Pleiotrophin

PTN
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2N6F
Identifiers
Aliases	PTN, HARP, HBGF8, HBNF, NEGF1, HB-GAM, HBBM, HBGF-8, HBNF-1, OSF-1, pleiotrophin
External IDs	OMIM: 162095; MGI: 97804; HomoloGene: 2117; GeneCards: PTN; OMA:PTN - orthologs
Gene location (Human) Chr. Chromosome 7 (human) Band 7q33 Start 137,227,341 bp End 137,343,774 bp
Gene location (Mouse) Chr. Chromosome 6 (mouse) Band 6 B1|6 15.48 cM Start 36,691,864 bp End 36,787,155 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in ventricular zone ganglionic eminence trigeminal ganglion optic nerve ventral tegmental area Amygdala periodontal fiber corpus callosum nucleus accumbens Pons Top expressed in genital tubercle optic nerve efferent ductule vestibular sensory epithelium median eminence Gonadal ridge gastrula vas deferens abdominal wall ventricular zone More reference expression data BioGPS More reference expression data
Gene ontology Molecular function glycosaminoglycan binding protein phosphatase inhibitor activity heparan sulfate binding heparin binding growth factor activity chondroitin sulfate binding protein kinase binding chondroitin sulfate proteoglycan binding vascular endothelial growth factor binding proteoglycan binding Cellular component cytoplasm membrane neuromuscular junction basement membrane cell surface extracellular region endoplasmic reticulum perinuclear region of cytoplasm extracellular space protein-containing complex presynapse postsynapse Biological process positive regulation of hepatocyte proliferation bone mineralization response to estradiol ossification lung development thalamus development response to kainic acid estrous cycle cellular response to UV negative regulation of glial cell proliferation response to ciliary neurotrophic factor response to progesterone response to nerve growth factor cellular response to organic cyclic compound hindbrain development cellular response to platelet-derived growth factor stimulus cellular response to vitamin D learning response to activity negative regulation of membrane potential cerebellum development nervous system development positive regulation of skeletal muscle acetylcholine-gated channel clustering rod bipolar cell differentiation heart development transmembrane receptor protein tyrosine phosphatase signaling pathway brain development negative regulation of cell migration retina development in camera-type eye negative regulation of neuromuscular junction development spinal cord development regulation of cell shape positive regulation of neuron projection development positive regulation of apoptotic process negative regulation of epithelial cell proliferation negative regulation of angiogenesis retinal rod cell differentiation endothelial cell differentiation liver development negative regulation of mesenchymal cell proliferation cellular response to hypoxia positive regulation of cell division long-term potentiation positive regulation of cell-substrate adhesion positive regulation of cell population proliferation regulation of signaling receptor activity negative regulation of phosphoprotein phosphatase activity Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 5764 19242 Ensembl ENSG00000105894 ENSMUSG00000029838 UniProt P21246 P63089 RefSeq (mRNA) NM_002825 NM_001321386 NM_001321387 NM_008973 RefSeq (protein) NP_001308315 NP_001308316 NP_002816 NP_032999 Location (UCSC) Chr 7: 137.23 – 137.34 Mb Chr 6: 36.69 – 36.79 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

Pleiotrophin (PTN) also known as heparin-binding brain mitogen (HBBM) or heparin-binding growth factor 8 (HBGF-8) or neurite growth-promoting factor 1 (NEGF1) or heparin affinity regulatory peptide (HARP) or heparin binding growth associated molecule (HB-GAM) is a protein that in humans is encoded by the PTN gene. Pleiotrophin is an 18-kDa growth factor that has a high affinity for heparin. It is structurally related to midkine and retinoic acid induced heparin-binding protein.

Function

Pleiotrophin was initially recognized as a neurite outgrowth-promoting factor present in rat brain around birth and as a mitogen toward fibroblasts isolated from bovine uterus tissue. Together with midkine these growth-factors constitute a family of (developmentally regulated) secreted heparin-binding proteins now known as the neurite growth-promoting factor (NEGF) family. During embryonic and early postnatal development, pleiotrophin is expressed in the central and peripheral nervous system and also in several non-neural tissues, notably lung, kidney, gut and bone. Pleiotrophin is also expressed by several tumor cells and is thought to be involved in tumor angiogenesis. In the adult central nervous system, pleiotrophin is expressed in an activity-dependent manner in the hippocampus where it can suppress long term potentiation induction. Pleiotrophin expression is low in other areas of the adult brain, but it can be induced by ischemic insults. or targeted neuronal damaged in the entorhinal cortex or in the substantia nigra pars compacta.

Clinical significance

Pleiotrophin binds to cell-surface nucleolin as a low affinity receptor. This binding can inhibit HIV infection.

Further reading

• Milner PG, Shah D, Veile R, et al. (1993). "Cloning, nucleotide sequence, and chromosome localization of the human pleiotrophin gene". Biochemistry. 31 (48): 12023–8. doi:10.1021/bi00163a009. PMID 1457401.
• Li YS, Hoffman RM, Le Beau MM, et al. (1993). "Characterization of the human pleiotrophin gene. Promoter region and chromosomal localization". J. Biol. Chem. 267 (36): 26011–6. doi:10.1016/S0021-9258(18)35709-0. PMID 1464612.
• Tezuka K, Takeshita S, Hakeda Y, et al. (1991). "Isolation of mouse and human cDNA clones encoding a protein expressed specifically in osteoblasts and brain tissues". Biochem. Biophys. Res. Commun. 173 (1): 246–51. doi:10.1016/S0006-291X(05)81048-4. PMID 1701634.
• Wellstein A, Fang WJ, Khatri A, et al. (1992). "A heparin-binding growth factor secreted from breast cancer cells homologous to a developmentally regulated cytokine". J. Biol. Chem. 267 (4): 2582–7. doi:10.1016/S0021-9258(18)45920-0. PMID 1733956.
• Kretschmer PJ, Fairhurst JL, Decker MM, et al. (1992). "Cloning, characterization and developmental regulation of two members of a novel human gene family of neurite outgrowth-promoting proteins". Growth Factors. 5 (2): 99–114. doi:10.3109/08977199109000275. PMID 1768439.
• Li YS, Milner PG, Chauhan AK, et al. (1991). "Cloning and expression of a developmentally regulated protein that induces mitogenic and neurite outgrowth activity". Science. 250 (4988): 1690–4. Bibcode:1990Sci...250.1690L. doi:10.1126/science.2270483. PMID 2270483.
• Huber D, Gautschi-Sova P, Böhlen P (1990). "Amino-terminal sequences of a novel heparin-binding protein from human, bovine, rat, and chick brain: high interspecies homology". Neurochem. Res. 15 (4): 435–9. doi:10.1007/BF00969930. PMID 2388713. S2CID 24896178.
• Asundi VK, Carey DJ (1995). "Self-association of N-syndecan (syndecan-3) core protein is mediated by a novel structural motif in the transmembrane domain and ectodomain flanking region". J. Biol. Chem. 270 (44): 26404–10. doi:10.1074/jbc.270.44.26404. PMID 7592855.
• Raulo E, Chernousov MA, Carey DJ, et al. (1994). "Isolation of a neuronal cell surface receptor of heparin binding growth-associated molecule (HB-GAM). Identification as N-syndecan (syndecan-3)". J. Biol. Chem. 269 (17): 12999–3004. doi:10.1016/S0021-9258(18)99975-8. PMID 8175719.
• Fabri L, Maruta H, Muramatsu H, et al. (1993). "Structural characterisation of native and recombinant forms of the neurotrophic cytokine MK". J. Chromatogr. 646 (1): 213–25. doi:10.1016/S0021-9673(99)87023-X. PMID 8408430.
• Kretschmer PJ, Fairhurst JL, Hulmes JD, et al. (1993). "Genomic organization of the human HBNF gene and characterization of an HBNF variant protein as a splice mutant". Biochem. Biophys. Res. Commun. 192 (2): 420–9. doi:10.1006/bbrc.1993.1432. PMID 8484754.
• Hulmes JD, Seddon AP, Decker MM, Böhlen P (1993). "Comparison of the disulfide bond arrangements of human recombinant and bovine brain heparin binding neurite-promoting factors". Biochem. Biophys. Res. Commun. 192 (2): 738–46. doi:10.1006/bbrc.1993.1476. PMID 8484780.
• Kinnunen T, Raulo E, Nolo R, et al. (1996). "Neurite outgrowth in brain neurons induced by heparin-binding growth-associated molecule (HB-GAM) depends on the specific interaction of HB-GAM with heparan sulfate at the cell surface". J. Biol. Chem. 271 (4): 2243–8. doi:10.1074/jbc.271.4.2243. PMID 8567685.
• Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Res. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
• Masuda H, Tsujimura A, Yoshioka M, et al. (1997). "Bone mass loss due to estrogen deficiency is compensated in transgenic mice overexpressing human osteoblast stimulating factor-1". Biochem. Biophys. Res. Commun. 238 (2): 528–33. doi:10.1006/bbrc.1997.7188. PMID 9299545.
• Milev P, Chiba A, Häring M, et al. (1998). "High affinity binding and overlapping localization of neurocan and phosphacan/protein-tyrosine phosphatase-zeta/beta with tenascin-R, amphoterin, and the heparin-binding growth-associated molecule". J. Biol. Chem. 273 (12): 6998–7005. doi:10.1074/jbc.273.12.6998. PMID 9507007.
• Fages C, Kaksonen M, Kinnunen T, et al. (1998). "Regulation of mRNA localization by transmembrane signalling: local interaction of HB-GAM (heparin-binding growth-associated molecule) with the cell surface localizes beta-actin mRNA". J. Cell Sci. 111 (20): 3073–80. doi:10.1242/jcs.111.20.3073. PMID 9739080.
• Zhang N, Zhong R, Deuel TF (1999). "Domain structure of pleiotrophin required for transformation". J. Biol. Chem. 274 (19): 12959–62. doi:10.1074/jbc.274.19.12959. PMID 10224041.
• Bernard-Pierrot I, Héroult M, Lemaître G, et al. (2000). "Glycosaminoglycans promote HARP/PTN dimerization". Biochem. Biophys. Res. Commun. 266 (2): 437–42. doi:10.1006/bbrc.1999.1835. PMID 10600521.
• Meng K, Rodriguez-Peña A, Dimitrov T, et al. (2000). "Pleiotrophin signals increased tyrosine phosphorylation of beta beta-catenin through inactivation of the intrinsic catalytic activity of the receptor-type protein tyrosine phosphatase beta/zeta". Proc. Natl. Acad. Sci. U.S.A. 97 (6): 2603–8. doi:10.1073/pnas.020487997. PMC 15975. PMID 10706604.
• Murasugi A, Kido I, Kumai H, Asami Y (2003). "Efficient production of recombinant human pleio-trophin in yeast, Pichia pastoris". Biosci. Biotechnol. Biochem. 67 (10): 2288–90. doi:10.1271/bbb.67.2288. PMID 14586125.