CNRG_HUMAN
ID CNRG_HUMAN Reviewed; 87 AA.
AC P18545; Q3KP63; Q7Z3U8;
DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1990, sequence version 1.
DT 03-AUG-2022, entry version 185.
DE RecName: Full=Retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit gamma;
DE Short=GMP-PDE gamma;
DE EC=3.1.4.35;
GN Name=PDE6G; Synonyms=PDEG;
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].
RC TISSUE=Retina;
RX PubMed=2161380; DOI=10.1016/0378-1119(90)90035-p;
RA Tuteja N., Danciger M., Klisak I., Tuteja R., Inana G., Mohandas T.,
RA Sparkes R.S., Farber D.B.;
RT "Isolation and characterization of cDNA encoding the gamma-subunit of cGMP
RT phosphodiesterase in human retina.";
RL Gene 88:227-232(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Retina;
RX PubMed=1965799;
RA Piriyev N.I., Purishko V.A., Khramtsov N.V., Lipkin V.M.;
RT "The organization of the gamma-subunit gene of human photoreceptor cyclic
RT GMP phosphodiesterase.";
RL Dokl. Akad. Nauk SSSR 315:229-231(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT HIS-27.
RX PubMed=8125719;
RA Hahn L.B., Berson E.L., Dryja T.P.;
RT "Evaluation of the gene encoding the gamma subunit of rod phosphodiesterase
RT in retinitis pigmentosa.";
RL Invest. Ophthalmol. Vis. Sci. 35:1077-1082(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Retina;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [7]
RP INVOLVEMENT IN RP57.
RX PubMed=20655036; DOI=10.1016/j.ajhg.2010.06.016;
RA Dvir L., Srour G., Abu-Ras R., Miller B., Shalev S.A., Ben-Yosef T.;
RT "Autosomal-recessive early-onset retinitis pigmentosa caused by a mutation
RT in PDE6G, the gene encoding the gamma subunit of rod cGMP
RT phosphodiesterase.";
RL Am. J. Hum. Genet. 87:258-264(2010).
CC -!- FUNCTION: Participates in processes of transmission and amplification
CC of the visual signal. cGMP-PDEs are the effector molecules in G-
CC protein-mediated phototransduction in vertebrate rods and cones.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3',5'-cyclic GMP + H2O = GMP + H(+); Xref=Rhea:RHEA:16957,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:57746,
CC ChEBI:CHEBI:58115; EC=3.1.4.35;
CC -!- SUBUNIT: Oligomer composed of two catalytic chains (alpha and beta), an
CC inhibitory chain (gamma) and the delta chain.
CC -!- INTERACTION:
CC P18545; O14503: BHLHE40; NbExp=3; IntAct=EBI-2622029, EBI-711810;
CC P18545; Q96JM7: L3MBTL3; NbExp=3; IntAct=EBI-2622029, EBI-2686809;
CC P18545; D3DTS7: PMP22; NbExp=3; IntAct=EBI-2622029, EBI-25882629;
CC P18545; O43741: PRKAB2; NbExp=3; IntAct=EBI-2622029, EBI-1053424;
CC P18545; Q8R511: Fnbp1; Xeno; NbExp=2; IntAct=EBI-2622029, EBI-1111424;
CC P18545; P62994: Grb2; Xeno; NbExp=2; IntAct=EBI-2622029, EBI-401775;
CC P18545; Q9QY17: Pacsin2; Xeno; NbExp=4; IntAct=EBI-2622029, EBI-491201;
CC P18545; Q63787: Pik3r1; Xeno; NbExp=2; IntAct=EBI-2622029, EBI-518443;
CC -!- DISEASE: Retinitis pigmentosa 57 (RP57) [MIM:613582]: A retinal
CC dystrophy belonging to the group of pigmentary retinopathies. Retinitis
CC pigmentosa is characterized by retinal pigment deposits visible on
CC fundus examination and primary loss of rod photoreceptor cells followed
CC by secondary loss of cone photoreceptors. Patients typically have night
CC vision blindness and loss of midperipheral visual field. As their
CC condition progresses, they lose their far peripheral visual field and
CC eventually central vision as well. {ECO:0000269|PubMed:20655036}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- SIMILARITY: Belongs to the rod/cone cGMP-PDE gamma subunit family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAD97656.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=EAW89666.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Mutations of the PDE6A/B/G genes; Note=Retina
CC International's Scientific Newsletter;
CC URL="https://www.retina-international.org/files/sci-news/pdemut.htm";
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DR EMBL; M36476; AAA60044.1; -; mRNA.
DR EMBL; X62025; CAA43975.1; -; Genomic_DNA.
DR EMBL; U00482; AAA03653.1; -; Genomic_DNA.
DR EMBL; U00481; AAA03653.1; JOINED; Genomic_DNA.
DR EMBL; BX537414; CAD97656.1; ALT_INIT; mRNA.
DR EMBL; CH471099; EAW89666.1; ALT_INIT; Genomic_DNA.
DR EMBL; BC106884; AAI06885.1; -; mRNA.
DR CCDS; CCDS11783.1; -.
DR PIR; JH0142; JH0142.
DR RefSeq; NP_002593.1; NM_002602.3.
DR RefSeq; XP_006722005.1; XM_006721942.3.
DR RefSeq; XP_016880224.1; XM_017024735.1.
DR RefSeq; XP_016880225.1; XM_017024736.1.
DR PDB; 3JWR; X-ray; 2.99 A; C/D=70-87.
DR PDBsum; 3JWR; -.
DR AlphaFoldDB; P18545; -.
DR SMR; P18545; -.
DR BioGRID; 111174; 26.
DR IntAct; P18545; 11.
DR MINT; P18545; -.
DR STRING; 9606.ENSP00000328412; -.
DR BindingDB; P18545; -.
DR ChEMBL; CHEMBL2097163; -.
DR ChEMBL; CHEMBL2363066; -.
DR DrugBank; DB07954; 3-isobutyl-1-methyl-7H-xanthine.
DR DrugBank; DB00203; Sildenafil.
DR DrugBank; DB00820; Tadalafil.
DR DrugBank; DB00862; Vardenafil.
DR DrugCentral; P18545; -.
DR iPTMnet; P18545; -.
DR PhosphoSitePlus; P18545; -.
DR BioMuta; PDE6G; -.
DR DMDM; 116583; -.
DR MassIVE; P18545; -.
DR PaxDb; P18545; -.
DR PeptideAtlas; P18545; -.
DR PRIDE; P18545; -.
DR ProteomicsDB; 53576; -.
DR Antibodypedia; 57116; 130 antibodies from 19 providers.
DR DNASU; 5148; -.
DR Ensembl; ENST00000331056.10; ENSP00000328412.5; ENSG00000185527.12.
DR Ensembl; ENST00000571004.1; ENSP00000461464.1; ENSG00000185527.12.
DR Ensembl; ENST00000571224.5; ENSP00000458167.1; ENSG00000185527.12.
DR GeneID; 5148; -.
DR KEGG; hsa:5148; -.
DR MANE-Select; ENST00000331056.10; ENSP00000328412.5; NM_002602.4; NP_002593.1.
DR UCSC; uc002kay.4; human.
DR CTD; 5148; -.
DR DisGeNET; 5148; -.
DR GeneCards; PDE6G; -.
DR GeneReviews; PDE6G; -.
DR HGNC; HGNC:8789; PDE6G.
DR HPA; ENSG00000185527; Tissue enriched (retina).
DR MalaCards; PDE6G; -.
DR MIM; 180073; gene.
DR MIM; 613582; phenotype.
DR neXtProt; NX_P18545; -.
DR OpenTargets; ENSG00000185527; -.
DR Orphanet; 791; Retinitis pigmentosa.
DR PharmGKB; PA33137; -.
DR VEuPathDB; HostDB:ENSG00000185527; -.
DR eggNOG; ENOG502S20G; Eukaryota.
DR GeneTree; ENSGT00390000013260; -.
DR HOGENOM; CLU_170469_0_0_1; -.
DR OMA; KGRGWHP; -.
DR OrthoDB; 1574918at2759; -.
DR PhylomeDB; P18545; -.
DR TreeFam; TF333297; -.
DR PathwayCommons; P18545; -.
DR Reactome; R-HSA-2485179; Activation of the phototransduction cascade.
DR Reactome; R-HSA-2514859; Inactivation, recovery and regulation of the phototransduction cascade.
DR Reactome; R-HSA-4086398; Ca2+ pathway.
DR SignaLink; P18545; -.
DR SIGNOR; P18545; -.
DR BioGRID-ORCS; 5148; 20 hits in 1075 CRISPR screens.
DR EvolutionaryTrace; P18545; -.
DR GeneWiki; PDE6G; -.
DR GenomeRNAi; 5148; -.
DR Pharos; P18545; Tclin.
DR PRO; PR:P18545; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; P18545; protein.
DR Bgee; ENSG00000185527; Expressed in granulocyte and 129 other tissues.
DR Genevisible; P18545; HS.
DR GO; GO:0097381; C:photoreceptor disc membrane; TAS:Reactome.
DR GO; GO:0042622; C:photoreceptor outer segment membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0047555; F:3',5'-cyclic-GMP phosphodiesterase activity; IEA:UniProtKB-EC.
DR GO; GO:0030553; F:cGMP binding; IEA:InterPro.
DR GO; GO:0004857; F:enzyme inhibitor activity; TAS:ProtInc.
DR GO; GO:0030507; F:spectrin binding; IEA:Ensembl.
DR GO; GO:0045742; P:positive regulation of epidermal growth factor receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0045745; P:positive regulation of G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IEA:Ensembl.
DR GO; GO:0050896; P:response to stimulus; IEA:UniProtKB-KW.
DR GO; GO:0007601; P:visual perception; TAS:ProtInc.
DR Gene3D; 4.10.1120.10; -; 1.
DR InterPro; IPR006952; PDE6_gamma.
DR InterPro; IPR037030; PDE6_gamma_sf.
DR PANTHER; PTHR12122; PTHR12122; 1.
DR Pfam; PF04868; PDE6_gamma; 1.
DR PIRSF; PIRSF000969; 35-cGMP_Pdiase_g; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; cGMP; Hydrolase; Reference proteome;
KW Retinitis pigmentosa; Sensory transduction; Vision.
FT CHAIN 1..87
FT /note="Retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic
FT phosphodiesterase subunit gamma"
FT /id="PRO_0000166117"
FT REGION 1..55
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:P04972"
FT VARIANT 27
FT /note="P -> H"
FT /evidence="ECO:0000269|PubMed:8125719"
FT /id="VAR_009294"
FT TURN 75..77
FT /evidence="ECO:0007829|PDB:3JWR"
FT HELIX 78..83
FT /evidence="ECO:0007829|PDB:3JWR"
SQ SEQUENCE 87 AA; 9643 MW; 5D7DEE59D7DDB9E0 CRC64;
MNLEPPKAEF RSATRVAGGP VTPRKGPPKF KQRQTRQFKS KPPKKGVQGF GDDIPGMEGL
GTDITVICPW EAFNHLELHE LAQYGII
