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Protein

Midkine

Gene

Mdk

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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 (By similarity). Involved in neointima formation after arterial injury, possibly by mediating leukocyte recruitment. Also involved in early fetal adrenal gland development.By similarity1 Publication

GO - Molecular functioni

GO - Biological processi

  • adrenal gland development Source: UniProtKB
  • behavioral fear response Source: DFLAT
  • cell differentiation Source: UniProtKB-KW
  • cell migration Source: Ensembl
  • cerebellar granular layer development Source: DFLAT
  • cerebral cortex development Source: DFLAT
  • defecation Source: DFLAT
  • dentate gyrus development Source: DFLAT
  • hippocampus development Source: DFLAT
  • negative regulation of neuron apoptotic process Source: DFLAT
  • negative regulation of neuron death Source: DFLAT
  • positive regulation of cell division Source: UniProtKB-KW
  • positive regulation of transcription, DNA-templated Source: DFLAT
  • regulation of behavior Source: DFLAT
  • response to drug Source: Ensembl
  • response to glucocorticoid Source: Ensembl
  • response to wounding Source: UniProtKB
  • short-term memory Source: DFLAT
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Growth factor, Mitogen

Keywords - Biological processi

Differentiation

Keywords - Ligandi

Heparin-binding

Enzyme and pathway databases

ReactomeiR-MMU-2979096. NOTCH2 Activation and Transmission of Signal to the Nucleus.

Names & Taxonomyi

Protein namesi
Recommended name:
Midkine
Short name:
MK
Alternative name(s):
Retinoic acid-induced differentiation factor
Gene namesi
Name:Mdk
Synonyms:Mk
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:96949. Mdk.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2222Sequence analysisAdd
BLAST
Chaini23 – 140118MidkinePRO_0000024663Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi34 ↔ 58By similarity
Disulfide bondi42 ↔ 67By similarity
Disulfide bondi49 ↔ 71By similarity
Disulfide bondi81 ↔ 113By similarity
Disulfide bondi91 ↔ 123By similarity

Keywords - PTMi

Disulfide bond

Proteomic databases

MaxQBiP12025.
PaxDbiP12025.
PRIDEiP12025.

PTM databases

iPTMnetiP12025.
PhosphoSiteiP12025.

Expressioni

Developmental stagei

Is expressed temporarily during the early stages of retinoic acid-induced differentiation of embryonal carcinoma cells and during the mid-gestation period of mouse embryogenesis. In late embryos and in adults expression is restricted to the kidney.

Inductioni

By retinoic acid.

Gene expression databases

BgeeiP12025.
CleanExiMM_MDK.
GenevisibleiP12025. MM.

Interactioni

Subunit structurei

Homodimer. Interacts with ALK.By similarity

Protein-protein interaction databases

DIPiDIP-5791N.
STRINGi10090.ENSMUSP00000028672.

Structurei

3D structure databases

ProteinModelPortaliP12025.
SMRiP12025. Positions 31-127.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the pleiotrophin family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410J0E8. Eukaryota.
ENOG4111ZWP. LUCA.
GeneTreeiENSGT00390000007640.
HOGENOMiHOG000231473.
HOVERGENiHBG008317.
InParanoidiP12025.
KOiK06828.
OMAiYKFESWG.
OrthoDBiEOG7B05G6.
PhylomeDBiP12025.
TreeFamiTF332376.

Family and domain databases

Gene3Di2.20.60.10. 1 hit.
2.30.90.10. 1 hit.
InterProiIPR000762. Midkine_heparin-bd_GF.
IPR020090. PTN/MK_C_dom.
IPR020091. PTN/MK_diS.
IPR020089. PTN/MK_N_dom.
IPR020092. PTN_MK_heparin-bd_GF_CS.
[Graphical view]
PANTHERiPTHR13850. PTHR13850. 1 hit.
PfamiPF01091. PTN_MK_C. 1 hit.
PF05196. PTN_MK_N. 1 hit.
[Graphical view]
PRINTSiPR00269. PTNMIDKINE.
ProDomiPD005592. PTN_MK_hepar_bd. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTiSM00193. PTN. 1 hit.
[Graphical view]
SUPFAMiSSF57288. SSF57288. 2 hits.
PROSITEiPS00619. PTN_MK_1. 1 hit.
PS00620. PTN_MK_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

P12025-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MQHRGFFLLA LLALLVVTSA VAKKKEKVKK GSECSEWTWG PCTPSSKDCG
60 70 80 90 100
MGFREGTCGA QTQRVHCKVP CNWKKEFGAD CKYKFESWGA CDGSTGTKAR
110 120 130 140
QGTLKKARYN AQCQETIRVT KPCTSKTKSK TKAKKGKGKD
Length:140
Mass (Da):15,434
Last modified:August 1, 1991 - v2
Checksum:iDAE31FEC94B29CF7
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M19662 mRNA. Translation: AAA39710.1.
M34327 mRNA. Translation: AAA39712.1.
M34328 mRNA. Translation: AAA39715.1.
M35833 mRNA. Translation: AAA39714.1.
M34094 Genomic DNA. Translation: AAA39717.1.
BC012244 mRNA. Translation: AAH12244.1.
CCDSiCCDS16440.1.
PIRiA27684.
A35305.
RefSeqiNP_001012335.1. NM_001012335.2.
NP_001012336.1. NM_001012336.2.
NP_001278410.1. NM_001291481.1.
NP_034914.1. NM_010784.5.
UniGeneiMm.906.

Genome annotation databases

EnsembliENSMUST00000028672; ENSMUSP00000028672; ENSMUSG00000027239.
ENSMUST00000069423; ENSMUSP00000068413; ENSMUSG00000027239.
ENSMUST00000090602; ENSMUSP00000088090; ENSMUSG00000027239.
ENSMUST00000111309; ENSMUSP00000106941; ENSMUSG00000027239.
GeneIDi17242.
KEGGimmu:17242.
UCSCiuc008kww.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M19662 mRNA. Translation: AAA39710.1.
M34327 mRNA. Translation: AAA39712.1.
M34328 mRNA. Translation: AAA39715.1.
M35833 mRNA. Translation: AAA39714.1.
M34094 Genomic DNA. Translation: AAA39717.1.
BC012244 mRNA. Translation: AAH12244.1.
CCDSiCCDS16440.1.
PIRiA27684.
A35305.
RefSeqiNP_001012335.1. NM_001012335.2.
NP_001012336.1. NM_001012336.2.
NP_001278410.1. NM_001291481.1.
NP_034914.1. NM_010784.5.
UniGeneiMm.906.

3D structure databases

ProteinModelPortaliP12025.
SMRiP12025. Positions 31-127.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-5791N.
STRINGi10090.ENSMUSP00000028672.

PTM databases

iPTMnetiP12025.
PhosphoSiteiP12025.

Proteomic databases

MaxQBiP12025.
PaxDbiP12025.
PRIDEiP12025.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000028672; ENSMUSP00000028672; ENSMUSG00000027239.
ENSMUST00000069423; ENSMUSP00000068413; ENSMUSG00000027239.
ENSMUST00000090602; ENSMUSP00000088090; ENSMUSG00000027239.
ENSMUST00000111309; ENSMUSP00000106941; ENSMUSG00000027239.
GeneIDi17242.
KEGGimmu:17242.
UCSCiuc008kww.2. mouse.

Organism-specific databases

CTDi4192.
MGIiMGI:96949. Mdk.

Phylogenomic databases

eggNOGiENOG410J0E8. Eukaryota.
ENOG4111ZWP. LUCA.
GeneTreeiENSGT00390000007640.
HOGENOMiHOG000231473.
HOVERGENiHBG008317.
InParanoidiP12025.
KOiK06828.
OMAiYKFESWG.
OrthoDBiEOG7B05G6.
PhylomeDBiP12025.
TreeFamiTF332376.

Enzyme and pathway databases

ReactomeiR-MMU-2979096. NOTCH2 Activation and Transmission of Signal to the Nucleus.

Miscellaneous databases

PROiP12025.
SOURCEiSearch...

Gene expression databases

BgeeiP12025.
CleanExiMM_MDK.
GenevisibleiP12025. MM.

Family and domain databases

Gene3Di2.20.60.10. 1 hit.
2.30.90.10. 1 hit.
InterProiIPR000762. Midkine_heparin-bd_GF.
IPR020090. PTN/MK_C_dom.
IPR020091. PTN/MK_diS.
IPR020089. PTN/MK_N_dom.
IPR020092. PTN_MK_heparin-bd_GF_CS.
[Graphical view]
PANTHERiPTHR13850. PTHR13850. 1 hit.
PfamiPF01091. PTN_MK_C. 1 hit.
PF05196. PTN_MK_N. 1 hit.
[Graphical view]
PRINTSiPR00269. PTNMIDKINE.
ProDomiPD005592. PTN_MK_hepar_bd. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTiSM00193. PTN. 1 hit.
[Graphical view]
SUPFAMiSSF57288. SSF57288. 2 hits.
PROSITEiPS00619. PTN_MK_1. 1 hit.
PS00620. PTN_MK_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Structure of a retinoic acid-responsive gene, MK, which is transiently activated during the differentiation of embryonal carcinoma cells and the mid-gestation period of mouse embryogenesis."
    Matsubara S., Tomomura M., Kadomatsu K., Muramatsu T.
    J. Biol. Chem. 265:9441-9443(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
  2. "A retinoic acid-responsive gene, MK, found in the teratocarcinoma system. Heterogeneity of the transcript and the nature of the translation product."
    Tomomura M., Kadomatsu K., Matsubara S., Muramatsu T.
    J. Biol. Chem. 265:10765-10770(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  3. "cDNA cloning and sequencing of a new gene intensely expressed in early differentiation stages of embryonal carcinoma cells and in mid-gestation period of mouse embryogenesis."
    Kadomatsu K., Tomomura M., Muramatsu T.
    Biochem. Biophys. Res. Commun. 151:1312-1318(1988) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: FVB/N.
    Tissue: Salivary gland.
  5. "Midkine, a heparin-binding growth/differentiation factor, exhibits nerve cell adhesion and guidance activity for neurite outgrowth in vitro."
    Kaneda N., Talukder A.H., Nishiyama H., Koizumi S., Muramatsu T.
    J. Biochem. 119:1150-1156(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE OF 1-42.
  6. Cited for: FUNCTION.

Entry informationi

Entry nameiMK_MOUSE
AccessioniPrimary (citable) accession number: P12025
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1989
Last sequence update: August 1, 1991
Last modified: June 8, 2016
This is version 124 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.