ORMDL regulator 3 biosinteze sfingolipida je protein koji je kod ljudi kodiran genom ORMDL3.[5] Ovaj gen povezan je s astmom u djetinjstvu.[6] Transgeni miševi koji prekomerno eksprimiraju ljudski ORMDL3 povećali su nivo IgE. To je povezano sa povećanim brojem makrofaga, neutrofila, eozinofila , CD4 + T-ćelija antitumorske imunosti CD4 + i pojačanog Th2 nivoa citokina u plućnom tkivu.[7]

OSBR 3
Identifikatori
AliasiORMDL3
Vanjski ID-jeviOMIM: 610075 MGI: 1913862 HomoloGene: 57032 GeneCards: ORMDL3
Lokacija gena (čovjek)
Hromosom 17 (čovjek)
Hrom.Hromosom 17 (čovjek)[1]
Hromosom 17 (čovjek)
Genomska lokacija za OSBR 3
Genomska lokacija za OSBR 3
Bend17q21.1Početak39,921,041 bp[1]
Kraj39,927,601 bp[1]
Lokacija gena (miš)
Hromosom 11 (miš)
Hrom.Hromosom 11 (miš)[2]
Hromosom 11 (miš)
Genomska lokacija za OSBR 3
Genomska lokacija za OSBR 3
Bend11|11 DPočetak98,472,082 bp[2]
Kraj98,478,194 bp[2]
Ontologija gena
Molekularna funkcija GO:0001948, GO:0016582 protein binding
Ćelijska komponenta integral component of membrane
SPOTS complex
endoplasmic reticulum membrane
Endoplazmatski retikulum
membrana
Ćelijska membrana
secretory granule membrane
specific granule membrane
Biološki proces ceramide metabolic process
cellular sphingolipid homeostasis
neutrophil degranulation
negative regulation of ceramide biosynthetic process
Izvori:Amigo / QuickGO
Ortolozi
VrsteČovjekMiš
Entrez
Ensembl
UniProt
RefSeq (mRNK)

NM_139280
NM_001320801
NM_001320802
NM_001320803
NM_016471

NM_025661

RefSeq (bjelančevina)

NP_001307730
NP_001307731
NP_001307732
NP_644809

NP_079937

Lokacija (UCSC)Chr 17: 39.92 – 39.93 MbChr 11: 98.47 – 98.48 Mb
PubMed pretraga[3][4]
Wikipodaci
Pogledaj/uredi – čovjekPogledaj/uredi – miš

Dužina polipeptidnog lanca je 153 aminokiselina, sa molekulskom težinom od 17.495.[8].

Aminokiselinska sekvenca

Simboli
1020304050
MNVGTAHSEVNPNTRVMNSRGIWLSYVLAIGLLHIVLLSIPFVSVPVVWT
LTNLIHNMGMYIFLHTVKGTPFETPDQGKARLLTHWEQMDYGVQFTASRK
FLTITPIVLYFLTSFYTKYDQIHFVLNTVSLMSVLIPKLPQLHGVRIFGI
NKY

Lokalizacija uredi

Gen ORMDL3 miša i čovjeka kodira sekvencu od 153 aa. Porodica ORMDL sastoji se od tri člana (ORMDL1-3), koji su lokalizovani u membrani endoplazmatskog retikuluma (ER).[9] Ljudski ORMDL1, ORMDL2 i ORMDL3 lokalizirani su u hromosomimskim pozicijama 2q32, 12q13.2 a 17q21.[10]

Funkcija uredi

ORMDL3 ima ulogu u sintezi sfingolipida, kao negativnih regulatora.[9][11] Također ima ulogu u regulaciji nivoa Ca2+ u endoplazmatskom retikulumu. ER je vrlo važan za stvaranje, signalizaciju, funkcioniranje i skladištenje unutarćelijskog Ca2+. Postoje kanali koji kontroliraju izlaz Ca 2+ + iz ER u citoplazmu, a također pumpe (sarkoplazmatski retikulum Ca2+ATPaza (SERCA)) koje vraćaju Ca2+ natrag u ER.[12] Disregulacija Ca2+ ima ključnu ulogu u nekoliko patoloških stanja, poput disfunkcije SERCA, astme,[13] i Alzheimerove bolesti.[14]

Klinički značaj uredi

Mutacije u ORMDL3 povezane su sa upalnim bolestima, kao što su Crohnova bolest, tip 1 diabetes mellitus tip 1,[15] i reumatiodni artritis.[16]

Reference uredi

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000172057 - Ensembl, maj 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000038150 - Ensembl, maj 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ "Entrez Gene: ORMDL sphingolipid biosynthesis regulator 3".
  6. ^ Moffatt MF, Kabesch M, Liang L, Dixon AL, Strachan D, Heath S, et al. (juli 2007). "Genetic variants regulating ORMDL3 expression contribute to the risk of childhood asthma" (PDF). Nature. 448 (7152): 470–3. Bibcode:2007Natur.448..470M. doi:10.1038/nature06014. hdl:2027.42/62682. PMID 17611496. S2CID 4373589.
  7. ^ Miller M, Rosenthal P, Beppu A, Mueller JL, Hoffman HM, Tam AB, et al. (april 2014). "ORMDL3 transgenic mice have increased airway remodeling and airway responsiveness characteristic of asthma". Journal of Immunology. 192 (8): 3475–87. doi:10.4049/jimmunol.1303047. PMC 3981544. PMID 24623133.
  8. ^ "UniProt, Q8N138". Pristupljeno September 12, 2017.
  9. ^ a b Davis D, Kannan M, Wattenberg B (decembar 2018). "Orm/ORMDL proteins: Gate guardians and master regulators". Advances in Biological Regulation. Sphingolipid Signaling in Chronic Disease. 70: 3–18. doi:10.1016/j.jbior.2018.08.002. PMC 6251742. PMID 30193828.
  10. ^ Hjelmqvist L, Tuson M, Marfany G, Herrero E, Balcells S, Gonzàlez-Duarte R (2002). "ORMDL proteins are a conserved new family of endoplasmic reticulum membrane proteins". Genome Biology. 3 (6): RESEARCH0027. doi:10.1186/gb-2002-3-6-research0027. PMC 116724. PMID 12093374.
  11. ^ Breslow DK, Collins SR, Bodenmiller B, Aebersold R, Simons K, Shevchenko A, et al. (februar 2010). "Orm family proteins mediate sphingolipid homeostasis". Nature. 463 (7284): 1048–53. Bibcode:2010Natur.463.1048B. doi:10.1038/nature08787. PMC 2877384. PMID 20182505.
  12. ^ Berridge MJ, Lipp P, Bootman MD (oktobar 2000). "The versatility and universality of calcium signalling". Nature Reviews. Molecular Cell Biology. 1 (1): 11–21. doi:10.1038/35036035. PMID 11413485. S2CID 13150466.
  13. ^ Mahn K, Hirst SJ, Ying S, Holt MR, Lavender P, Ojo OO, et al. (juni 2009). "Diminished sarco/endoplasmic reticulum Ca2+ ATPase (SERCA) expression contributes to airway remodelling in bronchial asthma". Proceedings of the National Academy of Sciences of the United States of America. 106 (26): 10775–80. Bibcode:2009PNAS..10610775M. doi:10.1073/pnas.0902295106. PMC 2699374. PMID 19541629.
  14. ^ Green KN, LaFerla FM (juli 2008). "Linking calcium to Abeta and Alzheimer's disease". Neuron. 59 (2): 190–4. doi:10.1016/j.neuron.2008.07.013. PMID 18667147. S2CID 17020942.
  15. ^ Verlaan DJ, Berlivet S, Hunninghake GM, Madore AM, Larivière M, Moussette S, et al. (septembar 2009). "Allele-specific chromatin remodeling in the ZPBP2/GSDMB/ORMDL3 locus associated with the risk of asthma and autoimmune disease". American Journal of Human Genetics. 85 (3): 377–93. doi:10.1016/j.ajhg.2009.08.007. PMC 2771592. PMID 19732864.
  16. ^ Kurreeman FA, Stahl EA, Okada Y, Liao K, Diogo D, Raychaudhuri S, et al. (mart 2012). "Use of a multiethnic approach to identify rheumatoid- arthritis-susceptibility loci, 1p36 and 17q12". American Journal of Human Genetics. 90 (3): 524–32. doi:10.1016/j.ajhg.2012.01.010. PMC 3309197. PMID 22365150.

Dopunska literatura uredi