF317409; -.
DR Reactome; R-MMU-114608; Platelet degranulation.
DR BioGRID-ORCS; 21859; 2 hits in 70 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 261 other tissues.
DR ExpressionAtlas; P39876; baseline and differential.
DR Genevisible; P39876; MM.
DR GO; GO:0005604; C:basement membrane; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO: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:0010951; P:negative regulation of endopeptidase activity; IBA:GO_Central.
DR GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; 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:1903984; P:positive regulation of TRAIL-activated apoptotic signaling pathway; 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 GO; GO:0010033; P:response to organic substance; IBA:GO_Central.
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 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
