ID R4RL2_MOUSE Reviewed; 420 AA. AC Q7M6Z0; A2RTJ0; Q3UQ62; DT 07-FEB-2006, integrated into UniProtKB/Swiss-Prot. DT 15-DEC-2003, sequence version 1. DT 27-MAR-2024, entry version 154. DE RecName: Full=Reticulon-4 receptor-like 2; DE AltName: Full=Nogo receptor-like 3; DE AltName: Full=Nogo-66 receptor homolog 1; DE AltName: Full=Nogo-66 receptor-related protein 2; DE Short=NgR2 {ECO:0000303|PubMed:19367338}; DE Flags: Precursor; GN Name=Rtn4rl2 {ECO:0000312|MGI:MGI:2669796}; GN Synonyms=Ngrl3 {ECO:0000312|EMBL:AAP82837.1}; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] {ECO:0000305, ECO:0000312|EMBL:AAP82837.1} RP NUCLEOTIDE SEQUENCE [MRNA], AND DEVELOPMENTAL STAGE. RC TISSUE=Brain {ECO:0000269|PubMed:14664809}; RX PubMed=14664809; DOI=10.1016/s1044-7431(03)00199-4; RA Lauren J., Airaksinen M.S., Saarma M., Timmusk T.; RT "Two novel mammalian nogo receptor homologs differentially expressed in the RT central and peripheral nervous systems."; RL Mol. Cell. Neurosci. 24:581-594(2003). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; 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 [3] {ECO:0000305, ECO:0000312|EMBL:BAE25181.1} RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 379-420. RC STRAIN=C57BL/6J {ECO:0000312|EMBL:BAE25181.1}; RC TISSUE=Heart {ECO:0000312|EMBL:BAE25181.1}; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J., RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [4] {ECO:0000312|EMBL:DAA01386.1} RP IDENTIFICATION. RX PubMed=12839991; DOI=10.1093/emboj/cdg325; RA Barton W.A., Liu B.P., Tzvetkova D., Jeffrey P.D., Fournier A.E., Sah D., RA Cate R., Strittmatter S.M., Nikolov D.B.; RT "Structure and axon outgrowth inhibitor binding of the Nogo-66 receptor and RT related proteins."; RL EMBO J. 22:3291-3302(2003). RN [5] RP DISRUPTION PHENOTYPE. RX PubMed=15673660; DOI=10.1523/jneurosci.4464-04.2005; RA Venkatesh K., Chivatakarn O., Lee H., Joshi P.S., Kantor D.B., Newman B.A., RA Mage R., Rader C., Giger R.J.; RT "The Nogo-66 receptor homolog NgR2 is a sialic acid-dependent receptor RT selective for myelin-associated glycoprotein."; RL J. Neurosci. 25:808-822(2005). RN [6] RP DISRUPTION PHENOTYPE. RX PubMed=19367338; DOI=10.1371/journal.pone.0005218; RA Woerter V., Schweigreiter R., Kinzel B., Mueller M., Barske C., Boeck G., RA Frentzel S., Bandtlow C.E.; RT "Inhibitory activity of myelin-associated glycoprotein on sensory neurons RT is largely independent of NgR1 and NgR2 and resides within Ig-Like domains RT 4 and 5."; RL PLoS ONE 4:E5218-E5218(2009). RN [7] RP DISRUPTION PHENOTYPE, AND FUNCTION. RX PubMed=22406547; DOI=10.1038/nn.3070; RA Dickendesher T.L., Baldwin K.T., Mironova Y.A., Koriyama Y., Raiker S.J., RA Askew K.L., Wood A., Geoffroy C.G., Zheng B., Liepmann C.D., Katagiri Y., RA Benowitz L.I., Geller H.M., Giger R.J.; RT "NgR1 and NgR3 are receptors for chondroitin sulfate proteoglycans."; RL Nat. Neurosci. 15:703-712(2012). RN [8] RP DISRUPTION PHENOTYPE, FUNCTION, SUBCELLULAR LOCATION, AND TISSUE RP SPECIFICITY. RX PubMed=22325200; DOI=10.1016/j.neuron.2011.11.029; RA Wills Z.P., Mandel-Brehm C., Mardinly A.R., McCord A.E., Giger R.J., RA Greenberg M.E.; RT "The Nogo receptor family restricts synapse number in the developing RT hippocampus."; RL Neuron 73:466-481(2012). RN [9] RP DISRUPTION PHENOTYPE, AND FUNCTION. RX PubMed=26335717; DOI=10.1038/cddis.2015.228; RA Palandri A., Salvador V.R., Wojnacki J., Vivinetto A.L., Schnaar R.L., RA Lopez P.H.; RT "Myelin-associated glycoprotein modulates apoptosis of motoneurons during RT early postnatal development via NgR/p75(NTR) receptor-mediated activation RT of RhoA signaling pathways."; RL Cell Death Dis. 6:E1876-E1876(2015). RN [10] RP DISRUPTION PHENOTYPE, AND FUNCTION. RX PubMed=27339102; DOI=10.1002/cne.24064; RA Yoo S.W., Motari M.G., Schnaar R.L.; RT "Agenesis of the corpus callosum in Nogo receptor deficient mice."; RL J. Comp. Neurol. 525:291-301(2017). CC -!- FUNCTION: Cell surface receptor that plays a functionally redundant CC role in the inhibition of neurite outgrowth mediated by MAG (By CC similarity). Plays a functionally redundant role in postnatal brain CC development (PubMed:27339102). Contributes to normal axon migration CC across the brain midline and normal formation of the corpus callosum CC (PubMed:27339102). Does not seem to play a significant role in CC regulating axon regeneration in the adult central nervous system CC (PubMed:22406547). Protects motoneurons against apoptosis; protection CC against apoptosis is probably mediated by MAG (PubMed:26335717). Like CC other family members, plays a role in restricting the number dendritic CC spines and the number of synapses that are formed during brain CC development (PubMed:22325200). Signaling mediates activation of Rho and CC downstream reorganization of the actin cytoskeleton (PubMed:22325200). CC {ECO:0000250|UniProtKB:Q80WD1, ECO:0000269|PubMed:22325200, CC ECO:0000269|PubMed:22406547, ECO:0000269|PubMed:26335717, CC ECO:0000269|PubMed:27339102}. CC -!- SUBUNIT: Interaction with MAG is controversial, and may be indirect CC (Probable). Interacts with MAG. Does not interact with OMG and RTN4 (By CC similarity). {ECO:0000250|UniProtKB:Q80WD1, ECO:0000305}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q86UN3}; CC Lipid-anchor, GPI-anchor {ECO:0000250|UniProtKB:Q86UN3}. Membrane raft CC {ECO:0000250|UniProtKB:Q80WD1}. Cell projection, dendrite CC {ECO:0000269|PubMed:22325200}. Cell projection, axon CC {ECO:0000269|PubMed:22325200}. Perikaryon CC {ECO:0000250|UniProtKB:Q80WD1}. Note=Localized to the surface of CC neurons, including axons. Detected close to synapses, but is excluded CC from synapses. {ECO:0000269|PubMed:22325200}. CC -!- TISSUE SPECIFICITY: Detected in brain (PubMed:22406547). Detected in CC hippocampus neurons (at protein level) (PubMed:22325200). CC {ECO:0000269|PubMed:22325200, ECO:0000269|PubMed:22406547}. CC -!- DEVELOPMENTAL STAGE: At 13.5 dpc, strongly expressed in PNS ganglia and CC developing heart, and weakly expressed in brain and spinal cord. By CC postnatal day 1, strongly expressed in dorsal root ganglia and in CC dorsal and gray matter areas of spinal cord. Expressed in various adult CC brain structures including the amygdala, cerebral cortex, cerebellum, CC hippocampus and olfactory bulb. {ECO:0000269|PubMed:14664809}. CC -!- PTM: Undergoes zinc metalloproteinase-mediated ectodomain shedding in CC neuroblastoma cells; is released both as a full-length ectodomain and CC an N-terminal fragment containing the leucine-rich repeat (LRR) region CC of the protein. {ECO:0000250|UniProtKB:Q86UN3}. CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:Q86UN3}. CC -!- DISRUPTION PHENOTYPE: No visible phenotype (PubMed:19367338). Mutant CC sensory neurons show no decrease of the inhibition of neurite outgrowth CC by MAG (PubMed:19367338). Compared to wild-type littermates, cultured CC hippocampus neurons from mutant mice display an increased number of CC excitatory synapses (PubMed:22325200). Likewise, mice lacking both CC Rtn4r and Rtn4rl2 display no visible phenotype (PubMed:19367338). CC Sensory neurons from mice lacking both Rtn4r and Rtn4rl2 show CC moderately decreased inhibition of neurite outgrowth by MAG CC (PubMed:19367338). Mice with a triple gene disruption that lack Rtn4r, CC Rtn4rl1 and Rtn4rl2 have no visible phenotype, are healthy and viable CC (PubMed:22406547, PubMed:22325200). Mice with a triple gene disruption CC that lack Rtn4r, Rtn4rl1 and Rtn4rl2 have normal brain size and grossly CC normal brain anatomy, but display disruption of medial brain CC structures, including an absence of the fasciola cinereum, corpus CC callosum agenesis and formation of bilateral Probst bundles indicative CC of the failure of callosally projecting neurons to extend across the CC midline (PubMed:27339102). Mice with a triple gene disruption of Rtn4r, CC Rtn4rl1 and Rtn4rl2 display impaired ability to stay on a rotarod and CC increased spontaneous locomotion (PubMed:27339102). These mice display CC an increased number of excitatory synapses in the apical dendritic CC regions of hippocampus neurons, an increase in the complexity of CC dendrite structure and increased total dendrite length CC (PubMed:22325200). One month after birth, mice with a triple gene CC disruption that lack Rtn4r, Rtn4rl1 and Rtn4rl2 show a significant CC reduction in the survival of motoneurons (PubMed:26335717). Compared to CC wild-type or single mutants, cerebellar granule cells from mice lacking CC Rtn4r, Rtn4rl1 and Rtn4rl2 show decreased myelin-mediated inhibition of CC neurite outgrowth, an inhibition that is strongly decreased on myelin CC deficient in Mag, Rtn4 and Omg (PubMed:22406547). Mice lacking both CC Rtn4r and Rtn4rl1 show increased axon regeneration after injury; the CC same effect is observed when Rtn4r, Rtn4rl1 and Rtn4rl2 are disrupted CC (PubMed:22406547). Combined disruption of Rtn4r, Rtn4rl1 and Ptprs CC further increases axon regeneration after injury (PubMed:22406547). CC Single gene disruption of Rtn4r, Rtn4rl1 and Rtn4rl2 and combined CC disruption of Rtn4r and Rtn4rl2 have no effect on axon regeneration CC (PubMed:22406547). {ECO:0000269|PubMed:19367338, CC ECO:0000269|PubMed:22325200, ECO:0000269|PubMed:22406547, CC ECO:0000269|PubMed:26335717, ECO:0000269|PubMed:27339102}. CC -!- SIMILARITY: Belongs to the Nogo receptor family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAE25181.1; Type=Erroneous translation; Note=Wrong choice of frame.; 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; AY250220; AAP82837.1; -; mRNA. DR EMBL; BC132523; AAI32524.1; -; mRNA. DR EMBL; BC138154; AAI38155.1; -; mRNA. DR EMBL; AK142743; BAE25181.1; ALT_SEQ; mRNA. DR EMBL; BK001303; DAA01386.1; -; mRNA. DR CCDS; CCDS16197.1; -. DR RefSeq; NP_954693.1; NM_199223.1. DR AlphaFoldDB; Q7M6Z0; -. DR SMR; Q7M6Z0; -. DR STRING; 10090.ENSMUSP00000057725; -. DR GlyCosmos; Q7M6Z0; 3 sites, No reported glycans. DR GlyGen; Q7M6Z0; 3 sites. DR iPTMnet; Q7M6Z0; -. DR PhosphoSitePlus; Q7M6Z0; -. DR SwissPalm; Q7M6Z0; -. DR PaxDb; 10090-ENSMUSP00000118362; -. DR ProteomicsDB; 300369; -. DR ABCD; Q7M6Z0; 1 sequenced antibody. DR Antibodypedia; 62766; 174 antibodies from 24 providers. DR Ensembl; ENSMUST00000054514.6; ENSMUSP00000057725.6; ENSMUSG00000050896.13. DR GeneID; 269295; -. DR KEGG; mmu:269295; -. DR UCSC; uc008kjm.1; mouse. DR AGR; MGI:2669796; -. DR CTD; 349667; -. DR MGI; MGI:2669796; Rtn4rl2. DR VEuPathDB; HostDB:ENSMUSG00000050896; -. DR eggNOG; KOG0619; Eukaryota. DR GeneTree; ENSGT00940000158505; -. DR HOGENOM; CLU_000288_18_6_1; -. DR InParanoid; Q7M6Z0; -. DR OMA; PTASCQS; -. DR OrthoDB; 5394956at2759; -. DR Reactome; R-MMU-163125; Post-translational modification: synthesis of GPI-anchored proteins. DR BioGRID-ORCS; 269295; 6 hits in 79 CRISPR screens. DR PRO; PR:Q7M6Z0; -. DR Proteomes; UP000000589; Chromosome 2. DR RNAct; Q7M6Z0; Protein. DR Bgee; ENSMUSG00000050896; Expressed in lumbar dorsal root ganglion and 123 other cell types or tissues. DR ExpressionAtlas; Q7M6Z0; baseline and differential. DR GO; GO:0030424; C:axon; ISS:UniProtKB. DR GO; GO:0009986; C:cell surface; ISS:UniProtKB. DR GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell. DR GO; GO:0009897; C:external side of plasma membrane; ISO:MGI. DR GO; GO:0031012; C:extracellular matrix; IBA:GO_Central. DR GO; GO:0005615; C:extracellular space; IBA:GO_Central. DR GO; GO:0045121; C:membrane raft; ISS:UniProtKB. DR GO; GO:0043005; C:neuron projection; ISS:UniProtKB. DR GO; GO:0043204; C:perikaryon; ISS:UniProtKB. DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB. DR GO; GO:0038023; F:signaling receptor activity; ISS:UniProtKB. DR GO; GO:0031103; P:axon regeneration; TAS:UniProtKB. DR GO; GO:0007166; P:cell surface receptor signaling pathway; ISS:UniProtKB. DR GO; GO:0022038; P:corpus callosum development; IMP:UniProtKB. DR GO; GO:0010977; P:negative regulation of neuron projection development; IMP:UniProtKB. DR Gene3D; 3.80.10.10; Ribonuclease Inhibitor; 1. DR InterPro; IPR000483; Cys-rich_flank_reg_C. DR InterPro; IPR001611; Leu-rich_rpt. DR InterPro; IPR003591; Leu-rich_rpt_typical-subtyp. DR InterPro; IPR032675; LRR_dom_sf. DR PANTHER; PTHR24373:SF272; RETICULON-4 RECEPTOR-LIKE 2; 1. DR PANTHER; PTHR24373; SLIT RELATED LEUCINE-RICH REPEAT NEURONAL PROTEIN; 1. DR Pfam; PF00560; LRR_1; 1. DR Pfam; PF13855; LRR_8; 2. DR SMART; SM00369; LRR_TYP; 8. DR SMART; SM00082; LRRCT; 1. DR SUPFAM; SSF52058; L domain-like; 1. DR Genevisible; Q7M6Z0; MM. PE 1: Evidence at protein level; KW Cell membrane; Cell projection; Disulfide bond; Glycoprotein; GPI-anchor; KW Leucine-rich repeat; Lipoprotein; Membrane; Receptor; Reference proteome; KW Repeat; Signal. FT SIGNAL 1..30 FT /evidence="ECO:0000255" FT CHAIN 31..398 FT /note="Reticulon-4 receptor-like 2" FT /id="PRO_0000046050" FT PROPEP 399..420 FT /note="Removed in mature form" FT /evidence="ECO:0000255" FT /id="PRO_0000046051" FT DOMAIN 31..60 FT /note="LRRNT" FT REPEAT 61..82 FT /note="LRR 1" FT REPEAT 83..104 FT /note="LRR 2" FT REPEAT 107..129 FT /note="LRR 3" FT REPEAT 132..153 FT /note="LRR 4" FT REPEAT 156..177 FT /note="LRR 5" FT REPEAT 180..201 FT /note="LRR 6" FT REPEAT 204..225 FT /note="LRR 7" FT REPEAT 228..249 FT /note="LRR 8" FT DOMAIN 261..312 FT /note="LRRCT" FT REGION 286..399 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 315..327 FT /note="Important for interaction with MAG" FT /evidence="ECO:0000250|UniProtKB:Q80WD1" FT COMPBIAS 350..364 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT LIPID 398 FT /note="GPI-anchor amidated glycine" FT /evidence="ECO:0000255" FT CARBOHYD 50 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000250|UniProtKB:Q80WD1" FT CARBOHYD 93 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000250|UniProtKB:Q80WD1" FT CARBOHYD 236 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000250|UniProtKB:Q80WD1" FT DISULFID 31..37 FT /evidence="ECO:0000250|UniProtKB:Q80WD1" FT DISULFID 35..46 FT /evidence="ECO:0000250|UniProtKB:Q80WD1" FT DISULFID 265..288 FT /evidence="ECO:0000250|UniProtKB:Q80WD1" FT DISULFID 267..310 FT /evidence="ECO:0000250|UniProtKB:Q80WD1" SQ SEQUENCE 420 AA; 46075 MW; 412500FEE8154B47 CRC64; MLPGLRRLLQ GPASACLLLT LLALPSVTPS CPMLCTCYSS PPTVSCQANN FSSVPLSLPP STQRLFLQNN LIRSLRPGTF GPNLLTLWLF SNNLSTIHPG TFRHLQALEE LDLGDNRHLR SLEPDTFQGL ERLQSLHLYR CQLSSLPGNI FRGLVSLQYL YLQENSLLHL QDDLFADLAN LSHLFLHGNR LRLLTEHVFR GLGSLDRLLL HGNRLQGVHR AAFHGLSRLT ILYLFNNSLA SLPGEALADL PALEFLRLNA NPWACDCRAR PLWAWFQRAR VSSSDVTCAT PPERQGRDLR ALRDSDFQAC PPPTPTRPGS RARGNSSSNH LYGVAEAGAP PADPSTLYRD LPAEDSRGRQ GGDAPTEDDY WGGYGGEDQR GEQTCPGAAC QAPADSRGPA LSAGLRTPLL CLLPLALHHL //