TIMP1_MOUSE
ID TIMP1_MOUSE Reviewed; 205 AA.
AC P12032; P20064; Q61720;
DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1991, sequence version 2.
DT 03-AUG-2022, entry version 190.
DE RecName: Full=Metalloproteinase inhibitor 1;
DE AltName: Full=Collagenase inhibitor 16C8 fibroblast;
DE AltName: Full=Erythroid-potentiating activity;
DE Short=EPA;
DE AltName: Full=TPA-S1;
DE AltName: Full=TPA-induced protein;
DE AltName: Full=Tissue inhibitor of metalloproteinases 1;
DE Short=TIMP-1;
DE Flags: Precursor;
GN Name=Timp1; Synonyms=Timp, Timp-1;
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 [GENOMIC DNA].
RX PubMed=3034603; DOI=10.1002/j.1460-2075.1987.tb04804.x;
RA Gewert D.R., Coulombe B., Castelino M., Skup D., Williams B.R.G.;
RT "Characterization and expression of a murine gene homologous to human
RT EPA/TIMP: a virus-induced gene in the mouse.";
RL EMBO J. 6:651-657(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Fibroblast;
RX PubMed=3024122; DOI=10.1093/nar/14.22.8863;
RA Edwards D.R., Waterhouse P., Holman M.L., Denhardt D.T.;
RT "A growth-responsive gene (16C8) in normal mouse fibroblasts homologous to
RT a human collagenase inhibitor with erythroid-potentiating activity:
RT evidence for inducible and constitutive transcripts.";
RL Nucleic Acids Res. 14:8863-8878(1986).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C3H/HeJ;
RX PubMed=3670294; DOI=10.1128/mcb.7.8.2821-2829.1987;
RA Johnson M.D., Housey G.M., Kirschmeier P.T., Weinstein I.B.;
RT "Molecular cloning of gene sequences regulated by tumor promoters and
RT mitogens through protein kinase C.";
RL Mol. Cell. Biol. 7:2821-2829(1987).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary gland, and Osteoblast;
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 [5]
RP PARTIAL NUCLEOTIDE SEQUENCE, AND DEVELOPMENTAL STAGE.
RC TISSUE=Embryo;
RX PubMed=2744464; DOI=10.1101/gad.3.6.848;
RA Brenner C.A., Adler R.R., Rappolee D.A., Pedersen R.A., Werb Z.;
RT "Genes for extracellular-matrix-degrading metalloproteinases and their
RT inhibitor, TIMP, are expressed during early mammalian development.";
RL Genes Dev. 3:848-859(1989).
RN [6]
RP NUCLEOTIDE SEQUENCE OF 168-205.
RX PubMed=6179042; DOI=10.1093/nar/10.10.3069;
RA Skup D., Windass J.D., Sor F.S., George H., Williams B.R., Fukuhara H.,
RA de Maeyer-Guignard J., de Maeyer E.;
RT "Molecular cloning of partial cDNA copies of two distinct mouse IFN-beta
RT mRNAs.";
RL Nucleic Acids Res. 10:3069-3084(1982).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH CD63, AND IDENTIFICATION
RP 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).
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 (By similarity). Also
CC functions as a growth factor that regulates cell differentiation,
CC migration and cell death and activates cellular signaling cascades via
CC CD63 and ITGB1. Plays a role in integrin signaling. {ECO:0000250,
CC ECO:0000269|PubMed:23522389}.
CC -!- SUBUNIT: Interacts with MMP1, MMP3, MMP10 and MMP13, but has only very
CC low affinity for MMP14 (By similarity). Interacts with CD63; identified
CC in a complex with CD63 and ITGB1. {ECO:0000250,
CC ECO:0000269|PubMed:23522389}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:23522389}.
CC -!- TISSUE SPECIFICITY: Found in fetal and adult tissues. Highest levels
CC are found in bone. Also found in lung, ovary and uterus.
CC -!- DEVELOPMENTAL STAGE: Present in unfertilized eggs and at the zygote and
CC cleavage stages. Levels increase at the blastocyst stage and with
CC endoderm differentiation. {ECO:0000269|PubMed:2744464}.
CC -!- INDUCTION: Regulated by tumor promoters and mitogens through protein
CC kinase C. Also induced by viruses.
CC -!- PTM: The activity of TIMP1 is dependent on the presence of disulfide
CC bonds. {ECO:0000250}.
CC -!- PTM: N-glycosylated. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protease inhibitor I35 (TIMP) family.
CC {ECO:0000305}.
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DR EMBL; M28312; AAB42179.1; -; Genomic_DNA.
DR EMBL; M28308; AAB42179.1; JOINED; Genomic_DNA.
DR EMBL; M28309; AAB42179.1; JOINED; Genomic_DNA.
DR EMBL; M28310; AAB42179.1; JOINED; Genomic_DNA.
DR EMBL; M28311; AAB42179.1; JOINED; Genomic_DNA.
DR EMBL; X04684; CAA28387.1; -; mRNA.
DR EMBL; M17243; AAA40471.1; -; mRNA.
DR EMBL; BC008107; AAH08107.1; -; mRNA.
DR EMBL; BC034260; AAH34260.1; -; mRNA.
DR EMBL; BC051260; AAH51260.1; -; mRNA.
DR EMBL; V00755; CAA24132.1; -; mRNA.
DR CCDS; CCDS30046.1; -.
DR PIR; A26917; A26106.
DR RefSeq; NP_001037849.1; NM_001044384.1.
DR RefSeq; NP_035723.2; NM_011593.2.
DR AlphaFoldDB; P12032; -.
DR SMR; P12032; -.
DR STRING; 10090.ENSMUSP00000009530; -.
DR GlyGen; P12032; 2 sites.
DR PhosphoSitePlus; P12032; -.
DR CPTAC; non-CPTAC-3503; -.
DR MaxQB; P12032; -.
DR PaxDb; P12032; -.
DR PeptideAtlas; P12032; -.
DR PRIDE; P12032; -.
DR ProteomicsDB; 259395; -.
DR Antibodypedia; 11411; 1125 antibodies from 51 providers.
DR DNASU; 21857; -.
DR Ensembl; ENSMUST00000009530; ENSMUSP00000009530; ENSMUSG00000001131.
DR Ensembl; ENSMUST00000115342; ENSMUSP00000110999; ENSMUSG00000001131.
DR GeneID; 21857; -.
DR KEGG; mmu:21857; -.
DR UCSC; uc009sty.1; mouse.
DR CTD; 7076; -.
DR MGI; MGI:98752; Timp1.
DR VEuPathDB; HostDB:ENSMUSG00000001131; -.
DR eggNOG; KOG4745; Eukaryota.
DR GeneTree; ENSGT00940000161081; -.
DR HOGENOM; CLU_084029_0_0_1; -.
DR InParanoid; P12032; -.
DR OMA; TWQSLRP; -.
DR OrthoDB; 1122531at2759; -.
DR PhylomeDB; P12032; -.
DR TreeFam; TF317409; -.
DR Reactome; R-MMU-114608; Platelet degranulation.
DR Reactome; R-MMU-1592389; Activation of Matrix Metalloproteinases.
DR Reactome; R-MMU-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-MMU-8957275; Post-translational protein phosphorylation.
DR BioGRID-ORCS; 21857; 3 hits in 72 CRISPR screens.
DR PRO; PR:P12032; -.
DR Proteomes; UP000000589; Chromosome X.
DR RNAct; P12032; protein.
DR Bgee; ENSMUSG00000001131; Expressed in vault of skull and 201 other tissues.
DR Genevisible; P12032; MM.
DR GO; GO:0005604; C:basement membrane; IDA:MGI.
DR GO; GO:0031012; C:extracellular matrix; IDA:MGI.
DR GO; GO:0005615; C:extracellular space; HDA:BHF-UCL.
DR GO; GO:0005125; F:cytokine activity; ISS:UniProtKB.
DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR GO; GO:0008191; F:metalloendopeptidase inhibitor activity; ISS:UniProtKB.
DR GO; GO:0030414; F:peptidase inhibitor activity; ISO:MGI.
DR GO; GO:0002020; F:protease binding; ISO:MGI.
DR GO; GO:0008270; F:zinc ion binding; ISO:MGI.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0051216; P:cartilage development; IEA:Ensembl.
DR GO; GO:0001775; P:cell activation; ISO:MGI.
DR GO; GO:0071492; P:cellular response to UV-A; ISS:UniProtKB.
DR GO; GO:0002248; P:connective tissue replacement involved in inflammatory response wound healing; IDA:MGI.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:MGI.
DR GO; GO:0043086; P:negative regulation of catalytic activity; ISS:UniProtKB.
DR GO; GO:0010951; P:negative regulation of endopeptidase activity; ISS:UniProtKB.
DR GO; GO:0051045; P:negative regulation of membrane protein ectodomain proteolysis; ISO:MGI.
DR GO; GO:1905049; P:negative regulation of metallopeptidase activity; ISO:MGI.
DR GO; GO:1901164; P:negative regulation of trophoblast cell migration; ISO:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:2001044; P:regulation of integrin-mediated signaling pathway; ISS: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 Disulfide bond; Glycoprotein; Growth factor; Metal-binding;
KW Metalloenzyme inhibitor; Metalloprotease inhibitor; Phosphoprotein;
KW Protease inhibitor; Reference proteome; Secreted; Signal; Zinc.
FT SIGNAL 1..24
FT CHAIN 25..205
FT /note="Metalloproteinase inhibitor 1"
FT /id="PRO_0000034325"
FT DOMAIN 25..148
FT /note="NTR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT REGION 25..28
FT /note="Involved in metalloproteinase-binding"
FT /evidence="ECO:0000250|UniProtKB:P16035"
FT REGION 91..92
FT /note="Involved in metalloproteinase-binding"
FT /evidence="ECO:0000250|UniProtKB:P16035"
FT BINDING 25
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 38
FT /note="Involved in metalloproteinase-binding"
FT /evidence="ECO:0000250|UniProtKB:P16035"
FT MOD_RES 179
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P01033"
FT CARBOHYD 54
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 102
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 25..94
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT DISULFID 27..123
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT DISULFID 37..148
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT DISULFID 151..197
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT DISULFID 156..161
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT DISULFID 169..189
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT CONFLICT 52
FT /note="E -> R (in Ref. 1; AAB42179)"
FT /evidence="ECO:0000305"
FT CONFLICT 66
FT /note="M -> MM (in Ref. 1; AAB42179)"
FT /evidence="ECO:0000305"
FT CONFLICT 117..118
FT /note="NL -> KF (in Ref. 1; AAB42179)"
FT /evidence="ECO:0000305"
FT CONFLICT 121
FT /note="S -> N (in Ref. 1; AAB42179)"
FT /evidence="ECO:0000305"
FT CONFLICT 139
FT /note="A -> V (in Ref. 1)"
FT /evidence="ECO:0000305"
FT CONFLICT 143
FT /note="T -> KN (in Ref. 1)"
FT /evidence="ECO:0000305"
FT CONFLICT 194
FT /note="P -> L (in Ref. 1 and 6)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 205 AA; 22628 MW; FACA952D49A50FD7 CRC64;
MMAPFASLAS GILLLLSLIA SSKACSCAPP HPQTAFCNSD LVIRAKFMGS PEINETTLYQ
RYKIKMTKML KGFKAVGNAA DIRYAYTPVM ESLCGYAHKS QNRSEEFLIT GRLRNGNLHI
SACSFLVPWR TLSPAQQRAF SKTYSAGCGV CTVFPCLSIP CKLESDTHCL WTDQVLVGSE
DYQSRHFACL PRNPGLCTWR SLGAR
