RTN2_MOUSE
ID RTN2_MOUSE Reviewed; 471 AA.
AC O70622; O70620;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1998, sequence version 1.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=Reticulon-2;
DE AltName: Full=Neuroendocrine-specific protein-like 1 {ECO:0000303|PubMed:9530622};
DE Short=NSP-like protein 1 {ECO:0000303|PubMed:9530622};
DE AltName: Full=Neuroendocrine-specific protein-like I;
DE Short=NSP-like protein I;
DE Short=NSPLI;
GN Name=Rtn2 {ECO:0000312|MGI:MGI:107612};
GN Synonyms=Nspl1 {ECO:0000303|PubMed:9530622};
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]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2), AND TISSUE
RP SPECIFICITY.
RC STRAIN=129/Sv, and FVB/N; TISSUE=Cerebellum, and Skeletal muscle;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Retina;
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 [3]
RP SUBCELLULAR LOCATION.
RX PubMed=10672514; DOI=10.1023/a:1005533013926;
RA Geisler J.G., Palmer R.J., Stubbs L.J., Mucenski M.L.;
RT "Nspl1, a new Z-band-associated protein.";
RL J. Muscle Res. Cell Motil. 20:661-668(1999).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-44, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic brain;
RX PubMed=15345747; DOI=10.1074/mcp.m400085-mcp200;
RA Ballif B.A., Villen J., Beausoleil S.A., Schwartz D., Gygi S.P.;
RT "Phosphoproteomic analysis of the developing mouse brain.";
RL Mol. Cell. Proteomics 3:1093-1101(2004).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=19720795; DOI=10.2337/db09-0756;
RA Ikemoto T., Hosoya T., Takata K., Aoyama H., Hiramatsu T., Onoe H.,
RA Suzuki M., Endo M.;
RT "Functional role of neuroendocrine-specific protein-like 1 in membrane
RT translocation of GLUT4.";
RL Diabetes 58:2802-2812(2009).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-44; SER-226 AND SER-228, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Lung, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Inhibits amyloid precursor protein processing, probably by
CC blocking BACE1 activity (By similarity). 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 (PubMed:19720795).
CC {ECO:0000250|UniProtKB:O75298, ECO:0000250|UniProtKB:Q6WN19,
CC ECO:0000269|PubMed:19720795}.
CC -!- SUBUNIT: Interacts with SPAST (By similarity). Interacts with BACE1 (By
CC similarity). Interacts (via first transmembrane domain) with
CC ARL6IP5/GTRAP3-18 (By similarity). Interacts (via N-terminus) with
CC SLC1A1/EAAC1; the interaction promotes cell surface expression of
CC SLC1A1 (By similarity). {ECO:0000250|UniProtKB:O75298,
CC ECO:0000250|UniProtKB:Q6WN19}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:O75298}; Multi-pass membrane protein
CC {ECO:0000255}. Sarcoplasmic reticulum membrane
CC {ECO:0000269|PubMed:19720795}; 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:0000269|PubMed:19720795}; Multi-pass membrane protein
CC {ECO:0000255}. Cell membrane, sarcolemma, T-tubule
CC {ECO:0000269|PubMed:19720795}; Multi-pass membrane protein
CC {ECO:0000255}. Cytoplasm, myofibril, sarcomere, Z line
CC {ECO:0000269|PubMed:10672514}. Cytoplasm, cytoskeleton
CC {ECO:0000269|PubMed:10672514}. Note=Localizes to intermediate filaments
CC in mononucleated myoblasts and to Z lines in mature myotubes.
CC {ECO:0000269|PubMed:10672514}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Brain;
CC IsoId=O70622-1; Sequence=Displayed;
CC Name=2; Synonyms=Muscle;
CC IsoId=O70622-2; Sequence=VSP_005650, VSP_005651;
CC -!- TISSUE SPECIFICITY: Detected in skeletal and cardiac muscle (at protein
CC level) (PubMed:19720795). Expressed predominantly in neural and
CC muscular tissues (PubMed:9530622). {ECO:0000269|PubMed:19720795,
CC ECO:0000269|PubMed:9530622}.
CC -!- DISRUPTION PHENOTYPE: Impaired exercise-induced SLC2A4/GLUT4
CC translocation to the cell membrane, impaired exercise-induced glucose
CC uptake in skeletal muscle cells and impaired ability to reduce blood
CC glucose levels on contraction/exercise. {ECO:0000269|PubMed:19720795}.
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DR EMBL; AF038537; AAC14906.1; -; Genomic_DNA.
DR EMBL; AF038537; AAC14907.1; -; Genomic_DNA.
DR EMBL; AF038538; AAC14908.1; -; mRNA.
DR EMBL; AF038539; AAC14909.1; -; mRNA.
DR EMBL; AF093624; AAD13195.1; -; Genomic_DNA.
DR EMBL; BC031370; AAH31370.1; -; mRNA.
DR CCDS; CCDS20896.1; -. [O70622-1]
DR CCDS; CCDS39797.1; -. [O70622-2]
DR RefSeq; NP_001020535.1; NM_001025364.3. [O70622-2]
DR RefSeq; NP_038676.1; NM_013648.6. [O70622-1]
DR AlphaFoldDB; O70622; -.
DR SMR; O70622; -.
DR BioGRID; 203033; 1.
DR STRING; 10090.ENSMUSP00000032559; -.
DR iPTMnet; O70622; -.
DR PhosphoSitePlus; O70622; -.
DR PaxDb; O70622; -.
DR PeptideAtlas; O70622; -.
DR PRIDE; O70622; -.
DR ProteomicsDB; 260954; -. [O70622-1]
DR ProteomicsDB; 260955; -. [O70622-2]
DR Antibodypedia; 31344; 145 antibodies from 27 providers.
DR DNASU; 20167; -.
DR Ensembl; ENSMUST00000032559; ENSMUSP00000032559; ENSMUSG00000030401. [O70622-1]
DR Ensembl; ENSMUST00000108468; ENSMUSP00000104108; ENSMUSG00000030401. [O70622-2]
DR GeneID; 20167; -.
DR KEGG; mmu:20167; -.
DR UCSC; uc009flh.2; mouse. [O70622-1]
DR CTD; 6253; -.
DR MGI; MGI:107612; Rtn2.
DR VEuPathDB; HostDB:ENSMUSG00000030401; -.
DR eggNOG; KOG1792; Eukaryota.
DR GeneTree; ENSGT00940000160599; -.
DR HOGENOM; CLU_508939_0_0_1; -.
DR InParanoid; O70622; -.
DR OMA; WRAIGWV; -.
DR PhylomeDB; O70622; -.
DR TreeFam; TF105431; -.
DR BioGRID-ORCS; 20167; 2 hits in 71 CRISPR screens.
DR ChiTaRS; Rtn2; mouse.
DR PRO; PR:O70622; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; O70622; protein.
DR Bgee; ENSMUSG00000030401; Expressed in triceps brachii and 223 other tissues.
DR ExpressionAtlas; O70622; baseline and differential.
DR Genevisible; O70622; MM.
DR GO; GO:0009986; C:cell surface; ISO:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005882; C:intermediate filament; IDA:UniProtKB.
DR GO; GO:0033017; C:sarcoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0030315; C:T-tubule; IDA:MGI.
DR GO; GO:0014802; C:terminal cisterna; IDA:MGI.
DR GO; GO:0030018; C:Z disc; IDA:UniProtKB.
DR GO; GO:0010467; P:gene expression; IPI:MGI.
DR GO; GO:0065002; P:intracellular protein transmembrane transport; IMP:MGI.
DR GO; GO:1902430; P:negative regulation of amyloid-beta formation; ISS:UniProtKB.
DR GO; GO:0015031; P:protein transport; ISO:MGI.
DR GO; GO:0046324; P:regulation of glucose import; IMP:MGI.
DR InterPro; IPR003388; Reticulon.
DR Pfam; PF02453; Reticulon; 1.
DR PROSITE; PS50845; RETICULON; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Cytoplasm; Cytoskeleton;
KW Endoplasmic reticulum; Membrane; Phosphoprotein; Reference proteome;
KW Sarcoplasmic reticulum; Transmembrane; Transmembrane helix.
FT CHAIN 1..471
FT /note="Reticulon-2"
FT /id="PRO_0000168162"
FT TRANSMEM 295..315
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 390..410
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 272..471
FT /note="Reticulon"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00170"
FT REGION 1..137
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 153..181
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 205..234
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 95..118
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 156..170
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 205..231
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 44
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:15345747,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 226
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 228
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT VAR_SEQ 1..267
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9530622"
FT /id="VSP_005650"
FT VAR_SEQ 268..271
FT /note="PLLL -> MGSK (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9530622"
FT /id="VSP_005651"
SQ SEQUENCE 471 AA; 51347 MW; 9BBD8F372CF63AD3 CRC64;
MGQVLPVFAH CKEAPSTASS TPDSTEGGND DSDFRELHTA REFSEDEEEE TTSQDWGTPR
ELTFSYIAFD GVVGSGGRRD SVVRRPRPQG RSVSEPRDPP QQSGLGDSLE SIPSLSQSPE
PGRRGDPDPV PPAERPLEEL RLRLDQLGWV VRSAGSGEDS ATSSSTPLEN EEPDGLEASE
AGEETNLELR LAQSLHLQLE VLTPQLSPSS GTPQAHTPSP QRSQDSNSGP DDEPLLNVVE
EHWRLLEQEP ITAQCLDSTD QSEFMLEPLL LVADLLYWKD TRTSGAVFTG LMASLLCLLH
FSIVSVAAHL ALLGLCATIS LRVYRKVLQA VHRGDGTNPF QAYLDMDLTL TREQTERLSQ
QIASHVVSTA TQLRHFFLVE DLVDSLKLAL LFYILTFVGA IFNGLTLVIL GVVALFTVPL
LYRQHQAQID QYVGLVTNQL SHIKAKIRAK IPGTGTLAPT ASVSGSKAKA E
