GUC2E_MOUSE
ID GUC2E_MOUSE Reviewed; 1108 AA.
AC P52785; B1ASX7;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Retinal guanylyl cyclase 1;
DE AltName: Full=Guanylate cyclase 2E;
DE AltName: Full=Guanylyl cyclase GC-E;
DE EC=4.6.1.2 {ECO:0000269|PubMed:21598940};
DE Flags: Precursor;
GN Name=Gucy2e; Synonyms=Guc2e;
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].
RC TISSUE=Liver;
RX PubMed=8838319; DOI=10.1006/geno.1996.0060;
RA Yang R.B., Fulle H.J., Garbers D.L.;
RT "Chromosomal localization and genomic organization of genes encoding
RT guanylyl cyclase receptors expressed in olfactory sensory neurons and
RT retina.";
RL Genomics 31:367-372(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=17255100; DOI=10.1074/jbc.m610369200;
RA Baehr W., Karan S., Maeda T., Luo D.G., Li S., Bronson J.D., Watt C.B.,
RA Yau K.W., Frederick J.M., Palczewski K.;
RT "The function of guanylate cyclase 1 and guanylate cyclase 2 in rod and
RT cone photoreceptors.";
RL J. Biol. Chem. 282:8837-8847(2007).
RN [5]
RP ACTIVITY REGULATION, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND FUNCTION.
RX PubMed=21598940; DOI=10.1021/bi200491b;
RA Peshenko I.V., Olshevskaya E.V., Savchenko A.B., Karan S., Palczewski K.,
RA Baehr W., Dizhoor A.M.;
RT "Enzymatic properties and regulation of the native isozymes of retinal
RT membrane guanylyl cyclase (RetGC) from mouse photoreceptors.";
RL Biochemistry 50:5590-5600(2011).
CC -!- FUNCTION: Catalyzes the synthesis of cyclic GMP (cGMP) in rods and
CC cones of photoreceptors. Plays an essential role in phototransduction,
CC by mediating cGMP replenishment (PubMed:21598940). May also participate
CC in the trafficking of membrane-asociated proteins to the photoreceptor
CC outer segment membrane (PubMed:17255100). {ECO:0000269|PubMed:17255100,
CC ECO:0000269|PubMed:21598940}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=GTP = 3',5'-cyclic GMP + diphosphate; Xref=Rhea:RHEA:13665,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:37565, ChEBI:CHEBI:57746; EC=4.6.1.2;
CC Evidence={ECO:0000269|PubMed:21598940};
CC -!- ACTIVITY REGULATION: Activated by GUCA1A when free calcium ions
CC concentration is low, and inhibited by GUCA1A when free calcium ions
CC concentration is high (PubMed:21598940). Negatively regulated by RD3;
CC RD3 inhibits the basal and GUCA1A-stimulated guanylate cyclase activity
CC (By similarity). {ECO:0000250|UniProtKB:Q02846,
CC ECO:0000269|PubMed:21598940}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.64 mM for GTP (in presence of GUCA1A)
CC {ECO:0000269|PubMed:21598940};
CC KM=0.7 mM for GTP (in presence of GUCA1B)
CC {ECO:0000269|PubMed:21598940};
CC KM=1.55 nM for GTP {ECO:0000269|PubMed:21598940};
CC -!- SUBUNIT: Homodimer; requires homodimerization for guanylyl cyclase
CC activity (By similarity). Interacts (via C-terminus) with RD3 (via C-
CC terminus); promotes the exit of GUCY2E from the endoplasmic reticulum
CC and its trafficking to the photoreceptor outer segments (By
CC similarity). Interaction with RD3 negatively regulates GUCY2E guanylate
CC cyclase activity (By similarity). {ECO:0000250|UniProtKB:P51840,
CC ECO:0000250|UniProtKB:Q02846}.
CC -!- SUBCELLULAR LOCATION: Photoreceptor outer segment membrane
CC {ECO:0000269|PubMed:21598940}; Single-pass type I membrane protein
CC {ECO:0000255}. Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q02846}; Single-pass type I membrane protein
CC {ECO:0000255}.
CC -!- PTM: There are 9 conserved cysteine residues in sensory guanylate
CC cyclases, 6 in the extracellular domain, which may be involved in
CC intra- or interchain disulfide bonds.
CC -!- DISRUPTION PHENOTYPE: Deficient mice exhibit abnormal retinal cone cell
CC morphology, impaired cone and rod electrophysiology, and severe retinal
CC cone cell degeneration. GUCY2E and GUCY2F double knockout mice does not
CC show any photoresponse, their rods and cones degenerate and the
CC intracellular transport of some phototransduction proteins is impaired.
CC {ECO:0000269|PubMed:17255100}.
CC -!- MISCELLANEOUS: The gene name nomenclature of retinal guanylyl cyclase 1
CC is confusing; for mouse the gene name is GUCY2E whereas the gene name
CC is GUCY2D for human and rat orthologs. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the adenylyl cyclase class-4/guanylyl cyclase
CC family. {ECO:0000255|PROSITE-ProRule:PRU00099}.
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DR EMBL; L41933; AAC42081.1; -; Genomic_DNA.
DR EMBL; AL645527; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466601; EDL10484.1; -; Genomic_DNA.
DR CCDS; CCDS24887.1; -.
DR RefSeq; NP_032218.2; NM_008192.3.
DR RefSeq; XP_006532307.1; XM_006532244.2.
DR AlphaFoldDB; P52785; -.
DR SMR; P52785; -.
DR BioGRID; 200127; 8.
DR IntAct; P52785; 1.
DR STRING; 10090.ENSMUSP00000021259; -.
DR GlyGen; P52785; 1 site.
DR iPTMnet; P52785; -.
DR PhosphoSitePlus; P52785; -.
DR MaxQB; P52785; -.
DR PaxDb; P52785; -.
DR PRIDE; P52785; -.
DR ProteomicsDB; 271065; -.
DR Antibodypedia; 12365; 266 antibodies from 29 providers.
DR DNASU; 14919; -.
DR Ensembl; ENSMUST00000021259; ENSMUSP00000021259; ENSMUSG00000020890.
DR Ensembl; ENSMUST00000108664; ENSMUSP00000104304; ENSMUSG00000020890.
DR Ensembl; ENSMUST00000108665; ENSMUSP00000104305; ENSMUSG00000020890.
DR GeneID; 14919; -.
DR KEGG; mmu:14919; -.
DR UCSC; uc007jpn.2; mouse.
DR CTD; 14919; -.
DR MGI; MGI:105123; Gucy2e.
DR VEuPathDB; HostDB:ENSMUSG00000020890; -.
DR eggNOG; KOG1023; Eukaryota.
DR GeneTree; ENSGT00940000161326; -.
DR HOGENOM; CLU_001072_1_0_1; -.
DR InParanoid; P52785; -.
DR OMA; YEGDRVW; -.
DR OrthoDB; 229634at2759; -.
DR PhylomeDB; P52785; -.
DR TreeFam; TF106338; -.
DR Reactome; R-MMU-2514859; Inactivation, recovery and regulation of the phototransduction cascade.
DR BioGRID-ORCS; 14919; 2 hits in 79 CRISPR screens.
DR ChiTaRS; Gucy2e; mouse.
DR PRO; PR:P52785; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; P52785; protein.
DR Bgee; ENSMUSG00000020890; Expressed in retinal neural layer and 17 other tissues.
DR Genevisible; P52785; MM.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0001750; C:photoreceptor outer segment; ISO:MGI.
DR GO; GO:0042622; C:photoreceptor outer segment membrane; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:InterPro.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0004383; F:guanylate cyclase activity; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0001653; F:peptide receptor activity; IBA:GO_Central.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0004672; F:protein kinase activity; IEA:InterPro.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0006182; P:cGMP biosynthetic process; IDA:UniProtKB.
DR GO; GO:0019934; P:cGMP-mediated signaling; ISO:MGI.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR GO; GO:0007168; P:receptor guanylyl cyclase signaling pathway; IBA:GO_Central.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR GO; GO:0007601; P:visual perception; IEA:UniProtKB-KW.
DR CDD; cd07302; CHD; 1.
DR Gene3D; 3.30.70.1230; -; 1.
DR InterPro; IPR001054; A/G_cyclase.
DR InterPro; IPR018297; A/G_cyclase_CS.
DR InterPro; IPR001828; ANF_lig-bd_rcpt.
DR InterPro; IPR011645; HNOB_dom_associated.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR029787; Nucleotide_cyclase.
DR InterPro; IPR028082; Peripla_BP_I.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR Pfam; PF01094; ANF_receptor; 1.
DR Pfam; PF00211; Guanylate_cyc; 1.
DR Pfam; PF07701; HNOBA; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR SMART; SM00044; CYCc; 1.
DR SUPFAM; SSF53822; SSF53822; 1.
DR SUPFAM; SSF55073; SSF55073; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00452; GUANYLATE_CYCLASE_1; 1.
DR PROSITE; PS50125; GUANYLATE_CYCLASE_2; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PE 1: Evidence at protein level;
KW Cell projection; cGMP biosynthesis; Disulfide bond; Endoplasmic reticulum;
KW Glycoprotein; GTP-binding; Lyase; Membrane; Nucleotide-binding;
KW Reference proteome; Sensory transduction; Signal; Transmembrane;
KW Transmembrane helix; Vision.
FT SIGNAL 1..54
FT /evidence="ECO:0000250|UniProtKB:P55203"
FT CHAIN 55..1108
FT /note="Retinal guanylyl cyclase 1"
FT /id="PRO_0000012383"
FT TOPO_DOM 55..465
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 466..490
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 491..1108
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 491..811
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 883..1013
FT /note="Guanylate cyclase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT REGION 1069..1108
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1088..1102
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 300
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 108..136
FT /evidence="ECO:0000250"
FT DISULFID 452
FT /note="Interchain"
FT /evidence="ECO:0000250"
FT DISULFID 460
FT /note="Interchain"
FT /evidence="ECO:0000250"
FT CONFLICT 15
FT /note="G -> R (in Ref. 1; AAC42081)"
FT /evidence="ECO:0000305"
FT CONFLICT 92
FT /note="A -> G (in Ref. 1; AAC42081)"
FT /evidence="ECO:0000305"
FT CONFLICT 135
FT /note="A -> G (in Ref. 1; AAC42081)"
FT /evidence="ECO:0000305"
FT CONFLICT 1033
FT /note="A -> S (in Ref. 1; AAC42081)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1108 AA; 120638 MW; F3F4FE69D38EB1C8 CRC64;
MSAWLLPAGG LPGAGFCVPA RQSPSSFSRV LRWPRPGLPG LLLLLLLPSP SALSAVFKVG
VLGPWACDPI FARARPDLAA RLAANRLNRD FALDGGPRFE VALLPEPCLT PGSLGAVSSA
LSRVSGLVGP VNPAACRPAE LLAQEAGVAL VPWGCPGTRA AGTTAPAVTP AADALYVLLR
AFRWARVALI TAPQDLWVEA GRALSTALRA RGLPVALVTS METSDRSGAR EALGRIRDGP
RVRVVIMVMH SVLLGGEEQR YLLEAAEELA LTDGSLVFLP FDTLHYALSP GPEALAAFVN
SSQLRRAHDA VLTLTRRCPP GGSVQDSLRR AQEHQELPLD LNLKQVSPLF GTIYDAVFLL
AGGVKRARTA VGGGWVSGAS VARQVREAQV SGFCGVLGRT EEPSFVLLDT DASGEQLFAT
HLLDPVLGSL RSAGTPMHFP RGGPAPGPDP SCWFDPDVIC NGGVEPGLVF VGFLLVIGMG
LTGAFLAHYL RHRLLHMQMA SGPNKIILTL EDVTFLHPPG GSSRKVVQGS RSSLATRSAS
DIRSVPSQPQ ESTNVGLYEG DWVWLKKFPG EHHMAIRPAT KTAFSKLREL RHENVALYLG
LFLAGTADSP ATPGEGILAV VSEHCARGSL HDLLAQREIK LDWMFKSSLL LDLIKGMRYL
HHRGVAHGRL KSRNCVVDGR FVLKVTDHGH GRLLEAQRVL PEPPSAEDQL WTAPELLRDP
SLERRGTLAG DVFSLAIIMQ EVVCRSTPYA MLELTPEEVI QRVRSPPPLC RPLVSMDQAP
MECIQLMTQC WAEHPELRPS MDLTFDLFKS INKGRKTNII DSMLRMLEQY SSNLEDLIRE
RTEELEQEKQ KTDRLLTQML PPSVAEALKM GTSVEPEYFE EVTLYFSDIV GFTTISAMSE
PIEVVDLLND LYTLFDAIIG AHDVYKVETI GDAYMVASGL PQRNGQRHAA EIANMSLDIL
SAVGSFRMRH MPEVPVRIRI GLHSGPCVAG VVGLTMPRYC LFGDTVNTAS RMESTGLPYR
IHVNMSTVRI LRALDQGFQM ECRGRTELKG KGIEDTYWLV GRLGFNKPIP KPPDLQPGAS
NHGISLQEIP PERRKKLEKA RPGQFTGK
