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Symbol MDK contributors: mct - updated : 21-10-2019
HGNC name midkine (neurite growth-promoting factor 2)
HGNC id 6972
Location 11p11.2      Physical location : 46.402.617 - 46.405.374
Synonym name
  • amphiregulin-associated protein
  • midgestation and kidney protein
  • neurite growth-promoting factor 2
  • neurite outgrowth-promoting factor 2
  • retinoic acid inducible factor
  • Synonym symbol(s) NEGF2, FLJ27379, MK, ARAP
    TYPE functioning gene
    STRUCTURE 3.05 kb     5 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Binding site   transcription factor
    text structure
  • sequence activating transcroption of an exogenous suicide gene in pancreatic cancer
  • promoter of the MDK gene has a putative SP1 binding site (SP1 binds to the promoter of the MDK gene and directly regulates MDK expression)
  • MAPPING cloned Y linked N status confirmed
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    5 - 1015 - 143 - 1997 9384573
    5 - 969 - 143 - 1997 9384573
    5 - 854 - 143 - 1997 9384573
    4 - 1194 - 143 - 1997 9384573
    4 - 1152 - 143 - 1997 9384573
    4 - 686 - 87 - 1997 9384573
    Type ubiquitous
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    Digestivestomach   highly
    Endocrinepancreas   highly
    Nervousbrainbasal nucleistriatum highly Homo sapiensFetal
    Reproductivefemale systemovary  highly
    cell lineage
    cell lines teratocarcinomas cell lines, pancreatic cancer cell lines
    at STAGE
    isoforms Precursor a 121AA mature protein
    interspecies ortholog to murine Mk
    intraspecies homolog to NEGF1
    FAMILY pleiotrophin family
    CATEGORY adhesion , signaling cytokine growth factor
    basic FUNCTION
  • essential for normal development of the catecholamine and renin-angiotensin pathways and the synthesis of different collagens
  • involved in nervous system development
  • mediator for intercellular transfer of drug resistance
  • promoting the migration of inflammatory leukocytes
  • playing important roles in the formation of intraperitoneal adhesions, at least partly by promoting the migration of macrophages and neutrophils to the omentum
  • implicated in the tumorigenesis of benign and plexiform neurofibromas, and therefore arising malignant peripheral nerve sheath tumors (MPNSTs)
  • factor that plays a role in the nigrostriatal system during development and in response to disease, and may therefore be useful for neuroprotection or reconstruction of the dopamine (DA) system
  • may maintain normal adult brain as a neurotrophic factor, and MDK may be released from leucocytes in brain of patients with meningitis as an immunological mediator
  • may contribute to neuronal regeneration
  • promotes tumor growth mainly by inducing angiogenesis
  • MDK is a pivotal player of angiogenesis during ischemia in nonmalignant tissue
  • critical role for the MDK-NOTCH2 signaling axis in neuroblastoma tumorigenesis, which implicates new strategies to treat neuroblastoma
  • cytokine midkine supports neutrophil trafficking during acute inflammation by promoting adhesion via beta2 integrins (CD11/CD18)
  • heparin-binding growth factor, which behaves like a cytokine, involved in various cellular processes such as cellular proliferation, differentiation, survival, adhesion, and migration
  • seems to be involved in the development of Henoch-Schönlein purpura (HSP)
  • serves an indispensable role in the NFATC1-regulated activation of CD4+ T cells and Th1 cell differentiation
  • is a heparin binding growth factor and is involved in neurogenesis, neural development and neuroprotection
  • may play a role in autism spectrum disorders (ASD) pathogenesis
  • MDK is responsible for increased plasma levels of vascular endothelial growth factor A (VEGFA), necessary and sufficient to promote endothelial cell proliferation in growing collaterals
  • role of midkine in endothelial proliferation are likely to be relevant for both, the process of arteriogenesis and angiogenesis
  • is a pleiotropic factor, which is involved in angiogenesis
  • CELLULAR PROCESS nucleotide, transcription
    text nervous tissue development and/or maintenance
    a component
    small molecule
  • binding to heparin
  • regulates PTN gene expression with a high degree of organ specificity
  • PLSCR1 is a novel MDK-interacting protein
  • PLSCR1 positively regulates hepatic carcinoma cell proliferation and migration through interacting with MDK, thus deepening our understanding on the regulation of midkine during hepatic carcinoma growth and metastasis
  • LTK in neural crest cells interacts with MDK emanating from the non-neural ectoderm to promote cell survival, revealing a new signaling pathway that is essential for neural crest development
  • cell & other
    induced by retinoic acid responsive
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral       loss of function
    in sporadic colorectal and gastric cancer
    tumoral     --over  
    in hepatocellular carcinomas
    tumoral     --over  
    in malignant peripheral nerve sheath tumor
    constitutional     --over  
    in autism spectrum disorder patients
    constitutional     --over  
    elevated plasma MDK and PTN levels in patients with systemic lupus erythematosus
    constitutional       loss of function
    exacerbates necrotizing glomerular injuries in progressive glomerulonephritis
    Variant & Polymorphism
    Candidate gene
  • urinary midkine as a biomarker in patients with acute kidney injury
  • MDK and PTN growth factors might be likely useful as markers for infection in pregnancies
  • co-expression of MDK and PTN is significantly correlated with prognosis in glioma patients
  • high expression of MDK and SDC3 may contribute to the highly perineural invasion and poor prognosis of human pancreatic cancer
  • could be taken as an ideal diagnostic marker of acute leukemia
  • Therapy target
    specific inhibitors for MDK as part of new therapeutic concepts against MPNSTs (malignant peripheral nerve sheath tumor)
    is a promising therapeutic target for various autoimmune diseases
    MDK-specific antagonists might prove beneficial in osteoporosis therapy
    could be taken as an ideal molecular target for the treatment of acute leukemia
  • Mdk-deficiency in mice has an anabolic effect on mechanically induced cortical bone formation