RD3_MOUSE
ID RD3_MOUSE Reviewed; 195 AA.
AC Q8BRE0; Q3SYJ8; Q9CRS3; Q9JMF2;
DT 19-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 104.
DE RecName: Full=Protein RD3;
DE AltName: Full=Retinal degeneration protein 3;
GN Name=Rd3;
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].
RC TISSUE=Brain;
RX PubMed=10679242; DOI=10.1006/bbrc.2000.2170;
RA Inoue S., Sano H., Ohta M.;
RT "Growth suppression of Escherichia coli by induction of expression of
RT mammalian genes with transmembrane or ATPase domains.";
RL Biochem. Biophys. Res. Commun. 268:553-561(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Head;
RA Adachi J., Aizawa K., Akimura T., Arakawa T., Bono H., Carninci P.,
RA Fukuda S., Furuno M., Hanagaki T., Hara A., Hashizume W., Hayashida K.,
RA Hayatsu N., Hiramoto K., Hiraoka T., Hirozane T., Hori F., Imotani K.,
RA Ishii Y., Itoh M., Kagawa I., Kasukawa T., Katoh H., Kawai J., Kojima Y.,
RA Kondo S., Konno H., Kouda M., Koya S., Kurihara C., Matsuyama T.,
RA Miyazaki A., Murata M., Nakamura M., Nishi K., Nomura K., Numazaki R.,
RA Ohno M., Ohsato N., Okazaki Y., Saito R., Saitoh H., Sakai C., Sakai K.,
RA Sakazume N., Sano H., Sasaki D., Shibata K., Shinagawa A., Shiraki T.,
RA Sogabe Y., Tagami M., Tagawa A., Takahashi F., Takaku-Akahira S.,
RA Takeda Y., Tanaka T., Tomaru A., Toya T., Yasunishi A., Muramatsu M.,
RA Hayashizaki Y.;
RL Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, and Eye;
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 DISEASE, AND FUNCTION.
RX PubMed=8486383; DOI=10.1006/geno.1993.1138;
RA Chang B., Heckenlively J.R., Hawes N.L., Roderick T.H.;
RT "New mouse primary retinal degeneration (rd-3).";
RL Genomics 16:45-49(1993).
RN [5]
RP TISSUE SPECIFICITY.
RX PubMed=12914764; DOI=10.1016/s0006-291x(03)01410-4;
RA Lavorgna G., Lestingi M., Ziviello C., Testa F., Simonelli F.,
RA Manitto M.P., Brancato R., Ferrari M., Rinaldi E., Ciccodicola A.,
RA Banfi S.;
RT "Identification and characterization of C1orf36, a transcript highly
RT expressed in photoreceptor cells, and mutation analysis in retinitis
RT pigmentosa.";
RL Biochem. Biophys. Res. Commun. 308:414-421(2003).
RN [6]
RP DISEASE, TISSUE SPECIFICITY, AND FUNCTION.
RX PubMed=17186464; DOI=10.1086/510021;
RA Friedman J.S., Chang B., Kannabiran C., Chakarova C., Singh H.P.,
RA Jalali S., Hawes N.L., Branham K., Othman M., Filippova E., Thompson D.A.,
RA Webster A.R., Andreasson S., Jacobson S.G., Bhattacharya S.S.,
RA Heckenlively J.R., Swaroop A.;
RT "Premature truncation of a novel protein, RD3, exhibiting subnuclear
RT localization is associated with retinal degeneration.";
RL Am. J. Hum. Genet. 79:1059-1070(2006).
RN [7]
RP TISSUE SPECIFICITY, SUBCELLULAR LOCATION, INTERACTION WITH GUCY2E AND
RP GUCY2F, AND FUNCTION.
RX PubMed=21078983; DOI=10.1073/pnas.1010460107;
RA Azadi S., Molday L.L., Molday R.S.;
RT "RD3, the protein associated with Leber congenital amaurosis type 12, is
RT required for guanylate cyclase trafficking in photoreceptor cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:21158-21163(2010).
RN [8]
RP FUNCTION, AND INTERACTION WITH GUCY2E.
RX PubMed=27471269; DOI=10.1074/jbc.m116.742288;
RA Peshenko I.V., Olshevskaya E.V., Dizhoor A.M.;
RT "Functional Study and Mapping Sites for Interaction with the Target Enzyme
RT in Retinal Degeneration 3 (RD3) Protein.";
RL J. Biol. Chem. 291:19713-19723(2016).
RN [9]
RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=29515371; DOI=10.3389/fnmol.2018.00052;
RA Wimberg H., Janssen-Bienhold U., Koch K.W.;
RT "Control of the Nucleotide Cycle in Photoreceptor Cell Extracts by Retinal
RT Degeneration Protein 3.";
RL Front. Mol. Neurosci. 11:52-52(2018).
CC -!- FUNCTION: Plays a critical role in the regulation of enzymes involved
CC in nucleotide cycle in photoreceptors (PubMed:21078983,
CC PubMed:27471269). Inhibits the basal catalytic activity and the GCAP-
CC stimulated activity of GUCY2E and GUCY2F, two retinal guanylyl cyclases
CC involved in the production of cGMP in photoreceptors (PubMed:27471269).
CC Involved in the transport of GUCY2E and GUCY2F to their target sites in
CC the photoreceptor outer segment (PubMed:21078983). Up-regulates the
CC activity of GUK1, a kinase that also plays an essential role for
CC recycling GMP and indirectly, cGMP (By similarity). Plays an important
CC role for the survival of rods and cones in the retina (PubMed:8486383,
CC PubMed:17186464). {ECO:0000250|UniProtKB:Q7Z3Z2,
CC ECO:0000269|PubMed:17186464, ECO:0000269|PubMed:21078983,
CC ECO:0000269|PubMed:27471269, ECO:0000269|PubMed:8486383}.
CC -!- SUBUNIT: Monomer (By similarity). Interacts with GUCY2E; promotes the
CC exit of GUCY2E from the endoplasmic reticulum and its trafficking to
CC the photoreceptor outer segments (PubMed:21078983). The interaction
CC with GUCY2E negatively regulates its activity (By similarity).
CC Interacts with GUCY2F; promotes the exit of GUCY2F from the endoplasmic
CC reticulum and its trafficking to the photoreceptor outer segments
CC (PubMed:21078983). The interaction with GUCY2F negatively regulates its
CC activity (By similarity). Interacts with GUK1; up-regulates GUK1
CC activity (By similarity). {ECO:0000250|UniProtKB:Q7Z3Z2,
CC ECO:0000269|PubMed:21078983}.
CC -!- SUBCELLULAR LOCATION: Cell projection, cilium, photoreceptor outer
CC segment {ECO:0000269|PubMed:21078983, ECO:0000269|PubMed:29515371}.
CC Photoreceptor inner segment {ECO:0000269|PubMed:21078983,
CC ECO:0000269|PubMed:29515371}. Endosome {ECO:0000269|PubMed:21078983}.
CC Nucleus {ECO:0000269|PubMed:17186464}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q7Z3Z2}. Cytoplasm, perinuclear region
CC {ECO:0000250|UniProtKB:Q7Z3Z2}. Note=Colocalizes with GUCY2E and GUCY2F
CC in rods and cones photoreceptors. Colocalizes with GUK1 in
CC photoreceptor inner segments and to a lesser extent in the outer
CC plexiform layer (PubMed:29515371). Strong dot-like perinuclear staining
CC in the epithelial cells (By similarity). {ECO:0000250|UniProtKB:Q7Z3Z2,
CC ECO:0000269|PubMed:29515371}.
CC -!- TISSUE SPECIFICITY: Expressed in the retina and in particular in the
CC inner nuclear layer, in rod and cone outer segments, in the outer
CC nuclear layer, in the outer plexiform layer and in the ganglion cell
CC layer. {ECO:0000269|PubMed:12914764, ECO:0000269|PubMed:17186464,
CC ECO:0000269|PubMed:21078983, ECO:0000269|PubMed:29515371}.
CC -!- DISEASE: Note=A spontaneous mutation leading to a frameshift and in an
CC unstable truncated protein lacking the C-terminal 89 amino acids causes
CC retinal degeneration. Homozygotes mice (called rd-3) display retinal
CC degeneration, beginning at 3 weeks of age, characterized by complete
CC loss of photoreceptor rod cells by 5 weeks, and cones by 8 weeks.
CC {ECO:0000269|PubMed:17186464, ECO:0000269|PubMed:8486383}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA92758.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAB29312.2; Type=Erroneous initiation; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AB030195; BAA92758.1; ALT_FRAME; mRNA.
DR EMBL; AK014383; BAB29312.2; ALT_INIT; mRNA.
DR EMBL; AK045045; BAC32196.1; -; mRNA.
DR EMBL; BC103778; AAI03779.1; -; mRNA.
DR EMBL; BC116935; AAI16936.1; -; mRNA.
DR EMBL; BC116937; AAI16938.1; -; mRNA.
DR CCDS; CCDS15626.3; -.
DR RefSeq; NP_001171371.2; NM_001177900.2.
DR RefSeq; NP_001290061.1; NM_001303132.1.
DR RefSeq; NP_076216.3; NM_023727.4.
DR RefSeq; XP_006497268.1; XM_006497205.2.
DR RefSeq; XP_006497269.1; XM_006497206.3.
DR AlphaFoldDB; Q8BRE0; -.
DR SMR; Q8BRE0; -.
DR IntAct; Q8BRE0; 46.
DR STRING; 10090.ENSMUSP00000050188; -.
DR PhosphoSitePlus; Q8BRE0; -.
DR PaxDb; Q8BRE0; -.
DR PRIDE; Q8BRE0; -.
DR ProteomicsDB; 255138; -.
DR Antibodypedia; 47112; 69 antibodies from 17 providers.
DR Ensembl; ENSMUST00000180463; ENSMUSP00000138049; ENSMUSG00000049353.
DR GeneID; 74023; -.
DR KEGG; mmu:74023; -.
DR UCSC; uc007edd.3; mouse.
DR CTD; 343035; -.
DR MGI; MGI:1921273; Rd3.
DR VEuPathDB; HostDB:ENSMUSG00000049353; -.
DR eggNOG; ENOG502QTP1; Eukaryota.
DR GeneTree; ENSGT00390000002089; -.
DR HOGENOM; CLU_107621_0_0_1; -.
DR InParanoid; Q8BRE0; -.
DR OMA; FRSRIKI; -.
DR OrthoDB; 1505645at2759; -.
DR PhylomeDB; Q8BRE0; -.
DR BioGRID-ORCS; 74023; 1 hit in 54 CRISPR screens.
DR ChiTaRS; Rd3; mouse.
DR PRO; PR:Q8BRE0; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q8BRE0; protein.
DR Bgee; ENSMUSG00000049353; Expressed in layer of retina and 37 other tissues.
DR ExpressionAtlas; Q8BRE0; baseline and differential.
DR Genevisible; Q8BRE0; MM.
DR GO; GO:0120199; C:cone photoreceptor outer segment; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005768; C:endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0001917; C:photoreceptor inner segment; IDA:UniProtKB.
DR GO; GO:0001750; C:photoreceptor outer segment; IDA:UniProtKB.
DR GO; GO:0120200; C:rod photoreceptor outer segment; IDA:UniProtKB.
DR GO; GO:0031283; P:negative regulation of guanylate cyclase activity; IMP:UniProtKB.
DR GO; GO:0015031; P:protein transport; ISO:MGI.
DR GO; GO:0050896; P:response to stimulus; IEA:UniProtKB-KW.
DR GO; GO:0060041; P:retina development in camera-type eye; IMP:UniProtKB.
DR GO; GO:0007601; P:visual perception; IMP:UniProtKB.
DR InterPro; IPR028092; RD3.
DR PANTHER; PTHR28489; PTHR28489; 1.
DR Pfam; PF14473; RD3; 1.
PE 1: Evidence at protein level;
KW Cell projection; Coiled coil; Cytoplasm; Endosome; Nucleus;
KW Reference proteome; Sensory transduction; Vision.
FT CHAIN 1..195
FT /note="Protein RD3"
FT /id="PRO_0000089249"
FT REGION 168..195
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 22..54
FT /evidence="ECO:0000255"
SQ SEQUENCE 195 AA; 22669 MW; 6C33550846800762 CRC64;
MSLIPWLRWN DTPPRLSART PAEMVLETLM MELAGQMREV ERQQRERRSA VRKICTGVDY
SWLANTPRPT YDISPGERLQ LEDVCAKIHP SYCGPAILRF RQLLAEREPE VQEVARLFRS
VLQEALEKMK QEEEAHKLTR QWSLRPRGSL SSFKTRARIA PFASDIRTIS EDVERDAPPP
PRTWSMPEFR APQAD
