ID   TIMP4_BOVIN             Reviewed;         224 AA.
AC   O97563; Q2KHW6;
DT   01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT   30-MAY-2006, sequence version 2.
DT   03-AUG-2022, entry version 119.
DE   RecName: Full=Metalloproteinase inhibitor 4;
DE   AltName: Full=Tissue inhibitor of metalloproteinases 4;
DE            Short=TIMP-4;
DE   Flags: Precursor;
GN   Name=TIMP4;
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 [LARGE SCALE MRNA].
RC   STRAIN=Hereford; TISSUE=Hypothalamus;
RG   NIH - Mammalian Gene Collection (MGC) project;
RL   Submitted (JAN-2006) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 71-177.
RC   TISSUE=Adrenal cortex;
RA   Hosseini G.H., Pepper M.S.;
RL   Submitted (DEC-1997) 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   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- SIMILARITY: Belongs to the protease inhibitor I35 (TIMP) family.
CC       {ECO:0000305}.
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DR   EMBL; BC112857; AAI12858.1; -; mRNA.
DR   EMBL; AF037273; AAD02097.1; -; mRNA.
DR   RefSeq; NP_001039336.1; NM_001045871.2.
DR   AlphaFoldDB; O97563; -.
DR   SMR; O97563; -.
DR   STRING; 9913.ENSBTAP00000026999; -.
DR   MEROPS; I35.004; -.
DR   PaxDb; O97563; -.
DR   GeneID; 317694; -.
DR   KEGG; bta:317694; -.
DR   CTD; 7079; -.
DR   eggNOG; KOG4745; Eukaryota.
DR   InParanoid; O97563; -.
DR   OrthoDB; 1122531at2759; -.
DR   Proteomes; UP000009136; 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; IPR015614; TIMP4.
DR   InterPro; IPR027465; TIMP_C.
DR   InterPro; IPR030490; TIMP_CS.
DR   PANTHER; PTHR11844; PTHR11844; 1.
DR   PANTHER; PTHR11844:SF26; PTHR11844:SF26; 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..29
FT                   /evidence="ECO:0000255"
FT   CHAIN           30..224
FT                   /note="Metalloproteinase inhibitor 4"
FT                   /id="PRO_0000220986"
FT   DOMAIN          30..156
FT                   /note="NTR"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT   REGION          30..33
FT                   /note="Involved in metalloproteinase-binding"
FT                   /evidence="ECO:0000250|UniProtKB:P16035"
FT   REGION          99..100
FT                   /note="Involved in metalloproteinase-binding"
FT                   /evidence="ECO:0000250|UniProtKB:P16035"
FT   BINDING         30
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            69
FT                   /note="Involved in metalloproteinase-binding"
FT                   /evidence="ECO:0000250|UniProtKB:P16035"
FT   DISULFID        30..102
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT   DISULFID        32..131
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT   DISULFID        42..156
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT   DISULFID        158..205
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT   DISULFID        163..168
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT   DISULFID        176..197
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT   CONFLICT        113
FT                   /note="R -> Q (in Ref. 2; AAD02097)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        151
FT                   /note="H -> R (in Ref. 2; AAD02097)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   224 AA;  25593 MW;  49BB075ABCB82CF3 CRC64;
     MPQSPRPVPS WALLLRLLAL LRPPGLGEAC SCAPAHPQQH VCHSALAIRA KISSEKVVPA
     STDPADPQKM IRYEIKQIKM FKGFEKVNDI QYIYTPFDSS LCGVKLEANS QKRYLLTGQI
     LSDGKVFVHL CNYIEPWENL SFLQRESLNH HYHLNCGCQI TTCYAVPCTI SAPNECLWTD
     WLLERKLYGY QAQHYVCMKH VDGSCSWYQG RLPLRKEFVD IIQP