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)
End	137,343,774 bp
Gene location (Mouse)
Chr.	Chromosome 6 (mouse)
End	36,787,155 bp
RNA expression pattern
	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
	; ; ; ;
	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
	5764
	19242
	ENSG00000105894
	ENSMUSG00000029838
	P21246
	P63089
	NM_002825; NM_001321386; NM_001321387
	NM_008973
	NP_001308315; NP_001308316; NP_002816
	NP_032999
	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.^[5] 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^[6] and as a mitogen toward fibroblasts isolated from bovine uterus tissue.^[7] Together with midkine these growth-factors constitute a family of (developmentally regulated) secreted heparin-binding proteins^[8] 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.^[9] Pleiotrophin is also expressed by several tumor cells and is thought to be involved in tumor angiogenesis.^[10] In the adult central nervous system, pleiotrophin is expressed in an activity-dependent manner in the hippocampus^[11]^[12] where it can suppress long term potentiation induction.^[13] Pleiotrophin expression is low in other areas of the adult brain, but it can be induced by ischemic insults.^[14]^[15] 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.^[16]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000105894 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000029838 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Entrez Gene: PTN pleiotrophin (heparin binding growth factor 8, neurite growth-promoting factor 1)".
^ Rauvala H, Pihlaskari R (1987). "Isolation and some characteristics of an adhesive factor of brain that enhances neurite outgrowth in central neurons". J. Biol. Chem. 262 (34): 16625–35. doi:10.1016/S0021-9258(18)49302-7. PMID 3680268.
^ Li YS, Milner PG, Chauhan AK, Watson MA, Hoffman RM, Kodner CM, Milbrandt J, Deuel TF (1990). "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.
^ Laaroubi K, Vacherot F, Delbé J, Caruelle D, Barritault D, Courty J (1995). "Biochemical and mitogenic properties of the heparin-binding growth factor HARP". Prog. Growth Factor Res. 6 (1): 25–34. doi:10.1016/0955-2235(95)00002-X. PMID 8714367.
^ Vanderwinden JM, Mailleux P, Schiffmann SN, Vanderhaeghen JJ (1992). "Cellular distribution of the new growth factor pleiotrophin (HB-GAM) mRNA in developing and adult rat tissues". Anat. Embryol. 186 (4): 387–406. doi:10.1007/BF00185989. PMID 1416088. S2CID 23579980.
^ Kadomatsu K, Muramatsu T (2004). "Midkine and pleiotrophin in neural development and cancer". Cancer Lett. 204 (2): 127–43. doi:10.1016/S0304-3835(03)00450-6. PMID 15013213.
^ Wanaka A, Carroll SL, Milbrandt J (1993). "Developmentally regulated expression of pleiotrophin, a novel heparin binding growth factor, in the nervous system of the rat". Brain Res. Dev. Brain Res. 72 (1): 133–44. doi:10.1016/0165-3806(93)90166-8. PMID 8453763.
^ Lauri SE, Taira T, Kaila K, Rauvala H (1996). "Activity-induced enhancement of HB-GAM expression in rat hippocampal slices". NeuroReport. 7 (10): 1670–4. doi:10.1097/00001756-199607080-00029. PMID 8904779.
^ Pavlov I, Võikar V, Kaksonen M, Lauri SE, Hienola A, Taira T, Rauvala H (2002). "Role of heparin-binding growth-associated molecule (HB-GAM) in hippocampal LTP and spatial learning revealed by studies on overexpressing and knockout mice". Mol. Cell. Neurosci. 20 (2): 330–42. doi:10.1006/mcne.2002.1104. PMID 12093164. S2CID 24655036.
^ Takeda A, Onodera H, Sugimoto A, Itoyama Y, Kogure K, Rauvala H, Shibahara S (1995). "Induction of heparin-binding growth-associated molecule expression in reactive astrocytes following hippocampal neuronal injury". Neuroscience. 68 (1): 57–64. doi:10.1016/0306-4522(95)00110-5. PMID 7477935. S2CID 32945854.
^ Yeh HJ, He YY, Xu J, Hsu CY, Deuel TF (1998). "Upregulation of pleiotrophin gene expression in developing microvasculature, macrophages, and astrocytes after acute ischemic brain injury". J. Neurosci. 18 (10): 3699–707. doi:10.1523/JNEUROSCI.18-10-03699.1998. PMC 6793139. PMID 9570800.
^ Said EA, Courty J, Svab J, Delbé J, Krust B, Hovanessian AG (September 2005). "Pleiotrophin inhibits HIV infection by binding the cell surface-expressed nucleolin". FEBS J. 272 (18): 4646–59. doi:10.1111/j.1742-4658.2005.04870.x. PMID 16156786. S2CID 21153881.

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. S2CID 23168994.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000105894 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000029838 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[entrez-5] "Entrez Gene: PTN pleiotrophin (heparin binding growth factor 8, neurite growth-promoting factor 1)".

[pmid3680268-6] Rauvala H, Pihlaskari R (1987). "Isolation and some characteristics of an adhesive factor of brain that enhances neurite outgrowth in central neurons". J. Biol. Chem. 262 (34): 16625–35. doi:10.1016/S0021-9258(18)49302-7. PMID 3680268.

[pmid2270483-7] Li YS, Milner PG, Chauhan AK, Watson MA, Hoffman RM, Kodner CM, Milbrandt J, Deuel TF (1990). "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.

[pmid8714367-8] Laaroubi K, Vacherot F, Delbé J, Caruelle D, Barritault D, Courty J (1995). "Biochemical and mitogenic properties of the heparin-binding growth factor HARP". Prog. Growth Factor Res. 6 (1): 25–34. doi:10.1016/0955-2235(95)00002-X. PMID 8714367.

[pmid1416088-9] Vanderwinden JM, Mailleux P, Schiffmann SN, Vanderhaeghen JJ (1992). "Cellular distribution of the new growth factor pleiotrophin (HB-GAM) mRNA in developing and adult rat tissues". Anat. Embryol. 186 (4): 387–406. doi:10.1007/BF00185989. PMID 1416088. S2CID 23579980.

[pmid15013213-10] Kadomatsu K, Muramatsu T (2004). "Midkine and pleiotrophin in neural development and cancer". Cancer Lett. 204 (2): 127–43. doi:10.1016/S0304-3835(03)00450-6. PMID 15013213.

[pmid8453763-11] Wanaka A, Carroll SL, Milbrandt J (1993). "Developmentally regulated expression of pleiotrophin, a novel heparin binding growth factor, in the nervous system of the rat". Brain Res. Dev. Brain Res. 72 (1): 133–44. doi:10.1016/0165-3806(93)90166-8. PMID 8453763.

[pmid8904779-12] Lauri SE, Taira T, Kaila K, Rauvala H (1996). "Activity-induced enhancement of HB-GAM expression in rat hippocampal slices". NeuroReport. 7 (10): 1670–4. doi:10.1097/00001756-199607080-00029. PMID 8904779.

[pmid12093164-13] Pavlov I, Võikar V, Kaksonen M, Lauri SE, Hienola A, Taira T, Rauvala H (2002). "Role of heparin-binding growth-associated molecule (HB-GAM) in hippocampal LTP and spatial learning revealed by studies on overexpressing and knockout mice". Mol. Cell. Neurosci. 20 (2): 330–42. doi:10.1006/mcne.2002.1104. PMID 12093164. S2CID 24655036.

[pmid7477935-14] Takeda A, Onodera H, Sugimoto A, Itoyama Y, Kogure K, Rauvala H, Shibahara S (1995). "Induction of heparin-binding growth-associated molecule expression in reactive astrocytes following hippocampal neuronal injury". Neuroscience. 68 (1): 57–64. doi:10.1016/0306-4522(95)00110-5. PMID 7477935. S2CID 32945854.

[pmid9570800-15] Yeh HJ, He YY, Xu J, Hsu CY, Deuel TF (1998). "Upregulation of pleiotrophin gene expression in developing microvasculature, macrophages, and astrocytes after acute ischemic brain injury". J. Neurosci. 18 (10): 3699–707. doi:10.1523/JNEUROSCI.18-10-03699.1998. PMC 6793139. PMID 9570800.

[pmid16156786-16] Said EA, Courty J, Svab J, Delbé J, Krust B, Hovanessian AG (September 2005). "Pleiotrophin inhibits HIV infection by binding the cell surface-expressed nucleolin". FEBS J. 272 (18): 4646–59. doi:10.1111/j.1742-4658.2005.04870.x. PMID 16156786. S2CID 21153881.

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Pleiotrophin

Function

Clinical significance

References

Further reading