Retikulon 4

Retikulon 4
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	2G31, 2JV5
Identifikatori
Aliasi	RTN4
Vanjski ID-jevi	OMIM: 604475 MGI: 1915835 HomoloGene: 10743 GeneCards: RTN4
Lokacija gena (čovjek)
Hrom.	Hromosom 2 (čovjek)
Kraj	55,112,621 bp
Lokacija gena (miš)
Hrom.	Hromosom 11 (miš)
Kraj	29,694,331 bp
Obrazac RNK ekspresije
	; ; ; ;
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• GO:0001948, GO:0016582 vezivanje za proteine; • vezivanje sa RNK; • cadherin binding; • ubiquitin protein ligase binding;
Ćelijska komponenta	• integral component of membrane; • projekcija ćelije; • nuclear envelope; • membrana; • integral component of endoplasmic reticulum membrane; • intracellular anatomical structure; • Endoplazmatski retikulum; • endoplasmic reticulum membrane; • ćelijska membrana; • Egzosom; • GO:0097483, GO:0097481 postsynaptic density; • endoplasmic reticulum tubular network; • neuronal cell body; • endoplasmic reticulum tubular network membrane; • međućelijske veze;
Biološki proces	• nuclear pore complex assembly; • regulation of apoptotic process; • cerebral cortex radial glia-guided migration; • regulation of branching morphogenesis of a nerve; • cardiac epithelial to mesenchymal transition; • negative regulation of axon extension; • GO:0097285 apoptoza; • negative regulation of axonogenesis; • nervous system development; • regulation of nervous system development; • endoplasmic reticulum tubular network formation; • endoplasmic reticulum tubular network organization; • regulation of cell migration; • negative regulation of cell growth; • axonal fasciculation; • positive regulation of epithelial cell migration; • positive regulation of mammary gland epithelial cell proliferation; • protein stabilization; • positive regulation of protein kinase B signaling; • positive regulation of protein localization to endoplasmic reticulum; • positive regulation of ERBB3 signaling pathway; • endoplasmic reticulum tubular network membrane organization; • blastocyst formation; • positive regulation of toll-like receptor 9 signaling pathway; • protein localization to lysosome; • cellular sphingolipid homeostasis;
	Izvori:Amigo / QuickGO
Ortolozi
	57142
	68585
	ENSG00000115310
	ENSMUSG00000020458
	Q9NQC3
	Q99P72
NM_007008; NM_020532; NM_153828; NM_207520; NM_207521;
	NM_001321859; NM_001321860; NM_001321861; NM_001321862; NM_001321863; NM_001321904
	NM_024226; NM_194051; NM_194052; NM_194053; NM_194054
NP_001308788; NP_001308789; NP_001308790; NP_001308791; NP_001308792;
	NP_001308833; NP_008939; NP_065393; NP_722550; NP_997403; NP_997404
	NP_077188; NP_918940; NP_918941; NP_918942; NP_918943
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Retikulon 4, znan i kao inhibitor izrastanja neurita ili Nogo, jest protein koji je kod ljudi kodiran genom RTN4 sa hromosoma 2.^[5]^[6]^[7] Identificiran je an kao inhibitor izrastanja neurita specifičnog za centralni nervni sistem. Tokom nervnog razvoja, Nogo se uglavnom eksprimira putem neurona i pruža inhibitorni signal za migraciju i klijanje endotelnih (vrh) ćelija CNS-a, čime se ograničava gustoća krvnih sudova.

Aminokiselinska sekvenca[uredi | uredi izvor]

Dužina polipeptidnog lanca je 473 aminokiseline, a molekulska težina 50.708 Da.^[7]

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
MKRASAGGSR	LLAWVLWLQA	WQVAAPCPGA	CVCYNEPKVT	TSCPQQGLQA
VPVGIPAASQ	RIFLHGNRIS	HVPAASFRAC	RNLTILWLHS	NVLARIDAAA
FTGLALLEQL	DLSDNAQLRS	VDPATFHGLG	RLHTLHLDRC	GLQELGPGLF
RGLAALQYLY	LQDNALQALP	DDTFRDLGNL	THLFLHGNRI	SSVPERAFRG
LHSLDRLLLH	QNRVAHVHPH	AFRDLGRLMT	LYLFANNLSA	LPTEALAPLR
ALQYLRLNDN	PWVCDCRARP	LWAWLQKFRG	SSSEVPCSLP	QRLAGRDLKR
LAANDLQGCA	VATGPYHPIW	TGRATDEEPL	GLPKCCQPDA	ADKASVLEPG
RPASAGNALK	GRVPPGDSPP	GNGSGPRHIN	DSPFGTLPGS	AEPPLTAVRP
EGSEPPGFPT	SGPRRRPGCS	RKNRTRSHCR	LGQAGSGGGG	TGDSEGSGAL
PSLTCSLTPL	GLALVLWTVL	GPC

Funkcija[uredi | uredi izvor]

Ovaj gen pripada porodici retikulonskih kodirajućih gena. Retikuloni su povezani s endoplazmatskim retikulumom i uključeni su u neuroendokrinu sekreciju ili u membranski promet u neuroendokrinim ćelijamama. Proizvod ovog gena je moćan inhibitor rasta neurita koji takođe može pomoći u blokiranju regeneracije centralnog nervnog sistema kod viših kičmenjaka. Identificirane su alternativno prerađene varijante transkripta izvedene iz diferencijalne prerade i upotrebe diferencijalnog promotora i kodiranja različitih izoformi.^[7] Postoje tri izoforme: Nogo A, B i C. Nogo- A ima dva poznata inhibitorna domena, uključujući amino-Nogo, na N-terminalu i Nogo-66, koji čini molekule vanćelijske petlje. I amino-Nogo i Nogo-66 su uključeni u inhibitorne odgovore, gdje je amino-Nogo jak inhibitor rasta neurita, a Nogo-66 uključen je u uništavanje konusa rasta.^[8]

Istraživanja sugeriraju da će blokiranje Nogo-A tokom oštećenja neurona (od bolesti kao što je multipla skleroza) pomoći u zaštiti ili obnavljanju oštećenih neurona.^[8]^[9] Istraživanje mehanizama djelovanja ovog proteina predstavlja veliki potencijal za liječenje autoimuno posredovanih demijelinizirajućih oboljenja i regeneracija povreda kičmene moždine. Također je utvrđeno da je ključni faktor u procesu u kojem fizička vježba poboljšava procese učenja i pamćenja u mozgu.^[10] Također se pokazalo da Nogo-A negativno regulira rast i popravak krvnih sudova nakon ishemijskog moždanog udara. Genetička delecija i blokada Nogo-A, posredovana antitijelima doveli su do poboljšane revaskularizacije i funkcionalnog oporavka u eksperimentalnom mišjem modelu moždanog udara.^[11]^[12]^[13] Moreover, vascular leakage, a major complication following stroke, was reduced following anti-Nogo-A antibody treatment.^[14]

Interakcije[uredi | uredi izvor]

Pokazalo se da retikulon 4 reaguje sa WWP1,^[15] BCL2-liki 1^[16] i Bcl-2.^[16]

Također pogledajte[uredi | uredi izvor]

Retikulonski receptor 4

Reference[uredi | uredi izvor]

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000115310 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000020458 - 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.
^ GrandPré T, Nakamura F, Vartanian T, Strittmatter SM (Jan 2000). "Identification of the Nogo inhibitor of axon regeneration as a Reticulon protein". Nature. 403 (6768): 439–44. Bibcode:2000Natur.403..439G. doi:10.1038/35000226. PMID 10667797. S2CID 1926168.
^ Yang J, Yu L, Bi AD, Zhao SY (June 2000). "Assignment of the human reticulon 4 gene (RTN4) to chromosome 2p14-->2p13 by radiation hybrid mapping". Cytogenetics and Cell Genetics. 88 (1–2): 101–2. doi:10.1159/000015499. PMID 10773680. S2CID 37521141.
^ ^a ^b ^c "Entrez Gene: RTN4 reticulon 4".
^ ^a ^b Karnezis T, Mandemakers W, McQualter JL, Zheng B, Ho PP, Jordan KA, et al. (July 2004). "The neurite outgrowth inhibitor Nogo A is involved in autoimmune-mediated demyelination". Nature Neuroscience. 7 (7): 736–44. doi:10.1038/nn1261. PMID 15184901. S2CID 9613584.
^ Sozmen EG, Rosenzweig S, Llorente IL, DiTullio DJ, Machnicki M, Vinters HV, et al. (December 2016). "Nogo receptor blockade overcomes remyelination failure after white matter stroke and stimulates functional recovery in aged mice". Proceedings of the National Academy of Sciences of the United States of America. 113 (52): E8453–E8462. doi:10.1073/pnas.1615322113. PMC 5206535. PMID 27956620.
^ Lee H, Raiker SJ, Venkatesh K, Geary R, Robak LA, Zhang Y, Yeh HH, Shrager P, Giger RJ (March 2008). "Synaptic function for the Nogo-66 receptor NgR1: regulation of dendritic spine morphology and activity-dependent synaptic strength". The Journal of Neuroscience. 28 (11): 2753–65. doi:10.1523/JNEUROSCI.5586-07.2008. PMC 6670664. PMID 18337405. Sažetak – Eurek Alert.
^ Rust R, Grönnert L, Gantner C, Enzler A, Mulders G, Weber RZ, et al. (July 2019). "Nogo-A targeted therapy promotes vascular repair and functional recovery following stroke". Proceedings of the National Academy of Sciences of the United States of America. 116 (28): 14270–14279. doi:10.1073/pnas.1905309116. PMC 6628809. PMID 31235580.
^ Rust, R; Grönnert, L; Weber, RZ; Mulders, G; Schwab, ME (September 2019). "Refueling the Ischemic CNS: Guidance Molecules for Vascular Repair". Trends in Neurosciences. 42 (9): 644–656. doi:10.1016/j.tins.2019.05.006. PMID 31285047. S2CID 195834057.
^ Rust, R; Gantner, C; Schwab, ME (January 2019). "Pro- and antiangiogenic therapies: current status and clinical implications". FASEB Journal. 33 (1): 34–48. doi:10.1096/fj.201800640RR. PMID 30085886. S2CID 51937342.
^ Rust R, Weber RZ, Grönnert L, Mulders G, Maurer MA, Hofer AS, et al. (December 2019). "Anti-Nogo-A antibodies prevent vascular leakage and act as pro-angiogenic factors following stroke". Scientific Reports. 9 (1): 20040. Bibcode:2019NatSR...920040R. doi:10.1038/s41598-019-56634-1. PMC 6934709. PMID 31882970.
^ Qin H, Pu HX, Li M, Ahmed S, Song J (Dec 2008). "Identification and structural mechanism for a novel interaction between a ubiquitin ligase WWP1 and Nogo-A, a key inhibitor for central nervous system regeneration". Biochemistry. 47 (51): 13647–58. doi:10.1021/bi8017976. PMID 19035836.
^ ^a ^b Tagami S, Eguchi Y, Kinoshita M, Takeda M, Tsujimoto Y (Nov 2000). "A novel protein, RTN-XS, interacts with both Bcl-XL and Bcl-2 on endoplasmic reticulum and reduces their anti-apoptotic activity". Oncogene. 19 (50): 5736–46. doi:10.1038/sj.onc.1203948. PMID 11126360.

Dopunska literatura[uredi | uredi izvor]

Teng FY, Tang BL (Aug 2008). "Cell autonomous function of Nogo and reticulons: The emerging story at the endoplasmic reticulum". Journal of Cellular Physiology. 216 (2): 303–8. doi:10.1002/jcp.21434. PMID 18330888. S2CID 34163142.
Ng CE, Tang BL (Mar 2002). "Nogos and the Nogo-66 receptor: factors inhibiting CNS neuron regeneration". Journal of Neuroscience Research. 67 (5): 559–65. doi:10.1002/jnr.10134. PMID 11891768. S2CID 26061828.
Watari A, Yutsudo M (Jan 2003). "Multi-functional gene ASY/Nogo/RTN-X/RTN4: apoptosis, tumor suppression, and inhibition of neuronal regeneration". Apoptosis. 8 (1): 5–9. doi:10.1023/A:1021639016300. PMID 12510146. S2CID 37206000.
Schweigreiter R, Bandtlow CE (2006). "Nogo in the injured spinal cord". Journal of Neurotrauma. 23 (3–4): 384–96. doi:10.1089/neu.2006.23.384. PMID 16629624.
Nagase T, Ishikawa K, Suyama M, Kikuno R, Hirosawa M, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O (Dec 1998). "Prediction of the coding sequences of unidentified human genes. XII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Research. 5 (6): 355–64. doi:10.1093/dnares/5.6.355. PMID 10048485.
Prinjha R, Moore SE, Vinson M, Blake S, Morrow R, Christie G, Michalovich D, Simmons DL, Walsh FS (Jan 2000). "Inhibitor of neurite outgrowth in humans". Nature. 403 (6768): 383–4. doi:10.1038/35000287. PMID 10667780. S2CID 205004005.
Chen MS, Huber AB, van der Haar ME, Frank M, Schnell L, Spillmann AA, Christ F, Schwab ME (Jan 2000). "Nogo-A is a myelin-associated neurite outgrowth inhibitor and an antigen for monoclonal antibody IN-1". Nature. 403 (6768): 434–9. Bibcode:2000Natur.403..434C. doi:10.1038/35000219. PMID 10667796. S2CID 4388618.
Zhang QH, Ye M, Wu XY, Ren SX, Zhao M, Zhao CJ, Fu G, Shen Y, Fan HY, Lu G, Zhong M, Xu XR, Han ZG, Zhang JW, Tao J, Huang QH, Zhou J, Hu GX, Gu J, Chen SJ, Chen Z (Oct 2000). "Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells". Genome Research. 10 (10): 1546–60. doi:10.1101/gr.140200. PMC 310934. PMID 11042152.
Hartley JL, Temple GF, Brasch MA (Nov 2000). "DNA cloning using in vitro site-specific recombination". Genome Research. 10 (11): 1788–95. doi:10.1101/gr.143000. PMC 310948. PMID 11076863.
Tagami S, Eguchi Y, Kinoshita M, Takeda M, Tsujimoto Y (Nov 2000). "A novel protein, RTN-XS, interacts with both Bcl-XL and Bcl-2 on endoplasmic reticulum and reduces their anti-apoptotic activity". Oncogene. 19 (50): 5736–46. doi:10.1038/sj.onc.1203948. PMID 11126360.
Fournier AE, GrandPre T, Strittmatter SM (Jan 2001). "Identification of a receptor mediating Nogo-66 inhibition of axonal regeneration". Nature. 409 (6818): 341–6. Bibcode:2001Natur.409..341F. doi:10.1038/35053072. PMID 11201742. S2CID 4404627.
Josephson A, Widenfalk J, Widmer HW, Olson L, Spenger C (Jun 2001). "NOGO mRNA expression in adult and fetal human and rat nervous tissue and in weight drop injury". Experimental Neurology. 169 (2): 319–28. doi:10.1006/exnr.2001.7659. PMID 11358445. S2CID 23996169.
Zhou ZM, Sha JH, Li JM, Lin M, Zhu H, Zhou YD, Wang LR, Zhu H, Wang YQ, Zhou KY (Feb 2002). "Expression of a novel reticulon-like gene in human testis". Reproduction. 123 (2): 227–34. doi:10.1530/rep.0.1230227. PMID 11866689.
GrandPré T, Li S, Strittmatter SM (May 2002). "Nogo-66 receptor antagonist peptide promotes axonal regeneration". Nature. 417 (6888): 547–51. Bibcode:2002Natur.417..547G. doi:10.1038/417547a. PMID 12037567. S2CID 4414714.
Hu WH, Hausmann ON, Yan MS, Walters WM, Wong PK, Bethea JR (Apr 2002). "Identification and characterization of a novel Nogo-interacting mitochondrial protein (NIMP)". Journal of Neurochemistry. 81 (1): 36–45. doi:10.1046/j.1471-4159.2002.00788.x. PMID 12067236. S2CID 38794348.
Liu BP, Fournier A, GrandPré T, Strittmatter SM (Aug 2002). "Myelin-associated glycoprotein as a functional ligand for the Nogo-66 receptor". Science. 297 (5584): 1190–3. Bibcode:2002Sci...297.1190L. doi:10.1126/science.1073031. PMID 12089450. S2CID 1357777.
Dupuis L, Gonzalez de Aguilar JL, di Scala F, Rene F, de Tapia M, Pradat PF, Lacomblez L, Seihlan D, Prinjha R, Walsh FS, Meininger V, Loeffler JP (Aug 2002). "Nogo provides a molecular marker for diagnosis of amyotrophic lateral sclerosis". Neurobiology of Disease. 10 (3): 358–65. doi:10.1006/nbdi.2002.0522. PMID 12270696. S2CID 45996722.
Taketomi M, Kinoshita N, Kimura K, Kitada M, Noda T, Asou H, Nakamura T, Ide C (Oct 2002). "Nogo-A expression in mature oligodendrocytes of rat spinal cord in association with specific molecules". Neuroscience Letters. 332 (1): 37–40. doi:10.1016/S0304-3940(02)00910-2. hdl:2433/148718. PMID 12377379. S2CID 13433362.
Li M, Shi J, Wei Z, Teng FY, Tang BL, Song J (Sep 2004). "Structural characterization of the human Nogo-A functional domains. Solution structure of Nogo-40, a Nogo-66 receptor antagonist enhancing injured spinal cord regeneration". European Journal of Biochemistry. 271 (17): 3512–22. doi:10.1111/j.0014-2956.2004.04286.x. PMID 15317586.
Li M, Liu J, Song J (Aug 2006). "Nogo goes in the pure water: solution structure of Nogo-60 and design of the structured and buffer-soluble Nogo-54 for enhancing CNS regeneration". Protein Science. 15 (8): 1835–41. doi:10.1110/ps.062306906. PMC 2242580. PMID 16877707.
Li M, Song J (Jul 2007). "The N- and C-termini of the human Nogo molecules are intrinsically unstructured: bioinformatics, CD, NMR characterization, and functional implications". Proteins. 68 (1): 100–8. doi:10.1002/prot.21385. PMID 17397058. S2CID 21507005.
Li M, Song J (Aug 2007). "Nogo-B receptor possesses an intrinsically unstructured ectodomain and a partially folded cytoplasmic domain". Biochemical and Biophysical Research Communications. 360 (1): 128–34. doi:10.1016/j.bbrc.2007.06.031. PMID 17585875.

Vanjski linkovi[uredi | uredi izvor]

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000115310 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000020458 - 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.

[pmid10667797-5] GrandPré T, Nakamura F, Vartanian T, Strittmatter SM (Jan 2000). "Identification of the Nogo inhibitor of axon regeneration as a Reticulon protein". Nature. 403 (6768): 439–44. Bibcode:2000Natur.403..439G. doi:10.1038/35000226. PMID 10667797. S2CID 1926168.

[pmid10773680-6] Yang J, Yu L, Bi AD, Zhao SY (June 2000). "Assignment of the human reticulon 4 gene (RTN4) to chromosome 2p14-->2p13 by radiation hybrid mapping". Cytogenetics and Cell Genetics. 88 (1–2): 101–2. doi:10.1159/000015499. PMID 10773680. S2CID 37521141.

[entrez-7] "Entrez Gene: RTN4 reticulon 4".

[Karnezis2004-8] Karnezis T, Mandemakers W, McQualter JL, Zheng B, Ho PP, Jordan KA, et al. (July 2004). "The neurite outgrowth inhibitor Nogo A is involved in autoimmune-mediated demyelination". Nature Neuroscience. 7 (7): 736–44. doi:10.1038/nn1261. PMID 15184901. S2CID 9613584.

[9] Sozmen EG, Rosenzweig S, Llorente IL, DiTullio DJ, Machnicki M, Vinters HV, et al. (December 2016). "Nogo receptor blockade overcomes remyelination failure after white matter stroke and stimulates functional recovery in aged mice". Proceedings of the National Academy of Sciences of the United States of America. 113 (52): E8453–E8462. doi:10.1073/pnas.1615322113. PMC 5206535. PMID 27956620.

[pmid18337405-10] Lee H, Raiker SJ, Venkatesh K, Geary R, Robak LA, Zhang Y, Yeh HH, Shrager P, Giger RJ (March 2008). "Synaptic function for the Nogo-66 receptor NgR1: regulation of dendritic spine morphology and activity-dependent synaptic strength". The Journal of Neuroscience. 28 (11): 2753–65. doi:10.1523/JNEUROSCI.5586-07.2008. PMC 6670664. PMID 18337405. Sažetak – Eurek Alert.

[11] Rust R, Grönnert L, Gantner C, Enzler A, Mulders G, Weber RZ, et al. (July 2019). "Nogo-A targeted therapy promotes vascular repair and functional recovery following stroke". Proceedings of the National Academy of Sciences of the United States of America. 116 (28): 14270–14279. doi:10.1073/pnas.1905309116. PMC 6628809. PMID 31235580.

[12] Rust, R; Grönnert, L; Weber, RZ; Mulders, G; Schwab, ME (September 2019). "Refueling the Ischemic CNS: Guidance Molecules for Vascular Repair". Trends in Neurosciences. 42 (9): 644–656. doi:10.1016/j.tins.2019.05.006. PMID 31285047. S2CID 195834057.

[13] Rust, R; Gantner, C; Schwab, ME (January 2019). "Pro- and antiangiogenic therapies: current status and clinical implications". FASEB Journal. 33 (1): 34–48. doi:10.1096/fj.201800640RR. PMID 30085886. S2CID 51937342.

[14] Rust R, Weber RZ, Grönnert L, Mulders G, Maurer MA, Hofer AS, et al. (December 2019). "Anti-Nogo-A antibodies prevent vascular leakage and act as pro-angiogenic factors following stroke". Scientific Reports. 9 (1): 20040. Bibcode:2019NatSR...920040R. doi:10.1038/s41598-019-56634-1. PMC 6934709. PMID 31882970.

[pmid19035836-15] Qin H, Pu HX, Li M, Ahmed S, Song J (Dec 2008). "Identification and structural mechanism for a novel interaction between a ubiquitin ligase WWP1 and Nogo-A, a key inhibitor for central nervous system regeneration". Biochemistry. 47 (51): 13647–58. doi:10.1021/bi8017976. PMID 19035836.

[pmid11126360-16] Tagami S, Eguchi Y, Kinoshita M, Takeda M, Tsujimoto Y (Nov 2000). "A novel protein, RTN-XS, interacts with both Bcl-XL and Bcl-2 on endoplasmic reticulum and reduces their anti-apoptotic activity". Oncogene. 19 (50): 5736–46. doi:10.1038/sj.onc.1203948. PMID 11126360.

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