Gene description for MDK
Gene name midkine (neurite growth-promoting factor 2)
Gene symbol MDK
Other names/aliases ARAP
MK
NEGF2
Species Homo sapiens
 Database cross references - MDK
ExoCarta ExoCarta_4192
Vesiclepedia VP_4192
Entrez Gene 4192
HGNC 6972
MIM 162096
UniProt P21741  
 MDK identified in sEVs derived from the following tissue/cell type
Bone marrow mesenchymal stem cells 36408942    
Bone marrow mesenchymal stem cells 36408942    
Bone marrow mesenchymal stem cells 36408942    
Bone marrow mesenchymal stem cells 36408942    
Chondrocytes 35931686    
Chondrocytes 35931686    
Colorectal cancer cells 34887515    
Gastric cancer cells 33991177    
Gastric cancer cells 33991177    
Gastric cancer cells 33991177    
Melanoma cells 25950383    
Neuroblastoma cells 25944692    
 Gene ontology annotations for MDK
Molecular Function
    protein binding GO:0005515 IPI
    growth factor activity GO:0008083 IBA
    growth factor activity GO:0008083 NAS
    heparin binding GO:0008201 IDA
    chondroitin sulfate binding GO:0035374 ISS
    heparan sulfate binding GO:1904399 IDA
Biological Process
    behavioral fear response GO:0001662 IEA
    leukocyte chemotaxis involved in inflammatory response GO:0002232 IMP
    leukocyte chemotaxis involved in inflammatory response GO:0002232 ISS
    T cell activation involved in immune response GO:0002286 ISS
    positive regulation of leukocyte chemotaxis GO:0002690 ISS
    cytoskeleton organization GO:0007010 ISS
    negative regulation of cell adhesion GO:0007162 ISS
    signal transduction GO:0007165 NAS
    nervous system development GO:0007399 NAS
    short-term memory GO:0007614 IEA
    response to wounding GO:0009611 ISS
    negative regulation of cardiac muscle cell apoptotic process GO:0010667 IMP
    negative regulation of cardiac muscle cell apoptotic process GO:0010667 ISS
    positive regulation of epithelial to mesenchymal transition GO:0010718 IMP
    positive regulation of macrophage chemotaxis GO:0010759 IMP
    positive regulation of macrophage chemotaxis GO:0010759 ISS
    positive regulation of keratinocyte proliferation GO:0010838 IDA
    positive regulation of neuron projection development GO:0010976 IDA
    positive regulation of neuron projection development GO:0010976 IMP
    response to auditory stimulus GO:0010996 ISS
    dentate gyrus development GO:0021542 IEA
    cerebellar granular layer development GO:0021681 IEA
    cerebral cortex development GO:0021987 IEA
    cell differentiation GO:0030154 NAS
    negative regulation of ossification GO:0030279 ISS
    adrenal gland development GO:0030325 ISS
    positive regulation of cell migration GO:0030335 IDA
    defecation GO:0030421 IEA
    regulation of chondrocyte differentiation GO:0032330 ISS
    positive regulation of interleukin-12 production GO:0032735 IMP
    intracellular signal transduction GO:0035556 IDA
    tissue regeneration GO:0042246 ISS
    negative regulation of neuron apoptotic process GO:0043524 IDA
    estrous cycle GO:0044849 ISS
    positive regulation of T cell differentiation GO:0045582 ISS
    negative regulation of regulatory T cell differentiation GO:0045590 IMP
    positive regulation of cell adhesion GO:0045785 IDA
    positive regulation of DNA-templated transcription GO:0045893 IEA
    regulation of bone remodeling GO:0046850 ISS
    oogenesis GO:0048477 ISS
    positive regulation of oligodendrocyte differentiation GO:0048714 IDA
    positive regulation of inflammatory response GO:0050729 IMP
    regulation of behavior GO:0050795 IEA
    positive regulation of cell division GO:0051781 IEA
    positive regulation of cartilage development GO:0061036 ISS
    positive regulation of smooth muscle cell chemotaxis GO:0071673 IMP
    positive regulation of neutrophil chemotaxis GO:0090023 ISS
    negative regulation of canonical Wnt signaling pathway GO:0090090 ISS
    negative regulation of inflammatory response to wounding GO:0106015 ISS
    positive regulation of inflammatory response to wounding GO:0106016 ISS
    glial cell projection elongation GO:0106091 ISS
    positive regulation of substrate adhesion-dependent cell spreading GO:1900026 ISS
    positive regulation of leukocyte cell-cell adhesion GO:1903039 IMP
    negative regulation of epithelial cell apoptotic process GO:1904036 ISS
    positive regulation of leukocyte adhesion to vascular endothelial cell GO:1904996 ISS
    positive regulation of blood vessel branching GO:1905555 IMP
    positive regulation of vascular endothelial cell proliferation GO:1905564 ISS
    positive regulation of artery morphogenesis GO:1905653 ISS
    positive regulation of neural precursor cell proliferation GO:2000179 ISS
    positive regulation of hepatocyte proliferation GO:2000347 ISS
    positive regulation of neutrophil extravasation GO:2000391 ISS
    positive regulation of neuron migration GO:2001224 IMP
Subcellular Localization
    extracellular region GO:0005576 TAS
    collagen-containing extracellular matrix GO:0062023 HDA
 Experiment description of studies that identified MDK in sEVs
1
Experiment ID 489
MISEV standards
EM
Biophysical techniques
Cd9|Cd81|Cd63|Gapdh|Sdcbp|Lamp1|Aqp1|Rab5a|Icam1|Cd82|Itga2b|Tsg101|Lamp2|Rab35|Flot1|Flot2|Cd151|Rab5b|Tfrc|Uchl1
Enriched markers
Canx
Negative markers
NTA
Particle analysis
Identified molecule Protein
Identification method Mass spectrometry
PubMed ID 36408942    
Organism Rattus norvegicus
Experiment description Quantitative proteomic analysis of exosomes from umbilical cord mesenchymal stem cells and rat bone marrow stem cells
Authors "Xu X, Yin F, Guo M, Gan G, Lin G, Wen C, Wang J, Song P, Wang J, Qi ZQ, Zhong CQ."
Journal name Proteomics
Publication year 2023
Sample Bone marrow mesenchymal stem cells
Sample name BMSC - Passage 6
Isolation/purification methods Differential centrifugation
Filtration
Ultracentrifugation
Flotation density -
Molecules identified in the study Protein
Methods used in the study Western blotting
Mass spectometry
2
Experiment ID 490
MISEV standards
EM
Biophysical techniques
Cd9|Cd81|Cd63|Gapdh|Sdcbp|Lamp1|Aqp1|Rab5a|Icam1|Cd82|Itga2b|Tsg101|Lamp2|Rab35|Flot1|Flot2|Cd151|Rab5b|Tfrc|Uchl1
Enriched markers
Canx
Negative markers
NTA
Particle analysis
Identified molecule Protein
Identification method Mass spectrometry
PubMed ID 36408942    
Organism Rattus norvegicus
Experiment description Quantitative proteomic analysis of exosomes from umbilical cord mesenchymal stem cells and rat bone marrow stem cells
Authors "Xu X, Yin F, Guo M, Gan G, Lin G, Wen C, Wang J, Song P, Wang J, Qi ZQ, Zhong CQ."
Journal name Proteomics
Publication year 2023
Sample Bone marrow mesenchymal stem cells
Sample name BMSC - Passage 7
Isolation/purification methods Differential centrifugation
Filtration
Ultracentrifugation
Flotation density -
Molecules identified in the study Protein
Methods used in the study Western blotting
Mass spectometry
3
Experiment ID 491
MISEV standards
EM
Biophysical techniques
Cd9|Cd81|Cd63|Gapdh|Sdcbp|Lamp1|Aqp1|Rab5a|Icam1|Cd82|Itga2b|Tsg101|Lamp2|Rab35|Flot1|Flot2|Cd151|Rab5b|Tfrc|Uchl1
Enriched markers
Canx
Negative markers
NTA
Particle analysis
Identified molecule Protein
Identification method Mass spectrometry
PubMed ID 36408942    
Organism Rattus norvegicus
Experiment description Quantitative proteomic analysis of exosomes from umbilical cord mesenchymal stem cells and rat bone marrow stem cells
Authors "Xu X, Yin F, Guo M, Gan G, Lin G, Wen C, Wang J, Song P, Wang J, Qi ZQ, Zhong CQ."
Journal name Proteomics
Publication year 2023
Sample Bone marrow mesenchymal stem cells
Sample name BMSC - Passage 8
Isolation/purification methods Differential centrifugation
Filtration
Ultracentrifugation
Flotation density -
Molecules identified in the study Protein
Methods used in the study Western blotting
Mass spectometry
4
Experiment ID 492
MISEV standards
EM
Biophysical techniques
Cd9|Cd81|Cd63|Gapdh|Sdcbp|Lamp1|Aqp1|Rab5a|Icam1|Cd82|Itga2b|Tsg101|Lamp2|Rab35|Flot1|Flot2|Cd151|Rab5b|Tfrc|Uchl1
Enriched markers
Canx
Negative markers
NTA
Particle analysis
Identified molecule Protein
Identification method Mass spectrometry
PubMed ID 36408942    
Organism Rattus norvegicus
Experiment description Quantitative proteomic analysis of exosomes from umbilical cord mesenchymal stem cells and rat bone marrow stem cells
Authors "Xu X, Yin F, Guo M, Gan G, Lin G, Wen C, Wang J, Song P, Wang J, Qi ZQ, Zhong CQ."
Journal name Proteomics
Publication year 2023
Sample Bone marrow mesenchymal stem cells
Sample name BMSC - Passage 9
Isolation/purification methods Differential centrifugation
Filtration
Ultracentrifugation
Flotation density -
Molecules identified in the study Protein
Methods used in the study Western blotting
Mass spectometry
5
Experiment ID 497
MISEV standards
Biophysical techniques
CD9|CD151|CD63|CD81|CD82|FLOT1|FLOT2|GAPDH|LAMP1|LAMP2|RAB5A|SDCBP|TFRC|TSG101|UCHL1
Enriched markers
Negative markers
NTA
Particle analysis
Identified molecule Protein
Identification method Mass spectrometry
PubMed ID 35931686    
Organism Homo sapiens
Experiment description Extracellular vesicles enriched in connexin 43 promote a senescent phenotype in bone and synovial cells contributing to osteoarthritis progression
Authors "Varela-Eirín M, Carpintero-Fernández P, Guitián-Caamaño A, Varela-Vázquez A, García-Yuste A, Sánchez-Temprano A, Bravo-López SB, Yañez-Cabanas J, Fonseca E, Largo R, Mobasheri A, Caeiro JR, Mayán MD."
Journal name Cell Death Dis
Publication year 2022
Sample Chondrocytes
Sample name T/C-28a2
Isolation/purification methods Differential centrifugation
Filtration
Ultracentrifugation
Flotation density -
Molecules identified in the study Protein
Methods used in the study Western blotting
Mass spectometry
6
Experiment ID 498
MISEV standards
EM
Biophysical techniques
CD9|CD151|CD63|CD81|CD82|FLOT1|FLOT2|GAPDH|LAMP1|LAMP2|RAB5A|SDCBP|TFRC|TSG101|UCHL1
Enriched markers
Negative markers
NTA
Particle analysis
Identified molecule Protein
Identification method Mass spectrometry
PubMed ID 35931686    
Organism Homo sapiens
Experiment description Extracellular vesicles enriched in connexin 43 promote a senescent phenotype in bone and synovial cells contributing to osteoarthritis progression
Authors "Varela-Eirín M, Carpintero-Fernández P, Guitián-Caamaño A, Varela-Vázquez A, García-Yuste A, Sánchez-Temprano A, Bravo-López SB, Yañez-Cabanas J, Fonseca E, Largo R, Mobasheri A, Caeiro JR, Mayán MD."
Journal name Cell Death Dis
Publication year 2022
Sample Chondrocytes
Sample name T/C-28a2
Isolation/purification methods Differential centrifugation
Filtration
Ultracentrifugation
Flotation density -
Molecules identified in the study Protein
Methods used in the study Western blotting
Mass spectometry
7
Experiment ID 1203
MISEV standards
EM
Biophysical techniques
SDCBP|FLOT1|CD9|CD81|CD63|EPCAM|GAPDH|LAMP1|TFRC|CD151|CD82|LAMP2|RAB35|TSG101|FLOT2|RAB5B|ICAM1|RAB5A
Enriched markers
Negative markers
Particle analysis
Identified molecule protein
Identification method Mass spectrometry
PubMed ID 34887515    
Organism Homo sapiens
Experiment description Supermeres are functional extracellular nanoparticles replete with disease biomarkers and therapeutic targets
Authors "Zhang Q, Jeppesen DK, Higginbotham JN, Graves-Deal R, Trinh VQ, Ramirez MA, Sohn Y, Neininger AC, Taneja N, McKinley ET, Niitsu H, Cao Z, Evans R, Glass SE, Ray KC, Fissell WH, Hill S, Rose KL, Huh WJ, Washington MK, Ayers GD, Burnette DT, Sharma S, Rome LH, Franklin JL, Lee YA, Liu Q, Coffey RJ."
Journal name Nat Cell Biol
Publication year 2021
Sample Colorectal cancer cells
Sample name DiFi
Isolation/purification methods Differential centrifugation
Filtration
Centrifugal ultrafiltration
Ultracentrifugation
OptiPrep density gradient centrifugation
Flotation density -
Molecules identified in the study Protein
miRNA
Methods used in the study Western blotting
Mass spectrometry
RNA sequencing
8
Experiment ID 363
MISEV standards
Biophysical techniques
TSG101|GAPDH|AQP1|CD151|CD81|CD82|CD9|EPCAM|FLOT1|FLOT2|ICAM1|ITGA2B|LAMP2|RAB35|RAB5A|RAB5B|SDCBP|TFRC|UCHL1
Enriched markers
DCLK1
Negative markers
NTA
Particle analysis
Identified molecule Protein
Identification method Mass spectrometry
PubMed ID 33991177    
Organism Homo sapiens
Experiment description Cancer stem cell marker DCLK1 reprograms small extracellular vesicles toward migratory phenotype in gastric cancer cells
Authors "Carli ALE, Afshar-Sterle S, Rai A, Fang H, O'Keefe R, Tse J, Ferguson FM, Gray NS, Ernst M, Greening DW, Buchert M."
Journal name Proteomics
Publication year 2021
Sample Gastric cancer cells
Sample name MKN1 - 100K pellet
Isolation/purification methods Differential centrifugation
Ultracentrifugation
Flotation density -
Molecules identified in the study Protein
Methods used in the study Western blotting
Mass spectrometry
9
Experiment ID 364
MISEV standards
Biophysical techniques
TSG101|GAPDH|AQP1|CD151|CD81|CD82|CD9|EPCAM|FLOT1|FLOT2|ICAM1|ITGA2B|LAMP2|RAB35|RAB5A|RAB5B|SDCBP|TFRC|UCHL1
Enriched markers
DCLK1
Negative markers
NTA
Particle analysis
Identified molecule Protein
Identification method Mass spectrometry
PubMed ID 33991177    
Organism Homo sapiens
Experiment description Cancer stem cell marker DCLK1 reprograms small extracellular vesicles toward migratory phenotype in gastric cancer cells
Authors "Carli ALE, Afshar-Sterle S, Rai A, Fang H, O'Keefe R, Tse J, Ferguson FM, Gray NS, Ernst M, Greening DW, Buchert M."
Journal name Proteomics
Publication year 2021
Sample Gastric cancer cells
Sample name MKN1 - 100K pellet
Isolation/purification methods Differential centrifugation
Ultracentrifugation
Flotation density -
Molecules identified in the study Protein
Methods used in the study Western blotting
Mass spectrometry
10
Experiment ID 365
MISEV standards
Biophysical techniques
TSG101|GAPDH|AQP1|CD151|CD81|CD82|CD9|EPCAM|FLOT1|FLOT2|ICAM1|ITGA2B|LAMP2|RAB35|RAB5A|RAB5B|SDCBP|TFRC|UCHL1
Enriched markers
DCLK1
Negative markers
NTA
Particle analysis
Identified molecule Protein
Identification method Mass spectrometry
PubMed ID 33991177    
Organism Homo sapiens
Experiment description Cancer stem cell marker DCLK1 reprograms small extracellular vesicles toward migratory phenotype in gastric cancer cells
Authors "Carli ALE, Afshar-Sterle S, Rai A, Fang H, O'Keefe R, Tse J, Ferguson FM, Gray NS, Ernst M, Greening DW, Buchert M."
Journal name Proteomics
Publication year 2021
Sample Gastric cancer cells
Sample name MKN1 - 100K pellet
Isolation/purification methods Differential centrifugation
Ultracentrifugation
Flotation density -
Molecules identified in the study Protein
Methods used in the study Western blotting
Mass spectrometry
11
Experiment ID 258
MISEV standards
EM
Biophysical techniques
TSG101|FLOT1|CD81
Enriched markers
Negative markers
NTA
Particle analysis
Identified molecule protein
Identification method Mass spectrometry
PubMed ID 25950383    
Organism Homo sapiens
Experiment description Proteome characterization of melanoma exosomes reveals a specific signature for metastatic cell lines
Authors "Lazar I, Clement E, Ducoux-Petit M, Denat L, Soldan V, Dauvillier S, Balor S4, Burlet-Schiltz O1, Larue L, Muller C Nieto L"
Journal name Pigment Cell Melanoma Res
Publication year 2015
Sample Melanoma cells
Sample name SKMEL28
Isolation/purification methods Differential centrifugation
Unltracentrifugation
Sucrose density gradient
Flotation density 1.13 - 1.19 g/mL
Molecules identified in the study Protein
Methods used in the study Western blotting
Mass spectrometry
12
Experiment ID 224
MISEV standards
EM|AFM
Biophysical techniques
Alix|TSG101|CD63|CD81
Enriched markers
GOLGA2
Negative markers
Particle analysis
Identified molecule protein
Identification method Mass spectrometry
PubMed ID 25944692    
Organism Homo sapiens
Experiment description Proteogenomic analysis reveals exosomes are more oncogenic than ectosomes
Authors "Keerthikumar S, Gangoda L, Liem M, Fonseka P, Atukorala I, Ozcitti C, Mechler A, Adda CG, Ang CS, Mathivanan S"
Journal name Oncotarget
Publication year 2015
Sample Neuroblastoma cells
Sample name SH-SY5Y
Isolation/purification methods Differential centrifugation
Ultracentrifugation
OptiPrep density gradient
Flotation density 1.10 g/mL
Molecules identified in the study Protein
Methods used in the study Mass spectrometry
Western blotting
 Protein-protein interactions for MDK
  Protein Interactor ExoCarta ID Identification method PubMed Species
1 NID2 22795
Affinity Capture-MS Homo sapiens
2 KBTBD7  
Affinity Capture-MS Homo sapiens
Affinity Capture-MS Homo sapiens
3 UBQLN2 29978
Two-hybrid Homo sapiens
4 MECP2 4204
Affinity Capture-MS Homo sapiens
5 RPS27A 6233
Affinity Capture-MS Homo sapiens
Affinity Capture-MS Homo sapiens
6 PSMB10 5699
Affinity Capture-MS Homo sapiens
7 CCL3L1  
Affinity Capture-MS Homo sapiens
8 UBQLN4 56893
Two-hybrid Homo sapiens
9 RNF167 26001
Reconstituted Complex Homo sapiens
10 RBFA  
Two-hybrid Homo sapiens
11 SORL1 6653
Affinity Capture-MS Homo sapiens
12 SIN3A  
Affinity Capture-MS Homo sapiens
13 NOTCH2 4853
Affinity Capture-MS Homo sapiens
14 NOS1AP  
Affinity Capture-MS Homo sapiens
Affinity Capture-MS Homo sapiens
15 NFU1 27247
Two-hybrid Homo sapiens
16 SRPK2 6733
Biochemical Activity Homo sapiens
17 PNN 5411
Affinity Capture-MS Homo sapiens
Affinity Capture-MS Homo sapiens
18 MLLT3 4300
Affinity Capture-MS Homo sapiens
Affinity Capture-MS Homo sapiens
19 RPL35 11224
Affinity Capture-MS Homo sapiens
20 TNRC18  
Affinity Capture-MS Homo sapiens
Affinity Capture-MS Homo sapiens
21 TMED8 283578
Two-hybrid Homo sapiens
22 CLK2 1196
Affinity Capture-MS Homo sapiens
Affinity Capture-MS Homo sapiens
23 KCMF1 56888
Affinity Capture-MS Homo sapiens
24 EPB41L5 57669
Affinity Capture-MS Homo sapiens
Affinity Capture-MS Homo sapiens
25 NCAM1 4684
Affinity Capture-MS Homo sapiens
26 FOXA1  
Affinity Capture-MS Homo sapiens
27 USP12 219333
Affinity Capture-Western Homo sapiens
Affinity Capture-Western Homo sapiens
28 PTPN9 5780
Affinity Capture-MS Homo sapiens
Affinity Capture-MS Homo sapiens
29 BRD2  
Affinity Capture-MS Homo sapiens
Affinity Capture-MS Homo sapiens
30 HCK 3055
Two-hybrid Homo sapiens
31 DDX58 23586
Affinity Capture-RNA Homo sapiens
32 PBX3  
Two-hybrid Homo sapiens
33 TUBA1A 7846
Affinity Capture-MS Homo sapiens
34 SETD1A 9739
Affinity Capture-MS Homo sapiens
Affinity Capture-MS Homo sapiens
35 LRP1 4035
Affinity Capture-MS Homo sapiens
36 MYCN  
Affinity Capture-MS Homo sapiens
37 MAPK6  
Two-hybrid Homo sapiens
38 TUBB2B 347733
Affinity Capture-MS Homo sapiens
39 RPL18A 6142
Two-hybrid Homo sapiens
40 ZCCHC17  
Affinity Capture-MS Homo sapiens
41 NCL 4691
Reconstituted Complex Homo sapiens
42 MYC  
Affinity Capture-MS Homo sapiens
43 MIEF2  
Two-hybrid Homo sapiens
44 AFF4 27125
Affinity Capture-MS Homo sapiens
Affinity Capture-MS Homo sapiens
45 UBE2O 63893
Affinity Capture-MS Homo sapiens
46 CXXC1  
Affinity Capture-MS Homo sapiens
Affinity Capture-MS Homo sapiens
47 PTPRZ1  
Reconstituted Complex Homo sapiens
48 JOSD2  
Two-hybrid Homo sapiens
49 RPP25  
Affinity Capture-MS Homo sapiens
Affinity Capture-MS Homo sapiens
50 HIST1H1A 3024
Affinity Capture-MS Homo sapiens
Affinity Capture-MS Homo sapiens
51 NID1 4811
Affinity Capture-MS Homo sapiens
52 UBTF 7343
Affinity Capture-MS Homo sapiens
Affinity Capture-MS Homo sapiens
53 NPM1 4869
Affinity Capture-MS Homo sapiens
54 SRRM2 23524
Affinity Capture-MS Homo sapiens
Affinity Capture-MS Homo sapiens
55 CWC22 57703
Affinity Capture-MS Homo sapiens
Affinity Capture-MS Homo sapiens
56 RPL36AL 6166
Affinity Capture-MS Homo sapiens
Affinity Capture-MS Homo sapiens
57 OBSL1 23363
Affinity Capture-MS Homo sapiens
58 NAF1  
Affinity Capture-MS Homo sapiens
Affinity Capture-MS Homo sapiens
59 BOD1L1 259282
Affinity Capture-MS Homo sapiens
Affinity Capture-MS Homo sapiens
60 UBQLN1 29979
Two-hybrid Homo sapiens
61 TCEA2  
Two-hybrid Homo sapiens
62 ACTG1 71
Affinity Capture-MS Homo sapiens
63 NKAP 79576
Affinity Capture-MS Homo sapiens
64 CHD9 80205
Affinity Capture-MS Homo sapiens
Affinity Capture-MS Homo sapiens
65 PPIG 9360
Affinity Capture-MS Homo sapiens
Affinity Capture-MS Homo sapiens
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