R4RL2_MOUSE
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 03-AUG-2022, entry version 145.
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};
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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.ENSMUSP00000118362; -.
DR GlyGen; Q7M6Z0; 3 sites.
DR iPTMnet; Q7M6Z0; -.
DR PhosphoSitePlus; Q7M6Z0; -.
DR PaxDb; Q7M6Z0; -.
DR PRIDE; Q7M6Z0; -.
DR ProteomicsDB; 300369; -.
DR ABCD; Q7M6Z0; 1 sequenced antibody.
DR Antibodypedia; 62766; 152 antibodies from 24 providers.
DR Ensembl; ENSMUST00000054514; ENSMUSP00000057725; ENSMUSG00000050896.
DR GeneID; 269295; -.
DR KEGG; mmu:269295; -.
DR UCSC; uc008kjm.1; mouse.
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; TCYLSPP; -.
DR OrthoDB; 826997at2759; -.
DR Reactome; R-MMU-163125; Post-translational modification: synthesis of GPI-anchored proteins.
DR BioGRID-ORCS; 269295; 6 hits in 74 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 121 other tissues.
DR ExpressionAtlas; Q7M6Z0; baseline and differential.
DR Genevisible; Q7M6Z0; MM.
DR GO; GO:0046658; C:anchored component of plasma membrane; ISS:UniProtKB.
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: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; -; 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 Pfam; PF13855; LRR_8; 2.
DR SMART; SM00369; LRR_TYP; 8.
DR SMART; SM00082; LRRCT; 1.
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
