R4RL2_HUMAN
ID R4RL2_HUMAN Reviewed; 420 AA.
AC Q86UN3; Q0GGW3; Q17RL9; Q6X813;
DT 07-FEB-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 148.
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;
DE Flags: Precursor;
GN Name=RTN4RL2 {ECO:0000312|HGNC:HGNC:23053};
GN Synonyms=NGRH1 {ECO:0000303|PubMed:12694398, ECO:0000312|EMBL:AAP21835.1},
GN NGRL3 {ECO:0000312|EMBL:AAP82838.1};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1] {ECO:0000305, ECO:0000312|EMBL:AAP21835.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Brain {ECO:0000269|PubMed:12694398};
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] {ECO:0000305, ECO:0000312|EMBL:AAP82838.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
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 [3] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND ALTERNATIVE SPLICING.
RA Rader C., Hofer T., Giger R.J.;
RT "Splice variant of human RTN4RL2 (Nogo-66 receptor homolog NgR2).";
RL Submitted (JUL-2006) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 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 [6] {ECO:0000312|EMBL:DAA01385.1}
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 [7]
RP SUBCELLULAR LOCATION, PROTEOLYTIC CLEAVAGE, AND GLYCOSYLATION.
RX PubMed=15629437; DOI=10.1016/j.bbrc.2004.12.001;
RA Walmsley A.R., Mir A.K., Frentzel S.;
RT "Ectodomain shedding of human Nogo-66 receptor homologue-1 by zinc
RT metalloproteinases.";
RL Biochem. Biophys. Res. Commun. 327:112-116(2005).
RN [8]
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).
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. Contributes to normal axon migration across the brain
CC midline and normal formation of the corpus callosum. Does not seem to
CC play a significant role in regulating axon regeneration in the adult
CC central nervous system. Protects motoneurons against apoptosis;
CC protection against apoptosis is probably mediated by MAG (By
CC similarity). Like other family members, plays a role in restricting the
CC number dendritic spines and the number of synapses that are formed
CC during brain development (PubMed:22325200). Signaling mediates
CC activation of Rho and downstream reorganization of the actin
CC cytoskeleton (PubMed:22325200). {ECO:0000250|UniProtKB:Q7M6Z0,
CC ECO:0000250|UniProtKB:Q80WD1, ECO:0000269|PubMed:22325200}.
CC -!- SUBUNIT: Interaction with MAG is controversial, and may be indirect
CC (Probable). Does not interact with MAG, OMG and RTN4 (PubMed:12839991).
CC Interacts with MAG (By similarity). {ECO:0000250|UniProtKB:Q80WD1,
CC ECO:0000269|PubMed:12839991, ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12694398,
CC ECO:0000269|PubMed:12839991}; Lipid-anchor, GPI-anchor
CC {ECO:0000269|PubMed:12694398}. Membrane raft
CC {ECO:0000269|PubMed:12694398}. Cell projection, dendrite
CC {ECO:0000250|UniProtKB:Q7M6Z0}. Perikaryon
CC {ECO:0000250|UniProtKB:Q80WD1}. Cell projection, axon
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:0000250|UniProtKB:Q7M6Z0}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q86UN3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q86UN3-2; Sequence=VSP_047767, VSP_047768;
CC -!- TISSUE SPECIFICITY: Highly expressed in brain and liver. Expressed at
CC lower levels in kidney, mammary gland, placenta, skeletal muscle,
CC spleen and thyroid. {ECO:0000269|PubMed:12694398,
CC 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:0000269|PubMed:15629437}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:15629437}.
CC -!- SIMILARITY: Belongs to the Nogo receptor family. {ECO:0000305}.
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DR EMBL; AF532858; AAP21835.1; -; mRNA.
DR EMBL; AY250221; AAP82838.1; -; mRNA.
DR EMBL; DQ864979; ABI23432.1; -; mRNA.
DR EMBL; AP002893; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC113673; AAI13674.1; -; mRNA.
DR EMBL; BC117276; AAI17277.1; -; mRNA.
DR EMBL; BK001302; DAA01385.1; -; mRNA.
DR CCDS; CCDS7957.1; -. [Q86UN3-1]
DR RefSeq; NP_848665.1; NM_178570.2. [Q86UN3-1]
DR AlphaFoldDB; Q86UN3; -.
DR SMR; Q86UN3; -.
DR BioGRID; 131566; 18.
DR IntAct; Q86UN3; 5.
DR STRING; 9606.ENSP00000335397; -.
DR GlyGen; Q86UN3; 3 sites.
DR iPTMnet; Q86UN3; -.
DR PhosphoSitePlus; Q86UN3; -.
DR BioMuta; RTN4RL2; -.
DR DMDM; 74759401; -.
DR jPOST; Q86UN3; -.
DR MassIVE; Q86UN3; -.
DR MaxQB; Q86UN3; -.
DR PaxDb; Q86UN3; -.
DR PeptideAtlas; Q86UN3; -.
DR PRIDE; Q86UN3; -.
DR ProteomicsDB; 58756; -.
DR ProteomicsDB; 69834; -. [Q86UN3-1]
DR ABCD; Q86UN3; 1 sequenced antibody.
DR Antibodypedia; 62766; 152 antibodies from 24 providers.
DR DNASU; 349667; -.
DR Ensembl; ENST00000335099.8; ENSP00000335397.3; ENSG00000186907.8. [Q86UN3-1]
DR Ensembl; ENST00000395120.2; ENSP00000378552.2; ENSG00000186907.8. [Q86UN3-2]
DR GeneID; 349667; -.
DR KEGG; hsa:349667; -.
DR MANE-Select; ENST00000335099.8; ENSP00000335397.3; NM_178570.3; NP_848665.1.
DR UCSC; uc010rjt.4; human. [Q86UN3-1]
DR CTD; 349667; -.
DR DisGeNET; 349667; -.
DR GeneCards; RTN4RL2; -.
DR HGNC; HGNC:23053; RTN4RL2.
DR HPA; ENSG00000186907; Group enriched (brain, liver, thyroid gland).
DR MIM; 610462; gene.
DR neXtProt; NX_Q86UN3; -.
DR OpenTargets; ENSG00000186907; -.
DR PharmGKB; PA134964131; -.
DR VEuPathDB; HostDB:ENSG00000186907; -.
DR eggNOG; KOG0619; Eukaryota.
DR GeneTree; ENSGT00940000158505; -.
DR HOGENOM; CLU_000288_18_6_1; -.
DR InParanoid; Q86UN3; -.
DR OMA; TCYLSPP; -.
DR OrthoDB; 826997at2759; -.
DR PhylomeDB; Q86UN3; -.
DR TreeFam; TF330080; -.
DR PathwayCommons; Q86UN3; -.
DR Reactome; R-HSA-163125; Post-translational modification: synthesis of GPI-anchored proteins.
DR SignaLink; Q86UN3; -.
DR BioGRID-ORCS; 349667; 13 hits in 1070 CRISPR screens.
DR GenomeRNAi; 349667; -.
DR Pharos; Q86UN3; Tbio.
DR PRO; PR:Q86UN3; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q86UN3; protein.
DR Bgee; ENSG00000186907; Expressed in right lobe of liver and 93 other tissues.
DR ExpressionAtlas; Q86UN3; baseline and differential.
DR Genevisible; Q86UN3; HS.
DR GO; GO:0046658; C:anchored component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0030424; C:axon; ISS:UniProtKB.
DR GO; GO:0009986; C:cell surface; IDA:DFLAT.
DR GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0031012; C:extracellular matrix; IBA:GO_Central.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
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; TAS:Reactome.
DR GO; GO:0038023; F:signaling receptor activity; IDA: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:0010977; P:negative regulation of neuron projection development; ISS: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 Alternative splicing; Cell membrane; Cell projection; Disulfide bond;
KW Glycoprotein; GPI-anchor; Leucine-rich repeat; Lipoprotein; Membrane;
KW Receptor; Reference proteome; Repeat; Signal.
FT SIGNAL 1..46
FT /evidence="ECO:0000255"
FT CHAIN 47..390
FT /note="Reticulon-4 receptor-like 2"
FT /id="PRO_0000046048"
FT PROPEP 391..420
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000046049"
FT DOMAIN 47..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 308..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 390
FT /note="GPI-anchor amidated cysteine"
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"
FT VAR_SEQ 172..193
FT /note="DDLFADLANLSHLFLHGNRLRL -> GPLPKGLCSCFSHPPSSLPTSR (in
FT isoform 2)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_047767"
FT VAR_SEQ 194..420
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_047768"
FT CONFLICT 78
FT /note="G -> S (in Ref. 2; AAP82838)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 420 AA; 46106 MW; 09B9E875BC88A0E8 CRC64;
MLPGLRRLLQ APASACLLLM LLALPLAAPS CPMLCTCYSS PPTVSCQANN FSSVPLSLPP
STQRLFLQNN LIRTLRPGTF GSNLLTLWLF SNNLSTIYPG TFRHLQALEE LDLGDNRHLR
SLEPDTFQGL ERLQSLHLYR CQLSSLPGNI FRGLVSLQYL YLQENSLLHL QDDLFADLAN
LSHLFLHGNR LRLLTEHVFR GLGSLDRLLL HGNRLQGVHR AAFRGLSRLT ILYLFNNSLA
SLPGEALADL PSLEFLRLNA NPWACDCRAR PLWAWFQRAR VSSSDVTCAT PPERQGRDLR
ALREADFQAC PPAAPTRPGS RARGNSSSNH LYGVAEAGAP PADPSTLYRD LPAEDSRGRQ
GGDAPTEDDY WGGYGGEDQR GEQMCPGAAC QAPPDSRGPA LSAGLPSPLL CLLLLVPHHL
