RTN2_HUMAN
ID RTN2_HUMAN Reviewed; 545 AA.
AC O75298; O60509; Q7RTM6; Q7RTN1; Q7RTN2;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=Reticulon-2;
DE AltName: Full=Neuroendocrine-specific protein-like 1;
DE Short=NSP-like protein 1;
DE AltName: Full=Neuroendocrine-specific protein-like I;
DE Short=NSP-like protein I;
DE Short=NSPLI;
GN Name=RTN2; Synonyms=NSPL1;
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]
RP NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING, AND TISSUE SPECIFICITY.
RC TISSUE=Lung carcinoma;
RX PubMed=9693037; DOI=10.1006/geno.1997.5175;
RA Roebroek A.J.M., Contreras B., Pauli I.G.L., Van de Ven W.J.M.;
RT "cDNA cloning, genomic organization, and expression of the human RTN2 gene,
RT a member of a gene family encoding reticulons.";
RL Genomics 51:98-106(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 108-545 (ISOFORM RTN2-B).
RC TISSUE=Brain;
RX PubMed=9530622; DOI=10.1007/s003359900748;
RA Geisler J.G., Stubbs L.J., Wasserman W.W., Mucenski M.L.;
RT "Molecular cloning of a novel mouse gene with predominant muscle and neural
RT expression.";
RL Mamm. Genome 9:274-282(1998).
RN [3]
RP REVIEW.
RX PubMed=12832288; DOI=10.1096/fj.02-1166hyp;
RA Oertle T., Klinger M., Stuermer C.A.O., Schwab M.E.;
RT "A reticular rhapsody: phylogenic evolution and nomenclature of the
RT RTN/Nogo gene family.";
RL FASEB J. 17:1238-1247(2003).
RN [4]
RP FUNCTION, AND INTERACTION WITH BACE1.
RX PubMed=15286784; DOI=10.1038/nm1088;
RA He W., Lu Y., Qahwash I., Hu X.-Y., Chang A., Yan R.;
RT "Reticulon family members modulate BACE1 activity and amyloid-beta peptide
RT generation.";
RL Nat. Med. 10:959-965(2004).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [6]
RP SUBCELLULAR LOCATION, INTERACTION WITH SPAST, AND VARIANT SPG12 PHE-367.
RX PubMed=22232211; DOI=10.1172/jci60560;
RA Montenegro G., Rebelo A.P., Connell J., Allison R., Babalini C.,
RA D'Aloia M., Montieri P., Schule R., Ishiura H., Price J., Strickland A.,
RA Gonzalez M.A., Baumbach-Reardon L., Deconinck T., Huang J., Bernardi G.,
RA Vance J.M., Rogers M.T., Tsuji S., De Jonghe P., Pericak-Vance M.A.,
RA Schols L., Orlacchio A., Reid E., Zuchner S.;
RT "Mutations in the ER-shaping protein reticulon 2 cause the axon-
RT degenerative disorder hereditary spastic paraplegia type 12.";
RL J. Clin. Invest. 122:538-544(2012).
RN [7]
RP INTERACTION WITH TMEM33.
RX PubMed=25612671;
RA Urade T., Yamamoto Y., Zhang X., Ku Y., Sakisaka T.;
RT "Identification and characterization of TMEM33 as a reticulon-binding
RT protein.";
RL Kobe J. Med. Sci. 60:E57-E65(2014).
CC -!- FUNCTION: Inhibits amyloid precursor protein processing, probably by
CC blocking BACE1 activity (PubMed:15286784). Enhances trafficking of the
CC glutamate transporter SLC1A1/EAAC1 from the endoplasmic reticulum to
CC the cell surface (By similarity). Plays a role in the translocation of
CC SLC2A4/GLUT4 from intracellular membranes to the cell membrane which
CC facilitates the uptake of glucose into the cell (By similarity).
CC {ECO:0000250|UniProtKB:O70622, ECO:0000250|UniProtKB:Q6WN19,
CC ECO:0000269|PubMed:15286784}.
CC -!- SUBUNIT: Interacts with isoform 1 but not isoform 3 of SPAST
CC (PubMed:22232211). Interacts with BACE1 (PubMed:15286784). Interacts
CC (via first transmembrane domain) with ARL6IP5/GTRAP3-18 (By
CC similarity). Interacts (via N-terminus) with SLC1A1/EAAC1; the
CC interaction promotes cell surface expression of SLC1A1 (By similarity).
CC {ECO:0000250|UniProtKB:Q6WN19, ECO:0000269|PubMed:15286784,
CC ECO:0000269|PubMed:22232211}.
CC -!- SUBUNIT: [Isoform RTN2-B]: Interacts with TMEM33.
CC {ECO:0000269|PubMed:25612671}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:22232211}; Multi-pass membrane protein
CC {ECO:0000255}. Sarcoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:O70622}; Multi-pass membrane protein
CC {ECO:0000255}. Cell membrane {ECO:0000250|UniProtKB:Q6WN19}; Multi-pass
CC membrane protein {ECO:0000255}. Cell membrane, sarcolemma
CC {ECO:0000250|UniProtKB:O70622}; Multi-pass membrane protein
CC {ECO:0000255}. Cell membrane, sarcolemma, T-tubule
CC {ECO:0000250|UniProtKB:O70622}; Multi-pass membrane protein
CC {ECO:0000255}. Cytoplasm, myofibril, sarcomere, Z line
CC {ECO:0000250|UniProtKB:O70622}. Cytoplasm, cytoskeleton
CC {ECO:0000250|UniProtKB:O70622}. Note=Localizes to intermediate
CC filaments in mononucleated myoblasts and to Z lines in mature myotubes.
CC {ECO:0000250|UniProtKB:O70622}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing, Alternative initiation; Named isoforms=3;
CC Name=RTN2-A;
CC IsoId=O75298-1; Sequence=Displayed;
CC Name=RTN2-B;
CC IsoId=O75298-2; Sequence=VSP_005649;
CC Name=RTN2-C;
CC IsoId=O75298-3; Sequence=VSP_018870;
CC -!- TISSUE SPECIFICITY: [Isoform RTN2-C]: Highly expressed in skeletal
CC muscle. {ECO:0000269|PubMed:9693037}.
CC -!- DISEASE: Spastic paraplegia 12, autosomal dominant (SPG12)
CC [MIM:604805]: A form of spastic paraplegia, a neurodegenerative
CC disorder characterized by a slow, gradual, progressive weakness and
CC spasticity of the lower limbs. Rate of progression and the severity of
CC symptoms are quite variable. Initial symptoms may include difficulty
CC with balance, weakness and stiffness in the legs, muscle spasms, and
CC dragging the toes when walking. In some forms of the disorder, bladder
CC symptoms (such as incontinence) may appear, or the weakness and
CC stiffness may spread to other parts of the body.
CC {ECO:0000269|PubMed:22232211}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: [Isoform RTN2-C]: Produced by alternative initiation at
CC Met-341 of isoform RTN2-A. {ECO:0000305}.
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DR EMBL; AF004222; AAC32542.1; -; mRNA.
DR EMBL; AF004223; AAC32543.1; -; mRNA.
DR EMBL; AF004224; AAC32544.1; -; mRNA.
DR EMBL; AF038540; AAC14910.1; -; mRNA.
DR EMBL; BK001686; DAA01944.1; -; mRNA.
DR EMBL; BK001687; DAA01932.1; -; mRNA.
DR EMBL; BK001688; DAA01933.1; -; mRNA.
DR CCDS; CCDS12665.1; -. [O75298-1]
DR CCDS; CCDS12666.1; -. [O75298-2]
DR CCDS; CCDS46114.1; -. [O75298-3]
DR RefSeq; NP_005610.1; NM_005619.4. [O75298-1]
DR RefSeq; NP_996783.1; NM_206900.2. [O75298-2]
DR RefSeq; NP_996784.1; NM_206901.2. [O75298-3]
DR AlphaFoldDB; O75298; -.
DR BioGRID; 112166; 43.
DR CORUM; O75298; -.
DR IntAct; O75298; 20.
DR STRING; 9606.ENSP00000245923; -.
DR iPTMnet; O75298; -.
DR PhosphoSitePlus; O75298; -.
DR BioMuta; RTN2; -.
DR EPD; O75298; -.
DR jPOST; O75298; -.
DR MassIVE; O75298; -.
DR MaxQB; O75298; -.
DR PaxDb; O75298; -.
DR PeptideAtlas; O75298; -.
DR PRIDE; O75298; -.
DR ProteomicsDB; 49880; -. [O75298-1]
DR ProteomicsDB; 49881; -. [O75298-2]
DR ProteomicsDB; 49882; -. [O75298-3]
DR Antibodypedia; 31344; 145 antibodies from 27 providers.
DR DNASU; 6253; -.
DR Ensembl; ENST00000245923.9; ENSP00000245923.3; ENSG00000125744.12. [O75298-1]
DR Ensembl; ENST00000344680.8; ENSP00000345127.3; ENSG00000125744.12. [O75298-2]
DR Ensembl; ENST00000430715.6; ENSP00000398178.1; ENSG00000125744.12. [O75298-3]
DR GeneID; 6253; -.
DR KEGG; hsa:6253; -.
DR MANE-Select; ENST00000245923.9; ENSP00000245923.3; NM_005619.5; NP_005610.1.
DR UCSC; uc002pcb.5; human. [O75298-1]
DR CTD; 6253; -.
DR DisGeNET; 6253; -.
DR GeneCards; RTN2; -.
DR HGNC; HGNC:10468; RTN2.
DR HPA; ENSG00000125744; Group enriched (skeletal muscle, tongue).
DR MalaCards; RTN2; -.
DR MIM; 603183; gene.
DR MIM; 604805; phenotype.
DR neXtProt; NX_O75298; -.
DR OpenTargets; ENSG00000125744; -.
DR Orphanet; 100993; Autosomal dominant spastic paraplegia type 12.
DR PharmGKB; PA34881; -.
DR VEuPathDB; HostDB:ENSG00000125744; -.
DR eggNOG; KOG1792; Eukaryota.
DR GeneTree; ENSGT00940000160599; -.
DR HOGENOM; CLU_048580_2_1_1; -.
DR InParanoid; O75298; -.
DR OMA; WRAIGWV; -.
DR PhylomeDB; O75298; -.
DR TreeFam; TF105431; -.
DR PathwayCommons; O75298; -.
DR SignaLink; O75298; -.
DR BioGRID-ORCS; 6253; 21 hits in 1081 CRISPR screens.
DR ChiTaRS; RTN2; human.
DR GeneWiki; RTN2; -.
DR GenomeRNAi; 6253; -.
DR Pharos; O75298; Tbio.
DR PRO; PR:O75298; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; O75298; protein.
DR Bgee; ENSG00000125744; Expressed in skeletal muscle tissue of rectus abdominis and 182 other tissues.
DR ExpressionAtlas; O75298; baseline and differential.
DR Genevisible; O75298; HS.
DR GO; GO:0009986; C:cell surface; IEA:Ensembl.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IBA:GO_Central.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; NAS:UniProtKB.
DR GO; GO:0005882; C:intermediate filament; ISS:UniProtKB.
DR GO; GO:0033017; C:sarcoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0030315; C:T-tubule; ISS:UniProtKB.
DR GO; GO:0014802; C:terminal cisterna; ISS:UniProtKB.
DR GO; GO:0030018; C:Z disc; ISS:UniProtKB.
DR GO; GO:0010467; P:gene expression; IEA:Ensembl.
DR GO; GO:0065002; P:intracellular protein transmembrane transport; ISS:UniProtKB.
DR GO; GO:1902430; P:negative regulation of amyloid-beta formation; IDA:UniProtKB.
DR GO; GO:0046324; P:regulation of glucose import; ISS:UniProtKB.
DR InterPro; IPR003388; Reticulon.
DR Pfam; PF02453; Reticulon; 1.
DR PROSITE; PS50845; RETICULON; 1.
PE 1: Evidence at protein level;
KW Alternative initiation; Alternative splicing; Cell membrane; Cytoplasm;
KW Cytoskeleton; Disease variant; Endoplasmic reticulum;
KW Hereditary spastic paraplegia; Membrane; Neurodegeneration; Phosphoprotein;
KW Reference proteome; Sarcoplasmic reticulum; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..545
FT /note="Reticulon-2"
FT /id="PRO_0000030351"
FT TRANSMEM 368..388
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 463..483
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 345..545
FT /note="Reticulon"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00170"
FT REGION 1..183
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 199..250
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 28..45
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 80..94
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 95..118
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 127..146
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 155..170
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 199..229
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 230..247
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 44
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O70622"
FT MOD_RES 227
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O70622"
FT MOD_RES 229
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O70622"
FT VAR_SEQ 1..340
FT /note="Missing (in isoform RTN2-C)"
FT /evidence="ECO:0000305"
FT /id="VSP_018870"
FT VAR_SEQ 272..344
FT /note="Missing (in isoform RTN2-B)"
FT /evidence="ECO:0000303|PubMed:9530622"
FT /id="VSP_005649"
FT VARIANT 367
FT /note="S -> F (in SPG12; dbSNP:rs140494585)"
FT /evidence="ECO:0000269|PubMed:22232211"
FT /id="VAR_067562"
FT VARIANT 425
FT /note="R -> Q (in dbSNP:rs35461805)"
FT /id="VAR_053632"
SQ SEQUENCE 545 AA; 59264 MW; 971FD2F909E1E9E6 CRC64;
MGQVLPVFAH CKEAPSTASS TPDSTEGGND DSDFRELHTA REFSEEDEEE TTSQDWGTPR
ELTFSYIAFD GVVGSGGRRD STARRPRPQG RSVSEPRDQH PQPSLGDSLE SIPSLSQSPE
PGRRGDPDTA PPSERPLEDL RLRLDHLGWV ARGTGSGEDS STSSSTPLED EEPQEPNRLE
TGEAGEELDL RLRLAQPSSP EVLTPQLSPG SGTPQAGTPS PSRSRDSNSG PEEPLLEEEE
KQWGPLEREP VRGQCLDSTD QLEFTVEPRL LGTAMEWLKT SLLLAVYKTV PILELSPPLW
TAIGWVQRGP TPPTPVLRVL LKWAKSPRSS GVPSLSLGAD MGSKVADLLY WKDTRTSGVV
FTGLMVSLLC LLHFSIVSVA AHLALLLLCG TISLRVYRKV LQAVHRGDGA NPFQAYLDVD
LTLTREQTER LSHQITSRVV SAATQLRHFF LVEDLVDSLK LALLFYILTF VGAIFNGLTL
LILGVIGLFT IPLLYRQHQA QIDQYVGLVT NQLSHIKAKI RAKIPGTGAL ASAAAAVSGS
KAKAE
