Disease	Score

Substances	Interaction	Organism	Category

Substances	Interaction	Organism	Category

     From NCBI Gene: Spondyloepimetaphyseal dysplasia, Missouri typeMetaphyseal chondrodysplasia, Spahr typeFrom UniProt: Metaphyseal anadysplasia 1 (MANDP1): A bone development disorder characterized by skeletal anomalies that resolve spontaneously with age. Clinical characteristics are evident from the first months of life and include slight shortness of stature and a mild varus deformity of the legs. Patients attain a normal stature in adolescence and show improvement or complete resolution of varus deformity of the legs and rhizomelic micromelia. [MIM:602111] Metaphyseal dysplasia, Spahr type (MDST): An autosomal recessive, rare disease characterized by moderate short stature, mild genua vara, and radiographic signs of metaphyseal dysplasia, but no biochemical signs of rickets. [MIM:250400] Spondyloepimetaphyseal dysplasia Missouri type (SEMD-MO): A bone disease characterized by moderate to severe metaphyseal changes, mild epiphyseal involvement, rhizomelic shortening of the lower limbs with bowing of the femora and/or tibiae, coxa vara, genu varum and pear-shaped vertebrae in childhood. Epimetaphyseal changes improve with age. [MIM:602111]

     From NCBI Gene: This gene encodes a member of the peptidase M10 family of matrix metalloproteinases (MMPs). Proteins in this family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. The encoded preproprotein is proteolytically processed to generate the mature protease. This protease cleaves type II collagen more efficiently than types I and III. It may be involved in articular cartilage turnover and cartilage pathophysiology associated with osteoarthritis. Mutations in this gene are associated with metaphyseal anadysplasia. This gene is part of a cluster of MMP genes on chromosome 11. [provided by RefSeq, Jan 2016] From UniProt: Plays a role in the degradation of extracellular matrix proteins including fibrillar collagen, fibronectin, TNC and ACAN. Cleaves triple helical collagens, including type I, type II and type III collagen, but has the highest activity with soluble type II collagen. Can also degrade collagen type IV, type XIV and type X. May also function by activating or degrading key regulatory proteins, such as TGFB1 and CTGF. Plays a role in wound healing, tissue remodeling, cartilage degradation, bone development, bone mineralization and ossification. Required for normal embryonic bone development and ossification. Plays a role in the healing of bone fractures via endochondral ossification. Plays a role in wound healing, probably by a mechanism that involves proteolytic activation of TGFB1 and degradation of CTGF. Plays a role in keratinocyte migration during wound healing. May play a role in cell migration and in tumor cell invasion.

Condition	Change (log2fold)	Comparison	Species	Experimental variables	Experiment name

Condition	Change (log2fold)	Comparison	Species	Experimental variables	Experiment name

The following transcription factors affect gene expression:

• GR
• GR-alpha
• GR-beta
• p53
• AP-1
• c-Jun
• c-Fos
• STAT1
• STAT1beta
• STAT1alpha

Tissue specificity:

Detected in fetal cartilage and calvaria, in chondrocytes of hypertrophic cartilage in vertebrae and in the dorsal end of ribs undergoing ossification, as well as in osteoblasts and periosteal cells below the inner periosteal region of ossified ribs. Detected in chondrocytes from in joint cartilage that have been treated with TNF and IL1B, but not in untreated chondrocytes. Detected in T lymphocytes. Detected in breast carcinoma tissue.

Induction:

Up-regulated by TNF and IL1B.

Enzyme Regulation:

Inhibited by TIMP1, TIMP2 and TIMP3. Inhibited by acetohydroxamic acid and other zinc chelators.

Cofactor:

Binds 2 Zn(2+) ions per subunit.

Molecular Function:

• Metalloendopeptidase Activity
• Serine-Type Endopeptidase Activity
• Calcium Ion Binding
• Collagen Binding
• Zinc Ion Binding

Biological Processes:

• Luteolysis
• Osteoblast Differentiation
• Response To Hypoxia
• Endochondral Ossification
• Growth Plate Cartilage Development
• Proteolysis
• Heart Development
• Parturition
• Response To Mechanical Stimulus
• Extracellular Matrix Disassembly
• Bone Mineralization
• Collagen Catabolic Process
• Embryonic Hindlimb Morphogenesis
• Peptide Catabolic Process
• Response To Estrogen
• Cellular Protein Metabolic Process
• Estrous Cycle
• Bone Morphogenesis
• Cellular Response To Fluid Shear Stress
• Positive Regulation Of Pancreatic Trypsinogen Secretion

Drug Bank:

• Marimastat

*synonyms