PTN_HUMAN
ID PTN_HUMAN Reviewed; 168 AA.
AC P21246; Q5U0B0; Q6ICQ5; Q9UCC6;
DT 01-MAY-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1991, sequence version 1.
DT 03-AUG-2022, entry version 197.
DE RecName: Full=Pleiotrophin {ECO:0000303|PubMed:1457401, ECO:0000303|PubMed:2270483};
DE Short=PTN {ECO:0000303|PubMed:1457401, ECO:0000303|PubMed:2270483};
DE AltName: Full=Heparin-binding brain mitogen {ECO:0000303|PubMed:2388713};
DE Short=HBBM {ECO:0000303|PubMed:2388713};
DE AltName: Full=Heparin-binding growth factor 8 {ECO:0000250|UniProtKB:P21782};
DE Short=HBGF-8 {ECO:0000250|UniProtKB:P21782};
DE AltName: Full=Heparin-binding growth-associated molecule {ECO:0000250|UniProtKB:P63090};
DE Short=HB-GAM {ECO:0000250|UniProtKB:P63090};
DE AltName: Full=Heparin-binding neurite outgrowth-promoting factor {ECO:0000303|PubMed:8484754};
DE Short=HBNF {ECO:0000303|PubMed:8484754};
DE AltName: Full=Heparin-binding neurite outgrowth-promoting factor 1 {ECO:0000303|PubMed:1768439};
DE Short=HBNF-1 {ECO:0000303|PubMed:1768439};
DE AltName: Full=Osteoblast-specific factor 1 {ECO:0000303|PubMed:1701634};
DE Short=OSF-1 {ECO:0000303|PubMed:1701634};
DE Flags: Precursor;
GN Name=PTN {ECO:0000312|HGNC:HGNC:9630}; Synonyms=HBNF1, NEGF1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=1701634; DOI=10.1016/s0006-291x(05)81048-4;
RA Tezuka K.I., Takeshita S., Hakeda Y., Kumegawa M., Kikuno R.,
RA Hashimoto-Gotoh T.;
RT "Isolation of mouse and human cDNA clones encoding a protein expressed
RT specifically in osteoblasts and brain tissues.";
RL Biochem. Biophys. Res. Commun. 173:246-251(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Placenta;
RX PubMed=2270483; DOI=10.1126/science.2270483;
RA Li Y.-S., Milner P.G., Chauhan A.K., Watson M.A., Hoffman R.M.,
RA Kodner C.M., Milbrandt J., Deuel T.F.;
RT "Cloning and expression of a developmentally regulated protein that induces
RT mitogenic and neurite outgrowth activity.";
RL Science 250:1690-1694(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND INDUCTION.
RX PubMed=1768439; DOI=10.3109/08977199109000275;
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 of a
RT novel human gene family of neurite outgrowth-promoting proteins.";
RL Growth Factors 5:99-114(1991).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1457401; DOI=10.1021/bi00163a009;
RA Milner P.G., Shah D., Veile R., Donis-Keller H., Kumar B.V.;
RT "Cloning, nucleotide sequence, and chromosome localization of the human
RT pleiotrophin gene.";
RL Biochemistry 31:12023-12028(1992).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8484754; DOI=10.1006/bbrc.1993.1432;
RA Kretschmer P.J., Fairhurst J.L., Hulmes J.D., Popjes M.L., Boehlen P.,
RA Kovesdi I.;
RT "Genomic organization of the human HBNF gene and characterization of an
RT HBNF variant protein as a splice mutant.";
RL Biochem. Biophys. Res. Commun. 192:420-429(1993).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9299545; DOI=10.1006/bbrc.1997.7188;
RA Masuda H., Tsujimura A., Yoshioka M., Arai Y., Kuboki Y., Mukai T.,
RA Nakamura T., Tsuji H., Nakagawa M., Hashimoto-Gotoh T.;
RT "Bone mass loss due to estrogen deficiency is compensated in transgenic
RT mice overexpressing human osteoblast stimulating factor-1.";
RL Biochem. Biophys. Res. Commun. 238:528-533(1997).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, and Cerebellum;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12690205; DOI=10.1126/science.1083423;
RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D.,
RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S.,
RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R.,
RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N.,
RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E.,
RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R.,
RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T.,
RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W.,
RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A.,
RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X.,
RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E.,
RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J.,
RA Adams M.D., Tsui L.-C.;
RT "Human chromosome 7: DNA sequence and biology.";
RL Science 300:767-772(2003).
RN [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [12]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Prostate;
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 [13]
RP PROTEIN SEQUENCE OF 33-58.
RC TISSUE=Brain;
RX PubMed=2388713; DOI=10.1007/bf00969930;
RA Huber D., Gautschi-Sova P., Bohlen P.;
RT "Amino-terminal sequences of a novel heparin-binding protein from human,
RT bovine, rat, and chick brain: high interspecies homology.";
RL Neurochem. Res. 15:435-439(1990).
RN [14]
RP PROTEIN SEQUENCE OF 33-52, SUBCELLULAR LOCATION, HEPARIN-BINDING, AND
RP FUNCTION.
RX PubMed=1733956; DOI=10.1016/s0021-9258(18)45920-0;
RA Wellsein A., Fang W., Khatri A., Lu Y., Swain S.S., Dickson R.B., Sasse J.,
RA Riegel A.T., Lippman M.E.;
RT "A heparin-binding growth factor secreted from breast cancer cells
RT homologous to a developmentally regulated cytokine.";
RL J. Biol. Chem. 267:2582-2587(1992).
RN [15]
RP PROTEIN SEQUENCE OF 33-49, INDUCTION, AND SUBCELLULAR LOCATION.
RC TISSUE=Plasma;
RX PubMed=8241100; DOI=10.1161/01.atv.13.12.1798;
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 [16]
RP DISULFIDE BONDS.
RX PubMed=8484780; DOI=10.1006/bbrc.1993.1476;
RA Hulmes J.D., Seddon A.P., Decker M.M., Bohlen P.;
RT "Comparison of the disulfide bond arrangements of human recombinant and
RT bovine brain heparin binding neurite-promoting factors.";
RL Biochem. Biophys. Res. Commun. 192:738-746(1993).
RN [17]
RP INTERACTION WITH PTPRZ1, AND FUNCTION.
RX PubMed=10706604; DOI=10.1073/pnas.020487997;
RA Meng K., Rodriguez-Pena A., Dimitrov T., Chen W., Yamin M., Noda M.,
RA Deuel T.F.;
RT "Pleiotrophin signals increased tyrosine phosphorylation of beta beta-
RT catenin through inactivation of the intrinsic catalytic activity of the
RT receptor-type protein tyrosine phosphatase beta/zeta.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:2603-2608(2000).
RN [18]
RP INTERACTION WITH ALK, AND FUNCTION.
RX PubMed=11278720; DOI=10.1074/jbc.m010660200;
RA Stoica G.E., Kuo A., Aigner A., Sunitha I., Souttou B., Malerczyk C.,
RA Caughey D.J., Wen D., Karavanov A., Riegel A.T., Wellstein A.;
RT "Identification of anaplastic lymphoma kinase as a receptor for the growth
RT factor pleiotrophin.";
RL J. Biol. Chem. 276:16772-16779(2001).
RN [19]
RP FUNCTION, AND INTERACTION WITH PTPRZ1.
RX PubMed=16814777; DOI=10.1016/j.febslet.2006.06.041;
RA Fukada M., Fujikawa A., Chow J.P., Ikematsu S., Sakuma S., Noda M.;
RT "Protein tyrosine phosphatase receptor type Z is inactivated by ligand-
RT induced oligomerization.";
RL FEBS Lett. 580:4051-4056(2006).
RN [20]
RP FUNCTION.
RX PubMed=17681947; DOI=10.1074/jbc.m704505200;
RA Perez-Pinera P., Zhang W., Chang Y., Vega J.A., Deuel T.F.;
RT "Anaplastic lymphoma kinase is activated through the pleiotrophin/receptor
RT protein-tyrosine phosphatase beta/zeta signaling pathway: an alternative
RT mechanism of receptor tyrosine kinase activation.";
RL J. Biol. Chem. 282:28683-28690(2007).
RN [21]
RP FUNCTION.
RX PubMed=19442624; DOI=10.1016/j.bone.2009.01.004;
RA Imai S., Heino T.J., Hienola A., Kurata K., Bueki K., Matsusue Y.,
RA Vaeaenaenen H.K., Rauvala H.;
RT "Osteocyte-derived HB-GAM (pleiotrophin) is associated with bone formation
RT and mechanical loading.";
RL Bone 44:785-794(2009).
RN [22]
RP INTERACTION WITH PTPRZ1; ITGB3 AND ITGA5, AND FUNCTION.
RX PubMed=19141530; DOI=10.1096/fj.08-117564;
RA Mikelis C., Sfaelou E., Koutsioumpa M., Kieffer N., Papadimitriou E.;
RT "Integrin alpha(v)beta(3) is a pleiotrophin receptor required for
RT pleiotrophin-induced endothelial cell migration through receptor protein
RT tyrosine phosphatase beta/zeta.";
RL FASEB J. 23:1459-1469(2009).
RN [23]
RP INTERACTION WITH NEK6, AND PHOSPHORYLATION BY NEK6.
RX PubMed=20873783; DOI=10.1021/pr100562w;
RA Vaz Meirelles G., Ferreira Lanza D.C., da Silva J.C., Santana Bernachi J.,
RA Paes Leme A.F., Kobarg J.;
RT "Characterization of hNek6 interactome reveals an important role for its
RT short N-terminal domain and colocalization with proteins at the
RT centrosome.";
RL J. Proteome Res. 9:6298-6316(2010).
RN [24]
RP FUNCTION.
RX PubMed=27445335; DOI=10.1074/jbc.m116.742536;
RA Kuboyama K., Fujikawa A., Suzuki R., Tanga N., Noda M.;
RT "Role of Chondroitin Sulfate (CS) Modification in the Regulation of
RT Protein-tyrosine Phosphatase Receptor Type Z (PTPRZ) Activity:
RT PLEIOTROPHIN-PTPRZ-A SIGNALING IS INVOLVED IN OLIGODENDROCYTE
RT DIFFERENTIATION.";
RL J. Biol. Chem. 291:18117-18128(2016).
RN [25]
RP FUNCTION.
RX PubMed=30667096; DOI=10.1002/glia.23583;
RA Tanga N., Kuboyama K., Kishimoto A., Kiyonari H., Shiraishi A., Suzuki R.,
RA Watanabe T., Fujikawa A., Noda M.;
RT "The PTN-PTPRZ signal activates the AFAP1L2-dependent PI3K-AKT pathway for
RT oligodendrocyte differentiation: Targeted inactivation of PTPRZ activity in
RT mice.";
RL Glia 67:967-984(2019).
RN [26] {ECO:0007744|PDB:2N6F}
RP STRUCTURE BY NMR OF 33-168, FUNCTION, SUBUNIT, AND DISULFIDE BONDS.
RX PubMed=26896299; DOI=10.1111/febs.13686;
RA Ryan E., Shen D., Wang X.;
RT "Structural studies reveal an important role for the pleiotrophin C-
RT terminus in mediating interactions with chondroitin sulfate.";
RL FEBS J. 283:1488-1503(2016).
CC -!- FUNCTION: Secreted growth factor that mediates its signal through cell-
CC surface proteoglycan and non-proteoglycan receptors (PubMed:16814777,
CC PubMed:11278720, PubMed:19141530). Binds cell-surface proteoglycan
CC receptor via their chondroitin sulfate (CS) groups (PubMed:26896299,
CC PubMed:27445335). Thereby regulates many processes like cell
CC proliferation, cell survival, cell growth, cell differentiation and
CC cell migration in several tissues namely neuron and bone
CC (PubMed:1733956, PubMed:1768439, PubMed:11278720, PubMed:19141530,
CC PubMed:27445335, PubMed:30667096, PubMed:19442624). Also plays a role
CC in synaptic plasticity and learning-related behavior by inhibiting
CC long-term synaptic potentiation (By similarity). Binds PTPRZ1, leading
CC to neutralization of the negative charges of the CS chains of PTPRZ1,
CC inducing PTPRZ1 clustering, thereby causing the dimerization and
CC inactivation of its phosphatase activity leading to increased tyrosine
CC phosphorylation of each of the PTPRZ1 substrates like ALK, CTNNB1 or
CC AFAP1L2 in order to activate the PI3K-AKT pathway (PubMed:17681947,
CC PubMed:27445335, PubMed:30667096, PubMed:16814777, PubMed:10706604).
CC Through PTPRZ1 binding controls oligodendrocyte precursor cell
CC differentiation by enhancing the phosphorylation of AFAP1L2 in order to
CC activate the PI3K-AKT pathway (PubMed:27445335, PubMed:30667096). Forms
CC a complex with PTPRZ1 and integrin alpha-V/beta-3 (ITGAV:ITGB3) that
CC stimulates endothelial cell migration through SRC dephosphorylation and
CC activation that consequently leads to ITGB3 'Tyr-773' phosphorylation
CC (PubMed:19141530). In adult hippocampus promotes dendritic
CC arborization, spine development, and functional integration and
CC connectivity of newborn granule neurons through ALK by activating AKT
CC signaling pathway (By similarity). Binds GPC2 and chondroitin sulfate
CC proteoglycans (CSPGs) at the neuron surface, leading to abrogation of
CC binding between PTPRS and CSPGs and neurite outgrowth promotion (By
CC similarity). Binds SDC3 and mediates bone formation by recruiting and
CC attaching osteoblasts/osteoblast precursors to the sites for new bone
CC deposition (By similarity). Binds ALK and promotes cell survival and
CC cell proliferation through MAPK pathway activation (PubMed:11278720).
CC Inhibits proliferation and enhances differentiation of neural stem
CC cells by inhibiting FGF2-induced fibroblast growth factor receptor
CC signaling pathway (By similarity). Mediates regulatory mechanisms in
CC normal hemostasis and in hematopoietic regeneration and in maintaining
CC the balance of myeloid and lymphoid regeneration (By similarity). In
CC addition may play a role in the female reproductive system, auditory
CC response and the progesterone-induced decidualization pathway (By
CC similarity). {ECO:0000250|UniProtKB:P63089,
CC ECO:0000250|UniProtKB:P63090, ECO:0000269|PubMed:10706604,
CC ECO:0000269|PubMed:11278720, ECO:0000269|PubMed:16814777,
CC ECO:0000269|PubMed:1733956, ECO:0000269|PubMed:17681947,
CC ECO:0000269|PubMed:1768439, ECO:0000269|PubMed:19141530,
CC ECO:0000269|PubMed:19442624, ECO:0000269|PubMed:26896299,
CC ECO:0000269|PubMed:27445335, ECO:0000269|PubMed:30667096}.
CC -!- SUBUNIT: Interacts with ALK and NEK6 (PubMed:11278720,
CC PubMed:20873783). Interacts with PTPRZ1 (via chondroitin sulfate
CC groups); promotes formation of homooligomers; oligomerization impairs
CC tyrosine phosphatase activity (PubMed:16814777) (Probable). Forms a
CC complex with PTPRZ1 and CTNNB1; this complex inactivates PTPRZ1 protein
CC tyrosine phosphatase activity through PTN interaction and stimulates
CC tyrosine phosphorylation of CTNNB1 (PubMed:10706604). Interacts with
CC ITGB3 AND ITGA5 (PubMed:19141530). Forms a complex with PTPRZ1 and
CC integrin alpha-V/beta-3 (ITGAV:ITGB3) that stimulates endothelial cell
CC migration through ITGB3 'Tyr-773' phosphorylation (PubMed:19141530).
CC Interacts with SDC3 (via heparan sulfate chains); this interaction
CC mediates the neurite outgrowth-promoting signal from PTN to the
CC cytoskeleton of growing neurites; this interaction mediates osteoblast
CC recruitment. Interacts with GPC2 (via heparan sulfate); this
CC interaction promotes neurite outgrowth through binding of PTN with
CC chondroitin sulfate of proteoglycans, thereby releasing PTPRS of
CC chondroitin sulfate proteoglycans (CSPGs) and leading to binding with
CC heparan sulfate of GPC2 (By similarity). {ECO:0000250|UniProtKB:P63090,
CC ECO:0000269|PubMed:10706604, ECO:0000269|PubMed:11278720,
CC ECO:0000269|PubMed:16814777, ECO:0000269|PubMed:19141530,
CC ECO:0000269|PubMed:20873783, ECO:0000305|PubMed:26896299}.
CC -!- INTERACTION:
CC P21246; Q12797-6: ASPH; NbExp=3; IntAct=EBI-473725, EBI-12092171;
CC P21246; P11215: ITGAM; NbExp=3; IntAct=EBI-473725, EBI-2568251;
CC P21246; Q92876: KLK6; NbExp=3; IntAct=EBI-473725, EBI-2432309;
CC P21246; P17612: PRKACA; NbExp=3; IntAct=EBI-473725, EBI-476586;
CC P21246; P50454: SERPINH1; NbExp=3; IntAct=EBI-473725, EBI-350723;
CC P21246; P37173: TGFBR2; NbExp=3; IntAct=EBI-473725, EBI-296151;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:1733956,
CC ECO:0000269|PubMed:8241100}.
CC -!- TISSUE SPECIFICITY: Osteoblast and brain. {ECO:0000269|PubMed:1701634}.
CC -!- INDUCTION: By heparin and retinoic acid. {ECO:0000269|PubMed:1768439,
CC ECO:0000269|PubMed:8241100}.
CC -!- PTM: Phosphorylated by NEK6. {ECO:0000269|PubMed:20873783}.
CC -!- SIMILARITY: Belongs to the pleiotrophin family. {ECO:0000305}.
CC -!- CAUTION: According to a first report, interacts with ALK leading to
CC stimulation of ALK tyrosine phosphorylation (PubMed:11278720).
CC According to a second report, ALK is phosphorylated independently of a
CC direct interaction with PTN but through PTPRZ1 which is inactivated in
CC PTN-stimulated cells; the sites that are autophosphorylated in ALK no
CC longer can be dephosphorylated by PTPRZ1; thus, autoactivation and
CC tyrosine phosphorylation of ALK rapidly increase (PubMed:17681947).
CC {ECO:0000269|PubMed:11278720, ECO:0000269|PubMed:17681947}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Pleiotrophin entry;
CC URL="https://en.wikipedia.org/wiki/Pleiotrophin";
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/PTNID41904ch7q33.html";
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DR EMBL; D90226; BAA14261.1; -; mRNA.
DR EMBL; X52946; CAA37121.1; -; mRNA.
DR EMBL; M57399; AAA35961.1; -; mRNA.
DR EMBL; S50409; AAB24425.1; -; Genomic_DNA.
DR EMBL; S50405; AAB24425.1; JOINED; Genomic_DNA.
DR EMBL; S50408; AAB24425.1; JOINED; Genomic_DNA.
DR EMBL; S50394; AAB24425.1; JOINED; Genomic_DNA.
DR EMBL; S60110; AAB26456.1; -; Genomic_DNA.
DR EMBL; S59641; AAB26456.1; JOINED; Genomic_DNA.
DR EMBL; S60111; AAB26456.1; JOINED; Genomic_DNA.
DR EMBL; S60736; AAB26456.1; JOINED; Genomic_DNA.
DR EMBL; AB004306; BAA22944.1; -; Genomic_DNA.
DR EMBL; AK290488; BAF83177.1; -; mRNA.
DR EMBL; AK313424; BAG36216.1; -; mRNA.
DR EMBL; CR450338; CAG29334.1; -; mRNA.
DR EMBL; BT019692; AAV38498.1; -; mRNA.
DR EMBL; CH236950; EAL24052.1; -; Genomic_DNA.
DR EMBL; CH471070; EAW83869.1; -; Genomic_DNA.
DR EMBL; BC005916; AAH05916.1; -; mRNA.
DR CCDS; CCDS5844.1; -.
DR PIR; JN0474; C37780.
DR RefSeq; NP_001308315.1; NM_001321386.2.
DR RefSeq; NP_001308316.1; NM_001321387.2.
DR RefSeq; NP_002816.1; NM_002825.6.
DR PDB; 2N6F; NMR; -; A=33-168.
DR PDBsum; 2N6F; -.
DR AlphaFoldDB; P21246; -.
DR SMR; P21246; -.
DR BioGRID; 111731; 98.
DR DIP; DIP-5953N; -.
DR IntAct; P21246; 98.
DR MINT; P21246; -.
DR STRING; 9606.ENSP00000341170; -.
DR BindingDB; P21246; -.
DR ChEMBL; CHEMBL4523199; -.
DR iPTMnet; P21246; -.
DR PhosphoSitePlus; P21246; -.
DR BioMuta; PTN; -.
DR DMDM; 131553; -.
DR EPD; P21246; -.
DR jPOST; P21246; -.
DR MassIVE; P21246; -.
DR PaxDb; P21246; -.
DR PeptideAtlas; P21246; -.
DR PRIDE; P21246; -.
DR ProteomicsDB; 53854; -.
DR Antibodypedia; 4323; 542 antibodies from 40 providers.
DR DNASU; 5764; -.
DR Ensembl; ENST00000348225.7; ENSP00000341170.2; ENSG00000105894.12.
DR GeneID; 5764; -.
DR KEGG; hsa:5764; -.
DR MANE-Select; ENST00000348225.7; ENSP00000341170.2; NM_002825.7; NP_002816.1.
DR UCSC; uc003vtq.4; human.
DR CTD; 5764; -.
DR DisGeNET; 5764; -.
DR GeneCards; PTN; -.
DR HGNC; HGNC:9630; PTN.
DR HPA; ENSG00000105894; Tissue enhanced (brain, parathyroid gland).
DR MIM; 162095; gene.
DR neXtProt; NX_P21246; -.
DR OpenTargets; ENSG00000105894; -.
DR PharmGKB; PA33974; -.
DR VEuPathDB; HostDB:ENSG00000105894; -.
DR eggNOG; ENOG502RXV7; Eukaryota.
DR GeneTree; ENSGT00390000007640; -.
DR HOGENOM; CLU_136864_1_0_1; -.
DR InParanoid; P21246; -.
DR OMA; PKWRERR; -.
DR OrthoDB; 1489280at2759; -.
DR PhylomeDB; P21246; -.
DR TreeFam; TF332376; -.
DR PathwayCommons; P21246; -.
DR Reactome; R-HSA-201556; Signaling by ALK.
DR SignaLink; P21246; -.
DR SIGNOR; P21246; -.
DR BioGRID-ORCS; 5764; 5 hits in 1070 CRISPR screens.
DR ChiTaRS; PTN; human.
DR GeneWiki; Pleiotrophin; -.
DR GenomeRNAi; 5764; -.
DR Pharos; P21246; Tchem.
DR PRO; PR:P21246; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; P21246; protein.
DR Bgee; ENSG00000105894; Expressed in ventricular zone and 200 other tissues.
DR ExpressionAtlas; P21246; baseline and differential.
DR Genevisible; P21246; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:LIFEdb.
DR GO; GO:0005576; C:extracellular region; IBA:GO_Central.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IEA:GOC.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0035374; F:chondroitin sulfate binding; IDA:UniProtKB.
DR GO; GO:0008083; F:growth factor activity; IDA:UniProtKB.
DR GO; GO:0008201; F:heparin binding; IDA:UniProtKB.
DR GO; GO:0005178; F:integrin binding; IPI:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR GO; GO:0004864; F:protein phosphatase inhibitor activity; IDA:UniProtKB.
DR GO; GO:0030282; P:bone mineralization; IEA:Ensembl.
DR GO; GO:0046697; P:decidualization; ISS:UniProtKB.
DR GO; GO:0140059; P:dendrite arborization; ISS:UniProtKB.
DR GO; GO:0031104; P:dendrite regeneration; ISS:UniProtKB.
DR GO; GO:0044849; P:estrous cycle; ISS:UniProtKB.
DR GO; GO:0007229; P:integrin-mediated signaling pathway; IDA:UniProtKB.
DR GO; GO:0007612; P:learning; ISS:UniProtKB.
DR GO; GO:0002232; P:leukocyte chemotaxis involved in inflammatory response; ISS:UniProtKB.
DR GO; GO:0007613; P:memory; ISS:UniProtKB.
DR GO; GO:1900272; P:negative regulation of long-term synaptic potentiation; ISS:UniProtKB.
DR GO; GO:0007406; P:negative regulation of neuroblast proliferation; ISS:UniProtKB.
DR GO; GO:0007399; P:nervous system development; TAS:ProtInc.
DR GO; GO:0048477; P:oogenesis; ISS:UniProtKB.
DR GO; GO:0043932; P:ossification involved in bone remodeling; IDA:UniProtKB.
DR GO; GO:0048680; P:positive regulation of axon regeneration; ISS:UniProtKB.
DR GO; GO:0030501; P:positive regulation of bone mineralization; ISS:UniProtKB.
DR GO; GO:0051781; P:positive regulation of cell division; IEA:UniProtKB-KW.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:UniProtKB.
DR GO; GO:1900006; P:positive regulation of dendrite development; ISS:UniProtKB.
DR GO; GO:2000347; P:positive regulation of hepatocyte proliferation; ISS:UniProtKB.
DR GO; GO:0002690; P:positive regulation of leukocyte chemotaxis; ISS:UniProtKB.
DR GO; GO:0010976; P:positive regulation of neuron projection development; ISS:UniProtKB.
DR GO; GO:0048714; P:positive regulation of oligodendrocyte differentiation; IDA:UniProtKB.
DR GO; GO:0045778; P:positive regulation of ossification; ISS:UniProtKB.
DR GO; GO:2000738; P:positive regulation of stem cell differentiation; ISS:UniProtKB.
DR GO; GO:0043113; P:receptor clustering; IDA:UniProtKB.
DR GO; GO:0010594; P:regulation of endothelial cell migration; ISS:UniProtKB.
DR GO; GO:1903706; P:regulation of hemopoiesis; ISS:UniProtKB.
DR GO; GO:0031641; P:regulation of myelination; ISS:UniProtKB.
DR GO; GO:2000036; P:regulation of stem cell population maintenance; ISS:UniProtKB.
DR GO; GO:0048167; P:regulation of synaptic plasticity; ISS:UniProtKB.
DR GO; GO:0010996; P:response to auditory stimulus; ISS:UniProtKB.
DR GO; GO:0042246; P:tissue regeneration; ISS:UniProtKB.
DR GO; GO:0007185; P:transmembrane receptor protein tyrosine phosphatase signaling pathway; TAS:ProtInc.
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 3D-structure; Direct protein sequencing; Disulfide bond; Growth factor;
KW Heparin-binding; Mitogen; Reference proteome; Secreted; Signal.
FT SIGNAL 1..32
FT /evidence="ECO:0000269|PubMed:1733956,
FT ECO:0000269|PubMed:2388713, ECO:0000269|PubMed:8241100"
FT CHAIN 33..168
FT /note="Pleiotrophin"
FT /id="PRO_0000024659"
FT REGION 92..99
FT /note="Chondroitin sulfate binding"
FT /evidence="ECO:0000269|PubMed:26896299"
FT REGION 123..131
FT /note="Chondroitin sulfate binding"
FT /evidence="ECO:0000269|PubMed:26896299"
FT REGION 139..168
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 147..168
FT /note="Chondroitin sulfate A binding"
FT /evidence="ECO:0000269|PubMed:26896299"
FT COMPBIAS 148..168
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT DISULFID 47..76
FT /evidence="ECO:0000269|PubMed:26896299,
FT ECO:0000269|PubMed:8484780, ECO:0007744|PDB:2N6F"
FT DISULFID 55..85
FT /evidence="ECO:0000269|PubMed:26896299,
FT ECO:0000269|PubMed:8484780, ECO:0007744|PDB:2N6F"
FT DISULFID 62..89
FT /evidence="ECO:0000269|PubMed:26896299,
FT ECO:0000269|PubMed:8484780, ECO:0007744|PDB:2N6F"
FT DISULFID 99..131
FT /evidence="ECO:0000269|PubMed:26896299,
FT ECO:0000269|PubMed:8484780, ECO:0007744|PDB:2N6F"
FT DISULFID 109..141
FT /evidence="ECO:0000269|PubMed:26896299,
FT ECO:0000269|PubMed:8484780, ECO:0007744|PDB:2N6F"
FT CONFLICT 42
FT /note="V -> K (in Ref. 14; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 47
FT /note="C -> D (in Ref. 14; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 75
FT /note="E -> G (in Ref. 9; AAV38498)"
FT /evidence="ECO:0000305"
FT STRAND 48..52
FT /evidence="ECO:0007829|PDB:2N6F"
FT STRAND 60..62
FT /evidence="ECO:0007829|PDB:2N6F"
FT STRAND 66..72
FT /evidence="ECO:0007829|PDB:2N6F"
FT STRAND 78..84
FT /evidence="ECO:0007829|PDB:2N6F"
FT STRAND 97..104
FT /evidence="ECO:0007829|PDB:2N6F"
FT TURN 111..114
FT /evidence="ECO:0007829|PDB:2N6F"
FT STRAND 115..124
FT /evidence="ECO:0007829|PDB:2N6F"
FT STRAND 133..142
FT /evidence="ECO:0007829|PDB:2N6F"
FT TURN 163..166
FT /evidence="ECO:0007829|PDB:2N6F"
SQ SEQUENCE 168 AA; 18942 MW; 0359C08B6497B579 CRC64;
MQAQQYQQQR RKFAAAFLAF IFILAAVDTA EAGKKEKPEK KVKKSDCGEW QWSVCVPTSG
DCGLGTREGT RTGAECKQTM KTQRCKIPCN WKKQFGAECK YQFQAWGECD LNTALKTRTG
SLKRALHNAE CQKTVTISKP CGKLTKPKPQ AESKKKKKEG KKQEKMLD
