ASPROSIINI (asprosin) glukoosihomeostaasiin vaikuttava tekijä ( FBN1 gene 15q21.1)

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Aliases for FBN1 Gene (15q21.1)

• GeneCards Symbol: FBN1 ²
• Fibrillin 1 ^{2 3 5}
• MASS ^{2 3 5}
• OCTD ^{2 3 5}
• SGS ^{2 3 5}
• FBN ^{3 4 5}
• Fibrillin-1 ^{3 4}
• Asprosin ^{2 3}
• MFS1 ^{3 5}
• WMS ^{3 5}
• Epididymis Secretory Sperm Binding Protein ³

• Fibrillin 1 (Marfan Syndrome) ²
• Fibrillin-1 Preproprotein ³
• Marfan Syndrome ²
• Fibrillin 15 ³
• GPHYSD2 ³
• ACMICD ³
• ECTOL1 ³
• MFLS ³
• SSKS ³
• WMS2 ³

External Ids for FBN1 Gene

ww.genecards.org/cgi-bin/carddisp.pl?gene=FBN1&keywords=fibrillin,1

Summaries for FBN1 Gene

NCBI Gene Summary for FBN1 Gene

• This gene encodes a member of the fibrillin family of proteins. The encoded preproprotein is proteolytically processed to generate two proteins including the extracellular matrix component fibrillin-1 and the protein hormone asprosin. Fibrillin-1 is an extracellular matrix glycoprotein that serves as a structural component of calcium-binding microfibrils. These microfibrils provide force-bearing structural support in elastic and nonelastic connective tissue throughout the body. Asprosin, secreted by white adipose tissue, has been shown to regulate glucose homeostasis. Mutations in this gene are associated with Marfan syndrome and the related MASS phenotype, as well as ectopia lentis syndrome, Weill-Marchesani syndrome, Shprintzen-Goldberg syndrome and neonatal progeroid syndrome. [provided by RefSeq, Apr 2016]

GeneCards Summary for FBN1 Gene

FBN1 (Fibrillin 1) is a Protein Coding gene. Diseases associated with FBN1 include Marfan Syndrome and Stiff Skin Syndrome. Among its related pathways are Integrin Pathway and ERK Signaling. Gene Ontology (GO) annotations related to this gene include calcium ion binding and extracellular matrix structural constituent. An important paralog of this gene is FBN2.

UniProtKB/Swiss-Prot Summary for FBN1 Gene

[Fibrillin-1]: Structural component of the 10-12 nm diameter microfibrils of the extracellular matrix, which conveys both structural and regulatory properties to load-bearing connective tissues (PubMed:1860873, 15062093). Fibrillin-1-containing microfibrils provide long-term force bearing structural support (PubMed:27026396). In tissues such as the lung, blood vessels and skin, microfibrils form the periphery of the elastic fiber, acting as a scaffold for the deposition of elastin (PubMed:27026396). In addition, microfibrils can occur as elastin-independent networks in tissues such as the ciliary zonule, tendon, cornea and glomerulus where they provide tensile strength and have anchoring roles (PubMed:27026396). Fibrillin-1 also plays a key role in tissue homeostasis through specific interactions with growth factors, such as the bone morphogenetic proteins (BMPs), growth and differentiation factors (GDFs) and latent transforming growth factor-beta-binding proteins (LTBPs), cell-surface integrins and other extracellular matrix protein and proteoglycan components (PubMed:27026396). Regulates osteoblast maturation by controlling TGF-beta bioavailability and calibrating TGF-beta and BMP levels, respectively (By similarity). Negatively regulates osteoclastogenesis by binding and sequestering an osteoclast differentiation and activation factor TNFSF11 (PubMed:24039232). This leads to disruption of TNFSF11-induced Ca(2+) signaling and impairment of TNFSF11-mediated nuclear translocation and activation of transcription factor NFATC1 which regulates genes important for osteoclast differentiation and function (PubMed:24039232). Mediates cell adhesion via its binding to cell surface receptors integrins ITGAV:ITGB3 and ITGA5:ITGB1 (PubMed:12807887, 17158881). Binds heparin and this interaction has an important role in the assembly of microfibrils (PubMed:11461921). ( FBN1_HUMAN,P35555 )

[Asprosin]: Adipokine secreted by white adipose tissue that plays an important regulatory role in the glucose metabolism of liver, muscle and pancreas (PubMed:27087445, 30853600). Hormone that targets the liver in response to fasting to increase plasma glucose levels (PubMed:27087445). Binds the olfactory receptor OR4M1 at the surface of hepatocytes and promotes hepatocyte glucose release by activating the protein kinase A activity in the liver, resulting in rapid glucose release into the circulation (PubMed:27087445, 31230984). May act as a regulator of adaptive thermogenesis by inhibiting browning and energy consumption, while increasing lipid deposition in white adipose tissue (By similarity). Also acts as an orexigenic hormone that increases appetite: crosses the blood brain barrier and exerts effects on the hypothalamus (By similarity). In the arcuate nucleus of the hypothalamus, asprosin directly activates orexigenic AgRP neurons and indirectly inhibits anorexigenic POMC neurons, resulting in appetite stimulation (By similarity). Activates orexigenic AgRP neurons via binding to the olfactory receptor OR4M1 (By similarity). May also play a role in sperm motility in testis via interaction with OR4M1 receptor (By similarity). ( FBN1_HUMAN,P35555 )

Gene Wiki entry for FBN1 Gen

Protein attributes for FBN1 Gene

Size:

2871 amino acids

Molecular mass:

312298 Da

Protein existence level:

PE1

Quaternary structure:

• [Fibrillin-1]: Interacts with COL16A1 (PubMed:15165854).
  Interacts with integrin alpha-V/beta-3 (PubMed:15062093).
  Interacts with ADAMTS10; this interaction promotes microfibril assembly (PubMed:21402694).
  Interacts with THSD4; this interaction promotes fibril formation (By similarity).
  Interacts (via N-terminal domain) with FBLN2 and FBLN5 (PubMed:15790312, 17255108).
  Interacts with ELN (PubMed:15790312).
  Forms a ternary complex with ELN and FBLN2 or FBLN5 and a significant interaction with ELN seen only in the presence of FBLN2 or FBLN5 (PubMed:17255108).
  Interacts (via N-terminal domain) with LTBP2 (via C-terminal domain) in a Ca(+2)-dependent manner (PubMed:17293099).
  Interacts (via N-terminal domain) with LTBP1 (via C-terminal domain) (PubMed:17293099).
  Interacts with integrins ITGA5:ITGB1, ITGAV:ITGB3 and ITGAV:ITGB6 (PubMed:17158881, 12807887).
  Interacts (via N-terminal domain) with BMP2, BMP4, BMP7, BMP10 and GDF5 (PubMed:18339631).
  Interacts (via N-terminal domain) with MFAP2 and MFAP5 (PubMed:15131124).
  Interacts with ADAMTSL5 (PubMed:23010571).
  Interacts with MFAP4 (PubMed:26601954).
  Interacts (via N-terminal domain) with TNFSF11 in a Ca(+2)-dependent manner (PubMed:24039232).
  Interacts (via N-terminal domain) with EFEMP2; this interaction inhibits EFEMP2 binding to LOX and ELN (PubMed:17255108, 19349279, 19570982).

Sequence caution:

• The sequence CAA45118.1 differs from that shown. Reason: Erroneous initiation Extended N-terminus. {ECO:0000305}

Miscellaneous:

• [Asprosin]: Was named after the Greek word for white, because of the reduction in subcutaneous white adipose tissue that is displayed by asprosin-deficient patients.

 ASPROSIININ LIIKAERITYKSESTÄ on artikkeleita:

https://en.wikipedia.org/wiki/Asprosin

 

(ASPROSIININ  funktiomekanismi  kekushermoston puolella on kuvattu myös: kosotaan huolimatta  sitä menee harvinaisen paljon veriaivoesteen läpi aivojen puolelle ja se säätelee  ravinnonottoaja täten  ravintoaineiden saantia ja sokeritasapainoa. mainitaan tie, mitä kautta se vaikuttaa: Se sitoutuu proteiinityrosiinifosfataasireseptori deltaan PTPRD.  Jos tuota reseptoria puuttuu seuraa  äärimmäminen rakenteellsiten kudosten vaje  (laihuus) ja ruokahalun kato, siis proteiinernergiavaje, malnutritio ja anorektinen tila. Tätä on tutkittu koe-eläimissä . Luulisi että tämäkin puoli asprosiinin metaboliasa olisi lääkekellisesti autettavissa. Varsinainen asprosiinin geneettinen  vaje tai  vähäisyys  antaa vaikutuksesna  riippuen myös tuosta PTPRD- reseptorin  tilasta. 

STRING kartta. osoittaa asian laajuuden. https://string-db.org/cgi/network?taskId=b7pCY90Jm51Z&sessionId=bMvOhMepV0Lw

 

Asprosin can also exit the bloodstream and cross the blood–brain barrier to function in the brain. The first indication that asprosin was in fact a cerebrospinal fluid (CSF) protein, in addition to being a plasma protein, was the observation of asprosin in the CSF of rats at concentrations 5- to 10-fold lower than in the plasma. Additionally, intravenously introduced asprosin showed a dramatic ability to cross the blood–brain barrier and enter the CSF.^[2]

A central mechanism of appetite regulation is via orexigenic AgRP neurons and anorexigenic POMC neurons in the arcuate nucleus of the hypothalamus. Asprosin directly activates orexigenic AgRP neurons and, using the neurotransmitter GABA, indirectly inhibits anorexigenic POMC neurons.^[2]

Asprosin’s orexigenic effects are mediated through binding to protein tyrosine phosphatase receptor delta (PTPRD).^[16] Genetic ablation of PTPRD results in extreme leanness and loss of appetite. More specifically, resistance to diet-induced obesity can occur through the loss of PTPRD in AgRP neurons.  When asprosin binds to PTPRD, this leads to the de-phosphorylation and de-activation of Stat3. PTPRD is highly expressed throughout the entire brain, especially in the cerebellum and cerebellar hemisphere. PTPRD is also highly expressed in the coronary arteries, the aorta, and the ovaries.