P21246 · PTN_HUMAN
- ProteinPleiotrophin
- GenePTN
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids168 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Secreted growth factor that mediates its signal through cell-surface proteoglycan and non-proteoglycan receptors (PubMed:11278720, PubMed:16814777, PubMed:19141530).
Binds cell-surface proteoglycan receptor via their chondroitin sulfate (CS) groups (PubMed:26896299, PubMed:27445335).
Thereby regulates many processes like cell proliferation, cell survival, cell growth, cell differentiation and cell migration in several tissues namely neuron and bone (PubMed:11278720, PubMed:1733956, PubMed:1768439, PubMed:19141530, PubMed:19442624, PubMed:27445335, PubMed:30667096).
Also plays a role in synaptic plasticity and learning-related behavior by inhibiting long-term synaptic potentiation (By similarity).
Binds PTPRZ1, leading to neutralization of the negative charges of the CS chains of PTPRZ1, inducing PTPRZ1 clustering, thereby causing the dimerization and inactivation of its phosphatase activity leading to increased tyrosine phosphorylation of each of the PTPRZ1 substrates like ALK, CTNNB1 or AFAP1L2 in order to activate the PI3K-AKT pathway (PubMed:10706604, PubMed:16814777, PubMed:17681947, PubMed:27445335, PubMed:30667096).
Through PTPRZ1 binding controls oligodendrocyte precursor cell differentiation by enhancing the phosphorylation of AFAP1L2 in order to activate the PI3K-AKT pathway (PubMed:27445335, PubMed:30667096).
Forms a complex with PTPRZ1 and integrin alpha-V/beta-3 (ITGAV:ITGB3) that stimulates endothelial cell migration through SRC dephosphorylation and activation that consequently leads to ITGB3 'Tyr-773' phosphorylation (PubMed:19141530).
In adult hippocampus promotes dendritic arborization, spine development, and functional integration and connectivity of newborn granule neurons through ALK by activating AKT signaling pathway (By similarity).
Binds GPC2 and chondroitin sulfate proteoglycans (CSPGs) at the neuron surface, leading to abrogation of binding between PTPRS and CSPGs and neurite outgrowth promotion (By similarity).
Binds SDC3 and mediates bone formation by recruiting and attaching osteoblasts/osteoblast precursors to the sites for new bone deposition (By similarity).
Binds ALK and promotes cell survival and cell proliferation through MAPK pathway activation (PubMed:11278720).
Inhibits proliferation and enhances differentiation of neural stem cells by inhibiting FGF2-induced fibroblast growth factor receptor signaling pathway (By similarity).
Mediates regulatory mechanisms in normal hemostasis and in hematopoietic regeneration and in maintaining the balance of myeloid and lymphoid regeneration (By similarity).
In addition may play a role in the female reproductive system, auditory response and the progesterone-induced decidualization pathway (By similarity).
Binds cell-surface proteoglycan receptor via their chondroitin sulfate (CS) groups (PubMed:26896299, PubMed:27445335).
Thereby regulates many processes like cell proliferation, cell survival, cell growth, cell differentiation and cell migration in several tissues namely neuron and bone (PubMed:11278720, PubMed:1733956, PubMed:1768439, PubMed:19141530, PubMed:19442624, PubMed:27445335, PubMed:30667096).
Also plays a role in synaptic plasticity and learning-related behavior by inhibiting long-term synaptic potentiation (By similarity).
Binds PTPRZ1, leading to neutralization of the negative charges of the CS chains of PTPRZ1, inducing PTPRZ1 clustering, thereby causing the dimerization and inactivation of its phosphatase activity leading to increased tyrosine phosphorylation of each of the PTPRZ1 substrates like ALK, CTNNB1 or AFAP1L2 in order to activate the PI3K-AKT pathway (PubMed:10706604, PubMed:16814777, PubMed:17681947, PubMed:27445335, PubMed:30667096).
Through PTPRZ1 binding controls oligodendrocyte precursor cell differentiation by enhancing the phosphorylation of AFAP1L2 in order to activate the PI3K-AKT pathway (PubMed:27445335, PubMed:30667096).
Forms a complex with PTPRZ1 and integrin alpha-V/beta-3 (ITGAV:ITGB3) that stimulates endothelial cell migration through SRC dephosphorylation and activation that consequently leads to ITGB3 'Tyr-773' phosphorylation (PubMed:19141530).
In adult hippocampus promotes dendritic arborization, spine development, and functional integration and connectivity of newborn granule neurons through ALK by activating AKT signaling pathway (By similarity).
Binds GPC2 and chondroitin sulfate proteoglycans (CSPGs) at the neuron surface, leading to abrogation of binding between PTPRS and CSPGs and neurite outgrowth promotion (By similarity).
Binds SDC3 and mediates bone formation by recruiting and attaching osteoblasts/osteoblast precursors to the sites for new bone deposition (By similarity).
Binds ALK and promotes cell survival and cell proliferation through MAPK pathway activation (PubMed:11278720).
Inhibits proliferation and enhances differentiation of neural stem cells by inhibiting FGF2-induced fibroblast growth factor receptor signaling pathway (By similarity).
Mediates regulatory mechanisms in normal hemostasis and in hematopoietic regeneration and in maintaining the balance of myeloid and lymphoid regeneration (By similarity).
In addition may play a role in the female reproductive system, auditory response and the progesterone-induced decidualization pathway (By similarity).
GO annotations
Keywords
- Molecular function
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended namePleiotrophin
- Short namesPTN
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP21246
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Disease & Variants
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 172 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for signal, chain, disulfide bond.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-32 | |||||
Sequence: MQAQQYQQQRRKFAAAFLAFIFILAAVDTAEA | ||||||
Chain | PRO_0000024659 | 33-168 | Pleiotrophin | |||
Sequence: GKKEKPEKKVKKSDCGEWQWSVCVPTSGDCGLGTREGTRTGAECKQTMKTQRCKIPCNWKKQFGAECKYQFQAWGECDLNTALKTRTGSLKRALHNAECQKTVTISKPCGKLTKPKPQAESKKKKKEGKKQEKMLD | ||||||
Disulfide bond | 47↔76 | |||||
Sequence: CGEWQWSVCVPTSGDCGLGTREGTRTGAEC | ||||||
Disulfide bond | 55↔85 | |||||
Sequence: CVPTSGDCGLGTREGTRTGAECKQTMKTQRC | ||||||
Disulfide bond | 62↔89 | |||||
Sequence: CGLGTREGTRTGAECKQTMKTQRCKIPC | ||||||
Disulfide bond | 99↔131 | |||||
Sequence: CKYQFQAWGECDLNTALKTRTGSLKRALHNAEC | ||||||
Disulfide bond | 109↔141 | |||||
Sequence: CDLNTALKTRTGSLKRALHNAECQKTVTISKPC |
Post-translational modification
Phosphorylated by NEK6.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Osteoblast and brain.
Induction
By heparin and retinoic acid.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Interacts with ALK and NEK6 (PubMed:11278720, PubMed:20873783).
Interacts with PTPRZ1 (via chondroitin sulfate groups); promotes formation of homooligomers; oligomerization impairs tyrosine phosphatase activity (Probable) (PubMed:16814777).
Forms a complex with PTPRZ1 and CTNNB1; this complex inactivates PTPRZ1 protein tyrosine phosphatase activity through PTN interaction and stimulates tyrosine phosphorylation of CTNNB1 (PubMed:10706604).
Interacts with ITGB3 and ITGA5 (PubMed:19141530).
Forms a complex with PTPRZ1 and integrin alpha-V/beta-3 (ITGAV:ITGB3) that stimulates endothelial cell migration through ITGB3 'Tyr-773' phosphorylation (PubMed:19141530).
Interacts with SDC3 (via heparan sulfate chains); this interaction mediates the neurite outgrowth-promoting signal from PTN to the cytoskeleton of growing neurites; this interaction mediates osteoblast recruitment. Interacts with GPC2 (via heparan sulfate); this interaction promotes neurite outgrowth through binding of PTN with chondroitin sulfate of proteoglycans, thereby releasing PTPRS of chondroitin sulfate proteoglycans (CSPGs) and leading to binding with heparan sulfate of GPC2 (By similarity).
Interacts with PTPRZ1 (via chondroitin sulfate groups); promotes formation of homooligomers; oligomerization impairs tyrosine phosphatase activity (Probable) (PubMed:16814777).
Forms a complex with PTPRZ1 and CTNNB1; this complex inactivates PTPRZ1 protein tyrosine phosphatase activity through PTN interaction and stimulates tyrosine phosphorylation of CTNNB1 (PubMed:10706604).
Interacts with ITGB3 and ITGA5 (PubMed:19141530).
Forms a complex with PTPRZ1 and integrin alpha-V/beta-3 (ITGAV:ITGB3) that stimulates endothelial cell migration through ITGB3 'Tyr-773' phosphorylation (PubMed:19141530).
Interacts with SDC3 (via heparan sulfate chains); this interaction mediates the neurite outgrowth-promoting signal from PTN to the cytoskeleton of growing neurites; this interaction mediates osteoblast recruitment. Interacts with GPC2 (via heparan sulfate); this interaction promotes neurite outgrowth through binding of PTN with chondroitin sulfate of proteoglycans, thereby releasing PTPRS of chondroitin sulfate proteoglycans (CSPGs) and leading to binding with heparan sulfate of GPC2 (By similarity).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P21246 | ASPH Q12797-6 | 3 | EBI-473725, EBI-12092171 | |
BINARY | P21246 | ITGAM P11215 | 3 | EBI-473725, EBI-2568251 | |
BINARY | P21246 | KLK6 Q92876 | 3 | EBI-473725, EBI-2432309 | |
BINARY | P21246 | PRKACA P17612 | 3 | EBI-473725, EBI-476586 | |
BINARY | P21246 | SERPINH1 P50454 | 3 | EBI-473725, EBI-350723 | |
BINARY | P21246 | TGFBR2 P37173 | 3 | EBI-473725, EBI-296151 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 92-99 | Chondroitin sulfate binding | ||||
Sequence: KKQFGAEC | ||||||
Region | 123-131 | Chondroitin sulfate binding | ||||
Sequence: KRALHNAEC | ||||||
Region | 139-168 | Disordered | ||||
Sequence: KPCGKLTKPKPQAESKKKKKEGKKQEKMLD | ||||||
Region | 147-168 | Chondroitin sulfate A binding | ||||
Sequence: PKPQAESKKKKKEGKKQEKMLD | ||||||
Compositional bias | 148-168 | Basic and acidic residues | ||||
Sequence: KPQAESKKKKKEGKKQEKMLD |
Sequence similarities
Belongs to the pleiotrophin family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length168
- Mass (Da)18,942
- Last updated1991-05-01 v1
- Checksum0359C08B6497B579
Computationally mapped potential isoform sequences
There are 2 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
C9JR52 | C9JR52_HUMAN | PTN | 166 | ||
A0A8V8TNI1 | A0A8V8TNI1_HUMAN | PTN | 167 |
Features
Showing features for sequence conflict, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 42 | in Ref. 14; AA sequence | ||||
Sequence: V → K | ||||||
Sequence conflict | 47 | in Ref. 14; AA sequence | ||||
Sequence: C → D | ||||||
Sequence conflict | 75 | in Ref. 9; AAV38498 | ||||
Sequence: E → G | ||||||
Compositional bias | 148-168 | Basic and acidic residues | ||||
Sequence: KPQAESKKKKKEGKKQEKMLD |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
D90226 EMBL· GenBank· DDBJ | BAA14261.1 EMBL· GenBank· DDBJ | mRNA | ||
X52946 EMBL· GenBank· DDBJ | CAA37121.1 EMBL· GenBank· DDBJ | mRNA | ||
M57399 EMBL· GenBank· DDBJ | AAA35961.1 EMBL· GenBank· DDBJ | mRNA | ||
S50409 EMBL· GenBank· DDBJ | AAB24425.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
S50405 EMBL· GenBank· DDBJ | AAB24425.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
S50408 EMBL· GenBank· DDBJ | AAB24425.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
S50394 EMBL· GenBank· DDBJ | AAB24425.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
S60110 EMBL· GenBank· DDBJ | AAB26456.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
S59641 EMBL· GenBank· DDBJ | AAB26456.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
S60111 EMBL· GenBank· DDBJ | AAB26456.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
S60736 EMBL· GenBank· DDBJ | AAB26456.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AB004306 EMBL· GenBank· DDBJ | BAA22944.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AK290488 EMBL· GenBank· DDBJ | BAF83177.1 EMBL· GenBank· DDBJ | mRNA | ||
AK313424 EMBL· GenBank· DDBJ | BAG36216.1 EMBL· GenBank· DDBJ | mRNA | ||
CR450338 EMBL· GenBank· DDBJ | CAG29334.1 EMBL· GenBank· DDBJ | mRNA | ||
BT019692 EMBL· GenBank· DDBJ | AAV38498.1 EMBL· GenBank· DDBJ | mRNA | ||
CH236950 EMBL· GenBank· DDBJ | EAL24052.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471070 EMBL· GenBank· DDBJ | EAW83869.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC005916 EMBL· GenBank· DDBJ | AAH05916.1 EMBL· GenBank· DDBJ | mRNA |