GUC2D_MOUSE
ID GUC2D_MOUSE Reviewed; 1117 AA.
AC A0A0U1RPR8;
DT 11-DEC-2019, integrated into UniProtKB/Swiss-Prot.
DT 17-FEB-2016, sequence version 1.
DT 03-AUG-2022, entry version 46.
DE RecName: Full=Guanylate cyclase D;
DE EC=4.6.1.2 {ECO:0000250|UniProtKB:P51839};
DE Flags: Precursor;
GN Name=Gucy2d {ECO:0000312|MGI:MGI:106030};
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 [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 [2]
RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=9096404; DOI=10.1073/pnas.94.7.3388;
RA Juilfs D.M., Fuelle H.J., Zhao A.Z., Houslay M.D., Garbers D.L.,
RA Beavo J.A.;
RT "A subset of olfactory neurons that selectively express cGMP-stimulated
RT phosphodiesterase (PDE2) and guanylyl cyclase-D define a unique olfactory
RT signal transduction pathway.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:3388-3395(1997).
RN [3]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=17724338; DOI=10.1073/pnas.0704965104;
RA Leinders-Zufall T., Cockerham R.E., Michalakis S., Biel M., Garbers D.L.,
RA Reed R.R., Zufall F., Munger S.D.;
RT "Contribution of the receptor guanylyl cyclase GC-D to chemosensory
RT function in the olfactory epithelium.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:14507-14512(2007).
RN [4]
RP FUNCTION.
RX PubMed=17702944; DOI=10.1126/science.1144233;
RA Hu J., Zhong C., Ding C., Chi Q., Walz A., Mombaerts P., Matsunami H.,
RA Luo M.;
RT "Detection of near-atmospheric concentrations of CO2 by an olfactory
RT subsystem in the mouse.";
RL Science 317:953-957(2007).
RN [5]
RP FUNCTION.
RX PubMed=20637621; DOI=10.1016/j.cub.2010.06.021;
RA Munger S.D., Leinders-Zufall T., McDougall L.M., Cockerham R.E., Schmid A.,
RA Wandernoth P., Wennemuth G., Biel M., Zufall F., Kelliher K.R.;
RT "An olfactory subsystem that detects carbon disulfide and mediates food-
RT related social learning.";
RL Curr. Biol. 20:1438-1444(2010).
CC -!- FUNCTION: Functions as an olfactory receptor activated by urine
CC odorants, uroguanylin and guanylin and as well by the volatile
CC semiochemicals carbon disulfide (CS2) and carbon dioxide (CO2)
CC (PubMed:17724338, PubMed:17702944, PubMed:20637621). Has guanylate
CC cyclase activity upon binding of the ligand (By similarity). Activation
CC of GUCY2D neurons leads to the cGMP-dependent activation of the CNGA3
CC channels, membrane depolarization and an increase in action potential
CC frequency (PubMed:17724338, PubMed:20637621). Signaling pathways
CC activated by GUCY2D may trigger social behaviors such as acquisition of
CC food preference (PubMed:20637621). {ECO:0000250|UniProtKB:P51839,
CC ECO:0000269|PubMed:17702944, ECO:0000269|PubMed:17724338,
CC ECO:0000269|PubMed:20637621}.
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:0000250|UniProtKB:P51839};
CC -!- ACTIVITY REGULATION: Activated by Ca(2+).
CC {ECO:0000250|UniProtKB:P51839}.
CC -!- SUBUNIT: Interacts (via the catalytic domain) with NCALD.
CC {ECO:0000250|UniProtKB:P51839}.
CC -!- SUBCELLULAR LOCATION: Cell projection, cilium membrane
CC {ECO:0000269|PubMed:9096404}; Single-pass type I membrane protein.
CC -!- TISSUE SPECIFICITY: Found in a subset of olfactory neurons in the main
CC olfactory epithelium. {ECO:0000269|PubMed:9096404}.
CC -!- DOMAIN: The protein kinase domain is predicted to be catalytically
CC inactive. {ECO:0000305}.
CC -!- DISRUPTION PHENOTYPE: Deficient mice lack olfactory response to
CC uroguanylin and guanylin. {ECO:0000269|PubMed:17724338}.
CC -!- SIMILARITY: Belongs to the adenylyl cyclase class-4/guanylyl cyclase
CC family. {ECO:0000305}.
CC -!- CAUTION: The gene names for receptor guanylyl cyclases are inconsistent
CC between mouse and human. The ortholog of the mouse Gucy2d gene is a
CC pseudogene in humans. The mouse Gucy2d is not an ortholog of the human
CC GUCY2D gene, the latter of which encodes a retinal receptor guanylyl
CC cyclase involved in phototransduction. {ECO:0000305}.
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DR EMBL; AC111084; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC115069; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS85343.1; -.
DR RefSeq; NP_001124165.1; NM_001130693.3.
DR AlphaFoldDB; A0A0U1RPR8; -.
DR SMR; A0A0U1RPR8; -.
DR STRING; 10090.ENSMUSP00000095875; -.
DR PhosphoSitePlus; A0A0U1RPR8; -.
DR Ensembl; ENSMUST00000206435; ENSMUSP00000146093; ENSMUSG00000074003.
DR GeneID; 14918; -.
DR KEGG; mmu:14918; -.
DR CTD; 3000; -.
DR MGI; MGI:106030; Gucy2d.
DR VEuPathDB; HostDB:ENSMUSG00000074003; -.
DR GeneTree; ENSGT00940000162702; -.
DR OMA; TFLAHKN; -.
DR OrthoDB; 229634at2759; -.
DR BioGRID-ORCS; 14918; 3 hits in 33 CRISPR screens.
DR ChiTaRS; Gucy2d; mouse.
DR PRO; PR:A0A0U1RPR8; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; A0A0U1RPR8; protein.
DR Bgee; ENSMUSG00000074003; Expressed in spermatid and 9 other tissues.
DR ExpressionAtlas; A0A0U1RPR8; baseline and differential.
DR GO; GO:0060170; C:ciliary membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; ISO:MGI.
DR GO; GO:0097730; C:non-motile cilium; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:InterPro.
DR GO; GO:0004383; F:guanylate cyclase activity; ISS:UniProtKB.
DR GO; GO:0016941; F:natriuretic peptide receptor activity; ISO:MGI.
DR GO; GO:0005549; F:odorant binding; IMP:UniProtKB.
DR GO; GO:0004984; F:olfactory receptor activity; IMP:UniProtKB.
DR GO; GO:0001653; F:peptide receptor activity; IBA:GO_Central.
DR GO; GO:0004672; F:protein kinase activity; IEA:InterPro.
DR GO; GO:0006182; P:cGMP biosynthetic process; ISS:UniProtKB.
DR GO; GO:0003031; P:detection of carbon dioxide; IMP:UniProtKB.
DR GO; GO:0050911; P:detection of chemical stimulus involved in sensory perception of smell; IMP:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR GO; GO:0042048; P:olfactory behavior; IMP:UniProtKB.
DR GO; GO:0008355; P:olfactory learning; IMP:UniProtKB.
DR GO; GO:0010753; P:positive regulation of cGMP-mediated signaling; IDA:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR GO; GO:0007168; P:receptor guanylyl cyclase signaling pathway; ISS:UniProtKB.
DR GO; GO:0007608; P:sensory perception of smell; IMP:UniProtKB.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
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; 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; 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 2: Evidence at transcript level;
KW Cell membrane; Cell projection; cGMP biosynthesis; Disulfide bond; Lyase;
KW Membrane; Nucleotide-binding; Reference proteome; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..66
FT /evidence="ECO:0000255"
FT CHAIN 67..1117
FT /note="Guanylate cyclase D"
FT /id="PRO_0000448832"
FT TOPO_DOM 67..479
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 480..500
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 501..1117
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT DOMAIN 541..812
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 887..1017
FT /note="Guanylate cyclase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT REGION 529..557
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 874..915
FT /note="Interaction with NCALD"
FT /evidence="ECO:0000250|UniProtKB:P51839"
FT REGION 1096..1117
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT DISULFID 121..149
FT /evidence="ECO:0000250"
FT DISULFID 462
FT /note="Interchain"
FT /evidence="ECO:0000250"
FT DISULFID 470
FT /note="Interchain"
FT /evidence="ECO:0000250"
SQ SEQUENCE 1117 AA; 122528 MW; 2954272B64C6E69C CRC64;
MAGLQQGCHF EGQNWTAPHW KTCLPCQGPW RLTVSHLKTV SSISVLSVVF WSVLLWADSL
SLLAWARETF TLGVLGPWDC DPIFAQALPS IATQLAVDQV NQDASLLPGS QLDFKVLPTG
CDTPHALATF VAHKNIVAAF VGPVNPGFCS AAALLAQGWG KSLFSWACEA PEGGGDLVPT
LPSAADVLLS VMRHFGWARW AIVSSHQDIW VTTAQQLATA FRTHGLPIGL VTSLGPGEKG
ATEVCKQLHS VHGLKIVVLC MHSALLGGLE QTTLLHCAWE EGLTDGRLVF LPYDTLLFAL
PYGNRSYLVL DDHGPLQEAY DAVLTVSLES SPESHAFTAT EMSGGATANL EPEQVSPLFG
TIYDAVILLA HALNRSETHG AGLSGAHLGD HVRALDVAGF SQRIRTDGKG RRLAQYVILD
TDGEGSQLVP THILDTSTWQ VQPLGKPIHF PGGSPPAHDA SCWFDPNTLC IRGVQPLGSL
LTLTIACVLA LVGGFLAYFI RLGLQQLRLL RGPHRILLTS QELTFLQRTP SRRRPHVDSG
SESRSVVDGG SPRSVTQGSA RSLPAFLEHT NVALYQGEWV WLKKFEAGVA PDLRPSSLSF
LRKLREMRHE NVTAFLGLFV GPGVSAMVLE HCARGSLEDL LQNENLRLDW TFKASLLLDL
IRGLRYLHHR RFPHGRLKSR NCVVDTRFVL KITDHGYAEF LESHCSSRPQ PAPEELLWTA
PELLRGPGKA TFKGDVFSLA IILQEVLTRD PPYCSWGLSA EEIIRKVASP PPLCRPLVSP
DQGPLECIQL MQLCWEEAPD DRPSLDQIYT QFKSINQGKK TSVVDSMLRM LEKYSESLED
LVQERTEELE LERRKTERLL SQMLPPSVAH ALKMGTTVEP EYFDQVTIYF SDIVGFTTIS
ALSEPIEVVG FLNDLYTLFD AVLDSHDVYK VETIGDAYMV ASGLPRRNGN RHAAEIANLA
LDILSYAGNF RMRHAPDVPI RVRAGLHSGP CVAGVVGLTM PRYCLFGDTV NTASRMESTG
LPYRIHVSQS TVQALLSLDE GYKIDVRGQT ELKGKGLEET YWLTGKVGFC RPLPTPLSIK
PGDPWQDRIN QEIRTGFAKA RQGLAEPRKS GEAGPGP
