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FLASH GENE

Symbol

MDK

contributors: mct - updated : 21-10-2019

HGNC name	midkine (neurite growth-promoting factor 2)
HGNC id	6972

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type	ubiquitous

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart       highly Digestive stomach       highly Endocrine pancreas       highly Nervous brain basal nuclei striatum   highly Homo sapiens Fetal Reproductive female system ovary     highly

cell lineage
cell lines	teratocarcinomas cell lines, pancreatic cancer cell lines
fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

isoforms

Precursor

a 121AA mature protein

HOMOLOGY

interspecies

ortholog to murine Mk

intraspecies

homolog to NEGF1

Homologene

FAMILY

pleiotrophin family

CATEGORY

adhesion , signaling cytokine growth factor

SUBCELLULAR LOCALIZATION	extracellular
	intracellular
	intracellular,cytoplasm

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

PHYSIOLOGICAL PROCESS

development

text	nervous tissue development and/or maintenance

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	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

REGULATION

induced by

retinoic acid responsive

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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

Susceptibility

Variant & Polymorphism

Candidate gene
Marker	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
	System Type Disorder Pubmed tumor     specific inhibitors for MDK as part of new therapeutic concepts against MPNSTs (malignant peripheral nerve sheath tumor) immunology autoimmune   is a promising therapeutic target for various autoimmune diseases osteoarticular bone ostéoporosis MDK-specific antagonists might prove beneficial in osteoporosis therapy cancer hemopathy   could be taken as an ideal molecular target for the treatment of acute leukemia

ANIMAL & CELL MODELS

Mdk-deficiency in mice has an anabolic effect on mechanically induced cortical bone formation