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R4RL1_HUMAN
ID   R4RL1_HUMAN             Reviewed;         441 AA.
AC   Q86UN2; A1A5E3; Q8ND46;
DT   07-FEB-2006, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-2003, sequence version 1.
DT   03-AUG-2022, entry version 145.
DE   RecName: Full=Reticulon-4 receptor-like 1;
DE   AltName: Full=Nogo receptor-like 2;
DE   AltName: Full=Nogo-66 receptor homolog 2 {ECO:0000303|PubMed:12694398};
DE   AltName: Full=Nogo-66 receptor-related protein 3;
DE            Short=NgR3;
DE   Flags: Precursor;
GN   Name=RTN4RL1 {ECO:0000312|HGNC:HGNC:21329};
GN   Synonyms=NGRH2 {ECO:0000303|PubMed:12694398, ECO:0000312|EMBL:AAP21836.1},
GN   NGRL2 {ECO:0000312|EMBL:AAP82836.1};
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:AAP82836.1}
RP   NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
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:0000305, ECO:0000312|EMBL:AAP21836.1}
RP   NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
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   [3] {ECO:0000312|EMBL:CAD39071.1}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 19-441.
RC   TISSUE=Brain;
RX   PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA   Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA   Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA   Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA   Wiemann S., Schupp I.;
RT   "The full-ORF clone resource of the German cDNA consortium.";
RL   BMC Genomics 8:399-399(2007).
RN   [6] {ECO:0000312|EMBL:DAA01388.1}
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   [7]
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. Plays a functionally redundant role in
CC       postnatal brain development and in regulating axon regeneration in the
CC       adult central nervous system. Contributes to normal axon migration
CC       across the brain midline and normal formation of the corpus callosum.
CC       Protects motoneurons against apoptosis; protection against apoptosis is
CC       probably mediated by MAG. Plays a role in inhibiting neurite outgrowth
CC       and axon regeneration via its binding to neuronal chondroitin sulfate
CC       proteoglycans. Binds heparin (By similarity). Like other family
CC       members, plays a role in restricting the number dendritic spines and
CC       the number of synapses that are formed during brain development
CC       (PubMed:22325200). Signaling mediates activation of Rho and downstream
CC       reorganization of the actin cytoskeleton (PubMed:22325200).
CC       {ECO:0000250|UniProtKB:Q8K0S5, ECO:0000269|PubMed:22325200}.
CC   -!- SUBUNIT: Identified in a complex that contains RTN4R, RTN4RL1 and NGFR;
CC       the interaction depends on the presence of chondroitin sulfate
CC       proteoglycans. Does not interact with MAG, OMG and RTN4.
CC       {ECO:0000250|UniProtKB:Q8K0S5}.
CC   -!- INTERACTION:
CC       Q86UN2; Q07627: KRTAP1-1; NbExp=3; IntAct=EBI-10258951, EBI-11959885;
CC       Q86UN2; P60409: KRTAP10-7; NbExp=3; IntAct=EBI-10258951, EBI-10172290;
CC       Q86UN2; P60410: KRTAP10-8; NbExp=3; IntAct=EBI-10258951, EBI-10171774;
CC       Q86UN2; Q7Z3S9: NOTCH2NLA; NbExp=3; IntAct=EBI-10258951, EBI-945833;
CC       Q86UN2; P0DPK4: NOTCH2NLC; NbExp=3; IntAct=EBI-10258951, EBI-22310682;
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12694398};
CC       Lipid-anchor, GPI-anchor {ECO:0000269|PubMed:12694398}. Membrane raft
CC       {ECO:0000269|PubMed:12694398}. 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: Predominantly expressed in brain. Expressed at
CC       lower levels in kidney, lung, mammary gland, placenta, salivary gland,
CC       skeletal muscle and spleen. {ECO:0000269|PubMed:12694398,
CC       ECO:0000269|PubMed:14664809}.
CC   -!- SIMILARITY: Belongs to the Nogo receptor family. {ECO:0000305}.
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DR   EMBL; AY250219; AAP82836.1; -; mRNA.
DR   EMBL; AF532859; AAP21836.1; -; mRNA.
DR   EMBL; CH471108; EAW90570.1; -; Genomic_DNA.
DR   EMBL; BC128608; AAI28609.1; -; mRNA.
DR   EMBL; AL834409; CAD39071.1; -; mRNA.
DR   EMBL; BK001305; DAA01388.1; -; mRNA.
DR   CCDS; CCDS45569.1; -.
DR   RefSeq; NP_848663.1; NM_178568.3.
DR   AlphaFoldDB; Q86UN2; -.
DR   SMR; Q86UN2; -.
DR   BioGRID; 127008; 11.
DR   IntAct; Q86UN2; 5.
DR   STRING; 9606.ENSP00000330631; -.
DR   GlyGen; Q86UN2; 1 site.
DR   iPTMnet; Q86UN2; -.
DR   PhosphoSitePlus; Q86UN2; -.
DR   BioMuta; RTN4RL1; -.
DR   DMDM; 74714017; -.
DR   MassIVE; Q86UN2; -.
DR   PaxDb; Q86UN2; -.
DR   PeptideAtlas; Q86UN2; -.
DR   PRIDE; Q86UN2; -.
DR   ProteomicsDB; 69833; -.
DR   Antibodypedia; 50502; 150 antibodies from 24 providers.
DR   DNASU; 146760; -.
DR   Ensembl; ENST00000331238.7; ENSP00000330631.4; ENSG00000185924.7.
DR   GeneID; 146760; -.
DR   KEGG; hsa:146760; -.
DR   MANE-Select; ENST00000331238.7; ENSP00000330631.4; NM_178568.4; NP_848663.1.
DR   UCSC; uc002ftp.4; human.
DR   CTD; 146760; -.
DR   DisGeNET; 146760; -.
DR   GeneCards; RTN4RL1; -.
DR   HGNC; HGNC:21329; RTN4RL1.
DR   HPA; ENSG00000185924; Tissue enhanced (brain).
DR   MIM; 610461; gene.
DR   neXtProt; NX_Q86UN2; -.
DR   OpenTargets; ENSG00000185924; -.
DR   PharmGKB; PA134973992; -.
DR   VEuPathDB; HostDB:ENSG00000185924; -.
DR   eggNOG; KOG0619; Eukaryota.
DR   GeneTree; ENSGT00940000157112; -.
DR   HOGENOM; CLU_000288_18_6_1; -.
DR   InParanoid; Q86UN2; -.
DR   OMA; HRKPGKN; -.
DR   OrthoDB; 826997at2759; -.
DR   PhylomeDB; Q86UN2; -.
DR   TreeFam; TF330080; -.
DR   PathwayCommons; Q86UN2; -.
DR   Reactome; R-HSA-163125; Post-translational modification: synthesis of GPI-anchored proteins.
DR   SignaLink; Q86UN2; -.
DR   BioGRID-ORCS; 146760; 14 hits in 1069 CRISPR screens.
DR   ChiTaRS; RTN4RL1; human.
DR   GenomeRNAi; 146760; -.
DR   Pharos; Q86UN2; Tbio.
DR   PRO; PR:Q86UN2; -.
DR   Proteomes; UP000005640; Chromosome 17.
DR   RNAct; Q86UN2; protein.
DR   Bgee; ENSG00000185924; Expressed in cortical plate and 115 other tissues.
DR   Genevisible; Q86UN2; HS.
DR   GO; GO:0046658; C:anchored component of plasma membrane; IDA:UniProtKB.
DR   GO; GO:0042995; C:cell projection; IEA:UniProtKB-SubCell.
DR   GO; GO:0009986; C:cell surface; IDA:DFLAT.
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; IEA:UniProtKB-SubCell.
DR   GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR   GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR   GO; GO:0035374; F:chondroitin sulfate binding; ISS:UniProtKB.
DR   GO; GO:0008201; F:heparin binding; ISS:UniProtKB.
DR   GO; GO:0038023; F:signaling receptor activity; IDA:UniProtKB.
DR   GO; GO:0031103; P:axon regeneration; TAS:UniProtKB.
DR   GO; GO:0022038; P:corpus callosum development; IEA:Ensembl.
DR   GO; GO:0048681; P:negative regulation of axon regeneration; 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; 7.
DR   SMART; SM00082; LRRCT; 1.
DR   PROSITE; PS51450; LRR; 6.
PE   1: Evidence at protein level;
KW   Cell membrane; Cell projection; Glycoprotein; GPI-anchor;
KW   Leucine-rich repeat; Lipoprotein; Membrane; Receptor; Reference proteome;
KW   Repeat; Signal.
FT   SIGNAL          1..24
FT                   /evidence="ECO:0000255"
FT   CHAIN           25..420
FT                   /note="Reticulon-4 receptor-like 1"
FT                   /id="PRO_0000046042"
FT   PROPEP          421..441
FT                   /note="Removed in mature form"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000046043"
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          304..382
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          397..417
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        332..356
FT                   /note="Basic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   LIPID           420
FT                   /note="GPI-anchor amidated serine"
FT                   /evidence="ECO:0000255"
FT   CONFLICT        22
FT                   /note="G -> S (in Ref. 5; CAD39071)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   441 AA;  49065 MW;  745272014C5304D3 CRC64;
     MLRKGCCVEL LLLLVAAELP LGGGCPRDCV CYPAPMTVSC QAHNFAAIPE GIPVDSERVF
     LQNNRIGLLQ PGHFSPAMVT LWIYSNNITY IHPSTFEGFV HLEELDLGDN RQLRTLAPET
     FQGLVKLHAL YLYKCGLSAL PAGVFGGLHS LQYLYLQDNH IEYLQDDIFV DLVNLSHLFL
     HGNKLWSLGP GTFRGLVNLD RLLLHENQLQ WVHHKAFHDL RRLTTLFLFN NSLSELQGEC
     LAPLGALEFL RLNGNPWDCG CRARSLWEWL QRFRGSSSAV PCVSPGLRHG QDLKLLRAED
     FRNCTGPASP HQIKSHTLTT TDRAARKEHH SPHGPTRSKG HPHGPRPGHR KPGKNCTNPR
     NRNQISKAGA GKQAPELPDY APDYQHKFSF DIMPTARPKR KGKCARRTPI RAPSGVQQAS
     SASSLGASLL AWTLGLAVTL R
 
 
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