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måndag 19 november 2018

Elafiinista lisätietoja WAP-domeeni ja Cementoiini domeeni (Trappin-2)

 https://en.wikipedia.org/wiki/Elafin

 Protein PI3 PDB 1fle.png



Elafiinilla on useampi nimi ja artikkeleista  ja geenitiedosta selviää nimen  tausta (PubMed Gene) 
Preferred Names
elafin
Names
PI-3
WAP four-disulfide core domain 14
WAP four-disulfide core domain protein 14
elastase-specific inhibitor
peptidase inhibitor 3, skin-derived
pre-elafin
protease inhibitor 3, skin-derived (SKALP)
protease inhibitor WAP3
skin-derived antileukoproteinase
trappin-2
 Rakenteen domeenit:WAP (Whey Acidic protein)  ja trappin-2(sementoiini)

Domeenien merkityksestä on myös lisätietoja- kuten  4 disulfidin ydin domeenista. https://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=197580


ja  sementoiinista , trappiini-2 proteiinin kaltaisesta  jaksosta,  jossa on transglutaminaasia sitova domeeni (gqdtvk,  gqdpvk , gqdkvk):  transglutaminaasi  tunnistaa jakson gqdpvk  ja  linkkii tähän ECM proteiineja (laminiini, beta-krystalliini, colIV, fibrinogeeni, elastiini)
(2) summary
smart00217
Location:72117
kpgsCpiil irCamlnppn rClkdtdCpg ikkCCegsCg maCfvpq
//
WAP; Four-disulfide core domains
pfam10511
Location:3147
Cementoin; Trappin protein transglutaminase binding domain
qdtvkgrvp fngqdpvkgq vsvkgqd


                     /db_xref="MIM:182257"
ORIGIN      
        1 mrassflivv vfliagtlvl eaavtgvpvk gqdtvkgrvp fngqdpvkgq vsvkgqdkvk
       61 aqepvkgpvs tkpgscpiil ircamlnppn rclkdtdcpg ikkccegscg macfvpq
//

WAP domain,   WheyAcidic Protein-domain muissa proteiineissa: 

 Bildresultat för WAP-domain elafin

 https://www.sciencedirect.com/science/article/pii/S0006291X03027669

Lisätietoja tämän domeenin  merkityksestä:Exemples
2007

2007 Jul 8;252(1):65-74. Epub 2007 Jan 9.Reduction of tumorigenesis and invasion of human breast cancer cells by whey acidic protein (WAP).
Whey acidic protein (WAP) is a major component of whey, which has two or three WAP motif domains characterized by a four-disulfide core (4-DSC) structure similar to the serine protease inhibitor. We have previously found that WAP inhibits the proliferation of mammary epithelial cells in vitro and in vivo [N. Nukumi, K. Ikeda, M. Osawa, T. Iwamori, K. Naito, H. Tojo, Regulatory function of whey acidic protein in the proliferation of mouse mammary epithelial cells in vivo and in vitro, Dev. Biol. 274 (2004) 31-44]. We report herein that WAP also reduces the progression of human breast cancer cells (MCF-7 and MDA-MB-453 cells). We have demonstrated that the forced expression of WAP in MCF-7 cells reduces the proliferation in either the presence or absence of estrogen. The tumor progression of WAP-expressing MCF-7 cells in nude mice is significantly suppressed more than that of mock-MCF-7 cells following the reduced expression of angiopoietin-2 gene. We have confirmed that the invasive activity of breast cancer cells is reduced to approximately 30% of that of mock cells by the forced expression of exogenous WAP through its inhibition of degradation of laminin. These data suggest that WAP has a protease-inhibitory function on the progression of breast cancer cells. It is therefore possible to utilize WAP as therapeutic protein against tumorigenesis of breast cancer.
  • PMID:17215074
  • DOI:10.1016/j.canlet.2006.12.005
  • [Indexed for MEDLINE] 
  •  
  • 2.  Aktivoitunut mikroglia erittää WAP- proteiinia AMWAP , joka on neuroprotektiivinen.

    tämä artikkeli selvittää WAP- merkitystä.
     https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-015-0296-6
    Conclusions



    We have shown that AMWAP is a secreted anti-inflammatory protein of reactive microglia that acts in a paracrine fashion. Endocytosed AMWAP is localized in a perinuclear region where it prevents NFκB signaling via inhibition of IRAK-1 and IκBα proteolytic degradation. AMWAP does not affect phosphorylation or ubiquitination of these signaling proteins and has no influence on overall 20S proteasome activity. On a functional level, AMWAP inhibits pro-inflammatory gene expression, reduces microglial neurotoxicity, promotes filopodia formation, and increases phagocytic uptake of apoptotic debris. In conclusion, our data suggest that AMWAP triggers a neuroprotective phenotype in microglia and that whey acidic proteins may be potential therapeutics to inhibit a detrimental microglial phenotype in neurodegenerative diseases of the brain and retina.

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