TIMP2_CANLF
ID TIMP2_CANLF Reviewed; 220 AA.
AC Q9TTY1; O77804; Q9TTE9;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 15-MAY-2002, sequence version 2.
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 Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=11182158; DOI=10.1016/s0165-2427(00)00261-0;
RA Campbell S.E., Nasir L., Argyle D.J., Gault E.A., Duthie S., Bennett D.;
RT "Cloning of canine IL-1ra, TNFR and TIMP-2.";
RL Vet. Immunol. Immunopathol. 78:207-214(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 48-138.
RA Carter S.D., Barnes A., Clegg P.D.;
RT "Molecular studies of tissue inhibitors of metalloproteinases (TIMPs) in
RT canine joints.";
RL Submitted (SEP-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 69-220.
RC TISSUE=Fibrosarcoma;
RA Balkin R., Fang Y., Kitchell B.;
RT "Canine tissue inhibitor of matrix metalloproteinase-2 (TIMP-2).";
RL Submitted (SEP-1999) 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}.
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DR EMBL; AF112115; AAF21942.1; -; mRNA.
DR EMBL; AF095638; AAC63382.1; -; mRNA.
DR EMBL; AF188489; AAF01049.1; -; mRNA.
DR RefSeq; NP_001003082.1; NM_001003082.1.
DR AlphaFoldDB; Q9TTY1; -.
DR SMR; Q9TTY1; -.
DR STRING; 9612.ENSCAFP00000035219; -.
DR MEROPS; I35.002; -.
DR PaxDb; Q9TTY1; -.
DR PRIDE; Q9TTY1; -.
DR Ensembl; ENSCAFT00000109291; ENSCAFP00000068588; ENSCAFG00000058977.
DR Ensembl; ENSCAFT00040005922; ENSCAFP00040005109; ENSCAFG00040003116.
DR GeneID; 403633; -.
DR KEGG; cfa:403633; -.
DR CTD; 7077; -.
DR eggNOG; KOG4745; Eukaryota.
DR InParanoid; Q9TTY1; -.
DR OrthoDB; 1122531at2759; -.
DR Proteomes; UP000002254; Unplaced.
DR GO; GO:0031012; C:extracellular matrix; IBA:GO_Central.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0008191; F:metalloendopeptidase inhibitor activity; IBA:GO_Central.
DR GO; GO:0002020; F:protease binding; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR GO; GO:0010951; P:negative regulation of endopeptidase activity; IBA:GO_Central.
DR GO; GO:0051045; P:negative regulation of membrane protein ectodomain proteolysis; IBA:GO_Central.
DR GO; GO:0034097; P:response to cytokine; IBA:GO_Central.
DR GO; GO:0009725; P:response to hormone; IBA:GO_Central.
DR GO; GO:0010033; P:response to organic substance; IBA:GO_Central.
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_0000034332"
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"
FT CONFLICT 154
FT /note="C -> R (in Ref. 3; AAF01049)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 220 AA; 24297 MW; FBA49CAF58E20F72 CRC64;
MGAAARSLRL ALGLLLLATL PRPADACSCS PVHPQQAFCN ADVVIRAKAV SVKEVDSGND
IYGNPIKRIQ YEIKQIKMFK GPDKDIEFIY TAPSSAVCGV SLDIGGKKEY LIAGKAEGNG
KMHITLCDFI VPWDTLSSTQ KKSLNHRYQM GCECKITRCP MIPCYISSPD ECLWMDWVTE
KSINGHQAKF FACIKRSDGS CAWYRGAAPP KQEFLDIEDP
