R4RL1_MOUSE
ID R4RL1_MOUSE Reviewed; 445 AA.
AC Q8K0S5;
DT 07-FEB-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=Reticulon-4 receptor-like 1;
DE AltName: Full=Nogo receptor-like 2;
DE AltName: Full=Nogo-66 receptor homolog 2;
DE AltName: Full=Nogo-66 receptor-related protein 3;
DE Short=NgR3 {ECO:0000303|PubMed:22406547};
DE Flags: Precursor;
GN Name=Rtn4rl1 {ECO:0000312|MGI:MGI:2661375};
GN Synonyms=Ngrl2 {ECO:0000312|EMBL:AAP82835.1};
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:AAP82835.1}
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] {ECO:0000312|EMBL:BAC28223.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:BAC28223.1};
RC TISSUE=Medulla oblongata {ECO:0000312|EMBL:BAE24396.1}, and
RC Testis {ECO:0000312|EMBL:BAC28223.1};
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4] {ECO:0000312|EMBL:AAH30471.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye {ECO:0000312|EMBL:AAH30471.1};
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 [5] {ECO:0000312|EMBL:DAA01387.1}
RP IDENTIFICATION, SUBCELLULAR LOCATION, AND LACK OF INTERACTION WITH MAG; OMG
RP AND RTN4.
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 [6]
RP DISRUPTION PHENOTYPE, FUNCTION, IDENTIFICATION IN A COMPLEX WITH RTN4R;
RP RTN4RL1 AND NGFR, AND TISSUE SPECIFICITY.
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 [7]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
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 [8]
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 [9]
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 postnatal brain development and in regulating axon regeneration
CC in the adult central nervous system (PubMed:22406547, PubMed:27339102).
CC Contributes to normal axon migration across the brain midline and
CC normal formation of the corpus callosum (PubMed:27339102). Protects
CC motoneurons against apoptosis; protection against apoptosis is probably
CC mediated by MAG (PubMed:26335717). Plays a role in inhibiting neurite
CC outgrowth and axon regeneration via its binding to neuronal chondroitin
CC sulfate proteoglycans (PubMed:22406547). Binds heparin
CC (PubMed:22406547). Like other family members, plays a role in
CC restricting the number dendritic spines and the number of synapses that
CC are formed during brain development (PubMed:22325200). Signaling
CC mediates activation of Rho and downstream reorganization of the actin
CC cytoskeleton (PubMed:22325200). {ECO:0000269|PubMed:22325200,
CC ECO:0000269|PubMed:22406547, ECO:0000269|PubMed:26335717,
CC ECO:0000269|PubMed:27339102}.
CC -!- SUBUNIT: Identified in a complex that contains RTN4R, RTN4RL1 and NGFR;
CC the interaction depends on the presence of chondroitin sulfate
CC proteoglycans (PubMed:22406547). Does not interact with MAG, OMG and
CC RTN4 (PubMed:12839991). {ECO:0000269|PubMed:12839991,
CC ECO:0000269|PubMed:22406547}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12839991};
CC Lipid-anchor, GPI-anchor {ECO:0000250|UniProtKB:Q80WD0}. Membrane raft
CC {ECO:0000250|UniProtKB:Q86UN2}. Perikaryon
CC {ECO:0000250|UniProtKB:Q80WD0}. Cell projection
CC {ECO:0000250|UniProtKB:Q80WD0}. Note=Localized to the surface of
CC neurons, including axons. {ECO:0000250|UniProtKB:Q80WD0}.
CC -!- TISSUE SPECIFICITY: Detected in brain (at protein level)
CC (PubMed:22406547). Detected in retina ganglion cell layer and inner
CC nuclear layer (PubMed:22406547). {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, caudate putamen, cerebellum,
CC cerebral cortex, hippocampus, olfactory bulb and thalamus.
CC {ECO:0000269|PubMed:14664809}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype (PubMed:22406547). Mice are
CC born at the expected Mendelian rate, are viable and fertile
CC (PubMed:22406547). Compared to wild-type littermates, cultured
CC hippocampus neurons from mutant mice display an increased number of
CC excitatory synapses (PubMed:22325200). Likewise, mice with a triple
CC gene disruption that lack Rtn4r, Rtn4rl1 and Rtn4rl2 have no visible
CC phenotype, are healthy and viable (PubMed:22406547, PubMed:22325200).
CC Mice with a triple gene disruption that lack Rtn4r, Rtn4rl1 and Rtn4rl2
CC have normal brain size and grossly normal brain anatomy, but display
CC defects of medial brain structures, including an absence of the
CC fasciola cinereum, corpus callosum agenesis and formation of bilateral
CC Probst bundles indicative of the failure of callosally projecting
CC neurons to extend across the midline (PubMed:27339102). Mice with a
CC triple gene disruption of Rtn4r, Rtn4rl1 and Rtn4rl2 display impaired
CC ability to stay on a rotarod and increased spontaneous locomotion
CC (PubMed:27339102). These mice display an increased number of excitatory
CC synapses in the apical dendritic regions of hippocampus neurons, an
CC increase in the complexity of dendrite structure and increased total
CC dendrite length (PubMed:22325200). One month after birth, mice with a
CC triple gene disruption that lack Rtn4r, Rtn4rl1 and Rtn4rl2 show a
CC significant reduction in the survival of motoneurons (PubMed:26335717).
CC Compared to wild-type or single mutants, cerebellar granule cells from
CC mice lacking Rtn4r, Rtn4rl1 and Rtn4rl2 show decreased myelin-mediated
CC inhibition of neurite outgrowth, an inhibition that is strongly
CC decreased on myelin deficient in Mag, Rtn4 and Omg (PubMed:22406547).
CC Mice lacking both Rtn4r and Rtn4rl1 show increased axon regeneration
CC after injury; the same effect is observed when Rtn4r, Rtn4rl1 and
CC Rtn4rl2 are disrupted (PubMed:22406547). Combined disruption of Rtn4r,
CC Rtn4rl1 and Ptprs further increases axon regeneration after injury
CC (PubMed:22406547). Single gene disruption of Rtn4r, Rtn4rl1 and Rtn4rl2
CC and combined disruption of Rtn4r and Rtn4rl2 have no effect on axon
CC regeneration (PubMed:22406547). {ECO:0000269|PubMed:22325200,
CC ECO:0000269|PubMed:22406547, ECO:0000269|PubMed:26335717,
CC ECO:0000269|PubMed:27339102}.
CC -!- SIMILARITY: Belongs to the Nogo receptor family. {ECO:0000305}.
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DR EMBL; AY250218; AAP82835.1; -; mRNA.
DR EMBL; AK033286; BAC28223.1; -; mRNA.
DR EMBL; AK140456; BAE24396.1; -; mRNA.
DR EMBL; AL603905; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC030471; AAH30471.1; -; mRNA.
DR EMBL; BK001304; DAA01387.1; -; mRNA.
DR CCDS; CCDS25043.1; -.
DR RefSeq; NP_808376.1; NM_177708.5.
DR AlphaFoldDB; Q8K0S5; -.
DR SMR; Q8K0S5; -.
DR STRING; 10090.ENSMUSP00000099572; -.
DR GlyConnect; 2682; 3 N-Linked glycans (1 site).
DR GlyGen; Q8K0S5; 1 site, 3 N-linked glycans (1 site).
DR iPTMnet; Q8K0S5; -.
DR PhosphoSitePlus; Q8K0S5; -.
DR MaxQB; Q8K0S5; -.
DR PaxDb; Q8K0S5; -.
DR PeptideAtlas; Q8K0S5; -.
DR PRIDE; Q8K0S5; -.
DR ProteomicsDB; 301910; -.
DR Antibodypedia; 50502; 150 antibodies from 24 providers.
DR DNASU; 237847; -.
DR Ensembl; ENSMUST00000102514; ENSMUSP00000099572; ENSMUSG00000045287.
DR GeneID; 237847; -.
DR KEGG; mmu:237847; -.
DR UCSC; uc007kdh.1; mouse.
DR CTD; 146760; -.
DR MGI; MGI:2661375; Rtn4rl1.
DR VEuPathDB; HostDB:ENSMUSG00000045287; -.
DR eggNOG; KOG0619; Eukaryota.
DR GeneTree; ENSGT00940000157112; -.
DR HOGENOM; CLU_000288_18_6_1; -.
DR InParanoid; Q8K0S5; -.
DR OMA; SNTVTLW; -.
DR OrthoDB; 826997at2759; -.
DR PhylomeDB; Q8K0S5; -.
DR TreeFam; TF330080; -.
DR BioGRID-ORCS; 237847; 1 hit in 72 CRISPR screens.
DR ChiTaRS; Rtn4rl1; mouse.
DR PRO; PR:Q8K0S5; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q8K0S5; protein.
DR Bgee; ENSMUSG00000045287; Expressed in lumbar dorsal root ganglion and 228 other tissues.
DR Genevisible; Q8K0S5; MM.
DR GO; GO:0046658; C:anchored component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0042995; C:cell projection; IEA:UniProtKB-SubCell.
DR GO; GO:0009986; C:cell surface; ISS:UniProtKB.
DR GO; GO:0009897; C:external side of plasma membrane; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0045121; C:membrane raft; ISO:MGI.
DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR GO; GO:0035374; F:chondroitin sulfate binding; IDA:UniProtKB.
DR GO; GO:0008201; F:heparin binding; IMP:UniProtKB.
DR GO; GO:0048495; F:Roundabout binding; IBA:GO_Central.
DR GO; GO:0038023; F:signaling receptor activity; ISS:UniProtKB.
DR GO; GO:0007411; P:axon guidance; IBA:GO_Central.
DR GO; GO:0022038; P:corpus callosum development; IMP:UniProtKB.
DR GO; GO:0050919; P:negative chemotaxis; IBA:GO_Central.
DR GO; GO:0048681; P:negative regulation of axon regeneration; IMP:UniProtKB.
DR GO; GO:0010977; P:negative regulation of neuron projection development; IMP:UniProtKB.
DR Gene3D; 3.80.10.10; -; 1.
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; 3.
DR SMART; SM00369; LRR_TYP; 7.
DR PROSITE; PS51450; LRR; 6.
PE 1: Evidence at protein level;
KW Cell membrane; Cell projection; Glycoprotein; GPI-anchor; Heparin-binding;
KW Leucine-rich repeat; Lipoprotein; Membrane; Receptor; Reference proteome;
KW Repeat; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT CHAIN 25..424
FT /note="Reticulon-4 receptor-like 1"
FT /id="PRO_0000046044"
FT PROPEP 425..445
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000046045"
FT TRANSMEM 424..444
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 25..54
FT /note="LRRNT"
FT REPEAT 55..76
FT /note="LRR 1"
FT REPEAT 77..98
FT /note="LRR 2"
FT REPEAT 101..123
FT /note="LRR 3"
FT REPEAT 126..147
FT /note="LRR 4"
FT REPEAT 150..171
FT /note="LRR 5"
FT REPEAT 174..195
FT /note="LRR 6"
FT REPEAT 198..219
FT /note="LRR 7"
FT REPEAT 222..243
FT /note="LRR 8"
FT DOMAIN 255..306
FT /note="LRRCT"
FT REGION 307..377
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 401..424
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 320..345
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 355..377
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT LIPID 424
FT /note="GPI-anchor amidated serine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 445 AA; 49836 MW; 8285A01C1250D18A CRC64;
MLRKGCCVEL LLLLLAGELP LGGGCPRDCV CYPAPMTVSC QAHNFAAIPE GIPEDSERIF
LQNNRITFLQ QGHFSPAMVT LWIYSNNITF IAPNTFEGFV HLEELDLGDN RQLRTLAPET
FQGLVKLHAL YLYKCGLSAL PAGIFGGLHS LQYLYLQDNH IEYLQDDIFV DLVNLSHLFL
HGNKLWSLGQ GIFRGLVNLD RLLLHENQLQ WVHHKAFHDL HRLTTLFLFN NSLTELQGDC
LAPLVALEFL RLNGNAWDCG CRARSLWEWL RRFRGSSSAV PCATPELRQG QDLKLLRVED
FRNCTGPVSP HQIKSHTLTT SDRAARKEHH PSHGASRDKG HPHGHPPGSR SGYKKAGKNC
TSHRNRNQIS KVSSGKELTE LQDYAPDYQH KFSFDIMPTA RPKRKGKCAR RTPIRAPSGV
QQASSGTALG APLLAWILGL AVTLR
