ID RTN4_RAT Reviewed; 1163 AA. AC Q9JK11; Q9JK10; Q9R0D9; Q9WUE9; Q9WUF0; DT 16-NOV-2001, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2000, sequence version 1. DT 27-MAR-2024, entry version 164. DE RecName: Full=Reticulon-4; DE AltName: Full=Foocen; DE AltName: Full=Glut4 vesicle 20 kDa protein; DE AltName: Full=Neurite outgrowth inhibitor; DE Short=Nogo protein; GN Name=Rtn4; Synonyms=Nogo; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM C), AND PARTIAL PROTEIN SEQUENCE. RC STRAIN=Sprague-Dawley; TISSUE=Adipocyte; RX PubMed=10231557; DOI=10.1016/s0167-4889(99)00033-6; RA Morris N.J., Ross S.A., Neveu J.M., Lane W.S., Lienhard G.E.; RT "Cloning and characterization of a 22 kDa protein from rat adipocytes: a RT new member of the reticulon family."; RL Biochim. Biophys. Acta 1450:68-76(1999). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A; B AND C). RX PubMed=10667796; DOI=10.1038/35000219; RA Chen M.S., Huber A.B., Van der Haar M.E., Frank M., Schnell L., RA Spillmann A.A., Christ F., Schwab M.E.; RT "Nogo-A is a myelin-associated neurite outgrowth inhibitor and an antigen RT for monoclonal antibody IN-1."; RL Nature 403:434-439(2000). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS B AND B2). RC STRAIN=Wistar Kyoto; TISSUE=Vascular smooth muscle; RA Ito T., Schwartz S.M.; RT "Cloning of a member of the reticulon gene family in rat: one of two minor RT splice variants."; RL Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases. RN [4] RP FUNCTION, AND DOMAIN. RX PubMed=12037567; DOI=10.1038/417547a; RA GrandPre T., Li S., Strittmatter S.M.; RT "Nogo-66 receptor antagonist peptide promotes axonal regeneration."; RL Nature 417:547-551(2002). RN [5] RP INTERACTION WITH CNTNAP1. RX PubMed=14592966; DOI=10.1093/emboj/cdg570; RA Nie D.-Y., Zhou Z.-H., Ang B.-T., Teng F.Y.H., Xu G., Xiang T., Wang C.-Y., RA Zeng L., Takeda Y., Xu T.-L., Ng Y.K., Faivre-Sarrailh C., Popko B., RA Ling E.-A., Schachner M., Watanabe K., Pallen C.J., Tang B.L., Xiao Z.-C.; RT "Nogo-A at CNS paranodes is a ligand of Caspr: possible regulation of K(+) RT channel localization."; RL EMBO J. 22:5666-5678(2003). RN [6] RP FUNCTION (ISOFORM A). RX PubMed=12843238; DOI=10.1523/jneurosci.23-13-05393.2003; RA Oertle T., van der Haar M.E., Bandtlow C.E., Robeva A., Burfeind P., RA Buss A., Huber A.B., Simonen M., Schnell L., Brosamle C., Kaupmann K., RA Vallon R., Schwab M.E.; RT "Nogo-A inhibits neurite outgrowth and cell spreading with three discrete RT regions."; RL J. Neurosci. 23:5393-5406(2003). RN [7] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-107, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=16641100; DOI=10.1073/pnas.0600895103; RA Hoffert J.D., Pisitkun T., Wang G., Shen R.-F., Knepper M.A.; RT "Quantitative phosphoproteomics of vasopressin-sensitive renal cells: RT regulation of aquaporin-2 phosphorylation at two sites."; RL Proc. Natl. Acad. Sci. U.S.A. 103:7159-7164(2006). RN [8] 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 [9] RP FUNCTION (ISOFORM A). RX PubMed=20573699; DOI=10.1242/dev.048371; RA Petrinovic M.M., Duncan C.S., Bourikas D., Weinman O., Montani L., RA Schroeter A., Maerki D., Sommer L., Stoeckli E.T., Schwab M.E.; RT "Neuronal Nogo-A regulates neurite fasciculation, branching and extension RT in the developing nervous system."; RL Development 137:2539-2550(2010). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-16; SER-329; SER-333; RP SER-425; THR-429; SER-689; SER-766; SER-830; THR-832 AND SER-922, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22673903; DOI=10.1038/ncomms1871; RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., RA Olsen J.V.; RT "Quantitative maps of protein phosphorylation sites across 14 different rat RT organs and tissues."; RL Nat. Commun. 3:876-876(2012). CC -!- FUNCTION: Required to induce the formation and stabilization of CC endoplasmic reticulum (ER) tubules. They regulate membrane CC morphogenesis in the ER by promoting tubular ER production. They CC influence nuclear envelope expansion, nuclear pore complex formation CC and proper localization of inner nuclear membrane proteins. However CC each isoform have specific functions mainly depending on their tissue CC expression specificities. {ECO: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:12037567, CC PubMed:12843238, PubMed:20573699). Regulates the radial migration of CC cortical neurons via an RTN4R-LINGO1 containing receptor complex. 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:12037567, ECO:0000269|PubMed:12843238, CC ECO:0000269|PubMed:20573699}. CC -!- FUNCTION: [Isoform B]: Mainly function in endothelial cells and CC vascular smooth muscle cells, is also involved in immune system CC regulation (By similarity). Modulator of vascular remodeling, promotes CC the migration of endothelial cells but inhibits the migration of CC vascular smooth muscle cells. Regulates endothelial sphingolipid CC biosynthesis with direct effects on vascular function and blood CC pressure. Inhibits serine palmitoyltransferase, SPTLC1, the rate- CC limiting enzyme of the novo sphingolipid biosynthetic pathway, thereby CC controlling production of endothelial sphingosine-1-phosphate (S1P). CC Required to promote macrophage homing and functions such as CC cytokine/chemokine gene expression involved in angiogenesis, CC arteriogenesis and tissue repair. Mediates ICAM1 induced CC transendothelial migration of leukocytes such as monocytes and CC neutrophils and acute inflammation. Necessary for immune responses CC triggered by nucleic acid sensing TLRs, such as TLR9, is required for CC proper TLR9 location to endolysosomes. Also involved in immune response CC to LPS. Plays a role in liver regeneration through the modulation of CC hepatocytes proliferation (By similarity). Reduces the anti-apoptotic CC activity of Bcl-xl and Bcl-2. This is likely consecutive to their CC change in subcellular location, from the mitochondria to the CC endoplasmic reticulum, after binding and sequestration. With isoform C, CC inhibits BACE1 activity and amyloid precursor protein processing (By CC similarity). {ECO:0000250|UniProtKB:Q99P72, CC ECO:0000250|UniProtKB:Q9NQC3}. 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 (By similarity). CC {ECO:0000250|UniProtKB:Q99P72, ECO:0000250|UniProtKB:Q9NQC3}. CC -!- SUBUNIT: Binds to RTN4R (By similarity). Interacts with ATL1 CC (PubMed:19665976). Interacts with TMEM170A (By similarity). Interacts CC with RTN4IP1 (By similarity). {ECO:0000250|UniProtKB:Q99P72, CC ECO:0000250|UniProtKB:Q9NQC3, ECO:0000269|PubMed:19665976}. CC -!- SUBUNIT: [Isoform A]: Interacts in trans with CNTNAP1 CC (PubMed:14592966). Interacts with REEP5 (By similarity). Interacts with CC synaptic plasticity regulator PANTS; the interaction results in CC enhanced RTN4-mediated inhibition of AMPA receptor clustering (By CC similarity). Interacts with GPR50 (By similarity). CC {ECO:0000250|UniProtKB:Q9NQC3, ECO:0000269|PubMed:14592966}. CC -!- SUBUNIT: [Isoform B]: Homodimer (By similarity). Interacts with CC BAD/Bcl-xl and BCL2. Interact with RTN3 (By similarity). Interacts with CC NGBR (By similarity). Interacts with SPTLC1 (By similarity). Interacts CC with GRAMD4 (By similarity). Interacts with CDH5 (By similarity). CC Interacts with BACE1 and BACE2 (By similarity). Interacts with REEP5 CC (By similarity). Interacts with RETREG3 (By similarity). CC {ECO:0000250|UniProtKB:Q99P72, ECO:0000250|UniProtKB:Q9NQC3}. CC -!- SUBUNIT: [Isoform C]: Interacts with BACE1 and BACE2 (By similarity). CC Interacts with TMEM33 (By similarity). {ECO:0000250|UniProtKB:Q9NQC3}. CC -!- INTERACTION: CC Q9JK11-1; Q6PST4: Atl1; NbExp=6; IntAct=EBI-919989, EBI-2410213; CC Q9JK11-1; P48722: Hspa4l; Xeno; NbExp=6; IntAct=EBI-919989, EBI-8314699; CC Q9JK11-1; O95136: S1PR2; Xeno; NbExp=2; IntAct=EBI-919989, EBI-10634606; CC Q9JK11-1; P52592: S1pr2; Xeno; NbExp=3; IntAct=EBI-919989, EBI-16091339; CC Q9JK11-3; Q8WXF7: ATL1; Xeno; NbExp=2; IntAct=EBI-920002, EBI-2410266; CC -!- SUBCELLULAR LOCATION: [Isoform A]: Endoplasmic reticulum membrane CC {ECO:0000250|UniProtKB:Q9NQC3}; Multi-pass membrane protein CC {ECO:0000255}. Cell membrane {ECO:0000250|UniProtKB:Q9NQC3}; Multi-pass CC membrane protein {ECO:0000255}; Cytoplasmic side CC {ECO:0000250|UniProtKB:Q9NQC3}. Synapse {ECO:0000250|UniProtKB:Q99P72}. CC Note=Anchored to the membrane of the endoplasmic reticulum (ER) through CC 2 putative transmembrane domains. Localizes throughout the ER tubular CC network. Co-localizes with TMEM33 at the ER sheets. CC {ECO:0000250|UniProtKB:Q9NQC3}. CC -!- SUBCELLULAR LOCATION: [Isoform B]: Endoplasmic reticulum membrane CC {ECO:0000250|UniProtKB:Q9NQC3}; Multi-pass membrane protein CC {ECO:0000255}. Cell membrane {ECO:0000250|UniProtKB:Q9NQC3}; Multi-pass CC membrane protein {ECO:0000255}; Extracellular side CC {ECO:0000250|UniProtKB:Q9NQC3}. Cell junction CC {ECO:0000250|UniProtKB:Q9NQC3}. Note=Mainly located on endoplasmic CC reticulum tubules and sheet edges. Upon ICAM1 engagement, redistributed CC toward endothelial junctions where interacts with CDH5. CC {ECO:0000250|UniProtKB:Q9NQC3}. CC -!- SUBCELLULAR LOCATION: [Isoform C]: Endoplasmic reticulum membrane CC {ECO:0000250|UniProtKB:Q9NQC3}; Multi-pass membrane protein CC {ECO:0000255}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=A; Synonyms=Nogo-A, NI-220-250; CC IsoId=Q9JK11-1; Sequence=Displayed; CC Name=B; Synonyms=Nogo-B, Foocen-M1; CC IsoId=Q9JK11-2; Sequence=VSP_005658; CC Name=C; Synonyms=Nogo-C, VP20; CC IsoId=Q9JK11-3; Sequence=VSP_005656, VSP_005657; CC Name=B2; Synonyms=Foocen-M2; CC IsoId=Q9JK11-4; Sequence=VSP_005659; CC -!- TISSUE SPECIFICITY: Isoforms A, B and C are present in optic nerve, CC spinal cord and cerebral cortex. Isoforms A and B are present in dorsal CC root ganglion, sciatic nerve and PC12 cells after longer exposure. CC Isoforms B and C are detected in kidney, cartilage, skin, lung and CC spleen. Isoform C is expressed at high level in skeletal muscle. In CC adult animals isoform A is expressed mainly in the nervous system. 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. {ECO:0000269|PubMed:12037567}. CC -!- DOMAIN: [Isoform B]: N-terminal part, called Am-Nogo-B(1-200), is the CC functional domain for RTN4B-mediated signaling in endothelial and CC vascular smooth muscle cells. {ECO:0000250|UniProtKB:Q9NQC3}. CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Nerve regrowth: nipped by a CC no-go - Issue 69 of April 2006; CC URL="https://web.expasy.org/spotlight/back_issues/069"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF051335; AAF01564.1; -; mRNA. DR EMBL; AJ242961; CAB71027.1; -; mRNA. DR EMBL; AJ242962; CAB71028.1; -; mRNA. DR EMBL; AJ242963; CAB71029.1; -; mRNA. DR EMBL; AF132045; AAD31019.1; -; mRNA. DR EMBL; AF132046; AAD31020.1; -; mRNA. DR RefSeq; NP_114019.1; NM_031831.1. DR RefSeq; XP_006251670.2; XM_006251608.2. [Q9JK11-2] DR RefSeq; XP_006251671.1; XM_006251609.3. [Q9JK11-3] DR RefSeq; XP_017454882.1; XM_017599393.1. [Q9JK11-4] DR AlphaFoldDB; Q9JK11; -. DR BMRB; Q9JK11; -. DR SMR; Q9JK11; -. DR BioGRID; 249825; 7. DR DIP; DIP-37179N; -. DR IntAct; Q9JK11; 17. DR MINT; Q9JK11; -. DR STRING; 10116.ENSRNOP00000006443; -. DR iPTMnet; Q9JK11; -. DR PhosphoSitePlus; Q9JK11; -. DR jPOST; Q9JK11; -. DR PaxDb; 10116-ENSRNOP00000006443; -. DR ABCD; Q9JK11; 1 sequenced antibody. DR Ensembl; ENSRNOT00000042965.4; ENSRNOP00000040760.2; ENSRNOG00000004621.9. [Q9JK11-3] DR GeneID; 83765; -. DR KEGG; rno:83765; -. DR UCSC; RGD:620989; rat. [Q9JK11-1] DR AGR; RGD:620989; -. DR CTD; 57142; -. DR RGD; 620989; Rtn4. DR VEuPathDB; HostDB:ENSRNOG00000004621; -. DR eggNOG; KOG1792; Eukaryota. DR GeneTree; ENSGT00940000156568; -. DR HOGENOM; CLU_048580_0_0_1; -. DR InParanoid; Q9JK11; -. DR OMA; DGQKKHW; -. DR OrthoDB; 7284at2759; -. DR PhylomeDB; Q9JK11; -. DR Reactome; R-RNO-193634; Axonal growth inhibition (RHOA activation). DR PRO; PR:Q9JK11; -. DR Proteomes; UP000002494; Chromosome 14. DR Bgee; ENSRNOG00000004621; Expressed in quadriceps femoris and 19 other cell types or tissues. DR ExpressionAtlas; Q9JK11; baseline and differential. DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-SubCell. DR GO; GO:0030424; C:axon; ISO:RGD. DR GO; GO:0030054; C:cell junction; ISS:UniProtKB. DR GO; GO:0042995; C:cell projection; ISO:RGD. DR GO; GO:0044294; C:dendritic growth cone; ISO:RGD. DR GO; GO:0005783; C:endoplasmic reticulum; ISO:RGD. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB. DR GO; GO:0071782; C:endoplasmic reticulum tubular network; ISO:RGD. DR GO; GO:0098826; C:endoplasmic reticulum tubular network membrane; ISS:UniProtKB. DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO. DR GO; GO:0043005; C:neuron projection; IBA:GO_Central. DR GO; GO:0043025; C:neuronal cell body; IDA:RGD. DR GO; GO:0005635; C:nuclear envelope; ISS:UniProtKB. DR GO; GO:0098794; C:postsynapse; IDA:SynGO. DR GO; GO:0014069; C:postsynaptic density; ISO:RGD. DR GO; GO:0098839; C:postsynaptic density membrane; IDA:SynGO. DR GO; GO:0032991; C:protein-containing complex; IDA:RGD. DR GO; GO:0045202; C:synapse; ISS:UniProtKB. DR GO; GO:0044877; F:protein-containing complex binding; IDA:RGD. DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:RGD. DR GO; GO:0007413; P:axonal fasciculation; IDA:UniProtKB. DR GO; GO:0001825; P:blastocyst formation; ISO:RGD. DR GO; GO:0007420; P:brain development; IBA:GO_Central. DR GO; GO:0060317; P:cardiac epithelial to mesenchymal transition; ISO:RGD. DR GO; GO:0120078; P:cell adhesion involved in sprouting angiogenesis; ISS: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:0022009; P:central nervous system vasculogenesis; ISS:UniProtKB. DR GO; GO:0021801; P:cerebral cortex radial glia-guided migration; ISS:UniProtKB. DR GO; GO:0071787; P:endoplasmic reticulum tubular network formation; ISS:UniProtKB. DR GO; GO:1990809; P:endoplasmic reticulum tubular network membrane organization; ISS:UniProtKB. DR GO; GO:0071786; P:endoplasmic reticulum tubular network organization; ISS:UniProtKB. DR GO; GO:0090156; P:intracellular sphingolipid homeostasis; ISO:RGD. DR GO; GO:0002523; P:leukocyte migration involved in inflammatory response; ISS:UniProtKB. DR GO; GO:0050804; P:modulation of chemical synaptic transmission; ISO:RGD. DR GO; GO:1902430; P:negative regulation of amyloid-beta formation; ISS:UniProtKB. DR GO; GO:0030517; P:negative regulation of axon extension; IDA:UniProtKB. DR GO; GO:0050771; P:negative regulation of axonogenesis; IDA:RGD. DR GO; GO:0030308; P:negative regulation of cell growth; ISO:RGD. DR GO; GO:0045665; P:negative regulation of neuron differentiation; IDA:RGD. DR GO; GO:0010977; P:negative regulation of neuron projection development; IDA:RGD. DR GO; GO:0070571; P:negative regulation of neuron projection regeneration; IMP:RGD. DR GO; GO:2001213; P:negative regulation of vasculogenesis; ISS:UniProtKB. DR GO; GO:0007399; P:nervous system development; ISO:RGD. DR GO; GO:0030182; P:neuron differentiation; IBA:GO_Central. DR GO; GO:0051292; P:nuclear pore complex assembly; ISS:UniProtKB. DR GO; GO:0021553; P:olfactory nerve development; IEP:RGD. DR GO; GO:0048709; P:oligodendrocyte differentiation; IEP:RGD. 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:0033603; P:positive regulation of dopamine secretion; IMP:RGD. DR GO; GO:0010634; P:positive regulation of epithelial cell migration; ISO:RGD. DR GO; GO:1905580; P:positive regulation of ERBB3 signaling pathway; ISO:RGD. DR GO; GO:0045687; P:positive regulation of glial cell differentiation; IDA:RGD. 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; ISO:RGD. DR GO; GO:1902624; P:positive regulation of neutrophil migration; ISS:UniProtKB. DR GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; ISO:RGD. DR GO; GO:1905552; P:positive regulation of protein localization to endoplasmic reticulum; ISO:RGD. 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; ISO:RGD. DR GO; GO:2000172; P:regulation of branching morphogenesis of a nerve; IDA:UniProtKB. DR GO; GO:0051960; P:regulation of nervous system development; ISO:RGD. DR GO; GO:0014823; P:response to activity; IEP:RGD. DR DisProt; DP01152; -. DR Gene3D; 1.20.5.2480; -; 1. DR InterPro; IPR003388; Reticulon. DR InterPro; IPR046964; RTN1-4. DR PANTHER; PTHR45799:SF1; RETICULON-4; 1. DR PANTHER; PTHR45799; RETICULON-LIKE PROTEIN; 1. DR Pfam; PF02453; Reticulon; 1. DR PROSITE; PS50845; RETICULON; 1. DR Genevisible; Q9JK11; RN. PE 1: Evidence at protein level; KW Acetylation; Alternative splicing; Cell junction; Cell membrane; KW Direct protein sequencing; Endoplasmic reticulum; Membrane; Neurogenesis; KW Phosphoprotein; Reference proteome; Synapse; Transmembrane; KW Transmembrane helix. FT CHAIN 1..1163 FT /note="Reticulon-4" FT /id="PRO_0000168167" FT TOPO_DOM 1..989 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 990..1010 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 1011..1104 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 1105..1125 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 1126..1163 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 976..1163 FT /note="Reticulon" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00170" FT REGION 1..184 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 244..270 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 406..437 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 454..474 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 31..54 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 88..102 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 137..161 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 406..422 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0000250|UniProtKB:Q9NQC3" FT MOD_RES 7 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9NQC3" FT MOD_RES 16 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:22673903" FT MOD_RES 107 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:16641100" FT MOD_RES 149 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q99P72" FT MOD_RES 169 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9NQC3" FT MOD_RES 171 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q99P72" FT MOD_RES 329 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:22673903" FT MOD_RES 333 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:22673903" FT MOD_RES 343 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q99P72" FT MOD_RES 347 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q99P72" FT MOD_RES 425 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:22673903" FT MOD_RES 429 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:22673903" FT MOD_RES 488 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q99P72" FT MOD_RES 689 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:22673903" FT MOD_RES 726 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q99P72" FT MOD_RES 766 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:22673903" FT MOD_RES 830 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:22673903" FT MOD_RES 832 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:22673903" FT MOD_RES 855 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q99P72" FT MOD_RES 922 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:22673903" FT MOD_RES 962 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9NQC3" FT MOD_RES 1075 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:Q9NQC3" FT VAR_SEQ 1..964 FT /note="Missing (in isoform C)" FT /evidence="ECO:0000303|PubMed:10231557, FT ECO:0000303|PubMed:10667796" FT /id="VSP_005656" FT VAR_SEQ 173..975 FT /note="Missing (in isoform B)" FT /evidence="ECO:0000303|PubMed:10667796, ECO:0000303|Ref.3" FT /id="VSP_005658" FT VAR_SEQ 192..975 FT /note="Missing (in isoform B2)" FT /evidence="ECO:0000303|Ref.3" FT /id="VSP_005659" FT VAR_SEQ 965..975 FT /note="AVLSAELSKTS -> MDGQKKHWKDK (in isoform C)" FT /evidence="ECO:0000303|PubMed:10231557, FT ECO:0000303|PubMed:10667796" FT /id="VSP_005657" FT CONFLICT 1130..1131 FT /note="Missing (in Ref. 3; AAD31020)" FT /evidence="ECO:0000305" SQ SEQUENCE 1163 AA; 126388 MW; 8CB894B09E94F0B6 CRC64; MEDIDQSSLV SSSTDSPPRP PPAFKYQFVT EPEDEEDEEE EEDEEEDDED LEELEVLERK PAAGLSAAAV PPAAAAPLLD FSSDSVPPAP RGPLPAAPPA APERQPSWER SPAAPAPSLP PAAAVLPSKL PEDDEPPARP PPPPPAGASP LAEPAAPPST PAAPKRRGSG SVDETLFALP AASEPVIPSS AEKIMDLMEQ PGNTVSSGQE DFPSVLLETA ASLPSLSPLS TVSFKEHGYL GNLSAVSSSE GTIEETLNEA SKELPERATN PFVNRDLAEF SELEYSEMGS SFKGSPKGES AILVENTKEE VIVRSKDKED LVCSAALHSP QESPVGKEDR VVSPEKTMDI FNEMQMSVVA PVREEYADFK PFEQAWEVKD TYEGSRDVLA ARANVESKVD RKCLEDSLEQ KSLGKDSEGR NEDASFPSTP EPVKDSSRAY ITCASFTSAT ESTTANTFPL LEDHTSENKT DEKKIEERKA QIITEKTSPK TSNPFLVAVQ DSEADYVTTD TLSKVTEAAV SNMPEGLTPD LVQEACESEL NEATGTKIAY ETKVDLVQTS EAIQESLYPT AQLCPSFEEA EATPSPVLPD IVMEAPLNSL LPSAGASVVQ PSVSPLEAPP PVSYDSIKLE PENPPPYEEA MNVALKALGT KEGIKEPESF NAAVQETEAP YISIACDLIK ETKLSTEPSP DFSNYSEIAK FEKSVPEHAE LVEDSSPESE PVDLFSDDSI PEVPQTQEEA VMLMKESLTE VSETVAQHKE ERLSASPQEL GKPYLESFQP NLHSTKDAAS NDIPTLTKKE KISLQMEEFN TAIYSNDDLL SSKEDKIKES ETFSDSSPIE IIDEFPTFVS AKDDSPKLAK EYTDLEVSDK SEIANIQSGA DSLPCLELPC DLSFKNIYPK DEVHVSDEFS ENRSSVSKAS ISPSNVSALE PQTEMGSIVK SKSLTKEAEK KLPSDTEKED RSLSAVLSAE LSKTSVVDLL YWRDIKKTGV VFGASLFLLL SLTVFSIVSV TAYIALALLS VTISFRIYKG VIQAIQKSDE GHPFRAYLES EVAISEELVQ KYSNSALGHV NSTIKELRRL FLVDDLVDSL KFAVLMWVFT YVGALFNGLT LLILALISLF SIPVIYERHQ VQIDHYLGLA NKSVKDAMAK IQAKIPGLKR KAD //