PTN_PIG
ID PTN_PIG Reviewed; 168 AA.
AC P79281;
DT 13-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 03-AUG-2022, entry version 106.
DE RecName: Full=Pleiotrophin {ECO:0000250|UniProtKB:P21246};
DE Short=PTN {ECO:0000250|UniProtKB:P21246};
DE AltName: Full=Pleiotrophic factor beta {ECO:0000303|Ref.1};
DE Short=PTF-beta {ECO:0000303|Ref.1};
DE Flags: Precursor;
GN Name=PTN {ECO:0000250|UniProtKB:P21246};
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RA Tsujimura A., Yasojima K., Hashimoto T.;
RT "Isolation of pig pleiotrophic factor beta.";
RL Submitted (NOV-1996) to the EMBL/GenBank/DDBJ databases.
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 (By similarity). Also plays a
CC role 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. Through PTPRZ1
CC binding controls oligodendrocyte precursor cell differentiation by
CC enhancing the phosphorylation of AFAP1L2 in order to activate the PI3K-
CC AKT pathway. Forms a complex with PTPRZ1 and integrin alpha-V/beta-3
CC (ITGAV:ITGB3) that stimulates endothelial cell migration through SRC
CC dephosphorylation and activation that consequently leads to ITGB3 'Tyr-
CC 773' phosphorylation (By similarity). In adult hippocampus promotes
CC dendritic arborization, spine development, and functional integration
CC and connectivity of newborn granule neurons through ALK by activating
CC AKT signaling pathway (By similarity). Binds GPC2 and chondroitin
CC sulfate proteoglycans (CSPGs) at the neuron surface, leading to
CC abrogation of binding between PTPRS and CSPGs and neurite outgrowth
CC promotion. 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 (By similarity).
CC Inhibits proliferation and enhances differentiation of neural stem
CC cells by inhibiting FGF2-induced fibroblast growth factor receptor
CC signaling pathway. Mediates regulatory mechanisms in normal hemostasis
CC and in hematopoietic regeneration and in maintaining the balance of
CC myeloid and lymphoid regeneration. In addition may play a role in the
CC female reproductive system, auditory response and the progesterone-
CC induced decidualization pathway (By similarity).
CC {ECO:0000250|UniProtKB:P21246, ECO:0000250|UniProtKB:P63089,
CC ECO:0000250|UniProtKB:P63090}.
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 -!- SIMILARITY: Belongs to the pleiotrophin family. {ECO:0000305}.
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DR EMBL; D89546; BAA13972.1; -; mRNA.
DR RefSeq; NP_999501.1; NM_214336.1.
DR RefSeq; XP_013841040.1; XM_013985586.1.
DR AlphaFoldDB; P79281; -.
DR SMR; P79281; -.
DR STRING; 9823.ENSSSCP00000017506; -.
DR PaxDb; P79281; -.
DR PRIDE; P79281; -.
DR Ensembl; ENSSSCT00000017990; ENSSSCP00000017506; ENSSSCG00000016522.
DR Ensembl; ENSSSCT00005030257; ENSSSCP00005018467; ENSSSCG00005019128.
DR Ensembl; ENSSSCT00005030288; ENSSSCP00005018491; ENSSSCG00005019128.
DR Ensembl; ENSSSCT00015103764; ENSSSCP00015043326; ENSSSCG00015076742.
DR Ensembl; ENSSSCT00025012986; ENSSSCP00025005098; ENSSSCG00025009799.
DR Ensembl; ENSSSCT00035018199; ENSSSCP00035006336; ENSSSCG00035014369.
DR Ensembl; ENSSSCT00045039627; ENSSSCP00045027585; ENSSSCG00045023122.
DR Ensembl; ENSSSCT00045039661; ENSSSCP00045027609; ENSSSCG00045023122.
DR Ensembl; ENSSSCT00055055972; ENSSSCP00055044698; ENSSSCG00055028221.
DR Ensembl; ENSSSCT00065006326; ENSSSCP00065002824; ENSSSCG00065004603.
DR Ensembl; ENSSSCT00070051178; ENSSSCP00070043291; ENSSSCG00070025592.
DR GeneID; 397609; -.
DR KEGG; ssc:397609; -.
DR CTD; 5764; -.
DR VGNC; VGNC:91965; PTN.
DR eggNOG; ENOG502RXV7; Eukaryota.
DR GeneTree; ENSGT00390000007640; -.
DR HOGENOM; CLU_136864_1_0_1; -.
DR InParanoid; P79281; -.
DR OMA; PKWRERR; -.
DR OrthoDB; 1489280at2759; -.
DR TreeFam; TF332376; -.
DR Reactome; R-SSC-201556; Signaling by ALK.
DR Proteomes; UP000008227; Chromosome 18.
DR Proteomes; UP000314985; Chromosome 18.
DR Bgee; ENSSSCG00000016522; Expressed in Ammon's horn and 40 other tissues.
DR ExpressionAtlas; P79281; baseline and differential.
DR Genevisible; P79281; SS.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:Ensembl.
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:0032991; C:protein-containing complex; IEA:Ensembl.
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:0005178; F:integrin binding; IEA:Ensembl.
DR GO; GO:0019901; F:protein kinase binding; IEA:Ensembl.
DR GO; GO:0004864; F:protein phosphatase inhibitor activity; ISS: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; 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 2: Evidence at transcript level;
KW Disulfide bond; Heparin-binding; Mitogen; Reference proteome; Secreted;
KW Signal.
FT SIGNAL 1..32
FT /evidence="ECO:0000255"
FT CHAIN 33..168
FT /note="Pleiotrophin"
FT /id="PRO_0000239426"
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 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: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:0000250|UniProtKB:P21246"
FT DISULFID 55..85
FT /evidence="ECO:0000250|UniProtKB:P21246"
FT DISULFID 62..89
FT /evidence="ECO:0000250|UniProtKB:P21246"
FT DISULFID 99..131
FT /evidence="ECO:0000250|UniProtKB:P21246"
FT DISULFID 109..141
FT /evidence="ECO:0000250|UniProtKB:P21246"
SQ SEQUENCE 168 AA; 18910 MW; BFA2A91DA2C6DCA0 CRC64;
MQTPQFLQQR RKFAAAFLAF IFLLAVVDTA EAGKKEKPEK KVKKSDCGEW QWSVCVPTSG
DCGLGTREGT RTGAECKQTM KTQRCKIPCN WKKQFGAECK YQFQAWGECD LNTALKTRTG
SLKRALHNAD CQKTVTISKP CGKVTKPKPQ AESKKKKKEG KKQEKMLD
