TIMP2_RABIT
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 03-AUG-2022, entry version 102.
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 MEROPS; I35.002; -.
DR PRIDE; Q9TRZ7; -.
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 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; 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
