TIMP3_RAT
ID TIMP3_RAT Reviewed; 211 AA.
AC P48032;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 1.
DT 03-AUG-2022, entry version 134.
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=Timp-3;
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].
RX PubMed=8654952; DOI=10.1016/0378-1119(95)00783-0;
RA Wu I., Moses M.A.;
RT "Cloning and expression of the cDNA encoding rat tissue inhibitor of
RT metalloproteinase 3 (TIMP-3).";
RL Gene 168:243-246(1996).
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 -!- SIMILARITY: Belongs to the protease inhibitor I35 (TIMP) family.
CC {ECO:0000305}.
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DR EMBL; U27201; AAA75002.1; -; mRNA.
DR PIR; JC4630; JC4630.
DR AlphaFoldDB; P48032; -.
DR SMR; P48032; -.
DR STRING; 10116.ENSRNOP00000005746; -.
DR BindingDB; P48032; -.
DR ChEMBL; CHEMBL3881; -.
DR MEROPS; I35.003; -.
DR PaxDb; P48032; -.
DR PRIDE; P48032; -.
DR UCSC; RGD:3865; rat.
DR RGD; 3865; Timp3.
DR eggNOG; KOG4745; Eukaryota.
DR InParanoid; P48032; -.
DR PhylomeDB; P48032; -.
DR Reactome; R-RNO-114608; Platelet degranulation.
DR PRO; PR:P48032; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005604; C:basement membrane; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0031012; C:extracellular matrix; IBA:GO_Central.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
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:0007568; P:aging; IEP:RGD.
DR GO; GO:0071310; P:cellular response to organic substance; ISO:RGD.
DR GO; GO:0007417; P:central nervous system development; IEP:RGD.
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:RGD.
DR GO; GO:0051045; P:negative regulation of membrane protein ectodomain proteolysis; ISO:RGD.
DR GO; GO:1904684; P:negative regulation of metalloendopeptidase activity; ISO:RGD.
DR GO; GO:0045861; P:negative regulation of proteolysis; IMP:RGD.
DR GO; GO:1903984; P:positive regulation of TRAIL-activated apoptotic signaling pathway; ISO:RGD.
DR GO; GO:0043200; P:response to amino acid; IEP:RGD.
DR GO; GO:0034097; P:response to cytokine; IBA:GO_Central.
DR GO; GO:0043627; P:response to estrogen; IEP:RGD.
DR GO; GO:0051593; P:response to folic acid; IEP:RGD.
DR GO; GO:0009725; P:response to hormone; IEP:RGD.
DR GO; GO:0009612; P:response to mechanical stimulus; IEP:RGD.
DR GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
DR GO; GO:0010033; P:response to organic substance; IEP:RGD.
DR GO; GO:0042246; P:tissue regeneration; 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; 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 2: Evidence at transcript 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_0000034345"
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"
SQ SEQUENCE 211 AA; 24226 MW; 142FD4EB4BA8791E CRC64;
MTPWLGLVVL LSCWSLGHWG TEACTCSPSH PQDAFCNSDI VIRAKVVGKK LVKEGPFGTL
VYTIKQMKMY RGFSKMPHVQ YIHTEASESL CGLKLEVNKY QYLLTGRVYE GKMYTGLCNF
VERWDHLTLS QRKGLNYRYH LGCNCKIKSC YYLPCFVTSK KECLWTDMLS NFGYPGYQSK
HYACIRQKGG YCSWYRGWAP PDKSISNATD P
