MK_MOUSE
ID MK_MOUSE Reviewed; 140 AA.
AC P12025;
DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1991, sequence version 2.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Midkine {ECO:0000303|PubMed:8827451};
DE Short=MK {ECO:0000303|PubMed:2345177};
DE AltName: Full=Retanoic acid-responsive protein {ECO:0000303|PubMed:2355021};
DE AltName: Full=Retinoic acid-induced differentiation factor;
DE Flags: Precursor;
GN Name=Mdk {ECO:0000312|MGI:MGI:96949}; Synonyms=Mk;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], AND INDUCTION.
RX PubMed=2345177; DOI=10.1016/s0021-9258(19)38868-4;
RA Matsubara S., Tomomura M., Kadomatsu K., Muramatsu T.;
RT "Structure of a retinoic acid-responsive gene, MK, which is transiently
RT activated during the differentiation of embryonal carcinoma cells and the
RT mid-gestation period of mouse embryogenesis.";
RL J. Biol. Chem. 265:9441-9443(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2355021; DOI=10.1016/s0021-9258(18)87013-2;
RA Tomomura M., Kadomatsu K., Matsubara S., Muramatsu T.;
RT "A retinoic acid-responsive gene, MK, found in the teratocarcinoma system.
RT Heterogeneity of the transcript and the nature of the translation
RT product.";
RL J. Biol. Chem. 265:10765-10770(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3355557; DOI=10.1016/s0006-291x(88)80505-9;
RA Kadomatsu K., Tomomura M., Muramatsu T.;
RT "cDNA cloning and sequencing of a new gene intensely expressed in early
RT differentiation stages of embryonal carcinoma cells and in mid-gestation
RT period of mouse embryogenesis.";
RL Biochem. Biophys. Res. Commun. 151:1312-1318(1988).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Salivary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE OF 1-42.
RX PubMed=8827451; DOI=10.1093/oxfordjournals.jbchem.a021361;
RA Kaneda N., Talukder A.H., Nishiyama H., Koizumi S., Muramatsu T.;
RT "Midkine, a heparin-binding growth/differentiation factor, exhibits nerve
RT cell adhesion and guidance activity for neurite outgrowth in vitro.";
RL J. Biochem. 119:1150-1156(1996).
RN [6]
RP INTERACTION WITH SDC1 AND SDC3.
RX PubMed=9089390;
RA Nakanishi T., Kadomatsu K., Okamoto T., Ichihara-Tanaka K., Kojima T.,
RA Saito H., Tomoda Y., Muramatsu T.;
RT "Expression of syndecan-1 and -3 during embryogenesis of the central
RT nervous system in relation to binding with midkine.";
RL J. Biochem. 121:197-205(1997).
RN [7]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=10096022; DOI=10.1046/j.1365-2443.1998.00231.x;
RA Nakamura E., Kadomatsu K., Yuasa S., Muramatsu H., Mamiya T., Nabeshima T.,
RA Fan Q.W., Ishiguro K., Igakura T., Matsubara S., Kaname T., Horiba M.,
RA Saito H., Muramatsu T.;
RT "Disruption of the midkine gene (Mdk) resulted in altered expression of a
RT calcium binding protein in the hippocampus of infant mice and their
RT abnormal behaviour.";
RL Genes Cells 3:811-822(1998).
RN [8]
RP MUTAGENESIS OF ARG-100; LYS-105 AND LYS-106, INTERACTION WITH PTPRZ1, AND
RP SITE.
RX PubMed=10212223; DOI=10.1074/jbc.274.18.12474;
RA Maeda N., Ichihara-Tanaka K., Kimura T., Kadomatsu K., Muramatsu T.,
RA Noda M.;
RT "A receptor-like protein-tyrosine phosphatase PTPzeta/RPTPbeta binds a
RT heparin-binding growth factor midkine. Involvement of arginine 78 of
RT midkine in the high affinity binding to PTPzeta.";
RL J. Biol. Chem. 274:12474-12479(1999).
RN [9]
RP FUNCTION.
RX PubMed=10978312; DOI=10.1074/jbc.m002538200;
RA Ueoka C., Kaneda N., Okazaki I., Nadanaka S., Muramatsu T., Sugahara K.;
RT "Neuronal cell adhesion, mediated by the heparin-binding neuroregulatory
RT factor midkine, is specifically inhibited by chondroitin sulfate E.
RT Structural ans functional implications of the over-sulfated chondroitin
RT sulfate.";
RL J. Biol. Chem. 275:37407-37413(2000).
RN [10]
RP FUNCTION.
RX PubMed=10683378; DOI=10.1172/jci7208;
RA Horiba M., Kadomatsu K., Nakamura E., Muramatsu H., Ikematsu S., Sakuma S.,
RA Hayashi K., Yuzawa Y., Matsuo S., Kuzuya M., Kaname T., Hirai M., Saito H.,
RA Muramatsu T.;
RT "Neointima formation in a restenosis model is suppressed in midkine-
RT deficient mice.";
RL J. Clin. Invest. 105:489-495(2000).
RN [11]
RP INTERACTION WITH SDC3.
RX PubMed=12084985; DOI=10.1023/a:1016042303253;
RA Kurosawa N., Chen G.Y., Kadomatsu K., Ikematsu S., Sakuma S., Muramatsu T.;
RT "Glypican-2 binds to midkine: the role of glypican-2 in neuronal cell
RT adhesion and neurite outgrowth.";
RL Glycoconj. J. 18:499-507(2001).
RN [12]
RP FUNCTION.
RX PubMed=15509530; DOI=10.1016/s0002-9440(10)63417-7;
RA Kawai H., Sato W., Yuzawa Y., Kosugi T., Matsuo S., Takei Y., Kadomatsu K.,
RA Muramatsu T.;
RT "Lack of the growth factor midkine enhances survival against cisplatin-
RT induced renal damage.";
RL Am. J. Pathol. 165:1603-1612(2004).
RN [13]
RP FUNCTION.
RX PubMed=15482347; DOI=10.1111/j.1478-3231.2004.0990.x;
RA Ochiai K., Muramatsu H., Yamamoto S., Ando H., Muramatsu T.;
RT "The role of midkine and pleiotrophin in liver regeneration.";
RL Liver Int. 24:484-491(2004).
RN [14]
RP FUNCTION, AND INDUCTION.
RX PubMed=17015789; DOI=10.1161/circulationaha.106.632273;
RA Horiba M., Kadomatsu K., Yasui K., Lee J.K., Takenaka H., Sumida A.,
RA Kamiya K., Chen S., Sakuma S., Muramatsu T., Kodama I.;
RT "Midkine plays a protective role against cardiac ischemia/reperfusion
RT injury through a reduction of apoptotic reaction.";
RL Circulation 114:1713-1720(2006).
RN [15]
RP DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, AND FUNCTION.
RX PubMed=17121547; DOI=10.1111/j.1365-2443.2006.01028.x;
RA Muramatsu H., Zou P., Kurosawa N., Ichihara-Tanaka K., Maruyama K.,
RA Inoh K., Sakai T., Chen L., Sato M., Muramatsu T.;
RT "Female infertility in mice deficient in midkine and pleiotrophin, which
RT form a distinct family of growth factors.";
RL Genes Cells 11:1405-1417(2006).
RN [16]
RP INTERACTION WITH CSPG5, AND FUNCTION.
RX PubMed=16901907; DOI=10.1074/jbc.m602228200;
RA Ichihara-Tanaka K., Oohira A., Rumsby M., Muramatsu T.;
RT "Neuroglycan C is a novel midkine receptor involved in process elongation
RT of oligodendroglial precursor-like cells.";
RL J. Biol. Chem. 281:30857-30864(2006).
RN [17]
RP FUNCTION.
RX PubMed=17230638; DOI=10.1111/j.1471-4159.2006.04138.x;
RA Zou P., Muramatsu H., Miyata T., Muramatsu T.;
RT "Midkine, a heparin-binding growth factor, is expressed in neural precursor
RT cells and promotes their growth.";
RL J. Neurochem. 99:1470-1479(2006).
RN [18]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=16619002; DOI=10.1038/labinvest.3700428;
RA Zou P., Muramatsu H., Sone M., Hayashi H., Nakashima T., Muramatsu T.;
RT "Mice doubly deficient in the midkine and pleiotrophin genes exhibit
RT deficits in the expression of beta-tectorin gene and in auditory
RT response.";
RL Lab. Invest. 86:645-653(2006).
RN [19]
RP FUNCTION, AND INDUCTION.
RX PubMed=19060126; DOI=10.1152/ajpheart.00733.2008;
RA Takenaka H., Horiba M., Ishiguro H., Sumida A., Hojo M., Usui A., Akita T.,
RA Sakuma S., Ueda Y., Kodama I., Kadomatsu K.;
RT "Midkine prevents ventricular remodeling and improves long-term survival
RT after myocardial infarction.";
RL Am. J. Physiol. 296:H462-H469(2009).
RN [20]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=20200993; DOI=10.1002/jbmr.75;
RA Neunaber C., Catala-Lehnen P., Beil F.T., Marshall R.P., Kanbach V.,
RA Baranowsky A., Lehmann W., Streichert T., Ignatius A., Muramatsu T.,
RA Schinke T., Amling M.;
RT "Increased trabecular bone formation in mice lacking the growth factor
RT midkine.";
RL J. Bone Miner. Res. 25:1724-1735(2010).
RN [21]
RP FUNCTION.
RX PubMed=21185956; DOI=10.1016/j.bone.2010.12.019;
RA Liedert A., Mattausch L., Roentgen V., Blakytny R., Vogele D., Pahl M.,
RA Bindl R., Neunaber C., Schinke T., Harroch S., Amling M., Ignatius A.;
RT "Midkine-deficiency increases the anabolic response of cortical bone to
RT mechanical loading.";
RL Bone 48:945-951(2011).
RN [22]
RP INDUCTION.
RX PubMed=22323540; DOI=10.4049/jimmunol.1102346;
RA Sonobe Y., Li H., Jin S., Kishida S., Kadomatsu K., Takeuchi H., Mizuno T.,
RA Suzumura A.;
RT "Midkine inhibits inducible regulatory T cell differentiation by
RT suppressing the development of tolerogenic dendritic cells.";
RL J. Immunol. 188:2602-2611(2012).
RN [23]
RP FUNCTION.
RX PubMed=24458438; DOI=10.1182/blood-2013-06-510875;
RA Weckbach L.T., Gola A., Winkelmann M., Jakob S.M., Groesser L.,
RA Borgolte J., Pogoda F., Pick R., Pruenster M., Mueller-Hoecker J.,
RA Deindl E., Sperandio M., Walzog B.;
RT "The cytokine midkine supports neutrophil trafficking during acute
RT inflammation by promoting adhesion via beta2 integrins (CD11/CD18).";
RL Blood 123:1887-1896(2014).
RN [24]
RP INDUCTION, AND FUNCTION.
RX PubMed=25551381; DOI=10.1371/journal.pone.0116282;
RA Haffner-Luntzer M., Heilmann A., Rapp A.E., Beie S., Schinke T., Amling M.,
RA Ignatius A., Liedert A.;
RT "Midkine-deficiency delays chondrogenesis during the early phase of
RT fracture healing in mice.";
RL PLoS ONE 9:E116282-E116282(2014).
RN [25]
RP FUNCTION.
RX PubMed=28183532; DOI=10.1016/j.ajpath.2016.12.006;
RA Masuda T., Maeda K., Sato W., Kosugi T., Sato Y., Kojima H., Kato N.,
RA Ishimoto T., Tsuboi N., Uchimura K., Yuzawa Y., Maruyama S., Kadomatsu K.;
RT "Growth Factor Midkine Promotes T-Cell Activation through Nuclear Factor of
RT Activated T Cells Signaling and Th1 Cell Differentiation in Lupus
RT Nephritis.";
RL Am. J. Pathol. 187:740-751(2017).
RN [26]
RP FUNCTION.
RX PubMed=29233575; DOI=10.1016/j.ebiom.2017.11.020;
RA Lautz T., Lasch M., Borgolte J., Troidl K., Pagel J.I.,
RA Caballero-Martinez A., Kleinert E.C., Walzog B., Deindl E.;
RT "Midkine Controls Arteriogenesis by Regulating the Bioavailability of
RT Vascular Endothelial Growth Factor A and the Expression of Nitric Oxide
RT Synthase 1 and 3.";
RL EBioMedicine 27:237-246(2018).
CC -!- FUNCTION: Secreted protein that functions as cytokine and growth factor
CC and mediates its signal through cell-surface proteoglycan and non-
CC proteoglycan receptors (PubMed:16901907). Binds cell-surface
CC proteoglycan receptors via their chondroitin sulfate (CS) groups
CC (PubMed:17230638). Thereby regulates many processes like inflammatory
CC response, cell proliferation, cell adhesion, cell growth, cell
CC survival, tissue regeneration, cell differentiation and cell migration
CC (PubMed:17230638, PubMed:19060126, PubMed:17015789, PubMed:28183532,
CC PubMed:10683378, PubMed:15482347, PubMed:15509530, PubMed:24458438,
CC PubMed:25551381, PubMed:29233575). Participates in inflammatory
CC processes by exerting two different activities. Firstly, mediates
CC neutrophils and macrophages recruitment to the sites of inflammation
CC both by direct action by cooperating namely with ITGB2 via LRP1 and by
CC inducing chemokine expression (PubMed:10683378, PubMed:15509530,
CC PubMed:24458438, PubMed:28183532). This inflammation can be accompanied
CC by epithelial cell survival and smooth muscle cell migration after
CC renal and vessel damage, respectively (PubMed:15509530,
CC PubMed:10683378). Secondly, suppresses the development of tolerogenic
CC dendric cells thereby inhibiting the differentiation of regulatory T
CC cells and also promote T cell expansion through NFAT signaling and Th1
CC cell differentiation (PubMed:28183532). Promotes tissue regeneration
CC after injury or trauma. After heart damage negatively regulates the
CC recruitment of inflammatory cells and mediates cell survival through
CC activation of anti-apoptotic signaling pathways via MAPKs and AKT
CC pathways through the activation of angiogenesis (PubMed:17015789,
CC PubMed:19060126). Also facilitates liver regeneration as well as bone
CC repair by recruiting macrophage at trauma site and by promoting
CC cartilage development by facilitating chondrocyte differentiation
CC (PubMed:15482347, PubMed:25551381). Plays a role in brain by promoting
CC neural precursor cells survival and growth through interaction with
CC heparan sulfate proteoglycans (PubMed:17230638). Binds PTPRZ1 and
CC promotes neuronal migration and embryonic neurons survival (By
CC similarity). Binds SDC3 or GPC2 and mediates neurite outgrowth and cell
CC adhesion (By similarity). Binds chondroitin sulfate E and heparin
CC leading to inhibition of neuronal cell adhesion induced by binding with
CC GPC2 (PubMed:10978312). Binds CSPG5 and promotes elongation of
CC oligodendroglial precursor-like cells (PubMed:16901907). Also binds
CC ITGA6:ITGB1 complex; this interaction mediates MDK-induced neurite
CC outgrowth (By similarity). Binds LRP1; promotes neuronal survival (By
CC similarity). Binds ITGA4:ITGB1 complex; this interaction mediates MDK-
CC induced osteoblast cells migration through PXN phosphorylation (By
CC similarity). Binds anaplastic lymphoma kinase (ALK) which induces ALK
CC activation and subsequent phosphorylation of the insulin receptor
CC substrate (IRS1), followed by the activation of mitogen-activated
CC protein kinase (MAPK) and PI3-kinase, and the induction of cell
CC proliferation (By similarity). Promotes epithelial to mesenchymal
CC transition through interaction with NOTCH2 (By similarity). During
CC arteriogenesis, plays a role in vascular endothelial cell proliferation
CC by inducing VEGFA expression and release which in turn induces nitric
CC oxide synthase expression. Moreover activates vasodilation through
CC nitric oxide synthase activation (PubMed:29233575). Negatively
CC regulates bone formation in response to mechanical load by inhibiting
CC Wnt/beta-catenin signaling in osteoblasts (PubMed:21185956,
CC PubMed:20200993). In addition plays a role in hippocampal development,
CC working memory, auditory response, early fetal adrenal gland
CC development and the female reproductive system (PubMed:16619002,
CC PubMed:17121547, PubMed:10096022). {ECO:0000250|UniProtKB:P21741,
CC ECO:0000269|PubMed:10096022, ECO:0000269|PubMed:10683378,
CC ECO:0000269|PubMed:10978312, ECO:0000269|PubMed:15482347,
CC ECO:0000269|PubMed:15509530, ECO:0000269|PubMed:16619002,
CC ECO:0000269|PubMed:16901907, ECO:0000269|PubMed:17015789,
CC ECO:0000269|PubMed:17121547, ECO:0000269|PubMed:17230638,
CC ECO:0000269|PubMed:19060126, ECO:0000269|PubMed:20200993,
CC ECO:0000269|PubMed:21185956, ECO:0000269|PubMed:24458438,
CC ECO:0000269|PubMed:25551381, ECO:0000269|PubMed:28183532,
CC ECO:0000269|PubMed:29233575}.
CC -!- SUBUNIT: Homodimer. Interacts with ALK. Interacts with LRP1; promotes
CC neuronal survival. Interacts with LRP2. Interacts with NCAM1 (By
CC similarity). Interacts (via C-terminal) with PTPRZ1 (via chondroitin
CC sulfate chains); this interaction is inhibited by PTN; this interaction
CC promotes neuronal migration (PubMed:10212223). Interacts with NCL; this
CC interaction promotes NCL clustering and lateral movements of this
CC complex into lipid rafts leading to MDK internalization. Interacts with
CC LRP6 and LRP8: this interaction is calcium dependent. Interacts with
CC ITGA4. Interacts with ITGA6. Interacts with ITGB1. Interacts with
CC ITGA4:ITGB1 complex; this interaction mediates MDK-induced osteoblast
CC cells migration through PXN phosphorylation. Interacts with ITGA6:ITGB1
CC complex; this interaction mediates MDK-induced neurite outgrowth.
CC Interacts with NOTCH2; this interactio mediates a nuclear accumulation
CC of NOTCH2 and therefore activation of NOTCH2 signaling leading to
CC interaction between HES1 and STAT3. Interacts with GPC2 (via heparan
CC sulfate chain); this interaction is inhibited by heparin followed by
CC chondroitin sulfate E; this interaction induces GPC2 clustering through
CC heparan sulfate chain; this interaction induces neuronal cell adhesion
CC and neurite outgrowth (By similarity). Interacts with SDC3; this
CC interaction induces SDC3 clustering; this interaction induces neuronal
CC cell adhesion and neurite outgrowth (PubMed:9089390, PubMed:12084985).
CC Interacts with SDC1 (PubMed:9089390). Interacts with CSPG5; this
CC interaction promotes elongation of oligodendroglial precursor-like
CC cells (PubMed:16901907). {ECO:0000250|UniProtKB:P21741,
CC ECO:0000269|PubMed:10212223, ECO:0000269|PubMed:12084985,
CC ECO:0000269|PubMed:16901907, ECO:0000269|PubMed:9089390}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Expressed in the follicular epithelium and
CC granulosa cells of the ovary. {ECO:0000269|PubMed:17121547}.
CC -!- DEVELOPMENTAL STAGE: Is expressed temporarily during the early stages
CC of retinoic acid-induced differentiation of embryonal carcinoma cells
CC and during the mid-gestation period of mouse embryogenesis. In late
CC embryos and in adults expression is restricted to the kidney.
CC -!- INDUCTION: By retinoic acid (PubMed:2345177). Induced after tissue
CC damage (PubMed:17015789, PubMed:19060126). Induced by inflammatory
CC cells, in particular, CD4(+) T cells under inflammatory conditions
CC (PubMed:22323540). Induced during the early and intermediate phase of
CC fracture repair (PubMed:25551381). {ECO:0000269|PubMed:17015789,
CC ECO:0000269|PubMed:19060126, ECO:0000269|PubMed:22323540,
CC ECO:0000269|PubMed:2345177, ECO:0000269|PubMed:25551381}.
CC -!- DISRUPTION PHENOTYPE: Homozygous knockout MDK mice are viable and
CC reproduce normally. Mice have no apparent abnormalities except that
CC postnatal development of the hippocampus is delayed. However 4 weeks
CC after birth, mice have a deficit in their working memory and have an
CC increased anxiety (PubMed:10096022). Knockout MDK mice exhibit low to
CC moderate levels of auditory deficits and generally respond at around 50
CC dB. PTN and MDK double knockoutmice have a deficit of auditory response
CC (PubMed:16619002). PTN and MDK double knockout mice are born in only
CC one third the number expected by Mendelian segregation and 4 weeks
CC after birth weigh about half as much as wild-type mice. Most of the
CC female are infertile. Both male and female one-month-old mice show a
CC defect in spontaneous locomotive activity of 50-60% of that of wild-
CC type mice. Although the difference in activity decrease with age, the
CC activity of 3-month-old male double knockout mice is still about 80% of
CC that of the wild-type mice. The diestrus and proestrus periods are long
CC and the estrus period is short. Furthermore, vaginal abnormality is
CC found in about half of the double deficient mice (PubMed:17121547).
CC Homozygous knockout MDK mice display not significant difference from
CC wild-type until the age of 6 month. Mice at 12 and 18 months of age
CC show an increased trabecular bone volume, accompanied by cortical
CC porosity (PubMed:20200993). {ECO:0000269|PubMed:10096022,
CC ECO:0000269|PubMed:16619002, ECO:0000269|PubMed:17121547,
CC ECO:0000269|PubMed:20200993}.
CC -!- SIMILARITY: Belongs to the pleiotrophin family. {ECO:0000305}.
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DR EMBL; M19662; AAA39710.1; -; mRNA.
DR EMBL; M34327; AAA39712.1; -; mRNA.
DR EMBL; M34328; AAA39715.1; -; mRNA.
DR EMBL; M35833; AAA39714.1; -; mRNA.
DR EMBL; M34094; AAA39717.1; -; Genomic_DNA.
DR EMBL; BC012244; AAH12244.1; -; mRNA.
DR CCDS; CCDS16440.1; -.
DR PIR; A27684; A27684.
DR PIR; A35305; A35305.
DR RefSeq; NP_001012335.1; NM_001012335.2.
DR RefSeq; NP_001012336.1; NM_001012336.2.
DR RefSeq; NP_001278410.1; NM_001291481.1.
DR RefSeq; NP_034914.1; NM_010784.5.
DR AlphaFoldDB; P12025; -.
DR SMR; P12025; -.
DR BioGRID; 201369; 4.
DR DIP; DIP-5791N; -.
DR IntAct; P12025; 3.
DR STRING; 10090.ENSMUSP00000028672; -.
DR iPTMnet; P12025; -.
DR PhosphoSitePlus; P12025; -.
DR MaxQB; P12025; -.
DR PaxDb; P12025; -.
DR PeptideAtlas; P12025; -.
DR PRIDE; P12025; -.
DR ProteomicsDB; 290257; -.
DR DNASU; 17242; -.
DR Ensembl; ENSMUST00000028672; ENSMUSP00000028672; ENSMUSG00000027239.
DR Ensembl; ENSMUST00000069423; ENSMUSP00000068413; ENSMUSG00000027239.
DR Ensembl; ENSMUST00000090602; ENSMUSP00000088090; ENSMUSG00000027239.
DR Ensembl; ENSMUST00000111309; ENSMUSP00000106941; ENSMUSG00000027239.
DR GeneID; 17242; -.
DR KEGG; mmu:17242; -.
DR UCSC; uc008kww.2; mouse.
DR CTD; 4192; -.
DR MGI; MGI:96949; Mdk.
DR VEuPathDB; HostDB:ENSMUSG00000027239; -.
DR eggNOG; ENOG502S022; Eukaryota.
DR GeneTree; ENSGT00390000007640; -.
DR HOGENOM; CLU_136864_0_0_1; -.
DR InParanoid; P12025; -.
DR OMA; CKYKFGA; -.
DR OrthoDB; 1489280at2759; -.
DR PhylomeDB; P12025; -.
DR TreeFam; TF332376; -.
DR Reactome; R-MMU-201556; Signaling by ALK.
DR BioGRID-ORCS; 17242; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Mdk; mouse.
DR PRO; PR:P12025; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; P12025; protein.
DR Bgee; ENSMUSG00000027239; Expressed in hindlimb bud and 183 other tissues.
DR Genevisible; P12025; MM.
DR GO; GO:0042995; C:cell projection; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0035374; F:chondroitin sulfate binding; IDA:UniProtKB.
DR GO; GO:0008083; F:growth factor activity; IBA:GO_Central.
DR GO; GO:1904399; F:heparan sulfate binding; ISS:UniProtKB.
DR GO; GO:0008201; F:heparin binding; IDA:UniProtKB.
DR GO; GO:0030325; P:adrenal gland development; ISS:UniProtKB.
DR GO; GO:0001662; P:behavioral fear response; IMP:DFLAT.
DR GO; GO:0016477; P:cell migration; ISO:MGI.
DR GO; GO:0021681; P:cerebellar granular layer development; IMP:DFLAT.
DR GO; GO:0021987; P:cerebral cortex development; IEP:DFLAT.
DR GO; GO:0007010; P:cytoskeleton organization; IMP:UniProtKB.
DR GO; GO:0030421; P:defecation; IMP:DFLAT.
DR GO; GO:0021542; P:dentate gyrus development; IEP:DFLAT.
DR GO; GO:0044849; P:estrous cycle; IMP:UniProtKB.
DR GO; GO:0106091; P:glial cell projection elongation; IDA:UniProtKB.
DR GO; GO:0021766; P:hippocampus development; IMP:DFLAT.
DR GO; GO:0002232; P:leukocyte chemotaxis involved in inflammatory response; IMP:UniProtKB.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IMP:UniProtKB.
DR GO; GO:0010667; P:negative regulation of cardiac muscle cell apoptotic process; IMP:UniProtKB.
DR GO; GO:0007162; P:negative regulation of cell adhesion; IDA:UniProtKB.
DR GO; GO:1904036; P:negative regulation of epithelial cell apoptotic process; IMP:UniProtKB.
DR GO; GO:0106015; P:negative regulation of inflammatory response to wounding; IMP:UniProtKB.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IDA:DFLAT.
DR GO; GO:1901215; P:negative regulation of neuron death; IDA:DFLAT.
DR GO; GO:0030279; P:negative regulation of ossification; IMP:UniProtKB.
DR GO; GO:0045590; P:negative regulation of regulatory T cell differentiation; ISS:UniProtKB.
DR GO; GO:0048477; P:oogenesis; IMP:UniProtKB.
DR GO; GO:1905653; P:positive regulation of artery morphogenesis; IMP:UniProtKB.
DR GO; GO:1905555; P:positive regulation of blood vessel branching; ISS:UniProtKB.
DR GO; GO:0061036; P:positive regulation of cartilage development; IMP:UniProtKB.
DR GO; GO:0045785; P:positive regulation of cell adhesion; ISS:UniProtKB.
DR GO; GO:0051781; P:positive regulation of cell division; IEA:UniProtKB-KW.
DR GO; GO:0030335; P:positive regulation of cell migration; ISS:UniProtKB.
DR GO; GO:0010718; P:positive regulation of epithelial to mesenchymal transition; ISS:UniProtKB.
DR GO; GO:2000347; P:positive regulation of hepatocyte proliferation; IMP:UniProtKB.
DR GO; GO:0050729; P:positive regulation of inflammatory response; ISS:UniProtKB.
DR GO; GO:0106016; P:positive regulation of inflammatory response to wounding; IMP:UniProtKB.
DR GO; GO:0032735; P:positive regulation of interleukin-12 production; ISS:UniProtKB.
DR GO; GO:0010838; P:positive regulation of keratinocyte proliferation; ISS:UniProtKB.
DR GO; GO:1904996; P:positive regulation of leukocyte adhesion to vascular endothelial cell; IMP:UniProtKB.
DR GO; GO:1903039; P:positive regulation of leukocyte cell-cell adhesion; ISS:UniProtKB.
DR GO; GO:0002690; P:positive regulation of leukocyte chemotaxis; IMP:UniProtKB.
DR GO; GO:0010759; P:positive regulation of macrophage chemotaxis; IMP:UniProtKB.
DR GO; GO:2000179; P:positive regulation of neural precursor cell proliferation; IMP:UniProtKB.
DR GO; GO:2001224; P:positive regulation of neuron migration; ISS:UniProtKB.
DR GO; GO:0010976; P:positive regulation of neuron projection development; ISS:UniProtKB.
DR GO; GO:0090023; P:positive regulation of neutrophil chemotaxis; IMP:UniProtKB.
DR GO; GO:2000391; P:positive regulation of neutrophil extravasation; IMP:UniProtKB.
DR GO; GO:0048714; P:positive regulation of oligodendrocyte differentiation; ISS:UniProtKB.
DR GO; GO:0071673; P:positive regulation of smooth muscle cell chemotaxis; ISS:UniProtKB.
DR GO; GO:1900026; P:positive regulation of substrate adhesion-dependent cell spreading; IMP:UniProtKB.
DR GO; GO:0045582; P:positive regulation of T cell differentiation; IMP:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:DFLAT.
DR GO; GO:1905564; P:positive regulation of vascular endothelial cell proliferation; IMP:UniProtKB.
DR GO; GO:2000249; P:regulation of actin cytoskeleton reorganization; ISS:UniProtKB.
DR GO; GO:0050795; P:regulation of behavior; IMP:DFLAT.
DR GO; GO:0046850; P:regulation of bone remodeling; IMP:UniProtKB.
DR GO; GO:0032330; P:regulation of chondrocyte differentiation; IMP:UniProtKB.
DR GO; GO:0010996; P:response to auditory stimulus; IMP:UniProtKB.
DR GO; GO:0051384; P:response to glucocorticoid; IEA:Ensembl.
DR GO; GO:0009611; P:response to wounding; IDA:UniProtKB.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0007614; P:short-term memory; IMP:DFLAT.
DR GO; GO:0002286; P:T cell activation involved in immune response; IMP:UniProtKB.
DR GO; GO:0042246; P:tissue regeneration; IMP:UniProtKB.
DR Gene3D; 2.20.60.10; -; 1.
DR Gene3D; 2.30.90.10; -; 1.
DR InterPro; IPR000762; Midkine_heparin-bd_GF.
DR InterPro; IPR020090; PTN/MK_C_dom.
DR InterPro; IPR038130; PTN/MK_C_dom_sf.
DR InterPro; IPR020091; PTN/MK_diS_sf.
DR InterPro; IPR020089; PTN/MK_N_dom.
DR InterPro; IPR037122; PTN/MK_N_dom_sf.
DR InterPro; IPR020092; PTN_MK_heparin-bd_GF_CS.
DR PANTHER; PTHR13850; PTHR13850; 1.
DR Pfam; PF01091; PTN_MK_C; 1.
DR Pfam; PF05196; PTN_MK_N; 1.
DR PRINTS; PR00269; PTNMIDKINE.
DR SMART; SM00193; PTN; 1.
DR SUPFAM; SSF57288; SSF57288; 2.
DR PROSITE; PS00619; PTN_MK_1; 1.
DR PROSITE; PS00620; PTN_MK_2; 1.
PE 1: Evidence at protein level;
KW Developmental protein; Differentiation; Disulfide bond; Growth factor;
KW Heparin-binding; Mitogen; Reference proteome; Secreted; Signal.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..140
FT /note="Midkine"
FT /id="PRO_0000024663"
FT SITE 100
FT /note="Required for high affinity binding to PTRZ1 by
FT interacting with the chondroitin sulfate chains of PTRZ1"
FT /evidence="ECO:0000269|PubMed:10212223"
FT DISULFID 34..58
FT /evidence="ECO:0000250"
FT DISULFID 42..67
FT /evidence="ECO:0000250"
FT DISULFID 49..71
FT /evidence="ECO:0000250"
FT DISULFID 81..113
FT /evidence="ECO:0000250"
FT DISULFID 91..123
FT /evidence="ECO:0000250"
FT MUTAGEN 100
FT /note="R->Q: Decreases affinity binding to PTPRZ1.
FT Decreases affinity binding to PTPRZ1; when associated with
FT Q-105 and Q-106. Decreases neuron migration. Decreases
FT neuron migration; when associated with Q-105 and Q-106."
FT /evidence="ECO:0000269|PubMed:10212223"
FT MUTAGEN 105
FT /note="K->Q: Does not affect binding with PTPRZ1. Does not
FT affect binding with PTPRZ1; when associated with Q-106.
FT Does not affect positive regulation of neuron migration."
FT /evidence="ECO:0000269|PubMed:10212223"
FT MUTAGEN 106
FT /note="K->Q: Does not affect binding with PTPRZ1. Does not
FT affect binding with PTPRZ1; when associated with Q-105.
FT Does not affect positive regulation of neuron migration."
FT /evidence="ECO:0000269|PubMed:10212223"
SQ SEQUENCE 140 AA; 15434 MW; DAE31FEC94B29CF7 CRC64;
MQHRGFFLLA LLALLVVTSA VAKKKEKVKK GSECSEWTWG PCTPSSKDCG MGFREGTCGA
QTQRVHCKVP CNWKKEFGAD CKYKFESWGA CDGSTGTKAR QGTLKKARYN AQCQETIRVT
KPCTSKTKSK TKAKKGKGKD
