Target Information
Target General Information | Top | |||||
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Target ID |
T03878
(Former ID: TTDR00404)
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Target Name |
Midgestation and kidney protein (Midkine)
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Synonyms |
Neurite outgrowth-promoting protein; Neurite outgrowth-promoting factor 2; NEGF2; MK1; MK; Amphiregulin-associated protein; ARAP
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Gene Name |
MDK
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Target Type |
Literature-reported target
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[1] | ||||
Function |
Binds cell-surface proteoglycan receptors via their chondroitin sulfate (CS) groups. Thereby regulates many processes like inflammatory response, cell proliferation, cell adhesion, cell growth, cell survival, tissue regeneration, cell differentiation and cell migration. Participates in inflammatory processes by exerting two different activities. Firstly, mediates neutrophils and macrophages recruitment to the sites of inflammation both by direct action by cooperating namely with ITGB2 via LRP1 and by inducing chemokine expression. This inflammation can be accompanied by epithelial cell survival and smooth muscle cell migration after renal and vessel damage, respectively. Secondly, suppresses the development of tolerogenic dendric cells thereby inhibiting the differentiation of regulatory T cells and also promote T cell expansion through NFAT signaling and Th1 cell differentiation. Promotes tissue regeneration after injury or trauma. After heart damage negatively regulates the recruitment of inflammatory cells and mediates cell survival through activation of anti-apoptotic signaling pathways via MAPKs and AKT pathways through the activation of angiogenesis. Also facilites liver regeneration as well as bone repair by recruiting macrophage at trauma site and by promoting cartilage development by facilitating chondrocyte differentiation. Plays a role in brain by promoting neural precursor cells survival and growth through interaction with heparan sulfate proteoglycans. Binds PTPRZ1 and promotes neuronal migration and embryonic neurons survival. Binds SDC3 or GPC2 and mediates neurite outgrowth and cell adhesion. Binds chondroitin sulfate E and heparin leading to inhibition of neuronal cell adhesion induced by binding with GPC2. Binds CSPG5 and promotes elongation of oligodendroglial precursor-like cells. Also binds ITGA6:ITGB1 complex; this interaction mediates MDK-induced neurite outgrowth. Binds LRP1; promotes neuronal survival. Binds ITGA4:ITGB1 complex; this interaction mediates MDK-induced osteoblast cells migration through PXN phosphorylation. Binds anaplastic lymphoma kinase (ALK) which induces ALK activation and subsequent phosphorylation of the insulin receptor substrate (IRS1), followed by the activation of mitogen-activated protein kinase (MAPK) and PI3-kinase, and the induction of cell proliferation. Promotes epithelial to mesenchymal transition through interaction with NOTCH2. During arteriogenesis, plays a role in vascular endothelial cell proliferation by inducing VEGFA expression and release which in turn induces nitric oxide synthase expression. Moreover activates vasodilation through nitric oxide synthase activation. Negatively regulates bone formation in response to mechanical load by inhibiting Wnt/beta-catenin signaling in osteoblasts. In addition plays a role in hippocampal development, working memory, auditory response, early fetal adrenal gland development and the female reproductive system. Secreted protein that functions as cytokine and growth factor and mediates its signal through cell-surface proteoglycan and non-proteoglycan receptors.
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UniProt ID | ||||||
Sequence |
MQHRGFLLLTLLALLALTSAVAKKKDKVKKGGPGSECAEWAWGPCTPSSKDCGVGFREGT
CGAQTQRIRCRVPCNWKKEFGADCKYKFENWGACDGGTGTKVRQGTLKKARYNAQCQETI RVTKPCTPKTKAKAKAKKGKGKD Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
HIT2.0 ID | T02HVB |
Cell-based Target Expression Variations | Top | |||||
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Cell-based Target Expression Variations |
Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Tissue Distribution
Biological Network Descriptors
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There is no similarity protein (E value < 0.005) for this target
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Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
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Degree | 6 | Degree centrality | 6.45E-04 | Betweenness centrality | 5.58E-04 |
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Closeness centrality | 2.08E-01 | Radiality | 1.36E+01 | Clustering coefficient | 0.00E+00 |
Neighborhood connectivity | 1.05E+01 | Topological coefficient | 1.73E-01 | Eccentricity | 12 |
Download | Click to Download the Full PPI Network of This Target | ||||
Chemical Structure based Activity Landscape of Target | Top |
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Target Poor or Non Binders | Top | |||||
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Target Poor or Non Binders |
Target Regulators | Top | |||||
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Target-regulating Transcription Factors |
References | Top | |||||
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REF 1 | Recent progress of midkine research on cancer. Nihon Rinsho. 2000 Jun;58(6):1337-47. |
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