REEP6_MOUSE
ID REEP6_MOUSE Reviewed; 201 AA.
AC Q9JM62; Q8K0X2;
DT 20-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 115.
DE RecName: Full=Receptor expression-enhancing protein 6;
DE AltName: Full=Polyposis locus protein 1-like 1;
DE AltName: Full=TB2 protein-like 1;
GN Name=Reep6; Synonyms=Dp1l1, Tb2l1;
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 [MRNA] (ISOFORM 1).
RX PubMed=15550249; DOI=10.1016/j.cell.2004.11.021;
RA Saito H., Kubota M., Roberts R.W., Chi Q., Matsunami H.;
RT "RTP family members induce functional expression of mammalian odorant
RT receptors.";
RL Cell 119:679-691(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC STRAIN=C57BL/6J; TISSUE=Retina;
RX PubMed=15728532; DOI=10.1167/iovs.04-0867;
RA Sato H., Tomita H., Nakazawa T., Wakana S., Tamai M.;
RT "Deleted in polyposis 1-like 1 gene (Dp1l1): a novel gene richly expressed
RT in retinal ganglion cells.";
RL Invest. Ophthalmol. Vis. Sci. 46:791-796(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=FVB/N; TISSUE=Liver;
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 [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, Liver, Lung, Pancreas, and Testis;
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).
RN [5]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=24098485; DOI=10.1371/journal.pone.0076366;
RA Bjork S., Hurt C.M., Ho V.K., Angelotti T.;
RT "REEPs are membrane shaping adapter proteins that modulate specific G
RT protein-coupled receptor trafficking by affecting ER cargo capacity.";
RL PLoS ONE 8:E76366-E76366(2013).
RN [6]
RP FUNCTION, ALTERNATIVE SPLICING (ISOFORMS 1 AND 2), TISSUE SPECIFICITY, AND
RP DEVELOPMENTAL STAGE.
RX PubMed=24691551; DOI=10.1093/hmg/ddu143;
RA Hao H., Veleri S., Sun B., Kim D.S., Keeley P.W., Kim J.W., Yang H.J.,
RA Yadav S.P., Manjunath S.H., Sood R., Liu P., Reese B.E., Swaroop A.;
RT "Regulation of a novel isoform of receptor expression enhancing protein
RT REEP6 in rod photoreceptors by bZIP transcription factor NRL.";
RL Hum. Mol. Genet. 23:4260-4271(2014).
RN [7]
RP FUNCTION, INTERACTION WITH CLATHRIN AND STX3, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=28369466; DOI=10.1093/hmg/ddx111;
RA Veleri S., Nellissery J., Mishra B., Manjunath S.H., Brooks M.J., Dong L.,
RA Nagashima K., Qian H., Gao C., Sergeev Y.V., Huang X.F., Qu J., Lu F.,
RA Cideciyan A.V., Li T., Jin Z.B., Fariss R.N., Ratnapriya R., Jacobson S.G.,
RA Swaroop A.;
RT "REEP6 mediates trafficking of a subset of Clathrin-coated vesicles and is
RT critical for rod photoreceptor function and survival.";
RL Hum. Mol. Genet. 26:2218-2230(2017).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=28475715; DOI=10.1093/hmg/ddx149;
RA Agrawal S.A., Burgoyne T., Eblimit A., Bellingham J., Parfitt D.A.,
RA Lane A., Nichols R., Asomugha C., Hayes M.J., Munro P.M., Xu M., Wang K.,
RA Futter C.E., Li Y., Chen R., Cheetham M.E.;
RT "REEP6 deficiency leads to retinal degeneration through disruption of ER
RT homeostasis and protein trafficking.";
RL Hum. Mol. Genet. 26:2667-2677(2017).
CC -!- FUNCTION: Required for correct function and survival of retinal
CC photoreceptors (PubMed:24098485, PubMed:24691551, PubMed:28475715).
CC Required for retinal development (PubMed:28369466). In rod
CC photoreceptors, facilitates stability and/or trafficking of guanylate
CC cyclases and is required to maintain endoplasmic reticulum and
CC mitochondrial homeostasis (PubMed:28475715). May play a role in
CC clathrin-coated intracellular vesicle trafficking of proteins from the
CC endoplasmic reticulum to the retinal rod plasma membrane
CC (PubMed:24098485, PubMed:28369466). {ECO:0000269|PubMed:24098485,
CC ECO:0000269|PubMed:24691551, ECO:0000269|PubMed:28369466,
CC ECO:0000269|PubMed:28475715}.
CC -!- SUBUNIT: Interacts with STX3 (PubMed:28369466). Interacts with clathrin
CC (PubMed:28369466). {ECO:0000269|PubMed:28369466}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:24098485, ECO:0000269|PubMed:28475715}; Multi-pass
CC membrane protein {ECO:0000255}. Cytoplasmic vesicle, clathrin-coated
CC vesicle membrane {ECO:0000269|PubMed:28369466}; Multi-pass membrane
CC protein {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9JM62-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9JM62-2; Sequence=VSP_016631, VSP_016632;
CC -!- TISSUE SPECIFICITY: Expressed in the inner segment of rod
CC photoreceptors and outer plexiform layer of the retina (at protein
CC level) (PubMed:24691551, PubMed:28369466, PubMed:28475715). Expressed
CC in liver, but not detected in brain, muscle, kidney, retinal cone
CC photoreceptors or retinal ganglion cells (at protein level)
CC (PubMed:24691551). Highly expressed in the ganglion cell layer of the
CC retina and in liver, and also detected at low levels in kidney and
CC testis (PubMed:15728532). Isoform 1: Expressed in the retina
CC (PubMed:15728532, PubMed:24691551). Isoform 2: Expressed in liver
CC (PubMed:24691551). {ECO:0000269|PubMed:15728532,
CC ECO:0000269|PubMed:24691551, ECO:0000269|PubMed:28369466,
CC ECO:0000269|PubMed:28475715}.
CC -!- DEVELOPMENTAL STAGE: Isoform 1 shows increasing levels of expression in
CC the retina from birth, reaching maximal levels by 12 days of age.
CC {ECO:0000269|PubMed:24691551}.
CC -!- DISRUPTION PHENOTYPE: Viable, however mice develop progressive
CC deterioration in retinal response, and male mice are sterile
CC (PubMed:28369466, PubMed:28475715). Progressive retinal rod dysfunction
CC first evident from one month of age progressing to almost undetectable
CC scotopic response at one year of age (PubMed:28369466). Progressive
CC degeneration of photopic response by retinal cone receptors first
CC evident at one year of age (PubMed:28369466). Defective retinal
CC morphology with significant thinning of the outer nuclear layer and
CC reduced rows of nuclei (PubMed:28369466, PubMed:28475715). Accumulation
CC of vacuole-like structures at the apical inner segment of the retina
CC (PubMed:28369466). Reduced and disorganised photoreceptors with
CC shortened fragmented outer segment (PubMed:28475715). Altered
CC endoplasmic reticulum (ER) organization with increased ER area near the
CC base of the outer segment, increased number of mitochondria in the rod
CC ellipsoid region and induction of ER stress (PubMed:28475715). Reduced
CC retinal expression of phototransduction proteins Cngb1 and Gnat1 and of
CC Aipl1 (PubMed:28369466). Reduced expression of guanylate cyclases
CC Gucy2e/GC1 and Gucy2f/GC2 in the rod outer segment and mislocalization
CC of Pde6a from the outer segment to the inner segment and outer nuclear
CC layer (PubMed:28475715). {ECO:0000269|PubMed:28369466,
CC ECO:0000269|PubMed:28475715}.
CC -!- SIMILARITY: Belongs to the DP1 family. {ECO:0000305}.
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DR EMBL; AY562234; AAT70679.1; -; mRNA.
DR EMBL; AB039933; BAA94544.1; -; mRNA.
DR EMBL; BC029741; AAH29741.1; -; mRNA.
DR CCDS; CCDS35979.1; -. [Q9JM62-1]
DR CCDS; CCDS56735.1; -. [Q9JM62-2]
DR RefSeq; NP_001191860.1; NM_001204931.1. [Q9JM62-2]
DR RefSeq; NP_647453.1; NM_139292.2. [Q9JM62-1]
DR AlphaFoldDB; Q9JM62; -.
DR BioGRID; 213988; 2.
DR STRING; 10090.ENSMUSP00000100991; -.
DR iPTMnet; Q9JM62; -.
DR PhosphoSitePlus; Q9JM62; -.
DR jPOST; Q9JM62; -.
DR MaxQB; Q9JM62; -.
DR PaxDb; Q9JM62; -.
DR PeptideAtlas; Q9JM62; -.
DR PRIDE; Q9JM62; -.
DR ProteomicsDB; 255175; -. [Q9JM62-1]
DR ProteomicsDB; 255176; -. [Q9JM62-2]
DR DNASU; 70335; -.
DR Ensembl; ENSMUST00000105354; ENSMUSP00000100991; ENSMUSG00000035504. [Q9JM62-1]
DR Ensembl; ENSMUST00000105355; ENSMUSP00000100992; ENSMUSG00000035504. [Q9JM62-2]
DR Ensembl; ENSMUST00000186864; ENSMUSP00000140840; ENSMUSG00000035504. [Q9JM62-1]
DR GeneID; 70335; -.
DR KEGG; mmu:70335; -.
DR UCSC; uc007gct.2; mouse. [Q9JM62-1]
DR UCSC; uc007gcu.2; mouse. [Q9JM62-2]
DR CTD; 92840; -.
DR MGI; MGI:1917585; Reep6.
DR VEuPathDB; HostDB:ENSMUSG00000035504; -.
DR eggNOG; KOG1725; Eukaryota.
DR GeneTree; ENSGT00470000042565; -.
DR InParanoid; Q9JM62; -.
DR OrthoDB; 1473891at2759; -.
DR PhylomeDB; Q9JM62; -.
DR TreeFam; TF314913; -.
DR BioGRID-ORCS; 70335; 2 hits in 75 CRISPR screens.
DR PRO; PR:Q9JM62; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; Q9JM62; protein.
DR Bgee; ENSMUSG00000035504; Expressed in retinal neural layer and 168 other tissues.
DR ExpressionAtlas; Q9JM62; baseline and differential.
DR Genevisible; Q9JM62; MM.
DR GO; GO:0045177; C:apical part of cell; IDA:MGI.
DR GO; GO:0030665; C:clathrin-coated vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0001917; C:photoreceptor inner segment; ISS:UniProtKB.
DR GO; GO:0044317; C:rod spherule; IDA:UniProtKB.
DR GO; GO:0050908; P:detection of light stimulus involved in visual perception; ISS:UniProtKB.
DR GO; GO:0032386; P:regulation of intracellular transport; IDA:UniProtKB.
DR InterPro; IPR004345; TB2_DP1_HVA22.
DR PANTHER; PTHR12300; PTHR12300; 1.
DR Pfam; PF03134; TB2_DP1_HVA22; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasmic vesicle; Endoplasmic reticulum; Membrane;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..201
FT /note="Receptor expression-enhancing protein 6"
FT /id="PRO_0000101819"
FT TRANSMEM 36..56
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 89..109
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 117..137
FT /note="Helical"
FT /evidence="ECO:0000255"
FT VAR_SEQ 173..174
FT /note="VL -> AK (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_016631"
FT VAR_SEQ 175..201
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_016632"
SQ SEQUENCE 201 AA; 22204 MW; 4A742CF012F351BD CRC64;
MDGLRQRFER FLEQKNVATE ALGALEARTG VEKRYLAAGA LALLGLYLLF GYGASLLCNV
IGFVYPAYAS VKAIESPSKE DDTVWLTYWV VYALFGLVEF FSDLLLFWFP FYYAGKCAFL
LFCMTPGPWN GALLLYHRVI RPLFLKHHMA LDSAASQLSG RALDLAAGIT RDVLQALARG
RALVTPASTS EPPAALELDP K
