Protein: Metalloproteinase inhibitor 1 (Erythroid-potentiating activity) (EPA) (Fibroblast collagenase inhibitor) (Collagenase inhibitor) (Tissue inhibitor of metalloproteinases 1) (TIMP-1) (P01033)
Organism: Homo sapiens (Human)
Function: Metalloproteinase inhibitor that functions by forming one to one complexes with target metalloproteinases, such as collagenases, and irreversibly inactivates them by binding to their catalytic zinc cofactor. Acts on MMP1, MMP2, MMP3, MMP7, MMP8, MMP9, MMP10, MMP11, MMP12, MMP13 and MMP16. Does not act on MMP14. Also functions as a growth factor that regulates cell differentiation, migration and cell death and activates cellular signaling cascades via CD63 and ITGB1. Plays a role in integrin signaling. Mediates erythropoiesis in vitro; but, unlike IL3, it is species-specific, stimulating the growth and differentiation of only human and murine erythroid progenitors.
Subcellular location: Secreted {ECO:0000269|PubMed:1730286, ECO:0000269|PubMed:24635319, ECO:0000269|PubMed:3010309, ECO:0000269|PubMed:3839290, ECO:0000269|PubMed:3903517, ECO:0000269|PubMed:8541540}.
Sequence: MAPFEPLASGILLLLWLIAPSRACTCVPPHPQTAFCNSDLVIRAKFVGTPEVNQTTLYQRYEIKMTKMYKGFQALGDAADIRFVYTPAMESVCGYFHRSHNRSEEFLIAGKLQDGLLHITTCSFVAPWNSLSLAQRRGFTKTYTVGCEECTVFPCLSIPCKLQSGTHCLWTDQLLQGSEKGFQSRHLACLPREPGLCTWQSLRSQIA
InterPro domains: - IPR027465: Proteinase inhibitor I35b (TIMP), C-terminal (homologous_superfamily) [24-199]
- IPR001820: Protease inhibitor I35 (TIMP) (family) [9-205]
- IPR008993: Tissue inhibitor of metalloproteinases-like, OB-fold (homologous_superfamily) [24-202]
- IPR001134: Netrin domain (domain) [24-147]
- IPR030490: Tissue inhibitor of metalloproteinase, conserved site (conserved_site) [24-36]
Interaction partners: - Matrix metalloproteinase-9
- Stromelysin-1
- Matrix metalloproteinase-14
- Interstitial collagenase
- CD63 antigen
- 72 kDa type IV collagenase
- Stromelysin-2
- Interleukin-10
- Fibronectin
- Interleukin-6
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0098772 (molecular function regulator activity), GO:0005488 (binding), GO:0030234 (enzyme regulator activity), GO:0005515 (protein binding), GO:0140678 (molecular function inhibitor activity), GO:0061134 (peptidase regulator activity), GO:0004857 (enzyme inhibitor activity), GO:0061135 (endopeptidase regulator activity), GO:0030414 (peptidase inhibitor activity), GO:0004866 (endopeptidase inhibitor activity), GO:0008191 (metalloendopeptidase inhibitor activity)
Biological Process (BP): GO:0008150 (biological process), GO:0065007 (biological regulation), GO:0050896 (response to stimulus), GO:0050789 (regulation of biological process), GO:0009987 (cellular process), GO:0048519 (negative regulation of biological process), GO:0042221 (response to chemical), GO:0019222 (regulation of metabolic process), GO:0051716 (cellular response to stimulus), GO:0065009 (regulation of molecular function), GO:0009892 (negative regulation of metabolic process), GO:0050790 (regulation of catalytic activity), GO:0051172 (negative regulation of nitrogen compound metabolic process), GO:0070887 (cellular response to chemical stimulus), GO:0010605 (negative regulation of macromolecule metabolic process), GO:0044092 (negative regulation of molecular function), GO:0051171 (regulation of nitrogen compound metabolic process), GO:0060255 (regulation of macromolecule metabolic process), GO:0080090 (regulation of primary metabolic process), GO:0010033 (response to organic substance), GO:0043086 (negative regulation of catalytic activity), GO:0051246 (regulation of protein metabolic process), GO:0071310 (cellular response to organic substance), GO:0051336 (regulation of hydrolase activity), GO:0051248 (negative regulation of protein metabolic process), GO:0051346 (negative regulation of hydrolase activity), GO:0030162 (regulation of proteolysis), GO:0052547 (regulation of peptidase activity), GO:0045861 (negative regulation of proteolysis), GO:1905048 (regulation of metallopeptidase activity), GO:0052548 (regulation of endopeptidase activity), GO:0010466 (negative regulation of peptidase activity), GO:0010951 (negative regulation of endopeptidase activity)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0030312 (external encapsulating structure), GO:0071944 (cell periphery), GO:0005737 (cytoplasm), GO:0031974 (membrane-enclosed lumen), GO:0012505 (endomembrane system), GO:0005576 (extracellular region), GO:0030141 (secretory granule), GO:0031410 (cytoplasmic vesicle), GO:0043229 (intracellular organelle), GO:0031012 (extracellular matrix), GO:0043233 (organelle lumen), GO:0043227 (membrane-bounded organelle), GO:0060205 (cytoplasmic vesicle lumen), GO:0031983 (vesicle lumen), GO:0099503 (secretory vesicle), GO:0043231 (intracellular membrane-bounded organelle), GO:0062023 (collagen-containing extracellular matrix), GO:0034774 (secretory granule lumen), GO:0070013 (intracellular organelle lumen), GO:0031982 (vesicle), GO:0097708 (intracellular vesicle), GO:0005634 (nucleus)