ID   TIMP2_RABIT             Reviewed;         194 AA.
AC   Q9TRZ7; O97589;
DT   30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-2000, sequence version 1.
DT   24-JAN-2024, entry version 107.
DE   RecName: Full=Metalloproteinase inhibitor 2;
DE   AltName: Full=Tissue inhibitor of metalloproteinases 2;
DE            Short=TIMP-2;
GN   Name=TIMP2;
OS   Oryctolagus cuniculus (Rabbit).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX   NCBI_TaxID=9986;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=8548358; DOI=10.1007/bf01778292;
RA   Wertheimer S.J., Katz S.L.;
RT   "Molecular cloning and characterization of rabbit TIMP2.";
RL   Inflamm. Res. 44:S121-S122(1995).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 17-154.
RC   STRAIN=New Zealand white;
RX   PubMed=9837780; DOI=10.1006/bbrc.1998.9734;
RA   Reno C., Boykiw R., Martinez M.L., Hart D.A.;
RT   "Temporal alterations in mRNA levels for proteinases and inhibitors and
RT   their potential regulators in the healing medial collateral ligament.";
RL   Biochem. Biophys. Res. Commun. 252:757-763(1998).
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   -!- 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}.
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DR   EMBL; AF069713; AAC95005.1; -; mRNA.
DR   AlphaFoldDB; Q9TRZ7; -.
DR   SMR; Q9TRZ7; -.
DR   STRING; 9986.ENSOCUP00000005290; -.
DR   MEROPS; I35.002; -.
DR   InParanoid; Q9TRZ7; -.
DR   Proteomes; UP000001811; Unplaced.
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   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; Zinc.
FT   CHAIN           1..194
FT                   /note="Metalloproteinase inhibitor 2"
FT                   /id="PRO_0000220984"
FT   DOMAIN          1..126
FT                   /note="NTR"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT   REGION          1..4
FT                   /note="Involved in metalloproteinase-binding"
FT                   /evidence="ECO:0000250|UniProtKB:P16035"
FT   REGION          69..70
FT                   /note="Involved in metalloproteinase-binding"
FT                   /evidence="ECO:0000250|UniProtKB:P16035"
FT   BINDING         1
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            14
FT                   /note="Involved in metalloproteinase-binding"
FT                   /evidence="ECO:0000250|UniProtKB:P16035"
FT   SITE            35
FT                   /note="Involved in metalloproteinase-binding"
FT                   /evidence="ECO:0000250|UniProtKB:P16035"
FT   SITE            41
FT                   /note="Involved in metalloproteinase-binding"
FT                   /evidence="ECO:0000250|UniProtKB:P16035"
FT   DISULFID        1..72
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT   DISULFID        3..101
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT   DISULFID        13..126
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT   DISULFID        128..175
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT   DISULFID        133..138
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT   DISULFID        146..167
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT   CONFLICT        17
FT                   /note="I -> V (in Ref. 2; AAC95005)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        25..26
FT                   /note="NK -> SE (in Ref. 2; AAC95005)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        58
FT                   /note="Q -> K (in Ref. 2; AAC95005)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        78
FT                   /note="I -> V (in Ref. 2; AAC95005)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        93..95
FT                   /note="NGN -> DGR (in Ref. 2; AAC95005)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        109
FT                   /note="T -> S (in Ref. 2; AAC95005)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        112
FT                   /note="A -> S (in Ref. 2; AAC95005)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        131
FT                   /note="T -> S (in Ref. 2; AAC95005)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   194 AA;  21849 MW;  CDC8101A2D38C4A9 CRC64;
     CSCSPVHPQQ AFCNADIVIR AKAVNKKEVD SGNDIYGNPI KRIQYEIKQI KMFKGPDQDI
     EFIYTAPSSA VCGVSLDIGG KKEYLIAGKA EGNGNMHITL CDFIVPWDTL SATQKKSLNH
     RYQMGCECKI TRCPMIPCYI SSPDECLWMD WVTEKNINRH QAKFFACIKR SDGSCAWYRG
     AAPPKQEFLD IEDP
//