MDK midkine [Homo sapiens (human)] - Gene

Summary

Official Symbol: MDKprovided by HGNC
Official Full Name: midkineprovided by HGNC
Primary source: HGNC:HGNC:6972
See related: Ensembl:ENSG00000110492 MIM:162096; AllianceGenome:HGNC:6972
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: MK; ARAP; NEGF2
Summary: This gene encodes a member of a small family of secreted growth factors that binds heparin and responds to retinoic acid. The encoded protein promotes cell growth, migration, and angiogenesis, in particular during tumorigenesis. This gene has been targeted as a therapeutic for a variety of different disorders. Alternatively spliced transcript variants encoding multiple isoforms have been observed. [provided by RefSeq, Jul 2012]
Expression: Broad expression in ovary (RPKM 88.5), endometrium (RPKM 55.5) and 14 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 11p11.2

Exon count:: 6

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	11	NC_000011.10 (46380784..46383837)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	11	NC_060935.1 (46536860..46539912)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	11	NC_000011.9 (46402334..46405387)

Chromosome 11 - NC_000011.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

MDK promotes M2 macrophage polarization to remodel the tumour microenvironment in clear cell renal cell carcinoma.
Title: MDK promotes M2 macrophage polarization to remodel the tumour microenvironment in clear cell renal cell carcinoma.
Spatial and single-cell colocalisation analysis reveals MDK-mediated immunosuppressive environment with regulatory T cells in colorectal carcinogenesis.
Title: Spatial and single-cell colocalisation analysis reveals MDK-mediated immunosuppressive environment with regulatory T cells in colorectal carcinogenesis.
Midkine (MDK) in Hepatocellular Carcinoma: More than a Biomarker.
Title: Midkine (MDK) in Hepatocellular Carcinoma: More than a Biomarker.
Elevated Midkine Serum Levels Are Associated with Long-Term Survival in Critically Ill Patients.
Title: Elevated Midkine Serum Levels Are Associated with Long-Term Survival in Critically Ill Patients.
Single-cell RNA-sequencing analysis reveals enhanced non-canonical neurotrophic factor signaling in the subacute phase of traumatic brain injury.
Title: Single-cell RNA-sequencing analysis reveals enhanced non-canonical neurotrophic factor signaling in the subacute phase of traumatic brain injury.
Midkine characterization in human ovaries: potential new variants in follicles.
Title: Midkine characterization in human ovaries: potential new variants in follicles.
Differential Production of Midkine and Pleiotrophin by Innate APCs upon Stimulation through Nucleic Acid-Sensing TLRs.
Title: Differential Production of Midkine and Pleiotrophin by Innate APCs upon Stimulation through Nucleic Acid-Sensing TLRs.
Secreted proteins MDK, WFDC2, and CXCL14 as candidate biomarkers for early diagnosis of lung adenocarcinoma.
Title: Secreted proteins MDK, WFDC2, and CXCL14 as candidate biomarkers for early diagnosis of lung adenocarcinoma.
Long noncoding RNA HOTAIR and Midkine as biomarkers in thyroid cancer.
Title: Long noncoding RNA HOTAIR and Midkine as biomarkers in thyroid cancer.
CAF-derived midkine promotes EMT and cisplatin resistance by upregulating lncRNA ST7-AS1 in gastric cancer.
Title: CAF-derived midkine promotes EMT and cisplatin resistance by upregulating lncRNA ST7-AS1 in gastric cancer.

Submit: New GeneRIF Correction See all GeneRIFs (162)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Association of IFIH1 and other autoimmunity risk alleles with selective IgA deficiency. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

MARC_2215-2216:991932659:1 (e-PCR)
- UniSTS:230913

MDK (e-PCR)
- UniSTS:49160

SGC33101 (e-PCR)
- UniSTS:66369

DGKZ_1591 (e-PCR)
- UniSTS:277163

D11S4595 (e-PCR)
- UniSTS:35283

RH12588 (e-PCR)
- UniSTS:2807

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables chondroitin sulfate binding	ISS Inferred from Sequence or Structural Similarity more info
enables growth factor activity	IBA Inferred from Biological aspect of Ancestor more info
enables growth factor activity	NAS Non-traceable Author Statement more info	PubMed
enables heparan sulfate binding	IDA Inferred from Direct Assay more info	PubMed
enables heparin binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in T cell activation involved in immune response	ISS Inferred from Sequence or Structural Similarity more info
involved_in adrenal gland development	ISS Inferred from Sequence or Structural Similarity more info
involved_in behavioral fear response	IEA Inferred from Electronic Annotation more info
involved_in cell differentiation	NAS Non-traceable Author Statement more info	PubMed
involved_in cerebellar granular layer development	IEA Inferred from Electronic Annotation more info
involved_in cerebral cortex development	IEA Inferred from Electronic Annotation more info
involved_in cytoskeleton organization	ISS Inferred from Sequence or Structural Similarity more info
involved_in defecation	IEA Inferred from Electronic Annotation more info
involved_in dentate gyrus development	IEA Inferred from Electronic Annotation more info
involved_in estrous cycle	ISS Inferred from Sequence or Structural Similarity more info
involved_in glial cell projection elongation	ISS Inferred from Sequence or Structural Similarity more info
involved_in intracellular signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in leukocyte chemotaxis involved in inflammatory response	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in leukocyte chemotaxis involved in inflammatory response	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of canonical Wnt signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of cardiac muscle cell apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of cardiac muscle cell apoptotic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of cell adhesion	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of epithelial cell apoptotic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of inflammatory response to wounding	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of neuron apoptotic process	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of ossification	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of regulatory T cell differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in nervous system development	NAS Non-traceable Author Statement more info	PubMed
involved_in oogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of DNA-templated transcription	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of T cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of artery morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of blood vessel branching	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of cartilage development	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of cell adhesion	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of cell division	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of cell migration	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of epithelial to mesenchymal transition	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of hepatocyte proliferation	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of inflammatory response	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of inflammatory response to wounding	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of interleukin-12 production	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of keratinocyte proliferation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of leukocyte adhesion to vascular endothelial cell	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of leukocyte cell-cell adhesion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of leukocyte chemotaxis	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of macrophage chemotaxis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of macrophage chemotaxis	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of neural precursor cell proliferation	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of neuron migration	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of neuron projection development	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of neuron projection development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of neutrophil chemotaxis	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of neutrophil extravasation	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of oligodendrocyte differentiation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of smooth muscle cell chemotaxis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of substrate adhesion-dependent cell spreading	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of vascular endothelial cell proliferation	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of behavior	IEA Inferred from Electronic Annotation more info
involved_in regulation of bone remodeling	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of chondrocyte differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in response to auditory stimulus	ISS Inferred from Sequence or Structural Similarity more info
involved_in response to wounding	ISS Inferred from Sequence or Structural Similarity more info
involved_in short-term memory	IEA Inferred from Electronic Annotation more info
involved_in signal transduction	NAS Non-traceable Author Statement more info	PubMed
involved_in tissue regeneration	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
colocalizes_with collagen-containing extracellular matrix	HDA more info	PubMed
located_in extracellular region	TAS Traceable Author Statement more info

General protein information

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Preferred Names: midkine

Names: amphiregulin-associated protein; midgestation and kidney protein; neurite growth-promoting factor 2; neurite outgrowth-promoting factor 2; retinoic acid inducible factor

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001012333.3 → NP_001012333.1 midkine isoform a precursor

See identical proteins and their annotated locations for NP_001012333.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR, compared to variant 1. Variants 1, 2, 3, 4, and 5 encode the same isoform (a).

Source sequence(s)

AC116021, AI494596, BC011704, BI915189, BM016739

Consensus CDS

CCDS7919.1

UniProtKB/Swiss-Prot

P21741, Q2LEK4, Q9UCC7

UniProtKB/TrEMBL

E9PPJ5

Related

ENSP00000378932.1, ENST00000395565.5

Conserved Domains (1) summary

smart00193
Location:37 → 116

PTN; Pleiotrophin / midkine family
NM_001012334.2 → NP_001012334.1 midkine isoform a precursor

See identical proteins and their annotated locations for NP_001012334.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longer isoform (a). Variants 1, 2, 3, 4, and 5 encode the same isoform (a).

Source sequence(s)

AI494596, AK130889

Consensus CDS

CCDS7919.1

UniProtKB/Swiss-Prot

P21741, Q2LEK4, Q9UCC7

UniProtKB/TrEMBL

E9PPJ5

Related

ENSP00000352852.2, ENST00000359803.7

Conserved Domains (1) summary

smart00193
Location:37 → 116

PTN; Pleiotrophin / midkine family
NM_001270550.1 → NP_001257479.1 midkine isoform a precursor

See identical proteins and their annotated locations for NP_001257479.1

Status: REVIEWED

Description

Transcript Variant: This variant (4) differs in the 5' UTR, compared to variant 1. Variants 1, 2, 3, 4, and 5 encode the same isoform (a).

Source sequence(s)

AC116021, AI494596, AK309963, CN266369

Consensus CDS

CCDS7919.1

UniProtKB/Swiss-Prot

P21741, Q2LEK4, Q9UCC7

UniProtKB/TrEMBL

E9PPJ5

Related

ENSP00000385451.2, ENST00000405308.6

Conserved Domains (1) summary

smart00193
Location:37 → 116

PTN; Pleiotrophin / midkine family
NM_001270551.3 → NP_001257480.1 midkine isoform a precursor

See identical proteins and their annotated locations for NP_001257480.1

Status: REVIEWED

Description

Transcript Variant: This variant (5) differs in the 5' UTR, compared to variant 1. Variants 1, 2, 3, 4, and 5 encode the same isoform (a).

Source sequence(s)

AC116021, AI494596, BF684205, BI915189, BX346163

Consensus CDS

CCDS7919.1

UniProtKB/Swiss-Prot

P21741, Q2LEK4, Q9UCC7

UniProtKB/TrEMBL

E9PPJ5

Related

ENSP00000384034.1, ENST00000407067.1

Conserved Domains (1) summary

smart00193
Location:37 → 116

PTN; Pleiotrophin / midkine family
NM_001270552.3 → NP_001257481.1 midkine isoform b precursor

See identical proteins and their annotated locations for NP_001257481.1

Status: REVIEWED

Description

Transcript Variant: This variant (6) differs in the 5' UTR, and lacks an exon in the coding region, but maintains the reading frame, compared to variant 1. The encoded isoform (b) is shorter than isoform a.

Source sequence(s)

AI494596, DQ323888

Consensus CDS

CCDS59226.1

UniProtKB/Swiss-Prot

P21741

Related

ENSP00000378936.4, ENST00000395569.8

Conserved Domains (1) summary

pfam01091
Location:26 → 72

PTN_MK_C; PTN/MK heparin-binding protein family, C-terminal domain
NM_002391.6 → NP_002382.1 midkine isoform a precursor

See identical proteins and their annotated locations for NP_002382.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) differs in the 5' UTR, compared to variant 1. Variants 1, 2, 3, 4, and 5 encode the same isoform (a).

Source sequence(s)

AC116021, BC011704, BM887813

Consensus CDS

CCDS7919.1

UniProtKB/Swiss-Prot

P21741, Q2LEK4, Q9UCC7

UniProtKB/TrEMBL

E9PPJ5

Related

ENSP00000378933.4, ENST00000395566.9

Conserved Domains (1) summary

smart00193
Location:37 → 116

PTN; Pleiotrophin / midkine family

RNA

NR_073039.3 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (7) uses an alternate 5' exon and lacks an internal exon, compared to variant 1. This variant is represented as non-coding because it lacks an in-frame ORF, compared to variant 1.

Source sequence(s)

AI494596, BM887813, CN266354