ID RTN4_MOUSE Reviewed; 1162 AA. AC Q99P72; Q5DTK9; Q78NS1; Q7TNB7; Q80W95; Q8BGK7; Q8BGM9; Q8BH78; Q8BHF5; AC Q8K290; Q8K3G8; Q9CTE3; DT 16-NOV-2001, integrated into UniProtKB/Swiss-Prot. DT 02-MAY-2006, sequence version 2. DT 27-MAR-2024, entry version 193. DE RecName: Full=Reticulon-4 {ECO:0000305}; DE AltName: Full=Neurite outgrowth inhibitor; DE Short=Nogo protein {ECO:0000303|PubMed:27786289}; GN Name=Rtn4 {ECO:0000312|MGI:MGI:1915835}; GN Synonyms=Kiaa0886, Nogo {ECO:0000303|PubMed:27786289}; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS A; B; B2; C AND D), AND RP ALTERNATIVE SPLICING. RC STRAIN=129/Sv; RX PubMed=12488097; DOI=10.1016/s0022-2836(02)01179-8; RA Oertle T., Huber C., van der Putten H., Schwab M.E.; RT "Genomic structure and functional characterisation of the promoters of RT human and mouse nogo/rtn4."; RL J. Mol. Biol. 325:299-323(2003). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM C). RC TISSUE=Adipocyte; RA Coulson A.C., Craggs P.D., Morris N.J.; RT "Mouse vp20/RTN4C cDNA."; RL Submitted (DEC-2000) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A). RC STRAIN=BALB/cJ; RA Jin W., Long M., Li R., Ju G.; RT "Cloning and expression of the mouse Nogo-A protein."; RL Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A). RC TISSUE=Fetal brain; RA Okazaki N., Kikuno R.F., Ohara R., Inamoto S., Nagase T., Ohara O., RA Koga H.; RT "Prediction of the coding sequences of mouse homologues of KIAA gene. The RT complete nucleotide sequences of mouse KIAA-homologous cDNAs identified by RT screening of terminal sequences of cDNA clones randomly sampled from size- RT fractionated libraries."; RL Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=C57BL/6J; RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112; RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S., RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., RA Eichler E.E., Ponting C.P.; RT "Lineage-specific biology revealed by a finished genome assembly of the RT mouse."; RL PLoS Biol. 7:E1000112-E1000112(2009). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A). RC STRAIN=C57BL/6J; TISSUE=Brain, and Mammary gland; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP NUCLEOTIDE SEQUENCE [MRNA] OF 585-1162. RA Tozaki H., Hirata T.; RT "The partial sequence of mouse nogo-A cDNA clone#4109."; RL Submitted (OCT-2001) to the EMBL/GenBank/DDBJ databases. RN [9] RP PROTEIN SEQUENCE OF 975-982; 1061-1074 AND 1079-1090, AND IDENTIFICATION BY RP MASS SPECTROMETRY. RC STRAIN=C57BL/6J; TISSUE=Brain; RA Lubec G., Kang S.U.; RL Submitted (APR-2007) to UniProtKB. RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1133-1162. RC STRAIN=C57BL/6J; TISSUE=Embryo; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J., RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [11] RP INTERACTION WITH RTN4IP1. RX PubMed=12067236; DOI=10.1046/j.1471-4159.2002.00788.x; RA Hu W.-H., Hausmann O.N., Yan M.-S., Walters W.M., Wong P.K.Y., Bethea J.R.; RT "Identification and characterization of a novel Nogo-interacting RT mitochondrial protein (NIMP)."; RL J. Neurochem. 81:36-45(2002). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-145 AND SER-690, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic brain; RX PubMed=15345747; DOI=10.1074/mcp.m400085-mcp200; RA Ballif B.A., Villen J., Beausoleil S.A., Schwartz D., Gygi S.P.; RT "Phosphoproteomic analysis of the developing mouse brain."; RL Mol. Cell. Proteomics 3:1093-1101(2004). RN [13] RP FUNCTION (ISOFORMS A AND B), DISRUPTION PHENOTYPE (ISOFORMS A AND B), AND RP TISSUE SPECIFICITY. RX PubMed=15034570; DOI=10.1038/nm1020; RA Acevedo L., Yu J., Erdjument-Bromage H., Miao R.Q., Kim J.E., Fulton D., RA Tempst P., Strittmatter S.M., Sessa W.C.; RT "A new role for Nogo as a regulator of vascular remodeling."; RL Nat. Med. 10:382-388(2004). RN [14] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain; RX PubMed=16452087; DOI=10.1074/mcp.t500041-mcp200; RA Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L.; RT "Comprehensive identification of phosphorylation sites in postsynaptic RT density preparations."; RL Mol. Cell. Proteomics 5:914-922(2006). RN [15] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain cortex; RX PubMed=17114649; DOI=10.1074/mcp.m600046-mcp200; RA Munton R.P., Tweedie-Cullen R., Livingstone-Zatchej M., Weinandy F., RA Waidelich M., Longo D., Gehrig P., Potthast F., Rutishauser D., Gerrits B., RA Panse C., Schlapbach R., Mansuy I.M.; RT "Qualitative and quantitative analyses of protein phosphorylation in naive RT and stimulated mouse synaptosomal preparations."; RL Mol. Cell. Proteomics 6:283-293(2007). RN [16] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=17242355; DOI=10.1073/pnas.0609836104; RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.; RT "Large-scale phosphorylation analysis of mouse liver."; RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007). RN [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-145; SER-344 AND SER-489, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006; RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M., RA Thibault P.; RT "The phagosomal proteome in interferon-gamma-activated macrophages."; RL Immunity 30:143-154(2009). RN [18] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-16 AND SER-105, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic fibroblast; RX PubMed=19131326; DOI=10.1074/mcp.m800451-mcp200; RA Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.; RT "Large scale localization of protein phosphorylation by use of electron RT capture dissociation mass spectrometry."; RL Mol. Cell. Proteomics 8:904-912(2009). RN [19] RP FUNCTION (ISOFORM B), DISRUPTION PHENOTYPE, AND INDUCTION BY ISCHEMIA RP (ISOFORMS B AND B2). RX PubMed=19805174; DOI=10.1073/pnas.0907359106; RA Yu J., Fernandez-Hernando C., Suarez Y., Schleicher M., Hao Z., RA Wright P.L., DiLorenzo A., Kyriakides T.R., Sessa W.C.; RT "Reticulon 4B (Nogo-B) is necessary for macrophage infiltration and tissue RT repair."; RL Proc. Natl. Acad. Sci. U.S.A. 106:17511-17516(2009). RN [20] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-165; SER-167; SER-344; RP THR-348; SER-489; SER-690; SER-727; SER-768 AND SER-857, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, RC Pancreas, Spleen, and Testis; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [21] RP FUNCTION (ISOFORM A), DISRUPTION PHENOTYPE (ISOFORM A), AND DEVELOPMENTAL RP STAGE (ISOFORM A). RX PubMed=20093372; DOI=10.1093/cercor/bhp307; RA Mathis C., Schroeter A., Thallmair M., Schwab M.E.; RT "Nogo-a regulates neural precursor migration in the embryonic mouse RT cortex."; RL Cereb. Cortex 20:2380-2390(2010). RN [22] RP FUNCTION (ISOFORM A), AND DISRUPTION PHENOTYPE (ISOFORM A). RX PubMed=20573699; DOI=10.1242/dev.048371; RA Petrinovic M.M., Duncan C.S., Bourikas D., Weinman O., Montani L., RA Schroeter A., Maerki D., Sommer L., Stoeckli E.T., Schwab M.E.; RT "Neuronal Nogo-A regulates neurite fasciculation, branching and extension RT in the developing nervous system."; RL Development 137:2539-2550(2010). RN [23] RP FUNCTION (ISOFORM B), AND DISRUPTION PHENOTYPE (ISOFORMS A AND B). RX PubMed=21183689; DOI=10.1182/blood-2010-04-281956; RA Di Lorenzo A., Manes T.D., Davalos A., Wright P.L., Sessa W.C.; RT "Endothelial reticulon-4B (Nogo-B) regulates ICAM-1-mediated leukocyte RT transmigration and acute inflammation."; RL Blood 117:2284-2295(2011). RN [24] RP FUNCTION (ISOFORM B), AND DEVELOPMENTAL STAGE. RX PubMed=23299899; DOI=10.1002/hep.26235; RA Gao L., Utsumi T., Tashiro K., Liu B., Zhang D., Swenson E.S., Iwakiri Y.; RT "Reticulon 4B (Nogo-B) facilitates hepatocyte proliferation and liver RT regeneration in mice."; RL Hepatology 57:1992-2003(2013). RN [25] RP FUNCTION (ISOFORM A), DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, AND RP DEVELOPMENTAL STAGE. RX PubMed=23625008; DOI=10.1073/pnas.1216203110; RA Waelchli T., Pernet V., Weinmann O., Shiu J.Y., Guzik-Kornacka A., RA Decrey G., Yueksel D., Schneider H., Vogel J., Ingber D.E., Vogel V., RA Frei K., Schwab M.E.; RT "Nogo-A is a negative regulator of CNS angiogenesis."; RL Proc. Natl. Acad. Sci. U.S.A. 110:E1943-E1952(2013). RN [26] RP FUNCTION (ISOFORM B), DISRUPTION PHENOTYPE (ISOFORMS A AND B), TISSUE RP SPECIFICITY (ISOFORMS B AND B2), INTERACTION WITH GRAMD4 (ISOFORM B), AND RP SUBCELLULAR LOCATION (ISOFORM B). RX PubMed=25917084; DOI=10.4049/jimmunol.1402006; RA Kimura T., Endo S., Inui M., Saitoh S., Miyake K., Takai T.; RT "Endoplasmic Protein Nogo-B (RTN4-B) Interacts with GRAMD4 and Regulates RT TLR9-Mediated Innate Immune Responses."; RL J. Immunol. 194:5426-5436(2015). RN [27] RP FUNCTION (ISOFORM B), SUBCELLULAR LOCATION (ISOFORM B), INTERACTION WITH RP SPTLC1, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY (ISOFORM B). RX PubMed=26301690; DOI=10.1038/nm.3934; RA Cantalupo A., Zhang Y., Kothiya M., Galvani S., Obinata H., Bucci M., RA Giordano F.J., Jiang X.C., Hla T., Di Lorenzo A.; RT "Nogo-B regulates endothelial sphingolipid homeostasis to control vascular RT function and blood pressure."; RL Nat. Med. 21:1028-1037(2015). RN [28] RP FUNCTION (ISOFORM B), INDUCTION BY LPS (ISOFORM B), AND TISSUE SPECIFICITY RP (ISOFORM B). RX PubMed=26174362; DOI=10.1038/srep12061; RA Xu W., Zhu Y., Ning Y., Dong Y., Huang H., Zhang W., Sun Q., Li Q.; RT "Nogo-B protects mice against lipopolysaccharide-induced acute lung RT injury."; RL Sci. Rep. 5:12061-12061(2015). RN [29] RP FUNCTION (ISOFORM C), DISRUPTION PHENOTYPE (ISOFORM C), TISSUE SPECIFICITY RP (ISOFORM C), AND INDUCTION BY HYPOXIA. RX PubMed=27763637; DOI=10.1038/cddis.2016.331; RA Jia S., Qiao X., Ye J., Fang X., Xu C., Cao Y., Zheng M.; RT "Nogo-C regulates cardiomyocyte apoptosis during mouse myocardial RT infarction."; RL Cell Death Dis. 7:E2432-E2432(2016). RN [30] RP FUNCTION (ISOFORM 2), SUBCELLULAR LOCATION (ISOFORMS A AND B), AND TISSUE RP SPECIFICITY (ISOFORMS A; B AND C). RX PubMed=27786289; DOI=10.1038/srep35969; RA Raemoe O., Kumar D., Gucciardo E., Joensuu M., Saarekas M., Vihinen H., RA Belevich I., Smolander O.P., Qian K., Auvinen P., Jokitalo E.; RT "NOGO-A/RTN4A and NOGO-B/RTN4B are simultaneously expressed in epithelial, RT fibroblast and neuronal cells and maintain ER morphology."; RL Sci. Rep. 6:35969-35969(2016). RN [31] RP INTERACTION WITH REEP5, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY RP (ISOFORMS A AND B). RX PubMed=32075961; DOI=10.1038/s41467-019-14143-9; RA Lee S.H., Hadipour-Lakmehsari S., Murthy H.R., Gibb N., Miyake T., RA Teng A.C.T., Cosme J., Yu J.C., Moon M., Lim S., Wong V., Liu P., RA Billia F., Fernandez-Gonzalez R., Stagljar I., Sharma P., Kislinger T., RA Scott I.C., Gramolini A.O.; RT "REEP5 depletion causes sarco-endoplasmic reticulum vacuolization and RT cardiac functional defects."; RL Nat. Commun. 11:965-965(2020). RN [32] RP INTERACTION WITH PANTS, AND SUBCELLULAR LOCATION. RX PubMed=35771867; DOI=10.1371/journal.pone.0269404; RA Kragness S., Clark Z., Mullin A., Guidry J., Earls L.R.; RT "An Rtn4/Nogo-A-interacting micropeptide modulates synaptic plasticity with RT age."; RL PLoS ONE 17:e0269404-e0269404(2022). CC -!- FUNCTION: Required to induce the formation and stabilization of CC endoplasmic reticulum (ER) tubules. They regulate membrane CC morphogenesis in the ER by promoting tubular ER production. They CC influence nuclear envelope expansion, nuclear pore complex formation CC and proper localization of inner nuclear membrane proteins. However CC each isoform have specific functions mainly depending on their tissue CC expression specificities. {ECO:0000250|UniProtKB:Q9NQC3}. CC -!- FUNCTION: [Isoform A]: Developmental neurite growth regulatory factor CC with a role as a negative regulator of axon-axon adhesion and growth, CC and as a facilitator of neurite branching. Regulates neurite CC fasciculation, branching and extension in the developing nervous system CC (PubMed:20573699). Involved in down-regulation of growth, stabilization CC of wiring and restriction of plasticity in the adult CNS (By CC similarity). Regulates the radial migration of cortical neurons via an CC RTN4R-LINGO1 containing receptor complex (PubMed:20573699). Acts as a CC negative regulator of central nervous system angiogenesis. Inhibits CC spreading, migration and sprouting of primary brain microvascular CC endothelial cells (MVECs). Also induces the retraction of MVECs CC lamellipodia and filopodia in a ROCK pathway-dependent manner CC (PubMed:23625008). {ECO:0000250|UniProtKB:Q9NQC3, CC ECO:0000269|PubMed:20573699, ECO:0000269|PubMed:23625008}. CC -!- FUNCTION: [Isoform B]: Mainly function in endothelial cells and CC vascular smooth muscle cells, is also involved in immune system CC regulation (Probable). Modulator of vascular remodeling, promotes the CC migration of endothelial cells but inhibits the migration of vascular CC smooth muscle cells (PubMed:15034570). Regulates endothelial CC sphingolipid biosynthesis with direct effects on vascular function and CC blood pressure. Inhibits serine palmitoyltransferase, SPTLC1, the rate- CC limiting enzyme of the novo sphingolipid biosynthetic pathway, thereby CC controlling production of endothelial sphingosine-1-phosphate (S1P) CC (PubMed:26301690). Required to promote macrophage homing and functions CC such as cytokine/chemokine gene expression involved in angiogenesis, CC arteriogenesis and tissue repair (PubMed:19805174). Mediates ICAM1 CC induced transendothelial migration of leukocytes such as monocytes and CC neutrophils and acute inflammation (PubMed:21183689). Necessary for CC immune responses triggered by nucleic acid sensing TLRs, such as TLR9, CC is required for proper TLR9 location to endolysosomes CC (PubMed:25917084). Also involved in immune response to LPS CC (PubMed:26174362). Plays a role in liver regeneration through the CC modulation of hepatocytes proliferation (PubMed:23299899). Reduces the CC anti-apoptotic activity of Bcl-xl and Bcl-2. This is likely consecutive CC to their change in subcellular location, from the mitochondria to the CC endoplasmic reticulum, after binding and sequestration. With isoform C, CC inhibits BACE1 activity and amyloid precursor protein processing (By CC similarity). {ECO:0000250|UniProtKB:Q9NQC3, CC ECO:0000269|PubMed:15034570, ECO:0000269|PubMed:19805174, CC ECO:0000269|PubMed:21183689, ECO:0000269|PubMed:23299899, CC ECO:0000269|PubMed:25917084, ECO:0000269|PubMed:26174362, CC ECO:0000269|PubMed:26301690, ECO:0000305}. CC -!- FUNCTION: [Isoform C]: Regulates cardiomyocyte apoptosis upon hypoxic CC conditions (PubMed:27763637). With isoform B, inhibits BACE1 activity CC and amyloid precursor protein processing (By similarity). CC {ECO:0000250|UniProtKB:Q9NQC3, ECO:0000269|PubMed:27763637}. CC -!- SUBUNIT: Binds to RTN4R (By similarity). Interacts with ATL1 (By CC similarity). Interacts with TMEM170A (By similarity). Interacts with CC RTN4IP1 (PubMed:12067236). {ECO:0000250|UniProtKB:Q9NQC3, CC ECO:0000269|PubMed:12067236}. CC -!- SUBUNIT: [Isoform A]: Interacts in trans with CNTNAP1 (By similarity). CC Interacts with REEP5 (PubMed:32075961). Interacts with GPR50 (By CC similarity). Interacts with synaptic plasticity regulator PANTS; the CC interaction results in enhanced RTN4-mediated inhibition of AMPA CC receptor clustering (PubMed:35771867). {ECO:0000250|UniProtKB:Q9JK11, CC ECO:0000269|PubMed:32075961}. CC -!- SUBUNIT: [Isoform B]: Homodimer (By similarity). Interacts with CC BAD/Bcl-xl and BCL2. Interact with RTN3 (By similarity). Interacts with CC NGBR (By similarity). Interacts with SPTLC1 (PubMed:26301690). CC Interacts with GRAMD4 (PubMed:25917084). Interacts with CDH5 (By CC similarity). Interacts with BACE1 and BACE2 (By similarity). Interacts CC with REEP5 (PubMed:32075961). Interacts with RETREG3 (By similarity). CC {ECO:0000250|UniProtKB:Q9NQC3, ECO:0000269|PubMed:25917084, CC ECO:0000269|PubMed:26301690, ECO:0000269|PubMed:32075961}. CC -!- SUBUNIT: [Isoform C]: Interacts with BACE1 and BACE2 (By similarity). CC Interacts with TMEM33 (By similarity). {ECO:0000250|UniProtKB:Q9NQC3}. CC -!- INTERACTION: CC Q99P72; P48722: Hspa4l; NbExp=4; IntAct=EBI-3869532, EBI-8314699; CC Q99P72; P52592: S1pr2; NbExp=2; IntAct=EBI-3869532, EBI-16091339; CC -!- SUBCELLULAR LOCATION: [Isoform A]: Endoplasmic reticulum membrane CC {ECO:0000269|PubMed:27786289, ECO:0000269|PubMed:32075961}; Multi-pass CC membrane protein {ECO:0000255}. Cell membrane CC {ECO:0000250|UniProtKB:Q9NQC3}; Multi-pass membrane protein CC {ECO:0000255}; Cytoplasmic side {ECO:0000250|UniProtKB:Q9NQC3}. Synapse CC {ECO:0000269|PubMed:35771867}. Note=Anchored to the membrane of the CC endoplasmic reticulum (ER) through 2 putative transmembrane domains. CC Localizes throughout the ER tubular network. Co-localizes with TMEM33 CC at the ER sheets. {ECO:0000250|UniProtKB:Q9NQC3}. CC -!- SUBCELLULAR LOCATION: [Isoform B]: Endoplasmic reticulum membrane CC {ECO:0000269|PubMed:25917084, ECO:0000269|PubMed:27786289, CC ECO:0000269|PubMed:32075961}; Multi-pass membrane protein CC {ECO:0000255}. Cell membrane {ECO:0000250|UniProtKB:Q9NQC3}; Multi-pass CC membrane protein {ECO:0000255}; Extracellular side CC {ECO:0000250|UniProtKB:Q9NQC3}. Cell junction CC {ECO:0000250|UniProtKB:Q9NQC3}. Note=Mainly located on endoplasmic CC reticulum tubules and sheet edges (PubMed:27786289). Upon ICAM1 CC engagement, redistributed toward endothelial junctions where interacts CC with CDH5 (By similarity). {ECO:0000250|UniProtKB:Q9NQC3, CC ECO:0000269|PubMed:27786289}. CC -!- SUBCELLULAR LOCATION: [Isoform C]: Endoplasmic reticulum membrane CC {ECO:0000250|UniProtKB:Q9NQC3}; Multi-pass membrane protein CC {ECO:0000255}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=5; CC Name=A; Synonyms=RTN4A {ECO:0000303|PubMed:12488097, CC ECO:0000303|PubMed:27786289}, Nogo-A {ECO:0000303|PubMed:12488097, CC ECO:0000303|PubMed:27786289}, RTN-xL {ECO:0000250|UniProtKB:Q9NQC3}; CC IsoId=Q99P72-2; Sequence=Displayed; CC Name=D; Synonyms=RTN4D {ECO:0000303|PubMed:12488097, CC ECO:0000303|PubMed:27786289}, Nogo-D {ECO:0000303|PubMed:12488097, CC ECO:0000303|PubMed:27786289}; CC IsoId=Q99P72-3; Sequence=VSP_018089, VSP_018090; CC Name=C; Synonyms=RTN4C {ECO:0000303|PubMed:12488097, CC ECO:0000303|PubMed:27786289}, Nogo-C {ECO:0000303|PubMed:12488097, CC ECO:0000303|PubMed:27786289}; CC IsoId=Q99P72-1; Sequence=VSP_018088, VSP_018091; CC Name=B2; Synonyms=RTN4B2 {ECO:0000303|PubMed:12488097}, Nogo-B2 CC {ECO:0000303|PubMed:12488097}; CC IsoId=Q99P72-4; Sequence=VSP_060063; CC Name=B; Synonyms=RTN4B {ECO:0000303|PubMed:27786289}, Nogo-B CC {ECO:0000303|PubMed:27786289}, RTN4B1 {ECO:0000303|PubMed:12488097}, CC Nogo-B1 {ECO:0000303|PubMed:12488097}; CC IsoId=Q99P72-5; Sequence=VSP_060062; CC -!- TISSUE SPECIFICITY: [Isoform A]: Expressed in cardiomyocytes (at CC protein level) (PubMed:32075961). Highly expressed in brain but not CC deteceted in aorta, femoral and carotid arteries (PubMed:15034570). CC Main isoform expressed in neurons (PubMed:23625008, PubMed:27786289). CC {ECO:0000269|PubMed:15034570, ECO:0000269|PubMed:23625008, CC ECO:0000269|PubMed:27786289, ECO:0000269|PubMed:32075961}. CC -!- TISSUE SPECIFICITY: [Isoform B]: Expressed in cardiomyocytes (at CC protein level) (PubMed:32075961). Expressed in splenocytes, T-cells, B- CC cells, bone marrow derived dendritic cells and macrophages (at protein CC level) (PubMed:19805174, PubMed:25917084). Expressed in neurons CC (PubMed:23625008, PubMed:27786289). Highly expressed in endothelial CC cells and vascular smooth muscle cells, including blood vessels and CC mesenteric arteries (PubMed:15034570, PubMed:26301690). Expressed in CC bronchial and alveolar epithelial cells as well as vascular endothelial CC cells of lungs (PubMed:26174362). {ECO:0000269|PubMed:15034570, CC ECO:0000269|PubMed:19805174, ECO:0000269|PubMed:23625008, CC ECO:0000269|PubMed:25917084, ECO:0000269|PubMed:26174362, CC ECO:0000269|PubMed:26301690, ECO:0000269|PubMed:27786289, CC ECO:0000269|PubMed:32075961}. CC -!- TISSUE SPECIFICITY: [Isoform B2]: Expressed in B-cells, bone marrow CC dendritic cells and macrophages (at protein level). CC {ECO:0000269|PubMed:25917084}. CC -!- TISSUE SPECIFICITY: [Isoform C]: Expressed in cardiomyocytes. CC {ECO:0000269|PubMed:27763637}. CC -!- TISSUE SPECIFICITY: [Isoform D]: Expressed at very low levels in CC neurons. {ECO:0000269|PubMed:23625008, ECO:0000269|PubMed:27786289}. CC -!- DEVELOPMENTAL STAGE: Expressed in radial glial cells, migrating CC postmitotic as well as postmigratory neurons of the embryonic cortex CC (PubMed:20093372). Expression is down-regulated in the ganglion cell CC layer and in the plexiform layer of the retina at P8 (PubMed:20093372). CC Isoform B: expression increases in regenirating liver CC (PubMed:23299899). {ECO:0000269|PubMed:20093372, CC ECO:0000269|PubMed:23299899}. CC -!- INDUCTION: Isoform C: expression is induced by hypoxic treatments or CC myocardial infarction (PubMed:27763637). Isoform C: is negatively CC regulated by the microRNA miR-182 (PubMed:27763637). Isoform B: CC expression is down-regulated by LPS in alveolar epithelium CC (PubMed:26174362). Isoform B: induced during tissue ischemia CC (PubMed:19805174). Isoform B2: induced during tissue ischemia CC (PubMed:19805174). {ECO:0000269|PubMed:19805174, CC ECO:0000269|PubMed:26174362, ECO:0000269|PubMed:27763637}. CC -!- DOMAIN: Three regions, residues 59-172, 544-725 and the loop 66 amino CC acids, between the two transmembrane domains, known as Nogo-66 loop, CC appear to be responsible for the inhibitory effect on neurite outgrowth CC and the spreading of neurons. This Nogo-66 loop, mediates also the CC binding of RTN4 to its receptor (By similarity). CC {ECO:0000250|UniProtKB:Q9JK11}. CC -!- DOMAIN: [Isoform B]: N-terminal part, called Am-Nogo-B(1-200), is the CC functional domain for RTN4B-mediated signaling in endothelial and CC vascular smooth muscle cells. {ECO:0000250|UniProtKB:Q9NQC3}. CC -!- DISRUPTION PHENOTYPE: Isoform A mutant embryos show defects in the CC development of fore- and hindlimb innervation. Increased fasciculation CC and decreased branching of nerves innervating fore- and hindlimbs seen. CC Disturbances of the radial migration pattern of neuronal precursor CC cells seen in embryonic cortex (PubMed:20093372, PubMed:20573699). CC Isoform A mutants show increased density of blood vessels in postnatal CC brain, which is lost in adult brain (PubMed:23625008). Knockout mice CC for isoforms A and B are markedly hypotensive compared to control mice, CC with no significant increase of heart rate. They have mesenteric CC arteries thinner than controls (PubMed:26301690). Upon vascular injury CC mutants show markedly enhanced neointima formation and, in some cases, CC complete occlusion of the femoral artery (PubMed:15034570). Mutants for CC isoforms A and B show a marked reduction in neutrophil and monocyte CC recruitment to sites of inflammation (PubMed:21183689). Mutants for CC isoforms A and B are insensitive to stimulation with TLR9, TLR3 and CC TLR7 ligands (PubMed:25917084). Mutant mice for isoform C display CC improved cardiac function, smaller infarct area and less apoptotic CC cells after myocardial infarction (PubMed:27763637). Knockout mice show CC impaired responses to tissue injury (PubMed:19805174). CC {ECO:0000269|PubMed:15034570, ECO:0000269|PubMed:19805174, CC ECO:0000269|PubMed:20093372, ECO:0000269|PubMed:20573699, CC ECO:0000269|PubMed:21183689, ECO:0000269|PubMed:23625008, CC ECO:0000269|PubMed:25917084, ECO:0000269|PubMed:26301690, CC ECO:0000269|PubMed:27763637}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH32192.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=BC056373; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Nerve regrowth: nipped by a CC no-go - Issue 69 of April 2006; CC URL="https://web.expasy.org/spotlight/back_issues/069"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AY102280; AAM73502.1; -; mRNA. DR EMBL; AY102281; AAM73503.1; -; mRNA. DR EMBL; AY102282; AAM73504.1; -; mRNA. DR EMBL; AY102283; AAM73505.1; -; mRNA. DR EMBL; AY102284; AAM73506.1; -; mRNA. DR EMBL; AY102286; AAM73507.1; -; Genomic_DNA. DR EMBL; AY102286; AAM73508.1; -; Genomic_DNA. DR EMBL; AY102286; AAM73509.1; -; Genomic_DNA. DR EMBL; AY102286; AAM73510.1; -; Genomic_DNA. DR EMBL; AY102286; AAM73511.1; -; Genomic_DNA. DR EMBL; AF326337; AAK08076.1; -; mRNA. DR EMBL; AY114152; AAM77068.1; -; mRNA. DR EMBL; AK220511; BAD90301.1; -; mRNA. DR EMBL; CH466604; EDL23794.1; -; Genomic_DNA. DR EMBL; AL929371; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC032192; AAH32192.1; ALT_INIT; mRNA. DR EMBL; BC056373; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; AB073672; BAC75974.1; -; mRNA. DR EMBL; AK003859; -; NOT_ANNOTATED_CDS; mRNA. DR CCDS; CCDS24499.1; -. [Q99P72-5] DR CCDS; CCDS24500.1; -. [Q99P72-4] DR CCDS; CCDS24501.1; -. [Q99P72-2] DR CCDS; CCDS24502.1; -. [Q99P72-3] DR CCDS; CCDS24503.1; -. [Q99P72-1] DR RefSeq; NP_077188.1; NM_024226.4. [Q99P72-1] DR RefSeq; NP_918940.1; NM_194051.3. [Q99P72-3] DR RefSeq; NP_918941.1; NM_194052.3. [Q99P72-5] DR RefSeq; NP_918942.1; NM_194053.3. [Q99P72-4] DR RefSeq; NP_918943.1; NM_194054.3. [Q99P72-2] DR PDB; 2KO2; NMR; -; A=1025-1090. DR PDBsum; 2KO2; -. DR AlphaFoldDB; Q99P72; -. DR BMRB; Q99P72; -. DR SMR; Q99P72; -. DR BioGRID; 212938; 26. DR CORUM; Q99P72; -. DR DIP; DIP-41976N; -. DR IntAct; Q99P72; 6. DR MINT; Q99P72; -. DR STRING; 10090.ENSMUSP00000099907; -. DR GlyGen; Q99P72; 4 sites, 1 O-linked glycan (4 sites). DR iPTMnet; Q99P72; -. DR PhosphoSitePlus; Q99P72; -. DR SwissPalm; Q99P72; -. DR EPD; Q99P72; -. DR jPOST; Q99P72; -. DR MaxQB; Q99P72; -. DR PaxDb; 10090-ENSMUSP00000099907; -. DR PeptideAtlas; Q99P72; -. DR ProteomicsDB; 256639; -. [Q99P72-2] DR ProteomicsDB; 256640; -. [Q99P72-3] DR ProteomicsDB; 256641; -. [Q99P72-1] DR ProteomicsDB; 331244; -. DR ProteomicsDB; 343118; -. DR Pumba; Q99P72; -. DR Antibodypedia; 3949; 637 antibodies from 44 providers. DR DNASU; 68585; -. DR Ensembl; ENSMUST00000060992.6; ENSMUSP00000053754.5; ENSMUSG00000020458.17. [Q99P72-1] DR Ensembl; ENSMUST00000078830.11; ENSMUSP00000077875.5; ENSMUSG00000020458.17. [Q99P72-5] DR Ensembl; ENSMUST00000102841.8; ENSMUSP00000099905.2; ENSMUSG00000020458.17. [Q99P72-3] DR Ensembl; ENSMUST00000102842.10; ENSMUSP00000099906.4; ENSMUSG00000020458.17. [Q99P72-4] DR Ensembl; ENSMUST00000102843.10; ENSMUSP00000099907.4; ENSMUSG00000020458.17. [Q99P72-2] DR Ensembl; ENSMUST00000170731.8; ENSMUSP00000126413.2; ENSMUSG00000020458.17. [Q99P72-5] DR GeneID; 68585; -. DR KEGG; mmu:68585; -. DR UCSC; uc007ihk.2; mouse. [Q99P72-2] DR UCSC; uc007ihl.2; mouse. DR UCSC; uc007ihm.2; mouse. DR UCSC; uc007ihn.2; mouse. [Q99P72-3] DR UCSC; uc007iho.2; mouse. DR AGR; MGI:1915835; -. DR CTD; 57142; -. DR MGI; MGI:1915835; Rtn4. DR VEuPathDB; HostDB:ENSMUSG00000020458; -. DR eggNOG; KOG1792; Eukaryota. DR GeneTree; ENSGT00940000156568; -. DR HOGENOM; CLU_048580_0_0_1; -. DR InParanoid; Q99P72; -. DR OMA; DGQKKHW; -. DR OrthoDB; 7284at2759; -. DR PhylomeDB; Q99P72; -. DR TreeFam; TF105431; -. DR Reactome; R-MMU-193634; Axonal growth inhibition (RHOA activation). DR BioGRID-ORCS; 68585; 3 hits in 73 CRISPR screens. DR ChiTaRS; Rtn4; mouse. DR EvolutionaryTrace; Q99P72; -. DR PRO; PR:Q99P72; -. DR Proteomes; UP000000589; Chromosome 11. DR RNAct; Q99P72; Protein. DR Bgee; ENSMUSG00000020458; Expressed in dorsal striatum and 285 other cell types or tissues. DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-SubCell. DR GO; GO:0030054; C:cell junction; ISS:UniProtKB. DR GO; GO:0042995; C:cell projection; IDA:MGI. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:MGI. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB. DR GO; GO:0071782; C:endoplasmic reticulum tubular network; ISO:MGI. DR GO; GO:0098826; C:endoplasmic reticulum tubular network membrane; ISS:UniProtKB. DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO. DR GO; GO:0043005; C:neuron projection; IBA:GO_Central. DR GO; GO:0043025; C:neuronal cell body; ISO:MGI. DR GO; GO:0005635; C:nuclear envelope; ISS:UniProtKB. DR GO; GO:0005886; C:plasma membrane; ISO:MGI. DR GO; GO:0098794; C:postsynapse; IDA:SynGO. DR GO; GO:0014069; C:postsynaptic density; IDA:MGI. DR GO; GO:0098839; C:postsynaptic density membrane; ISO:MGI. DR GO; GO:0032991; C:protein-containing complex; ISO:MGI. DR GO; GO:0045202; C:synapse; IDA:UniProtKB. DR GO; GO:0045296; F:cadherin binding; ISO:MGI. DR GO; GO:0046872; F:metal ion binding; ISO:MGI. DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB. DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI. DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI. DR GO; GO:0007413; P:axonal fasciculation; IMP:UniProtKB. DR GO; GO:0001825; P:blastocyst formation; IMP:MGI. DR GO; GO:0007420; P:brain development; IBA:GO_Central. DR GO; GO:0060317; P:cardiac epithelial to mesenchymal transition; IMP:MGI. DR GO; GO:0120078; P:cell adhesion involved in sprouting angiogenesis; ISS:UniProtKB. DR GO; GO:0035441; P:cell migration involved in vasculogenesis; IMP:UniProtKB. DR GO; GO:0071456; P:cellular response to hypoxia; IDA:UniProtKB. DR GO; GO:0022009; P:central nervous system vasculogenesis; IMP:UniProtKB. DR GO; GO:0021801; P:cerebral cortex radial glia-guided migration; IMP:UniProtKB. DR GO; GO:0007029; P:endoplasmic reticulum organization; ISO:MGI. DR GO; GO:0071787; P:endoplasmic reticulum tubular network formation; ISS:UniProtKB. DR GO; GO:1990809; P:endoplasmic reticulum tubular network membrane organization; ISS:UniProtKB. DR GO; GO:0071786; P:endoplasmic reticulum tubular network organization; ISS:UniProtKB. DR GO; GO:0090156; P:intracellular sphingolipid homeostasis; IMP:UniProtKB. DR GO; GO:0002523; P:leukocyte migration involved in inflammatory response; IMP:UniProtKB. DR GO; GO:0050804; P:modulation of chemical synaptic transmission; IDA:SynGO. DR GO; GO:1902430; P:negative regulation of amyloid-beta formation; ISS:UniProtKB. DR GO; GO:0030517; P:negative regulation of axon extension; IMP:UniProtKB. DR GO; GO:0050771; P:negative regulation of axonogenesis; ISO:MGI. DR GO; GO:0030308; P:negative regulation of cell growth; ISO:MGI. DR GO; GO:0045665; P:negative regulation of neuron differentiation; ISO:MGI. DR GO; GO:0010977; P:negative regulation of neuron projection development; ISO:MGI. DR GO; GO:0070571; P:negative regulation of neuron projection regeneration; ISO:MGI. DR GO; GO:2001213; P:negative regulation of vasculogenesis; IMP:UniProtKB. DR GO; GO:0007399; P:nervous system development; IDA:MGI. DR GO; GO:0030182; P:neuron differentiation; IBA:GO_Central. DR GO; GO:0051292; P:nuclear pore complex assembly; ISS:UniProtKB. DR GO; GO:0045766; P:positive regulation of angiogenesis; IMP:UniProtKB. DR GO; GO:1905653; P:positive regulation of artery morphogenesis; IMP:UniProtKB. DR GO; GO:0033603; P:positive regulation of dopamine secretion; ISO:MGI. DR GO; GO:0010634; P:positive regulation of epithelial cell migration; ISO:MGI. DR GO; GO:1905580; P:positive regulation of ERBB3 signaling pathway; ISO:MGI. DR GO; GO:0045687; P:positive regulation of glial cell differentiation; ISO:MGI. DR GO; GO:2000347; P:positive regulation of hepatocyte proliferation; IMP:UniProtKB. DR GO; GO:0060907; P:positive regulation of macrophage cytokine production; IMP:UniProtKB. DR GO; GO:1905523; P:positive regulation of macrophage migration; IMP:UniProtKB. DR GO; GO:0033601; P:positive regulation of mammary gland epithelial cell proliferation; ISO:MGI. DR GO; GO:1902624; P:positive regulation of neutrophil migration; IMP:UniProtKB. DR GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; ISO:MGI. DR GO; GO:1905552; P:positive regulation of protein localization to endoplasmic reticulum; ISO:MGI. DR GO; GO:0035022; P:positive regulation of Rac protein signal transduction; IMP:UniProtKB. DR GO; GO:0034165; P:positive regulation of toll-like receptor 9 signaling pathway; IMP:UniProtKB. DR GO; GO:0061462; P:protein localization to lysosome; IMP:UniProtKB. DR GO; GO:0050821; P:protein stabilization; IMP:CAFA. DR GO; GO:2000172; P:regulation of branching morphogenesis of a nerve; IMP:UniProtKB. DR GO; GO:0030334; P:regulation of cell migration; ISS:UniProtKB. DR GO; GO:0051960; P:regulation of nervous system development; IMP:UniProtKB. DR Gene3D; 1.20.5.2480; -; 1. DR InterPro; IPR003388; Reticulon. DR InterPro; IPR046964; RTN1-4. DR PANTHER; PTHR45799:SF1; RETICULON-4; 1. DR PANTHER; PTHR45799; RETICULON-LIKE PROTEIN; 1. DR Pfam; PF02453; Reticulon; 1. DR PROSITE; PS50845; RETICULON; 1. DR Genevisible; Q99P72; MM. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Cell junction; KW Cell membrane; Direct protein sequencing; Endoplasmic reticulum; Membrane; KW Neurogenesis; Phosphoprotein; Reference proteome; Synapse; Transmembrane; KW Transmembrane helix. FT CHAIN 1..1162 FT /note="Reticulon-4" FT /id="PRO_0000168166" FT TOPO_DOM 1..988 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 989..1009 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 1010..1078 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 1079..1099 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 1100..1162 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 975..1162 FT /note="Reticulon" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00170" FT REGION 1..183 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 406..432 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 711..730 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 31..53 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 86..100 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 135..157 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 406..423 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0007744|PubMed:17242355" FT MOD_RES 7 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9NQC3" FT MOD_RES 16 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19131326" FT MOD_RES 105 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19131326" FT MOD_RES 145 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:15345747, FT ECO:0007744|PubMed:19144319" FT MOD_RES 165 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 167 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 329 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9JK11" FT MOD_RES 344 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19144319, FT ECO:0007744|PubMed:21183079" FT MOD_RES 348 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 426 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9JK11" FT MOD_RES 430 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q9JK11" FT MOD_RES 489 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19144319, FT ECO:0007744|PubMed:21183079" FT MOD_RES 690 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:15345747, FT ECO:0007744|PubMed:21183079" FT MOD_RES 727 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 768 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 832 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9JK11" FT MOD_RES 834 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q9JK11" FT MOD_RES 857 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 961 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9NQC3" FT MOD_RES 1074 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:Q9NQC3" FT VAR_SEQ 1..963 FT /note="Missing (in isoform C)" FT /evidence="ECO:0000303|PubMed:12488097, ECO:0000303|Ref.2" FT /id="VSP_018088" FT VAR_SEQ 1..116 FT /note="Missing (in isoform D)" FT /evidence="ECO:0000303|PubMed:12488097" FT /id="VSP_018089" FT VAR_SEQ 117..169 FT /note="LPPAAAVLPSKLPEDDEPPARPPAPAGASPLAEPAAPPSTPAAPKRRGSGSV FT D -> MAPPLAGGGQKGGAASEAWVPSLFVGVSGSTCTAAKSLVPIPARSSRLSAARN FT (in isoform D)" FT /evidence="ECO:0000303|PubMed:12488097" FT /id="VSP_018090" FT VAR_SEQ 167..974 FT /note="SVDETLFALPAASEPVIPSSAEKIMDLKEQPGNTVSSGQEDFPSVLFETAAS FT LPSLSPLSTVSFKEHGYLGNLSAVASTEGTIEETLNEASRELPERATNPFVNRESAEFS FT VLEYSEMGSSFNGSPKGESAMLVENTKEEVIVRSKDKEDLVCSAALHNPQESPATLTKV FT VKEDGVMSPEKTMDIFNEMKMSVVAPVREEYADFKPFEQAWEVKDTYEGSRDVLAARAN FT MESKVDKKCFEDSLEQKGHGKDSESRNENASFPRTPELVKDGSRAYITCDSFSSATEST FT AANIFPVLEDHTSENKTDEKKIEERKAQIITEKTSPKTSNPFLVAIHDSEADYVTTDNL FT SKVTEAVVATMPEGLTPDLVQEACESELNEATGTKIAYETKVDLVQTSEAIQESIYPTA FT QLCPSFEEAEATPSPVLPDIVMEAPLNSLLPSTGASVAQPSASPLEVPSPVSYDGIKLE FT PENPPPYEEAMSVALKTSDSKEEIKEPESFNAAAQEAEAPYISIACDLIKETKLSTEPS FT PEFSNYSEIAKFEKSVPDHCELVDDSSPESEPVDLFSDDSIPEVPQTQEEAVMLMKESL FT TEVSETVTQHKHKERLSASPQEVGKPYLESFQPNLHITKDAASNEIPTLTKKETISLQM FT EEFNTAIYSNDDLLSSKEDKMKESETFSDSSPIEIIDEFPTFVSAKDDSPKEYTDLEVS FT NKSEIANVQSGANSLPCSELPCDLSFKNTYPKDEAHVSDEFSKSRSSVSKVPLLLPNVS FT ALESQIEMGNIVKPKVLTKEAEEKLPSDTEKEDRSLTAVLSAELNKTS -> SV (in FT isoform B)" FT /evidence="ECO:0000303|PubMed:12488097" FT /id="VSP_060062" FT VAR_SEQ 188..974 FT /note="Missing (in isoform B2)" FT /evidence="ECO:0000303|PubMed:12488097" FT /id="VSP_060063" FT VAR_SEQ 964..974 FT /note="AVLSAELNKTS -> MDDQKKRWKDK (in isoform C)" FT /evidence="ECO:0000303|PubMed:12488097, ECO:0000303|Ref.2" FT /id="VSP_018091" FT CONFLICT 4 FT /note="I -> V (in Ref. 4; BAD90301)" FT /evidence="ECO:0000305" FT CONFLICT 16 FT /note="S -> R (in Ref. 4; BAD90301)" FT /evidence="ECO:0000305" FT CONFLICT 21 FT /note="P -> L (in Ref. 4; BAD90301)" FT /evidence="ECO:0000305" FT CONFLICT 67 FT /note="A -> V (in Ref. 3; AAM77068)" FT /evidence="ECO:0000305" FT CONFLICT 413 FT /note="G -> S (in Ref. 3; AAM77068 and 4; BAD90301)" FT /evidence="ECO:0000305" FT CONFLICT 429 FT /note="R -> S (in Ref. 3; AAM77068 and 4; BAD90301)" FT /evidence="ECO:0000305" FT CONFLICT 448 FT /note="S -> T (in Ref. 3; AAM77068 and 4; BAD90301)" FT /evidence="ECO:0000305" FT CONFLICT 487..490 FT /note="KTSP -> HASA (in Ref. 7; AAH32192)" FT /evidence="ECO:0000305" FT CONFLICT 651 FT /note="S -> A (in Ref. 3; AAM77068, 7; AAH32192 and 4; FT BAD90301)" FT /evidence="ECO:0000305" FT CONFLICT 665 FT /note="A -> V (in Ref. 4; BAD90301)" FT /evidence="ECO:0000305" FT CONFLICT 692 FT /note="E -> G (in Ref. 3; AAM77068 and 8; BAC75974)" FT /evidence="ECO:0000305" FT CONFLICT 733 FT /note="E -> D (in Ref. 4; BAD90301)" FT /evidence="ECO:0000305" FT CONFLICT 772 FT /note="V -> L (in Ref. 4; BAD90301)" FT /evidence="ECO:0000305" FT CONFLICT 916 FT /note="S -> F (in Ref. 8; BAC75974)" FT /evidence="ECO:0000305" FT CONFLICT 990 FT /note="V -> VY (in Ref. 3; AAM77068)" FT /evidence="ECO:0000305" FT HELIX 1026..1029 FT /evidence="ECO:0007829|PDB:2KO2" FT HELIX 1031..1035 FT /evidence="ECO:0007829|PDB:2KO2" FT TURN 1037..1040 FT /evidence="ECO:0007829|PDB:2KO2" FT HELIX 1044..1053 FT /evidence="ECO:0007829|PDB:2KO2" FT HELIX 1057..1063 FT /evidence="ECO:0007829|PDB:2KO2" FT TURN 1065..1067 FT /evidence="ECO:0007829|PDB:2KO2" FT HELIX 1068..1082 FT /evidence="ECO:0007829|PDB:2KO2" FT HELIX 1087..1089 FT /evidence="ECO:0007829|PDB:2KO2" SQ SEQUENCE 1162 AA; 126613 MW; 855697FBEE11781F CRC64; MEDIDQSSLV SSSADSPPRP PPAFKYQFVT EPEDEEDEED EEEEEDDEDL EELEVLERKP AAGLSAAPVP PAAAPLLDFS SDSVPPAPRG PLPAAPPTAP ERQPSWERSP AASAPSLPPA AAVLPSKLPE DDEPPARPPA PAGASPLAEP AAPPSTPAAP KRRGSGSVDE TLFALPAASE PVIPSSAEKI MDLKEQPGNT VSSGQEDFPS VLFETAASLP SLSPLSTVSF KEHGYLGNLS AVASTEGTIE ETLNEASREL PERATNPFVN RESAEFSVLE YSEMGSSFNG SPKGESAMLV ENTKEEVIVR SKDKEDLVCS AALHNPQESP ATLTKVVKED GVMSPEKTMD IFNEMKMSVV APVREEYADF KPFEQAWEVK DTYEGSRDVL AARANMESKV DKKCFEDSLE QKGHGKDSES RNENASFPRT PELVKDGSRA YITCDSFSSA TESTAANIFP VLEDHTSENK TDEKKIEERK AQIITEKTSP KTSNPFLVAI HDSEADYVTT DNLSKVTEAV VATMPEGLTP DLVQEACESE LNEATGTKIA YETKVDLVQT SEAIQESIYP TAQLCPSFEE AEATPSPVLP DIVMEAPLNS LLPSTGASVA QPSASPLEVP SPVSYDGIKL EPENPPPYEE AMSVALKTSD SKEEIKEPES FNAAAQEAEA PYISIACDLI KETKLSTEPS PEFSNYSEIA KFEKSVPDHC ELVDDSSPES EPVDLFSDDS IPEVPQTQEE AVMLMKESLT EVSETVTQHK HKERLSASPQ EVGKPYLESF QPNLHITKDA ASNEIPTLTK KETISLQMEE FNTAIYSNDD LLSSKEDKMK ESETFSDSSP IEIIDEFPTF VSAKDDSPKE YTDLEVSNKS EIANVQSGAN SLPCSELPCD LSFKNTYPKD EAHVSDEFSK SRSSVSKVPL LLPNVSALES QIEMGNIVKP KVLTKEAEEK LPSDTEKEDR SLTAVLSAEL NKTSVVDLLY WRDIKKTGVV FGASLFLLLS LTVFSIVSVT AYIALALLSV TISFRIYKGV IQAIQKSDEG HPFRAYLESE VAISEELVQK YSNSALGHVN STIKELRRLF LVDDLVDSLK FAVLMWVFTY VGALFNGLTL LILALISLFS IPVIYERHQA QIDHYLGLAN KSVKDAMAKI QAKIPGLKRK AE //