TIMP1_CANLF
ID TIMP1_CANLF Reviewed; 207 AA.
AC P81546; Q9TQS5;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2000, sequence version 2.
DT 03-AUG-2022, entry version 132.
DE RecName: Full=Metalloproteinase inhibitor 1;
DE AltName: Full=Tissue inhibitor of metalloproteinases 1;
DE Short=TIMP-1;
DE Flags: Precursor;
GN Name=TIMP1;
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].
RC STRAIN=Cocker spaniel; TISSUE=Kidney;
RX PubMed=10411101; DOI=10.1023/a:1006596620406;
RA Noritake H., Miyamori H., Goto C., Seiki M., Sato H.;
RT "Overexpression of tissue inhibitor of matrix metalloproteinases-1 (TIMP-1)
RT in metastatic MDCK cells transformed by v-src.";
RL Clin. Exp. Metastasis 17:105-110(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RX PubMed=9931441; DOI=10.1016/s0378-1119(98)00521-6;
RA Zeiss C.J., Acland G.M., Aguirre G.D., Ray K.;
RT "TIMP-1 expression is increased in X-linked progressive retinal atrophy
RT despite its exclusion as a candidate gene.";
RL Gene 225:67-75(1998).
RN [3]
RP CHARACTERIZATION.
RX PubMed=1794505; DOI=10.1042/bst019372s;
RA Chopra R., Koklitis P.A., Bergin S., Rowe J., Angal S.;
RT "Purification of recombinant dog tissue inhibitor of metalloproteinases.";
RL Biochem. Soc. Trans. 19:372S-372S(1991).
CC -!- FUNCTION: Metalloproteinase inhibitor that functions by forming one to
CC one complexes with target metalloproteinases, such as collagenases, and
CC irreversibly inactivates them by binding to their catalytic zinc
CC cofactor. Acts on MMP1, MMP2, MMP3, MMP7, MMP8, MMP9, MMP10, MMP11,
CC MMP12, MMP13 and MMP16. Does not act on MMP14. Also functions as a
CC growth factor that regulates cell differentiation, migration and cell
CC death and activates cellular signaling cascades via CD63 and ITGB1.
CC Plays a role in integrin signaling.
CC -!- SUBUNIT: Interacts with MMP1, MMP3, MMP10 and MMP13, but has only very
CC low affinity for MMP14. Interacts with CD63; identified in a complex
CC with CD63 and ITGB1 (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed. Highest expression in
CC kidney and ovary.
CC -!- PTM: The activity of TIMP1 is dependent on the presence of disulfide
CC bonds.
CC -!- PTM: N-glycosylated. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protease inhibitor I35 (TIMP) family.
CC {ECO:0000305}.
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DR EMBL; AB016817; BAA32393.1; -; mRNA.
DR EMBL; AF077817; AAD10632.1; -; mRNA.
DR EMBL; AF079767; AAD10633.1; -; Genomic_DNA.
DR RefSeq; NP_001003182.1; NM_001003182.1.
DR AlphaFoldDB; P81546; -.
DR SMR; P81546; -.
DR STRING; 9612.ENSCAFP00000022333; -.
DR PaxDb; P81546; -.
DR GeneID; 403816; -.
DR KEGG; cfa:403816; -.
DR CTD; 7076; -.
DR eggNOG; KOG4745; Eukaryota.
DR InParanoid; P81546; -.
DR Proteomes; UP000002254; Unplaced.
DR GO; GO:0031012; C:extracellular matrix; IBA:GO_Central.
DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR GO; GO:0005125; F:cytokine activity; ISS:UniProtKB.
DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008191; F:metalloendopeptidase inhibitor activity; ISS:UniProtKB.
DR GO; GO:0002020; F:protease binding; IBA:GO_Central.
DR GO; GO:0071492; P:cellular response to UV-A; ISS:UniProtKB.
DR GO; GO:0043086; P:negative regulation of catalytic activity; ISS:UniProtKB.
DR GO; GO:0010951; P:negative regulation of endopeptidase activity; ISS:UniProtKB.
DR GO; GO:0051045; P:negative regulation of membrane protein ectodomain proteolysis; IBA:GO_Central.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:2001044; P:regulation of integrin-mediated signaling pathway; ISS:UniProtKB.
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; IPR015611; TIMP1.
DR InterPro; IPR027465; TIMP_C.
DR PANTHER; PTHR11844; PTHR11844; 1.
DR PANTHER; PTHR11844:SF20; PTHR11844:SF20; 1.
DR Pfam; PF00965; TIMP; 1.
DR SMART; SM00206; NTR; 1.
DR SUPFAM; SSF50242; SSF50242; 1.
DR PROSITE; PS50189; NTR; 1.
PE 1: Evidence at protein level;
KW Disulfide bond; Glycoprotein; Growth factor; Metal-binding;
KW Metalloenzyme inhibitor; Metalloprotease inhibitor; Phosphoprotein;
KW Protease inhibitor; Reference proteome; Secreted; Signal; Zinc.
FT SIGNAL 1..23
FT /evidence="ECO:0000250"
FT CHAIN 24..207
FT /note="Metalloproteinase inhibitor 1"
FT /id="PRO_0000034321"
FT DOMAIN 24..147
FT /note="NTR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT REGION 24..27
FT /note="Involved in metalloproteinase-binding"
FT /evidence="ECO:0000250|UniProtKB:P16035"
FT REGION 90..91
FT /note="Involved in metalloproteinase-binding"
FT /evidence="ECO:0000250|UniProtKB:P16035"
FT BINDING 24
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 37
FT /note="Involved in metalloproteinase-binding"
FT /evidence="ECO:0000250|UniProtKB:P16035"
FT MOD_RES 178
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P01033"
FT CARBOHYD 53
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 77
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 101
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 24..93
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT DISULFID 26..122
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT DISULFID 36..147
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT DISULFID 150..197
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT DISULFID 155..160
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT DISULFID 168..189
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT CONFLICT 17
FT /note="V -> L (in Ref. 1; BAA32393)"
FT /evidence="ECO:0000305"
FT CONFLICT 35
FT /note="L -> F (in Ref. 1; BAA32393)"
FT /evidence="ECO:0000305"
FT CONFLICT 173
FT /note="H -> Q (in Ref. 1; BAA32393)"
FT /evidence="ECO:0000305"
FT CONFLICT 203
FT /note="Missing (in Ref. 1; BAA32393)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 207 AA; 22852 MW; D36C8A67BB3B784D CRC64;
MAPFAPLASC ILLLLWVTAP SRACTCAPPH PQTALCNSQI VIRAKFVGTA EVNQTDLNRR
YEIKMTKMFK GFSALGNASD IRFVDTPALE SVCGYLHRSQ NRSEEFLVAG NLRDGHLQIN
TCSFVAPWSS LSTAQRRGFT KTYAAGCEGC TVFTCSSIPC KLQSDTHCLW TDHFLTGSDK
GFQSRHLACL PREPGICTWQ SLRPRMA
