PTN,(7q33), pleiotrofiinigeeni ja sen koodaama pleitrofiini

https://www.ncbi.nlm.nih.gov/gene/5764
Tällä PTN- geenillä on muitakin nimiä.  HARP; HBBM; HBNF; HBGF8; NEGF1; OSF-1; HB-GAM; HBGF-8; HBNF-1.
Geenin koodaama påroteiini on eräs erittynyt hepariinia sitova kasvutekijä.(HBGF8). Tällä proteiinilla on merkitseviä osia solukasvussa ja solun elossapysymisessä, solun migroitumisessa, angiogeneesissä ja tumorigeneesissä.
Tästä geenistä tuolee monenlaisia  transkriptivariantteja vaihtoehtoispleissuksella ( silmukoinnilla)  ja vaihtoehtoisia promoottoreita käyttämällä.
Geeniä ilmentyy  laajalti aivoissa, prostatassa ja 17 muussa kudoksessa.

PTN

Official Full Name

pleiotrophin

Gene type

protein coding

RefSeq status

REVIEWED

Organism

Homo sapiens

Also known as

HARP; HBBM; HBNF; HBGF8; NEGF1; OSF-1; HB-GAM; HBGF-8; HBNF-1

Summary

The protein encoded by this gene is a secreted heparin-binding growth factor. The protein has significant roles in cell growth and survival, cell migration, angiogenesis and tumorigenesis. Alternative splicing and the use of alternative promoters results in multiple transcript variants. [provided by RefSeq, Oct 2016]

Expression: Broad expression in brain (RPKM 83.5), prostate (RPKM 56.7) and 17 other tissues See more

Orthologs: mouse all.

Preferred Names

pleiotrophin

Names

heparin affin regulatory protein (HARP)

heparin-binding brain mitogen (HBBM)

heparin-binding growth factor 8 (HBGF8)

heparin-binding growth-associated molecule (HB-GAM)

heparin-binding neurite outgrowth promoting factor

heparin-binding neurite outgrowth-promoting factor 1 (HBNF-1)

osteoblast-specific factor 1 (OSF-1)

pleiotrophin (PTN) 

 (heparin binding growth factor 8, neurite growth-promoting factor 1(NEGF-1)

Peptidestructure (Rakenne-esimerkki: isoformi 1 prekursori)  

https://www.ncbi.nlm.nih.gov/protein/NP_001308315.1 

 History:  mentioned first  1990:

REFERENCE   10 (residues 1 to 168)
  AUTHORS   Tezuka K, Takeshita S, Hakeda Y, Kumegawa M, Kikuno R and
            Hashimoto-Gotoh T.
  TITLE     Isolation of mouse and human cDNA clones encoding a protein
            expressed specifically in osteoblasts and brain tissues
  JOURNAL   Biochem. Biophys. Res. Commun. 173 (1), 246-251 (1990)

Gene PTN cloned 1992:  HBGF, homologous to a cytokine.

 REFERENCE   8  (residues 1 to 168)
  AUTHORS   Milner PG, Shah D, Veile R, Donis-Keller H and Kumar BV.
  TITLE     Cloning, nucleotide sequence, and chromosome localization of the
            human pleiotrophin gene
  JOURNAL   Biochemistry 31 (48), 12023-12028 (1992)
   PUBMED   1457401
REFERENCE   9  (residues 1 to 168)
  AUTHORS   Wellstein A, Fang WJ, Khatri A, Lu Y, Swain SS, Dickson RB, Sasse
            J, Riegel AT and Lippman ME.
  TITLE     A heparin-binding growth factor secreted from breast cancer cells
            homologous to a developmentally regulated cytokine
  JOURNAL   J. Biol. Chem. 267 (4), 2582-2587 (1992)
   PUBMED   1733956

PTN-HERV  insertio havaittu 1996. 

REFERENCE   6  (residues 1 to 168)
  AUTHORS   Schulte AM, Lai S, Kurtz A, Czubayko F, Riegel AT and Wellstein A.
  TITLE     Human trophoblast and choriocarcinoma expression of the growth
            factor pleiotrophin attributable to germ-line insertion of an
            endogenous retrovirus (ERV, Human ERV , HERV) 
  JOURNAL   Proc. Natl. Acad. Sci. U.S.A. 93 (25), 14759-14764 (1996)
   PUBMED   8962128

2017  noticed:  NK-cells secrete pleiotrophin.

REFERENCE   5  (residues 1 to 168)
  AUTHORS   Fu B, Zhou Y, Ni X, Tong X, Xu X, Dong Z, Sun R, Tian Z and Wei H.
  TITLE     Natural Killer Cells Promote Fetal Development through the
            Secretion of Growth-Promoting Factors
  JOURNAL   Immunity 47 (6), 1100-1113 (2017)
   PUBMED   29262349
  REMARK    GeneRIF: NK cells promote fetal development through the secretion
            of growth-promoting factors, pleiotrophin and osteoglycin.

 2018 noticed: pleitrophin  a prognostic  factor in cancer. 

 REFERENCE   3  (residues 1 to 168)

 AUTHORS   Zhou J, Yang Y, Zhang Y, Liu H and Dou Q.
  TITLE     A meta-analysis on the role of pleiotrophin (PTN) as a prognostic
            factor in cancer
  JOURNAL   PLoS ONE 13 (11), e0207473 (2018)

2019 noticed a mechanism behind chemotherapy resistence in Ca mammae. 

 
REFERENCE   2  (residues 1 to 168)
  AUTHORS   Huang P, Ouyang DJ, Chang S, Li MY, Li L, Li QY, Zeng R, Zou QY, Su
            J, Zhao P, Pei L and Yi WJ.
  TITLE     Chemotherapy-driven increases in the CDKN1A/PTN/PTPRZ1 axis promote
            chemoresistance by activating the NF-kappaB pathway in breast
            cancer cells
  JOURNAL   Cell Commun. Signal 16 (1), 92 (2018)
   PUBMED   30497491

2019 noticed that PTN inhibits PTPase."Protein tyrosine phosphatase receptor type Z

 (PTPRZ) maintains oligodendrocyte precursor cells (OPCs) in an undifferentiated

 state. The inhibition of PTPase by its ligand pleiotrophin
 (PTN) promotes OPC differentiation;  the substrate molecules of
 PTPRZ involved in the differentiation ..elucidated in detail.. concluded that 

the PTN-PTPRZ signal stimulates OPC differentiation 
partly by enhancing the tyrosine phosphorylation of (adaptor) AFAP1L2 in order to 
activate the PI3K-AKT pathway.

 PTN isoform aminoacidsequence:

 ORIGIN      
        1 mqaqqyqqqr rkfaaaflaf ifilaavdta eagkkekpek kvkksdcgew qwsvcvptsg
       61 dcglgtregt rtgaeckqtm ktqrckipcn wkkqfgaeck yqfqawgecd lntalktrtg
      121 slkralhnae cqktvtiskp cgkltkpkpq aeskkkkkeg kkqekmld
//

  sig_peptide     1..32   (        1 mqaqqyqqqr rkfaaaflaf ifilaavdta ea)
                     /inference="COORDINATES: ab initio prediction:SignalP:4.0"
                     /calculated_mol_wt=3647
     mat_peptide     33..168
                     /product="Pleiotrophin"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="propagated from UniProtKB/Swiss-Prot (P21246.1)"
                     /calculated_mol_wt=15313
     Region          47..131
                     /region_name="PTN_MK_N" (47 qwsvcvptsg
       61 dcglgtregt rtgaeckqtm ktqrckipcn wkkqfgaeck yqfqawgecd lntalktrtg
      121 slkralhnae c) 
                     /note="PTN/MK heparin-binding protein family, N-terminal
                     domain; cl02505"
                     /db_xref="CDD:321956"
     Region          92..99    (92 kkqfgaec)
                     /region_name="Chondroitin sulfate binding.
                     {ECO:0000269|PubMed:26896299}"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="propagated from UniProtKB/Swiss-Prot (P21246.1)"
     Region          123..131  (123 kralhnae c)  
                     /region_name="Chondroitin sulfate binding.
                     {ECO:0000269|PubMed:26896299}"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="propagated from UniProtKB/Swiss-Prot (P21246.1)"
     Region          147..168  ( 147 pkpq aeskkkkkeg kkqekmld)
                     /region_name="Chondroitin sulfate A binding.
                     {ECO:0000269|PubMed:26896299}"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="propagated from UniProtKB/Swiss-Prot (P21246.1)"
     CDS             1..168
                     /gene="PTN"
                     /gene_synonym="HARP; HB-GAM; HBBM; HBGF-8; HBGF8; HBNF;
                     HBNF-1; NEGF1; OSF-1"
                     /coded_by="NM_001321386.2:534..1040"
                     /note="isoform 1 precursor is encoded by transcript
                     variant 2"
                     /db_xref="CCDS:CCDS5844.1"
                     /db_xref="GeneID:5764"
                     /db_xref="HGNC:HGNC:9630"
                     /db_xref="MIM:162095"

 

  PubMed ref.

Bibliography

Related articles in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Proliferative  vitreoretinopathy(PVR) and PTN

 https://link.springer.com/article/10.1007%2Fs00417-016-3582-9

kommenttini GU uusi väitöskirja 4.9. 2019 :

AD biomerkitsijänä toimii  eräs C-terminaalinen fragmentti pleiotrofiinia:

 https://www.ncbi.nlm.nih.gov/pubmed?cmd=Retrieve&db=PubMed&list_uids=29042634 Abstract

We present a new, quantification-driven proteomic approach to identifying biomarkers. In contrast to the identification-driven approach, limited in scope to peptides that are identified by database searching in the first step, all MS data are considered to select biomarker candidates. The endopeptidome of cerebrospinal fluid from 40 Alzheimer's disease (AD) patients, 40 subjects with mild cognitive impairment, and 40 controls with subjective cognitive decline was analyzed using multiplex isobaric labeling. Spectral clustering was used to match MS/MS spectra. The top biomarker candidate cluster (215% higher in AD compared to controls, area under ROC curve = 0.96) was identified as a fragment of pleiotrophin located near the protein's C-terminus. Analysis of another cohort (n = 60 over four clinical groups) verified that the biomarker was increased in AD patients while no change in controls, Parkinson's disease or progressive supranuclear palsy was observed. The identification of the novel biomarker pleiotrophin 151-166

( 151 aeskkkkkeg kkqekm) 

demonstrates that our quantification-driven proteomic approach is a promising method for biomarker discovery, which may be universally applicable in clinical proteomics.

PMID:

29042634

PMCID:

PMC5645330

DOI:

10.1038/s41598-017-13831-0