TIMP2_CAVPO
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 03-AUG-2022, entry version 122.
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}.
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; 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; ENSCPOP00000007780; ENSCPOG00000008663.
DR GeneID; 100135629; -.
DR KEGG; cpoc:100135629; -.
DR CTD; 7077; -.
DR eggNOG; KOG4745; Eukaryota.
DR GeneTree; ENSGT00940000158348; -.
DR HOGENOM; CLU_084029_0_0_1; -.
DR InParanoid; Q9WUC6; -.
DR OMA; DHYACIK; -.
DR OrthoDB; 1122531at2759; -.
DR TreeFam; TF317409; -.
DR Proteomes; UP000005447; Unassembled WGS sequence.
DR Bgee; ENSCPOG00000008663; Expressed in hypothalamus and 13 other 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 GO; GO:1905049; P:negative regulation of metallopeptidase activity; IEA:Ensembl.
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; 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