PTN_BOVIN
ID PTN_BOVIN Reviewed; 168 AA.
AC P21782; P20157; Q3SZU1;
DT 01-MAY-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1991, sequence version 2.
DT 03-AUG-2022, entry version 131.
DE RecName: Full=Pleiotrophin {ECO:0000303|PubMed:2270483};
DE Short=PTN {ECO:0000303|PubMed:2270483};
DE AltName: Full=Heparin-binding brain mitogen {ECO:0000250|UniProtKB:P21246};
DE Short=HBBM {ECO:0000250|UniProtKB:P21246};
DE AltName: Full=Heparin-binding growth factor 8 {ECO:0000303|PubMed:2610682};
DE Short=HBGF-8 {ECO:0000303|PubMed:2610682};
DE AltName: Full=Heparin-binding growth-associated molecule {ECO:0000303|PubMed:1550956};
DE Short=HB-GAM {ECO:0000303|PubMed:1550956};
DE AltName: Full=Heparin-binding neurite-promoting factor {ECO:0000303|PubMed:2229039};
DE AltName: Full=p18 {ECO:0000303|PubMed:2229039};
DE Flags: Precursor;
GN Name=PTN {ECO:0000250|UniProtKB:P21246};
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Uterus;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Crossbred X Angus; TISSUE=Liver;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP PROTEIN SEQUENCE OF 33-168, FUNCTION, AND MASS SPECTROMETRY.
RC TISSUE=Brain;
RX PubMed=1550956; DOI=10.1091/mbc.3.1.85;
RA Hampton B.S., Marshak D.R., Burgess W.H.;
RT "Structural and functional characterization of full-length heparin-binding
RT growth associated molecule.";
RL Mol. Biol. Cell 3:85-93(1992).
RN [4]
RP PROTEIN SEQUENCE OF 33-151.
RC TISSUE=Brain;
RX PubMed=2229039; DOI=10.1016/s0021-9258(17)30574-4;
RA Kuo M.-D., Oda Y., Huang J.S., Huang S.S.;
RT "Amino acid sequence and characterization of a heparin-binding neurite-
RT promoting factor (p18) from bovine brain.";
RL J. Biol. Chem. 265:18749-18752(1990).
RN [5]
RP PROTEIN SEQUENCE OF 33-57.
RC TISSUE=Uterus;
RX PubMed=2610682; DOI=10.1016/0006-291x(89)92715-0;
RA Milner P.G., Yue-Sheng L., Hoffman R.M., Kodner C.M., Siegel N.R.,
RA Deuel T.F.;
RT "A novel 17 kD heparin-binding growth factor (HBGF-8) in bovine uterus:
RT purification and N-terminal amino acid sequence.";
RL Biochem. Biophys. Res. Commun. 165:1096-1103(1989).
RN [6]
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).
CC -!- FUNCTION: Secreted growth factor that mediates its signal through cell-
CC surface proteoglycan and non-proteoglycan receptors. Binds cell-surface
CC proteoglycan receptor via their chondroitin sulfate (CS) groups.
CC Thereby regulates many processes like cell proliferation, cell
CC survival, cell growth, cell differentiation and cell migration in
CC several tissues namely neuron and bone (PubMed:1550956) (By
CC similarity). Also plays a role in synaptic plasticity and learning-
CC related behavior by inhibiting long-term synaptic potentiation (By
CC similarity). Binds PTPRZ1, leading to neutralization of the negative
CC charges of the CS chains of PTPRZ1, inducing PTPRZ1 clustering, thereby
CC causing the dimerization and inactivation of its phosphatase activity
CC leading to increased tyrosine phosphorylation of each of the PTPRZ1
CC substrates like ALK, CTNNB1 or AFAP1L2 in order to activate the PI3K-
CC AKT pathway. Through PTPRZ1 binding controls oligodendrocyte precursor
CC cell differentiation by enhancing the phosphorylation of AFAP1L2 in
CC order to activate the PI3K-AKT pathway. Forms a complex with PTPRZ1 and
CC integrin alpha-V/beta-3 (ITGAV:ITGB3) that stimulates endothelial cell
CC migration through SRC dephosphorylation and activation that
CC consequently leads to ITGB3 'Tyr-773' phosphorylation (By similarity).
CC In adult hippocampus promotes dendritic arborization, spine
CC development, and functional integration and connectivity of newborn
CC granule neurons through ALK by activating AKT signaling pathway (By
CC similarity). Binds GPC2 and chondroitin sulfate proteoglycans (CSPGs)
CC at the neuron surface, leading to abrogation of binding between PTPRS
CC and CSPGs and neurite outgrowth promotion. Binds SDC3 and mediates bone
CC formation by recruiting and attaching osteoblasts/osteoblast precursors
CC to the sites for new bone deposition (By similarity). Binds ALK and
CC promotes cell survival and cell proliferation through MAPK pathway
CC activation (By similarity). Inhibits proliferation and enhances
CC differentiation of neural stem cells by inhibiting FGF2-induced
CC fibroblast growth factor receptor signaling pathway. Mediates
CC regulatory mechanisms in normal hemostasis and in hematopoietic
CC regeneration and in maintaining the balance of myeloid and lymphoid
CC regeneration. In addition may play a role in the female reproductive
CC system, auditory response and the progesterone-induced decidualization
CC pathway (By similarity). {ECO:0000250|UniProtKB:P21246,
CC ECO:0000250|UniProtKB:P63089, ECO:0000250|UniProtKB:P63090,
CC ECO:0000269|PubMed:1550956}.
CC -!- SUBUNIT: Interacts with ALK and NEK6. Interacts with PTPRZ1 (via
CC chondroitin sulfate groups); promotes formation of homooligomers;
CC oligomerization impairs tyrosine phosphatase activity. Forms a complex
CC with PTPRZ1 and CTNNB1; this complex inactivates PTPRZ1 protein
CC tyrosine phosphatase activity through PTN interaction and stimulates
CC tyrosine phosphorylation of CTNNB1. Interacts with ITGB3 AND ITGA5.
CC Forms a complex with PTPRZ1 and integrin alpha-V/beta-3 (ITGAV:ITGB3)
CC that stimulates endothelial cell migration through ITGB3 'Tyr-773'
CC phosphorylation (By similarity). Interacts with SDC3 (via heparan
CC sulfate chains); this interaction mediates the neurite outgrowth-
CC promoting signal from PTN to the cytoskeleton of growing neurites; this
CC interaction mediates osteoblast recruitment. Interacts with GPC2 (via
CC heparan sulfate); this interaction promotes neurite outgrowth through
CC binding of PTN with chondroitin sulfate of proteoglycans, thereby
CC releasing PTPRS of chondroitin sulfate proteoglycans (CSPGs) and
CC leading to binding with heparan sulfate of GPC2 (By similarity).
CC {ECO:0000250|UniProtKB:P21246, ECO:0000250|UniProtKB:P63090}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P21246}.
CC -!- PTM: Phosphorylated by NEK6. {ECO:0000250|UniProtKB:P21246}.
CC -!- MASS SPECTROMETRY: Mass=15291; Method=Plasma desorption;
CC Evidence={ECO:0000269|PubMed:1550956};
CC -!- SIMILARITY: Belongs to the pleiotrophin family. {ECO:0000305}.
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DR EMBL; X52945; CAA37120.1; -; mRNA.
DR EMBL; BC102712; AAI02713.1; -; mRNA.
DR PIR; A37780; A37780.
DR RefSeq; NP_776380.1; NM_173955.1.
DR RefSeq; XP_005205847.1; XM_005205790.3.
DR AlphaFoldDB; P21782; -.
DR SMR; P21782; -.
DR STRING; 9913.ENSBTAP00000002983; -.
DR PaxDb; P21782; -.
DR Ensembl; ENSBTAT00000002983; ENSBTAP00000002983; ENSBTAG00000002317.
DR GeneID; 280904; -.
DR KEGG; bta:280904; -.
DR CTD; 5764; -.
DR VEuPathDB; HostDB:ENSBTAG00000002317; -.
DR VGNC; VGNC:33521; PTN.
DR eggNOG; ENOG502RXV7; Eukaryota.
DR GeneTree; ENSGT00390000007640; -.
DR HOGENOM; CLU_136864_1_0_1; -.
DR InParanoid; P21782; -.
DR OMA; PKWRERR; -.
DR OrthoDB; 1489280at2759; -.
DR TreeFam; TF332376; -.
DR Proteomes; UP000009136; Chromosome 4.
DR Bgee; ENSBTAG00000002317; Expressed in myometrium and 102 other tissues.
DR ExpressionAtlas; P21782; baseline and differential.
DR GO; GO:0005576; C:extracellular region; ISS:UniProtKB.
DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IEA:GOC.
DR GO; GO:0035374; F:chondroitin sulfate binding; ISS:UniProtKB.
DR GO; GO:0008083; F:growth factor activity; ISS:UniProtKB.
DR GO; GO:0008201; F:heparin binding; ISS:UniProtKB.
DR GO; GO:0004864; F:protein phosphatase inhibitor activity; ISS:UniProtKB.
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; ISS: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:0048477; P:oogenesis; ISS:UniProtKB.
DR GO; GO:0043932; P:ossification involved in bone remodeling; ISS: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:0045597; P:positive regulation of cell differentiation; 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; ISS: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; ISS: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; ISS: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 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 Direct protein sequencing; Disulfide bond; Growth factor; Heparin-binding;
KW Mitogen; Reference proteome; Secreted; Signal.
FT SIGNAL 1..32
FT /evidence="ECO:0000269|PubMed:1550956,
FT ECO:0000269|PubMed:2229039, ECO:0000269|PubMed:2610682"
FT CHAIN 33..168
FT /note="Pleiotrophin"
FT /id="PRO_0000024658"
FT REGION 92..99
FT /note="Chondroitin sulfate binding"
FT /evidence="ECO:0000250|UniProtKB:P21246"
FT REGION 123..131
FT /note="Chondroitin sulfate binding"
FT /evidence="ECO:0000250|UniProtKB:P21246"
FT REGION 141..168
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 147..168
FT /note="Chondroitin sulfate A binding"
FT /evidence="ECO:0000250|UniProtKB:P21246"
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:8484780"
FT DISULFID 55..85
FT /evidence="ECO:0000269|PubMed:8484780"
FT DISULFID 62..89
FT /evidence="ECO:0000269|PubMed:8484780"
FT DISULFID 99..131
FT /evidence="ECO:0000269|PubMed:8484780"
FT DISULFID 109..141
FT /evidence="ECO:0000269|PubMed:8484780"
FT CONFLICT 78
FT /note="Q -> E (in Ref. 4; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 151
FT /note="Missing (in Ref. 2; AAI02713)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 168 AA; 18902 MW; 22CA0DFD8678D09A CRC64;
MQTPQYLQQR RKFAAAFLAF IFILAAVDTA EAGKKEKPEK KVKKSDCGEW QWSVCVPTSG
DCGLGTREGT RTGAECKQTM KTQRCKIPCN WKKQFGAECK YQFQAWGECD LNTALKTRTG
SLKRALHNAD CQKTVTISKP CGKLTKSKPQ AESKKKKKEG KKQEKMLD
