TIMP1_RAT
ID TIMP1_RAT Reviewed; 217 AA.
AC P30120; P70533; Q53YM7;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 2.
DT 03-AUG-2022, entry version 168.
DE RecName: Full=Metalloproteinase inhibitor 1;
DE AltName: Full=Tissue inhibitor of metalloproteinases 1;
DE Short=TIMP-1;
DE Flags: Precursor;
GN Name=Timp1; Synonyms=Timp-1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Wistar; TISSUE=Dorsal skin;
RX PubMed=7926820; DOI=10.1016/0378-1119(94)90088-4;
RA Okada A., Garnier J.-M., Vicaire S., Basset P.;
RT "Cloning of the cDNA encoding rat tissue inhibitor of metalloproteinase 1
RT (TIMP-1), amino acid comparison with other TIMPs, and gene expression in
RT rat tissues.";
RL Gene 147:301-302(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Mammary gland;
RA Gibbons K.L., O'Grady R.L., Piper A.A.;
RT "Analysis of the cDNA encoding rat tissue inhibitor of metalloproteinases-
RT 1.";
RL Submitted (JAN-1996) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Dai W.-J., Jiang H.-C., Fu S.-B.;
RT "Rat TIMP-1 mRNA sequence.";
RL Submitted (FEB-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Prostate;
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 NUCLEOTIDE SEQUENCE [MRNA] OF 30-205.
RC TISSUE=Liver;
RX PubMed=8707259; DOI=10.1002/hep.510240129;
RA Iredale J.P., Benyon R.C., Arthur M.J.P., Ferris W.F., Alcolado R.,
RA Winwood P.J., Clark N., Murphy G.;
RT "Tissue inhibitor of metalloproteinase-1 messenger RNA expression is
RT enhanced relative to interstitial collagenase messenger RNA in experimental
RT liver injury and fibrosis.";
RL Hepatology 24:176-184(1996).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 39-156, PROTEIN SEQUENCE OF 24-38, INDUCTION,
RP FUNCTION, AND SUBCELLULAR LOCATION.
RC STRAIN=Sprague-Dawley; TISSUE=Sertoli cell;
RX PubMed=7777858; DOI=10.1126/science.7777858;
RA Boujrad N., Ogwuegbu S.O., Garnier M., Lee C.-H., Martin B.M.,
RA Papadopoulos V.;
RT "Identification of a stimulator of steroid hormone synthesis isolated from
RT testis.";
RL Science 268:1609-1612(1995).
RN [7]
RP PROTEIN SEQUENCE OF 24-45, FUNCTION, SUBCELLULAR LOCATION, AND
RP GLYCOSYLATION.
RX PubMed=1309971; DOI=10.1016/0003-9861(92)90009-l;
RA Roswit W.T., McCourt D.W., Partridge N.C., Jeffrey J.J.;
RT "Purification and sequence analysis of two rat tissue inhibitors of
RT metalloproteinases.";
RL Arch. Biochem. Biophys. 292:402-410(1992).
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. Also stimulates steroidogenesis by
CC Leydig and ovarian granuloma cells; procathepsin L is required for
CC maximal activity. {ECO:0000269|PubMed:1309971,
CC ECO:0000269|PubMed:7777858}.
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 (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:1309971,
CC ECO:0000269|PubMed:7777858}.
CC -!- INDUCTION: By follicle-stimulating hormone (FSH).
CC {ECO:0000269|PubMed:7777858}.
CC -!- PTM: The activity of TIMP1 is dependent on the presence of disulfide
CC bonds. {ECO:0000250}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:1309971}.
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; U06179; AAA85780.1; -; mRNA.
DR EMBL; L31883; AAA85373.1; -; mRNA.
DR EMBL; AY550026; AAS55641.1; -; mRNA.
DR EMBL; BC099821; AAH99821.1; -; mRNA.
DR EMBL; L29512; AAB08483.1; -; mRNA.
DR EMBL; U16022; AAA51653.1; ALT_SEQ; mRNA.
DR PIR; JC2557; JC2557.
DR RefSeq; NP_446271.1; NM_053819.1.
DR RefSeq; XP_006256670.1; XM_006256608.2.
DR AlphaFoldDB; P30120; -.
DR SMR; P30120; -.
DR STRING; 10116.ENSRNOP00000013745; -.
DR GlyGen; P30120; 2 sites.
DR PaxDb; P30120; -.
DR PRIDE; P30120; -.
DR Ensembl; ENSRNOT00000013745; ENSRNOP00000013745; ENSRNOG00000010208.
DR GeneID; 116510; -.
DR KEGG; rno:116510; -.
DR UCSC; RGD:621675; rat.
DR CTD; 7076; -.
DR RGD; 621675; Timp1.
DR eggNOG; KOG4745; Eukaryota.
DR GeneTree; ENSGT00940000161081; -.
DR HOGENOM; CLU_084029_0_0_1; -.
DR InParanoid; P30120; -.
DR OMA; TWQSLRP; -.
DR OrthoDB; 1122531at2759; -.
DR PhylomeDB; P30120; -.
DR TreeFam; TF317409; -.
DR Reactome; R-RNO-114608; Platelet degranulation.
DR Reactome; R-RNO-1592389; Activation of Matrix Metalloproteinases.
DR Reactome; R-RNO-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-RNO-8957275; Post-translational protein phosphorylation.
DR PRO; PR:P30120; -.
DR Proteomes; UP000002494; Chromosome X.
DR Bgee; ENSRNOG00000010208; Expressed in ovary and 19 other tissues.
DR Genevisible; P30120; RN.
DR GO; GO:0005604; C:basement membrane; IDA:RGD.
DR GO; GO:0031012; C:extracellular matrix; ISO:RGD.
DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
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:RGD.
DR GO; GO:0002020; F:protease binding; IPI:RGD.
DR GO; GO:0008270; F:zinc ion binding; ISO:RGD.
DR GO; GO:0007568; P:aging; IEP:RGD.
DR GO; GO:0051216; P:cartilage development; IEP:RGD.
DR GO; GO:0001775; P:cell activation; IMP:RGD.
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; ISO:RGD.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:RGD.
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:RGD.
DR GO; GO:1905049; P:negative regulation of metallopeptidase activity; ISO:RGD.
DR GO; GO:1901164; P:negative regulation of trophoblast cell migration; ISO:RGD.
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; IEP:RGD.
DR GO; GO:0009725; P:response to hormone; IBA:GO_Central.
DR GO; GO:0010033; P:response to organic substance; IEP:RGD.
DR GO; GO:0043434; P:response to peptide hormone; IEP:RGD.
DR GO; GO:0006694; P:steroid biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0042060; P:wound healing; IEP:RGD.
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 Direct protein sequencing; Disulfide bond; Glycoprotein; Growth factor;
KW Metal-binding; Metalloenzyme inhibitor; Metalloprotease inhibitor;
KW Phosphoprotein; Protease inhibitor; Reference proteome; Secreted; Signal;
KW Steroidogenesis; Zinc.
FT SIGNAL 1..23
FT /evidence="ECO:0000269|PubMed:1309971,
FT ECO:0000269|PubMed:7777858"
FT CHAIN 24..217
FT /note="Metalloproteinase inhibitor 1"
FT /id="PRO_0000034329"
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:0000250|UniProtKB:P16035"
FT REGION 90..91
FT /note="Involved in metalloproteinase-binding"
FT /evidence="ECO:0000250|UniProtKB:P16035"
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 MOD_RES 178
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P01033"
FT CARBOHYD 77
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 101
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 24..93
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT DISULFID 26..122
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT DISULFID 36..147
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT DISULFID 150..197
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT DISULFID 155..160
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT DISULFID 168..189
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT CONFLICT 80..81
FT /note="GF -> DI (in Ref. 5; AAB08483)"
FT /evidence="ECO:0000305"
FT CONFLICT 88
FT /note="A -> V (in Ref. 6; AAA51653)"
FT /evidence="ECO:0000305"
FT CONFLICT 103
FT /note="S -> R (in Ref. 5; AAB08483)"
FT /evidence="ECO:0000305"
FT CONFLICT 129..130
FT /note="HN -> AS (in Ref. 5; AAB08483)"
FT /evidence="ECO:0000305"
FT CONFLICT 136..140
FT /note="QKAFV -> RKGLT (in Ref. 5; AAB08483)"
FT /evidence="ECO:0000305"
FT CONFLICT 149
FT /note="V -> L (in Ref. 6; AAA51653)"
FT /evidence="ECO:0000305"
FT CONFLICT 157
FT /note="A -> V (in Ref. 5; AAB08483)"
FT /evidence="ECO:0000305"
FT CONFLICT 166
FT /note="S -> T (in Ref. 5; AAB08483)"
FT /evidence="ECO:0000305"
FT CONFLICT 185..187
FT /note="DHF -> RHL (in Ref. 5; AAB08483)"
FT /evidence="ECO:0000305"
FT CONFLICT 195
FT /note="D -> G (in Ref. 5; AAB08483)"
FT /evidence="ECO:0000305"
FT CONFLICT 201
FT /note="Y -> S (in Ref. 5; AAB08483)"
FT /evidence="ECO:0000305"
FT CONFLICT 204..205
FT /note="VS -> SR (in Ref. 5; AAB08483)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 217 AA; 23794 MW; C5AC240A61C1A1DF CRC64;
MAPFASLASG ILLLLSLIAS SKACSCAPTH PQTAFCNSDL VIRAKFMGSP EIIETTLYQR
YEIKMTKMLK GFDAVGNATG FRFAYTPAME SLCGYVHKSQ NRSEEFLIAG RLRNGNLHIT
ACSFLVPWHN LSPAQQKAFV KTYSAGCGVC TVFPCSAIPC KLESDSHCLW TDQILMGSEK
GYQSDHFACL PRNPDLCTWQ YLGVSMTRSL PLAKAEA
