GUC2D_RAT
ID GUC2D_RAT Reviewed; 1110 AA.
AC P51839; F1M245;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 11-DEC-2019, sequence version 2.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=Guanylate cyclase 2D;
DE EC=4.6.1.2 {ECO:0000269|PubMed:11580282, ECO:0000269|PubMed:18178149};
DE AltName: Full=Guanylate cyclase, olfactory;
DE AltName: Full=ONE-GC {ECO:0000303|PubMed:18178149};
DE AltName: Full=Olfactory guanylyl cyclase GC-D {ECO:0000303|PubMed:7724600};
DE Short=GC-D {ECO:0000303|PubMed:7724600};
DE Flags: Precursor;
GN Name=Gucy2d; Synonyms=Gucy2e {ECO:0000312|RGD:69322};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley; TISSUE=Olfactory neuron;
RX PubMed=7724600; DOI=10.1073/pnas.92.8.3571;
RA Fuelle H.-J., Vassar R., Foster D.C., Yang R.-B., Axel R., Garbers D.L.;
RT "A receptor guanylyl cyclase expressed specifically in olfactory sensory
RT neurons.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:3571-3575(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND IDENTIFICATION.
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [3]
RP CATALYTIC ACTIVITY, FUNCTION, SUBCELLULAR LOCATION, ACTIVITY REGULATION,
RP TISSUE SPECIFICITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=11580282; DOI=10.1021/bi0108406;
RA Duda T., Jankowska A., Venkataraman V., Nagele R.G., Sharma R.K.;
RT "A novel calcium-regulated membrane guanylate cyclase transduction system
RT in the olfactory neuroepithelium.";
RL Biochemistry 40:12067-12077(2001).
RN [4]
RP CATALYTIC ACTIVITY, FUNCTION, INTERACTION WITH NCALD, AND LIGAND-BINDING.
RX PubMed=18178149; DOI=10.1016/j.bbrc.2007.12.153;
RA Duda T., Sharma R.K.;
RT "ONE-GC membrane guanylate cyclase, a trimodal odorant signal transducer.";
RL Biochem. Biophys. Res. Commun. 367:440-445(2008).
CC -!- FUNCTION: Functions as an olfactory receptor activated by a urine
CC odorant, uroguanylin (PubMed:18178149). Activated as well by the
CC volatile semiochemicals carbon disulfide (CS2) and carbon dioxide (CO2)
CC (By similarity). Has guanylate cyclase activity upon binding of the
CC ligand (PubMed:18178149). Activation of GUCY2D neurons leads to the
CC cGMP-dependent activation of the CNGA3 channels, membrane
CC depolarization and an increase in action potential frequency. Signaling
CC pathways activated by GUCY2D may trigger social behaviors such as
CC acquisition of food preference (By similarity).
CC {ECO:0000250|UniProtKB:A0A0U1RPR8, ECO:0000269|PubMed:18178149}.
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:11580282, ECO:0000269|PubMed:18178149};
CC -!- ACTIVITY REGULATION: Activated by Ca(2+) (PubMed:11580282). Activated
CC by NCALD in a Ca(2+)-dependent fashion (PubMed:11580282).
CC {ECO:0000269|PubMed:11580282}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=71 uM for GTP {ECO:0000269|PubMed:11580282};
CC -!- SUBUNIT: Interacts (via the catalytic domain) with NCALD.
CC {ECO:0000269|PubMed:18178149}.
CC -!- SUBCELLULAR LOCATION: Cell projection, cilium membrane
CC {ECO:0000269|PubMed:11580282}; Single-pass type I membrane protein
CC {ECO:0000269|PubMed:18178149}. Note=Colocalized with NCALD at the
CC apical region of the cilia (PubMed:11580282). Coexpresses with PDE2 (By
CC similarity). {ECO:0000250|UniProtKB:A0A0U1RPR8,
CC ECO:0000269|PubMed:11580282}.
CC -!- TISSUE SPECIFICITY: Specifically expressed in a subpopulation of
CC olfactory sensory neurons (PubMed:7724600). Expressed in the cilia of
CC the olfactory epithelium (PubMed:11580282).
CC {ECO:0000269|PubMed:11580282, ECO:0000269|PubMed:7724600}.
CC -!- DOMAIN: The protein kinase domain is predicted to be catalytically
CC inactive. {ECO:0000305}.
CC -!- MISCELLANEOUS: In contrast to mouse, guanylin, a urine odorant, does
CC not stimulate GUCY2D. {ECO:0000269|PubMed:18178149}.
CC -!- SIMILARITY: Belongs to the adenylyl cyclase class-4/guanylyl cyclase
CC family. {ECO:0000255|PROSITE-ProRule:PRU00099}.
CC -!- CAUTION: The nomenclature for members of the GUCY2 gene family is not
CC consistent across species. In mice the GUCY2D gene encodes the protein
CC guanylate cyclase 2D specifically expressed in a subpopulation of
CC olfactory sensory neurons. In rat the official name is GUCY2E for
CC guanylate cyclase 2D. In human this gene is a pseudogene.
CC {ECO:0000305}.
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DR EMBL; L37203; AAC42057.1; -; mRNA.
DR EMBL; AABR07004868; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR PIR; I59370; I59370.
DR RefSeq; NP_570093.1; NM_130737.4.
DR AlphaFoldDB; P51839; -.
DR SMR; P51839; -.
DR STRING; 10116.ENSRNOP00000020513; -.
DR CarbonylDB; P51839; -.
DR GlyGen; P51839; 2 sites.
DR PhosphoSitePlus; P51839; -.
DR PaxDb; P51839; -.
DR PRIDE; P51839; -.
DR GeneID; 113911; -.
DR KEGG; rno:113911; -.
DR UCSC; RGD:69322; rat.
DR CTD; 14919; -.
DR RGD; 69322; Gucy2e.
DR VEuPathDB; HostDB:ENSRNOG00000015058; -.
DR eggNOG; KOG1023; Eukaryota.
DR HOGENOM; CLU_001072_1_0_1; -.
DR InParanoid; P51839; -.
DR OMA; TFLAHKN; -.
DR OrthoDB; 229634at2759; -.
DR PhylomeDB; P51839; -.
DR TreeFam; TF106338; -.
DR PRO; PR:P51839; -.
DR Proteomes; UP000002494; Chromosome 1.
DR GO; GO:0060170; C:ciliary membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IDA:RGD.
DR GO; GO:0097730; C:non-motile cilium; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
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:0016941; F:natriuretic peptide receptor activity; IDA:UniProtKB.
DR GO; GO:0005549; F:odorant binding; ISO:RGD.
DR GO; GO:0004984; F:olfactory receptor activity; ISO:RGD.
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; IDA:UniProtKB.
DR GO; GO:0003031; P:detection of carbon dioxide; ISO:RGD.
DR GO; GO:0050911; P:detection of chemical stimulus involved in sensory perception of smell; ISO:RGD.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR GO; GO:0042048; P:olfactory behavior; ISO:RGD.
DR GO; GO:0008355; P:olfactory learning; ISO:RGD.
DR GO; GO:0010753; P:positive regulation of cGMP-mediated signaling; ISO:RGD.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR GO; GO:0007168; P:receptor guanylyl cyclase signaling pathway; IDA:UniProtKB.
DR GO; GO:0007608; P:sensory perception of smell; ISO:RGD.
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 1: Evidence at protein level;
KW Cell membrane; Cell projection; cGMP biosynthesis; Disulfide bond;
KW Glycoprotein; GTP-binding; Lyase; Membrane; Nucleotide-binding; Olfaction;
KW Reference proteome; Sensory transduction; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..66
FT /evidence="ECO:0000255"
FT CHAIN 67..1110
FT /note="Guanylate cyclase 2D"
FT /id="PRO_0000012382"
FT TOPO_DOM 67..475
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 476..500
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 501..1110
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 541..818
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 893..1023
FT /note="Guanylate cyclase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT REGION 529..556
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 880..921
FT /note="Interaction with NCALD"
FT /evidence="ECO:0000269|PubMed:18178149"
FT CARBOHYD 304
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 374
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
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"
FT CONFLICT 25..27
FT /note="PCQ -> ALP (in Ref. 1; AAC42057)"
FT CONFLICT 280
FT /note="K -> E (in Ref. 1; AAC42057)"
FT CONFLICT 346
FT /note="T -> A (in Ref. 1; AAC42057)"
FT CONFLICT 378
FT /note="A -> T (in Ref. 1; AAC42057)"
FT CONFLICT 458
FT /note="R -> H (in Ref. 1; AAC42057)"
FT CONFLICT 729
FT /note="R -> G (in Ref. 1; AAC42057)"
FT CONFLICT 1110
FT /note="G -> C (in Ref. 1; AAC42057)"
SQ SEQUENCE 1110 AA; 122093 MW; 1AE40004074BC33F CRC64;
MAGLQQGCHP EGQDWTAPHW KTCRPCQGPR GLTVRHLRTV SSISVFSVVF WGVLLWADSL
SLPAWARETF TLGVLGPWDC DPIFAQALPS MATQLAVDRV NQDASLLLGS QLDFKILPTG
CDTPHALATF VAHRNTVAAF IGPVNPGYCP AAALLAQGWG KSLFSWACGA PEGGGALVPT
LPSMADVLLS VMRHFGWARL AIVSSHQDIW VTTAQQLATA FRAHGLPIGL ITSLGPGEKG
ATEVCKQLHS VHGLKIVVLC MHSALLGGLE QTVLLRCARK EGLTDGRLVF LPYDTLLFAL
PYRNRSYLVL DDDGPLQEAY DAVLTISLDT SPESHAFTAT KMRGGTAANL GPEQVSPLFG
TIYDAVILLA HALNHSEAHG TGLSGAHLGN HIRALDVAGF SQRIRIDGKG RRLPQYVILD
TNGEGSQLVP THILDVSTQQ VQPLGTAVHF PGGSPPARDA SCWFDPNTLC IRGVQPLGSL
LTLTITCVLA LVGGFLAYFI RLGLQQLRLL RGPHRILLTP QELTFLQRTP SRRRPHVDSG
SESRSVVDGG SPQSVIQGST RSVPAFLEHT NVALYQGEWV WLKKFEAGTA PDLRPSSLSL
LRKMREMRHE NVTAFLGLFV GPEVSAMVLE HCARGSLEDL LRNEDLRLDW TFKASLLLDL
IRGLRYLHHR HFPHGRLKSR NCVVDTRFVL KITDHGYAEF LESHCSFRPQ PAPEELLWTA
PELLRGPRRP WGPGKATFKG DVFSLGIILQ EVLTRDPPYC SWGLSAEEII RKVASPPPLC
RPLVSPDQGP LECIQLMQLC WEEAPDDRPS LDQIYTQFKS INQGKKTSVA DSMLRMLEKY
SQSLEGLVQE RTEELELERR KTERLLSQML PPSVAHALKM GTTVEPEYFD QVTIYFSDIV
GFTTISALSE PIEVVGFLND LYTMFDAVLD SHDVYKVETI GDAYMVASGL PRRNGNRHAA
EIANMALEIL SYAGNFRMRH APDVPIRVRA GLHSGPCVAG VVGLTMPRYC LFGDTVNTAS
RMESTGLPYR IHVSRNTVQA LLSLDEGYKI DVRGQTELKG KGLEETYWLT GKTGFCRSLP
TPLSIQPGDP WQDHINQEIR TGFAKLARVG
