XLRS1_MOUSE
ID XLRS1_MOUSE Reviewed; 224 AA.
AC Q9Z1L4;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=Retinoschisin;
DE AltName: Full=X-linked juvenile retinoschisis protein homolog;
DE Flags: Precursor;
GN Name=Rs1; Synonyms=Rs1h, Xlrs1;
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].
RC STRAIN=129/SvJ;
RX PubMed=10051329; DOI=10.1007/s003359900991;
RA Gehrig A.E., Warneke-Wittstock R., Sauer C.G., Weber B.H.F.;
RT "Isolation and characterization of the murine X-linked juvenile
RT retinoschisis (Rs1h) gene.";
RL Mamm. Genome 10:303-307(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C57BL/6J; TISSUE=Eye;
RA Brunner B., Todt T., Lenzner S., Stout K., Schulz U., Ropers H.-H.,
RA Kalscheuer V.M.;
RT "Genomic structure and comparative analysis of seven contiguous genes
RT disclose a large region with conserved gene order in human Xp22.2-p22.1.";
RL Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Retina;
RX PubMed=10023077; DOI=10.1016/s0378-1119(98)00578-2;
RA Reid S.N., Akhmedov N.B., Piriev N.I., Kozak C.A., Danciger M.,
RA Farber D.B.;
RT "The mouse X-linked juvenile retinoschisis cDNA: expression in
RT photoreceptors.";
RL Gene 227:257-266(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [5]
RP TISSUE SPECIFICITY.
RX PubMed=10915776; DOI=10.1093/hmg/9.12.1873;
RA Grayson C., Reid S.N., Ellis J.A., Rutherford A., Sowden J.C., Yates J.R.,
RA Farber D.B., Trump D.;
RT "Retinoschisin, the X-linked retinoschisis protein, is a secreted
RT photoreceptor protein, and is expressed and released by Weri-Rb1 cells.";
RL Hum. Mol. Genet. 9:1873-1879(2000).
RN [6]
RP DISRUPTION PHENOTYPE, FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=11983912; DOI=10.1073/pnas.092528599;
RA Weber B.H., Schrewe H., Molday L.L., Gehrig A., White K.L., Seeliger M.W.,
RA Jaissle G.B., Friedburg C., Tamm E., Molday R.S.;
RT "Inactivation of the murine X-linked juvenile retinoschisis gene, Rs1h,
RT suggests a role of retinoschisin in retinal cell layer organization and
RT synaptic structure.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:6222-6227(2002).
RN [7]
RP FUNCTION, DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, LIPID-BINDING, TISSUE
RP SPECIFICITY, AND MUTAGENESIS OF TYR-89 AND TRP-92.
RX PubMed=17325137; DOI=10.1167/iovs.06-0915;
RA Vijayasarathy C., Takada Y., Zeng Y., Bush R.A., Sieving P.A.;
RT "Retinoschisin is a peripheral membrane protein with affinity for anionic
RT phospholipids and affected by divalent cations.";
RL Invest. Ophthalmol. Vis. Sci. 48:991-1000(2007).
RN [8]
RP SUBCELLULAR LOCATION, AND LIPID-BINDING.
RX PubMed=20677810; DOI=10.1021/bi1007029;
RA Kotova S., Vijayasarathy C., Dimitriadis E.K., Ikonomou L., Jaffe H.,
RA Sieving P.A.;
RT "Retinoschisin (RS1) interacts with negatively charged lipid bilayers in
RT the presence of Ca2+: an atomic force microscopy study.";
RL Biochemistry 49:7023-7032(2010).
CC -!- FUNCTION: Binds negatively charged membrane lipids, such as
CC phosphatidylserine and phosphoinositides (PubMed:17325137,
CC PubMed:20677810). May play a role in cell-cell adhesion processes in
CC the retina, via homomeric interaction between octamers present on the
CC surface of two neighboring cells (By similarity). Required for normal
CC structure and function of the retina (PubMed:11983912,
CC PubMed:17325137). {ECO:0000250|UniProtKB:O15537,
CC ECO:0000269|PubMed:11983912, ECO:0000269|PubMed:17325137,
CC ECO:0000269|PubMed:20677810}.
CC -!- SUBUNIT: Homooctamer of 4 homodimers; disulfide-linked. The homooctamer
CC has a flat, cogwheel structure with a diameter of about 14 nm. Two
CC stacked octamers can assemble to form a hexadecamer.
CC {ECO:0000250|UniProtKB:O15537}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:O15537}. Cell
CC membrane {ECO:0000269|PubMed:17325137, ECO:0000305|PubMed:20677810};
CC Peripheral membrane protein {ECO:0000269|PubMed:17325137,
CC ECO:0000269|PubMed:20677810}; Extracellular side
CC {ECO:0000269|PubMed:17325137, ECO:0000305|PubMed:20677810}. Note=Binds
CC to phosphatidylserine-containing lipid membranes and embeds itself
CC partially into the lipid bilayer. Lipid-binding requires the presence
CC of Ca(2+) ions. {ECO:0000269|PubMed:20677810}.
CC -!- TISSUE SPECIFICITY: Detected in the eye cup (PubMed:11983912). Detected
CC in retina, in the inner segment of the photoreceptors, the inner
CC nuclear layer, the inner plexiform layer and the ganglion cell layer
CC (at protein level) (PubMed:10915776, PubMed:11983912, PubMed:17325137).
CC Restricted to the retina (PubMed:10023077, PubMed:10915776). At the
CC mRNA level, detected only within the photoreceptor cell layer, most
CC prominently within the inner segments of the photoreceptors
CC (PubMed:10023077, PubMed:10915776). Undetectable in the inner plexiform
CC layers and the inner nuclear layer (PubMed:10915776).
CC {ECO:0000269|PubMed:10023077, ECO:0000269|PubMed:10915776,
CC ECO:0000269|PubMed:11983912, ECO:0000269|PubMed:17325137}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype at birth (PubMed:11983912).
CC After two months, mutant males display a profound disorganization of
CC the inner and outer nuclear layer of the retina, with increased
CC extracellular spaces in the region of photoreceptor ribbon synapses and
CC the appearance of gaps, and a decrease in the number of photoreceptor
CC cell outer segments (PubMed:11983912, PubMed:17325137). The number of
CC cone photoreceptors is reduced threefold (PubMed:11983912). After three
CC months, mutant males display a layer of small, cyst-like structures in
CC the inner retina (PubMed:11983912). They have profoundly altered
CC electroretinograms, indicating a decreased light sensitivity due to a
CC decrease in the number of functional photoreceptors (PubMed:11983912).
CC {ECO:0000269|PubMed:11983912, ECO:0000269|PubMed:17325137}.
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DR EMBL; AF084561; AAD21808.1; -; mRNA.
DR EMBL; AF084567; AAD21809.1; -; Genomic_DNA.
DR EMBL; AF084562; AAD21809.1; JOINED; Genomic_DNA.
DR EMBL; AF084563; AAD21809.1; JOINED; Genomic_DNA.
DR EMBL; AF084564; AAD21809.1; JOINED; Genomic_DNA.
DR EMBL; AF084565; AAD21809.1; JOINED; Genomic_DNA.
DR EMBL; AF084566; AAD21809.1; JOINED; Genomic_DNA.
DR EMBL; AJ011381; CAA09601.1; -; mRNA.
DR EMBL; BC046422; AAH46422.1; -; mRNA.
DR CCDS; CCDS30505.1; -.
DR RefSeq; NP_035432.3; NM_011302.3.
DR AlphaFoldDB; Q9Z1L4; -.
DR SMR; Q9Z1L4; -.
DR IntAct; Q9Z1L4; 1.
DR STRING; 10090.ENSMUSP00000033650; -.
DR PhosphoSitePlus; Q9Z1L4; -.
DR MaxQB; Q9Z1L4; -.
DR PaxDb; Q9Z1L4; -.
DR PRIDE; Q9Z1L4; -.
DR ProteomicsDB; 300005; -.
DR Antibodypedia; 24146; 88 antibodies from 13 providers.
DR DNASU; 20147; -.
DR Ensembl; ENSMUST00000033650; ENSMUSP00000033650; ENSMUSG00000031293.
DR GeneID; 20147; -.
DR KEGG; mmu:20147; -.
DR UCSC; uc009utq.1; mouse.
DR CTD; 6247; -.
DR MGI; MGI:1336189; Rs1.
DR VEuPathDB; HostDB:ENSMUSG00000031293; -.
DR eggNOG; ENOG502QU6Y; Eukaryota.
DR GeneTree; ENSGT00940000161181; -.
DR InParanoid; Q9Z1L4; -.
DR OMA; CMPECLY; -.
DR OrthoDB; 1047682at2759; -.
DR PhylomeDB; Q9Z1L4; -.
DR BioGRID-ORCS; 20147; 2 hits in 72 CRISPR screens.
DR PRO; PR:Q9Z1L4; -.
DR Proteomes; UP000000589; Chromosome X.
DR RNAct; Q9Z1L4; protein.
DR Bgee; ENSMUSG00000031293; Expressed in retinal neural layer and 17 other tissues.
DR ExpressionAtlas; Q9Z1L4; baseline and differential.
DR Genevisible; Q9Z1L4; MM.
DR GO; GO:0005576; C:extracellular region; IDA:MGI.
DR GO; GO:0005615; C:extracellular space; ISO:MGI.
DR GO; GO:0019897; C:extrinsic component of plasma membrane; IDA:MGI.
DR GO; GO:0098984; C:neuron to neuron synapse; IDA:ARUK-UCL.
DR GO; GO:0001917; C:photoreceptor inner segment; IDA:ARUK-UCL.
DR GO; GO:0005547; F:phosphatidylinositol-3,4,5-trisphosphate binding; IDA:MGI.
DR GO; GO:0043325; F:phosphatidylinositol-3,4-bisphosphate binding; IDA:MGI.
DR GO; GO:0080025; F:phosphatidylinositol-3,5-bisphosphate binding; IDA:MGI.
DR GO; GO:0032266; F:phosphatidylinositol-3-phosphate binding; IDA:MGI.
DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; IDA:MGI.
DR GO; GO:0070273; F:phosphatidylinositol-4-phosphate binding; IDA:MGI.
DR GO; GO:0010314; F:phosphatidylinositol-5-phosphate binding; IDA:MGI.
DR GO; GO:0001786; F:phosphatidylserine binding; IDA:UniProtKB.
DR GO; GO:0016062; P:adaptation of rhodopsin mediated signaling; IMP:MGI.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:0051260; P:protein homooligomerization; ISS:UniProtKB.
DR GO; GO:0010842; P:retina layer formation; IMP:MGI.
DR GO; GO:0007601; P:visual perception; ISO:MGI.
DR CDD; cd00057; FA58C; 1.
DR InterPro; IPR000421; FA58C.
DR InterPro; IPR008979; Galactose-bd-like_sf.
DR Pfam; PF00754; F5_F8_type_C; 1.
DR SMART; SM00231; FA58C; 1.
DR SUPFAM; SSF49785; SSF49785; 1.
DR PROSITE; PS01285; FA58C_1; 1.
DR PROSITE; PS50022; FA58C_3; 1.
PE 1: Evidence at protein level;
KW Cell adhesion; Cell membrane; Disulfide bond; Lipid-binding; Membrane;
KW Reference proteome; Secreted; Sensory transduction; Signal; Vision.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..224
FT /note="Retinoschisin"
FT /id="PRO_0000022696"
FT DOMAIN 63..219
FT /note="F5/8 type C"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00081"
FT DISULFID 40
FT /note="Interchain"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00081"
FT DISULFID 59
FT /note="Interchain (with C-223)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00081"
FT DISULFID 63..219
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00081"
FT DISULFID 110..142
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00081"
FT DISULFID 223
FT /note="Interchain (with C-59)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00081"
FT MUTAGEN 89
FT /note="Y->C: Decreases phosphatidylserine binding."
FT /evidence="ECO:0000269|PubMed:17325137"
FT MUTAGEN 92
FT /note="W->C: Decreases phosphatidylserine binding."
FT /evidence="ECO:0000269|PubMed:17325137"
SQ SEQUENCE 224 AA; 25575 MW; 4536203CC00E90E4 CRC64;
MPHKIEGFFL LLLFGYEATL GLSSTEDEGE DPWYQKACKC DCQVGANALW SAGATSLDCI
PECPYHKPLG FESGEVTPDQ ITCSNPEQYV GWYSSWTANK ARLNSQGFGC AWLSKYQDSS
QWLQIDLKEI KVISGILTQG RCDIDEWVTK YSVQYRTDER LNWIYYKDQT GNNRVFYGNS
DRSSTVQNLL RPPIISRFIR LIPLGWHVRI AIRMELLECA SKCA
