TIMP2_BOVIN
ID TIMP2_BOVIN Reviewed; 220 AA.
AC P16368; Q3SZU3; Q9TVB1;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1991, sequence version 2.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=Metalloproteinase inhibitor 2;
DE AltName: Full=Collagenase inhibitor;
DE AltName: Full=Tissue inhibitor of metalloproteinases 2;
DE Short=TIMP-2;
DE Flags: Precursor;
GN Name=TIMP2;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2157214; DOI=10.1073/pnas.87.7.2800;
RA Boone T.C., Johnson M.J., de Clerck Y.A., Langley K.E.;
RT "cDNA cloning and expression of a metalloproteinase inhibitor related to
RT tissue inhibitor of metalloproteinases.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:2800-2804(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Crossbred X Angus; TISSUE=Liver;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 22-218.
RC TISSUE=Skeletal muscle;
RA Balcerzak D., Querengesser L., Dixon W.T., Baracos V.E.;
RT "Involvement of fibroblasts and muscle cells in the expression of an
RT extracellular proteolytic cascade in bovine skeletal muscle.";
RL Submitted (APR-1999) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP PROTEIN SEQUENCE OF 27-71.
RC TISSUE=Cartilage;
RX PubMed=3005321; DOI=10.1016/s0021-9258(17)35639-9;
RA Murray J.B., Allison K., Sudhalter J., Langer R.;
RT "Purification and partial amino acid sequence of a bovine cartilage-derived
RT collagenase inhibitor.";
RL J. Biol. Chem. 261:4154-4159(1986).
RN [5]
RP PROTEIN SEQUENCE OF 27-71.
RX PubMed=2551903; DOI=10.1016/s0021-9258(18)71515-9;
RA de Clerck Y.A., Yean T.D., Ratzkin B.J., Lu H.S., Langley K.E.;
RT "Purification and characterization of two related but distinct
RT metalloproteinase inhibitors secreted by bovine aortic endothelial cells.";
RL J. Biol. Chem. 264:17445-17453(1989).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 27-71.
RX PubMed=8424773; DOI=10.1042/bj2890065;
RA De Clerck Y.A., Yean T.D., Lee Y., Tomich J.M., Langley K.E.;
RT "Characterization of the functional domain of tissue inhibitor of
RT metalloproteinases-2 (TIMP-2).";
RL Biochem. J. 289:65-69(1993).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS) OF 27-210 IN COMPLEX WITH MMP-1.
RX PubMed=9724659; DOI=10.1093/emboj/17.17.5238;
RA Fernandez-Catalan C., Bode W., Huber R., Turk D., Calvete J.J., Lichte A.,
RA Tschesche H., Maskos K.;
RT "Crystal structure of the complex formed by the membrane type 1-matrix
RT metalloproteinase with the tissue inhibitor of metalloproteinases-2, the
RT soluble progelatinase A receptor.";
RL EMBO J. 17:5238-5248(1998).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 28-206 IN COMPLEX WITH MMP-13,
RP AND DISULFIDE BOND.
RX PubMed=17196980; DOI=10.1016/j.jmb.2006.11.072;
RA Maskos K., Lang R., Tschesche H., Bode W.;
RT "Flexibility and variability of TIMP binding: X-ray structure of the
RT complex between collagenase-3/MMP-13 and TIMP-2.";
RL J. Mol. Biol. 366:1222-1231(2007).
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.
CC -!- SIMILARITY: Belongs to the protease inhibitor I35 (TIMP) family.
CC {ECO:0000305}.
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DR EMBL; M32303; AAA30636.1; -; mRNA.
DR EMBL; BC102710; AAI02711.1; -; mRNA.
DR EMBL; AF144764; AAD30304.1; -; mRNA.
DR PIR; A35996; A35996.
DR RefSeq; NP_776897.2; NM_174472.4.
DR PDB; 1BQQ; X-ray; 2.75 A; T=27-210.
DR PDB; 1BUV; X-ray; 2.75 A; T=27-210.
DR PDB; 2E2D; X-ray; 2.00 A; C=27-206.
DR PDBsum; 1BQQ; -.
DR PDBsum; 1BUV; -.
DR PDBsum; 2E2D; -.
DR AlphaFoldDB; P16368; -.
DR SMR; P16368; -.
DR IntAct; P16368; 1.
DR STRING; 9913.ENSBTAP00000014476; -.
DR MEROPS; I35.002; -.
DR PaxDb; P16368; -.
DR GeneID; 282093; -.
DR KEGG; bta:282093; -.
DR CTD; 7077; -.
DR eggNOG; KOG4745; Eukaryota.
DR InParanoid; P16368; -.
DR OrthoDB; 1122531at2759; -.
DR EvolutionaryTrace; P16368; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0031012; C:extracellular matrix; IBA:GO_Central.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008191; F:metalloendopeptidase inhibitor activity; IBA:GO_Central.
DR GO; GO:0002020; F:protease binding; IBA:GO_Central.
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 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Disulfide bond; Metal-binding;
KW Metalloenzyme inhibitor; Metalloprotease inhibitor; Protease inhibitor;
KW Reference proteome; Secreted; Signal; Zinc.
FT SIGNAL 1..26
FT /evidence="ECO:0000269|PubMed:2551903,
FT ECO:0000269|PubMed:3005321"
FT CHAIN 27..220
FT /note="Metalloproteinase inhibitor 2"
FT /id="PRO_0000034331"
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:0000269|PubMed:17196980,
FT ECO:0007744|PDB:2E2D"
FT BINDING 27
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="ligand shared with metalloproteinase partner"
FT /evidence="ECO:0000269|PubMed:17196980,
FT ECO:0007744|PDB:2E2D"
FT SITE 64
FT /note="Involved in metalloproteinase-binding"
FT /evidence="ECO:0000269|PubMed:17196980,
FT ECO:0007744|PDB:2E2D"
FT SITE 96
FT /note="Involved in metalloproteinase-binding"
FT /evidence="ECO:0000269|PubMed:17196980,
FT ECO:0007744|PDB:2E2D"
FT SITE 158
FT /note="Involved in metalloproteinase-binding"
FT /evidence="ECO:0000269|PubMed:17196980,
FT ECO:0007744|PDB:2E2D"
FT SITE 177
FT /note="Involved in metalloproteinase-binding"
FT /evidence="ECO:0000269|PubMed:17196980,
FT ECO:0007744|PDB:2E2D"
FT DISULFID 27..98
FT /evidence="ECO:0000269|PubMed:17196980,
FT ECO:0007744|PDB:2E2D"
FT DISULFID 29..127
FT /evidence="ECO:0000269|PubMed:17196980,
FT ECO:0007744|PDB:2E2D"
FT DISULFID 39..152
FT /evidence="ECO:0000269|PubMed:17196980,
FT ECO:0007744|PDB:2E2D"
FT DISULFID 154..201
FT /evidence="ECO:0000269|PubMed:17196980,
FT ECO:0007744|PDB:2E2D"
FT DISULFID 159..164
FT /evidence="ECO:0000269|PubMed:17196980,
FT ECO:0007744|PDB:2E2D"
FT DISULFID 172..193
FT /evidence="ECO:0000269|PubMed:17196980,
FT ECO:0007744|PDB:2E2D"
FT CONFLICT 15
FT /note="L -> M (in Ref. 2; AAI02711)"
FT /evidence="ECO:0000305"
FT CONFLICT 42
FT /note="D -> C (in Ref. 4; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 56
FT /note="D -> E (in Ref. 4; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 68
FT /note="R -> S (in Ref. 4; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 88
FT /note="F -> L (in Ref. 2; AAI02711)"
FT /evidence="ECO:0000305"
FT CONFLICT 94..95
FT /note="AA -> SS (in Ref. 2; AAI02711)"
FT /evidence="ECO:0000305"
FT HELIX 34..40
FT /evidence="ECO:0007829|PDB:2E2D"
FT STRAND 42..59
FT /evidence="ECO:0007829|PDB:2E2D"
FT STRAND 61..64
FT /evidence="ECO:0007829|PDB:1BQQ"
FT STRAND 65..81
FT /evidence="ECO:0007829|PDB:2E2D"
FT STRAND 88..91
FT /evidence="ECO:0007829|PDB:2E2D"
FT HELIX 95..97
FT /evidence="ECO:0007829|PDB:2E2D"
FT STRAND 105..107
FT /evidence="ECO:0007829|PDB:2E2D"
FT STRAND 109..116
FT /evidence="ECO:0007829|PDB:2E2D"
FT STRAND 118..120
FT /evidence="ECO:0007829|PDB:1BQQ"
FT STRAND 121..123
FT /evidence="ECO:0007829|PDB:2E2D"
FT STRAND 130..132
FT /evidence="ECO:0007829|PDB:2E2D"
FT HELIX 133..135
FT /evidence="ECO:0007829|PDB:2E2D"
FT HELIX 138..143
FT /evidence="ECO:0007829|PDB:2E2D"
FT TURN 144..146
FT /evidence="ECO:0007829|PDB:2E2D"
FT HELIX 147..151
FT /evidence="ECO:0007829|PDB:2E2D"
FT STRAND 154..158
FT /evidence="ECO:0007829|PDB:2E2D"
FT STRAND 160..162
FT /evidence="ECO:0007829|PDB:2E2D"
FT STRAND 171..174
FT /evidence="ECO:0007829|PDB:2E2D"
FT HELIX 176..179
FT /evidence="ECO:0007829|PDB:2E2D"
FT STRAND 183..185
FT /evidence="ECO:0007829|PDB:1BQQ"
FT HELIX 186..190
FT /evidence="ECO:0007829|PDB:2E2D"
FT STRAND 192..195
FT /evidence="ECO:0007829|PDB:2E2D"
FT STRAND 197..204
FT /evidence="ECO:0007829|PDB:2E2D"
SQ SEQUENCE 220 AA; 24355 MW; 9A5438737110E7B7 CRC64;
MGAAARSLPL AFCLLLLGTL LPRADACSCS PVHPQQAFCN ADIVIRAKAV NKKEVDSGND
IYGNPIKRIQ YEIKQIKMFK GPDQDIEFIY TAPAAAVCGV SLDIGGKKEY LIAGKAEGNG
NMHITLCDFI VPWDTLSATQ KKSLNHRYQM GCECKITRCP MIPCYISSPD ECLWMDWVTE
KNINGHQAKF FACIKRSDGS CAWYRGAAPP KQEFLDIEDP
