RTN4_MOUSE
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 03-AUG-2022, entry version 184.
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, Pancreas,
RC 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).
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). {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). {ECO:0000250|UniProtKB:Q9NQC3,
CC ECO:0000269|PubMed:25917084, ECO:0000269|PubMed:26301690,
CC 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}.
CC Note=Anchored to the membrane of the endoplasmic reticulum (ER) through
CC 2 putative transmembrane domains. Localizes throughout the ER tubular
CC network. Co-localizes with TMEM33 at the ER sheets.
CC {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 ---------------------------------------------------------------------------
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CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
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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; 11.
DR CORUM; Q99P72; -.
DR DIP; DIP-41976N; -.
DR IntAct; Q99P72; 5.
DR MINT; Q99P72; -.
DR STRING; 10090.ENSMUSP00000099907; -.
DR iPTMnet; Q99P72; -.
DR PhosphoSitePlus; Q99P72; -.
DR SwissPalm; Q99P72; -.
DR EPD; Q99P72; -.
DR jPOST; Q99P72; -.
DR MaxQB; Q99P72; -.
DR PaxDb; Q99P72; -.
DR PeptideAtlas; Q99P72; -.
DR PRIDE; Q99P72; -.
DR ProteomicsDB; 256639; -. [Q99P72-2]
DR ProteomicsDB; 256640; -. [Q99P72-3]
DR ProteomicsDB; 256641; -. [Q99P72-1]
DR ProteomicsDB; 331244; -.
DR ProteomicsDB; 343118; -.
DR Antibodypedia; 3949; 508 antibodies from 44 providers.
DR DNASU; 68585; -.
DR Ensembl; ENSMUST00000060992; ENSMUSP00000053754; ENSMUSG00000020458. [Q99P72-1]
DR Ensembl; ENSMUST00000078830; ENSMUSP00000077875; ENSMUSG00000020458. [Q99P72-5]
DR Ensembl; ENSMUST00000102841; ENSMUSP00000099905; ENSMUSG00000020458. [Q99P72-3]
DR Ensembl; ENSMUST00000102842; ENSMUSP00000099906; ENSMUSG00000020458. [Q99P72-4]
DR Ensembl; ENSMUST00000102843; ENSMUSP00000099907; ENSMUSG00000020458. [Q99P72-2]
DR Ensembl; ENSMUST00000170731; ENSMUSP00000126413; ENSMUSG00000020458. [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 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; FEVVDYH; -.
DR OrthoDB; 212372at2759; -.
DR PhylomeDB; Q99P72; -.
DR TreeFam; TF105431; -.
DR Reactome; R-MMU-193634; Axonal growth inhibition (RHOA activation).
DR BioGRID-ORCS; 68585; 3 hits in 68 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 281 other tissues.
DR Genevisible; Q99P72; MM.
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:0005737; C:cytoplasm; ISO: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; ISO:MGI.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0099061; C:integral component of postsynaptic density membrane; ISO:MGI.
DR GO; GO:0043209; C:myelin sheath; ISO:MGI.
DR GO; GO:0043005; C:neuron projection; ISO:MGI.
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:0014069; C:postsynaptic density; IDA:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0045296; F:cadherin 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:0090156; P:cellular sphingolipid homeostasis; IMP: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:0002523; P:leukocyte migration involved in inflammatory response; IMP:UniProtKB.
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 protein kinase B signaling; 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 GO; GO:0051930; P:regulation of sensory perception of pain; ISO:MGI.
DR InterPro; IPR003388; Reticulon.
DR Pfam; PF02453; Reticulon; 1.
DR PROSITE; PS50845; RETICULON; 1.
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; 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
