OSBR 3

OSBR 3
Identifikatori
Aliasi	ORMDL3
Vanjski ID-jevi	OMIM: 610075 MGI: 1913862 HomoloGene: 57032 GeneCards: ORMDL3
Lokacija gena (čovjek)
Hrom.	Hromosom 17 (čovjek)
Kraj	39,927,601 bp
Lokacija gena (miš)
Hrom.	Hromosom 11 (miš)
Kraj	98,478,194 bp
Ontologija gena
Molekularna funkcija	• GO:0001948, GO:0016582 vezivanje za proteine;
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
	94103
	66612
	ENSG00000172057
	ENSMUSG00000038150
	Q8N138
	Q9CPZ6
	NM_139280; NM_001320801; NM_001320802; NM_001320803; NM_016471
	NM_025661
	NP_001307730; NP_001307731; NP_001307732; NP_644809
	NP_079937
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

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]

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

Aminokiselinska sekvenca

Simboli

C: Cistein
D: Asparaginska kiselina
E: Glutaminska kiselina

F: Fenilalanin
G: Glicin
H: Histidin
I: Izoleucin
K: Lizin
L: Leucin
M: Metionin
N: Asparagin
P: Prolin
Q: Glutamin
R: Arginin
S: Serin
T: Treonin
V: Valin
W: Triptofan
Y: Tirozin

10	20	30	40	50
MNVGTAHSEV	NPNTRVMNSR	GIWLSYVLAI	GLLHIVLLSI	PFVSVPVVWT
LTNLIHNMGM	YIFLHTVKGT	PFETPDQGKA	RLLTHWEQMD	YGVQFTASRK
FLTITPIVLY	FLTSFYTKYD	QIHFVLNTVS	LMSVLIPKLP	QLHGVRIFGI
NKY

Lokalizacija

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

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

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

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000172057 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000038150 - Ensembl, maj 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Entrez Gene: ORMDL sphingolipid biosynthesis regulator 3".
^ 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.
^ 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.
^ "UniProt, Q8N138". Pristupljeno September 12, 2017.
^ ^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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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

Hirota T, Harada M, Sakashita M, Doi S, Miyatake A, Fujita K, et al. (mart 2008). "Genetic polymorphism regulating ORM1-like 3 (Saccharomyces cerevisiae) expression is associated with childhood atopic asthma in a Japanese population". The Journal of Allergy and Clinical Immunology. 121 (3): 769–70. doi:10.1016/j.jaci.2007.09.038. PMID 18155279.
Galanter J, Choudhry S, Eng C, Nazario S, Rodríguez-Santana JR, Casal J, et al. (juni 2008). "ORMDL3 gene is associated with asthma in three ethnically diverse populations". American Journal of Respiratory and Critical Care Medicine. 177 (11): 1194–200. doi:10.1164/rccm.200711-1644OC. PMC 2408437. PMID 18310477.
Tavendale R, Macgregor DF, Mukhopadhyay S, Palmer CN (april 2008). "A polymorphism controlling ORMDL3 expression is associated with asthma that is poorly controlled by current medications". The Journal of Allergy and Clinical Immunology. 121 (4): 860–3. doi:10.1016/j.jaci.2008.01.015. PMID 18395550.
Sleiman PM, Annaiah K, Imielinski M, Bradfield JP, Kim CE, Frackelton EC, et al. (decembar 2008). "ORMDL3 variants associated with asthma susceptibility in North Americans of European ancestry". The Journal of Allergy and Clinical Immunology. 122 (6): 1225–7. doi:10.1016/j.jaci.2008.06.041. PMID 18760456.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000172057 - Ensembl, maj 2017

[refGRCm38Ensembl-2] 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.

[entrez-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.

[UniProt-8] "UniProt, Q8N138". Pristupljeno September 12, 2017.

[Davis_2018-9] 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.

[pmid12093374-10] 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.

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