ID   TIMP2_CAVPO             Reviewed;         220 AA.
AC   Q9WUC6;
DT   21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1999, sequence version 1.
DT   24-JAN-2024, entry version 128.
DE   RecName: Full=Metalloproteinase inhibitor 2;
DE   AltName: Full=Tissue inhibitor of metalloproteinases 2;
DE            Short=TIMP-2;
DE   Flags: Precursor;
GN   Name=TIMP2;
OS   Cavia porcellus (Guinea pig).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Hystricomorpha; Caviidae;
OC   Cavia.
OX   NCBI_TaxID=10141;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=Hartley; TISSUE=Lung;
RX   PubMed=10749751; DOI=10.1152/ajplung.2000.278.4.l737;
RA   Melendez J., Maldonado V., Selman M., Pardo A.;
RT   "Cloning and expression of guinea pig TIMP-2. Expression in normal and
RT   hyperoxic lung injury.";
RL   Am. J. Physiol. 278:L737-L743(2000).
CC   -!- FUNCTION: Complexes with metalloproteinases (such as collagenases) and
CC       irreversibly inactivates them by binding to their catalytic zinc
CC       cofactor.
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   -!- TISSUE SPECIFICITY: Predominantly expressed in the lung in alveolar
CC       macrophages and epithelial cells. Also found in brain, kidney,
CC       intestine, spleen and heart.
CC   -!- PTM: The activity of TIMP2 is dependent on the presence of disulfide
CC       bonds.
CC   -!- SIMILARITY: Belongs to the protease inhibitor I35 (TIMP) family.
CC       {ECO:0000305}.
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DR   EMBL; AF127803; AAD28252.1; -; mRNA.
DR   RefSeq; NP_001166495.1; NM_001173024.1.
DR   AlphaFoldDB; Q9WUC6; -.
DR   BMRB; Q9WUC6; -.
DR   SMR; Q9WUC6; -.
DR   STRING; 10141.ENSCPOP00000007780; -.
DR   MEROPS; I35.002; -.
DR   Ensembl; ENSCPOT00000008741.3; ENSCPOP00000007780.2; ENSCPOG00000008663.4.
DR   GeneID; 100135629; -.
DR   KEGG; cpoc:100135629; -.
DR   CTD; 7077; -.
DR   VEuPathDB; HostDB:ENSCPOG00000008663; -.
DR   eggNOG; KOG4745; Eukaryota.
DR   GeneTree; ENSGT00940000158348; -.
DR   HOGENOM; CLU_084029_0_0_1; -.
DR   InParanoid; Q9WUC6; -.
DR   OMA; SAQDECL; -.
DR   OrthoDB; 5403389at2759; -.
DR   TreeFam; TF317409; -.
DR   Proteomes; UP000005447; Unassembled WGS sequence.
DR   Bgee; ENSCPOG00000008663; Expressed in hypothalamus and 13 other cell types or tissues.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0008191; F:metalloendopeptidase inhibitor activity; IEA:UniProtKB-KW.
DR   GO; GO:0002020; F:protease binding; IEA:Ensembl.
DR   GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR   CDD; cd03585; NTR_TIMP; 1.
DR   Gene3D; 2.40.50.120; -; 1.
DR   Gene3D; 3.90.370.10; Tissue inhibitor of metalloproteinase-1. Chain B, domain 1; 1.
DR   InterPro; IPR001134; Netrin_domain.
DR   InterPro; IPR001820; TIMP.
DR   InterPro; IPR008993; TIMP-like_OB-fold.
DR   InterPro; IPR027465; TIMP_C.
DR   InterPro; IPR030490; TIMP_CS.
DR   PANTHER; PTHR11844; METALLOPROTEASE INHIBITOR; 1.
DR   PANTHER; PTHR11844:SF24; METALLOPROTEINASE INHIBITOR 2; 1.
DR   Pfam; PF00965; TIMP; 1.
DR   SMART; SM00206; NTR; 1.
DR   SUPFAM; SSF50242; TIMP-like; 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; Reference proteome;
KW   Secreted; Signal; Zinc.
FT   SIGNAL          1..26
FT                   /evidence="ECO:0000255"
FT   CHAIN           27..220
FT                   /note="Metalloproteinase inhibitor 2"
FT                   /id="PRO_0000034333"
FT   DOMAIN          27..152
FT                   /note="NTR"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT   REGION          27..30
FT                   /note="Involved in metalloproteinase-binding"
FT                   /evidence="ECO:0000250|UniProtKB:P16035"
FT   REGION          95..96
FT                   /note="Involved in metalloproteinase-binding"
FT                   /evidence="ECO:0000250|UniProtKB:P16035"
FT   BINDING         27
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            40
FT                   /note="Involved in metalloproteinase-binding"
FT                   /evidence="ECO:0000250|UniProtKB:P16035"
FT   SITE            61
FT                   /note="Involved in metalloproteinase-binding"
FT                   /evidence="ECO:0000250|UniProtKB:P16035"
FT   SITE            67
FT                   /note="Involved in metalloproteinase-binding"
FT                   /evidence="ECO:0000250|UniProtKB:P16035"
FT   DISULFID        27..98
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT   DISULFID        29..127
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT   DISULFID        39..152
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT   DISULFID        154..201
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT   DISULFID        159..164
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT   DISULFID        172..193
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
SQ   SEQUENCE   220 AA;  24318 MW;  2A2541764755B9AF CRC64;
     MGATARSLRL ALGLLLLGTL PRGADACSCS PVHPQQAFCN ADVVIRAKAV SEKEVDSGND
     IYGNPIKRIQ YEIKQIKMFK GPEKDIEFIY TAPSSAVCGV SLDVGGKKEY LIAGKAEGDG
     KMHITLCDFI VPWDTLSTTQ KKSLNHRYQM GCECKITRCP MIPCYISSPD ECLWMDWVTE
     KSINGHQAKF FACIKRSDGS CAWYRGAAPP KQEFLDIEDP
//