RTN4_HUMAN
ID RTN4_HUMAN Reviewed; 1192 AA.
AC Q9NQC3; O94962; Q7L7Q5; Q7L7Q6; Q7L7Q8; Q8IUA4; Q96B16; Q9BXG5; Q9H212;
AC Q9H3I3; Q9UQ42; Q9Y293; Q9Y2Y7; Q9Y5U6;
DT 16-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT 16-NOV-2001, sequence version 2.
DT 03-AUG-2022, entry version 216.
DE RecName: Full=Reticulon-4 {ECO:0000305};
DE AltName: Full=Foocen;
DE AltName: Full=Neurite outgrowth inhibitor;
DE Short=Nogo protein {ECO:0000303|PubMed:12488097};
DE AltName: Full=Neuroendocrine-specific protein;
DE Short=NSP;
DE AltName: Full=Neuroendocrine-specific protein C homolog;
DE AltName: Full=RTN-x;
DE AltName: Full=Reticulon-5;
GN Name=RTN4 {ECO:0000312|HGNC:HGNC:14085};
GN Synonyms=KIAA0886, NOGO {ECO:0000303|PubMed:12488097};
GN ORFNames=My043, SP1507;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A; B AND C).
RX PubMed=10773680; DOI=10.1159/000015499;
RA Yang J., Yu L., Bi A.D., Zhao S.-Y.;
RT "Assignment of the human reticulon 4 gene (RTN4) to chromosome 2p14-->2p13
RT by radiation hybrid mapping.";
RL Cytogenet. Cell Genet. 88:101-102(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A; B AND C).
RX PubMed=10667780; DOI=10.1038/35000287;
RA Prinjha R., Moore S.E., Vinson M., Blake S., Morrow R., Christie G.,
RA Michalovich D., Simmons D.L., Walsh F.S.;
RT "Inhibitor of neurite outgrowth in humans.";
RL Nature 403:383-384(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A AND B), AND FUNCTION (ISOFORM B).
RC TISSUE=Brain;
RX PubMed=11126360; DOI=10.1038/sj.onc.1203948;
RA Tagami S., Eguchi Y., Kinoshita M., Takeda M., Tsujimoto Y.;
RT "A novel protein, RTN-XS, interacts with both Bcl-XL and Bcl-2 on
RT endoplasmic reticulum and reduces their anti-apoptotic activity.";
RL Oncogene 19:5736-5746(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 6).
RC TISSUE=Testis;
RX PubMed=11866689; DOI=10.1530/rep.0.1230227;
RA Zhou Z.M., Sha J.H., Li J.M., Lin M., Zhu H., Zhou Y.D., Wang L.R., Zhu H.,
RA Wang Y.Q., Zhou K.Y.;
RT "Expression of a novel reticulon-like gene in human testis.";
RL Reproduction 123:227-234(2002).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS A; B; B2; C AND D), AND
RP ALTERNATIVE SPLICING.
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 [6]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B).
RC TISSUE=Fibroblast;
RA Yutsudo M.;
RT "Isolation of a cell death-inducing gene.";
RL Submitted (JUN-1998) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM C).
RC TISSUE=Pituitary;
RA Song H., Peng Y., Zhou J., Huang Q., Dai M., Mao Y.M., Yu Y., Xu X.,
RA Luo B., Hu R., Chen J.;
RT "Human neuroendocrine-specific protein C (NSP) homolog gene.";
RL Submitted (JUL-1998) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS B AND C).
RC TISSUE=Placenta, and Skeletal muscle;
RA Ito T., Schwartz S.M.;
RT "Cloning of a member of the reticulon gene family in human.";
RL Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B2).
RA Jin W.-L., Ju G.;
RT "Developmentally-regulated alternative splicing in a novel Nogo-A.";
RL Submitted (NOV-2000) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A).
RC TISSUE=Brain;
RX PubMed=10048485; DOI=10.1093/dnares/5.6.355;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 5:355-364(1998).
RN [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM C).
RC TISSUE=Umbilical cord blood;
RX PubMed=11042152; DOI=10.1101/gr.140200;
RA Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G.,
RA Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W.,
RA Tao J., Huang Q.-H., Zhou J., Hu G.-X., Gu J., Chen S.-J., Chen Z.;
RT "Cloning and functional analysis of cDNAs with open reading frames for 300
RT previously undefined genes expressed in CD34+ hematopoietic stem/progenitor
RT cells.";
RL Genome Res. 10:1546-1560(2000).
RN [12]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM C).
RX PubMed=15498874; DOI=10.1073/pnas.0404089101;
RA Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H., Qiu X.,
RA Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y., Shu H., Chen X.,
RA Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S., Gu J.;
RT "Large-scale cDNA transfection screening for genes related to cancer
RT development and progression.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004).
RN [13]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [14]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [15]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS B; C AND D).
RC TISSUE=Brain, Eye, Kidney, Ovary, Pancreas, Placenta, and Skeletal muscle;
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 [16]
RP PROTEIN SEQUENCE OF 1-24; 92-104; 1075-1090 AND 1158-1171, ACETYLATION AT
RP MET-1, PHOSPHORYLATION AT SER-15, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Ovarian carcinoma;
RA Bienvenut W.V.;
RL Submitted (JAN-2010) to UniProtKB.
RN [17]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 482-1192 (ISOFORMS A/B2).
RC TISSUE=Fetal brain;
RA Mao Y.M., Xie Y., Zheng Z.H.;
RL Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases.
RN [18]
RP TOPOLOGY, AND FUNCTION (ISOFORM A).
RC TISSUE=Brain;
RX PubMed=10667797; DOI=10.1038/35000226;
RA GrandPre T., Nakamura F., Vartanian T., Strittmatter S.M.;
RT "Identification of the Nogo inhibitor of axon regeneration as a Reticulon
RT protein.";
RL Nature 403:439-444(2000).
RN [19]
RP FUNCTION (ISOFORM A).
RC TISSUE=Brain;
RX PubMed=11201742; DOI=10.1038/35053072;
RA Fournier A.E., GrandPre T., Strittmatter S.M.;
RT "Identification of a receptor mediating Nogo-66 inhibition of axonal
RT regeneration.";
RL Nature 409:341-346(2001).
RN [20]
RP REVIEW.
RX PubMed=11891768; DOI=10.1002/jnr.10134;
RA Ng C.E.L., Tang B.L.;
RT "Nogos and the Nogo-66 receptor: factors inhibiting CNS neuron
RT regeneration.";
RL J. Neurosci. Res. 67:559-565(2002).
RN [21]
RP INTERACTION WITH RTN3 (ISOFORM B).
RX PubMed=12811824; DOI=10.1002/jcp.10297;
RA Qi B., Qi Y., Watari A., Yoshioka N., Inoue H., Minemoto Y., Yamashita K.,
RA Sasagawa T., Yutsudo M.;
RT "Pro-apoptotic ASY/Nogo-B protein associates with ASYIP.";
RL J. Cell. Physiol. 196:312-318(2003).
RN [22]
RP FUNCTION (ISOFORM B), TISSUE SPECIFICITY (ISOFORMS A AND B), SUBCELLULAR
RP LOCATION (ISOFORM B), AND DOMAIN (ISOFORM B).
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 [23]
RP INTERACTION WITH BACE1.
RX PubMed=15286784; DOI=10.1038/nm1088;
RA He W., Lu Y., Qahwash I., Hu X.-Y., Chang A., Yan R.;
RT "Reticulon family members modulate BACE1 activity and amyloid-beta peptide
RT generation.";
RL Nat. Med. 10:959-965(2004).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-7 AND SER-107, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [25]
RP INTERACTION WITH BACE1 AND BACE2 (ISOFORMS B AND C), IDENTIFICATION BY MASS
RP SPECTROMETRY, AND FUNCTION (ISOFORMS B AND C).
RX PubMed=16965550; DOI=10.1111/j.1460-9568.2006.05005.x;
RA Murayama K.S., Kametani F., Saito S., Kume H., Akiyama H., Araki W.;
RT "Reticulons RTN3 and RTN4-B/C interact with BACE1 and inhibit its ability
RT to produce amyloid beta-protein.";
RL Eur. J. Neurosci. 24:1237-1244(2006).
RN [26]
RP INTERACTION WITH RTN3 (ISOFORM B).
RX PubMed=16979658; DOI=10.1016/j.jmb.2006.07.094;
RA He W., Hu X., Shi Q., Zhou X., Lu Y., Fisher C., Yan R.;
RT "Mapping of interaction domains mediating binding between BACE1 and
RT RTN/Nogo proteins.";
RL J. Mol. Biol. 363:625-634(2006).
RN [27]
RP INTERACTION WITH NGBR (ISOFORM B).
RX PubMed=16835300; DOI=10.1073/pnas.0602427103;
RA Miao R.Q., Gao Y., Harrison K.D., Prendergast J., Acevedo L.M., Yu J.,
RA Hu F., Strittmatter S.M., Sessa W.C.;
RT "Identification of a receptor necessary for Nogo-B stimulated chemotaxis
RT and morphogenesis of endothelial cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:10997-11002(2006).
RN [28]
RP INTERACTS WITH RTN4R.
RX PubMed=19052207; DOI=10.1523/jneurosci.3828-08.2008;
RA Budel S., Padukkavidana T., Liu B.P., Feng Z., Hu F., Johnson S.,
RA Lauren J., Park J.H., McGee A.W., Liao J., Stillman A., Kim J.E.,
RA Yang B.Z., Sodi S., Gelernter J., Zhao H., Hisama F., Arnsten A.F.,
RA Strittmatter S.M.;
RT "Genetic variants of Nogo-66 receptor with possible association to
RT schizophrenia block myelin inhibition of axon growth.";
RL J. Neurosci. 28:13161-13172(2008).
RN [29]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [30]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-181 AND SER-182, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [31]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [32]
RP INTERACTION WITH ATL1.
RX PubMed=19665976; DOI=10.1016/j.cell.2009.05.025;
RA Hu J., Shibata Y., Zhu P.-P., Voss C., Rismanchi N., Prinz W.A.,
RA Rapoport T.A., Blackstone C.;
RT "A class of dynamin-like GTPases involved in the generation of the tubular
RT ER network.";
RL Cell 138:549-561(2009).
RN [33]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [34]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [35]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-1104, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [36]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, PHOSPHORYLATION [LARGE SCALE
RP ANALYSIS] AT SER-7 AND SER-15, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [37]
RP FUNCTION (ISOFORM B), SUBCELLULAR LOCATION (ISOFORM B), INTERACTION WITH
RP CDH5 (ISOFORM B), AND TISSUE SPECIFICITY.
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 [38]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [39]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, PHOSPHORYLATION [LARGE SCALE
RP ANALYSIS] AT SER-15 AND SER-107, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [40]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [41]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [42]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-7; SER-15; SER-181 AND
RP SER-991, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [43]
RP FUNCTION (ISOFORM C).
RX PubMed=24262037; DOI=10.1042/bj20131186;
RA Yamamoto Y., Yoshida A., Miyazaki N., Iwasaki K., Sakisaka T.;
RT "Arl6IP1 has the ability to shape the mammalian ER membrane in a reticulon-
RT like fashion.";
RL Biochem. J. 458:69-79(2014).
RN [44]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [45]
RP FUNCTION (ISOFORM C), SUBCELLULAR LOCATION (ISOFORM C), AND INTERACTION
RP WITH TMEM33 (ISOFORM C).
RX PubMed=25612671;
RA Urade T., Yamamoto Y., Zhang X., Ku Y., Sakisaka T.;
RT "Identification and characterization of TMEM33 as a reticulon-binding
RT protein.";
RL Kobe J. Med. Sci. 60:E57-E65(2014).
RN [46]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [47]
RP FUNCTION (ISOFORM A), AND SUBCELLULAR LOCATION (ISOFORM A).
RX PubMed=27619977; DOI=10.7554/elife.18605;
RA Wang S., Tukachinsky H., Romano F.B., Rapoport T.A.;
RT "Cooperation of the ER-shaping proteins atlastin, lunapark, and reticulons
RT to generate a tubular membrane network.";
RL Elife 5:0-0(2016).
RN [48]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH TMEM170A.
RX PubMed=26906412; DOI=10.1242/jcs.175273;
RA Christodoulou A., Santarella-Mellwig R., Santama N., Mattaj I.W.;
RT "Transmembrane protein TMEM170A is a novel regulator of ER and NE
RT morphogenesis in human cells.";
RL J. Cell Sci. 129:1552-1565(2016).
RN [49]
RP FUNCTION (ISOFORM B), SUBCELLULAR LOCATION (ISOFORMS A AND B), TISSUE
RP SPECIFICITY, AND SUBUNIT (ISOFORM B).
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 [50]
RP INTERACTION WITH REEP5.
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 [51] {ECO:0007744|PDB:2G31}
RP STRUCTURE BY NMR OF 1055-1114.
RX PubMed=16877707; DOI=10.1110/ps.062306906;
RA Li M., Liu J., Song J.;
RT "Nogo goes in the pure water: solution structure of Nogo-60 and design of
RT the structured and buffer-soluble Nogo-54 for enhancing CNS regeneration.";
RL Protein Sci. 15:1835-1841(2006).
RN [52]
RP VARIANT [LARGE SCALE ANALYSIS] VAL-429.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Required to induce the formation and stabilization of
CC endoplasmic reticulum (ER) tubules (PubMed:27619977, PubMed:25612671,
CC PubMed:24262037). They regulate membrane morphogenesis in the ER by
CC promoting tubular ER production (PubMed:27619977, PubMed:25612671,
CC PubMed:24262037, PubMed:27786289). They influence nuclear envelope
CC expansion, nuclear pore complex formation and proper localization of
CC inner nuclear membrane proteins (PubMed:26906412). However each isoform
CC have specific functions mainly depending on their tissue expression
CC specificities (Probable). {ECO:0000269|PubMed:24262037,
CC ECO:0000269|PubMed:25612671, ECO:0000269|PubMed:26906412,
CC ECO:0000269|PubMed:27619977, ECO:0000269|PubMed:27786289, ECO:0000305}.
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
CC system. Involved in down-regulation of growth, stabilization of wiring
CC and restriction of plasticity in the adult CNS (PubMed:10667797,
CC PubMed:11201742). Regulates the radial migration of cortical neurons
CC via an RTN4R-LINGO1 containing receptor complex (By similarity). Acts
CC as a negative regulator of central nervous system angiogenesis.
CC Inhibits spreading, migration and sprouting of primary brain
CC microvascular endothelial cells (MVECs). Also induces the retraction of
CC MVECs lamellipodia and filopodia in a ROCK pathway-dependent manner (By
CC similarity). {ECO:0000250|UniProtKB:Q99P72,
CC ECO:0000269|PubMed:10667797, ECO:0000269|PubMed:11201742}.
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. Regulates endothelial sphingolipid biosynthesis
CC with direct effects on vascular function and blood pressure. Inhibits
CC serine palmitoyltransferase, SPTLC1, the rate-limiting enzyme of the
CC novo sphingolipid biosynthetic pathway, thereby controlling production
CC of endothelial sphingosine-1-phosphate (S1P). Required to promote
CC macrophage homing and functions such as cytokine/chemokine gene
CC expression involved in angiogenesis, arteriogenesis and tissue repair.
CC Mediates ICAM1 induced transendothelial migration of leukocytes such as
CC monocytes and neutrophils and acute inflammation. Necessary for immune
CC responses triggered by nucleic acid sensing TLRs, such as TLR9, is
CC required for proper TLR9 location to endolysosomes. Also involved in
CC immune response to LPS. Plays a role in liver regeneration through the
CC modulation of hepatocytes proliferation (By similarity). 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
CC (PubMed:11126360). With isoform C, inhibits BACE1 activity and amyloid
CC precursor protein processing (PubMed:16965550).
CC {ECO:0000250|UniProtKB:Q99P72, ECO:0000269|PubMed:11126360,
CC ECO:0000269|PubMed:16965550, ECO:0000305}.
CC -!- FUNCTION: [Isoform C]: Regulates cardiomyocyte apoptosis upon hypoxic
CC conditions (By similarity). With isoform B, inhibits BACE1 activity and
CC amyloid precursor protein processing (PubMed:16965550).
CC {ECO:0000250|UniProtKB:Q99P72, ECO:0000269|PubMed:16965550}.
CC -!- SUBUNIT: Binds to RTN4R (PubMed:19052207). Interacts with ATL1
CC (PubMed:19665976). Interacts with TMEM170A (PubMed:19665976,
CC PubMed:26906412). Interacts with RTN4IP1 (By similarity).
CC {ECO:0000250|UniProtKB:Q99P72, ECO:0000269|PubMed:19052207,
CC ECO:0000269|PubMed:19665976, ECO:0000269|PubMed:26906412}.
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 (PubMed:27786289). Interacts with
CC BAD/Bcl-xl and BCL2. Interact with RTN3 (PubMed:12811824,
CC PubMed:16979658). Interacts with NGBR (PubMed:16835300). Interacts with
CC SPTLC1 (By similarity). Interacts with GRAMD4 (By similarity).
CC Interacts with CDH5 (PubMed:21183689). Interacts with BACE1 and BACE2
CC (PubMed:15286784, PubMed:16965550). Interacts with REEP5
CC (PubMed:32075961). {ECO:0000250|UniProtKB:Q99P72,
CC ECO:0000269|PubMed:12811824, ECO:0000269|PubMed:15286784,
CC ECO:0000269|PubMed:16835300, ECO:0000269|PubMed:16965550,
CC ECO:0000269|PubMed:16979658, ECO:0000269|PubMed:21183689,
CC ECO:0000269|PubMed:27786289, ECO:0000269|PubMed:32075961}.
CC -!- SUBUNIT: [Isoform C]: Interacts with BACE1 and BACE2 (PubMed:15286784,
CC PubMed:16965550). Interacts with TMEM33 (PubMed:25612671).
CC {ECO:0000269|PubMed:15286784, ECO:0000269|PubMed:16965550,
CC ECO:0000269|PubMed:25612671}.
CC -!- INTERACTION:
CC Q9NQC3; Q15041: ARL6IP1; NbExp=3; IntAct=EBI-715945, EBI-714543;
CC Q9NQC3; Q9Y5P4: CERT1; NbExp=3; IntAct=EBI-715945, EBI-739994;
CC Q9NQC3; O43639: NCK2; NbExp=2; IntAct=EBI-715945, EBI-713635;
CC Q9NQC3; Q13596: SNX1; NbExp=3; IntAct=EBI-715945, EBI-2822329;
CC Q9NQC3; Q9NRS6: SNX15; NbExp=4; IntAct=EBI-715945, EBI-725924;
CC Q9NQC3; Q17RD7: SYT16; NbExp=5; IntAct=EBI-715945, EBI-10238936;
CC Q9NQC3; Q9BQ24: ZFYVE21; NbExp=3; IntAct=EBI-715945, EBI-2849569;
CC Q9NQC3-1; Q8WXF7: ATL1; NbExp=2; IntAct=EBI-715972, EBI-2410266;
CC Q9NQC3-2; P56817-1: BACE1; NbExp=3; IntAct=EBI-10296096, EBI-2433297;
CC Q9NQC3-2; Q9BQ24: ZFYVE21; NbExp=3; IntAct=EBI-10296096, EBI-2849569;
CC Q9NQC3-3; P56817-1: BACE1; NbExp=2; IntAct=EBI-11526335, EBI-2433297;
CC Q9NQC3-5; O95197-3: RTN3; NbExp=3; IntAct=EBI-17721653, EBI-11525735;
CC -!- SUBCELLULAR LOCATION: [Isoform A]: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:25612671, ECO:0000269|PubMed:26906412,
CC ECO:0000269|PubMed:27619977, ECO:0000269|PubMed:27786289}; Multi-pass
CC membrane protein {ECO:0000255}. Cell membrane; Multi-pass membrane
CC protein {ECO:0000255}; Cytoplasmic side {ECO:0000269|PubMed:27786289}.
CC Note=Anchored to the membrane of the endoplasmic reticulum (ER) through
CC 2 putative transmembrane domains. Localizes throughout the ER tubular
CC network (PubMed:27619977). Co-localizes with TMEM33 at the ER sheets.
CC {ECO:0000269|PubMed:25612671, ECO:0000269|PubMed:27619977}.
CC -!- SUBCELLULAR LOCATION: [Isoform B]: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:27786289}; Multi-pass membrane protein
CC {ECO:0000255}. Cell membrane {ECO:0000269|PubMed:15034570}; Multi-pass
CC membrane protein {ECO:0000255}; Extracellular side
CC {ECO:0000269|PubMed:15034570}. Cell junction
CC {ECO:0000269|PubMed:21183689}. 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 (PubMed:21183689). {ECO:0000269|PubMed:21183689,
CC ECO:0000269|PubMed:27786289}.
CC -!- SUBCELLULAR LOCATION: [Isoform C]: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:25612671}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
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:0000303|PubMed:11126360};
CC IsoId=Q9NQC3-1; Sequence=Displayed;
CC Name=B; Synonyms=RTN4B {ECO:0000303|PubMed:27786289}, ASY
CC {ECO:0000303|PubMed:12811824}, Nogo-B {ECO:0000303|PubMed:27786289},
CC RTN-xS {ECO:0000303|PubMed:11126360}, Foocen-M, RTN4B1
CC {ECO:0000303|PubMed:12488097}, Nogo-B1 {ECO:0000303|PubMed:12488097};
CC IsoId=Q9NQC3-2; Sequence=VSP_005655;
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}, Foocen-S;
CC IsoId=Q9NQC3-3; Sequence=VSP_005652, VSP_005653;
CC Name=6;
CC IsoId=Q9NQC3-4; Sequence=VSP_005654;
CC Name=B2; Synonyms=RTN4B2 {ECO:0000269|PubMed:12488097}, Nogo-B2
CC {ECO:0000303|PubMed:12488097};
CC IsoId=Q9NQC3-5; Sequence=VSP_037113;
CC Name=D; Synonyms=Rtn-T, RTN4Aa {ECO:0000269|PubMed:12488097}, RTN4Ab
CC {ECO:0000269|PubMed:12488097}, RTN4D {ECO:0000269|PubMed:12488097},
CC RTN4E {ECO:0000269|PubMed:12488097}, RTN4F
CC {ECO:0000269|PubMed:12488097}, RTN4G {ECO:0000269|PubMed:12488097};
CC IsoId=Q9NQC3-6; Sequence=VSP_037112;
CC -!- TISSUE SPECIFICITY: Isoform A: is specifically expressed in brain and
CC testis and weakly in heart and skeletal muscle. Isoform B: widely
CC expressed except for the liver. Highly expressed in endothelial cells
CC and vascular smooth muscle cells, including blood vessels and
CC mesenteric arteries (PubMed:15034570, PubMed:21183689). Isoform C: is
CC expressed in brain, skeletal muscle and adipocytes. Isoform D is
CC testis-specific. {ECO:0000269|PubMed:15034570,
CC ECO:0000269|PubMed:21183689}.
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:0000269|PubMed:15034570}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD39920.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAG43160.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAG43160.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAA74909.2; Type=Erroneous initiation; Note=Extended N-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 -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/RTN4ID42182ch2p16.html";
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DR EMBL; AF087901; AAG12205.1; -; mRNA.
DR EMBL; AF148537; AAG12176.1; -; mRNA.
DR EMBL; AF148538; AAG12177.1; -; mRNA.
DR EMBL; AJ251383; CAB99248.1; -; mRNA.
DR EMBL; AJ251384; CAB99249.1; -; mRNA.
DR EMBL; AJ251385; CAB99250.1; -; mRNA.
DR EMBL; AB040462; BAB18927.1; -; mRNA.
DR EMBL; AB040463; BAB18928.1; -; mRNA.
DR EMBL; AF333336; AAK20831.1; -; mRNA.
DR EMBL; AY102285; AAM64240.1; -; Genomic_DNA.
DR EMBL; AY102285; AAM64241.1; -; Genomic_DNA.
DR EMBL; AY102285; AAM64242.1; -; Genomic_DNA.
DR EMBL; AY102285; AAM64243.1; -; Genomic_DNA.
DR EMBL; AY102285; AAM64244.1; -; Genomic_DNA.
DR EMBL; AY102276; AAM64245.1; -; mRNA.
DR EMBL; AY102277; AAM64246.1; -; mRNA.
DR EMBL; AY102278; AAM64247.1; -; mRNA.
DR EMBL; AY102279; AAM64248.1; -; mRNA.
DR EMBL; AY123245; AAM64249.1; -; mRNA.
DR EMBL; AY123246; AAM64250.1; -; mRNA.
DR EMBL; AY123247; AAM64251.1; -; mRNA.
DR EMBL; AY123248; AAM64252.1; -; mRNA.
DR EMBL; AY123249; AAM64253.1; -; mRNA.
DR EMBL; AY123250; AAM64254.1; -; mRNA.
DR EMBL; AB015639; BAA83712.1; -; mRNA.
DR EMBL; AF077050; AAD27783.1; -; mRNA.
DR EMBL; AF132047; AAD31021.1; -; mRNA.
DR EMBL; AF132048; AAD31022.1; -; mRNA.
DR EMBL; AF320999; AAG40878.1; -; mRNA.
DR EMBL; AB020693; BAA74909.2; ALT_INIT; mRNA.
DR EMBL; AF125103; AAD39920.1; ALT_FRAME; mRNA.
DR EMBL; AF177332; AAG17976.1; -; mRNA.
DR EMBL; AC013414; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC092461; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC093165; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471053; EAX00115.1; -; Genomic_DNA.
DR EMBL; CH471053; EAX00116.1; -; Genomic_DNA.
DR EMBL; CH471053; EAX00117.1; -; Genomic_DNA.
DR EMBL; CH471053; EAX00118.1; -; Genomic_DNA.
DR EMBL; CH471053; EAX00119.1; -; Genomic_DNA.
DR EMBL; CH471053; EAX00121.1; -; Genomic_DNA.
DR EMBL; CH471053; EAX00122.1; -; Genomic_DNA.
DR EMBL; CH471053; EAX00123.1; -; Genomic_DNA.
DR EMBL; CH471053; EAX00124.1; -; Genomic_DNA.
DR EMBL; CH471053; EAX00125.1; -; Genomic_DNA.
DR EMBL; CH471053; EAX00127.1; -; Genomic_DNA.
DR EMBL; CH471053; EAX00130.1; -; Genomic_DNA.
DR EMBL; CH471053; EAX00132.1; -; Genomic_DNA.
DR EMBL; BC001035; AAH01035.1; -; mRNA.
DR EMBL; BC007109; AAH07109.1; -; mRNA.
DR EMBL; BC010737; AAH10737.1; -; mRNA.
DR EMBL; BC012619; AAH12619.1; -; mRNA.
DR EMBL; BC014366; AAH14366.1; -; mRNA.
DR EMBL; BC016165; AAH16165.1; -; mRNA.
DR EMBL; BC026788; AAH26788.1; -; mRNA.
DR EMBL; BC068991; AAH68991.1; -; mRNA.
DR EMBL; BC150182; AAI50183.1; -; mRNA.
DR EMBL; BC152425; AAI52426.1; -; mRNA.
DR EMBL; BC152555; AAI52556.1; -; mRNA.
DR EMBL; AF063601; AAG43160.1; ALT_SEQ; mRNA.
DR CCDS; CCDS1851.1; -. [Q9NQC3-2]
DR CCDS; CCDS1852.1; -. [Q9NQC3-6]
DR CCDS; CCDS42683.1; -. [Q9NQC3-5]
DR CCDS; CCDS42684.1; -. [Q9NQC3-1]
DR CCDS; CCDS42685.1; -. [Q9NQC3-3]
DR RefSeq; NP_001308788.1; NM_001321859.1. [Q9NQC3-6]
DR RefSeq; NP_001308789.1; NM_001321860.1. [Q9NQC3-6]
DR RefSeq; NP_001308790.1; NM_001321861.1. [Q9NQC3-6]
DR RefSeq; NP_001308791.1; NM_001321862.1. [Q9NQC3-6]
DR RefSeq; NP_001308792.1; NM_001321863.1. [Q9NQC3-6]
DR RefSeq; NP_001308833.1; NM_001321904.1. [Q9NQC3-6]
DR RefSeq; NP_008939.1; NM_007008.2. [Q9NQC3-3]
DR RefSeq; NP_065393.1; NM_020532.4. [Q9NQC3-1]
DR RefSeq; NP_722550.1; NM_153828.2. [Q9NQC3-2]
DR RefSeq; NP_997403.1; NM_207520.1. [Q9NQC3-5]
DR RefSeq; NP_997404.1; NM_207521.1. [Q9NQC3-6]
DR RefSeq; XP_005264491.1; XM_005264434.3.
DR RefSeq; XP_016860007.1; XM_017004518.1.
DR RefSeq; XP_016860008.1; XM_017004519.1.
DR PDB; 2G31; NMR; -; A=1055-1114.
DR PDB; 2JV5; NMR; -; A=1055-1108.
DR PDBsum; 2G31; -.
DR PDBsum; 2JV5; -.
DR AlphaFoldDB; Q9NQC3; -.
DR BMRB; Q9NQC3; -.
DR SMR; Q9NQC3; -.
DR BioGRID; 121400; 246.
DR CORUM; Q9NQC3; -.
DR DIP; DIP-42003N; -.
DR IntAct; Q9NQC3; 101.
DR MINT; Q9NQC3; -.
DR STRING; 9606.ENSP00000337838; -.
DR BindingDB; Q9NQC3; -.
DR ChEMBL; CHEMBL3712895; -.
DR GuidetoPHARMACOLOGY; 2838; -.
DR GlyGen; Q9NQC3; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9NQC3; -.
DR MetOSite; Q9NQC3; -.
DR PhosphoSitePlus; Q9NQC3; -.
DR SwissPalm; Q9NQC3; -.
DR BioMuta; RTN4; -.
DR DMDM; 17369290; -.
DR EPD; Q9NQC3; -.
DR jPOST; Q9NQC3; -.
DR MassIVE; Q9NQC3; -.
DR MaxQB; Q9NQC3; -.
DR PaxDb; Q9NQC3; -.
DR PeptideAtlas; Q9NQC3; -.
DR PRIDE; Q9NQC3; -.
DR ProteomicsDB; 82133; -. [Q9NQC3-1]
DR ProteomicsDB; 82134; -. [Q9NQC3-2]
DR ProteomicsDB; 82135; -. [Q9NQC3-3]
DR ProteomicsDB; 82136; -. [Q9NQC3-4]
DR ProteomicsDB; 82137; -. [Q9NQC3-5]
DR ProteomicsDB; 82138; -. [Q9NQC3-6]
DR TopDownProteomics; Q9NQC3-2; -. [Q9NQC3-2]
DR TopDownProteomics; Q9NQC3-3; -. [Q9NQC3-3]
DR TopDownProteomics; Q9NQC3-4; -. [Q9NQC3-4]
DR TopDownProteomics; Q9NQC3-5; -. [Q9NQC3-5]
DR TopDownProteomics; Q9NQC3-6; -. [Q9NQC3-6]
DR ABCD; Q9NQC3; 3 sequenced antibodies.
DR Antibodypedia; 3949; 508 antibodies from 44 providers.
DR DNASU; 57142; -.
DR Ensembl; ENST00000317610.11; ENSP00000322147.7; ENSG00000115310.19. [Q9NQC3-2]
DR Ensembl; ENST00000337526.11; ENSP00000337838.6; ENSG00000115310.19. [Q9NQC3-1]
DR Ensembl; ENST00000357376.7; ENSP00000349944.3; ENSG00000115310.19. [Q9NQC3-6]
DR Ensembl; ENST00000357732.8; ENSP00000350365.4; ENSG00000115310.19. [Q9NQC3-5]
DR Ensembl; ENST00000394609.6; ENSP00000378107.2; ENSG00000115310.19. [Q9NQC3-3]
DR Ensembl; ENST00000394611.6; ENSP00000378109.2; ENSG00000115310.19. [Q9NQC3-6]
DR Ensembl; ENST00000404909.5; ENSP00000385650.1; ENSG00000115310.19. [Q9NQC3-6]
DR Ensembl; ENST00000405240.5; ENSP00000384471.1; ENSG00000115310.19. [Q9NQC3-6]
DR GeneID; 57142; -.
DR KEGG; hsa:57142; -.
DR MANE-Select; ENST00000337526.11; ENSP00000337838.6; NM_020532.5; NP_065393.1.
DR UCSC; uc002ryc.4; human. [Q9NQC3-1]
DR CTD; 57142; -.
DR DisGeNET; 57142; -.
DR GeneCards; RTN4; -.
DR HGNC; HGNC:14085; RTN4.
DR HPA; ENSG00000115310; Low tissue specificity.
DR MIM; 604475; gene.
DR neXtProt; NX_Q9NQC3; -.
DR OpenTargets; ENSG00000115310; -.
DR PharmGKB; PA34883; -.
DR VEuPathDB; HostDB:ENSG00000115310; -.
DR eggNOG; KOG1792; Eukaryota.
DR GeneTree; ENSGT00940000156568; -.
DR HOGENOM; CLU_048580_2_1_1; -.
DR InParanoid; Q9NQC3; -.
DR OMA; FEVVDYH; -.
DR OrthoDB; 212372at2759; -.
DR PhylomeDB; Q9NQC3; -.
DR TreeFam; TF105431; -.
DR PathwayCommons; Q9NQC3; -.
DR Reactome; R-HSA-193634; Axonal growth inhibition (RHOA activation).
DR SignaLink; Q9NQC3; -.
DR SIGNOR; Q9NQC3; -.
DR BioGRID-ORCS; 57142; 18 hits in 1098 CRISPR screens.
DR ChiTaRS; RTN4; human.
DR EvolutionaryTrace; Q9NQC3; -.
DR GeneWiki; Reticulon_4; -.
DR GenomeRNAi; 57142; -.
DR Pharos; Q9NQC3; Tbio.
DR PRO; PR:Q9NQC3; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q9NQC3; protein.
DR Bgee; ENSG00000115310; Expressed in pons and 205 other tissues.
DR ExpressionAtlas; Q9NQC3; baseline and differential.
DR Genevisible; Q9NQC3; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-SubCell.
DR GO; GO:0030054; C:cell junction; IDA:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0071782; C:endoplasmic reticulum tubular network; IDA:CAFA.
DR GO; GO:0098826; C:endoplasmic reticulum tubular network membrane; IDA:UniProtKB.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0005635; C:nuclear envelope; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0014069; C:postsynaptic density; IBA:GO_Central.
DR GO; GO:0045296; F:cadherin binding; HDA:BHF-UCL.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:CAFA.
DR GO; GO:0006915; P:apoptotic process; NAS:UniProtKB.
DR GO; GO:0007413; P:axonal fasciculation; ISS:UniProtKB.
DR GO; GO:0001825; P:blastocyst formation; IEA:Ensembl.
DR GO; GO:0007420; P:brain development; IBA:GO_Central.
DR GO; GO:0060317; P:cardiac epithelial to mesenchymal transition; IEA:Ensembl.
DR GO; GO:0120078; P:cell adhesion involved in sprouting angiogenesis; IDA:UniProtKB.
DR GO; GO:0035441; P:cell migration involved in vasculogenesis; ISS:UniProtKB.
DR GO; GO:0071456; P:cellular response to hypoxia; ISS:UniProtKB.
DR GO; GO:0090156; P:cellular sphingolipid homeostasis; IEA:Ensembl.
DR GO; GO:0022009; P:central nervous system vasculogenesis; ISS:UniProtKB.
DR GO; GO:0021801; P:cerebral cortex radial glia-guided migration; ISS:UniProtKB.
DR GO; GO:0007029; P:endoplasmic reticulum organization; IDA:UniProtKB.
DR GO; GO:0071787; P:endoplasmic reticulum tubular network formation; IDA:UniProtKB.
DR GO; GO:1990809; P:endoplasmic reticulum tubular network membrane organization; IMP:UniProtKB.
DR GO; GO:0071786; P:endoplasmic reticulum tubular network organization; IMP:UniProtKB.
DR GO; GO:0002523; P:leukocyte migration involved in inflammatory response; ISS:UniProtKB.
DR GO; GO:1902430; P:negative regulation of amyloid-beta formation; IDA:UniProtKB.
DR GO; GO:0030517; P:negative regulation of axon extension; IDA:UniProtKB.
DR GO; GO:0030308; P:negative regulation of cell growth; IMP:DFLAT.
DR GO; GO:2001213; P:negative regulation of vasculogenesis; ISS:UniProtKB.
DR GO; GO:0030182; P:neuron differentiation; IBA:GO_Central.
DR GO; GO:0051292; P:nuclear pore complex assembly; IMP:UniProtKB.
DR GO; GO:0045766; P:positive regulation of angiogenesis; ISS:UniProtKB.
DR GO; GO:1905653; P:positive regulation of artery morphogenesis; ISS:UniProtKB.
DR GO; GO:0010634; P:positive regulation of epithelial cell migration; IMP:CAFA.
DR GO; GO:1905580; P:positive regulation of ERBB3 signaling pathway; IMP:CAFA.
DR GO; GO:2000347; P:positive regulation of hepatocyte proliferation; ISS:UniProtKB.
DR GO; GO:0060907; P:positive regulation of macrophage cytokine production; ISS:UniProtKB.
DR GO; GO:1905523; P:positive regulation of macrophage migration; ISS:UniProtKB.
DR GO; GO:0033601; P:positive regulation of mammary gland epithelial cell proliferation; IMP:CAFA.
DR GO; GO:1902624; P:positive regulation of neutrophil migration; ISS:UniProtKB.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; IMP:CAFA.
DR GO; GO:1905552; P:positive regulation of protein localization to endoplasmic reticulum; IDA:CAFA.
DR GO; GO:0035022; P:positive regulation of Rac protein signal transduction; ISS:UniProtKB.
DR GO; GO:0034165; P:positive regulation of toll-like receptor 9 signaling pathway; ISS:UniProtKB.
DR GO; GO:0061462; P:protein localization to lysosome; ISS:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; IMP:CAFA.
DR GO; GO:0042981; P:regulation of apoptotic process; NAS:UniProtKB.
DR GO; GO:2000172; P:regulation of branching morphogenesis of a nerve; ISS:UniProtKB.
DR GO; GO:0030334; P:regulation of cell migration; IDA:MGI.
DR DisProt; DP01855; -. [Q9NQC3-1]
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..1192
FT /note="Reticulon-4"
FT /id="PRO_0000168165"
FT TOPO_DOM 1..1018
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1019..1039
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1040..1133
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 1134..1154
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1155..1192
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 1005..1192
FT /note="Reticulon"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00170"
FT REGION 1..204
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 427..458
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 722..762
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..19
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 31..52
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 88..106
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 108..122
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 140..173
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 427..442
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 724..738
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000269|Ref.16, ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:19413330, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:22223895,
FT ECO:0007744|PubMed:22814378, ECO:0007744|PubMed:25944712"
FT MOD_RES 7
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 15
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|Ref.16, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 107
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:21406692"
FT MOD_RES 152
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99P72"
FT MOD_RES 181
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 182
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 184
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99P72"
FT MOD_RES 361
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99P72"
FT MOD_RES 446
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9JK11"
FT MOD_RES 450
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9JK11"
FT MOD_RES 511
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99P72"
FT MOD_RES 749
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99P72"
FT MOD_RES 858
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9JK11"
FT MOD_RES 881
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99P72"
FT MOD_RES 991
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1104
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT VAR_SEQ 1..993
FT /note="Missing (in isoform C)"
FT /evidence="ECO:0000303|PubMed:10667780,
FT ECO:0000303|PubMed:10773680, ECO:0000303|PubMed:11042152,
FT ECO:0000303|PubMed:12488097, ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:15498874, ECO:0000303|Ref.7,
FT ECO:0000303|Ref.8"
FT /id="VSP_005652"
FT VAR_SEQ 1..206
FT /note="Missing (in isoform D)"
FT /evidence="ECO:0000303|PubMed:11866689,
FT ECO:0000303|PubMed:12488097"
FT /id="VSP_037112"
FT VAR_SEQ 58..289
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:12488097, ECO:0000303|Ref.9"
FT /id="VSP_005654"
FT VAR_SEQ 186..1004
FT /note="Missing (in isoform B)"
FT /evidence="ECO:0000303|PubMed:10667780,
FT ECO:0000303|PubMed:10773680, ECO:0000303|PubMed:11126360,
FT ECO:0000303|PubMed:12488097, ECO:0000303|PubMed:15489334,
FT ECO:0000303|Ref.6, ECO:0000303|Ref.8"
FT /id="VSP_005655"
FT VAR_SEQ 205..1004
FT /note="Missing (in isoform B2)"
FT /evidence="ECO:0000303|PubMed:12488097,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_037113"
FT VAR_SEQ 994..1004
FT /note="AIFSAELSKTS -> MDGQKKNWKDK (in isoform C)"
FT /evidence="ECO:0000303|PubMed:10667780,
FT ECO:0000303|PubMed:10773680, ECO:0000303|PubMed:11042152,
FT ECO:0000303|PubMed:12488097, ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:15498874, ECO:0000303|Ref.7,
FT ECO:0000303|Ref.8"
FT /id="VSP_005653"
FT VARIANT 357
FT /note="D -> V (in dbSNP:rs11677099)"
FT /id="VAR_053633"
FT VARIANT 429
FT /note="L -> V (in a colorectal cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035904"
FT VARIANT 899
FT /note="E -> Q (in dbSNP:rs6757519)"
FT /id="VAR_053634"
FT VARIANT 920
FT /note="S -> C (in dbSNP:rs6757705)"
FT /id="VAR_053635"
FT CONFLICT 107
FT /note="S -> C (in Ref. 6; BAA83712)"
FT /evidence="ECO:0000305"
FT CONFLICT 135
FT /note="E -> Q (in Ref. 6; BAA83712)"
FT /evidence="ECO:0000305"
FT CONFLICT 458
FT /note="S -> P (in Ref. 2; CAB99248)"
FT /evidence="ECO:0000305"
FT CONFLICT 564
FT /note="N -> S (in Ref. 4; AAK20831)"
FT /evidence="ECO:0000305"
FT TURN 1059..1062
FT /evidence="ECO:0007829|PDB:2G31"
FT HELIX 1063..1070
FT /evidence="ECO:0007829|PDB:2G31"
FT HELIX 1074..1094
FT /evidence="ECO:0007829|PDB:2G31"
FT HELIX 1095..1097
FT /evidence="ECO:0007829|PDB:2G31"
FT HELIX 1100..1107
FT /evidence="ECO:0007829|PDB:2G31"
SQ SEQUENCE 1192 AA; 129931 MW; CDE239BBF31589CA CRC64;
MEDLDQSPLV SSSDSPPRPQ PAFKYQFVRE PEDEEEEEEE EEEDEDEDLE ELEVLERKPA
AGLSAAPVPT APAAGAPLMD FGNDFVPPAP RGPLPAAPPV APERQPSWDP SPVSSTVPAP
SPLSAAAVSP SKLPEDDEPP ARPPPPPPAS VSPQAEPVWT PPAPAPAAPP STPAAPKRRG
SSGSVDETLF ALPAASEPVI RSSAENMDLK EQPGNTISAG QEDFPSVLLE TAASLPSLSP
LSAASFKEHE YLGNLSTVLP TEGTLQENVS EASKEVSEKA KTLLIDRDLT EFSELEYSEM
GSSFSVSPKA ESAVIVANPR EEIIVKNKDE EEKLVSNNIL HNQQELPTAL TKLVKEDEVV
SSEKAKDSFN EKRVAVEAPM REEYADFKPF ERVWEVKDSK EDSDMLAAGG KIESNLESKV
DKKCFADSLE QTNHEKDSES SNDDTSFPST PEGIKDRSGA YITCAPFNPA ATESIATNIF
PLLGDPTSEN KTDEKKIEEK KAQIVTEKNT STKTSNPFLV AAQDSETDYV TTDNLTKVTE
EVVANMPEGL TPDLVQEACE SELNEVTGTK IAYETKMDLV QTSEVMQESL YPAAQLCPSF
EESEATPSPV LPDIVMEAPL NSAVPSAGAS VIQPSSSPLE ASSVNYESIK HEPENPPPYE
EAMSVSLKKV SGIKEEIKEP ENINAALQET EAPYISIACD LIKETKLSAE PAPDFSDYSE
MAKVEQPVPD HSELVEDSSP DSEPVDLFSD DSIPDVPQKQ DETVMLVKES LTETSFESMI
EYENKEKLSA LPPEGGKPYL ESFKLSLDNT KDTLLPDEVS TLSKKEKIPL QMEELSTAVY
SNDDLFISKE AQIRETETFS DSSPIEIIDE FPTLISSKTD SFSKLAREYT DLEVSHKSEI
ANAPDGAGSL PCTELPHDLS LKNIQPKVEE KISFSDDFSK NGSATSKVLL LPPDVSALAT
QAEIESIVKP KVLVKEAEKK LPSDTEKEDR SPSAIFSAEL SKTSVVDLLY WRDIKKTGVV
FGASLFLLLS LTVFSIVSVT AYIALALLSV TISFRIYKGV IQAIQKSDEG HPFRAYLESE
VAISEELVQK YSNSALGHVN CTIKELRRLF LVDDLVDSLK FAVLMWVFTY VGALFNGLTL
LILALISLFS VPVIYERHQA QIDHYLGLAN KNVKDAMAKI QAKIPGLKRK AE
