RTN3_HUMAN
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 03-AUG-2022, entry version 194.
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 DDX58, 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).
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). Acts also as an inflammation-resolving regulator by
CC interacting with both TRIM25 and RIG-I/DDX58, subsequently impairing
CC DDX58 '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 the 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 DDX58 (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 ---------------------------------------------------------------------------
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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; 144.
DR CORUM; O95197; -.
DR IntAct; O95197; 47.
DR MINT; O95197; -.
DR STRING; 9606.ENSP00000367050; -.
DR GlyGen; O95197; 4 sites, 1 O-linked glycan (4 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; O95197; -.
DR PeptideAtlas; O95197; -.
DR PRIDE; 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 TopDownProteomics; O95197-2; -. [O95197-2]
DR TopDownProteomics; O95197-3; -. [O95197-3]
DR TopDownProteomics; O95197-4; -. [O95197-4]
DR Antibodypedia; 2923; 203 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 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; KYQDHVD; -.
DR OrthoDB; 423549at2759; -.
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; 24 hits in 1078 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 188 other tissues.
DR ExpressionAtlas; O95197; baseline and differential.
DR Genevisible; O95197; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
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:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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 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; 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
