Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Midkine

Gene

MDK

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Developmentally regulated, secreted growth factor homologous to pleiotrophin (PTN), which has heparin binding activity. 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. Involved in neointima formation after arterial injury, possibly by mediating leukocyte recruitment. Also involved in early fetal adrenal gland development (By similarity).By similarity2 Publications

GO - Molecular functioni

  • growth factor activity Source: UniProtKB
  • heparin binding Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionDevelopmental protein, Growth factor, Heparin-binding, Mitogen
Biological processDifferentiation

Enzyme and pathway databases

ReactomeiR-HSA-2979096 NOTCH2 Activation and Transmission of Signal to the Nucleus
SignaLinkiP21741
SIGNORiP21741

Names & Taxonomyi

Protein namesi
Recommended name:
Midkine
Short name:
MK
Alternative name(s):
Amphiregulin-associated protein
Short name:
ARAP
Midgestation and kidney protein
Neurite outgrowth-promoting factor 2
Neurite outgrowth-promoting protein
Gene namesi
Name:MDK
Synonyms:MK1, NEGF2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

EuPathDBiHostDB:ENSG00000110492.15
HGNCiHGNC:6972 MDK
MIMi162096 gene
neXtProtiNX_P21741

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi4192
OpenTargetsiENSG00000110492
PharmGKBiPA30717

Chemistry databases

ChEMBLiCHEMBL1949490

Polymorphism and mutation databases

DMDMi127116

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 203 PublicationsAdd BLAST20
ChainiPRO_000002466221 – 143MidkineAdd BLAST123

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi37 ↔ 61
Disulfide bondi45 ↔ 70
Disulfide bondi52 ↔ 74
Disulfide bondi84 ↔ 116
Disulfide bondi94 ↔ 126

Keywords - PTMi

Disulfide bond

Proteomic databases

EPDiP21741
MaxQBiP21741
PaxDbiP21741
PeptideAtlasiP21741
PRIDEiP21741
ProteomicsDBi53896

PTM databases

iPTMnetiP21741
PhosphoSitePlusiP21741

Expressioni

Tissue specificityi

Expressed in various tumor cell lines. In insulinoma tissue predominantly expressed in precancerous lesions.1 Publication

Inductioni

By heparin and retinoic acid.2 Publications

Gene expression databases

BgeeiENSG00000110492 Expressed in 91 organ(s), highest expression level in adenohypophysis
CleanExiHS_MDK
ExpressionAtlasiP21741 baseline and differential
GenevisibleiP21741 HS

Organism-specific databases

HPAiCAB010055
HPA057126

Interactioni

Subunit structurei

Homodimer. Interacts with ALK.1 Publication

GO - Molecular functioni

Protein-protein interaction databases

BioGridi110357, 43 interactors
DIPiDIP-5789N
IntActiP21741, 12 interactors
MINTiP21741
STRINGi9606.ENSP00000352852

Chemistry databases

BindingDBiP21741

Structurei

Secondary structure

1143
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP21741
SMRiP21741
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP21741

Family & Domainsi

Sequence similaritiesi

Belongs to the pleiotrophin family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410J0E8 Eukaryota
ENOG4111ZWP LUCA
GeneTreeiENSGT00390000007640
HOGENOMiHOG000231473
HOVERGENiHBG008317
InParanoidiP21741
KOiK06828
PhylomeDBiP21741
TreeFamiTF332376

Family and domain databases

Gene3Di2.20.60.10, 1 hit
2.30.90.10, 1 hit
InterProiView protein in InterPro
IPR000762 Midkine_heparin-bd_GF
IPR020090 PTN/MK_C_dom
IPR038130 PTN/MK_C_dom_sf
IPR020091 PTN/MK_diS_sf
IPR020089 PTN/MK_N_dom
IPR037122 PTN/MK_N_dom_sf
IPR020092 PTN_MK_heparin-bd_GF_CS
PANTHERiPTHR13850 PTHR13850, 1 hit
PfamiView protein in Pfam
PF01091 PTN_MK_C, 1 hit
PF05196 PTN_MK_N, 1 hit
PRINTSiPR00269 PTNMIDKINE
ProDomiView protein in ProDom or Entries sharing at least one domain
PD005592 PTN_MK_hepar_bd, 1 hit
SMARTiView protein in SMART
SM00193 PTN, 1 hit
SUPFAMiSSF57288 SSF57288, 2 hits
PROSITEiView protein in PROSITE
PS00619 PTN_MK_1, 1 hit
PS00620 PTN_MK_2, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 4 potential isoforms that are computationally mapped.iShow all

Isoform 1 (identifier: P21741-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MQHRGFLLLT LLALLALTSA VAKKKDKVKK GGPGSECAEW AWGPCTPSSK
60 70 80 90 100
DCGVGFREGT CGAQTQRIRC RVPCNWKKEF GADCKYKFEN WGACDGGTGT
110 120 130 140
KVRQGTLKKA RYNAQCQETI RVTKPCTPKT KAKAKAKKGK GKD
Length:143
Mass (Da):15,585
Last modified:May 1, 1991 - v1
Checksum:i414A627FF39953C3
GO
Isoform 2 (identifier: P21741-2) [UniParc]FASTAAdd to basket
Also known as: tMKA

The sequence of this isoform differs from the canonical sequence as follows:
     26-81: Missing.

Note: Found in cancer tissues with expression in the tumor bodies and surrounding normal cells.
Show »
Length:87
Mass (Da):9,512
Checksum:i555280233CBB0AC6
GO

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E9PLM6E9PLM6_HUMAN
Midkine
MDK
156Annotation score:
E9PPJ5E9PPJ5_HUMAN
Midkine
MDK
131Annotation score:
C9JHA4C9JHA4_HUMAN
Midkine
MDK
49Annotation score:
A0A087WXB6A0A087WXB6_HUMAN
Midkine
MDK
152Annotation score:

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00635321 – 22Missing in 35% of the chains. 2

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_04745226 – 81Missing in isoform 2. 1 PublicationAdd BLAST56

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M69148 mRNA Translation: AAA58478.1
X55110 mRNA Translation: CAA38908.1
D10604 Genomic DNA Translation: BAA01457.1
M94250 Genomic DNA Translation: AAA59850.1
DQ323888 mRNA Translation: ABC55425.1
AC116021 Genomic DNA No translation available.
BC011704 mRNA Translation: AAH11704.1
CCDSiCCDS59226.1 [P21741-2]
CCDS7919.1 [P21741-1]
PIRiJH0385
RefSeqiNP_001012333.1, NM_001012333.2 [P21741-1]
NP_001012334.1, NM_001012334.2 [P21741-1]
NP_001257479.1, NM_001270550.1 [P21741-1]
NP_001257480.1, NM_001270551.1 [P21741-1]
NP_001257481.1, NM_001270552.1 [P21741-2]
NP_002382.1, NM_002391.4 [P21741-1]
XP_011518418.1, XM_011520116.2 [P21741-1]
XP_016873253.1, XM_017017764.1 [P21741-1]
UniGeneiHs.82045

Genome annotation databases

EnsembliENST00000359803; ENSP00000352852; ENSG00000110492 [P21741-1]
ENST00000395565; ENSP00000378932; ENSG00000110492 [P21741-1]
ENST00000395566; ENSP00000378933; ENSG00000110492 [P21741-1]
ENST00000395569; ENSP00000378936; ENSG00000110492 [P21741-2]
ENST00000405308; ENSP00000385451; ENSG00000110492 [P21741-1]
ENST00000407067; ENSP00000384034; ENSG00000110492 [P21741-1]
GeneIDi4192
KEGGihsa:4192
UCSCiuc001nco.5 human [P21741-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiMK_HUMAN
AccessioniPrimary (citable) accession number: P21741
Secondary accession number(s): Q2LEK4, Q9UCC7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 1, 1991
Last sequence update: May 1, 1991
Last modified: September 12, 2018
This is version 170 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again