ID MK_HUMAN Reviewed; 143 AA. AC P21741; Q9UCC7; DT 01-MAY-1991, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-1991, sequence version 1. DT 19-JAN-2010, entry version 97. DE RecName: Full=Midkine; DE Short=MK; DE AltName: Full=Neurite outgrowth-promoting protein; DE AltName: Full=Midgestation and kidney protein; DE AltName: Full=Amphiregulin-associated protein; DE Short=ARAP; DE AltName: Full=Neurite outgrowth-promoting factor 2; DE Flags: Precursor; GN Name=MDK; Synonyms=MK1, NEGF2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Kidney; RX MEDLINE=91222250; PubMed=2025291; DOI=10.1016/S0006-291X(05)80255-4; RA Tsutsui J., Uehara K., Kadomatsu K., Matsubara S., Muramatsu T.; RT "A new family of heparin-binding factors: strong conservation of RT midkine (MK) sequences between the human and the mouse."; RL Biochem. Biophys. Res. Commun. 176:792-797(1991). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND INDUCTION. RC TISSUE=Fetal brain; RX MEDLINE=92118405; PubMed=1768439; RA Kretschmer P.J., Fairhurst J.L., Decker M.M., Chan C.P., Gluzman Y., RA Boehlen P., Kovesdi I.; RT "Cloning, characterization and developmental regulation of two members RT of a novel human gene family of neurite outgrowth-promoting RT proteins."; RL Growth Factors 5:99-114(1991). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX MEDLINE=92348340; PubMed=1639750; RA Uehara K., Matsubara S., Kadomatsu K., Tsutsui J., Muramatsu T.; RT "Genomic structure of human midkine (MK), a retinoic acid-responsive RT growth/differentiation factor."; RL J. Biochem. 111:563-567(1992). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC TISSUE=Fetal brain; RX MEDLINE=93228828; PubMed=8471163; DOI=10.1089/dna.1993.12.139; RA Fairhurst J.L., Kretschmer P.J., Gluzman Y., Boehlen P., Kovesdi I.; RT "Structure of the gene coding for the human retinoic acid-inducible RT factor, MK."; RL DNA Cell Biol. 12:139-147(1993). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Uterus; 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP PROTEIN SEQUENCE OF 21-143. RX MEDLINE=91354311; PubMed=1883381; DOI=10.1016/0006-291X(91)91409-6; RA Shoyab M., McDonald V.L., Dick K., Modrell B., Malik N., Plowman G.D.; RT "Amphiregulin-associated protein: complete amino acid sequence of a RT protein produced by the 12-0-tetradecanoylphorbol-13-acetate-treated RT human breast adenocarcinoma cell line MCF-7."; RL Biochem. Biophys. Res. Commun. 179:572-578(1991). RN [7] RP PROTEIN SEQUENCE OF 21-35, AND INDUCTION. RC TISSUE=Plasma; RX MEDLINE=94059921; PubMed=8241100; RA Novotny W.F., Maffi T., Mehta R.L., Milner P.G.; RT "Identification of novel heparin-releasable proteins, as well as the RT cytokines midkine and pleiotrophin, in human postheparin plasma."; RL Arterioscler. Thromb. 13:1798-1805(1993). RN [8] RP PROTEIN SEQUENCE OF 21-35. RX PubMed=15340161; DOI=10.1110/ps.04682504; RA Zhang Z., Henzel W.J.; RT "Signal peptide prediction based on analysis of experimentally RT verified cleavage sites."; RL Protein Sci. 13:2819-2824(2004). RN [9] RP STRUCTURE BY NMR OF 23-81 AND 84-126, AND HOMODIMERIZATION. RX MEDLINE=98046024; PubMed=9384573; DOI=10.1093/emboj/16.23.6936; RA Iwasaki W., Nagata K., Hatanaka H., Inui T., Kimura T., Muramatsu T., RA Yoshida K., Tasumi M., Inagaki F.; RT "Solution structure of midkine, a new heparin-binding growth factor."; RL EMBO J. 16:6936-6946(1997). CC -!- FUNCTION: Has heparin binding activity, and growth promoting CC activity. Involved in neointima formation after arterial injury, CC possibly by mediating leukocyte recruitment. Also involved in CC early fetal adrenal gland development (By similarity). CC -!- SUBUNIT: Homodimer. CC -!- SUBCELLULAR LOCATION: Secreted. CC -!- INDUCTION: By heparin and retinoic acid. CC -!- SIMILARITY: Belongs to the pleiotrophin family. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; M69148; AAA58478.1; -; mRNA. DR EMBL; X55110; CAA38908.1; -; mRNA. DR EMBL; D10604; BAA01457.1; -; Genomic_DNA. DR EMBL; M94250; AAA59850.1; -; Genomic_DNA. DR EMBL; BC011704; AAH11704.1; -; mRNA. DR IPI; IPI00010333; -. DR PIR; JH0385; JH0385. DR RefSeq; NP_001012333.1; -. DR RefSeq; NP_001012334.1; -. DR RefSeq; NP_002382.1; -. DR UniGene; Hs.82045; -. DR PDB; 1MKC; NMR; -; A=84-126. DR PDB; 1MKN; NMR; -; A=23-81. DR PDBsum; 1MKC; -. DR PDBsum; 1MKN; -. DR DIP; DIP-5789N; -. DR IntAct; P21741; 2. DR STRING; P21741; -. DR PRIDE; P21741; -. DR Ensembl; ENST00000359803; ENSP00000352852; ENSG00000110492; Homo sapiens. DR Ensembl; ENST00000395565; ENSP00000378932; ENSG00000110492; Homo sapiens. DR Ensembl; ENST00000395566; ENSP00000378933; ENSG00000110492; Homo sapiens. DR Ensembl; ENST00000405308; ENSP00000385451; ENSG00000110492; Homo sapiens. DR Ensembl; ENST00000405994; ENSP00000384824; ENSG00000110492; Homo sapiens. DR Ensembl; ENST00000407067; ENSP00000384034; ENSG00000110492; Homo sapiens. DR GeneID; 4192; -. DR KEGG; hsa:4192; -. DR UCSC; uc001nco.1; human. DR CTD; 4192; -. DR GeneCards; GC11P046359; -. DR H-InvDB; HIX0009601; -. DR HGNC; HGNC:6972; MDK. DR HPA; CAB010055; -. DR MIM; 162096; gene. DR PharmGKB; PA30717; -. DR eggNOG; prNOG20333; -. DR HOVERGEN; P21741; -. DR OMA; GFREGTC; -. DR OrthoDB; EOG9SR0G3; -. DR PhylomeDB; P21741; -. DR Pathway_Interaction_DB; glypican_2pathway; Glypican 2 network. DR Pathway_Interaction_DB; syndecan_4_pathway; Syndecan-4-mediated signaling events. DR NextBio; 16518; -. DR ArrayExpress; P21741; -. DR Bgee; P21741; -. DR CleanEx; HS_MDK; -. DR Genevestigator; P21741; -. DR GermOnline; ENSG00000110492; Homo sapiens. DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell. DR GO; GO:0008083; F:growth factor activity; NAS:UniProtKB. DR GO; GO:0008201; F:heparin binding; IDA:UniProtKB. DR GO; GO:0030325; P:adrenal gland development; ISS:UniProtKB. DR GO; GO:0030154; P:cell differentiation; NAS:UniProtKB. DR GO; GO:0007399; P:nervous system development; NAS:UniProtKB. DR GO; GO:0051781; P:positive regulation of cell division; IEA:UniProtKB-KW. DR GO; GO:0009611; P:response to wounding; ISS:UniProtKB. DR GO; GO:0007165; P:signal transduction; NAS:ProtInc. DR InterPro; IPR000762; Midkine_heparin-bd_GF. DR InterPro; IPR020090; Midkine_heparin-bd_GF_C. DR InterPro; IPR020092; Midkine_heparin-bd_GF_CS. DR InterPro; IPR020091; Midkine_heparin-bd_GF_diS. DR InterPro; IPR020089; Midkine_heparin-bd_GF_N. DR Gene3D; G3DSA:2.20.60.10; PTN_MK_hepar_bd; 1. DR Gene3D; G3DSA:2.30.90.10; PTN_MK_hepar_bd; 1. DR PANTHER; PTHR13850; PTN_MK_hepar_bd; 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 PROSITE; PS00619; PTN_MK_1; 1. DR PROSITE; PS00620; PTN_MK_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Complete proteome; Developmental protein; KW Differentiation; Direct protein sequencing; Disulfide bond; KW Growth factor; Heparin-binding; Mitogen; Polymorphism; Secreted; KW Signal. FT SIGNAL 1 20 FT CHAIN 21 143 Midkine. FT /FTId=PRO_0000024662. FT DISULFID 37 61 FT DISULFID 45 70 FT DISULFID 52 74 FT DISULFID 84 116 FT DISULFID 94 126 FT VARIANT 21 22 Missing (in 35% of the chains). FT /FTId=VAR_006353. FT STRAND 29 31 FT STRAND 38 43 FT STRAND 48 54 FT STRAND 57 63 FT STRAND 66 68 FT STRAND 76 79 FT STRAND 96 100 FT STRAND 111 115 FT STRAND 118 120 SQ SEQUENCE 143 AA; 15585 MW; 414A627FF39953C3 CRC64; MQHRGFLLLT LLALLALTSA VAKKKDKVKK GGPGSECAEW AWGPCTPSSK DCGVGFREGT CGAQTQRIRC RVPCNWKKEF GADCKYKFEN WGACDGGTGT KVRQGTLKKA RYNAQCQETI RVTKPCTPKT KAKAKAKKGK GKD //