TIMP1_BOVIN
ID TIMP1_BOVIN Reviewed; 207 AA.
AC P20414; Q3T098; Q53ZP2; Q9TVB0;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1991, sequence version 1.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Metalloproteinase inhibitor 1;
DE AltName: Full=Embryogenin-1;
DE Short=EG-1;
DE AltName: Full=Tissue inhibitor of metalloproteinases 1;
DE Short=TIMP-1;
DE Flags: Precursor;
GN Name=TIMP1;
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=2393392; DOI=10.1016/0006-291x(90)91384-5;
RA Freudenstein J., Wagner S., Luck R.M., Einspanier R., Scheit K.H.;
RT "mRNA of bovine tissue inhibitor of metalloproteinase: sequence and
RT expression in bovine ovarian tissue.";
RL Biochem. Biophys. Res. Commun. 171:250-256(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 25-52, SUBCELLULAR
RP LOCATION, AND FUNCTION.
RX PubMed=8199264; DOI=10.1095/biolreprod50.4.835;
RA Satoh T., Kobayashi K., Yamashita S., Kikuchi M., Sendai Y., Hoshi H.;
RT "Tissue inhibitor of metalloproteinases (TIMP-1) produced by granulosa and
RT oviduct cells enhances in vitro development of bovine embryo.";
RL Biol. Reprod. 50:835-844(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Adrenal cortex;
RX PubMed=15026182; DOI=10.1016/j.mce.2003.11.011;
RA Reichenstein M., Reich R., Lehoux J.-G., Hanukoglu I.;
RT "ACTH induces TIMP-1 expression and inhibits collagenase in adrenal cortex
RT cells.";
RL Mol. Cell. Endocrinol. 215:109-114(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Crossbred X Angus; TISSUE=Ileum;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 25-191.
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 [6]
RP PRELIMINARY PROTEIN SEQUENCE OF 24-69, AND SUBCELLULAR LOCATION.
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 [7]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=8417953;
RA Murate T., Yamashita K., Ohashi H., Kagami Y., Tsushita K., Kinoshita T.,
RA Hotta T., Saito H., Yoshida S., Mori K.J.;
RT "Erythroid potentiating activity of tissue inhibitor of metalloproteinases
RT on the differentiation of erythropoietin-responsive mouse erythroleukemia
RT cell line, ELM-I-1-3, is closely related to its cell growth potentiating
RT activity.";
RL Exp. Hematol. 21:169-176(1993).
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. {ECO:0000269|PubMed:8199264,
CC ECO:0000269|PubMed:8417953}.
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 {ECO:0000269|PubMed:2551903,
CC ECO:0000269|PubMed:8199264, ECO:0000269|PubMed:8417953}.
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; M60073; AAA30784.1; -; mRNA.
DR EMBL; S70841; AAB30892.1; -; mRNA.
DR EMBL; AY295346; AAP44413.1; -; mRNA.
DR EMBL; BC102489; AAI02490.1; -; mRNA.
DR EMBL; AF144763; AAD30303.1; -; mRNA.
DR PIR; A35685; A35685.
DR RefSeq; NP_776896.1; NM_174471.3.
DR AlphaFoldDB; P20414; -.
DR SMR; P20414; -.
DR STRING; 9913.ENSBTAP00000006653; -.
DR PaxDb; P20414; -.
DR GeneID; 282092; -.
DR KEGG; bta:282092; -.
DR CTD; 7076; -.
DR eggNOG; KOG4745; Eukaryota.
DR HOGENOM; CLU_084029_0_0_1; -.
DR InParanoid; P20414; -.
DR OrthoDB; 1122531at2759; -.
DR TreeFam; TF317409; -.
DR Proteomes; UP000009136; Unplaced.
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:0008191; F:metalloendopeptidase inhibitor activity; ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
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:0008284; P:positive regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:2001044; P:regulation of integrin-mediated signaling pathway; ISS:UniProtKB.
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 InterPro; IPR030490; TIMP_CS.
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.
DR PROSITE; PS00288; TIMP; 1.
PE 1: Evidence at protein level;
KW Direct protein sequencing; Disulfide bond; Glycoprotein; Growth factor;
KW Metal-binding; Metalloenzyme inhibitor; Metalloprotease inhibitor;
KW Phosphoprotein; Protease inhibitor; Reference proteome; Secreted; Signal;
KW Zinc.
FT SIGNAL 1..23
FT CHAIN 24..207
FT /note="Metalloproteinase inhibitor 1"
FT /id="PRO_0000034320"
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 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"
SQ SEQUENCE 207 AA; 23032 MW; E672BEE2E865F3F7 CRC64;
MAPFAPMASG ILLLLWLTAP SRACTCVPPH PQTAFCNSDV VIRAKFVGTA EVNETALYQR
YEIKMTKMFK GFSALRDAPD IRFIYTPAME SVCGYFHRSQ NRSEEFLIAG QLSNGHLHIT
TCSFVAPWNS MSSAQRRGFT KTYAAGCEEC TVFPCSSIPC KLQSDTHCLW TDQLLTGSDK
GFQSRHLACL PREPGLCTWQ SLRAQMA
