ID RTN3_HUMAN Reviewed; 1032 AA. AC O95197; B3KQS2; B7Z308; B7Z4M0; F5H774; Q147U9; Q496K2; Q53GN3; Q59EP0; AC Q5UEP2; Q6T930; Q7RTM7; Q7RTM8; Q7RTN3; DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot. DT 20-MAR-2007, sequence version 2. DT 27-MAR-2024, entry version 203. DE RecName: Full=Reticulon-3; DE AltName: Full=Homolog of ASY protein; DE Short=HAP; DE AltName: Full=Neuroendocrine-specific protein-like 2; DE Short=NSP-like protein 2; DE AltName: Full=Neuroendocrine-specific protein-like II; DE Short=NSP-like protein II; DE Short=NSPLII; GN Name=RTN3; Synonyms=ASYIP, NSPL2; 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 [GENOMIC DNA / MRNA] (ISOFORM 3), AND TISSUE RP SPECIFICITY. RC TISSUE=Retina; RX PubMed=10331947; DOI=10.1006/geno.1999.5807; RA Moreira E.F., Jaworski C.J., Rodriguez I.R.; RT "Cloning of a novel member of the reticulon gene family (RTN3): gene RT structure and chromosomal localization to 11q13."; RL Genomics 58:73-81(1999). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), HOMODIMERIZATION, INTERACTION WITH RP RTN4, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION. 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 [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), AND TISSUE SPECIFICITY. RX PubMed=14986927; RA Huang X., Yang H., Zhou Y., Liu J., Yin B., Peng X., Qiang B., Yuan J.; RT "Overexpression of human reticulon 3 (hRTN3) in astrocytoma."; RL Clin. Neuropathol. 23:1-7(2004). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY, AND RP VARIANT GLU-6. RC TISSUE=Brain; RX PubMed=15946766; DOI=10.1016/j.molbrainres.2005.04.020; RA Cai Y., Saiyin H., Lin Q., Zhang P., Tang L., Pan X., Yu L.; RT "Identification of a new RTN3 transcript, RTN3-A1, and its distribution in RT adult mouse brain."; RL Brain Res. Mol. Brain Res. 138:236-243(2005). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 4 AND 6). RC TISSUE=Brain, and Corpus callosum; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Kidney; RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., RA Tanaka A., Yokoyama S.; RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RX PubMed=16303743; DOI=10.1093/dnares/12.2.117; RA Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J., RA Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S., RA Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y., RA Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S., RA Isogai T.; RT "Signal sequence and keyword trap in silico for selection of full-length RT human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA RT libraries."; RL DNA Res. 12:117-126(2005). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16554811; DOI=10.1038/nature04632; RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G., RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., RA Hattori M., Rogers J., Lander E.S., Sakaki Y.; RT "Human chromosome 11 DNA sequence and analysis including novel gene RT identification."; RL Nature 440:497-500(2006). RN [9] 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Brain, Eye, and Lymph; 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 [11] RP IDENTIFICATION (ISOFORMS 3; 4 AND 5). RX PubMed=12832288; DOI=10.1096/fj.02-1166hyp; RA Oertle T., Klinger M., Stuermer C.A.O., Schwab M.E.; RT "A reticular rhapsody: phylogenic evolution and nomenclature of the RT RTN/Nogo gene family."; RL FASEB J. 17:1238-1247(2003). RN [12] RP INTERACTION WITH BACE1, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND RP FUNCTION. 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 [13] RP HOMODIMERIZATION, SUBCELLULAR LOCATION, AND FUNCTION. RX PubMed=16054885; DOI=10.1016/j.bbrc.2005.07.012; RA Wakana Y., Koyama S., Nakajima K., Hatsuzawa K., Nagahama M., Tani K., RA Hauri H.-P., Melancon P., Tagaya M.; RT "Reticulon 3 is involved in membrane trafficking between the endoplasmic RT reticulum and Golgi."; RL Biochem. Biophys. Res. Commun. 334:1198-1205(2005). RN [14] RP ALTERNATIVE SPLICING (ISOFORMS 1; 2; 3 AND 4). RX PubMed=15350194; DOI=10.1042/bj20040458; RA Di Scala F., Dupuis L., Gaiddon C., De Tapia M., Jokic N., RA Gonzalez de Aguilar J.-L., Raul J.-S., Ludes B., Loeffler J.-P.; RT "Tissue specificity and regulation of the N-terminal diversity of reticulon RT 3."; RL Biochem. J. 385:125-134(2005). RN [15] RP INTERACTION WITH FADD, SUBCELLULAR LOCATION, AND FUNCTION. RX PubMed=17031492; DOI=10.1007/s10495-006-0082-0; RA Xiang R., Liu Y., Zhu L., Dong W., Qi Y.; RT "Adaptor FADD is recruited by RTN3/HAP in ER-bound signaling complexes."; RL Apoptosis 11:1923-1932(2006). RN [16] 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 [17] RP INTERACTION WITH BACE1 AND BACE2. 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 [18] RP HOMODIMERIZATION, INTERACTION WITH BACE1 AND RTN4, AND SUBCELLULAR RP LOCATION. 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 [19] RP INDUCTION BY ER STRESS, INTERACTION WITH BCL2, SUBCELLULAR LOCATION, AND RP FUNCTION. RX PubMed=17191123; DOI=10.1007/s10495-006-0574-y; RA Wan Q., Kuang E., Dong W., Zhou S., Xu H., Qi Y., Liu Y.; RT "Reticulon 3 mediates Bcl-2 accumulation in mitochondria in response to RT endoplasmic reticulum stress."; RL Apoptosis 12:319-328(2007). RN [20] RP INTERACTION WITH POLIOVIRUS PROTEIN 2C (MICROBIAL INFECTION), INTERACTION RP WITH COXSACKIEVIRUS A16 PROTEIN 2C (MICROBIAL INFECTION), INTERACTION WITH RP HUMAN ENTEROVIRUS 71 PROTEIN 2C (MICROBIAL INFECTION), SUBCELLULAR RP LOCATION, AND FUNCTION (MICROBIAL INFECTION). RX PubMed=17182608; DOI=10.1074/jbc.m611145200; RA Tang W.-F., Yang S.-Y., Wu B.-W., Jheng J.-R., Chen Y.-L., Shih C.-H., RA Lin K.-H., Lai H.-C., Tang P., Horng J.-T.; RT "Reticulon 3 binds the 2C protein of enterovirus 71 and is required for RT viral replication."; RL J. Biol. Chem. 282:5888-5898(2007). RN [21] RP TOPOLOGY. RX PubMed=17699523; DOI=10.1074/jbc.m704181200; RA He W., Shi Q., Hu X., Yan R.; RT "The membrane topology of RTN3 and its effect on binding of RTN3 to RT BACE1."; RL J. Biol. Chem. 282:29144-29151(2007). RN [22] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-649 AND SER-650, 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 [23] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [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 [24] RP INTERACTION WITH ATL2. 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 [25] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], 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 [26] 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 [27] RP INTERACTION WITH ZFYVE27 AND KIF5A. RX PubMed=21976701; DOI=10.1091/mbc.e11-01-0068; RA Matsuzaki F., Shirane M., Matsumoto M., Nakayama K.I.; RT "Protrudin serves as an adaptor molecule that connects KIF5 and its cargoes RT in vesicular transport during process formation."; RL Mol. Biol. Cell 22:4602-4620(2011). RN [28] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], 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 [29] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [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 [30] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-30; SER-229; SER-246; SER-316 RP AND SER-453, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP 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 [31] RP SUBCELLULAR LOCATION. 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 [32] RP FUNCTION. 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 [33] RP IDENTIFICATION BY MASS 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 [34] RP INTERACTION WITH WEST NILE VIRUS PROTEIN NS4A, AND SUBCELLULAR LOCATION. RX PubMed=29117567; DOI=10.1016/j.celrep.2017.10.055; RA Aktepe T.E., Liebscher S., Prier J.E., Simmons C.P., Mackenzie J.M.; RT "The host protein reticulon 3.1A is utilized by flaviviruses to facilitate RT membrane remodelling."; RL Cell Rep. 21:1639-1654(2017). RN [35] RP FUNCTION, INTERACTION WITH TRIM25 AND RIGI, INDUCTION BY VIRAL INFECTION, RP AND SUBCELLULAR LOCATION. RX PubMed=34313226; DOI=10.7554/elife.68958; RA Yang Z., Wang J., He B., Zhang X., Li X., Kuang E.; RT "RTN3 inhibits RIG-I-mediated antiviral responses by impairing TRIM25- RT mediated K63-linked polyubiquitination."; RL Elife 10:0-0(2021). RN [36] {ECO:0007744|PDB:7BRU} RP X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 244-264 IN CHIMERIC CONSTRUCT RP WITH GABARAP. RX PubMed=32620754; DOI=10.1038/s41467-020-17163-y; RA Mochida K., Yamasaki A., Matoba K., Kirisako H., Noda N.N., Nakatogawa H.; RT "Super-assembly of ER-phagy receptor Atg40 induces local ER remodeling at RT contacts with forming autophagosomal membranes."; RL Nat. Commun. 11:3306-3306(2020). CC -!- FUNCTION: May be involved in membrane trafficking in the early CC secretory pathway. Inhibits BACE1 activity and amyloid precursor CC protein processing. May induce caspase-8 cascade and apoptosis. May CC favor BCL2 translocation to the mitochondria upon endoplasmic reticulum CC stress. Induces the formation of endoplasmic reticulum tubules CC (PubMed:25612671). Also acts as an inflammation-resolving regulator by CC interacting with both TRIM25 and RIGI, subsequently impairing RIGI CC 'Lys-63'-linked polyubiquitination leading to IRF3 and NF-kappa-B CC inhibition. {ECO:0000269|PubMed:15286784, ECO:0000269|PubMed:16054885, CC ECO:0000269|PubMed:17031492, ECO:0000269|PubMed:17191123, CC ECO:0000269|PubMed:25612671}. CC -!- FUNCTION: (Microbial infection) Plays a positive role in viral CC replication and pathogenesis of enteroviruses. CC {ECO:0000269|PubMed:17182608}. CC -!- SUBUNIT: Homodimer. Interacts with ATL1 (By similarity). Interacts with CC RTN4. Isoform 3 interacts with BACE1, BACE2, BCL2 and FADD. Interacts CC with ATL2. Interacts with TMEM33 (By similarity). Interacts with CC ZFYVE27 and with KIF5A in a ZFYVE27-dependent manner (PubMed:21976701). CC Interacts with RIGI (PubMed:34313226). Interacts with TRIM25 CC (PubMed:34313226). {ECO:0000250|UniProtKB:Q9ES97, CC ECO:0000269|PubMed:12811824, ECO:0000269|PubMed:15286784, CC ECO:0000269|PubMed:16965550, ECO:0000269|PubMed:16979658, CC ECO:0000269|PubMed:17031492, ECO:0000269|PubMed:17191123, CC ECO:0000269|PubMed:19665976, ECO:0000269|PubMed:21976701, CC ECO:0000269|PubMed:34313226}. CC -!- SUBUNIT: (Microbial infection) Interacts with Coxsackievirus A16, CC enterovirus 71 and poliovirus P2C proteins (PubMed:17182608). CC {ECO:0000269|PubMed:17182608, ECO:0000269|PubMed:29117567}. CC -!- SUBUNIT: (Microbial infection) Interacts with West Nile virus protein CC NS4A. {ECO:0000269|PubMed:29117567}. CC -!- INTERACTION: CC O95197; O14735: CDIPT; NbExp=3; IntAct=EBI-740467, EBI-358858; CC O95197; Q9Y5P4: CERT1; NbExp=3; IntAct=EBI-740467, EBI-739994; CC O95197; Q969Q6: PPP2R3C; NbExp=3; IntAct=EBI-740467, EBI-2561661; CC O95197; P43378: PTPN9; NbExp=5; IntAct=EBI-740467, EBI-742898; CC O95197; Q6IQ43: PTPN9; NbExp=3; IntAct=EBI-740467, EBI-10250413; CC O95197; Q13596: SNX1; NbExp=3; IntAct=EBI-740467, EBI-2822329; CC O95197; P54274: TERF1; NbExp=2; IntAct=EBI-740467, EBI-710997; CC O95197-3; P56817-1: BACE1; NbExp=2; IntAct=EBI-11525735, EBI-2433297; CC O95197-3; Q8TDT2: GPR152; NbExp=3; IntAct=EBI-11525735, EBI-13345167; CC O95197-3; Q8WV92: MITD1; NbExp=3; IntAct=EBI-11525735, EBI-2691489; CC O95197-3; Q9ULP0-2: NDRG4; NbExp=3; IntAct=EBI-11525735, EBI-11978907; CC O95197-3; P26678: PLN; NbExp=3; IntAct=EBI-11525735, EBI-692836; CC O95197-3; P43378: PTPN9; NbExp=3; IntAct=EBI-11525735, EBI-742898; CC O95197-3; Q96LZ7: RMDN2; NbExp=3; IntAct=EBI-11525735, EBI-2806908; CC O95197-3; Q9NQC3-5: RTN4; NbExp=3; IntAct=EBI-11525735, EBI-17721653; CC O95197-3; Q9NTJ5: SACM1L; NbExp=3; IntAct=EBI-11525735, EBI-3917235; CC O95197-3; Q99726: SLC30A3; NbExp=3; IntAct=EBI-11525735, EBI-10294651; CC O95197-3; Q8IWU4: SLC30A8; NbExp=3; IntAct=EBI-11525735, EBI-10262251; CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane CC {ECO:0000269|PubMed:12811824, ECO:0000269|PubMed:15286784, CC ECO:0000269|PubMed:16054885, ECO:0000269|PubMed:16979658, CC ECO:0000269|PubMed:17031492, ECO:0000269|PubMed:17182608, CC ECO:0000269|PubMed:17191123, ECO:0000269|PubMed:24262037, CC ECO:0000269|PubMed:29117567, ECO:0000269|PubMed:34313226}; Multi-pass CC membrane protein {ECO:0000255}. Golgi apparatus membrane CC {ECO:0000269|PubMed:15286784, ECO:0000269|PubMed:16054885, CC ECO:0000269|PubMed:16979658, ECO:0000269|PubMed:29117567}; Multi-pass CC membrane protein {ECO:0000255}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=7; CC Name=1; Synonyms=A1, A4b; CC IsoId=O95197-1; Sequence=Displayed; CC Name=2; Synonyms=A2, A3b; CC IsoId=O95197-2; Sequence=VSP_023759; CC Name=3; Synonyms=B1, A1; CC IsoId=O95197-3; Sequence=VSP_023759, VSP_023760; CC Name=4; Synonyms=B2, A2; CC IsoId=O95197-4; Sequence=VSP_023760; CC Name=5; CC IsoId=O95197-5; Sequence=VSP_023759, VSP_023760, VSP_023761; CC Name=6; CC IsoId=O95197-6; Sequence=VSP_045319, VSP_045320; CC Name=7; CC IsoId=O95197-7; Sequence=VSP_047008; CC -!- TISSUE SPECIFICITY: Isoform 3 is widely expressed, with highest levels CC in brain, where it is enriched in neuronal cell bodies from gray matter CC (at protein level). Three times more abundant in macula than in CC peripheral retina. Isoform 1 is expressed at high levels in brain and CC at low levels in skeletal muscle. Isoform 2 is only found in melanoma. CC {ECO:0000269|PubMed:10331947, ECO:0000269|PubMed:12811824, CC ECO:0000269|PubMed:14986927, ECO:0000269|PubMed:15286784, CC ECO:0000269|PubMed:15946766}. CC -!- INDUCTION: By endoplasmic reticulum stress (at protein level) CC (PubMed:17191123). Up-regulated and self-aggregates upon RNA viral CC infection (PubMed:34313226). {ECO:0000269|PubMed:17191123, CC ECO:0000269|PubMed:34313226}. CC -!- SEQUENCE CAUTION: CC Sequence=BAD93008.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF059524; AAC99319.1; -; mRNA. DR EMBL; AF059529; AAD20951.1; -; Genomic_DNA. DR EMBL; AF059525; AAD20951.1; JOINED; Genomic_DNA. DR EMBL; AF059526; AAD20951.1; JOINED; Genomic_DNA. DR EMBL; AF059527; AAD20951.1; JOINED; Genomic_DNA. DR EMBL; AF059528; AAD20951.1; JOINED; Genomic_DNA. DR EMBL; AF119297; AAD26810.1; -; mRNA. DR EMBL; AY427821; AAR02474.1; -; mRNA. DR EMBL; AY750848; AAU81930.1; -; mRNA. DR EMBL; AP000753; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AP006289; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AK297529; BAH12606.1; -; mRNA. DR EMBL; AB209771; BAD93008.1; ALT_INIT; mRNA. DR EMBL; AK075412; BAG52134.1; -; mRNA. DR EMBL; AK222898; BAD96618.1; -; mRNA. DR EMBL; AK295361; BAH12044.1; -; mRNA. DR EMBL; CH471076; EAW74170.1; -; Genomic_DNA. DR EMBL; BC000634; AAH00634.1; -; mRNA. DR EMBL; BC010556; AAH10556.1; -; mRNA. DR EMBL; BC011394; AAH11394.1; -; mRNA. DR EMBL; BC022993; AAH22993.1; -; mRNA. DR EMBL; BC100822; AAI00823.1; -; mRNA. DR EMBL; BC100823; AAI00824.1; -; mRNA. DR EMBL; BC105981; AAI05982.1; -; mRNA. DR EMBL; BC105982; AAI05983.1; -; mRNA. DR EMBL; BC118628; AAI18629.1; -; mRNA. DR EMBL; BC118550; AAI18551.1; -; mRNA. DR EMBL; BK001685; DAA01931.1; -; mRNA. DR EMBL; BK001681; DAA01941.1; -; mRNA. DR EMBL; BK001684; DAA01943.1; -; mRNA. DR CCDS; CCDS41664.1; -. [O95197-4] DR CCDS; CCDS58141.1; -. [O95197-1] DR CCDS; CCDS58142.1; -. [O95197-7] DR CCDS; CCDS58143.1; -. [O95197-6] DR CCDS; CCDS8048.1; -. [O95197-5] DR CCDS; CCDS8049.1; -. [O95197-3] DR CCDS; CCDS8050.1; -. [O95197-2] DR RefSeq; NP_001252518.1; NM_001265589.1. [O95197-1] DR RefSeq; NP_001252519.1; NM_001265590.1. [O95197-7] DR RefSeq; NP_001252520.1; NM_001265591.1. [O95197-6] DR RefSeq; NP_006045.1; NM_006054.3. [O95197-3] DR RefSeq; NP_958831.1; NM_201428.2. [O95197-2] DR RefSeq; NP_958832.1; NM_201429.2. [O95197-4] DR RefSeq; NP_958833.1; NM_201430.2. [O95197-5] DR PDB; 7BRU; X-ray; 2.15 A; A/B/C=244-264. DR PDBsum; 7BRU; -. DR AlphaFoldDB; O95197; -. DR SMR; O95197; -. DR BioGRID; 115598; 167. DR CORUM; O95197; -. DR IntAct; O95197; 46. DR MINT; O95197; -. DR STRING; 9606.ENSP00000367050; -. DR GlyCosmos; O95197; 4 sites, 1 glycan. DR GlyGen; O95197; 5 sites, 1 O-linked glycan (5 sites). DR iPTMnet; O95197; -. DR PhosphoSitePlus; O95197; -. DR SwissPalm; O95197; -. DR BioMuta; RTN3; -. DR EPD; O95197; -. DR jPOST; O95197; -. DR MassIVE; O95197; -. DR MaxQB; O95197; -. DR PaxDb; 9606-ENSP00000367050; -. DR PeptideAtlas; O95197; -. DR ProteomicsDB; 27402; -. DR ProteomicsDB; 50700; -. [O95197-1] DR ProteomicsDB; 50701; -. [O95197-2] DR ProteomicsDB; 50702; -. [O95197-3] DR ProteomicsDB; 50703; -. [O95197-4] DR ProteomicsDB; 50704; -. [O95197-5] DR ProteomicsDB; 6613; -. DR Pumba; O95197; -. DR TopDownProteomics; O95197-2; -. [O95197-2] DR TopDownProteomics; O95197-3; -. [O95197-3] DR TopDownProteomics; O95197-4; -. [O95197-4] DR Antibodypedia; 2923; 230 antibodies from 32 providers. DR DNASU; 10313; -. DR Ensembl; ENST00000339997.8; ENSP00000344106.4; ENSG00000133318.14. [O95197-2] DR Ensembl; ENST00000341307.6; ENSP00000340903.2; ENSG00000133318.14. [O95197-5] DR Ensembl; ENST00000354497.4; ENSP00000346492.4; ENSG00000133318.14. [O95197-6] DR Ensembl; ENST00000356000.7; ENSP00000348279.3; ENSG00000133318.14. [O95197-4] DR Ensembl; ENST00000377819.10; ENSP00000367050.5; ENSG00000133318.14. [O95197-1] DR Ensembl; ENST00000537981.5; ENSP00000440874.1; ENSG00000133318.14. [O95197-3] DR Ensembl; ENST00000540798.5; ENSP00000442733.1; ENSG00000133318.14. [O95197-7] DR GeneID; 10313; -. DR KEGG; hsa:10313; -. DR MANE-Select; ENST00000377819.10; ENSP00000367050.5; NM_001265589.2; NP_001252518.1. DR UCSC; uc001nxm.3; human. [O95197-1] DR AGR; HGNC:10469; -. DR CTD; 10313; -. DR DisGeNET; 10313; -. DR GeneCards; RTN3; -. DR HGNC; HGNC:10469; RTN3. DR HPA; ENSG00000133318; Tissue enhanced (brain). DR MIM; 604249; gene. DR neXtProt; NX_O95197; -. DR OpenTargets; ENSG00000133318; -. DR PharmGKB; PA34882; -. DR VEuPathDB; HostDB:ENSG00000133318; -. DR eggNOG; KOG1792; Eukaryota. DR GeneTree; ENSGT00940000157482; -. DR HOGENOM; CLU_048580_1_0_1; -. DR InParanoid; O95197; -. DR OMA; TLWYLFE; -. DR OrthoDB; 7284at2759; -. DR PhylomeDB; O95197; -. DR TreeFam; TF105431; -. DR PathwayCommons; O95197; -. DR Reactome; R-HSA-8849932; Synaptic adhesion-like molecules. DR SignaLink; O95197; -. DR BioGRID-ORCS; 10313; 38 hits in 1158 CRISPR screens. DR ChiTaRS; RTN3; human. DR GeneWiki; RTN3; -. DR GenomeRNAi; 10313; -. DR Pharos; O95197; Tbio. DR PRO; PR:O95197; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; O95197; Protein. DR Bgee; ENSG00000133318; Expressed in Brodmann (1909) area 9 and 190 other cell types or tissues. DR ExpressionAtlas; O95197; baseline and differential. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB. DR GO; GO:0005615; C:extracellular space; TAS:ProtInc. DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB. DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell. DR GO; GO:0043005; C:neuron projection; IBA:GO_Central. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0014069; C:postsynaptic density; IBA:GO_Central. DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW. DR GO; GO:0007420; P:brain development; IBA:GO_Central. DR GO; GO:0071787; P:endoplasmic reticulum tubular network formation; IDA:UniProtKB. DR GO; GO:0071786; P:endoplasmic reticulum tubular network organization; IMP:UniProtKB. DR GO; GO:1902430; P:negative regulation of amyloid-beta formation; IDA:UniProtKB. DR GO; GO:0030182; P:neuron differentiation; IBA:GO_Central. DR GO; GO:0016192; P:vesicle-mediated transport; IEA:UniProtKB-KW. DR Gene3D; 1.20.5.2480; -; 1. DR InterPro; IPR003388; Reticulon. DR InterPro; IPR046964; RTN1-4. DR PANTHER; PTHR45799:SF4; RETICULON-3; 1. DR PANTHER; PTHR45799; RETICULON-LIKE PROTEIN; 1. DR Pfam; PF02453; Reticulon; 1. DR PROSITE; PS50845; RETICULON; 1. DR Genevisible; O95197; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Apoptosis; KW Endoplasmic reticulum; ER-Golgi transport; Golgi apparatus; KW Host-virus interaction; Membrane; Phosphoprotein; Reference proteome; KW Stress response; Transmembrane; Transmembrane helix; Transport. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0007744|PubMed:19413330, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:22223895" FT CHAIN 2..1032 FT /note="Reticulon-3" FT /id="PRO_0000168163" FT TOPO_DOM 2..863 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT INTRAMEM 864..887 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 888..947 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT INTRAMEM 948..968 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 969..972 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT INTRAMEM 973..993 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 994..1032 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 844..1032 FT /note="Reticulon" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00170" FT REGION 1..61 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 545..617 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 696..726 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 987..1032 FT /note="Interaction with FADD" FT /evidence="ECO:0000269|PubMed:17031492" FT REGION 1000..1002 FT /note="Interaction with BACE1" FT COMPBIAS 1..21 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 37..61 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 545..568 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0007744|PubMed:19413330, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:22223895" FT MOD_RES 30 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 229 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 243 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9ES97" FT MOD_RES 246 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 283 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q6RJR6" FT MOD_RES 316 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 453 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 649 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 650 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 735 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9ES97" FT VAR_SEQ 48..843 FT /note="Missing (in isoform 6)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_045319" FT VAR_SEQ 48..159 FT /note="Missing (in isoform 7)" FT /evidence="ECO:0000305" FT /id="VSP_047008" FT VAR_SEQ 48..66 FT /note="Missing (in isoform 2, isoform 3 and isoform 5)" FT /evidence="ECO:0000303|PubMed:10331947, FT ECO:0000303|PubMed:12811824, ECO:0000303|PubMed:14986927, FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:15946766, FT ECO:0000303|PubMed:16303743, ECO:0000303|Ref.6" FT /id="VSP_023759" FT VAR_SEQ 67..843 FT /note="Missing (in isoform 3, isoform 4 and isoform 5)" FT /evidence="ECO:0000303|PubMed:10331947, FT ECO:0000303|PubMed:12811824, ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:14986927, ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:16303743, ECO:0000303|Ref.6" FT /id="VSP_023760" FT VAR_SEQ 914..1032 FT /note="AYLDVDITLSSEAFHNYMNAAMVHINRALKLIIRLFLVEDLVDSLKLAVFMW FT LMTYVGAVFNGITLLILAELLIFSVPIVYEKYKTQIDHYVGIARDQTKSIVEKIQAKLP FT GIAKKKAE -> PRLITMLASPEIRPSQLLKRSKQNSLESPKKRQNKYMETRNATVTKT FT PFNSYNVVTCTMKENTQCQLEPAFQAFFLIWCFLPSFPFNPQYQAQKLMD (in FT isoform 6)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_045320" FT VAR_SEQ 999..1032 FT /note="TQIDHYVGIARDQTKSIVEKIQAKLPGIAKKKAE -> DPSKTPWNRQKKGR FT ISTWKPEMQQLLKHHLIVITSLLVL (in isoform 5)" FT /evidence="ECO:0000305" FT /id="VSP_023761" FT VARIANT 6 FT /note="A -> E (in dbSNP:rs11551944)" FT /evidence="ECO:0000269|PubMed:15946766" FT /id="VAR_031164" FT VARIANT 501 FT /note="D -> H (in dbSNP:rs7936660)" FT /id="VAR_057713" FT CONFLICT 871 FT /note="A -> V (in Ref. 4; BAD93008)" FT /evidence="ECO:0000305" FT HELIX 254..260 FT /evidence="ECO:0007829|PDB:7BRU" FT TURN 261..263 FT /evidence="ECO:0007829|PDB:7BRU" SQ SEQUENCE 1032 AA; 112611 MW; 26B372B82BFC6361 CRC64; MAEPSAATQS HSISSSSFGA EPSAPGGGGS PGACPALGTK SCSSSCADSF VSSSSSQPVS LFSTSQEGLS SLCSDEPSSE IMTSSFLSSS EIHNTGLTIL HGEKSHVLGS QPILAKEGKD HLDLLDMKKM EKPQGTSNNV SDSSVSLAAG VHCDRPSIPA SFPEHPAFLS KKIGQVEEQI DKETKNPNGV SSREAKTALD ADDRFTLLTA QKPPTEYSKV EGIYTYSLSP SKVSGDDVIE KDSPESPFEV IIDKAAFDKE FKDSYKESTD DFGSWSVHTD KESSEDISET NDKLFPLRNK EAGRYPMSAL LSRQFSHTNA ALEEVSRCVN DMHNFTNEIL TWDLVPQVKQ QTDKSSDCIT KTTGLDMSEY NSEIPVVNLK TSTHQKTPVC SIDGSTPITK STGDWAEASL QQENAITGKP VPDSLNSTKE FSIKGVQGNM QKQDDTLAEL PGSPPEKCDS LGSGVATVKV VLPDDHLKDE MDWQSSALGE ITEADSSGES DDTVIEDITA DTSFENNKIQ AEKPVSIPSA VVKTGEREIK EIPSCEREEK TSKNFEELVS DSELHQDQPD ILGRSPASEA ACSKVPDTNV SLEDVSEVAP EKPITTENPK LPSTVSPNVF NETEFSLNVT TSAYLESLHG KNVKHIDDSS PEDLIAAFTE TRDKGIVDSE RNAFKAISEK MTDFKTTPPV EVLHENESGG SEIKDIGSKY SEQSKETNGS EPLGVFPTQG TPVASLDLEQ EQLTIKALKE LGERQVEKST SAQRDAELPS EEVLKQTFTF APESWPQRSY DILERNVKNG SDLGISQKPI TIRETTRVDA VSSLSKTELV KKHVLARLLT DFSVHDLIFW RDVKKTGFVF GTTLIMLLSL AAFSVISVVS YLILALLSVT ISFRIYKSVI QAVQKSEEGH PFKAYLDVDI TLSSEAFHNY MNAAMVHINR ALKLIIRLFL VEDLVDSLKL AVFMWLMTYV GAVFNGITLL ILAELLIFSV PIVYEKYKTQ IDHYVGIARD QTKSIVEKIQ AKLPGIAKKK AE //