ID   GUC2F_RAT               Reviewed;        1108 AA.
AC   P51842;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1996, sequence version 1.
DT   27-MAR-2024, entry version 176.
DE   RecName: Full=Retinal guanylyl cyclase 2;
DE            Short=RETGC-2;
DE            EC=4.6.1.2 {ECO:0000269|PubMed:7831337};
DE   AltName: Full=Guanylate cyclase 2F, retinal;
DE   AltName: Full=Guanylate cyclase F;
DE            Short=GC-F;
DE   AltName: Full=Rod outer segment membrane guanylate cyclase 2;
DE            Short=ROS-GC2;
DE   Flags: Precursor;
GN   Name=Gucy2f; Synonyms=Guc2f;
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], TISSUE SPECIFICITY, CATALYTIC ACTIVITY,
RP   SUBCELLULAR LOCATION, AND FUNCTION.
RC   STRAIN=Sprague-Dawley; TISSUE=Eye;
RX   PubMed=7831337; DOI=10.1073/pnas.92.2.602;
RA   Yang R.-B., Foster D.C., Garbers D.L., Fuelle H.-J.;
RT   "Two membrane forms of guanylyl cyclase found in the eye.";
RL   Proc. Natl. Acad. Sci. U.S.A. 92:602-606(1995).
RN   [2]
RP   SUBUNIT, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX   PubMed=9153227; DOI=10.1074/jbc.272.21.13738;
RA   Yang R.B., Garbers D.L.;
RT   "Two eye guanylyl cyclases are expressed in the same photoreceptor cells
RT   and form homomers in preference to heteromers.";
RL   J. Biol. Chem. 272:13738-13742(1997).
CC   -!- FUNCTION: Responsible for the synthesis of cyclic GMP (cGMP) in rods
CC       and cones of photoreceptors. Plays an essential role in
CC       phototransduction, by mediating cGMP replenishment (PubMed:7831337).
CC       May also participate in the trafficking of membrane-asociated proteins
CC       to the photoreceptor outer segment membrane (By similarity).
CC       {ECO:0000250|UniProtKB:Q5SDA5, ECO:0000269|PubMed:7831337}.
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:7831337};
CC   -!- ACTIVITY REGULATION: Activated by GUCA1B when free calcium ions
CC       concentration is low, and inhibited by GUCA1B when free calcium ions
CC       concentration is high (By similarity). Inhibited by RD3 (By
CC       similarity). {ECO:0000250|UniProtKB:O02740,
CC       ECO:0000250|UniProtKB:P51841}.
CC   -!- SUBUNIT: Homodimer (PubMed:9153227). Interacts with RD3; promotes the
CC       exit of GUCY2F from the endoplasmic reticulum and its trafficking to
CC       the photoreceptor outer segments (By similarity).
CC       {ECO:0000250|UniProtKB:Q5SDA5, ECO:0000269|PubMed:9153227}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:7831337}; Single-
CC       pass type I membrane protein. Photoreceptor outer segment membrane
CC       {ECO:0000250|UniProtKB:O02740}; Single-pass type I membrane protein
CC       {ECO:0000255}.
CC   -!- TISSUE SPECIFICITY: Expressed only in the eye.
CC       {ECO:0000269|PubMed:7831337}.
CC   -!- DOMAIN: The protein kinase domain is predicted to be catalytically
CC       inactive.
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   -!- SIMILARITY: Belongs to the adenylyl cyclase class-4/guanylyl cyclase
CC       family. {ECO:0000255|PROSITE-ProRule:PRU00099}.
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DR   EMBL; L36030; AAA65511.1; -; mRNA.
DR   PIR; B55915; B55915.
DR   RefSeq; NP_446283.1; NM_053831.1.
DR   AlphaFoldDB; P51842; -.
DR   SMR; P51842; -.
DR   STRING; 10116.ENSRNOP00000049500; -.
DR   PhosphoSitePlus; P51842; -.
DR   PaxDb; 10116-ENSRNOP00000049500; -.
DR   Ensembl; ENSRNOT00000046804.3; ENSRNOP00000049500.2; ENSRNOG00000019086.5.
DR   Ensembl; ENSRNOT00055042821; ENSRNOP00055034969; ENSRNOG00055024843.
DR   Ensembl; ENSRNOT00060032345; ENSRNOP00060026356; ENSRNOG00060018767.
DR   GeneID; 116556; -.
DR   KEGG; rno:116556; -.
DR   AGR; RGD:620439; -.
DR   CTD; 2986; -.
DR   RGD; 620439; Gucy2f.
DR   eggNOG; KOG1023; Eukaryota.
DR   GeneTree; ENSGT00940000162146; -.
DR   HOGENOM; CLU_001072_1_0_1; -.
DR   InParanoid; P51842; -.
DR   OMA; QDSQSMR; -.
DR   OrthoDB; 3683909at2759; -.
DR   PhylomeDB; P51842; -.
DR   TreeFam; TF106338; -.
DR   Reactome; R-RNO-2514859; Inactivation, recovery and regulation of the phototransduction cascade.
DR   PRO; PR:P51842; -.
DR   Proteomes; UP000002494; Chromosome X.
DR   GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR   GO; GO:0120200; C:rod photoreceptor outer segment; ISS:UniProtKB.
DR   GO; GO:0004016; F:adenylate cyclase activity; IBA:GO_Central.
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:RGD.
DR   GO; GO:0042802; F:identical protein binding; IPI: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:0044877; F:protein-containing complex binding; IPI:RGD.
DR   GO; GO:0006182; P:cGMP biosynthetic process; IBA:GO_Central.
DR   GO; GO:0019934; P:cGMP-mediated signaling; IDA:RGD.
DR   GO; GO:0050908; P:detection of light stimulus involved in visual perception; ISO:RGD.
DR   GO; GO:0007168; P:receptor guanylyl cyclase signaling pathway; IBA:GO_Central.
DR   CDD; cd07302; CHD; 1.
DR   CDD; cd06371; PBP1_sensory_GC_DEF-like; 1.
DR   Gene3D; 3.40.50.2300; -; 2.
DR   Gene3D; 3.30.70.1230; Nucleotide cyclase; 1.
DR   Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 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   PANTHER; PTHR11920; GUANYLYL CYCLASE; 1.
DR   PANTHER; PTHR11920:SF349; RETINAL GUANYLYL CYCLASE 2; 1.
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; SSF55073; Nucleotide cyclase; 1.
DR   SUPFAM; SSF53822; Periplasmic binding protein-like I; 1.
DR   SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR   PROSITE; PS00452; GUANYLATE_CYCLASE_1; 1.
DR   PROSITE; PS50125; GUANYLATE_CYCLASE_2; 1.
DR   PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR   Genevisible; P51842; RN.
PE   1: Evidence at protein level;
KW   Cell projection; cGMP biosynthesis; Disulfide bond; GTP-binding; Lyase;
KW   Membrane; Nucleotide-binding; Reference proteome; Sensory transduction;
KW   Signal; Transmembrane; Transmembrane helix; Vision.
FT   SIGNAL          1..50
FT                   /evidence="ECO:0000255"
FT   CHAIN           51..1108
FT                   /note="Retinal guanylyl cyclase 2"
FT                   /id="PRO_0000012387"
FT   TOPO_DOM        51..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          532..812
FT                   /note="Protein kinase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   DOMAIN          884..1014
FT                   /note="Guanylate cyclase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT   DISULFID        104..132
FT                   /evidence="ECO:0000250"
FT   DISULFID        452
FT                   /note="Interchain"
FT                   /evidence="ECO:0000250"
FT   DISULFID        460
FT                   /note="Interchain"
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   1108 AA;  124411 MW;  2A9147AF2202E4E3 CRC64;
     MFLGPWPFSR LLSWFAISSR LSGQHGLTSS KFLRYLCLLA LLPLIWWGQA LPYKIGVIGP
     WTCDPFFSKA LPEVAAALAI ERISRDMSFD RSYSFEYVIL NEDCQTSKAL TSFISHQQMA
     SGFVGPANPG YCEAASLLGN SWDKGIFSWA CVNHELDNKH SYPTFSRTLP SPIRVLVTVM
     KYFQWAHAGV ISSDEDIWVH TANQVSSALR SHGLPVGVVL TSGQDSRSIQ KALQQIRQAD
     RIRIIIMCMH SALIGGETQT HFLELAHDLK MTDGTYVFVP YDVLLYSLPY KHSPYQVLRN
     NQKLREAYDA VLTITVESHE KTFYEAFTEA AAGGEIPEKL DSHQVSPLFG TIYNSIYFIA
     QAMSNALKEN GQASAASLTR HSRNMQFYGF NQLIRTDSNG NGISEYVILD TNGKEWELRG
     TYTVDMETEL LRFRGTPIHF PGGRPTSADA KCWFAQGKIC QGGIDPALAM MVCFALLLAL
     LSINGFAYFI RRRINKIQLI KGPNRILLTL EDVTFINPHF GSKRGSRASV SFQIISEVQS
     GRSPRLSFSS GSLTPATYEN SNIAIYQGDW VWLKKFPPGD FGDIKSIKSS ASDVFEMMKD
     LRHENVNPLL GFFYDSGMFA IVSEFCSRRS LEDILTQDDV KLDWMFKSSL LLDLIKGMKY
     LHHREFIHGR LKSRNCVVDG RFVLKVTDYG FNNILEMLRL SEEEPSEEEL LWTAPELLRA
     PGGIRLGSFA GDVYSFAIIM QEVMVRGAPF CMMDLSAKEV IDRLKMPPPV YRPVVSPEFA
     PPECLQLMKQ CWAEAAEQRP TFDEIFNQFK TFNKGKKTNI IDSMLRMLEQ YSSNLEDLIR
     ERTEELEIEK QKTEKLLTQM LPPSVAESLK KGCTVEPEGF DLVTLYFSDI VGFTTISAMS
     EPIEVVDLLN DLYTLFDAII GSHDVYKVET IGDAYMVASG LPKRNGSRHA AEIANMSLDI
     LSSVGTFKMR HMPEVPVRIR IGLHTGPVVA GVVGLTMPRY CLFGDTVNTA SRMESTGLPY
     RIHVSLSTVT ILRTLSEGYE VELRGRTELK GKGTEETFWL VGKKGFTKPL PVPPPVGKDG
     QVGHGLQPAE IAAFQRRKAE RQLVRNKP
//