R4RL2_RAT
ID R4RL2_RAT Reviewed; 420 AA.
AC Q80WD1;
DT 07-FEB-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 131.
DE RecName: Full=Reticulon-4 receptor-like 2;
DE AltName: Full=Nogo receptor-like 3;
DE AltName: Full=Nogo-66 receptor homolog 1 {ECO:0000303|PubMed:12694398};
DE AltName: Full=Nogo-66 receptor-related protein 2;
DE Short=NgR2 {ECO:0000303|PubMed:15673660};
DE Flags: Precursor;
GN Name=Rtn4rl2 {ECO:0000312|RGD:727797};
GN Synonyms=Ngrh1 {ECO:0000303|PubMed:12694398, ECO:0000312|EMBL:AAP21837.1};
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] {ECO:0000305, ECO:0000312|EMBL:AAP21837.1}
RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley {ECO:0000312|EMBL:AAP21837.1};
RX PubMed=12694398; DOI=10.1046/j.1471-4159.2003.01710.x;
RA Pignot V., Hein A.E., Barske C., Wiessner C., Walmsley A.R., Kaupmann K.,
RA Mayeur H., Sommer B., Mir A.K., Frentzel S.;
RT "Characterization of two novel proteins, NgRH1 and NgRH2, structurally and
RT biochemically homologous to the Nogo-66 receptor.";
RL J. Neurochem. 85:717-728(2003).
RN [2]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH MAG, LACK OF INTERACTION
RP WITH OMP AND RTN4, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
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 [3]
RP INTERACTION WITH MAG, GLYCOSYLATION, AND SUBCELLULAR LOCATION.
RX PubMed=19420245; DOI=10.1523/jneurosci.4935-08.2009;
RA Robak L.A., Venkatesh K., Lee H., Raiker S.J., Duan Y., Lee-Osbourne J.,
RA Hofer T., Mage R.G., Rader C., Giger R.J.;
RT "Molecular basis of the interactions of the Nogo-66 receptor and its
RT homolog NgR2 with myelin-associated glycoprotein: development of NgROMNI-
RT Fc, a novel antagonist of CNS myelin inhibition.";
RL J. Neurosci. 29:5768-5783(2009).
RN [4]
RP 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 [5]
RP 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 [6]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 29-310, INTERACTION WITH MAG,
RP GLYCOSYLATION AT ASN-50; ASN-93 AND ASN-236, AND DISULFIDE BONDS.
RX PubMed=21308849; DOI=10.1002/pro.597;
RA Semavina M., Saha N., Kolev M.V., Goldgur Y., Giger R.J., Himanen J.P.,
RA Nikolov D.B.;
RT "Crystal structure of the Nogo-receptor-2.";
RL Protein Sci. 20:684-689(2011).
CC -!- FUNCTION: Cell surface receptor that plays a functionally redundant
CC role in the inhibition of neurite outgrowth mediated by MAG
CC (PubMed:15673660). Plays a functionally redundant role in postnatal
CC brain development. Contributes to normal axon migration across the
CC brain midline and normal formation of the corpus callosum. Does not
CC seem to play a significant role in regulating axon regeneration in the
CC adult central nervous system (By similarity). Protects motoneurons
CC against apoptosis; protection against apoptosis is probably mediated by
CC MAG (PubMed:26335717). 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:0000250|UniProtKB:Q7M6Z0,
CC ECO:0000269|PubMed:15673660, ECO:0000269|PubMed:22325200,
CC ECO:0000269|PubMed:26335717}.
CC -!- SUBUNIT: Interaction with MAG is controversial, and may be indirect
CC (Probable). Interacts with MAG (PubMed:15673660, PubMed:19420245,
CC PubMed:21308849). Does not interact with OMG and RTN4
CC (PubMed:15673660). {ECO:0000269|PubMed:15673660,
CC ECO:0000269|PubMed:19420245, ECO:0000269|PubMed:21308849, ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12694398,
CC ECO:0000269|PubMed:15673660, ECO:0000269|PubMed:19420245}; Lipid-
CC anchor, GPI-anchor {ECO:0000305}. Cell projection, dendrite
CC {ECO:0000250|UniProtKB:Q7M6Z0}. Perikaryon
CC {ECO:0000269|PubMed:12694398, ECO:0000269|PubMed:15673660}. Cell
CC projection, axon {ECO:0000269|PubMed:12694398,
CC ECO:0000269|PubMed:15673660}. Membrane raft
CC {ECO:0000269|PubMed:15673660}. Note=Localized to the surface of
CC neurons, including axons (PubMed:12694398, PubMed:15673660). Detected
CC close to synapses, but is excluded from synapses (By similarity).
CC {ECO:0000250|UniProtKB:Q7M6Z0, ECO:0000269|PubMed:12694398,
CC ECO:0000269|PubMed:15673660}.
CC -!- TISSUE SPECIFICITY: Detected in adult brain, in neocortex, hippocampus,
CC striatum and dorsal root ganglion neurons, and in retina (at protein
CC level) (PubMed:15673660). In brain, detected in cerebral cortex and
CC hippocampus. Weak or no expression detected in the cerebellum, thalamus
CC or striatum (PubMed:12694398). {ECO:0000269|PubMed:12694398,
CC ECO:0000269|PubMed:15673660}.
CC -!- DEVELOPMENTAL STAGE: Expression is high in adult, but very low in
CC neonate dorsal root ganglion neurons (at protein level).
CC {ECO:0000269|PubMed:15673660}.
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 (PubMed:19420245, PubMed:21308849). O-glycosylated
CC (PubMed:19420245). Contains terminal sialic acid groups on its glycan
CC chains (PubMed:19420245). {ECO:0000269|PubMed:19420245,
CC ECO:0000269|PubMed:21308849}.
CC -!- SIMILARITY: Belongs to the Nogo receptor family. {ECO:0000305}.
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DR EMBL; AF532860; AAP21837.1; -; mRNA.
DR RefSeq; NP_852045.1; NM_181380.2.
DR PDB; 4P8S; X-ray; 1.80 A; A=29-310.
DR PDB; 4P91; X-ray; 2.10 A; A=29-330.
DR PDBsum; 4P8S; -.
DR PDBsum; 4P91; -.
DR AlphaFoldDB; Q80WD1; -.
DR SMR; Q80WD1; -.
DR STRING; 10116.ENSRNOP00000032922; -.
DR GlyGen; Q80WD1; 3 sites.
DR iPTMnet; Q80WD1; -.
DR PaxDb; Q80WD1; -.
DR ABCD; Q80WD1; 1 sequenced antibody.
DR GeneID; 311169; -.
DR KEGG; rno:311169; -.
DR UCSC; RGD:727797; rat.
DR CTD; 349667; -.
DR RGD; 727797; Rtn4rl2.
DR VEuPathDB; HostDB:ENSRNOG00000021513; -.
DR eggNOG; KOG0619; Eukaryota.
DR HOGENOM; CLU_000288_18_6_1; -.
DR InParanoid; Q80WD1; -.
DR OMA; TCYLSPP; -.
DR OrthoDB; 826997at2759; -.
DR PhylomeDB; Q80WD1; -.
DR TreeFam; TF330080; -.
DR Reactome; R-RNO-163125; Post-translational modification: synthesis of GPI-anchored proteins.
DR PRO; PR:Q80WD1; -.
DR Proteomes; UP000002494; Chromosome 3.
DR Bgee; ENSRNOG00000021513; Expressed in frontal cortex and 11 other tissues.
DR GO; GO:0046658; C:anchored component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0030424; C:axon; IDA:UniProtKB.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell.
DR GO; GO:0009897; C:external side of plasma membrane; IDA:RGD.
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; IDA:UniProtKB.
DR GO; GO:0043005; C:neuron projection; IDA:UniProtKB.
DR GO; GO:0043204; C:perikaryon; IDA:UniProtKB.
DR GO; GO:0038023; F:signaling receptor activity; IMP:UniProtKB.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0022038; P:corpus callosum development; ISO:RGD.
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 3D-structure; Cell membrane; Cell projection; Disulfide bond; Glycoprotein;
KW GPI-anchor; Leucine-rich repeat; Lipoprotein; Membrane; Receptor;
KW Reference proteome; Repeat; Signal.
FT SIGNAL 1..30
FT /evidence="ECO:0000255"
FT CHAIN 31..390
FT /note="Reticulon-4 receptor-like 2"
FT /id="PRO_0000046052"
FT PROPEP 391..420
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000046053"
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..390
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 315..327
FT /note="Important for interaction with MAG"
FT /evidence="ECO:0000269|PubMed:19420245"
FT COMPBIAS 350..364
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT LIPID 390
FT /note="GPI-anchor amidated cysteine"
FT /evidence="ECO:0000255"
FT CARBOHYD 50
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:21308849,
FT ECO:0007744|PDB:4P91"
FT CARBOHYD 93
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:21308849,
FT ECO:0007744|PDB:4P91"
FT CARBOHYD 236
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:21308849,
FT ECO:0007744|PDB:4P91"
FT DISULFID 31..37
FT /evidence="ECO:0000269|PubMed:21308849,
FT ECO:0007744|PDB:4P8S, ECO:0007744|PDB:4P91"
FT DISULFID 35..46
FT /evidence="ECO:0000269|PubMed:21308849,
FT ECO:0007744|PDB:4P8S, ECO:0007744|PDB:4P91"
FT DISULFID 265..288
FT /evidence="ECO:0000269|PubMed:21308849,
FT ECO:0007744|PDB:4P8S, ECO:0007744|PDB:4P91"
FT DISULFID 267..310
FT /evidence="ECO:0000269|PubMed:21308849,
FT ECO:0007744|PDB:4P8S, ECO:0007744|PDB:4P91"
FT STRAND 36..38
FT /evidence="ECO:0007829|PDB:4P8S"
FT TURN 39..42
FT /evidence="ECO:0007829|PDB:4P8S"
FT STRAND 43..45
FT /evidence="ECO:0007829|PDB:4P8S"
FT STRAND 64..66
FT /evidence="ECO:0007829|PDB:4P8S"
FT STRAND 85..88
FT /evidence="ECO:0007829|PDB:4P8S"
FT TURN 99..104
FT /evidence="ECO:0007829|PDB:4P8S"
FT STRAND 110..112
FT /evidence="ECO:0007829|PDB:4P8S"
FT TURN 124..129
FT /evidence="ECO:0007829|PDB:4P8S"
FT STRAND 135..137
FT /evidence="ECO:0007829|PDB:4P8S"
FT TURN 148..153
FT /evidence="ECO:0007829|PDB:4P8S"
FT STRAND 159..161
FT /evidence="ECO:0007829|PDB:4P8S"
FT TURN 172..177
FT /evidence="ECO:0007829|PDB:4P8S"
FT STRAND 183..185
FT /evidence="ECO:0007829|PDB:4P8S"
FT TURN 196..201
FT /evidence="ECO:0007829|PDB:4P8S"
FT STRAND 207..209
FT /evidence="ECO:0007829|PDB:4P8S"
FT TURN 220..225
FT /evidence="ECO:0007829|PDB:4P8S"
FT STRAND 231..233
FT /evidence="ECO:0007829|PDB:4P8S"
FT HELIX 244..248
FT /evidence="ECO:0007829|PDB:4P8S"
FT STRAND 255..257
FT /evidence="ECO:0007829|PDB:4P8S"
FT HELIX 267..269
FT /evidence="ECO:0007829|PDB:4P8S"
FT HELIX 270..278
FT /evidence="ECO:0007829|PDB:4P8S"
FT STRAND 287..291
FT /evidence="ECO:0007829|PDB:4P8S"
FT HELIX 292..294
FT /evidence="ECO:0007829|PDB:4P8S"
FT HELIX 299..301
FT /evidence="ECO:0007829|PDB:4P8S"
FT HELIX 304..307
FT /evidence="ECO:0007829|PDB:4P8S"
SQ SEQUENCE 420 AA; 46184 MW; 27536A80B4E34EF1 CRC64;
MLPGLRRLLQ GPASACLLLT LLALPPVTPS CPMLCTCYSS PPTVSCQANN FSSVPLSLPP
STQRLFLQNN LIRSLRPGTF GPNLLTLWLF SNNLSTIYPG TFRHLQALEE LDLGDNRHLR
SLEPDTFQGL ERLQSLHLYR CQLSSLPGNI FRGLVSLQYL YLQENSLLHL QDDLFADLAN
LSHLFLHGNR LRLLTEHVFR GLGSLDRLLL HGNRLQGVHR AAFHGLSRLT ILYLFNNSLA
SLPGEALADL PALEFLRLNA NPWACDCRAR PLWAWFQRAR VSSSDVTCAT PPERQGRDLR
TLRDTDFQAC PPPTPTRPGS RARGNSSSNH LYGVAEAGAP PADPSTLYRD LPAEDSRGRQ
GGDAPTEDDY WGGYGGEDQR GEQTCPGAAC QAPADSRGPV LSAGLRTPLL CLLLLAPHHL
