ID   TIMP2_CRILO             Reviewed;         196 AA.
AC   Q60453;
DT   15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1996, sequence version 1.
DT   03-AUG-2022, entry version 98.
DE   RecName: Full=Metalloproteinase inhibitor 2;
DE   AltName: Full=Tissue inhibitor of metalloproteinases 2;
DE            Short=TIMP-2;
DE   Flags: Precursor; Fragment;
GN   Name=TIMP2;
OS   Cricetulus longicaudatus (Long-tailed dwarf hamster) (Chinese hamster).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC   Cricetidae; Cricetinae; Cricetulus.
OX   NCBI_TaxID=10030;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Ovary;
RA   Suzuki Y.;
RL   Submitted (NOV-1993) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: Complexes with metalloproteinases (such as collagenases) and
CC       irreversibly inactivates them by binding to their catalytic zinc
CC       cofactor. {ECO:0000250}.
CC   -!- SUBUNIT: Interacts (via the C-terminal) with MMP2 (via the C-terminal
CC       PEX domain); the interaction inhibits the MMP2 activity. {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- PTM: The activity of TIMP2 is dependent on the presence of disulfide
CC       bonds. {ECO:0000250}.
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; X75924; CAA53528.1; -; mRNA.
DR   PIR; S38624; S38624.
DR   AlphaFoldDB; Q60453; -.
DR   BMRB; Q60453; -.
DR   SMR; Q60453; -.
DR   BindingDB; Q60453; -.
DR   MEROPS; I35.002; -.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0008191; F:metalloendopeptidase inhibitor activity; IEA:UniProtKB-KW.
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; IPR015613; TIMP2.
DR   InterPro; IPR027465; TIMP_C.
DR   InterPro; IPR030490; TIMP_CS.
DR   PANTHER; PTHR11844; PTHR11844; 1.
DR   PANTHER; PTHR11844:SF24; PTHR11844:SF24; 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; Metal-binding; Metalloenzyme inhibitor;
KW   Metalloprotease inhibitor; Protease inhibitor; Secreted; Signal; Zinc.
FT   SIGNAL          <1..2
FT                   /evidence="ECO:0000250"
FT   CHAIN           3..196
FT                   /note="Metalloproteinase inhibitor 2"
FT                   /id="PRO_0000034334"
FT   DOMAIN          3..128
FT                   /note="NTR"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT   REGION          3..6
FT                   /note="Involved in metalloproteinase-binding"
FT                   /evidence="ECO:0000250|UniProtKB:P16035"
FT   REGION          71..72
FT                   /note="Involved in metalloproteinase-binding"
FT                   /evidence="ECO:0000250|UniProtKB:P16035"
FT   BINDING         3
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            16
FT                   /note="Involved in metalloproteinase-binding"
FT                   /evidence="ECO:0000250|UniProtKB:P16035"
FT   SITE            37
FT                   /note="Involved in metalloproteinase-binding"
FT                   /evidence="ECO:0000250|UniProtKB:P16035"
FT   SITE            43
FT                   /note="Involved in metalloproteinase-binding"
FT                   /evidence="ECO:0000250|UniProtKB:P16035"
FT   DISULFID        3..74
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT   DISULFID        5..103
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT   DISULFID        15..128
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT   DISULFID        130..177
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT   DISULFID        135..140
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT   DISULFID        148..169
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT   NON_TER         1
SQ   SEQUENCE   196 AA;  21941 MW;  2ADAB9B54AF75381 CRC64;
     RACSCSPVHP QQAFCNADVV IRAKAVSEKE VDSGNDIYGN PIKRIQYEIK QIKMFKGPDK
     DIEFIYTAPS SAVCGVSLDV GGKKEYLIAG KAEGDGKMHI TLCDFIVPWD TLSTTQKKSL
     NHRYQMGCEC KITRCPMIPC YISSPDECLW MDWVTEKSIN GHQAKFFACI KRSDGSCAWY
     RGAAPPKQEF LDIEDP